The effect of desalivation on 4-nitroquinoline-1-oxide-induced tongue carcinogenesis: a morphometric study of nucleolar organizer regions.

Saliva is an important factor in the oral cavity and could be significant in protecting against carcinogens. In experimental models of carcinogenesis, saliva was shown to have a temporary protective effect against the carcinogens DMBA and 4-nitroquinoline-oxide (4NQO). Silver-stained nucleolar organizer regions (AgNORs) are considered markers for both proliferative capacity and prognosis. The purpose of the present study was to investigate the effect of desalivation on AgNOR parameters in lesions induced by the carcinogen 4NQO in a rat model, in order to trace early nuclear changes. The study group consisted of 120 male Wistar-derived rats. The experimental group (n=56) underwent surgical desalivation; the control group (n=56) underwent a sham operation, and both groups were administered a solution of 0.001% 4NQO in the drinking water. A normal group (n=8) did not receive surgery and drank tap water. Rats were sacrificed at 7, 14, 22, and 28 weeks. Formalin fixed, paraffin embedded sections of the tongue were silver-stained and AgNOR parameters were analyzed using computerized image analysis. In both desalivated and control groups, the nuclear area was significantly higher than the normal. This difference was already evident at 7 weeks. The mean AgNOR area was significantly higher in the desalivated group at week 7 and continued to increase over time. The mean AgNOR number was also significantly higher in the desalivated group at week 7. Differences between the desalivated and control groups diminished with time. These changes in proliferative activity, as expressed by AgNOR parameters, presented earlier changes in comparison to those observed in microscopic examination of the same slides. Results suggest that saliva in the oral cavity can delay malignanttransformation, but continued exposure to the carcinogen overrides this effect. AgNOR stain seems to be sensitive and allows for early identification of intranuclear changes.

The academic medical center of the future: a center for integrative study.

The integrative sciences, which are of great practical and conceptual interest, investigate complex systems (cells, multicellular organisms, families, institutions, communities, nations, etc.) at the higher levels of organization. Academic medical centers are intrinsically integrative because of their mission and thus are likely places for integrative study to flourish. They also possess vast resources of the kind needed to implement integrative studies. They can thus begin to address, from a scholarly point of view, a variety of integrative issues: how myriad parts (molecules, cells, organisms) form stable, complex, living wholes; the dynamics of health, illness, healing, dying, and death; problems of integration relating to patient care, health care delivery systems, and medical education. If academic medical centers undertake this mission they can be springboards for scholarly advances that will potentially affect all areas of thought. The authors describe how an integrative studies program can be started, and share the experiences of the University of Kentucky's Office of Integrative Studies.

On the dynamics of dying.

This study is concerned with dynamic processes that underly the rapid, degenerative changes associated with the "dying" stage of the multicellular organism's life cycle. The interaction between negative and positive feedback cycles is discussed: negative feedback cycles underly the superstability characteristic of health and illness. When negative feedback cycles fade in the dying phase of life, positive feedback cycles, previously held in check by the negative feedback cycles to which they had been coupled, rise explosively, driving physiologic variables from their normal values towards extremes. This results in the rapid downturn that we associate with dying--an accelerating disintegration terminating in death. A medical case history is analyzed.

How many pounds of oxygen do we "eat" each day?

As teachers we feel the need to do more than merely teach basic facts and concepts. We want to make the subject matter more relevant; we would like to help integrate the various threads of the students' education and life experiences; and, finally, we wish to increase the students' interest and involvement in the learning process. There is the temptation, however, when thinking along these lines, to consider the use of time-consuming, complex methods of approach. These might involve slide presentations, videos, special lectures, special assignments, student, reports, etc: The very complexity of these approaches often reduces their effectiveness. Moreover, the time and effort required often keeps us from attempting them more than once or twice. Are simpler and more effective approaches to enrichment possible? Reflecting on our own education, many of us may recall the disproportionate impact of some revealing aside thrown by a teacher unexpectedly into an otherwise mundane lecture or discussion: perhaps a short, penetrating observation providing an unexpected perspective on what was being discussed, a bolt of lightening that briefly illuminated the dim landscape of the classroom. This we may remember when much from the course has been totally forgotten. These jewels of thought--epiphanies--can be shared by teachers to enrich, enlighten, and refresh their students and each other. The jewels we speak of need not be precious or rare. Indeed, the metaphors "a bolt of lightening" and "jewels" may mislead by their intensity and drama. Is it not in the often unexamined, simple, and humble all around us that wisdom can be found? The following is an example.

Integrative physiology: some texts and methods of integrative study.

The development of the integrative dimensions of physiology will require texts and forms of study that differ from those to which we have become accustomed in the areas of specialization. The following two types of texts lie at the heart of integrative study: framework statements and case histories. Framework statements are scientific aphorisms that summarize integrative insights; ordered chains of these statements form conceptual frameworks that stimulate integrative dialogue and thought. Case histories are stories that portray the events in the life of a living being, generally human. The nature of these texts, how framework statements are created, and methods of how texts of this kind may be used in group dialogues are discussed.

Integrative study in physiology and medicine: obstacles on the road to integration.

A recent report of the Long-Range Planning Committee of the American Physiological Society identifies physiology with "integrative biology" and urges that physiologists make their field "a unique branch of biology that deals with synthesis and integration." However, certain institutional, procedural, and psychological obstacles lie in the way of those who would embark upon this task. The hurdles to be overcome include the following: the erroneous belief that biomedical scientists are already integrative; the inapplicability of the powerful methods of areas of specialization to integrative study; the fear of failure; the identification of integrative biology with the study of function; the disregard of hierarchy; the undervaluation of the abstract; and the loss of a sense of mystery. These obstacles, though insidious, pervasive, and powerful, can be surmounted.

Complex medical case histories as portals to medical practice and integrative, scientific thought.

Complex clinicopathological conferences from the New England Journal of Medicine are used to introduce first-year medical and graduate students to scientific reasoning at the level of the whole organism and to help them mobilize and integrate the knowledge obtained in their previous studies. The approach involves outlining the etiology of the case history. This becomes a framework for thought allowing students to easily cope with the profusion of data. The method is cost effective: a single professor can interact with a large class, yet engage students on a one-to-one basis. It is a powerful adjunct to, but does not replace, lecture or small group activities such as problem-based learning. An annotated case history involving diabetes mellitus is provided.

The accelerated internal medicine program at the University of Kentucky.

Concern is growing about the ability of categorical medicine residency programs, structured within academic health centers, to provide balanced, progressive, postgraduate internal medicine education. Detrimental factors, including over-representation of critically ill patients, shortened length of hospitalization, stress, discontinuity between undergraduate and graduate training, rotational assignments driven by hospital service imperatives, and total costs, may all negatively affect internal medicine residency education. Therefore, an experimental accelerated internal medicine (AIM) curriculum combining 3 years of undergraduate with 3 years of graduate internal medicine education has been initiated by the Department of Medicine and the College of Medicine at the University of Kentucky. After completion of the third year and during the first 13 months of the AIM curriculum, selected students are rotated through an integrated series of educational experiences that incorporate all of the requirements for graduation from medical school and progressively advance the students' skills, knowledge, and responsibilities to that of a second-year resident. Thereafter, the curriculum is similar to that of the categorical residents, except that more ambulatory care and off-site rotations are interspersed to better provide the educational experiences representative of the practice of internal medicine. Evaluations of the first groups of AIM residents indicate that their performance has equaled that of the control residents who graduated after 4 years from the College of Medicine. Furthermore, the AIM residents report general acceptance by their fellow residents and attending physicians and report no undue stress in making the transition.

Experience with a physiology workshop for high school and college teachers.

Science education in the United States at all academic levels is widely perceived to need direct assistance from professional scientists. The current dearth of quality applicants from this country to medical and graduate schools suggests that our existing undergraduate and high school science curriculum is failing to provide the necessary stimulus for gifted students to seek careers in the health sciences. Recognizing the need to become more directly helpful to high school and college science teachers, members of the faculty of the Department of Physiology and Biophysics at the University of Kentucky College of Medicine held a 5.5-day Physiology Summer Workshop during June, 1989. Participants included 25 college teachers from Kentucky and 5 other states plus 22 Kentucky high school teachers. The presence of the two levels of educators provided communication about curricular concerns that would be best addressed by mutual action and/or interaction. Each day's activities included morning lectures on selected aspects of organ system and cellular physiology, a series on integrative physiology, and afternoon laboratory sessions. The laboratory setting allowed the instructor to expand on principles covered in lecture as well as provided the opportunity for in-depth discussion. A selection of evening sessions was presented on 1) grants available for research projects, 2) obtaining funds for laboratory equipment, and 3) graduate education in physiology.