bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Serotonin Type 1AReceptor Binding in Panic Disorder: Figure 1.
Authors: Neumeister Alexander , Bain Earle , Nugent Allison C. , Carson Richard E. , Bonne Omer , Luckenbaugh David A. , Eckelman William , Herscovitch Peter , Charney Dennis S. , Drevets Wayne C.
Published: January 2004

Recent animal models suggest that disturbances in serotonin type-1A receptor (5-HT1AR) function may contribute to chronic anxiety, although it is not clear at all whether such models constitute relevant models for panic disorder (PD) in humans. The selective 5-HT1AR radioligand [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (FCWAY) permitsin vivoassessment of central 5-HT1AR binding using positron emission tomography (PET). We studied 16 unmedicated symptomatic outpatients with PD and 15 matched healthy controls. Seven patients had an additional diagnosis of a current major depressive episode, however PD was the primary diagnosis. A 120 min PET study of 5-HT1AR binding was acquired using a GE Advance scanner in three-dimensional mode. Using quantitative PET image analysis, regional values were obtained for [18F]-FCWAY volume of distribution (DV), corrected for plasma protein binding, and K1, the delivery rate of [18F]-FCWAY from plasma to tissue. MRI scanning was performed using a GE Signa Scanner (3.0 Tesla) to provide an anatomical framework for image analysis and partial volume correction of PET data. PD patients showed lower DV in the anterior cingulate (t= 4.3;p< 0.001), posterior cingulate (t= 4.1;p< 0.001), and raphe (t= 3.1;p= 0.004). Comparing patients with PD, patients with PD and comorbid depression, and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression, whereas both patient groups differed significantly from controls. These results provide for the first timein vivoevidence for the involvement of 5-HT1ARs in the pathophysiology of PD.
Giant Coercive Field of Nanometer‐ Sized Iron Oxide
Authors: Jin J. , Ohkoshi S. , Hashimoto K.
Published: January 2004

Nanocrystals of iron oxide in a silica matrix exhibiting a giant Hc value of 2.0 T at room temperature are reported. The nanocomposite was obtained by combining reverse‐micelle and sol–gel methods. The nanocrystals of iron oxide are composed of the ϵ‐Fe2O3 phase, with rod‐like particles 100–140 nm long and 20–40 nm wide. The Figure shows the hysteresis curve of the nanocrystals.
Electric Field Singularity Assisted Nanopatterning
Authors: Ravishankar N. , Shenoy V. B. , Carter C. B.
Published: January 2004

Ordered arrays of Pt nanoparticles (see Figure) have been produced on a reconstructed alumina surface that serves as a template for nanopatterning. The Pt particles condense from an undersaturated vapor phase only along the crest regions on the reconstructed plane. It is shown that the presence of an electric field singularity leads at the crest regions to the highly site‐specific formation of nanoparticles.
Polyacrylonitrile Single‐Walled Carbon Nanotube Composite Fibers
Authors: Sreekumar T. V. , Liu T. , Min B. G. , Guo H. , Kumar S. , Hauge R. H. , Smalley R. E.
Published: January 2004

Polyacrylonitrile (PAN) fibers containing 10 wt.‐% single‐walled carbon nanotubes (SWNTs) exhibit a 100 % improvement in tensile modulus and reduced thermal shrinkage and polymer solubility. A 40 °C increase in glass transition temperature as compared to the control PAN fiber is also observed (see Figure). SWNT anisotropy has been observed using infrared spectroscopy.
Efficient Organic Blue‐Light‐Emitting Devices with Double Confinement on Terfluorenes with Ambipolar Carrier Transport Properties
Authors: Wu C.‐C. , Lin Y.‐T. , Wong K.‐T. , Chen R.‐T. , Chien Y.‐Y.
Published: January 2004

Ter(9,9‐diarylfluorene)s (TDAFs) exhibit many intriguing properties promising for blue light‐emitting devices, such as high thin‐film photoluminescence quantum yields (∼ 90 %), high glass‐transition temperatures (> 200 °C), and an unusual ambipolar carrier‐transport capability. Successful implementation of a double‐ heterostructure device configuration that provides effective confinement of both carriers and excitons in TDAFs results in an electroluminescence performance (5.3 % external quantum efficiency) promising for application in blue‐emitting devices.
In‐Situ Growth of “Fused”, Ozonized Single‐Walled Carbon Nanotubes—CdTe Quantum Dot Junctions
Authors: Banerjee S. , Wong S. S.
Published: January 2004

A molecular‐scale interface, consisting of a “fused” heterojunction between a nanotube and a quantum dot, has been prepared. This work is significant for the construction of functional hierarchical assemblies with unique properties. The Figure shows a schematic representation of a CdTe quantum dot grown directly onto the oxygenated surface of an ozonized single‐walled carbon nanotube template (see also inside cover).
Nanobelt‐Templated Growth of Carbon Nanotube Rows
Authors: Cao A. , Meng G. , Ajayan P. M.
Published: January 2004

Rows of aligned carbon nanotubes standing shoulder by shoulder (see Figure) have been synthesized by growing nanotubes inside Au micro‐ and nanotrenches created by nanobelts or nanowires. This simple non‐lithographic method can be used to fabricate nanotube rows with a width of less than 2 μm, and a length over hundreds of micrometers.
Micropixelated Luminescent Nanocrystal Arrays Synthesized by Ion Implantation
Authors: Meldrum A. , Buchanan K. S. , Hryciw A. , White C. W.
Published: January 2004

It is shown that a simple lithographic method can result in single‐ or two‐ color “micropixelated” arrays of luminescent silicon nanoparticles. Other colors should be readily possible. This combined spatial and color control may be important with respect to future applications of these highly luminescent nanocrystalline materials. The Figure shows a fluorescence image of a patterned nanocrystal array.
Laser‐Induced Thermal Imaging of Polymer Light‐Emitting Materials on Poly(3,4‐ethylenedioxythiophene): Silane Hole‐Transport Layer
Authors: Lee J. Y. , Lee S. T.
Published: January 2004

The addition of methacryloxypropyltrimethoxysilane to poly(3,4‐ ethylenedioxythiophene) has enabled laser‐induced thermal imaging (LITI) of polymer light‐emitting materials on a hole‐transport layer (see Figure for example). The I–V–L (current–voltage–luminance) performances of the device patterned by the LITI process are comparable to those of typical spin‐coated devices.
Electroluminescence in n‐ZnO Nanorod Arrays Vertically Grown on p‐GaN
Authors: Park W. I. , Yi G.‐C.
Published: January 2004

Electroluminescent (EL) devices (see Figure) have been fabricated using n‐ZnO nanorod arrays grown on p‐GaN epilayers. Simple heteroepitaxial growth yields vertically aligned ZnO nanorods with an abrupt interface on GaN. The p–n heterojunction EL device shows a high current density and strong electroluminescence even at a reverse‐bias voltage of 3 V.
Preparation of Arrays of Isolated Spherical Cavities by Self‐Assembly of Polystyrene Spheres on Self‐Assembled Pre‐patterned Macroporous Films
Authors: Abdelsalam M. E. , Bartlett P. N. , Baumberg J. J. , Coyle S.
Published: January 2004

Isolated metallic arrays of spherical cavities (see Figure) have been prepared using a simple scheme that combines two self‐assembly steps using monodisperse polystyrene spheres of two different sizes and electrochemical deposition. The ability to easily fabricate, at low cost, a large variety of such photonic metallic structures promises applicability in many diverse areas, ranging from biotechnology to optoelectronics.
SiC–SiO2–C Coaxial Nanocables and Chains of Carbon Nanotube–SiC Heterojunctions
Authors: Li Y. , Bando Y. , Golberg D.
Published: January 2004

Coaxial nanocables composed of a uniform single‐crystalline β‐SiC core, an amorphous SiO2 intermediate layer, and a graphitic carbon sheath (see Figure) have been synthesized via a simple chemical vapor deposition route. By annealing the nanocables, chains of carbon nanotube–SiC heterojunctions have been prepared. These nanostructures are suggested to be highly valuable as building blocks for nanoscale electronic devices.
Patterning Colloidal Crystals by Lift‐up Soft Lithography
Authors: Yao J. , Yan X. , Lu G. , Zhang K. , Chen X. , Jiang L. , Yang B.
Published: January 2004

Patterned colloidal crystals have been fabricated by a lift‐up soft lithography method based on the selective transfer of a single layer of close‐packed microspheres from the crystal film to the protruding surface of a poly(dimethylsiloxane) stamp. The Figure shows a scanning electron microscopy image of the ordered square array in the top layer of a 3D colloidal crystal that was produced using a two‐step lift‐up process.
Carbon Nanotubes on Carbon Nanofibers: A Novel Structure Based on Electrospun Polymer Nanofibers
Authors: Hou H. , Reneker D. H.
Published: January 2004

Electrospun nanofibers of polyacrylonitrile, containing an iron compound, have been converted to carbon nanofibers, with iron particles on their surfaces. The iron particles catalyze the growth of carbon nanotubes with iron tips (see Figure). A mechanically strong and electrically conducting path exists between each metal particle and the supporting nanofiber network, which extends to macroscopic dimensions.
A Fresh Look at Materials Science
Authors: Levy E.
Published: January 2004

2004 has brought a fresh look to Advanced Materials. This editorial highlights the improvements made to the layout of the journal as well as other events you can look forward to this year.
Supramolekulare Chemie von Gasen
Authors: Rudkevich Dmitry M.
Published: January 2004

Die molekulare Erkennung von Gasen ist ein neu aufkommendes Forschungsgebiet. Anhand von Prinzipien der supramolekularen Chemie können wir verstehen, wie Gase mit biologischen Molekülen wechselwirken, und Einzelheiten zum Mechanimus ihrer physiologischen Aktivität erfahren. Das Konzept der molekularen Erkennung wurde zur Gassensorik genutzt, wobei grundlegende Kenntnisse zur Struktur und Dynamik von Rezeptor‐Analyt‐Komplexen erhalten wurden. In diesem Zusammenhang gelang die Entwicklung neuer Gassensoren und Gasspeicherungselemente, für die sich auch in der Natur zahlreiche Beispiele finden lassen. Konzepte der supramolekularen Chemie liefern die Basis zur Umwandlung von Gasen in synthetisch nützliche Reagentien. Das rationale Design neuartiger Katalysatoren für Reaktionen mit Gasen und von Einlagerungskomplexen mit Gasen liefert ausgezeichnete Perspektiven für die präparative synthetische Chemie.
Neue katalytische Methoden in der stereoselektiven Friedel‐Crafts‐Alkylierung
Authors: Bandini Marco , Melloni Alfonso , Umani‐Ronchi Achille
Published: January 2004

Mehr als 125 Jahren nach ihrer Entdeckung zählt die Friedel‐Crafts‐Alkylierung zu den am besten untersuchten und am häufigsten eingesetzten Reaktionen der organischen Synthese. Worin liegt das Geheimnis dieses erstaunlichen Erfolgs? Vermutlich trägt die Vielseitigkeit dieser Reaktion dazu bei, dass sie auch heute noch entscheidenden Anteil hat an der Synthese immer komplexerer Verbindungen. Es dauerte allerdings mehr als ein Jahrhundert, bis asymmetrische katalytische Varianten für die Umsetzung einer großen Bandbreite aromatischer Substrate und Alkylierungsmittel entwickelt wurden. Hier berichten wir über neueste Entwicklungen und Anwendungen katalytischer stereoselektiver Alkylierungen aromatischer Substrate sowie über die Synthesen einer großen Auswahl enantiomerenangereicherter, hoch funktionalisierter Verbindungen.
Emerging Supramolecular Chemistry of Gases
Authors: Rudkevich Dmitry M.
Published: January 2004

Molecular recognition of gases is an emerging area of chemistry. Supramolecular chemistry helps us to understand how gases interact with biological molecules and offers delicate insights into the mechanisms of their physiological activity. Principles of molecular recognition have been used for gas sensing, and have provided fundamental knowledge about the structure and dynamics of receptor–analyte complexes, and novel materials for gas sensing and storage have been developed. Supramolecular chemistry is also enabling us to learn how to transform gases into synthetically useful reagents. The rational design of novel catalysts for gas conversion and, more recently, encapsulation complexes with gases open novel directions in preparative synthetic chemistry.
Cover Picture: σ‐Bond Stretching: A Static Approach for a Dynamic Process (Angew. Chem. Int. Ed. 5/2004)
Authors: Scheschkewitz David , Amii Hideki , Gornitzka Heinz , Schoeller Wolfgang W. , Bourissou Didier , Bertrand Guy
Published: January 2004

A motion picture of chemical transformation can be pieced together only from femtosecond spectroscopic techniques. The Communication by G. Bertrand and co‐workers on page 585 ff. describes how the reaction profile corresponding to the inversion of bicyclo[1.1.0]butane, which involves the stretching of the BB bond as symbolized by the tugging men, can be modeled by series of analogues that contain the boron–phosphorus ring.
Recombination in HIV and the evolution of drug resistance: for better or for worse?
Authors: Bretscher Michael T. , Althaus Christian L. , Müller Viktor , Bonhoeffer Sebastian
Published: January 2004

The rapid evolution of drug resistance remains a major obstacle for HIV therapy. The capacity of the virus for recombination is widely believed to facilitate the evolution of drug resistance. Here, we challenge this intuitive view. We develop a population genetic model of HIV replication that incorporates the processes of mutation, cellular superinfection, and recombination. We show that cellular superinfection increases the abundance of low fitness viruses at the expense of the fittest strains due to the mixing of viral proteins during virion assembly. Moreover, we argue that whether recombination facilitates the evolution of drug resistance depends critically on how resistance mutations interact to determine viral fitness. Contrary to the commonly held belief, we find that, under the most plausible biological assumptions, recombination is expected to slow down the rate of evolution of multi‐drug‐resistant virus during therapy. BioEssays 26:180–188, 2004. © 2004 Wiley Periodicals, Inc.
How mammalian sex chromosomes acquired their peculiar gene content
Authors: Vallender Eric J. , Lahn Bruce T.
Published: January 2004

It has become increasingly evident that gene content of the sex chromosomes is markedly different from that of the autosomes. Both sex chromosomes appear enriched for genes related to sexual differentiation and reproduction; but curiously, the human X chromosome also seems to bear a preponderance of genes linked to brain and muscle functions. In this review, we will synthesize several evolutionary theories that may account for this nonrandom assortment of genes on the sex chromosomes, including 1) asexual degeneration, 2) sexual antagonism, 3) constant selection, and 4) hemizygous exposure. Additionally, we will speculate on how the evolution of sex‐chromosome gene content might have impacted on the phenotypic evolution of mammals and particularly humans. Our discussion will focus on the mammalian sex chromosomes, but will cross reference other species where appropriate. BioEssays 26:159–169, 2004. © 2004 Wiley Periodicals, Inc.
LIMK1 and CLIP‐115: linking cytoskeletal defects to Williams syndrome
Authors: Hoogenraad Casper C. , Akhmanova Anna , Galjart Niels , De Zeeuw Chris I.
Published: January 2004

Williams Syndrome is a developmental disorder that is characterized by cardiovascular problems, particular facial features and several typical behavioral and neurological abnormalities. In Williams Syndrome patients, a heterozygous deletion is present of a region on chromosome 7q11.23 (the Williams Syndrome critical region), which spans approximately 20 genes. Two of these genes encode proteins that regulate dynamic aspects of the cytoskeleton of the cell, either via the actin filament system (LIM kinase 1, or LIMK1), or through the microtubule network (cytoplasmic linker protein of 115 kDa, or CLIP‐115). The recent findings that knockout mice lacking LIMK1 or CLIP‐115 have distinct neurological and behavioural phenotypes, indicates that cytoskeletal defects might play a role in the development of neurological symptoms in Williams Syndrome patients. In this review, we discuss the properties of LIMK and CLIP family proteins, their function in the regulation of the actin and microtubule cytoskeletal systems, respectively, and the relationship with neurodevelopmental aspects of Williams Syndrome. BioEssays 26:141–150, 2004. © 2004 Wiley Periodicals, Inc.
Post‐replication repair in DT40 cells: translesion polymerases versus recombinases
Authors: Hochegger Helfrid , Sonoda Eichiro , Takeda Shunichi
Published: January 2004

Replication forks inevitably stall at damaged DNA in every cell cycle. The ability to overcome DNA lesions is an essential feature of the replication machinery. A variety of specialized polymerases have recently been discovered, which enable cells to replicate past various forms of damage by a process termed translesion synthesis. Alternatively, homologous recombination can be used to restart DNA replication across the lesion. Genetic and biochemical studies have shed light on the impact of these two post‐replication repair pathways in bacteria and yeast. In vertebrates, however, a genetic approach to study post‐replication repair has been compromised because many of the genes involved appear to be essential for embryonic development. We have taken advantage of the chicken cell line DT40 to perform a genetic analysis of translesion synthesis and homologous recombination and to characterize genetic interactions between these two pathways in vertebrates. In this article, we aim to summarize our current understanding of post‐replication repair in DT40 in the perspective of bacterial, yeast and mammalian genetics. BioEssays 26:151–158, 2004. © 2004 Wiley Periodicals, Inc.
Deciphering the swordtail's tale: a molecular and evolutionary quest
Authors: Wilkins Adam S.
Published: January 2004

The power of sexual selection to influence the evolution of morphological traits was first proposed more than 130 years ago by Darwin. Though long a controversial idea, it has been documented in recent decades for a host of animal species. Yet few of the established sexually selected features have been explored at the level of their genetic or molecular foundations. In a recent report, Zauner et al.1 describe some of the molecular features associated with one of the best characterized of sexually selected traits, the male‐specific tail “sword” seen in certain species of the fish genus Xiphophorus. Zauner et al. find that the msxC gene, a gene previously implicated in fin development from work in zebrafish, is dramatically and specifically upregulated in the development of the ventral caudal fin rays, which give rise to the sword, in males. The results provide the first molecular insight into the development of this sexually selected trait while prompting new questions about the structure of the entire genetic network that underlies this trait. To fully understand the molecular‐genetic and evolutionary history of this network, however, it will be essential to determine whether sword‐development is a basal or derived trait in Xiphophorus. BioEssays 26:116–119, 2004. © 2004 Wiley Periodicals, Inc.
Expansion of the genetic code in yeast: making life more complex
Authors: Davis Brian K.
Published: January 2004

Proteins account for the catalytic and structural versatility displayed by all cells, yet they are assembled from a set of only 20 common amino acids. With few exceptions, only 61 nucleotide triplets also direct incorporation of these amino acids. Endeavors to expand the genetic code recently progressed to nucleus‐containing cells, after Chin et al.1 transferred Escherichia coli genes for a mutant tyrosine‐adaptor molecule and its synthetase into Saccharomyces cerevisiae. Transformed yeast cells were produced that exhibit efficient site‐specific incorporation of non‐biotic amino acids into proteins. This makes it likely that code complexity can be elevated experimentally in mammals. BioEssays 26:111–115, 2004. © 2004 Wiley Periodicals, Inc.
Helfen 3D‐Simulationen beim Lernen mit CHEMnet?
Authors: Nick Sabine , Urhahne Detlef
Published: January 2004

DAS INTERESSE am Einsatz neuer Informations‐ und Kommunikationstechnologien in Schule und Hochschule hat in den letzten Jahren stark zugenommen [1]. Auch für den Bereich der Chemie finden sich daher zahlreiche Beispiele von Angeboten im World Wide Web, die als Informationsquelle oder zum Lernen genutzt werden können [2].
The chemotaxis defect of Shwachman‐Diamond Syndrome leukocytes
Authors: Stepanovic Vesna , Wessels Deborah , Goldman Frederick D. , Geiger Jeremy , Soll David R.
Published: January 2004

Shwachman‐Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer‐assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158–174, 2004. © 2004 Wiley‐Liss, Inc.
Flagellar quiescence in Chlamydomonas: Characterization and defective quiescence in cells carrying sup‐pf‐1 and sup‐pf‐2 outer dynein arm mutations
Authors: Mitchell Beth Ferro , Grulich Laurie E. , Mader Michelle M.
Published: January 2004

Chlamydomonas reinhardtii can use their flagella for two distinct types of movement: swimming through liquid or gliding on a solid substrate. Cells switching from swimming to gliding motility undergo a reversible flagellar quiescence. This phenomenon appears to involve the outer dynein arms, since mutants having altered outer arm β and γ dyneins (sup‐pf‐1 and sup‐pf‐2) show a diminished ability to quiesce. Sup‐pf‐1 and sup‐pf‐2 were originally isolated as gain‐of‐function mutations that suppress the flagellar paralysis resulting from radial spoke or central pair defects. Defective quiescence is also a gain‐of‐function phenomenon, as cells completely lacking outer arm heavy chains show a normal quiescence phenotype. These data suggest that regulation of outer arm dynein activity is essential for flagellar quiescence and furthermore that regulation of quiescence involves a signal transduction pathway that shares elements with the radial spoke/central pair system. Cell Motil. Cytoskeleton 57:186–196, 2004. © 2004 Wiley‐Liss, Inc.
Proliferative activity in primary breast carcinomas is a salient prognostic factor
Authors: Michels Jean‐Jacques , Marnay Jacques , Delozier Thierry , Denoux Yves , Chasle Jacques
Published: January 2004

BACKGROUND

The goal of the current study was to investigate the prognostic impact of proliferative activity, together with the other classic clinicopathologic prognostic factors (tumor size, tumor grade, receptor status, ploidy, and lymph node status), in breast carcinoma by counting mitoses and evaluating S phase fraction (SPF) in fresh and frozen tumor samples.

METHODS

From March 1, 1990, to July 1, 1999, a total of 1984 previously untreated invasive breast carcinoma samples were snap‐frozen for flow cytometry.

RESULTS

After multivariate analysis incorporating all classic prognostic factors, SPF combined with mitotic activity (i.e., proliferative activity) remained the sole prognostic factor in the lymph node–negative group; proliferative activity was accompanied by tumor size as a prognostic factor in patients with lymph node–positive disease and by lymph node status, lymphatic invasion, and receptor status in the overall population. The predictive value of proliferative activity was superior to that of the reference standards (classic prognostic predictors according to the guidelines of our institution [common oncology practice] and the St. Gallen classification). A review of the literature, focusing on series in which fresh material was used, allowed us to demonstrate that there is widespread agreement regarding the correlation between SPF and prognosis, even after multivariate analysis.

CONCLUSIONS

S phase fraction is a valuable predictor of survival and can confidently be assessed in approximately 80% of cases. In conjunction with mitotic activity, SPF should become a prognostic factor that is used in daily practice by oncologists for the management of breast carcinoma. Cancer 2004. © 2003 American Cancer Society.
A retrospective analysis of health care costs for bone fractures in women with early‐stage breast carcinoma
Authors: Zhou Zhiyuang , Redaelli Alberto , Johnell Olof , Willke Richard J. , Massimini Giorgio
Published: January 2004

BACKGROUND

In this retrospective data base study, the authors sought to estimate direct costs for bone fractures in women age ≥ 65 years with early‐stage breast carcinoma and to compare those costs with treatment costs for bone fractures in older women without early‐stage breast carcinoma.

METHODS

Direct costs for bone fractures in patients with early‐stage breast carcinoma, which consist of excess treatment costs for bone fracture and excess costs of long‐term care for bone fracture, were evaluated by using the 1997–1998 Standard Analytical File. The statistical significance of the difference in inpatient costs, medical treatment costs, and long‐term care admission rates were determined with the t test and the Fisher chi‐square test, respectively.

RESULTS

For older women with early‐stage breast carcinoma, the direct costs for bone fracture were estimated at $45,579, and 57% of those costs came from treating the bone fracture (32% came from inpatient hospital costs, and 25% came from noninpatient hospital costs), 25% came from other excess treatment costs, and 18% came from excess long‐term care costs. The women who had early‐stage breast carcinoma and sustained bone fracture did not differ significantly from the women without early‐stage breast carcinoma who sustained a bone fracture.

CONCLUSIONS

Bone fracture was associated with high direct costs in older women with early‐stage breast carcinoma. Additional research should include appropriate, incidence‐based studies to investigate the potential benefit of an intervention for preventing bone fracture in this increasingly large patient population. Cancer 2004. © 2003 American Cancer Society.
Should decisions on internal mammary lymph node irradiation be based on current lymphoscintigraphy techniques for sentinel lymph node identification?
Authors: Benda Rashmi K. , Cendan Juan C. , Copeland Edward M. , Feezor Robert J. , Lind D. Scott , Morris Christopher G. , Mendenhall Nancy Price
Published: January 2004

BACKGROUND

Treatment of internal mammary lymph node (IMN) metastases remains controversial because of the difficulty in predicting involvement, potential treatment‐related morbidity, and questionable efficacy. Lymphoscintigraphy with sentinel lymph node biopsy offers a means to identify occult involvement of IMN, allowing appropriate patient selection for IMN treatment.

METHODS

The authors retrospectively reviewed 262 lymphoscintigraphies (LS) of 248 patients treated at the University of Florida (Gainesville, FL) between 1998 and 2002. Tumor characteristics were assessed for their value in predicting IMN drainage and their association with IMN radiation.

RESULTS

Lymph flow to the IMN was documented with LS in 23 of 262 tumor specimens (9%). Flow to the IMN was not correlated with any of the five factors: tumor location, tumor size, lymphovascular invasion, pathologic lymph node status, and laterality of the involved breast (right vs. left breast). Identification of IMN flow increased from 5.7% to 10.1% with the use of a deep injection technique. IMN radiotherapy was used more frequently in patients with larger tumors (15 of 188 in Tis/T1 vs. 31 of 70 in T2–T4; P < 0.0001) and positive lymph nodes (17 of 91 in lymph node–negative patients vs. 28 of 66 in lymph node–positive patients; P < 0.0001). In patients with T2N0 tumors (n = 32), IMN radiotherapy was used more frequently with medial tumors (5 of 11 [45%]) than with lateral tumors (4 of 21 [19%]).

CONCLUSIONS

The incidence of flow to the IMN documented with the current LS technique was low compared with other LS and extended radical mastectomy series. Histopathologic information was obtained for the sentinel IMN when IMN flow was identified on the LS. In the absence of histopathologic information, treatment decisions should continue to be based on clinical factors known to be correlated with occult IMN involvement. Cancer 2004. © 2003 American Cancer Society.
Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine
Authors: Shields Anthony F. , Zalupski Mark M. , Marshall John L. , Meropol Neal J.
Published: January 2004

BACKGROUND

The current study was designed to evaluate the antitumor activity and toxicity of capecitabine and oxaliplatin in previously untreated patients with advanced colorectal carcinoma. The primary endpoint of the study was to determine the objective response rate, and a secondary endpoint was to measure the time to disease progression.

METHODS

A 2‐stage trial was planned with an accrual goal of 35 patients. The treatment included oxaliplatin given at a dose of 130 mg/m2 on Day 1 of each 3‐week cycle. Initially, capecitabine at a dose of 2000 mg/m2/day in 2 divided doses was given on Days 1–14 of each cycle, but this was reduced to a dose of 1500 mg/m2/day because of toxicity. Patients were followed by computed tomography scans every two cycles to evaluate treatment response, and toxicity was monitored.

RESULTS

The first 13 patients on the trial received the higher dose of capecitabine. Although 5 responses (38.5%) were noted, 5 patients were hospitalized with diarrhea and dehydration. This toxicity led to a decrease in the dose of capecitabine to 1500 mg/m2/day and an additional 35 patients were treated. At the lower dose, the partial response rate was 37.1% (95% confidence interval [95% CI], 21.5–55.1%). The estimated median progression‐free survival was 6.9 months (95% CI, 4.4–8.2 months). At the lower dose, four patients were hospitalized with diarrhea/dehydration (with one death reported), one with febrile neutropenia, and one with ventricular fibrillation. Overall, Grade (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria) 3‐4 diarrhea was reported to develop in 20% of those patients treated at the capecitabine dose of 1500 mg/m2/day compared with 62% of patients treated at the dose of 2000 mg/m2/day.

CONCLUSIONS

The combination of oxaliplatin and capecitabine is an active and convenient regimen for the treatment of patients with advanced colorectal carcinoma and should be compared with other front‐line regimens as therapy for disease. Cancer 2004. © 2003 American Cancer Society.
Restaging of recurrent cervical carcinoma with dual‐phase [18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography
Authors: Lai Chyong‐Huey , Huang Kuan‐Gen , See Lai‐Chu , Yen Tzu‐Chen , Tsai Chien‐Sheng , Chang Ting‐Chang , Chou Hung‐Hsueh , Ng Koon‐Kwan , Hsueh Swei , Hong Ji‐Hong
Published: January 2004

BACKGROUND

The clinical value of positron emission tomography (PET) with [18F]fluoro‐2‐deoxy‐D‐glucose (FDG) for primary staging in cervical carcinoma appears to be promising. The authors sought to evaluate the diagnostic efficacy and benefit of PET in restaging cervical carcinoma at the time of first recurrence.

METHODS

Forty patients with cervical carcinoma who experienced confirmed treatment failure but who were feasible candidates for curative salvage therapy were enrolled prospectively in the current study. Restaging was performed with PET and with computed tomography and/or magnetic resonance imaging (CT/MRI). Dual‐phase PET was performed by adding 3‐hour‐delayed images to the 40‐minute scans. The results of the PET and CT/MRI scans were compared. Lesion status was determined by pathologic findings or by clinical follow‐up. The receiver operating characteristic curve method with calculation of area under the curve (AUC) was used to evaluate diagnostic efficacy. The primary endpoint was percent improvement in restaging (with improvement indicated by treatment modification) after PET. The secondary endpoint was 2‐year overall survival among study participants compared with comparable previously treated patients who did not undergo disease restaging with PET.

RESULTS

Twenty‐two patients (55%) had their treatment modified due to PET findings. PET was significantly superior to CT/MRI (sensitivity: 92% vs. 60%; AUC: 0.962 vs. 0.771;P< 0.0001) in identifying metastatic lesions. For individuals receiving primary surgery, a significantly better 2‐year overall survival rate was observed among study participants compared with patients who underwent disease restaging without PET (HR, 0.21 [95% confidence interval, 0.05–0.83];P= 0.020).

CONCLUSIONS

Dual‐phase FDG‐PET is superior to CT/MRI in the restaging of recurrent cervical carcinoma. Restaging with PET provides benefit by allowing the physician to offer optimal management of recurrent cervical carcinoma. Cancer 2004. © 2003 American Cancer Society.
Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high‐risk myelodysplastic syndrome undergoing induction chemotherapy
Authors: Mattiuzzi Gloria N. , Kantarjian Hagop , O'Brien Susan , Kontoyiannis Dimitrios P. , Giles Francis , Zhou Xian , Lim JoAnn , Bekele B. Nebiyou , Faderl Stefan , Cortes Jorge , Pierce Sherry , Leitz Gerhard J. , Raad Issam , Estey Elihu
Published: January 2004

BACKGROUND

Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high‐risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (I.V. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I).

METHODS

Patients with AML and high‐risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily.

RESULTS

One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with IV ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of IV ITRA was NCI Grade 3‐4 hyperbilirubinemia (6%).

CONCLUSIONS

Despite its theoretic advantages, the authors found no evidence that IV ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole. Cancer 2004. © 2003 American Cancer Society.
New agents in acute myeloid leukemia and other myeloid disorders
Authors: Ravandi Farhad , Kantarjian Hagop , Giles Francis , Cortes Jorge
Published: January 2004

Over the past several decades, improvements in chemotherapeutic agents and supportive care have resulted in significant progress in treating patients with acute myeloid leukemia (AML). More recently, advances in understanding the biology of AML have resulted in the identification of new therapeutic targets. The success of all‐trans‐retinoic acid in acute promyelocytic leukemia and of imatinib mesylate in chronic myeloid leukemia have demonstrated that targeted therapy may be more effective and less toxic when well defined targets are available. At the same time, understanding mechanisms of drug resistance and means to overcome them has led to modification of some of the existing cytotoxic agents. Rational design and conduct of clinical trials is necessary to ensure that the full potential of these new agents is realized. Cancer 2004. © 2003 American Cancer Society.
Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy
Authors: Mattiuzzi Gloria N. , Kantarjian Hagop , Faderl Stefan , Lim JoAnn , Kontoyiannis Dimitrios , Thomas Deborah , Wierda William , Raad Isaam , Garcia‐Manero Guillermo , Zhou Xian , Ferrajoli Alexandra , Bekele Nebiyou , Estey Elihu
Published: January 2004

BACKGROUND

The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high‐risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population.

METHODS

Newly diagnosed patients with AML or high‐risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L‐AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability.

RESULTS

The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L‐AmB (P = 0.95). Among 131 ABLC‐treated patients and 70 L‐AmB‐treated patients who ere assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC‐treated patients and in 4% of L‐AmB‐treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC‐treated and L‐AmB‐treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups.

CONCLUSIONS

ABLC and L‐AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high‐risk MDS who were undergoing induction chemotherapy. Cancer 2004. © 2003 American Cancer Society.
Noninflammatory breast carcinoma with skin involvement
Authors: Güth Uwe , Moch Holger , Herberich Linda , Holzgreve Wolfgang
Published: January 2004

BACKGROUND

According to the TNM Supplement, only breast carcinoma with macroscopic ‘classic’ skin changes (e.g., edema, peau d'orange, ulceration) should be placed in the T4 category; the classification of tumors with histologically proven skin involvement but no clinical skin changes or only discreet changes should be based on the size of the tumor (T1–3). To the authors' knowledge, no data supporting these recommendations have been reported to date.

METHODS

Seventy‐six patients with noninflammatory breast carcinoma and histologically proven skin involvement were classified based on the degree of their skin involvement. Fifty patients (66%) presented with clinically obvious skin involvement (Group A), and 26 patients (34%) had breast carcinoma with histologically proven skin involvement but without clinical skin changes (Group B). Reclassification was undertaken to assess the malignant potential of tumors independent of the morphologic parameter ‘skin involvement’.

RESULTS

Patients in Group A presented significantly more frequently with extensive disease at regional or distant sites (Stages IIIC and IV; P = 0.009). The clinical outcome of patients in Group B was significantly more favorable (P = 0.0003). The adjusted 3‐year survival rates in Group A and Group B were 46.7% and 92.3%, respectively, and the 5‐year rates were 38.1% and 83.7%, respectively. Patients in Group B were found to have significantly better (P = 0.036) distant recurrence–free survival (DRFS) rates. The DRFS rate at 3 years was 63.6% in Group A, compared with 91.7% in Group B, and the DRFS rate at 5 years was 56.9% in Group A, compared with 82.0% in Group B. Using a cutoff point of tumor size = 3 cm, similar findings were made.

CONCLUSIONS

Both study groups exhibited distinct clinical entities with significant differences in clinical course and prognosis. Cases with histologic skin involvement, relative to those with classic skin involvement, were found to have much less malignant potential. This corroborates the recommendation that cases with only histologic skin involvement should not be placed in the T4 category of the TNM classification. Cancer 2004. © 2003 American Cancer Society.
Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma
Authors: Esteva Francisco J. , Sahin Aysegul A. , Smith Terry L. , Yang Ying , Pusztai Lajos , Nahta Rita , Buchholz Thomas A. , Buzdar Aman U. , Hortobagyi Gabriel N. , Bacus Sarah S.
Published: January 2004

BACKGROUND

Chemotherapy‐induced p38 mitogen‐activated protein kinase (MAPK) phosphorylation reportedly leads to increased apoptosis in breast carcinoma cells. The goals of the current study were to assess the incidence of activated phosphorylated p38 MAPK (P‐p38) expression in invasive breast carcinoma, correlate expression of P‐p38 MAPK with HER‐2, and estimate the prognostic value of this marker in patients with lymph node‐positive breast carcinoma treated with adjuvant chemotherapy.

METHODS

P‐p38, HER‐2, and Ki‐67 were measured using immunohistochemistry (peroxidase method) in 96 patients with lymph node‐positive breast carcinoma treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. All markers were measured in the primary tumors, before the initiation of adjuvant chemotherapy. The median follow‐up period was 11 years after initial cancer surgery. P‐p38 MAPK expression was scored visually and quantified using an image analyzer.

RESULTS

The rate of P‐p38 MAPK expression ranged from 19–24%, depending on the scoring system used. There was a trend toward shorter progression‐free survival (PFS) for patients whose tumors expressed high levels of P‐p38 MAPK, although the difference was not statistically significant (P = 0.39). PFS was shorter in patients whose tumors overexpressed P‐p38 MAPK and had a high level of Ki‐67 (P = 0.04). In HER‐2–negative patients, P‐p38 MAPK overexpression was associated with a shorter PFS (P = 0.05).

CONCLUSIONS

P38 MAPK phosphorylation occurred in 20% of primary breast carcinomas and may be associated with poor outcome in patients with lymph node‐positive breast carcinoma. Further studies are needed to define the interaction between P‐p38 MAPK and HER‐2 expression in breast carcinoma. Cancer 2004. © 2003 American Cancer Society.
A potential role for perioperative hepatic arterial infusion chemotherapy?
Authors: Espat N. Joseph
Published: January 2004

The liver is the most common site of distant failure and cause of disease‐related mortality in patients with advanced colon carcinoma. In the study by Sadahiro et al., a randomized controlled study evaluated the effects of prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with TNM Stage II or Stage III colon carcinoma.

See also pages 590–7.
Survival experience of black patients and white patients with bladder carcinoma
Authors: Prout George R. , Wesley Margaret N. , McCarron Peter G. , Chen Vivien W. , Greenberg Raymond S. , Mayberry Robert M. , Edwards Brenda K.
Published: January 2004

BACKGROUND

Blacks are less likely than whites to develop bladder carcinoma. However, once they are diagnosed, black patients experience poorer survival. The authors investigated which factors were related to survival differences in black patients and white patients with bladder carcinoma stratified by extent of disease.

METHODS

A population‐based cohort of black patients with bladder carcinoma and a random sample of frequency‐matched white patients with bladder carcinoma, stratified by age and gender, were identified through cancer registry systems in Atlanta, New Orleans, and San Francisco/Oakland. Patients had no previous cancer history and were ages 20–79 years at the time they were diagnosed with bladder carcinoma in 1985–1987. Medical records were reviewed at initial diagnosis, and 77% of patients were interviewed. Tumor grade, T classification, and other variables, including age, socioeconomic position, symptom duration, smoking history, and comorbidities, were recorded. Survival of black patients and white patients by extent of disease was modeled using Cox regression analysis.

RESULTS

A greater proportion of black patients had histologic types of tumors that were associated with poorer survival. Among those with pure urothelial carcinoma, black patients had greater extent of disease at the time of diagnosis. Within specific extent‐of‐disease categories, there was some evidence of poorer survival for black patients with T2 tumors and strong evidence of poorer survival among those with T3 tumors compared with white patients. Black patients with muscle‐invasive carcinoma who died within 6 months of diagnosis tended to present with life‐threatening symptoms. Black patients and white patients did not differ with respect to diagnostic tests performed or therapy given.

CONCLUSIONS

Black patients with bladder carcinoma had poorer survival due to greater extent of disease at diagnosis and a higher proportion of more aggressive histologies compared with white patients. Within urothelial carcinomas, by extent of disease (clinical/pathologic stage) these black/white survival differences were limited to patients with muscle invasion (T2 and T3 tumors). Cancer 2004. Published 2003 by the American Cancer Society.