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At least 1,333 records · Page 74Linked to original sources
PubMed2003

Ham-Wasserman lecture: treatment of acute leukemia by inducing differentiation and apoptosis.

Conventional treatment of acute leukemia involves the use of cytotoxic agents (chemotherapy), but other strategies have been explored. All-trans retinoic acid (ATRA) and arsenic have clearly been effective in the treatment of acute promyelocytic leukemia (APL), which creates the possibility that other types of acute leukemia can be conquered by selectively inducing differentiation and/or apoptosis. A great number of investigations have been performed to elucidate the mechanisms and search for effective agents in the treatment of other types of acute leukemia by these new strategies. Progress at the molecular level has been achieved in explaining the mechanisms of action of ATRA and arsenic compounds, and several new agents have emerged, although their clinical effectiveness remains to be confirmed. Mechanism-/gene-based targeted therapy and a combination of different strategies will improve the treatment of acute leukemia.

Acute Disease↗
PubMed2003

Cecilie Greig memorial lecture 2002. Myocardial protection: an expanding or contracting discipline?

For the past thirty years cardiac surgeons have had a unique opportunity to study the consequences of myocardial ischemia and reperfusion. With the advent of an ability to intervene in acute myocardial syndromes, cardiologists have vigorously joined that effort as have fundamental scientists. Exogenous myocardial protective strategies have emerged as have novel strategies that take advantage of endogenous mechanisms of myocardial protection. As a consequence of improved myocardial protection, operative mortality and morbidity, in particular the low output syndrome, have diminished. However, despite important increases in the knowledge base referable to myocardial ischemia and reperfusion, major advances in myocardial protection have slowed in the past several years. This article explores potential untapped options for augmenting myocardial protection and focuses on the potential adverse interactions between cardiopulmonary bypass and myocardial protection as a prime target for future investigations leading to improved myocardial management during heart operations.

Cardiology↗
PubMed2003

American Cancer Society Award lecture. Psychological care of patients: psycho-oncology's contribution.

The centuries-old stigma attached to cancer precluded patients' being told their diagnoses, and thus, delayed any exploration of how they dealt with their illness. This situation changed in the United States in the 1970s when patients began to be told their cancer diagnosis, permitting the first formal study of the psychological impact of cancer. However, a second and equally long-held stigma attached to mental illness has been another barrier and this has kept patients from being willing to acknowledge their psychological problems and to seek counseling. This "double stigma" has slowed the development of psycho-oncology. However, we began to see rapid changes occurring in the last quarter of the 20th century. Valid assessment instruments were developed which were used in well-designed studies. Data from these studies and clinical observations led to increased recognition that psychosocial services are needed by many patients and provide significant assistance in coping with illness. Psycho-oncology has two dimensions: first, the study of the psychological reaction of patients at all stages of the disease, as well as of the family and oncology staff; second, exploring the psychological, social, and behavioral factors that impact on cancer risk and survival. Psycho-oncology now has a recognized role within the oncologic community through clinical care, research, and training as it relates to prevention of cancer through lifestyle changes, evaluation of quality of life, symptom control, palliative care and survivorship. Presently, there are sufficient research studies from which standards of care have been established. Both evidence and consensus-based clinical practice guidelines have been promulgated. It now possible to monitor the quality of existing psychosocial services by using these benchmarks of quality that have evolved in recent years.

Adaptation, Psychological↗
PubMed2003

2002 E. Mead Johnson Award for Research in Pediatrics Lecture: the molecular biology of the anemia of chronic disease: a hypothesis.

The anemia of chronic disease is a common disorder that afflicts patients with a wide variety of inflammatory conditions including arthritis, malignancies, infections, and inflammatory bowel disease. It results in significant morbidity and may be severe enough to require blood transfusions. The pathogenesis of anemia of chronic disease is not fully understood, but poor maintenance of red blood cell mass has been observed at three levels: 1) iron is not efficiently recycled from reticuloendothelial macrophages to erythroid precursors, 2) erythroid precursors respond poorly to erythropoietin, and 3) red blood cell survival is decreased. Whether each of these changes is related to the same effector of the inflammatory process is unknown. We have had the opportunity to investigate severe anemia of chronic disease in an unusual group of patients with glycogen storage disease type 1a. We found that anemia was directly related to the presence of large hepatic adenomas that inappropriately produced a new peptide hormone, hepcidin. Hepcidin has recently been identified as part of the innate immune response and is a key regulator of cellular iron egress. Based on our findings in this patient group, we propose a central role for hepcidin in anemia of chronic disease, linking the inflammatory process with iron recycling and erythropoiesis. We present a hypothesis based on our findings.

Adenoma↗
PubMed1996

A different approach to tumour suppression. The Alexandra Kefalides Memorial Lecture.

When tumour cells are fused with normal ones, malignancy is suppressed. It has been shown that this suppression is associated with the imposition on the hybrid cell of the terminal differentiation programme of the normal parent cell. We report here the consequences of imposing the synthesis of keratin 1 and keratin 10, markers of terminal differentiation in the epidermal keratinocyte, on malignant cells of keratinocyte and non-keratinocyte lineage. We find that there is extreme selection in vivo against cells making keratin 1: tumours arising from inocula of such cells are invariably produced by the selective overgrowth of cells in which keratin 1 synthesis has been drastically reduced, usually to trace levels. No such selection operates against keratin 10. It is possible that if substantial synthesis of keratin 1 could be induced in malignant cells in a clinical context, some therapeutic benefit might accrue.

Animals↗
PubMed2004

Garnett Passe and Rodney Williams Memorial Lecture: New clinical tests of unilateral vestibular dysfunction.

Vertigo is caused by unilateral vestibular dysfunction. Unilateral vestibular dysfunction represents either vestibular overactivity as benign positional vertigo or underactivity as in labyrinthitis or both, at different times, as in a Ménière's attack. Unilateral dysfunction could also be central rather than peripheral, such as in a lateral medullary syndrome. Unilateral vestibular dysfunction could affect any of the five different sensory areas in the labyrinth, the three semicircular canals and the two otoliths, or their brainstem connections. For rigorous diagnosis of the cause of vertigo, ideally one would have robust, reproducible, quantitative vestibular function tests sensitive to dysfunction of each of the five sensory regions in each ear. In working towards this ideal we have, over the last 15 years, developed three new vestibular function tests: (1) impulsive tests of individual semicircular canal function, (2) evoked potential tests of saccular function and (3) subjective visual horizontal tests of utricular function. The physiological rationale of these three tests is reviewed as well as the interpretation of their results in various diseases.

Evoked Potentials, Auditory↗