bluuebunny/crossref_metadata_2025 huggingface dataset:
Atypical Endometrial Hyperplasia: Grounds for Possible Misdiagnosis of Endometrial Adenocarcinoma
Authors: Valenzuela Pedro , Sanz J. Miguel , Keller Jerry
Published: October 2003

Objective: The diagnoses of atypical hyperplasia and well-differentiated adenocarcinoma imply totally different approaches because of clinical and patient-oriented ramifications, especially when morphological differences are not entirely conclusive. The purpose of this study was to examine the relationship between the diagnosis of atypical hyperplasia during curettage or endometrial biopsy and the definitive histological findings from hysterectomy material. Study Design: 23 patients were found fit for the current study and subsequently their clinical histories were reviewed for relevant clinical data, histopathological profiling and type of therapeutic interventions. Results: Adenocarcinoma was observed in 12 (52.17%) of 23 hysterectomy cases. The hyperplasia was found in 10 (43.47%) cases, although 4 of them lacked atypia and 1 case proved to be hyperplasia-free. Conclusion: Hysterectomy was prescribed as the next step in the diagnosis of atypical endometrial hyperplasia. Other wait-and-see approaches could have easily forfeited the chances of providing an adequate treatment for an operable and curable cancer in approximately half of the studied cases.
Hyper-Vascular Change and Formation of Advanced Glycation Endproducts in the Peritoneum Caused by Methylglyoxal and the Effect of an Anti-Oxidant, Sodium Sulfite
Authors: Nakayama Masaaki , Sakai Asahi , Numata Miwako , Hosoya Tatsuo
Published: October 2003

Objective: Methylglyoxal (MGO) in a heat-sterilized conventional PD solution may damage peritoneal cells directly and/or indirectly by producing advanced glycation endproducts (AGEs). This study was conducted to (a) examine the acute effect of MGO on the peritoneum (including AGE formation) and (b) study the possible AGE suppressive effect of an anti-oxidant, sodium sulfite. Method: (1) Human serum albumin (HAS) was continuously incubated with MGO (50 mM) at 37°C for as long as 14 days and the fluorescence intensity (FI) was determined (em. 440, ex. 370). (2) Three types of test solutions – (i) saline; (ii) MGO (20 mM), and (iii) MGO with sodium sulfite (30 mM) – were administered intraperitoneally to 8-week-old rats once a day for 5 consecutive days. The parietal peritoneum was examined macroscopically on the 6th day for immunostaining of anti-AGE antibodies. Result: (1) An increase in FI of HSA was observed as a function of the incubation period in the MGO solution. (2) Prominent hypervascularity and intense immunostaining of anti-AGE Ab were noted in MGO-treated rats, whereas the macroscopic alterations were suppressed in the rats that had been treated with sodium sulfite. Conclusion: MGO-induced hypervascularity and AGE formation in the peritoneum, as well as macroscopic alterations were suppressed by sodium sulfite. This may indicate that there is a risk of MGO causing a peritoneal injury and that the therapeutic potential of an anti-oxidant for this type of injury may exist.
Psychosis and Antipsychotic Medications in Alzheimer’s Disease: Clinical Management and Research Perspectives
Authors: Sultzer David L.
Published: October 2003

Psychosis is common in patients with Alzheimer’s disease (AD) and contributes substantially to patient morbidity and caregiver distress. Antipsychotic medications are used to treat psychosis and other psychiatric or behavioral symptoms in AD, although optimal treatment guidelines have been elusive. Choosing the most advantageous medication for an individual patient is challenging. This article provides an overview of clinical management principles and medication treatment strategies for patients with AD and psychosis. Effects of individual medications are also described. Medications in the conventional neuroleptic, atypical antipsychotic, cholinesterase inhibitor, and serotonergic classes have been shown to ameliorate psychosis and behavioral symptoms in patients with AD, although the evidence is not conclusive for many medications. Side effects vary substantially across medication classes and modestly among individual patients. Improvement in agitation, aggression, or other behaviors with antipsychotic medication treatment may not depend on distinct antipsychotic effects. In contrast, there is preliminary evidence that delusions and hallucinations may respond to treatment with medications outside the antipsychotic class. Many important clinical questions warrant further research study. In particular, studies to compare how individual symptoms respond to different medications, and to examine how to best manage overlapping symptoms or incomplete treatment response are needed.
Undifferentiated Carcinoma with Osteoclast-Like Multinucleated Giant Cells Arising in an Ovarian Mature Cystic Teratoma
Authors: Kita Naoki , Satoh Toyomi , Onuki-Tanabe Mamiko , Ainoya Yoko , Yamada Naoki , Oki Akinori , Tsunoda Hajime , Yoshikawa Hiroyuki
Published: October 2003

Malignant transformation is an unusual complication of mature cystic teratomas. Squamous cell carcinomas and adenocarcinomas are predominant among these malignant tumors. We present a 70-year-old Japanese woman with a giant ovarian tumor (30 × 23 × 9 cm) and multiple peritoneal dissemination. The huge tumor was filled with necrotic and fatty tissue and coagula accompanied with hair balls histologically diagnosed as undifferentiated carcinoma with multinucleated giant cells arising in an ovarian mature cystic teratoma. The residual disseminated tumors grew very rapidly and occupied the whole abdominal cavity again 3 weeks after the surgery. The patient died 5 weeks after the operation.
CD31 Regulates Direction and Rate of Neutrophil Migration over and under Endothelial Cells
Authors: Luu N. Thin , Rainger G. Ed , Buckley Christopher D. , Nash Gerard B.
Published: October 2003

Mechanisms guiding migration of neutrophils through endothelium are poorly understood. We showed previously that CD31-CD31 binding acted as an ‘accelerator’ for neutrophils migrating on platelets, while neutrophil αvβ3-integrin acted as a sensor to align migration with the direction of imposed flow. Here, we perfused neutrophils over human umbilical vein endothelial cells (HUVEC) treated with tumour necrosis factor-α, and characterised the kinetics of migration over, through and underneath the HUVEC. Before penetrating the monolayer, activated neutrophils migrated relatively slowly over the surface (∼6 µm/min), preferentially in the direction of flow. Once transmigrated, neutrophils moved more rapidly (∼14 µm/min) without preferred direction. Treatment of HUVEC and/or neutrophils with function-blocking antibodies against CD31 reduced directionality but not velocity of migration on top of HUVEC, and reduced velocity of migration underneath the monolayer. If neutrophils were pre-activated with formyl peptide, they did not migrate through the HUVEC, but migrated with increased velocity and directionality on top. Under these circumstances, both velocity and directionality were reduced by blocking CD31. αvβ3-integrin did not regulate migration under any conditions. We conclude that CD31-CD31 bonds act as robust sensors which can guide neutrophil migration, and also modify its velocity. Thus mechanical and adhesive signals can regulate neutrophil migration driven by locally-acting chemotactic agents.
Carvedilol, an Antihypertensive Drug with Antioxidant Properties, Protects against Glycerol-Induced Acute Renal Failure
Authors: Singh Devinder , Chander Vikas , Chopra Kanwaljit
Published: October 2003

Background/Aims: The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves, among other causes, ischaemia, vascular congestion and reactive oxygen metabolites. The aim of this study was to investigate the role of carvedilol, an antihypertensive drug with antioxidative potential, in glycerol-induced acute renal failure in rats. Methods: Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.) and group 3 was given glycerol plus carvedilol (3 mg/kg, i.p.). Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and enzymatic activity of catalase, glutathione reductase and superoxide dismutase. Results: Glycerol treatment resulted in marked renal oxidative stress and significantly deranged renal functions. Both of these factors were significantly improved by carvedilol treatment. Carvedilol, by its interaction with Fenton reaction chemistry and radical scavenging activity, protected the kidney against the oxidative stress and resultant renal dysfunction produced by glycerol. Conclusion: Based on these results, this study indicates the protective effect of carvedilol in this rhabdomyolysis-mimicking model.
Family-Related Allocentrism and HIV Risk Behavior in Central and Eastern Europe
Authors: Realo Anu , Goodwin Robin
Published: October 2003

The recent rapid spread of HIV infection in Eastern Europe raises important questions about the role of individual attitudes in the prediction and control of this epidemic. This article examines the relationship of family-related allocentrism (familism) to HIV risk behavior and perceived vulnerability to HIV/AIDS across five Central and Eastern European countries. Respondents completed questionnaires measuring allocentric attitudes, giving information about sexual activity during the previous 6 months and perceived vulnerability to HIV infection. As predicted, those scoring high on familism were more conservative in their sexual behavior, with this finding largely consistent across all five cultures and two different occupation groups. An analysis of the relationship between familism and perceived vulnerability to HIV/AIDS revealed a more complex pattern of findings that highlights the need to account for the individual's previous HIV risk behavior when trying to predict perceived vulnerability to HIV/AIDS from personality attributes and attitudes.
Can branding add value to business information?
Authors: Stilliard Sara
Published: October 2003

In view of the success consumer brands, which clearly work for manufacturers and service providers selling to businesses: it is argued that brands should also work for internal service providers who increasingly have to compete with external suppliers as the trend towards outsourcing increases. The main characteristics of brands and branding are discussed in terms of its mixture of tangible and intangible values and the projection of image. It also discusses the fact that the traditional low-key emphasis on technical expertise or in-house capabilities may no longer be a guarantee of survival for internal providers who fail to offer added value to their customers. This is in terms of: understanding of the industry; time saving; customized presentation formats; interpretation of information; original research; advanced use of technology; and wider selection of sources. Useful advice is given on the approaches to use, when planning branding strategies for business information departments, in order to project differentiation, quality, value and impact.
Managing information overload
Authors: Parnell Nick
Published: October 2003

The degree to which companies are failing in their attempts to manage the increasing amount of information becoming available to them is discussed in light of a study, undertaken in 1999 by Autonomy Corporation and based on interviews with over 200 managing directors, managers and heads of Information technology (IT) departments in some of the UK’s leading companies across the financial, media and publishing, legal and retail sectors. Many of the companies that turned to technology for a solution to their problems found that the technology exacerbated the problems they already faced. The ways in which information has become a problem for so many organizations are considered, including: the corporate perspective; employee contributions to information overload; ways in which businesses make room in their organization for information overload; electronic mail that no-one wants to throw away; the high price both of searching for information and for not finding information. Concludes by outlining the grounds that exist for optimism for improvement in the future: notably through the use of advanced pattern matching technology.
XML: Solution for the Future
Authors: Beesley Karen
Published: October 2003

An explanation of the function and potential of XML (Extensible Markup Language) in the creation of electronic documents within organizations. It is shown how, where Hypertext Markup Language (HTML) is the standard means of presenting and laying out browser-delivered content, XML allows users to tag that content, effectively turning every document into a database. Particular attention is drawn to the fact that the adoption of XML will necessitate the users’ commitment to a more detailed understanding of business processes and to the introduction of a degree of structure to both documents and processes. The particular strength of XML in helping companies to integrate their shop window with their backend business processes is noted. Other applications of XML consist of helping companies to gear their document practices to supply chain automation systems and the implementation of electronic commerce (E-commerce) and electronic business (E-business) strategies. It is concluded that all these will necessitate a closer look at how an organization does business and focus on the establishment of basic document management policies, particularly policies for electronic document management, as a crucial step in this process.
The value of qualifications in the modern information world
Authors: Amos Tamsin
Published: October 2003

The value of qualifications for information professionals operating in the modern information world is considered, pointing out that, with the growth in interest in knowledge management, skills such as thesaurus construction, abstracting and indexing have actually come back into vogue. The fact that the information world is developing rapidly and attracting increasing numbers of people, many of whom have had no formal information training is used as the focus for discussion of the issues involved. Since the relevance and value of a library school qualification have been brought into question an attempt is made to establish the potential value of this qualification and explain why qualified professionals are the most eligible candidates to continue the maturation of the information profession in the twenty-first century. It is concluded that the information profession, like most professions, has room for a whole spectrum of people with different qualifications and skills. However, the distinguishing factor is the necessity to recognize librarianship and information work as a profession.
The internal information audit: conducting the audit and implementing the results
Authors: Pantry Sheila , Griffiths Peter
Published: October 2003

Follows on from an earlier article (Business Information Review, 17 (4) December 2000, 205-214) which emphasized the importance of information auditing in building the foundations of an entrepreneurial library and information service for the corporate organization. Continues in this vein by examining in more detail the mechanisms involved in the information audit, which allows the information provider or information manager to gain a clear understanding of information requirements and use in the whole of the organization. The main elements of the audit comprise: identifying the organization’s real information needs; identifying who needs the information; understanding why people in the organization go elsewhere for information; and finding out where the customers are in the organization. This will result in a set of documents and plans allowing the library and information service to provide the information when it is needed and in the necessary format. Sets out in detail the major factors to be included in information audits, including: defining information resources and services; determining what the organization’s real information needs are; applying the results of the audit; budgets/finance; and evaluation. Concludes that the final results of the analysis of the information audit and related marketing activities should provide a unique understanding of the organization and the behaviour of the information users and information seekers in the organization.
Business newsletters
Authors: Tagg Lawrence
Published: October 2003

Analyses business newsletters in the UK. Discusses the nature of the medium, bibliographical control, markets, costs and the major suppliers.
Document delivery in management information: a state of the art survey
Authors: Harrison Paul
Published: October 2003

Surveys the current state of document delivery, reviewing the service providers.
Industrial market research: off-the-shelf report publishers
Authors: Gregg Paul
Published: October 2003

Identifies publishers of industrial market research in the UK.
Digital communities of interest
Authors: Ormerod Paul
Published: October 2003

Discusses the importance of digital communities (communities of interest) for the library and information science (LIS) profession, considers some of their evolutionary and ecological aspects and identifies ways of building and maintaining communities of interest. Identifies the rapid growth of the Internet and WWW, coupled with the globalization of business, as the key elements in the emergence of digital communities. Considers ways of identifying and establishing potential communities of interest and how they can be cultivated and maintained within a digital infrastructure. These include: understand the community’s needs, the way its members work and their underlying values; and establishing and sharing a common purpose. Content identification, capture and engineering and contextual design are key issues to be addressed. Communities of interest will only prosper if they share an economic model which makes sense. Sponsors and users have to perceive value that rewards their cost of involvement and it is often a major challenge to understand the economic impact of a networked community. Key skill-sets required for networking and digital communities include: market research and analysis; leadership, communication and persuasiveness; systems thinking in digital information product and service development; analytical and synthetic skills; networking technology skills; marketing skills; and customer management expertise.
Shaping the bright young graduate: a personal view
Authors: Cohen Manny
Published: October 2003

The Managing Director of The RM Group, the largest independent company providing online business information and other information services to the business community, offers his views on the employability of young people emerging from university and the quality of training provided to ensure that they can cope with the requirements of modern business information. Concludes that students graduate with a lack of understanding of the commercial world and the practical restraints that this imposes on online and other information gathering techniques. The vital importance of information to company decision-making means that freshly graduated information professionals require extensive monitoring with 12–18 months needed for a graduate to have a full grasp of the research job and perhaps three years to understand the information industry in any depth. Outlines the importance of the Internet and the Web to business information providers. Concludes that it is up to the information industry to take fresh graduates, shape them, make them interested and retain not just the brightest but also those that are hardworking and committed.
Restraining Trend in Plan Payments: Disease Management of Six Conditions May be the Key
Authors: Kelley Bruce C.
Published: October 2003

Employers can control costs through effective disease management programs aimed at chronic conditions. Large employers can significantly reduce overall medical plan expenses by carefully selecting and implementing effective disease management programs. This article details how six chronic conditions, such as asthma and diabetes, drive nearly half of large employers' plan payments, but less than 5% of plan participants have significant expenses for those six conditions. In addition, these 5% of employees account for more than one quarter of total plan expenses. It appears that disease management could affect more than one quarter of total plan expenses. By identifying the conditions that are driving the greatest costs, employers can offer disease management programs to affected employees, which will not only drive down costs but might also improve patient care outcomes.
A Method for the Evaluation of Primary Health Care Units' Practice in the Promotion, Protection, and Support of Breastfeeding: Results from the State of Rio de Janeiro, Brazil
Authors: de Oliveira Maria Inês Couto , Camacho Luiz Antonio Bastos , Tedstone Alison E.
Published: October 2003

A method to assess the effectiveness of primary health care (PHC) units in enabling mothers to breastfeed was developed from the tool used for accreditation of baby-friendly hospitals. A 10-step scoring system assessed the extent to which procedures known to be effective at extending breastfeeding duration were applied within PHC units. Using this method, 13 PHC units showed a fair performance, whereas 11 performed poorly in the state of Rio de Janeiro. More babies younger than 6 months were being exclusively breastfed in fair performance than in poor performance units (38.6% vs 23.6%, respectively, P < .001). Twice as many pregnant women and mothers in fair performance units (61.9%) were satisfied with the support provided for breastfeeding than in poor performance units (31.4%). The differences were not explained by hospital care or working status of the women. The association found between structure, process, and outcomes support the validity of the method. J Hum Lact. 19(4):365-373.
Brain injury in children with sickle cell disease: Prevalence and etiology
Authors: Steen R. Grant , Xiong Xiaoping , Langston James W. , Helton Kathleen J.
Published: October 2003

Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p< 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p< 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.
CCR1 is an early and specific marker of Alzheimer's disease
Authors: Halks‐Miller Meredith , Schroeder Miriam L. , Haroutunian Vahram , Moenning Ursula , Rossi Michael , Achim Cristian , Purohit Dushyant , Mahmoudi Mithra , Horuk Richard
Published: October 2003

Chemokines are a diverse group of small proteins that effect cell signaling by binding to G‐protein–coupled, seven‐trans‐membrane receptors. Our group had found previously that the chemokine receptor CCR1 was present in neurons and dystrophic processes in a small sample of Alzheimer's disease cases. This expanded immunohistochemical study shows that the number of CCR1‐positive plaque‐like structures in the hippocampus and entorhinal cortex is highly correlated to dementia state as measured by the clinical dementia rating score. CCR1 immunoreactivity is found in dystrophic, neurofilament‐positive, synaptophysin‐negative neurites that are associated with senile plaques containing amyloid beta peptides of the 1‐42 species (Aβ42). CCR1 was not, however, associated with diffuse deposits of Aβ42. There was limited expression of CCR1 in neurofibrillary tangle‐bearing neuritic processes. Astrocytes and microglia were typically negative for CCR1. Human brains from age‐matched, nondemented individuals rarely displayed either CCR1 or Aβ42 immunoreactivity. Seven other types of dementing neurodegenerative diseases were examined, and all failed to demonstrate CCR1 immunopositivity unless Aβ42‐positive plaques were also present. Thus, neuronal CCR1 is not a generalized marker of neurodegeneration. Rather, it appears to be part of the neuroimmune response to Aβ42‐positive neuritic plaques.
Dually infected (HSV‐1/VZV) single neurons in human trigeminal ganglia
Authors: Theil Diethilde , Paripovic Igor , Derfuss Tobias , Herberger Simone , Strupp Michael , Arbusow Viktor , Brandt Thomas
Published: October 2003

Human trigeminal ganglia were tested by double fluorescence in situ hybridization for the presence and distribution of herpes simplex virus type 1 (HSV‐1) and varicella‐zoster virus (VZV) latency. Latency transcripts of both viruses were detected in common areas within the ganglia. Also, a few single neurons were shown to harbor HSV‐1 and VZV together. Ann Neurol 2003;54:678–681
Protective role of tuftsin fragment 1‐3 in an animal model of intracerebral hemorrhage
Authors: Wang Jian , Rogove Andrew D. , Tsirka Anna E. , Tsirka Stella E.
Published: October 2003

Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Tissue plasminogen activator (tPA), a fibrinolytic serine protease, is routinely given for the treatment of stroke. However, tPA also can promote neuronal death, suggesting that caution should be exercised when using it. Furthermore, tPA upon brain injury mediates microglial activation and modulates neuronal survival. To investigate the role of tPA and microglia during brain hemorrhage, we induced experimentally ICH by intracerebral injection of collagenase. Seven days after the introduction of ICH, it persisted in tPA‐deficient (tPA−/−) mice but is drastically reduced in size in wild‐type mice. Three weeks after ICH, there are still red blood cells in tPA−/− but not in wild‐type animals. Activated microglia persist around the injury site. When microglial activation is inhibited by tuftsin fragment 1‐3 macrophage/microglial inhibitory factor (MIF), the stroke injury volume is significantly reduced, and the neurobehavioral deficits exhibited by the mice are improved. Our results suggest that endogenous tPA assists in the clearance of intracerebral hemorrhage, presumably by affecting microglial activation, and MIF could be a valuable neuroprotective agent for the treatment of ICH. Ann Neurol 2003;54:655–664
The Dutch‐Belted rabbit: An alternative breed for developmental toxicity testing
Authors: Spence Stan
Published: October 2003

BACKGROUND: Historical control data play a crucial role in the interpretation of observations made from developmental and reproductive toxicity studies. METHODS: In our effort to develop the Dutch‐Belted rabbit as an alternative breed of rabbit for testing of small molecule pharmaceuticals, data collected from 236 untreated pregnant Dutch Belted rabbits are summarized and compared to data collected from 350 untreated pregnant New Zealand White Rabbits. RESULTS: The data presented include mean maternal body weight and food consumption values, mean maternal hematological and serum biochemical values collected during gestation, maternal reproductive (laparotomy) parameters collected at cesarean section, and incidences of spontaneous fetal morphological alterations collected during 1999–2002. Due to their smaller size the use of this breed of rabbit would require approximately 40% less drug than studies conducted with New Zealand White rabbits. Because the Dutch‐Belted rabbit is pigmented this breed also offers the ability to test the potential effects of various xenobiotics on melanocyte development and to evaluate the potential sequela of drugs that have a propensity to bind melanin in the skin and pigmented retinal epithelium. CONCLUSIONS: Based on these data, the Dutch‐Belted rabbit is considered to be a practical alternative to use of the New Zealand White rabbit for these types of studies. Birth Defects Res B 68:439–448, 2003. © 2003 Wiley‐Liss, Inc.
An IQGAP‐like protein is involved in actin assembly together with Cdc42 in the sea urchin egg
Authors: Nishimura Yukako , Mabuchi Issei
Published: October 2003

We isolated a gene homologous to human cdc42 (ucdc42) from a sea urchin cDNA library. The GTPγS‐bound UCdc42 induced actin assembly in sea urchin egg extract. Proteins that are involved in this actin assembly system were searched using UCdc42‐bound agarose beads. A 180‐kDa protein (p180), which showed a homology to human IQGAPs, bound to the GTPγS‐UCdc42 beads. Immunodepletion of p180 from the sea urchin egg extract abolished this actin assembly on the UCdc42 beads. Immunofluorescent localization of p180 was similar to that of the actin cytoskeleton in the egg cortex and it was concentrated in the cleavage furrow during cytokinesis. A possible role of p180 in actin assembly is discussed. Cell Motil. Cytoskeleton 56:207–218, 2003. © 2003 Wiley‐Liss, Inc.
A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma
Authors: Gitlitz Barbara J. , Baker Carole , Chapman Yvonne , Allen Heather J. , Bosserman Linda D. , Patel Ravi , Sanchez James D. , Shapiro Richard M. , Figlin Robert A.
Published: October 2003

BACKGROUND

The objectives of the current study were to evaluate the safety and efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or ≥ N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the urothelial tract.

METHODS

A total of 27 patients were enrolled in the current multisite study, which was performed within the University of California‐Los Angeles Community Oncology Research Network. The first 10 patients in the study received 800 mg/m2 of gemcitabine intravenously on Days 1, 8, and 15 of a 28‐day treatment cycle. In addition, on Day 1, the first 10 patients received 80 mg/m2 of docetaxel intravenously after completion of the gemcitabine infusion. Because of dose‐limiting toxicity (neutropenia), the initial dose of docetaxel was reduced to 60 mg/m2 for the remaining patients who entered the study (n = 17 patients).

RESULTS

Neutropenia was the most common adverse event that occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at the Grade 4 toxicity level. Twenty‐five of 27 patients (92.6%) completed more than 1 cycle of combination therapy and were evaluated for antitumor responses. The frequency of objective clinical responses was 33.3% (9 of 27 patients). Complete responses to therapy were observed in 2 of 27 patients (7.4%), and partial responses were observed in 7 of 27 patients (25.9%). The median duration of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients (14.8%) remained alive at the time of the current data analysis.

CONCLUSIONS

The results of the current study suggested that combination therapy with gemcitabine and docetaxel was an effective treatment for patients with unresectable (Stage T4 or ≥ N1) metastatic or locally advanced TCC of the urothelial tract. Gemcitabine plus docetaxel appeared to be tolerated well, and treatment‐related toxicities were limited to hematologic toxicities. Because cisplatin‐containing regimens are contraindicated for patients with impaired renal function, the gemcitabine plus docetaxel combination may prove to be an effective and well tolerated treatment option for these patients. Cancer 2003. © 2003 American Cancer Society.
A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma
Authors: Talbot Susan M. , Keohan Mary Louise , Hesdorffer Mary , Orrico Russell , Bagiella Emilia , Troxel Andrea B. , Taub Robert N.
Published: October 2003

BACKGROUND

The objective of this study was to assess the efficacy and toxicity of the imidazotetrazine derivative temozolomide for patients with unresectable or metastatic soft tissue sarcoma.

METHODS

Twenty‐five of 26 patients were eligible and assessable for toxicity and response. Temozolomide was administered twice daily on a 12‐hour schedule for 5 days as an oral bolus dose of 200 mg/m2 followed by 9 doses of 90 mg/m2 every 4 weeks.

RESULTS

There were 2 partial responses, 2 mixed responses, and 3 patients with stable disease that lasted > 6 months, for an overall objective response rate of 8%. At a median follow‐up of 13.2 months, the median progression‐free survival and the median overall survival were 2.0 months (95% confidence interval [95% CI], 1.7–2.3) and 13.2 months (95% CI, 4.7–31.1), respectively. All responding patients had leiomyosarcoma of uterine or nonuterine origin; and, in a subset analysis of these patients, the objective response rate was 18% (2 of 11 patients), with disease stabilization occurring in 3 of 11 patients (27%). For this subgroup, at a median follow‐up of 24.4 months, the median progression‐free survival and the median overall survival were 3.9 months (95% CI, 1.9–21.9) and 30.8 months (lower‐bound 95% CI, 7.8), respectively. There were no treatment‐related deaths or National Cancer Institute Grade 4 toxicities. Grade 3 toxicities included nausea, anemia, fatigue, elevated alkaline phosphatase levels and nonneutropenic fever (1 patient each).

CONCLUSIONS

Temozolomide at the dose schedule employed in the current study was tolerated well and had modest activity against previously treated unresectable or metastatic leiomyosarcoma of both uterine and nonuterine origin. Cancer 2003. © 2003 American Cancer Society.
Vinblastine and estramustine phosphate in metastatic renal cell carcinoma
Authors: Haas Naomi B. , Giantonio Bruce J. , Litwin Samuel , Minniti Carl J. , Fox Stephen , Yeslow Gwen , Reilly Robert , Nahum Kenneth , Greenberg Richard , Halbherr Theresa , Hudes Gary R.
Published: October 2003

BACKGROUND

It is well known that metastatic renal cell carcinoma (RCC) exhibits constitutive resistance to chemotherapeutic agents. Antimicrotubule agents such as vinblastine are associated with low but reproducible response rates (approximately 12%) in patients with RCC. Estramustine has been shown to potentiate the antimicrotubule effects of vinblastine. The authors sought to increase the activity of vinblastine in RCC through the addition of estramustine.

METHODS

Twenty‐one patients with metastatic RCC not previously treated with chemotherapy received oral estramustine phosphate, 600 mg/m2, on Days 1, 2, and 3 weekly for 6 weeks, and intravenous vinblastine, 4 mg/m2 on Day 2 weekly for 6 weeks, repeated every 8 weeks. Twenty‐one patients received 31 cycles of therapy.

RESULTS

Two patients experienced Grade 3 and 4 hematologic toxicity, and three patients had Grade 3 nonhematologic toxicity consisting of neurologic toxicity, hepatic toxicity, or angioneurotic edema. One patient had a partial response with decreased liver metastases for 48 weeks; 9 patients had stable disease, for a median duration of 14 weeks (range, 11–31 weeks); and 11 patients demonstrated disease progression. The median overall time to progression was 8 weeks and the median overall survival period was 24 weeks.

CONCLUSIONS

Although well tolerated, the combination of oral estramustine phosphate with vinblastine administered on this schedule had minimal activity in patients with metastatic RCC. Cancer 2003. © 2003 American Cancer Society.
Metastasis of esophageal carcinoma to the brain
Authors: Weinberg Jeffrey S. , Suki Dima , Hanbali Fadi , Cohen Zvi R. , Lenzi Renato , Sawaya Raymond
Published: October 2003

BACKGROUND

Esophageal carcinoma rarely metastasizes to the brain. The objectives of the current study were to assess the frequency of brain metastasis from an esophageal primary tumor, to determine correlates of survival, and to describe treatment modalities and their outcomes.

METHODS

Between June, 1993 and July, 2001, 1588 patients with a primary esophageal carcinoma registered at The University of Texas M. D. Anderson Cancer Center; of those, 27 patients (1.7%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis.

RESULTS

The median age at the time patients were diagnosed with brain metastasis was 62 years. Tumor histologies were adenocarcinoma in 22 patients (82%), unclassified carcinoma in 3 patients (11%), and squamous cell carcinoma in 2 patients (7%). Twenty patients (74%) experienced symptoms related to the brain metastasis. The metastases were treated with whole‐brain radiation therapy (WBRT) alone in 15 patients (56%), and 10 patients (37%) underwent surgical resection, 4 of whom (15%) also received WBRT. Two patients (7%) underwent stereotactic radiosurgery. The median survival for the entire cohort after diagnosis of the primary tumor was 12.6 months (95% confidence interval [CI], 2.17–22.5 months), and the median survival after the diagnosis of brain metastasis was 3.8 months (95% CI, 1.1–6.5 months). The longest median survival observed after the diagnosis of brain metastasis (9.6 months) occurred in patients with a single brain lesion who underwent resection and received WBRT. There was a trend toward worse survival in patients with liver metastases and patients in recursive partitioning analysis (RPA) Class II–III versus RPA Class I (P= 0.10 for both; multivariate Cox proportional hazards model analysis).

CONCLUSIONS

Approximately 2% of patients with esophageal carcinoma had a diagnosis of brain metastasis. Improved outcome was associated with single brain lesions in patients who underwent surgery and received WBRT. Known liver metastasis and higher RPA scores were associated with a poorer survival trend. Cancer 2003. © 2003 American Cancer Society.
Cancer‐related fatigue
Authors: Stasi Roberto , Abriani Luca , Beccaglia Patrizia , Terzoli Edmondo , Amadori Sergio
Published: October 2003

BACKGROUND

Although fatigue is one of the most common complaints of patients with cancer, it went unrecognized or overlooked for many years, until clinicians achieved better control over the more acute symptoms of nausea, emesis, and pain. A number of treatment‐related and disease‐related factors may contribute to the development of fatigue, but its physiologic basis remains poorly understood, and many proposed interventions have not been studied systematically. The lack of a standard of care for the assessment or treatment of fatigue in patients with cancer has limited research in this field. A critical appraisal of these issues is presented in this review.

METHODS

The published literature was reviewed for definition, prevalence, causes, and means of managing cancer‐related fatigue (CRF).

RESULTS

Fatigue was reportedly present at the time of diagnosis in approximately 50–75% of cancer patients. The prevalence of CRF increased to 80–96% in patients undergoing chemotherapy and to 60–93% in patients receiving radiotherapy. Two tested interventions that showed consistent effects to alleviate CRF were treatment of cancer‐related anemia with erythropoietin agents (recombinant human erythropoietin and darbepotin α) and aerobic exercise.

CONCLUSIONS

Several lines of research are needed to bridge the specific gaps in the current knowledge of CRF. These involve the pathophysiology of the symptom, the validation of diagnostic criteria, and specific therapeutic interventions. Current practice guidelines are based on a combination of research and expert clinical judgment and should be used to guide care with the expectation that they will evolve to incorporate the results of studies currently underway. Cancer 2003. © 2003 American Cancer Society.
Rieger‐Christ KM, Mourtzinos A, Lee PJ, et al. Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection. Cancer. (2003) 98(4):737–44.
Authors: Rieger‐Christ Kimberly M , Medina Arthur , Lee Peter J
Published: October 2003

The original article to which this Erratum refers was published in Cancer (2003) 98(4) 737–44
Cripto‐1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF‐7 breast cancer cells
Authors: Normanno Nicola , Luca Antonella De , Bianco Caterina , Maiello Monica R. , Carriero Maria V. , Rehman Aasia , Wechselberger Christian , Arra Claudio , Strizzi Luigi , Sanicola Michele , Salomon David S.
Published: October 2003

Cripto‐1 (CR‐1) is an epidermal growth factor (EGF)‐CFC protein that has been shown to signal through nodal/Alk‐4, PI3K/Akt, and/or ras/raf/MEK/MAPK pathways in mammalian cells, and that is frequently expressed in human primary breast carcinomas. In the present study, the human estrogen receptor positive, MCF‐7 breast cancer cell line, that expresses low levels of endogenous CR‐1, was transfected with a CR‐1 expression vector. MCF‐7 CR‐1 cells expressed high levels of a 25 kDa recombinant CR‐1 protein that was not detected in MCF‐7 cells transfected with a control vector (MCF‐7 neo). Overexpression of CR‐1 did not induce an estrogen independent phenotype in MCF‐7 cells. In fact, MCF‐7 CR‐1 cells showed a response to exogenous estrogens that was similar to MCF‐7 neo cells, and failed to grow in immunosuppressed mice in absence of estrogen stimulation. However, MCF‐7 CR‐1 cells showed a rate of proliferation in serum free conditions, and an ability to form colonies in soft‐agar that were higher as compared with MCF‐7 neo cells. More importantly, overexpression of CR‐1 enhanced the resistance to anoikis and the invasion ability of MCF‐7 cells. MCF‐7 CR‐1 cells showed levels of activation of both Akt and Smad‐2 that were significantly higher as compared with MCF‐7 neo. These findings suggest that CR‐1 overexpression might be associated with the progression towards a more aggressive phenotype in breast carcinoma, through the activation of both Akt and Smad‐2 signalling pathways. J. Cell. Physiol. 198: 31–39, 2004. © 2003 Wiley‐Liss, Inc.
Wing design and morphology of the harbor porpoise dorsal fin
Authors: Pavlov Vadim V.
Published: October 2003

The correlation between skin structure and hydrodynamic design of the dorsal fin of the harbor porpoise (Phocoena phocoena) was examined. For the study of fin morphology and geometry, a scheme of sampling representing a two‐parameter mesh on the fin surface was used. At each data point the thickness of the epidermis, papillary and subpapillary layers of the dermis, the ligamentous layer of the fin, as well as the angle formed by the direction of dermal ridges and the fin root chord were measured. On the basis of fin cross‐sections the three‐dimensional surface models of the fin in a 1 : 1 scale were created with a CAD program. The shape of the model was evaluated by the wing and hydrofoil parameters (angle of leading edge sweep, leading edge radius, maximum thickness of the fin cross‐section, and position of maximum thickness from the leading edge). Hydrodynamic performance of the fin cross‐sections was studied with a CFD program. Regional variability of the parameters of morphology was compared with spanwise variability of the parameters of cross‐sectional geometry. It was found that skin structure parameters correlate with the hydrodynamically relevant parameters of the fin and fin cross‐sections. Regularities of skin structure of the harbor porpoise dorsal fin are considered indirect evidence of the adaptation of porpoise skin to the fin flow. J. Morphol. 258:284–295, 2003. © 2003 Wiley‐Liss, Inc.
Back to the future: Polish health care reform
Authors: Filinson Rachel , Chmielewski Piotr , Niklas Darek
Published: October 2003

In January 1999, the Polish government implemented a new law reorganizing the health care in the country. This paper includes an outline of the changes, the main impact of which consisted of introduction of universal health insurance administered by Health Insurance Funds (‘‘Kasy Chorych’’). In June 2001 and 2002, a survey of insurance administrators and health care workers provided data concerning the reception of the new system, the perceived inadequacies, and the postulated changes. The intended objective of privatization of health provisions appears as remote as it was before the changes. The major obstacles are identified as political hurdles, physician resistance, and continued dependence on state allocations.
Domestic political institutions in Ukraine and Russia and their responses to EU enlargement
Authors: Protsyk Oleh
Published: October 2003

This paper examines the roles that key political institutions play in formulating Ukraine’s and Russia’s responses to European Union (EU) enlargement. It provides a structured comparison of how EU-related policies are designed in the two countries. It shows how the differences in institutional setting, mindset of political actors occupying these institutions, and the character of the party system affect the variation in presidential, cabinet, and parliamentary terms of involvement in EU-related matters. It demonstrates that the variation in these terms of involvement has a lasting effect on the nature of policy output in this specific policy area.
The structural basis of light‐harvesting in purple bacteria
Authors: Cogdell Richard J , Isaacs Neil W , Freer Andrew A , Howard Tina D , Gardiner Alastair T , Prince Steve M , Papiz Miroslavr Z
Published: October 2003

A typical purple bacterial photosynthetic unit consists of two types of light‐harvesting complex (LH1 and LH2) together with a reaction centre. This short review presents a description of the structure of the LH2 complex from Rhodopseudomonas acidophila, which has recently been improved to a resolution of 2.0 Å [Papiz et al., J. Mol. Biol. 326 (2003) 1523–1538]. We show how this structure has helped to reveal the details of the various excitation energy transfer events in which it is involved.
Systematic search for compact structures of telomeric nucleosomes
Authors: Bešker Neva , Anselmi Claudio , Paparcone Raffaella , Scipioni Anita , Savino Maria , De Santis Pasquale
Published: October 2003

Telomeres are structures functionally and structurally distinct from bulk chromatin. They are constituted of highly conserved 5–7 bp tandemly repeated units, organized into nucleosomes with short linkers, whereas the knowledge of the linker histone role in telomeric chromatin is still fragmentary. Experimental evidence suggests the structural organization of telomeric nucleosomes is different from that of the bulk chromatin. This work presents a systematic search of the telomeric nucleosome arrangements. A low‐resolution molecular model was used to evaluate the relative nucleosome packing energy. Structures with favorable energy were found, reducing the possible telomeric chromatin conformations to two different three‐dimensional folds.