The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture

Recent data support the hypothesis that the fatty streak develops in response to specific phospholipids contained in LDL that become trapped in the artery wall and become oxidized as a result of exposure to the oxidative waste of the artery wall cells. The antioxidants present within both LDL and the microenvironments in which LDL is trapped function to prevent the formation of these biologically active, oxidized lipids. Enzymes associated with LDL and HDL (eg, platelet activating factor acetylhydrolase) or with HDL alone (eg, paraoxonase) destroy these biologically active lipids. The regulation and expression of these enzymes are determined genetically and are also significantly modified by environmental influences, including the acute-phase response or an atherogenic diet. The balance of these multiple factors leads to an induction or suppression of the inflammatory response in the artery wall and determines the clinical course.     

Berlyne Memorial Lecture.

Daniel Berlyne was a member of the faculty at the University of Toronto. His untimely death in 1976 at age 52 was noted by the establishment of the Berlyne Memorial Lecture to be given biennially by a distinguished psychologist. The inaugural lecture was given on 13 March 1978 by Jerome S. Bruner, Watts Professor of Psychology in Oxford University. The commemorative introduction--presented here--was by James M. Ham, Dean of the Graduate School and President-Elect of the University of Toronto (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Daniel Berlyne Memorial Lecture: Hormones and psychological processes.

In this lecture delivered at the University of Ontario in 1982, the author discusses the relationship of hormones to the psychological variables of perception, learning, and memory. Some examples of hormonal modification of perception include changes in food preferences, responses to sexual stimuli, and perceptual changes during the menstrual cycle. Perception may, in turn, affect hormones: A female's estrogen secretion may depend on how and how often she perceives the males around her. The effects of hormones on learning and memory are exemplified in animals in the learning that leads to the formation of permanent social bonds between mothers and their offspring. The hormonal state of the female undergoes rapid change at the end of pregnancy and immediately following parturition. Stimuli provided by the newborn are effective only during this period in animals such as sheep. However, once the mother has learned to recognize her newborn, the learning effects persist indefinitely without continuing hormonal support. Hormonal facilitation of memory occurs in some male birds when they first begin to sing. The hormone is not necessary for original learning, but it does influence activation of the putative memory trace. In turn, memory can inhibit or stimulate secretion of hormones. The author suggests that in investigations of complex behavior, psychological processes should be explored as mediators between hormones and behavior. (French abstract) (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Berlyne Memorial Lecture: Acquiring the uses of language.

Early language use begins with a transactional dialog, which is initially both nonverbal and dependent on shared knowledge. As the adult caretakers update their interpretation of the child's competence and make more sophisticated demands on his/her production the child takes a more active role. Two formats provide examples of this development: (a) "Bookreading" traces the child's development from the establishment of joint reference through pointing (through the development of turntaking) to eventual introduction of words in appropriate places in the dialog. (b) "Requesting" explores the production of pragmatic and semantic features in the child's language development. Three types of requests are examined: requests for objects, for joint role enactment, and for supportive action. In each type, the child's developing knowledge of the real world determines the way he or she guides the request and aids in making more complex requests. Both examples are taken from a study of 2 mother–infant dyads in which videotape recording of free play sessions were taken at fortnightly intervals in the child's home. One child was studied from 3 to 18 mo, the other from 5 to 24 mo of age. (French summary) (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hatfield Memorial Lecture 2007 Railways and materials: synergetic progress

Abstract

Railways were originally uniquely identified with the material of their initial construction and now are technically identified by the characteristic contact of 'steel wheel on steel rail'. Over 160 years ago failures of iron railway axles led to research into what we now know as metal fatigue. Accidents throughout the ages have acted as catalysts for research and improvements: this lecture will identify some key incidents. The change from iron to steel, following Bessemer's discovery of a method of bulk production and its implementation in Sheffield, resulted in fewer materials failures and enabled greater loads to be carried at greater speeds. Today's railways rely on a wide variety of materials from all the major classes of materials. The requirements of cost, weight, reliability, crashworthiness, maintainability and inspection are often in conflict as the service loadings imposed by the modern railway on materials have become more severe. It is not therefore surprising that despite our advances in knowledge and capabilities, costly failures still occasionally occur. Nevertheless, railways have benefited from, and contributed to, advances in material engineering way beyond the initial emphasis on iron.     

Sir Harold Gillies Memorial Lecture. Aesthetic plastic surgery and the future plastic surgeon

Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction in the tissue factor-mediated coagulation pathway. We measured plasma free-form TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and 22.00 h in 15 patients with coronary spastic angina, 13 patients with stable exertional angina, and 11 control subjects. There was a significant circadian variation in plasma free-form TFPI antigen levels in patients with coronary spastic angina (25.8+/-2.0 ng/ml at 06.00 h, 21.1+/-1.6 ng/ml at 14.00 h, and 20.2+/-1.4 ng/ml at 22.00 h; p<0.01). Furthermore, free-form TFPI antigen levels at 06.00 h were significantly higher in coronary spastic angina patients than in patients with stable exertional angina or control subjects (p<0.01). Free-form TFPI antigen levels increased after the ischemic attacks in coronary spastic angina (p<0.01). This circadian variation correlated with the frequency of attacks, with the peak level occurring between midnight to early morning in patients with coronary spastic angina.     

Initiatives with platinum- and quinazoline-based antitumor molecules--Fourteenth Bruce F. Cain Memorial Award Lecture

Carboplatin is a better-tolerated alternative to cisplatin. JM216, the first p.o.-administrable platinum complex possesses toxicities comparable to carboplatin in Phase I studies. Together with the trans-platinum complex JM335, it provides new chemical guidelines for the development of compounds that may circumvent cisplatin resistance in tumors. Systematic structure-activity investigations have led to the discovery and development of ZD1694 (Tomudex), an inhibitor of thymidylate synthase that exploits both the reduced folate carrier and folylpolyglutamate synthetase as major determinants of its growth-inhibitory activity. Phase II studies have revealed encouraging activity against colon cancer, and Phase III studies are nearing completion. An associated structure-activity investigation has led to the development of ZD9331, a potent thymidylate synthase inhibitor which exploits the reduced folate carrier for cell entry, but which is independent of polyglutamation for its thymidylate synthase-inhibitory activity. This compound possesses antitumor activity in vivo and has been selected for full development.     

Cancer as a complex developmental disorder--nineteenth Cornelius P. Rhoads Memorial Award Lecture

The processes of differentiation and tumorigenesis have been long thought to be connected. The recent identification of Patched, a gene essential for Drosophila embryonic development, as a tumor suppressor has focused attention on the concept that tumorigenesis involves abnormalities of development. In fact, a large number of genes in the signalling pathway of the Patched gene are either tumor suppressors or oncogenes. This supports the concept that growth control is a critical requirement of differentiation, and that aberrant cellular development can contribute to malignancy. Whereas the identification of genes that result in dominantly inherited cancer syndromes has played a vital role in understanding cancer, the vast majority of "sporadic" cancers have properties of a complex genetic disease. Approaches to identify common alleles in cancer-associated genes promise to increase our understanding of the disease and aid the rational design of preventative and therapeutic strategies.     

The ocular melanoma story. LIII Edward Jackson Memorial Lecture: Part II

PURPOSE: To trace the evolution and status of our knowledge of choroidal melanoma with regard to the nature, cause, and treatment of this tumor. METHODS: Historical materials beginning with Georg Bartisch's contributions in 1583 through to the Collaborative Ocular Melanoma Study and recent basic research are reviewed. RESULTS: Many individuals have made important contributions to our knowledge about this tumor. Basic information, however, regarding the natural history of the tumor, the most effective treatment, and its cause is lacking. CONCLUSION: The Collaborative Ocular Melanoma Study will provide important information regarding the choice of treatment between enucleation and radiotherapy as well as natural history information, quality of life, and definitive pathology findings. Definitive treatment of choroidal melanoma will depend on knowledge of the genetic defects that cause the tumor. Within the next 25 years, it is predicted that genetic defects will be determined and tumor samples will be obtained using small-needle aspiration and DNA probes located on microchips. In addition, treatment will then be based on drugs designed to inhibit molecules related to the genetic defect in the tumor.     

Eugene J. Keefe Memorial Lecture. The Canadian health care system: an overview

Canada has 21 years of experience with a national health care insurance program. This lecture describes the program, its evolution, financing, and attitudes and perceptions of the consumer, the provider (physicians and hospitals), and the funding agencies (governments). Comparisons, where appropriate, with the system in the United States are incorporated.     

Toynbee Memorial Lecture 1997. Middle ear mechanics in normal, diseased and reconstructed ears

A review of the structure-function relationships in normal, diseased and reconstructed middle ears is presented. Variables used to describe the system are sound pressure, volume velocity and acoustic impedance. We discuss the following: (1) Sound can be transmitted from the ear canal to the cochlea via two mechanisms: the tympanoossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). In the normal ear, middle-ear pressure gain, which is the result of ossicular coupling, is frequency-dependent and smaller than generally believed. Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. (2) The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapes-cochlear input impedance are compromised. Such analyses are used to explain the air-bone gaps associated with lesions such as ossicular interruption, ossicular fixation and tympanic membrane perforation. (3) With type IV and V tympanoplasty, hearing is determined solely by acoustic coupling. A quantitative analysis of structure-function relationships can both explain the wide range of observed post-operative hearing results and suggest surgical guidelines in order to optimize the post-operative results. (4) In tympanoplasty types I, II and III, the hearing result depends on the efficacy of the reconstructed tympanic membrane, the efficacy of the reconstructed ossicular chain and adequacy of middle-ear aeration. Currently, our knowledge of the mechanics of these three factors is incomplete. The mechanics of mastoidectomy and stapedectomy are also discussed.     

The physiological basis of training the skeleton. The Sir Frederick Smith Memorial Lecture

The skeleton consists of a series of elements with a variety of functions. In locations such as the skull, where shape or protection are of prime importance, the bone's architecture is achieved during growth under predominant genetic control. In locations such as the limbs, where the ability to withstand repetitive loading is important, only the general form of the bone will be achieved as a result of growth alone, the remaining characteristics resulting from an adaptive response to functional load bearing. In the horse, this functional load-bearing will be provided by the animal's natural activity pattern in box or paddock supplemented by the specific activities of the training regimen. It is the adaptive response to the total activity pattern that influences bone modelling and remodelling and so determines the bone's architecture. The objective of the training regimen is to ensure that this response achieves an appropriate match between bone architecture and the loads it is required to withstand during both training and athletic performance. We propose that for the match between architecture and load-bearing to be established, and maintained, subsequently, bone cells must be able to 'assess' directly or indirectly the functional strains produced within the bone tissue. Because these strains are used as feedback they are both the objective of functionally adaptive modelling and remodelling, and the stimulus for its control. The mechanisms whereby bone cells control skeletal modelling and remodelling to produce a functionally competent skeleton are unknown although some of the factors and sequence of events involved are presented here. The extent to which variation in training regimen affects bone architecture has not been studied systematically in any species.     

Phantom limbs, the self and the brain (the D. O. Hebb Memorial Lecture).

An examination of phantom limb phenomena has led to 4 conclusions: The experience of a phantom limb has the quality of reality because it is produced by the same brain processes that underlie the experience of the body when it is intact; neural networks in the brain generate all the qualities of experience that are felt to originate in the body; the experience of the body has a unitary, integrated quality that includes the quality of the "self"; and the neural network that underlies the experience of the body-self is genetically determined but can be modified by sensory experience. A theory is developed to explain these conclusions. It is proposed that we are born with a widespread neural network (the "neuromatrix") for the body-self, which is subsequently modified by experience. The neuromatrix imparts a pattern on all inputs from the body, so that experiences of one's own body have a quality of self and are imbued with affective tone and cognitive meaning. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The 1996 Helene Hudson Memorial Lecture. Work redesign and re-engineering: a challenge for professional nursing practice

Work redesign and re-engineering have become the buzzwords of the 1990s as all sectors of the health care arena struggle to meet the demands of patient care while coping with increasing fiscal constraint. Redesign and re-engineering are terms that describe a wide range of strategies in health care and radically different models of care delivery. These new approaches to care are shifting the way we view care delivery and how it is structured. This paper describes the principles of redesign and re-engineering, common applications in health care organizations, outcomes and evaluation. Multiskilling and use of genetic health care workers are addressed. The potential impact on the practice of oncology nurses is explored as well as strategies to meet the challenges of today's health care environment.