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At least 829 records · Page 46Linked to original sources
PubMed1999

Three pioneers in the early history of neuroradiology: the Snyder lecture.

The early history of neuroradiology is linked to three pioneers who worked during the first half of the 20th century. Two were neuropsychiatrists and one was a neurosurgeon. Arthur Schüller, a Viennese neuropsychiatrist, was the first to study systematically the X-ray skull changes caused by intracranial disease. He is generally regarded as the 'father of neuroradiology'. Walter Dandy, the great neurosurgeon of Johns Hopkins, introduced ventriculography and penumoencephalography. Egas Moniz, a Portuguese neuropsychiatrist, developed cerebral angiography, and was awarded the Nobel Prize in Medicine for originating prefrontal lobotomy. The work of these three pioneers laid the basis through which modern neuroradiology became a separate discipline.

Diagnostic Techniques, Neurological↗
PubMed1997

William L. McGuire Memorial Lecture. Antiestrogens: mechanisms of action and resistance in breast cancer.

Antiestrogens have proven to be highly effective in the treatment of hormone-responsive breast cancer. However, resistance to antiestrogen therapy often develops. In addition, although tamoxifen-like antiestrogens are largely inhibitory and function as estrogen antagonists in breast cancer cells, they also have some estrogen-like activity in other cells of the body. Thus, recent efforts are being directed toward the development of even more tissue-selective antiestrogens, i.e. compounds that are antiestrogenic on breast and uterus while maintaining the beneficial estrogen-like actions on bone and the cardiovascular system. Efforts are also being directed toward understanding ligand structure-estrogen receptor (ER) activity relationships and characterizing the molecular changes that underlie alterations in parallel signal transduction pathways that impact on the ER. Recent findings show that antiestrogens, which are known to exert most of their effects through the ER of breast cancer cells, contact a different set of amino acids in the hormone binding domain of the ER than those contacted by estrogen, and evoke a different receptor conformation that results in reduced or no transcriptional activity on most genes. Resistance to antiestrogen therapy may develop due to changes at the level of the ER itself, and at pre- and post-receptor points in the estrogen receptor-response pathway. Resistance could arise in at least four ways: (1) ER loss or mutation; (2) Post-receptor alterations including changes in cAMP and phosphorylation pathways, or changes in coregulator and transcription factor interactions that affect the transcriptional activity of the ER; (3) Changes in growth factor production/sensitivity or paracrine cell-cell interactions; or (4) Pharmacological changes in the antiestrogen itself, including altered uptake and retention or metabolism of the antiestrogen. Model cell systems have been developed to study changes that accompany and define the antiestrogen resistant versus sensitive breast cancer phenotype. This information should lead to the development of antiestrogens with optimized tissue selectivity and agents to which resistance may develop more slowly. In addition, antiestrogens which work through somewhat different mechanisms of interaction with the ER should prove useful in treatment of some breast cancers that become resistant to a different category of antiestrogens.

Breast Neoplasms↗
PubMed1998

The changing landscape of breast cancer clinical research. ESMO-Award Lecture, ECCO-9 Hamburg, 18 September 1997.

Clinical research for breast cancer is moving in three new directions following: 1) a critical analysis of three decades of randomized clinical trials for early disease; 2) increasing awareness of this lethal disease among women, generating women's associations which are pressing for improved breast cancer education, screening and treatment; 3) an exponential growth in our understanding of breast cancer molecular biology, leading to a number of innovative therapies with new targets in the cancer cell or its environment. It is the remarkable work of the Oxford Group which has finally vindicated the use of our three main weapons against breast cancer micro-metastases, namely tamoxifen, chemotherapy and ovarian ablation. There is now consensus that clinical research in the adjuvant setting may gain speed and efficiency through intergroup collaboration. Such an 'Intergroup' has been recently created in Europe and will collaborate with the American-Canadian Intergroup. Women's associations have only recently stepped forward to demand better care, and more effective therapies: they are becoming new partners in identifying critical issues in breast cancer research. Medical oncologists involved in breast cancer research are facing a new challenge: the optimal integration of traditional breast cancer therapies, namely endocrine treatments and chemotherapy, and entirely new strategies targeting signal transduction, apoptosis or angiogenesis. In view of the above, there is no doubt that we are entering a new and exciting era in breast cancer clinical research.

Antineoplastic Agents↗
PubMed2001

The Hofgeismar lectures: a contemporary overview of Horneyan psychoanalysis.

Part I of this paper describes Karen Horney's theory of neurosis. In the 1930s, Horney repudiated Freud's view of female developmental psychology. She argued that cultural factors rather than anatomy or innate biological drives were the primary determinants not only of female development but of personality, as well. When genetic and environmental circumstances together lead to basic anxiety early in life, she believed a deep inner conflict emerges in the individual leading to the need for elaborating layers of rigidified protective defenses. She called this the neurotic process. This process can result in discrete symptoms of mental disorder as well as the more generalized problems of alienation from the person's real self and reliance on neurotic solutions. In Part II, the practical application of Horney's theory to clinical work is demonstrated in a case presentation of a notably timid and perfectionistic man. Part III points up elaborations of Horney's theories by later workers of her school, the American Institute for Psychoanalysis, and provides a history of her school within the broader context of American psychoanalysis. The author's emphasis on postmodern and narrativist elements of Horneyan psychoanalysis are illuminated, as well.

Academies and Institutes↗
PubMedDate not supplied

Nobel Lecture. Yeast and cancer.

The discovery of genes that control cell division in yeast, and their relation to cancer, is reviewed.

Cell Cycle Proteins↗
PubMed1998

The 1998 Herbert L. Needleman Award Lecture. Adolescent health: priorities for the next millennium.

There have been dramatic changes in adolescent health status over the past decade that have resulted from successful interventions. Overall mortality rates are down 14%, and many morbidities have declined. Today we know many of the elements that reduce risk: parental caring and connectedness, parental expectations for school and parent availability all outweigh family structure, ethnicity, and income. Likewise, schools can be extremely protective when young people feel connectedness. Factors associated with successful interventions include: strengthening families; strengthening educational involvement; expanding economic opportunities; and supporting youth development, not just problem reduction. Priorities for the next decade include: establishing resiliency-building interventions; developing positive correlates of negative behaviors; establishing broader multisectorial interdisciplinary teams; and formulating a new, more inclusive framework for adolescent health and development.

Adolescent↗