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  • 2000-2004  (85,186)
  • 2003  (38,072)
  • 2001  (47,117)
Year
Language
  • 101
    Unknown
    New York : Cambridge University Press
    Keywords: Social sciences, Research, Australia.
    Pages: xix, 705 p.
    ISBN: 0-511-06196-X
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  • 102
    Unknown
    Cambridge, UK ; New York : Cambridge University Press
    Cambridge studies in linguistics  
    Keywords: Alliteration. ; English language, Phonology, Historical. ; English language, Middle English, 1100-1500, Phonology. ; English language, Middle English, 1100-1500, Versification. ; English language, Old English, ca. 450-1100, Phonology. ; English language, Old English, ca. 450-1100, Versification.
    Pages: xix, 400 p.
    ISBN: 0-511-03975-1
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  • 103
    Unknown
    London ; Sterling, VA : Kogan Page Ltd
    MBA masterclass series  
    Keywords: Intercultural communication. ; Management, Social aspects.
    Pages: v, 250 p.
    ISBN: 0-585-44374-2
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  • 104
    Keywords: Transportation, Planning, Mathematical models.
    Pages: 345 p.
    ISBN: 0-585-47522-9
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  • 105
    Unknown
    Washington, D.C : Brookings Institution Press
    Keywords: Public welfare, Contracting out, United States. ; Welfare recipients, Employment, United States.
    Notes: Public services and blurring sectoral boundaries: an introduction -- Contracting and competition: the changing shape of government -- Reforming welfare services through contracting: motivations and expectations -- Nonprofits: meeting new challenges -- For-profits: the increasing dominance of national firms -- When the private sector competes: challenges and risks
    Pages: xii, 159 p.
    ISBN: 0-8157-7706-X
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  • 106
    Unknown
    Washington, D.C : Brookings Institution
    Keywords: United States, Foreign relations, Philosophy. ; United States, Foreign relations, 2001- ; Bush, George W., (George Walker),, 1946-, Views on international relations. ; Balance of power. ; September 11 Terrorist Attacks, 2001, Influence. ; Unilateral acts (International law) ; War on Terrorism, 2001-, Diplomatic history.
    Notes: The Bush revolution -- George Bush and the Vulcans -- Bush's worldview -- Building a team -- The first eight months -- September 11 -- Onto the offensive -- The Bush strategy -- The inevitable showdown -- The Iraq war -- Who's next? -- The perils of power
    Pages: vii, 246 p.
    ISBN: 0-8157-9661-7
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  • 107
    Unknown
    Cambridge, Mass : MIT Press
    Keywords: Monetary policy. ; Money.
    Pages: xvii, 612 p.
    Edition: 2nd ed
    ISBN: 0-585-48117-2
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  • 108
    Keywords: Iraq, History, 1991-2003.
    Notes: The legacy of ancient Iraq -- The struggle for Islamic Iraq -- The soundtrack to modern Iraq -- The party's over : Saddam's privileged politicos and their future in Iraq -- State-building by the book : Islamic leadership in the new Iraq -- About face : reengineering the Iraqi army -- The wages of stability : stunted business and labor under sanctions and surveillance -- Iraq'n'roll : profit and gain in Iraq's globalization -- The editorial we : pluralism and Iraqi journalism -- Babylon take two : Iraqi cinema and entertainment -- Teachers and judges of truth
    Pages: xxii, 211 p.
    ISBN: 0-585-49200-X
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  • 109
    Unknown
    Lisse, The Netherlands ; Exton, 〈PA〉 : Swets & Zeitlinger Publishers
    Advances in engineering  
    Keywords: Railroads, Cars, Dynamics.
    Pages: xii, 286 p.
    ISBN: 0-203-97099-3
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  • 110
    Unknown
    Tokyo ; New York : United Nations University Press
    Keywords: Africa, Sub-Saharan, Commercial policy, Congresses. ; Africa, Sub-Saharan, Economic policy, Congresses. ; Asia, Southeastern, Commercial policy, Congresses. ; Asia, Southeastern, Economic policy, Congresses. ; Globalization, Congresses.
    Notes: The dynamics of globalization / Laurence Harris -- Economic policies and external performance in Southeast Asia and Sub-Saharan Africa / Ernest Aryeetey and Machiko Nissanke -- Governments and external performance in Africa / Beatrice Weder -- Local entrepreneurship in Southeast Asia and Sub-Saharan Africa / Deborah Bräutigam -- Resource exports and resource processing for export in Southeast Asia / Jomo Sundaram and Michael Rock -- Primary exports and primary processing for export in Sub-Saharan Africa / William Lyakurwa -- Export-oriented industrialisation and foreign direct investment in ASEAN countries / The Kian Wie -- Export-oriented industrialisation and foreign direct investment in Africa / Charles Soludo -- Management of financial flows in Southeast Asia / Pakorn Vichyanond -- Globalization of African financial markets / Lemma Senbet -- Aid and development / Haider Khan -- Foreign aid, debt, and development in sub-Saharan Africa / Sam Wangwe -- From recovery to accelerated development / Delphin Rwegasira
    Pages: ix, 418 p.
    ISBN: 0-585-48550-X
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  • 111
    Unknown
    Cambridge, Mass : MIT Press
    Keywords: Vitruvius Pollio., De architectura. ; Architecture, Early works to 1800.
    Pages: x, 493 p.
    ISBN: 0-585-48272-1
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  • 112
    Unknown
    Berkeley : University of California Press
    Keywords: Africa, Relations, Italy. ; Italy, Colonies, Africa. ; Italy, Relations, Africa. ; Popular culture, Italy, History.
    Notes: The myths, suppressions, denials, and defaults of Italian colonialism / Angelo Del Boca -- Studies and research on Fascist colonialism, 1922-1935 : reflections on the state of the art / Nicola Labanca -- Italian anthropology and the Africans : the early colonial period / Barbara Sòrgoni -- The construction of racial hierarchies in colonial Eritrea : the liberal and early Fascist period (1897-1934) / Giulia Barrera -- Gifts, sex, and guns : nineteenth-century Italian explorers in Africa / Cristina Lombardi-Diop -- Incorporating the exotic : from futurist excess to postmodern impasse / Cinzia Sartini-Blum -- Alexandria revisited : colonialism and the Egyptian works of Enrico Pea and Giuseppe Ungaretti -- Mass-mediated fantasies of feminine conquest, 1930-1940 / Robin Pickering-Iazzi -- Orphans for the empire : colonial propaganda and children's literature during the Imperial era / Patrizia Palumbo -- Colonial autism : whitened heroes, auditory rhetoric, and national identity in interwar Italian cinema / Giorgio Bertellini -- Black shirts/Black skins : Fascist Italy's colonial anxieties and Lo squadrone bianco / Cecilia Boggio -- Empty spaces : decolonization in Italy / Karen Pinkus
    Pages: 332 p.
    ISBN: 1-417-52281-X
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  • 113
    Keywords: United States, Politics and government, Public opinion. ; Political socialization, United States. ; Public opinion, United States. ; Students, United States, Political activity. ; Youth, United States, Attitudes. ; Youth, United States, Political activity.
    Notes: Becoming political : local environments and political socialization -- Communities and political socialization -- Racial group membership, neighborhood context, and political socialization -- Party identification, political context, and political socialization -- Religion and political socialization -- Schools, civic education, and political socialization -- The terrorist attacks as politically socializing events -- Local contexts and the multiple futures of Generation Y
    Pages: x, 278 p.
    ISBN: 0-8157-9614-5
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  • 114
    Unknown
    Palo Alto, Calif : Stanford Social Sciences, Stanford University Press
    Latin American development forum  
    Keywords: Caribbean Area, Economic conditions. ; Caribbean Area, Foreign economic relations. ; Latin America, Economic conditions. ; Latin America, Foreign economic relations. ; Economic development. ; Globalization.
    Pages: xv, 214 p.
    ISBN: 0-585-47966-6
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  • 115
    Unknown
    Cambridge, U.K ; New York : Cambridge University Press
    Keywords: Logic. ; Reasoning.
    Notes: Introduction -- Fields of argument and modals -- Probability -- The layout of arguments -- Working logic and idealised logic -- The origins of epistemological theory -- Conclusion
    Pages: xiv, 247 p.
    Edition: Updated ed
    ISBN: 0-511-06271-0
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  • 116
    Unknown
    Florham Park, N.J : Financial Executives Research Foundation
    Keywords: United States., Sarbanes-Oxley Act of 2002. ; Corporations, Accounting, Corrupt practices, United States. ; Corporations, Accounting, Law and legislation, United States. ; Financial statements, Law and legislation, United States. ; Misleading financial statements, United States.
    ISBN: 1-417-50082-4
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  • 117
    Keywords: Cognition ; Cognitive psychology ; Electronic books ; Self-organizing systems
    Notes: Intelligent behavior : a synergetic view / Hermann Haken -- Grounded in the world : developmental origins of the embodied mind / Esther Thelen -- Cognitive coordination dynamics / Scott Kelso -- What is coordinated in bimanual coordination? / Franz Mechsner and Wolfgang Prinz -- Cognition in action : the interplay of attention and bimanual coordination dynamics / Jean Jacques Temprado -- A synergetic approach to describe the stability and variability of motor behavior / Kerstin Witte ... [et al.] -- The role of synchronization in perception-action / Tin-cheun Chan ... [et al.] -- A mean-field approach to self-organization in spatially extended perception-action and psychological systems / Till Frank and Peter Beek -- Self-organizing systems show apparent intentionality / Wolfgang Tschacher, Jean-Pierre Dauwalder, and Hermann Haken -- The embodiment of intentionality / Scott Jordan -- Cognitive science, representations and dynamical systems theory / Pim Haselager, Raoul Bongers, and Iris van Rooij -- Self-steered self-organisation / Fred Keijzer -- Brain dynamics : methodological issues and applications in psychiatric and neurologic diseases / Laurent Pezard -- SIRN (synergetic inter-representation networks), artifacts and Snow's two cultures / Juval Portugali -- Dynamical systems theory : application to pedagogy / Jane Abraham
    Pages: xi, 330 p.
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  • 118
    Unknown
    Oxford ; New York : Berg
    Keywords: Ethnicity, Europe. ; Minority women, Europe. ; Women immigrants, Europe. ; Women, Europe, Identity.
    Notes: Introduction: The space between; gender politics and immigration politics in Europe / Jacqueling Andall -- pt. 1. Gender, ethnicity and migration. Gendered actors in migration / Annie Phizacklea ; Hierarchy and interdependence: the emergence of a service caste in Europe / Jacqueline Andall ; Migrant women in Spain: class, gender and ethnicity / Carlota Solé and Sònia Parella -- pt. 2. Gender, ethnicity and political mobilization. South Asian women and collective action in Britain / Ravi K. Thiara ; Women migrants and political activism in France / Cathie Lloyd -- pt. 3. Gender, ethnicity and Islam. Shifting meanings of Islam and multiple representations of modernity: the case of Muslim wwomen in Italy / Ruba Salih ; 'Nowadays your husband is your partner': ethnicity and emancipation as self-presentation in the Netherlands / Joke van der Zwaard ; Gendered and racialized experiences of citizenship in the life stories of women of Turkish background in Germany / Umut Erel -- pt. 4. Gender, ethnicity and identity. Mother Russia: changing attitudes to ethnicity and national identity in Russia's regions / Anne White ; Westenders: whiteness, women and sexuality in Southall, UK / Raminder Kaur
    Pages: xii, 238 p.
    ISBN: 0-585-48439-2
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  • 119
    Unknown
    Columbia : University of Missouri Press
    Keywords: Yorkshire (England), In literature. ; Brontë family. ; Brontë, Anne,, 1820-1849, Criticism and interpretation. ; Brontë, Charlotte,, 1816-1855, Criticism and interpretation. ; Brontë, Emily,, 1818-1848, Criticism and interpretation. ; Autobiography in literature. ; Family in literature. ; Self in literature. ; Sisters in literature. ; Women and literature, England, History, 19th century. ; Women and literature, England, Yorkshire.
    Notes: Family as context and content -- The Victorian context : self, family, and society -- The family context : writing as sibling relationship -- Jane Eyre : the pilgrimage of the "poor orphan child" -- Wuthering heights : the boundless passion of Catherine Earnshaw -- Agnes Grey and the tenant of Wildfell Hall : lessons of the family -- The professor and Shirley : industrial pollution of family relations and values -- Villette : authorial regeneration and the death of the family -- Life after Villette
    Pages: xi, 260 p.
    ISBN: 0-8262-6268-6
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  • 120
    Unknown
    New York : Kluwer Academic/Plenum
    Keywords: Dinners and dining, History. ; Food habits, History. ; Food, Political aspects.
    Notes: The Commensal Politics of Early States and Empires / Tamara L. Bray -- Feasts, Funerals, and Fast Food in Early Mesopotamian States / Susan Pollock -- Pharaohs, Feasts, and Foreigners: Cooking, Foodways, and Agency on Ancient Egypt's Southern Frontier / Stuart Tyson Smith -- Feasting the Ancestors in Early China / Sarah Milledge Nelson -- To Dine Splendidly: Imperial Pottery, Commensal Politics, and the Inca State / Tamara L. Bray -- From Stew-Eaters to Maize-Drinkers: The Chicha economy and the Tiwanaku Expansion / Paul S. Goldstein -- Pots, Politics, and Power: Huari Ceramic Assemblages and Imperial Administration / Anita G. Cook and Mary Glowacki -- Feasting at Home: Community and House Solidarity among the Maya of Southeastern Mesoamerica / Julia A. Hendon -- Aztec Feasts, Rituals, and Markets: Political Uses of Ceramic Vessels in a Commercial Economy / Michael E. Smith, Jennifer B. Wharton, and Jan Marie Olson -- Clearing the Table: Some Concluding Reflections on Commensal Politics and Imperial States / Michael Dietler -- Feasting and the Practice of Stately Manners / Joan M. Gero
    Pages: viii, 292 p.
    ISBN: 0-306-48246-0
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  • 121
    Keywords: Human capital. ; Organizational effectiveness. ; Personnel departments. ; Personnel management. ; Personnel management, Computer network resources. ; Personnel management, Technological innovations.
    Notes: Role of HR -- HR organizational approaches -- HR activities -- Talent strategies -- Shared services -- Outsourcing -- Use of IT -- eHR systems -- Effectiveness of eHR systems -- HR skills -- Effectiveness of the HR organization -- Determinants of HR effectiveness -- HR as a strategic partner
    Pages: xiv, 135 p.
    ISBN: 1-417-50147-2
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  • 122
    Unknown
    Honolulu : University of Hawaiʿi Press
    Keywords: Motion pictures, China, History. ; Sex role in motion pictures. ; Women in motion pictures.
    Notes: Part I. Early production. From shadow-play to a national cinema ; Reconstructing history: the (im)possible engagement between feminism and postmodernism in Stanley Kwan's Center stage -- Part II. Socialist cinema. Constructing and consuming the revolutionary narratives ; Gender politics and socialist discourse in Xie Jin's The red detachment of women -- Part III. The new wave. Screening China: national allegories and international receptions ; The search for male masculinity and sexuality in Zhang Yimou's Ju dou ; Subjected body and gendered identity: female impersonation in Chen Kaige's Farewell my concubine -- Part IV. Women's films. Feminism with Chinese characteristics? ; Desire in difference: female voice and point of view in Hu Mei's Army nurse ; Transgender masquerading in Huang Shuqin's Human, woman, demon
    Pages: xxvi, 304 p.
    ISBN: 0-585-47914-3
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  • 123
    Unknown
    Cambridge, Mass : MIT Press
    Keywords: Aesthetics, Modern, 20th century. ; Art, Modern, 20th century. ; Art, Attribution. ; Art, Reproduction.
    Pages: 307 p.
    ISBN: 0-585-47880-5
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  • 124
    Unknown
    Oxford ; Boston : Butterworth-Heinemann
    Keywords: Marketing.
    Pages: xxxviii, 834 p.
    Edition: 5th ed
    ISBN: 0-585-45952-5
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  • 125
    Unknown
    Iowa City : University of Iowa Press
    Studies in theatre history and culture  
    Keywords: American drama, 20th century, History and criticism. ; Theater, United States, History, 20th century.
    Notes: 1. A theater of containment liberalism -- 2. Empty boys, queer others, and consumerism -- 3. Family circles, racial others, and suburbanization -- 4. Fragmented heroes, female others, and the bomb
    Pages: xiv, 347 p.
    ISBN: 1-587-29447-8
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  • 126
    Keywords: Electronic commerce, Psychological aspects. ; Electronic commerce, Psychological aspects, Case studies. ; Interorganizational relations. ; Trust.
    Pages: x, 209 p.
    ISBN: 1-931777-76-4
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  • 127
    Unknown
    Cambridge, Mass : MIT Press
    Leonardo  
    Keywords: Art and electronics. ; Computer art. ; Panoramas. ; Virtual reality in art.
    Pages: xiv, 416 p.
    ISBN: 0-585-44679-2
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  • 128
    Unknown
    Cambridge, Mass : MIT Press
    Keywords: Corporate governance. ; Human capital. ; Management. ; Organizational change. ; Personnel management. ; Technological innovations, Management.
    Pages: xiv, 309 p.
    ISBN: 0-585-48110-5
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  • 129
    Unknown
    Cambridge, UK ; New York, NY : Cambridge University Press
    Keywords: Public welfare, OECD countries. ; Public welfare, Scandinavia.
    Notes: International integration and the welfare state / Torben M. Andersen -- The changing age structure and the public sector / Thomas Lindh -- Emigration from the Scandinavian welfare states / Peder J. Pedersen, Marianne Røed and Lena Schröder -- Productivity and costs in public production of services / Jørn Rattsø -- Use of fees in the provision of public services in OECD countries / Carl Emmerson and Howard Reed -- Privitisation of social insurance with reference to Sweden / Lars Söderström and Klas Rikner -- Occupational welfare / Ann-Charlotte St°ahlberg -- Pathways to retirement and retirement incentives in Sweden / M°arten Palme and Ingemar Svensson -- Social insurance and redistribution / Pierre Pestieau -- Assessing the effect of introducing welfare accounts in Sweden / Stefan Fölster ... [et al.] -- Taxation in a global economy / Bernd Huber and Erik Norrman -- Taxation and education investment in the tertiary sector / Fredrik Andersson and Kai A. Konrad -- Debt strategies for Sweden and Europe / Martin Flodén -- Policy options for reforming the welfare state / Torben M. Andersen and Per Molander
    Pages: xi, 383 p.
    ISBN: 0-511-06484-5
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  • 130
    Unknown
    Camnbridge, UK ; New York : Cambridge University Press
    Cambridge studies in philosophy  
    Keywords: Language and languages, Philosophy. ; Semantics (Philosophy)
    Notes: Speaker meaning -- Expression -- Alternative analyses -- Communication -- Reference -- Languages -- Basic word meaning -- Conventions -- Compositional word meaning -- Living languages -- Thought -- Sentences, propositions, and thoughts -- The constituency thesis -- Ideas or concepts -- The possession of concepts -- The acquisition of concepts -- The association of ideas -- Objects, images, and conceptions -- The language of thought hypothesis -- Objections to ideational theories -- Priority objections -- Incompleteness objections
    Pages: xvii, 654 p.
    ISBN: 0-511-06566-3
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  • 131
    Unknown
    New York : Oxford University Press
    Keywords: Crime in literature. ; Criminal liability in literature. ; Criminals in literature. ; English fiction, 19th century, History and criticism. ; Law and literature, History, 19th century. ; Legal stories, English, History and criticism. ; Responsibility in literature.
    Notes: Organizing crime : conduct and character in Oliver Twist : prologue to George Eliot's crimes -- "To fix our minds on that consequence" : minding consequences in Adam Bede and Felix Holt -- Middlemarch, Daniel Deronda, and the crime in mind -- James Fitzjames Stephen and the responsibilities of narrative -- Modern responsibilities
    Pages: viii, 275 p.
    ISBN: 0-19-518524-2
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  • 132
    Unknown
    Cambridge, U.K ; New York : Cambridge University Press
    Cambridge companions to religion  
    Keywords: Luther, Martin,, 1483-1546.
    Notes: Luther's life /Albrecht Beutel --Luther's Wittenberg /Helmar Junghans --Luther's writings /Timothy F. Lull --Luther as Bible translator /Eric W. Gritsch --Luther as an interpreter of holy scripture /Oswald Bayer --Luther's theology /Markus Wriedt --Luther's moral theology /Bernd Wannenwetsch --Luther as preacher of the word of God /Fred W. Meuser --Luther's spiritual journey /Jane E. Strohl --Luther's struggle with social-ethical issues /Carter Lindberg --Luther's political encounters /David M. Whitford. -- Luther's polemical controversies /Mark U. Edwards, Jr. --Luther's function in an age of confessionalization /Robert Kolb --The legacy of Martin Luther /Hans J. Hillerbrand --Approaching Luther /James Arne Nestingen --Luther and modern church history /James M. Kittelson --Luther's contemporary theological significance /Robert W. Jenson --Luther in the worldwide church today /Günther Gassmann.
    Pages: xviii, 320 p.
    ISBN: 0-511-07830-7
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  • 133
    Unknown
    Cambridge, U.K ; New York, NY : Cambridge University Press
    Keywords: American literature, Jewish authors, History and criticism. ; Jews in literature. ; Jews, United States, Intellectual life. ; Judaism and literature, United States. ; Judaism in literature.
    Notes: Introduction:Jewish American literatures in the making /Hana Wirth-Nesher,Michael P. Kramer --Beginnings and ends: the origins of Jewish American literary history /Michael P. Kramer --Imagining Judaism in America /Susannah Heschel --Of crucibles and grandfathers: the East European immigrants /Priscilla Wald --Coney Island, USA: America in the Yiddish literary imagination /David G. Roskies --Hebrew literature in America /Alan Mintz --Traces of the past: multilingual Jewish American writing /Hana Wirth-Nesher --Accents of the future: Jewish American popular culture /Donald Weber --Jewish American poetry /Maeera Y. Shreiber --Jewish American writers on the left /Alan Wald --Jewish American Renaissance /Ruth R. Wisse --Holocaust and the Jewish American imagination /Emily Miller Budick --Jewish American women writers and the race question /Susan Gubar --On contemporary literary theory and Jewish American poetics /Shira Wolosky --Identity matters: contemporary Jewish American writing /Tresa Grauer.
    Pages: xvi, 296 p.
    ISBN: 0-511-06311-3
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  • 134
    Keywords: Art, Roman, Social aspects. ; Art, Roman, Themes, motives. ; Social classes in art. ; Social status, Rome.
    Notes: pt. 1. Imperial representation of non-elites -- Augustus's and Trajan's messages to commoners -- The all-seeing emperor and ordinary viewers : Marcus Aurelius and Constantine -- pt. 2. Non-elites in the public sphere -- Everyman, everywoman, and the gods -- Everyman and everywoman at work -- Spectacle : entertainment, social control, self-advertising, and transgression -- Laughter and subversion in the tavern : image, text, and context -- Commemoration of life in the domain of the dead : non-elite tombs and sarcophagi -- pt. 3. Non-elites in the domestic sphere -- Minding your manners : banquets, behavior, and class -- Putting your best face forward : self-representation at home
    Pages: xi, 383 p.
    ISBN: 1-417-52332-8
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  • 135
    Unknown
    New York : Oxford University Press
    Keywords: Eliot, T. S., (Thomas Stearns),, 1888-1965, Views on war. ; Pound, Ezra,, 1885-1972, Views on war. ; Woolf, Virginia,, 1882-1941, Views on war. ; American poetry, 20th century, History and criticism. ; Americans, Great Britain, History, 20th century. ; Modernism (Literature), Great Britain. ; Modernism (Literature), United States. ; World War, 1914-1918, Great Britain, Literature and the war.
    Pages: xiii, 395 p.
    ISBN: 0-19-518055-0
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  • 136
    Keywords: Business logistics, Management.
    Pages: xxvi, 278 p.
    ISBN: 0-8144-2708-1
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  • 137
    Unknown
    Bloomington, IN : Indiana University Press
    Studies in Continental thought  
    Keywords: Heidegger, Martin,, 1889-1976., Beiträge zur Philosophie. ; Philosophy.
    Pages: viii, 121 p.
    ISBN: 0-253-10979-5
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  • 138
    Unknown
    Cambridge, U.K ; New York : Cambridge University Press
    Political economy of institutions and decisions  
    Keywords: Economic and Monetary Union. ; Banks and banking, Central, Europe. ; Banks and banking, Central, United States. ; Federal Reserve banks. ; Monetary policy, Europe. ; Monetary policy, United States.
    Notes: A formal model of the appointment process -- Estimating monetary policy preferences -- Empirically testing the model's predictions -- Appointments to the European Central Bank -- The origins of the Federal Reserve appointment process -- Conclusions
    Pages: xiv, 160 p.
    ISBN: 0-511-06209-5
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  • 139
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Inc
    The @breast journal 9 (2003), S. 0 
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The incidence of breast cancer and mortality from this disease remain high in countries with limited resources such as the Ukraine. Because of a lack of mammography equipment and formal screening programs, as well as educational and other factors, breast cancer is usually diagnosed in late stages in such countries. We report the experience of the PATH Breast Cancer Assistance Program in introducing a pilot breast cancer screening program in one territory of the Ukraine, the Chernihiv oblast. The program entailed educating the public, training health care providers in clinical breast examination (CBE) and mammography, opening a dedicated mammography facility, designating a center for breast cancer care, building diagnostic capacity, and fostering the formation of support groups. From 1998 to 2002, 18,000 women underwent screening with CBE and 8778 women underwent screening with mammography. When implementing the program we encountered various cultural, economic, and logistic difficulties, such as reservations about showing bare breasts in educational materials, the lack of an established system for collecting screening data, and barriers to follow-up in women with positive screening results. Screening mammography proved to be more effective in detecting small and nonpalpable lesions; 8.7% of cancers detected in the mammography group were in situ, compared with 0% in the CBE group. However, introduction of CBE as a screening modality required fewer financial resources compared with mammography and was recommended as a transitional method before the introduction of mammography screening programs in countries with limited resources. The introduction of screening was associated with favorable changes in indicators of breast cancer care, including an increase in the percentage of breast-preserving operations and new legislation to provide funding for breast cancer services. We conclude that this successful pilot program of breast cancer screening in a limited-resource setting can serve as an example for other similar programs. 
    Type of Medium: Electronic Resource
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  • 140
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Inc
    The @breast journal 9 (2003), S. 0 
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Mammography is the most sensitive available means for early detection of breast cancer, but both clinical breast examination (CBE) and breast self-examination (BSE) have the potential to advance the diagnosis of breast cancer without the expense of a mammography facility. CBE detects about 60% of cancers detected by mammography, as well as some cancers not detected by mammography. There have been no randomized trials comparing breast cancer mortality between women offered and not offered CBE. However, indirect evidence comes from a Canadian study in which women were randomly assigned to CBE alone or CBE plus mammography. Women in the two groups had similar rates of nodal involvement at diagnosis and of breast cancer mortality. Thus if receipt of mammography averts some deaths from breast cancer, the results of this study suggest that CBE has the potential to do so as well. Most studies have found that breast cancers detected by BSE are smaller than those detected without screening and are more likely to be confined to the breast; furthermore, survival after a diagnosis of breast cancer tends to be longer among women who practice BSE than among women who do not. However, neither observational nor randomized studies of BSE provide evidence that this screening modality reduces breast cancer mortality. A recent randomized study in Shanghai, China, found that women assigned to extensive BSE instruction and women assigned to another health intervention had similar distributions of cancer size and stage at diagnosis and similar breast cancer mortality rates. In summary, CBE appears to be a promising means of averting some deaths from breast cancer, whereas BSE appears to have little or no impact on breast cancer mortality. 
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  • 141
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    Topics: Medicine
    Notes: Abstract: Minimally invasive breast biopsy techniques, such as core needle biopsy (CNB) and fine-needle aspiration biopsy (FNAB), offer several advantages over surgical biopsy. Patients in whom minimally invasive biopsy techniques are used may undergo biopsy more quickly, are more likely to have only one surgery for treatment of the breast tumor and axillary staging, and are less likely to need reoperation after breast-conserving surgery because of positive margins. Knowledge of a diagnosis of cancer before surgery allows patients to participate in treatment decisions, and compared with surgical biopsy, minimally invasive biopsy has lower costs, produces less scarring, has nearly equivalent diagnostic accuracy, and does not require general anesthesia or sedation. Minimally invasive biopsy can permit accurate diagnosis and prompt intervention in a cost-effective manner, particularly in countries with limited resources, where patients often present with advanced-stage breast cancer. Several events characterize the implementation of a successful program in minimally invasive breast biopsy: public education about the less invasive nature of these techniques, which may encourage women to seek care at earlier stages; a change in the philosophy of medical personnel that favors involving patients in treatment decisions and acceptance of less extensive but accurate methods of diagnosis; education of medical personnel in the selection of patients for minimally invasive biopsy, performance of the biopsy, and interpretation of histologic and/or cytologic samples; quality assessment and use of the triple test (i.e., correlation of clinical, radiologic, and pathologic findings); and economical use of resources, which results from the lower costs of minimally invasive procedures and the avoidance of unnecessary surgery for benign conditions. 
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  • 142
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    Helicobacter 8 (2003), S. 0 
    ISSN: 1523-5378
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  • 143
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Genomic instability is one of the earliest features of cancer cell behavior and can lead to gene mutation, amplification, or deletion. Rarely one of these genomic events can give the cell a growth advantage or some other characteristic that contributes to carcinogenesis and also leads to clonal expansion. Solid tumors contain numerous genetic abnormalities and these vary among individuals. New techniques from the laboratory allow unprecedented levels of detail in cancer genetic analysis of human tumors. One technique called comparative genomic hybridization (CGH) can pinpoint areas of the genome that are amplified or deleted. These changes that occur at a high frequency are likely to represent genes that are important in cancer development and progression. How can this be translated into new biologic therapy as well as a better understanding of factors that predict responses to standard chemotherapy to allow better individualized tailoring of treatment? Through the linkage of CGH data on human tumors to their clinical outcomes, specific questions can be asked about the relationship of specific genes to clinical variables. For example, genes that are gained in patients who are resistant to anti-HER-2 antibody (Herceptin) might help select patients for such therapy or identify genes that could be pharmacologically targeted to overcome Herceptin resistance. Prospects for better treatment and recent advances in genomic research may lead to an increased understanding of the basic mechanisms resulting in initiation and progression of breast cancer. 
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  • 144
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Trastuzumab is a humanized monoclonal antibody against the epidermal growth factor family oncogene, Her-2/neu. It has revolutionized therapy for the 15–20% of patients with metastatic breast cancer whose tumors have gene amplification for Her-2/neu. Results of clinical trials with single agent trastuzumab and in combination with paclitaxel, docetaxel, vinorelbine, gemcitabine and platinum salts have been encouraging. Durable remissions in excess of 5 years have occasionally been reported. Subjectively the side effect profile of this novel, targeted therapy, has been mild. Cardiac toxicity, while reported in combination regimens with anthracyclines tend to be easily manageable and not absolute contradictions to continuation of trastuzumab. Outside of clinical trials, however, anthracycline/trastuzumab combinations should be avoided. Preliminary results of trials with various combinations of chemotherapeutic agents have been promising while combinations with hormonal and other biologic therapy are ongoing. Trastuzumab is an exciting new monoclonal antibody with interesting anti-tumor activity in patients with Her-2/neu gene amplified breast cancer. We look forward to ongoing clinical trials combining trastuzumab with a broad array of other chemotherapeutic, hormonal and biological agents.
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  • 145
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background. Dyspepsia is a very common problem in Thailand. Etiology of gastritis, incidence of Helicobacter pylori and mode of transmission of Helicobacter pylori infection in the country was proposed.Methods. A nation-wide study of gastric biopsy in 3776 dyspeptic patients from six different geographic regions for incidence of gastritis, type of gastritis, incidence of H. pylori infection, gastric atrophic change and intestinal metaplasia in three age-groups of each region was done.Results. 58.7% of dyspeptic patients had histological gastritis. Pangastritis was the most common type (77.3%) with mostly mild active inflammation (60.6%) and was found most commonly in the age group 31–60 years. Incidence of gastritis was slightly lower in the coastal and peninsular community compared with the mountain, jungle, semiarid plateau and fertile plain communities. Geographic factor, socioeconomic status and dietary habit were proposed to be important factors in inducing gastritis. H. pylori infection was found in 48.2% of dyspeptic patients with high incidence in the age-group 31–60 years (63.7%) and 98.2% of H. pylori infection was found to be associated with gastritis. Semi-arid plateau, mountain, jungle and fertile plain communities had high incidences of H. pylori infection varying from 54.0 to 67.1% while the coastal and peninsular communities had low incidences of 32%. Oral to oral spread is proposed to be the mode of bacterial transmission. Incidences of gastric atrophic change and intestinal metaplasia were low in this country and were found in 11.6% and 8.2% of subjects, respectively, with no significantly different distribution in geographic regions. Type I or intestinal type was found to be the most common type of intestinal metaplasia.
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  • 146
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    Topics: Medicine
    Notes: Background. Helicobacter pylori CagA is injected into the host cell and tyrosine-phosphorylated. We examined tyrosine-phosphorylation sites of CagA, as well as the function of CagA proteins in vivo and in vitro.Methods. After proteolytic digestion of CagA with lysyl endopeptidase, CagA tyrosine-phosphorylation sites were determined using quadropolar time-of-flight (Q-TOF) mass spectrometry analysis. Specific anti-pY CagA polyclonal and anti-CagA monoclonal antibodies were used to examine gastric mucosal biopsy specimens from H. pylori infected patients.Results. Mass spectrometry identified five crucial tyrosine-phosphorylation sites of CagA at Tyr893, Tyr912, Tyr965, Tyr999, and Tyr1033 within the five repeated EPIYA sequences of H. pylori (NCTC11637)-infected AGS cells. CagA protein also had an immuno-receptor tyrosine-based activation motif (ITAM)-like amino acid sequences in the 3′ region of the cagA, EPIYATIx27EIYATI, which closely resembled the ITAM. CagA proteins: (i) were localized to the 1% TritonX-100 resistant membrane fraction (lipid rafts); (ii) formed a cluster of phosphorylated CagA protein complexes; (iii) associated with tyrosine-phosphorylated GIT1/Cat1 (G protein-coupled receptor kinase-interactor 1/Cool-associated tyrosine-phosphorylated 1), substrate molecules of receptor type protein-tyrosine phosphatase (RPTPζ/β), which is the receptor of VacA; and (iv) were involved in a delay and negative regulation of VacA-induced signal. Furthermore, immunohistochemical staining of gastric mucosal biopsy specimens provided strong evidence that tyrosine-phosphorylated CagA is found together with CagA at the luminal surface of gastric foveola in vivo.Conclusion. These findings suggest an important role for CagA containing ITAM-like sequences in the pathogenesis of H. pylori-related disease.
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  • 147
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion.Materials and Methods. We undertook 24-hour pH-metry in 12 H. pylori-positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day.Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H+ concentration-time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL-1α, IL-8, IL-13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H+ concentration-time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori.Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.
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  • 148
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  • 149
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    The @breast journal 9 (2003), S. 0 
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  • 150
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  • 151
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Sentinel lymph node biopsy (SLNB) is widely employed to detect axillary lymph node metastases in breast cancer patients with clinically negative (N0) axillae. One of the few reported contraindications to SLNB is prior treatment with systemic chemotherapy (neoadjuvant/induction chemotherapy). Previous investigators reported difficulty identifying the sentinel node and an unacceptable false-negative rate in this patient cohort. We present one experienced surgeon's experience with SLNB following induction chemotherapy (n = 21). Following treatment with Adriamycin and Cytoxan (AC)-based cyclic chemotherapy, patients underwent SLNB, followed by levels I and II axillary lymph node dissection (ALND). At least one sentinel node was identified in all patients (100%). With respect to metastatic disease, the status of the sentinel node(s) accurately reflected the status of the axilla in 20 of 21 patients (95%). Eleven patients (52%) had axillary metastases identified by ALND. Of this group, SLNB failed to identify metastatic disease in one patient (9%). Previous treatment with induction chemotherapy should not be considered an absolute contraindication to SLNB. An experienced surgeon may utilize the technique in these patients, sparing them the added morbidity of axillary dissection. 
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  • 152
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  • 153
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  • 154
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Standard practice in surgical pathology dictates that random sections from the four quadrants of the breast be taken in mastectomy specimens. These sections are obtained in addition to sampling of any grossly visible lesions within the breast specimen. While tradition dictates the submission of these sections, we are unaware of any study supporting their efficacy. We have investigated the utility and significance of these random sections in a series of 78 mastectomy specimens. This retrospective study identified mastectomy specimens from pathology files of Magee Woman's Hospital, the University of Pittsburgh, and the University of Utah School of Medicine between 1997 and 2000. Clinical data (palpable versus nonpalpable), radiographic features (mammographic diagnosis, presence of mass density and/or calcification), and pathologic features (size, histopathologic type, etc.) were studied. The histologic sections of the cases were reviewed and the random sections were specifically studied for pathologic findings. Diagnosis and clinically significant features obtained from examining these random sections, but not demonstrable in grossly selected sections, were tabulated. A total of 78 mastectomy specimens were analyzed. Diagnoses rendered were infiltrating ductal carcinoma (23), infiltrating ductal carcinoma with ductal carcinoma in situ (DCIS) (16), DCIS (25), infiltrating lobular carcinoma (4), biopsy cavity with no residual malignancy (4), infiltrating lobular carcinoma with lobular carcinoma in situ (3), invasive ductal and lobular carcinoma (1), adenoid cystic carcinoma (1), and atypical ductal hyperplasia (1). The number of random sections ranged from 2 to 17 (mean 9). Random sections provided additional information in 21 of 78 mastectomies (27%). The multifocal/multicentric nature of the lesion was diagnosed in 20 cases: DCIS (6), lobular carcinoma in situ and invasive (2), invasive ductal carcinoma (6), invasive and in situ ductal carcinoma (5), invasive lobular carcinoma (1), invasive ductal and lobular carcinoma (1). Additional findings include lymphovascular invasion (2 cases), atypical ductal hyperplasia (1), DCIS at the operative margin (1), DCIS within less than 1 mm of an operative margin (1), and atypical lobular hyperplasia (1). In the remaining 57 cases, random sections did not provide any additional information. Histologic examination of random sections from breast quadrants yielded important information about the presence of multifocality, multicentricity, vascular invasion, and margin involvement by carcinoma in only a minority of cases, many of which had a lobular morphology. 
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  • 155
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  • 156
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  • 157
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  • 158
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    Topics: Medicine
    Notes: Abstract: Nodular fasciitis is a soft tissue lesion that in rare instances occurs in the breast. It can clinically and radiologically mimic malignant tumor. We describe a case of nodular fasciitis of the breast in a young woman that was misdiagnosed as phyllodes tumor. The histologic features and a review of the literature are presented. Awareness of such an entity in the breast obviates the need for unnecessary surgical intervention.
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  • 159
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    Topics: Medicine
    Notes: Abstract:  This study examines proliferative activity in tumor cells of patients with histologically documented invasive breast carcinoma treated with magnetic resonance-guided interstitial laser photocoagulation (MR-GILP). Immunohistochemical marker for proliferating cell nuclear antigen (PCNA), a nuclear protein abundant in actively proliferating cells, is used. The study demonstrates the effectiveness of MR-GILP in ablating tumor cells of infiltrating breast cancer. The diagnosis of infiltrating breast carcinoma was confirmed by core needle biopsies. Using a specially designed magnetic resonance imaging (MRI) device, rotating delivery of excitation off-resonance (RODEO), tumors were measured ranging from 1.8 to 4.0 cm in greatest dimension. Seven formalin-fixed, paraffin-embedded archival tissues from seven patients with infiltrating carcinoma, status post-MR-GILP, were analyzed. Using PCNA immunoperoxidase (Biomeda Corp.), the proliferative capability of the remaining tumor cells around the focus of laser photocoagulation was determined. The lesions were digitally acquired using a Nikon Eclipse E800 microscope with an automated stage. Images were analyzed using Cool SNAP image editing software (version 1.0). Appropriate thresholds were set for positive staining and limited concentric radial measurements of equal area between all samples were compared at radial millimeter intervals from the center of laser ablation. The integrated area occupied by PCNA-positive cells per radial millimeter from the charcoal site (the center of the laser) increased as the distance from this site increased (a mean average at each radial measurement revealed: at the 1 mm radius the positive integrated area was 0.0024 mm2; at 2 mm, 0.0145 mm2; at 3 mm, 0.0351 mm2; at 4 mm, 0.0696 mm2; at 5 mm, 0.1025 mm2; and at 6 mm, 0.1263 mm2). MR-GILP is an effective mean of ablating breast carcinoma. This treatment option may represent an alternative to lumpectomy for a single lesion ≤1 cm, or make patients with two separate lesions eligible for lumpectomy.
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  • 160
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  • 161
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  • 162
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    Topics: Medicine
    Notes: Abstract: The purpose of this study was to determine the frequency with which low-literacy patients in a developing country chose their treatment plan. In this study, data for 312 patients admitted to different hospitals in Egypt were reviewed regarding their disease stage, optimal management plan, and treatment. It was found that the majority of patients were primarily concerned with keeping their breasts, regardless of the disease stage. 
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  • 163
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    Topics: Medicine
    Notes: Abstract: Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients. 
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  • 164
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  • 165
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    Topics: Medicine
    Notes: Abstract: The management of lobular neoplasia (LN) found on percutaneous core biopsy remains a clinical dilemma. The purpose of this study was to establish guidelines for the management of LN when obtained on percutaneous core needle biopsy. A retrospective review of the Breast Imaging Tissue Sampling Database at New York Presbyterian Hospital–Columbia Comprehensive Breast Center was performed from 1998 to 2000. A total of 1460 percutaneous core breast biopsies were performed using 11- or 14-gauge needles with LN identified in 43 biopsies from 34 patients. Eleven biopsies were ultrasound guided for nonpalpable masses and 32 were stereotactically guided for mammographically detected densities (10) and microcalcifications (22). The 43 LN biopsies were divided into three groups based on additional findings associated with LN on core biopsy: group I (n = 19), LN with invasive cancer or ductal carcinoma in situ (DCIS); group II (n = 11), LN plus a second indication for open surgical biopsy, such as atypical ductal hyperplasia (ADH), radial scar, phyllodes tumor, or intraductal papilloma; and group III (n = 13), LN plus benign fibrocystic changes. In group I, 19 of 19 biopsies (100%) yielded invasive cancer or DCIS on surgical biopsy versus 3 of 11 (27%) for group II, and 1 of 13 (8%) for group III. Outcomes in group III are described as follows: three patients were lost to follow-up, three patients did not undergo surgical biopsy but demonstrated more than 1 year of mammographic stability following core biopsy. Of the remaining seven patients, two had LN and ADH on surgical biopsy (one had a contralateral cancer), one had atypical lobular hyperplasia (with a contralateral cancer), two had LN and benign fibrocystic changes, one had LN and intraductal papilloma, and one had LN and invasive ductal carcinoma (IDC) with DCIS (with a contralateral cancer). These results suggest that surgical biopsy is indicated for patients with LN when found on core biopsy and when the biopsy demonstrates invasive cancer, DCIS, or other indications for surgical biopsy such as ADH, or in the examination of a patient with a synchronous contralateral breast cancer. The diagnosis of LN alone without these indications on percutaneous biopsy may not warrant routine surgical biopsy. 
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  • 166
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    Topics: Medicine
    Notes: Abstract: Invasive lobular carcinoma (ILC) may be a difficult tumor to detect early by physical examination, mammography, or ultrasound. We undertook this study to describe the spectrum of gadolinium enhancement and morphologic features of ILC on magnetic resonance imaging (MRI). Nineteen patients with ILC who presented with a palpable mass, a mammographically visible abnormality, or an unknown primary underwent preoperative MRI of both breasts using a T1-weighted high-resolution gradient echo sequence (pre- and postcontrast), and an echoplanar sequence during the administration of gadolinium. Using a quantitative measure of gadolinium uptake over time, called the extraction flow (EF) product, and a normal tissue threshold EF level of 25 or less, enhancement for 15 of the 19 cancers was characterized. By consensus, three radiologists categorized the morphologic features of the lesions. For the 15 cases of ILC that had echoplanar data, analysis showed peak EFs ranging between 25 and 120, and the majority showed EFs in the 30s. A substantial portion of two tumors enhanced in a similar fashion to normal breast tissue, with EFs in the low 20s. Morphologically MRI showed a focal mass in eight cases, regional enhancement in five, segmental enhancement in one, segmental enhancement with multiple small nodules in one, a mixture of a focal mass and regional enhancement in one, diffuse enhancement in one, multiple small nodules in one, and bilateral disease in one. Of the focal masses, seven were irregular in shape and one was round; six had ill-defined margins and two had spiculated margins. All eight enhanced heterogeneously. Four cases had multifocal disease and one case had unsuspected contralateral disease discovered only on MRI. MRI using a combination of morphology and a quantitative measure of gadolinium uptake was able to detect the majority of cases of ILC. However, there was a variable morphologic appearance and contrast enhancement pattern on MRI. A few lesions were difficult to distinguish from normal tissue. This suggests that some cases of ILC may be difficult to detect on MRI. 
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  • 167
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    Helicobacter 8 (2003), S. 0 
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    Topics: Medicine
    Notes: The mechanisms by which Helicobacter pylori escape the host immune response remains an important topic. Regulatory T cells appear to play a role in the persistence of the infection and the control of tissue damage. In the thought that the host genetic background influences the cross-talk between pathogens and hosts, the impact of cytokine polymorphisms on the outcome of H. pylori has been further delineated in the review period. On the other hand, several additional genes of H. pylori have been shown to participate in the pro-inflammatory cytokine and chemokine response to the infection. Finally, progress has been achieved in vaccine development, with new vaccine delivery systems and routes of immunization tested in animal models and human volunteers.
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    Topics: Medicine
    Notes: Numerous studies are still published on diagnostic tests for Helicobacter pylori, essentially for noninvasive tests. The urea breath test is applied in different types of patients, and there are attempts to have quicker and simpler protocols. Stool tests using monoclonal antibodies are now evaluated while serology is still a subject of interest. The progress in PCR (multiplex PCR, real-time PCR) has also stimulated the research in this area of invasive tests, in order to get insight into virulence factors, macrolide susceptibility and to detect H. pylori in nonconventional specimens.
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  • 169
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    Topics: Medicine
    Notes: Abstract: Breast cancer treatment and research is becoming more multidisciplinary in nature. Several modalities and areas of expertise are critical for optimal patient management. The basis for medical decisions and recommendations must reflect outcomes and clinical trial data that are designed and interpreted with broad input across different fields. Hence there has been a trend for specialization in breast disease in many large community and academic practices. Furthermore, a system of communication and standardization of data values, procedures, and protocols has begun, but needs much further development. There are many natural barriers to the process of multidisciplinary care and research in terms of logistics, finances, and education. The example of preoperative neoadjuvant therapy for early stage locally advanced breast cancer is one that involves multiple disciplines in the formulation of a treatment and in future research that will define the optimal individualized approach. This process can also shed further light on biologic principles and potential for improved treatment. Solutions for overcoming barriers to multidisciplinary care should include incentives for collaborative and coordinated clinical care across disciplines. A model of increased efficiency because of pooled resources and specialization in several fields should also be accompanied by a demonstration of increased quality of care and patient satisfaction. Any process that adds to cost or inconvenience needs to be justified in an evidence-based manner. Finally, these initiatives need to be effectively communicated to the professional and policy-making communities and to the public at large through well-conceived and unbiased educational venues. 
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  • 171
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  • 172
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    Notes: The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management.This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues;• the current status of wound bed preparation;• an analysis of the acute and chronic wound environments;• how wound healing can take place in these environments;• the role of wound bed preparation in the clinic;• the clinical and cellular components of the wound bed preparation concept;• a detailed analysis of the components of wound bed preparation. (WOUND REP REG 2003;11:1–28)
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  • 173
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    Notes: Arginine is a basic amino acid that plays several pivotal roles in cellular physiology. Like any amino acid, it is involved with protein synthesis, but it is also intimately involved with cell signaling through the production of nitric oxide and cell proliferation through its metabolism to ornithine and the other polyamines. Because of these multiple functions, arginine is an essential substrate for wound healing processes. Numerous studies have shown that arginine supplementation can lead to normalization or improvement of healing. This article reviews the basic biochemistry and cell signaling within which arginine performs its functions. In particular, the requirement for this amino acid in tissue repair is highlighted. (WOUND REP REG 2003;11:419–423)
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  • 174
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    Topics: Medicine
    Notes: The orthodox view has been that reactive oxygen species are primarily damaging to cells. There is general agreement that while high (3%) doses of H2O2 may serve as a clinical disinfectant, its overall effect on healing is not positive. Current work shows that at very low concentrations, reactive oxygen species may regulate cellular signaling pathways by redox-dependent mechanisms. Recent discoveries show that almost all cells of the wound microenvironment contain specialized enzymes that utilize O2 to generate reactive oxygen species. Numerous aspects of wound healing are subject to redox control. An understanding of how endogenous reactive oxygen species are generated in wound-related cells may influence the healing process and could result in new redox-based therapeutic strategies. Current results with growth factor therapy of wounds have not met clinical expectations. Many of these growth factors, such as platelet-derived growth factor, rely on reactive oxygen species for functioning. Redox-based strategies may serve as effective adjuncts to jump-start healing of chronic wounds. The understanding of wound-site redox biology is also likely to provide novel insights into the fundamental mechanisms that would help to optimize conditions for oxygen therapy. While a window of therapeutic opportunity seems to exist under conditions of low concentrations of reactive oxygen species, high levels may complicate regeneration and remodeling of nascent tissue. (WOUND REP REG 2003;11:431–438)
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  • 175
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  • 176
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    Topics: Medicine
    Notes: The foot ulcer is one of most common and devastating complications of diabetes and is associated with considerable morbidity and mortality. The major causes of these ulcers are ischemia/hypoxia, neuropathy, and infection, and they often coexist. Despite conventional therapy including revascularization procedures when appropriate, three situations lead frequently to amputation: persistent critical limb ischemia, soft tissue infection, and impaired wound healing from osteomyelitis. In these conditions, hyperbaric oxygen therapy may be used as an adjunctive treatment and is associated with a better outcome. Randomized, prospective, controlled trails have shown the benefit of hyperbaric oxygen therapy in diabetic ulcers of the lower extremity. Transcutaneous oxygen measurement performed under hyperbaric oxygen therapy has a prognostic significance when used to select patients who are the most likely to benefit from therapy. Hyperbaric oxygen should be added to conventional treatment if the transcutaneous oxygen tension close to the trophic lesion in 2.5 ATA hyperbaric oxygen is over 200 mmHg. Peri-wound transcutaneous oxygen tensions over 400 mmHg in 2.5 ATA hyperbaric oxygen or over 50 mmHg in normobaric pure oxygen predict healing success with adjuncted hyperbaric oxygen therapy with high accuracy. (WOUND REP REG 2003;11:458–461)
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  • 177
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    Notes: Smad3 is involved in mediating intracellular signaling by members of the transforming growth factor-β superfamily and plays a critical role in the cellular proliferation, differentiation, migration, and elaboration of matrix pivotal to cutaneous wound healing. Cross-talk between Smad3 and hormone signaling in vitro has been suggested as an important control mechanism regulating cell activities; however, its relevance in vivo is unknown. Here we report that Smad3 plays a role in androgen-mediated inhibition of wound healing but not in the responses to estrogen modulation in vivo. Both wild-type and Smad3 null female mice exhibited delayed healing following ovariectomy, which could be reversed by estrogen replacement. By contrast, castration accelerated healing in wild-type male mice and was reversible by exogenous androgen treatment. Intriguingly, modulation of androgen levels resulted in no discernible perturbation in the healing response in the Smad3 null mice. Mutant monocytes could be lipopolysaccharide stimulated to produce specific pro-inflammatory agents (macrophage monocyte inhibitory factor) in a fashion similar to wild-type cells, but exhibited a muted response to androgen-mediated stimulation while maintaining a normal response to estrogen-induced macrophage inhibitory factor inhibition. These data suggest that Smad3 plays a role in mediating androgen signaling during the normal wound healing response and implicate Smad3 in the modulation of inflammatory cell activity by androgens. (WOUND REP REG 2003;11:468–473)
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  • 178
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    Topics: Medicine
    Notes: The participation of fibroblasts in wound repair is a coordinated effort requiring sequential cellular modulations to behavior including migration (entering), proliferation (increasing cell numbers), synthesis (depositing a collagen matrix), remodeling (organizing collagen), transformation into myofibroblasts, apoptosis, and elimination. Disruptions in that orderly sequence of behaviors will alter repair. Insights into controlling wound repair have focused on soluble factors such as cytokines and growth factors. Here we examine the direct communications between coupled cells through gap junctional intercellular communications. Molecules of less than 1000 MW pass directly between cells through gated gap junction channels. Sugars, amino acids, and oxygen, as well as second messengers such as cAMP, inositol phosphates, and calcium can pass directly between coupled cells. Does gap junctional intercellular communication affect fibroblast phenotype progression in granulation tissue maturation? In rats gap junctional intercellular communication uncouplers heptanol and endosulfan were injected daily into polyvinyl alcohol sponge implants. At 7 days, uncoupler-treated implants had capsules with increased fibroblast density, reduced cell penetration into the sponge, and diminished numbers of myofibroblasts. By polarized light, the uncouplers reduced the deposition and organization of collagen and thereby disrupted the coordinated phenotypic changes seen in fibroblasts during the repair process. It is proposed that gap junctional intercellular communication is critical for fibroblast progression from migratory cell to apoptosis as granulation tissue matures into scar. (WOUND REP REG 2003;11:481–489)
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  • 179
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    Topics: Medicine
    Notes: Work from Tom Hunt's laboratory first identified wound hypoxia as a potential regulator of the biology of cells participating in tissue repair. Current understanding of the role of oxygen in the regulation of gene expression begins to provide a mechanistic basis for the prediction that oxygen could be a fundamental regulator of wound healing made by the Hunt laboratory. The present article describes the experience of the authors' laboratory in defining the expression of two oxygen-regulated genes, those for the inducible form of nitric oxide synthase and for arginase I in experimental wounds. Observations made regarding these two genes are discussed in the context of the overall regulatory role of oxygen as a phenotypic modulator of inflammatory cells. (WOUND REP REG 2003;11:445–451)
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  • 180
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  • 181
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    Notes: For many years, lactate has been known to accelerate collagen deposition in cultured fibroblasts and, without detailed explanation, has been presumed to stimulate angiogenesis. Similarly, hypoxia has been linked to angiogenic effects and collagen deposition from cultured cells. Paradoxically, however, wound angiogenesis and collagen deposition are increased by breathing oxygen and decreased by hypoxia. Lactate accumulates to 4–12 mM in wounds for several reasons, only one of which is the result of hypoxia. Oxygen in wounds is usually low but can be increased by breathing oxygen (without change in lactate). We have reported that lactate elicits vascular endothelial growth factor (VECF) from macrophages, as well as collagen, some heat shock proteins, and VECF from endothelial cells, and collagen from fibroblasts, even in the presence of normal amounts of oxygen. Hypoxia exerts many of these same effects in cultured cells. In this study, we elevated extracellular lactate in wounds by implanting purified solid-state, hydrolysable polyglycolide. A steady-state 2–3 mM additional elevation of lactate resulted. With it, there was a significant short-term elevation of interleukin-1β, a long-term elevation of VECF (2×) and transforming growth factor-β1 (2–3×), a 50% elevation in collagen deposition, and a large reduction of insulin-like growth factor-1 (− 90%). We propose that lactate induces a biochemical “perception” of hypoxia and instigates several signals that activate growth factor/cytokine signals while the continued presence of molecular oxygen allows endothelial cells and fibroblasts to reproduce and deposit collagen. The data are consistent with ADP-ribosylation effects and oxidant signaling. (WOUND REP REG 2003;11:504–509)
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  • 182
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    Notes: Nearly 36 years ago Thomas K. Hunt, with Patrick Twomey, was the first to report that the level of lactate significantly increases in healing wounds. This observation convinced him that lactate, besides being the by-product of glycolysis, must have a regulatory role in the healing process. He set out to investigate this observation and found it to be so. This article is written in recognition of his foresight. It summarizes the salient findings emanating from this fundamental observation and describes the biochemical principles by which most of the lactate action may be explained. Down-regulation of the ubiquitous protein modification reaction called ADP-ribosylation turned out to be a basic signal behind the role of lactate in wound healing. (WOUND REP REG 2003;11:439–444)
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  • 183
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    Topics: Medicine
    Notes: Numerous reports support the concept that tissues require an adequate oxygen supply to heal well and to prevent complications of infection. Adequate oxygen supply to tissue depends on perfusion as well as arterial oxygen tension, and tissue oxygen tension, particularly in peripheral tissues, is dependent on adequate vascular volume. Therefore, potential benefits to wound healing and reduction in infection in postsurgical patients might be attained by judicious manipulation of supplemental oxygen and/or fluids in the perioperative period. This article reviews evidence that suggests such manipulations are beneficial and proposes that integrated care pathways be developed that include these interventions. (WOUND REP REG 2003;11:462–467)
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  • 184
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    Topics: Medicine
    Notes: Diabetic wound healing is characterized by deficiencies in both growth factor and collagen production. We have observed that expression of homeobox D3 (HoxD3), a collagen-inducing transcription factor, and expression of collagen are reduced in an established animal model of diabetic wound repair, the leptin-deficient diabetic (db/db) mouse. We sought to evaluate whether the diminished expression of collagen and HoxD3 would be maintained once fibroblasts were removed from the diabetic wound environment. Fibroblasts were isolated from both wild-type and diabetic animals and expression of HoxD3 and collagen assessed. We found that when removed from the diabetic wound environment, HoxD3 and type I collagen expression are increased in diabetic fibroblasts when compared to wild-type fibroblasts. The increase in type I collagen is not related to increased production or activation of transforming growth factor-β1. However, when the diabetic fibroblasts are cultured in a 3D collagen matrix, expression of type I collagen and HoxD3 is markedly reduced and reflects the pattern of gene expression observed in the in vivo diabetic wound environment. Thus, although diabetic fibroblasts can regain the capacity to express high levels of collagen and HoxD3 once removed from the diabetic wound environment, culturing cells in the presence of a 3D collagen matrix is sufficient to revert these fibroblasts to their previous nonsynthetic state. (WOUND REP REG 2003;11:474–480)
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  • 185
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    Topics: Medicine
    Notes: Although it is well recognized that pressure-induced ischemia initiates the formation of pressure ulcers, the many complex mechanisms responsible for the pathogenesis of these ulcers remain poorly understood. It has been reported that chronic ulcers contain an elevated level of proteolytic enzymes, especially neutrophil-derived matrix metalloproteinase-8 and elastase. This evidence suggests that neutrophils are a major component in the pathogenesis of chronic pressure ulcers. Therefore, this study characterized the cellular components of chronic pressure ulcers. Three-millimeter biopsies (6 mm deep) from granulation tissue in pressure ulcers were obtained from 11 patients. A total of 14 biopsies were obtained from these 11 patients for analysis. A portion of each specimen was fixed in formalin for routine histology. Other portions of biopsies were frozen for analysis of myeloperoxidase activity. In addition, cells on the surfaces of the ulcers were collected by lavage for histologic characterization. Routine histologic analysis of all 14 biopsies of the pressure ulcers showed regions near the surface of each that contained dense neutrophil infiltration associated with edema and apparent marked matrix dissociation. In the deeper regions there was an increased density of blood vessels, and many contained rounded endothelial cells surrounded by migrating neutrophils. Cells collected by lavage from the ulcer surface were prepared by Cytospin and found to be greater than 95% neutrophils with occasional large macrophages actively phagocytosing depleted neutrophils. In addition, there was a significant correlation of myeloperoxidase activity with actual neutrophil counts in the ulcer biopsies further confirming the dense presence of neutrophils. These studies directly show that there is extensive neutrophil infiltration in chronic pressure ulcer granulation tissue. Furthermore, the persistence of neutrophils and their destructive enzymes appears responsible for the extensive matrix dissociation and thus contributes to the chronicity of these ulcers. (WOUND REP REG 2003;11:490–495)
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  • 186
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  • 187
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    Notes: Tissue PO2 levels are known to directly modulate numerous processes involved in the reparative response to cutaneous tissue injury, including cell differentiation and migration, extracellular matrix synthesis and maturation, and effectiveness of endogenous and exogenous growth factors. Oxygen is therefore likely the critical variable determining the healing capabilities of any tissue. Significant advances in the understanding of cutaneous wound healing progressed with advances in the measurement of tissue PO2, which has advanced over the past several decades from implantable probes to now include molecular tools such as the transcription factor hypoxia inducible factor-1 (HIF-1). HIF-1 modulates the expression of genes that drive the cellular adaptive response to hypoxia and possess the HIF-1 binding sequence named hypoxia response element within their promoter sequence. Molecular biology techniques are now allowing exploitation of the HIF-1/hypoxia response element pathway to drive the expression of potential vulnerary ectopic genes. Here we show the utility of the hypoxia response element for hypoxia-driven expression of the transforming growth factor-β–signaling component Smad3 in vitro and the in vivo detection of ischemic hypoxia using luciferase. Smad3 is a positive effector of transforming growth factor-β superfamily signal transduction. Such approaches are the latest evolution of work championed by Hunt and colleagues over the past 4 decades. (WOUND REP REG 2003;11:496–503)
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  • 188
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    Notes: In previous studies, mice given a full-thickness scald injury had an influx of neutrophils into the skin that followed a local increase in a neutrophil chemoattractant. Because macrophages are known to infiltrate the wound area after neutrophils and are essential for normal wound repair, studies were designed to characterize the time course of macrophage accumulation in the wound and to identify the factor(s) responsible for this influx. A macrophage infiltrate into the wound was observed at 4 days post-injury and persisted through at least 10 days. This influx was preceded by an initial fourfold increase in dermal monocyte chemoattractant protein-1 levels at 24 hours post-injury (p 〈 0.05). This elevation in monocyte chemoattractant protein-1 was enhanced at 4 and 10 days postburn resulting in a sixfold increase over baseline (p 〈 0.01). Levels of tumor necrosis factor-α, a proinflammatory cytokine known to induce chemokine production, were elevated at 90 minutes after injury in burn- versus sham-injured groups (p 〈 0.05). Furthermore, administration of tumor necrosis factor-α neutralizing antibody in vivo reduced the dermal levels of monocyte chemoattractant protein-1 seen at 10 days postburn by 57% (p 〈 0.01); however, macrophage accumulation was not altered. Thus, elevated systemic TNF-α levels may influence the local chemokine milieu following burn injury. (WOUND REP REG 2003;11:110–119)
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  • 189
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    Notes: Impaired wound healing is characteristic of diabetic patients. Potential reasons include poor inflammatory response, granulation tissue formation, and abnormal patterns of cytokine release and response. Vascular endothelial growth factor, abnormally regulated during healing in diabetics, is the major factor stimulating angiogenesis during normal wound healing. We tested our hypothesis that topically applied vascular endothelial growth factor would improve wound closure rates in diabetic animals in a full-thickness wound model in genetically diabetic mice (C57 BL/KsJ db/db). Animals received either 1.0 µg of vascular endothelial growth factor165 or polyethylene glycol alone topically to wounds daily between days 0 and 4 postwounding. Wound area was measured at days 0, 5, 10, 15, and 21. Data were analyzed using probit analysis and expressed as length-of-time (LT) to 50, 90, and 95% wound closure. Among untreated animals, nondiabetics had an LT50 of 8.5 days (fiducial limits 8.3–8.7), while diabetics had an LT50 of 15.8 days (15.6–16.1). Vascular endothelial growth factor-treated animals had LT50 values of 7.8 (7.6–8.1) and 11.8 days (11.6–12.0) for nondiabetics and diabetics, respectively, representing a 25% improvement in time to 50% closure in treated diabetics. We conclude that topically applied vascular endothelial growth factor improves time to wound closure in the genetically diabetic mouse model. (WOUND REP REG 2003;11:127–131)
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    Notes: There is evidence from animal and human study that suggests clinical use of monocytes/macrophages may be of benefit in wound healing, tissue regeneration, and cancer therapy. To facilitate further study, a method was developed for sterile isolation and cryopreservation of adherent monocyte/macrophages from mononuclear cell apheresis units collected from unstimulated normal human donors. Preparations contained approximately 1 × 108 total cells and were comprised of approximately 60% monocytes, 38% lymphocytes, and 2% granulocytes. Cells could be cryopreserved for up to 8 months and subsequently thawed and stored at 1–6°C for up to 4 hours with retention of viability and adequate phagocytic function. These cells can be used in clinical trials to determine their possible therapeutic benefit, e.g., whether administration of exogenously supplied cells improves the healing of chronic wounds or promotes the regeneration of transected nerves. (WOUND REP REG 2003;11:145–149)
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    Notes: There is a great need to establish reproducible methods for evaluative studies of wound treatment and wound healing. Validation of the healing process through optical techniques, as well as histologic and immunohistochemical methodologies, have been improved and to some extent have become well-established assays. Data relating to biomechanical properties, e.g., evaluation of the tensile strength of scar tissue that forms in experimental wound treatment strategies, are less widely available. We chose the domestic pig as an animal model in which to examine epidermal wound healing. We implanted specially made chambers that served to isolate the wounds and prevent epidermal migration from the edges. We performed histologic and immunohistochemical analyses as well as evaluation of biomechanical qualities of scar tissue using laser tensiometry. Pig skin is well suited for wound healing studies, and wound creation, implantation of the chambers, and the regular changing of dressings could all be carried out in the operating theater. In addition to established macroscopic evaluation and microscopic documentation, the need for objective biomechanical assessment of scar tissue by measuring tensile strength has been met using laser tensiometry. By optimizing methods for measuring tensile strength, it is possible to evaluate the biomechanical quality of scar tissue formed following different courses of wound treatment, as well as histologic assessment. (WOUND REP REG 2003;11:150–157)
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  • 192
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    Notes: An altered metabolism of endothelial cell–derived nitric oxide has been implicated in the microvascular dysfunction associated with ischemia/reperfusion. The objective of this study was to examine whether S-nitroso human serum albumin, a novel nitric oxide-donor, improves flap viability and whether it influences edema formation after prolonged ischemia when administered prior to and in the initial phase of reperfusion. Denervated epigastric island skin flaps were elevated in 30 male Sprague Dawley rats, rendered ischemic for 8 hours, subsequently reperfused and further observed for either 3 hours (acute) or 7 days (chronic). In the sham rats (n = 6), skin flaps were elevated only. Starting 1 hour prior to reperfusion, S-nitroso human serum albumin (n = 12) or human serum albumin (n = 12) as placebo was infused systemically for 2 hours. In the chronic model, flap necrosis as well as viable flap size was evaluated after 7 days of reperfusion in six rats per group, comparing to sham rats. In the acute model, edema formation was evaluated after 3 hours of reperfusion in six rats per group. Administration of S-nitroso human serum albumin significantly decreased flap necrosis from 18.1 ± 15.6% in the human serum albumin group to 2.1 ± 1.5% in the S-nitroso human serum albumin group, which was similar to the sham group (2.5 ± 4.2%). Viable flap size (sham 13.4 ± 1.6 cm2) was also significantly improved in the S-nitroso human serum albumin group (10.1 ± 1 cm2) versus the human serum albumin group (7.0 ± 2.2 cm2). There was no significant difference between the groups regarding postischemic edema formation. These results show that administration of S-nitroso human serum albumin prior to and in the initial phase of reperfusion significantly improves flap viability after 7 days but does not influence early observable edema formation. These findings support the role of nitric oxide as an important mediator in the protection against skin flap ischemia/reperfusion injury. (WOUND REP REG 2003;11:3–10)
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    Notes: The objective of this study was to characterize fibroblasts at sequential time points during intra-oral wound healing in the rat. Experimental wounds were made at several time points in the mucoperiosteum of the palate of 35-day-old Wistar rats. Fibroblasts were cultured from the biopsies under standard conditions for the same number of passages. The expression of the integrin subunits α1, α6, and β1; and the intermediate filaments α-smooth muscle actin and vimentin were analyzed by flow cytometry. Western blot analysis was performed at 0, 8, and 60 days postwounding to confirm the expression of both intermediate filaments. The phenotypic profiles of fibroblasts cultured from subsequent stages in the wound healing process differed considerably. We conclude that distinct fibroblast phenotypes can be isolated from different stages in wound healing. These phenotypes remained stable during in vitro culturing. In addition, cryosections of the wound areas were made at identical time points and were immunohistochemically stained for the same antigens. The immunohistochemical staining correlated well to the flow-cytometric data. These results suggest the occurrence of multiple subpopulations of fibroblasts with a specialized function during wound healing. We hypothesize that undesirable consequences of wound healing might be prevented through the modulation of specific fibroblast subpopulations. (WOUND REP REG 2003;11:55–63)
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation. (WOUND REP REG 2003;11:25–34)
    Type of Medium: Electronic Resource
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    Wound repair and regeneration 11 (2003), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 196
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Type I collagen is a clinically approved biomaterial largely used in tissue engineering. It acts as a regenerative template in which the implanted collagen is progressively degraded and replaced by new cell-synthesized tissue. Apligraf®, a bioengineered living skin, is composed of a bovine collagen lattice containing living human fibroblasts overlaid with a fully differentiated epithelium made of human keratinocytes. To investigate its progressive remodeling, athymic mice were grafted and the cellular and the extracellular matrix components were studied from 0 to 365 days after grafting. Biopsies were analyzed using immunohistochemistry with species-specific antibodies and electron microscopy techniques. We observed that this bioengineered tissue provided living and bioactive cells to the wound site up to 1 year after grafting. The graft was rapidly incorporated within the host tissue and the bovine collagen present in the graft was progressively replaced by human and mouse collagens. A normal healing process was observed, i.e., type III collagen appeared transiently with type I collagen, the major collagen isoform present at later stages. New molecules, such as elastin, were produced by the living human cells contained within the graft. This animal model combined with species-specific immunohistochemistry tools is thus very useful for studying long-term tissue remodeling of bioengineered living tissues. (WOUND REP REG 2003;11:35–45)
    Type of Medium: Electronic Resource
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  • 197
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    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 11 (2003), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Upon stimulation, mast cells release a heterogeneous group of factors that promote inflammation and influence cell proliferation. Mast cells accumulate at sites of injury, further suggesting a critical role in wound healing. To assess the importance of mast cells in tissue repair, we compared wound healing in mast cell–deficient WBB6F1/J-KitW/KitW–v (KitW/KitW–v) and wild type WBB6F1/++ (WT) mice. During the inflammatory phase, neutrophil infiltration into wounds of the KitW/KitW–v mice was significantly less than that of WT mice (84.6 ± 10.3 vs. 218 ± 26.0 cells/10 high-power fields at day 3, p 〈 0.001), while wound macrophage and T cell infiltration were similar in both strains. The decrease in neutrophils could not be explained by changes in tumor necrosis factor-α or macrophage inflammatory protein-2 levels, because the amounts of these two neutrophil chemoattractants were similar in both KitW/KitW–v and WT mice. Surprisingly, the absence of mast cells had no effect on the proliferative aspects of wound healing, including reepithelialization, collagen synthesis, and angiogenesis. Although mast cells are known to release proangiogenic mediators, vascular endothelial growth factor levels were similar in WT and KitW/KitW–v mice. Moreover, levels of fibroblast growth factor-2 were increased in KitW/KitW–v mice (4206 ± 107 vs. 1865 ± 249 pg/ml, p 〈 0.01). These results suggest that mast cells modulate the recruitment of neutrophils into sites of injury, yet indicate that mast cells are unlikely to exert a major influence on the proliferative response within healing wounds. (WOUND REP REG 2003;11:46–54)
    Type of Medium: Electronic Resource
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  • 198
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    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 11 (2003), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Wounding skin generates an endogenous electric field of 100–200 mV/mm in the immediate vicinity of the wound. When keratinocytes are exposed to direct current electric fields of this magnitude, they exhibit galvanotaxis, or directional migration toward the cathode, suggesting that wound-generated electric fields provide migrational cues that contribute to wound healing. Because melanocytes must also migrate into the healing wound to repigment it, their motility in response to electric fields of physiologic magnitude was examined. Human skin–derived melanocytes, either exposed to 100 mV/mm direct current electric fields or nonexposed controls, both exhibited motility rates of 9 µm/hour, significantly (three- to five-fold) lower than the motility rates of keratinocytes under identical conditions. However, in sharp contrast to keratinocytes, melanocytes exhibited no directional migration in the electric field. Additionally, neither the number of primary dendrites per cell, nor the orientation of the dendrites with respect to the field vector, nor the average length of the dendrites was significantly different in melanocytes exposed to the electric field as compared to nonexposed controls. Thus, in marked contrast to keratinocytes, human skin–derived melanocytes do not respond to direct current electric fields of physiologic magnitude with either directional migration or reorientation of dendrites. This may account for the delay in repigmentation that often accompanies wound reepithelialization. (WOUND REP REG 2003;11:64–70)
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  • 199
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    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 11 (2003), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of this study was to investigate the structure and organization of collagen during the healing of penetrating rabbit corneal wounds. Full-thickness wounds were produced in both corneas of six New Zealand White rabbits with a 2-mm trephine. After 5, 10, and 16 months, wounds were examined using transmission electron microscopy and wide-angle synchrotron X-ray diffraction, which allowed the quantification of the relative amount of collagen and fibril orientation in different parts of the cornea. The intensity of the diffraction patterns taken from the wound edge was much higher than patterns collected at the wound center, indicating a greater amount of collagen near the wound edge. This collagen was shown to have a preferred orientation, forming a circular pattern around the wound. As the wounds healed, the amount of preferentially aligned collagen decreased and lamella formation and ordered fibrillar arrangement increased as shown by electron microscopy. The orientation of collagen fibrils in healing penetrating corneal wounds is not random. Instead, fibrils tend to be circularly arranged within and without the wound, gradually becoming more normal over time. We speculate that collagen is artefactually displaced during trephination, resulting in an abnormal alignment of the fibrils surrounding the wound edge, and that this influences the wound healing process. (WOUND REP REG 2003;11:71–78)
    Type of Medium: Electronic Resource
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  • 200
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Integrin-mediated cell adhesion and growth factor stimuli are both required for optimal control of cell proliferation. In the context of skin injury, cell-derived fibronectin and platelet-derived growth factor play important roles in the stimulation of cell proliferation and migration, activities that are crucial to the healing process. To assess the ability of exogenously supplied plasma-derived fibronectin to stimulate wound repair and to study its ability to cooperate with platelet-derived growth factor-BB during healing, we devised a novel topical delivery formulation that allows the controlled release of both molecules to a wound. Using this topical formulation and the rabbit ear model of dermal wound healing, we show that plasma fibronectin is a potent stimulator of the wound healing process. We also show that administration of fibronectin and platelet-derived growth factor-BB in combination has additive wound healing effects. Finally, we report novel findings on the ability of soluble plasma fibronectin to potentiate the mitogenic effects of platelet-derived growth factor-BB in vitro. These findings not only show that optimal concentrations of exogenous fibronectin administered using an effective delivery system stimulate wound healing; they also suggest that PDGF-BB should be administered with fibronectin to achieve optimal therapeutic stimulation of wound healing. (WOUND REP REG 2003;11:79–89)
    Type of Medium: Electronic Resource
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