Biomedical subjects
Publications and source records attributed to G M Lower.
While biological evolution is a well-defined and accepted phenomenon, the notion of conceptual evolution, however implicit in biomedical progress, remains less well-defined and accepted. Frameworks are provided which portray conceptual evolution in terms of the spatio-temporal and hierarchical cognitive embrace of the human external and internal environments.
There is an interesting story about Louis Pasteur, told a René Dubos, which bears on a discussion of specific, causation-related relationships in human neoplastic disease as a primary focus of biomedical research. The conceptual/axiomatic way in which Pasteur thought about infectious disease remains entirely relevant to efficacious, operationally-relevant thought about neoplastic disease. Approaches to the comprehension and control of neoplastic disease will almost certainly require organization of thought and effort within larger causation-related frameworks.
With the emergence of significant national efforts to comprehend and control the human cancers during the early 1970's, the existing biomedical disciplines of cellular pathology, virology and immunology seemed destined to play a central role in these efforts. Since that time, however, new biomedical disciplines, e.g., molecular toxicology, molecular epidemiology and molecular pathology/genetics, have emerged. Integration of the knowledge embraced by these disciplines provides a view of human cancer from natural historical perspectives embracing the causal chain, a view relevant to national priorities and policies in approaching cancer comprehension and control.
We reviewed emergency department records that spanned a period of 5 years at seven rural hospitals to provide more specific data concerning pediatric resuscitation. The purpose was to plan better for preventive programs and to help rural health care providers prepare better for these difficult patients. Patients entered in the study had either cardiorespiratory arrest or respiratory arrest. Although the distribution by age was similar to studies from other areas, the outcome for cardiorespiratory arrests was as bad or worse (70 arrests with 3 survivors), and the outcome of respiratory arrests was as good or better (25 arrests with 21 survivors) as reported previously. Survival of arrest from trauma and accidents was markedly worse (16%) than survival from nontraumatic arrests (44%). The etiologies of the arrests were dominated by sudden infant death syndrome and pulmonary disease but with very few drownings or farm-related fatalities. This study should encourage rural health care providers to increase efforts in specific areas of trauma and accident prevention. Also, respiratory illness needs to be monitored aggressively and respiratory arrests treated more effectively to avoid the much more consistently lethal cardiac arrests. In addition, more careful prospective study of these patients may be able to identify care patterns that can be improved to increase survival in these groups.
Since the initial epidemiologic confrontations of chronic, non-infectious diseases during the 1940's, there has emerged a periodic concern among epidemiologists regarding disciplinary boundaries and identity. With the development of hierarchical views of the natural history of human disease, the elaboration of mutation theories of chronic, non-infectious disease, and the identification of conceptual frameworks and causal relationships applicable to both the infectious and chronic, non-infectious diseases, it has become possible to reconsider the definitions and scope of epidemiology from within the confines of general epidemiologic-pathologic theory. Based upon natural history and discipline-related concepts of causation, it is possible to integrate the epidemiological and pathological characteristics of disease into a single, coherent systematic epidemiologic theory. Within these conceptual/axiomatic frameworks, systematic epidemiology emerges as the study of disease causality and control and is generally applicable to both the infectious and the chronic, non-infectious (i.e., neoplastic) diseases. Because epidemiologic theory begins with pathologic theory, it is fitting that systematic epidemiologic theory embrace both epidemiology and pathology as complimentary conceptual approaches to the comprehension of disease. Because the interdependent efforts of epidemiology and pathology provide the conceptual basis for action, it is also fitting that systematic epidemiologic theory embrace preventive medicine and public health as operational approaches to the control of disease.
Emphasis has recently been placed on the possibility of developing "unified" criteria of causality applicable to both the infectious and chronic, non-infectious diseases. Yet, contemporary efforts are essentially compilations of criteria established over the past 140 years, without provision of the conceptual basis allowing such a unification. From hierarchical views of the natural history of infectious and neoplastic (i.e., chronic non-infectious) disease, it is possible to identify discipline and natural history-related concepts of causation from which it is possible to derive conceptual criteria of causality and complementary operational criteria of causality. These criteria are entirely relevant to the comprehension of disease as both product and process and applicable to both the infectious and neoplastic diseases.
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The ecology of disease is framed in conceptual terms as the study of the relationships of entities and events in the natural history of disease, a definition allowing it to embrace both the infectious and neoplastic (i.e. chronic, non-infectious) diseases. Those relationships of most conceptual interest and operational relevance are the causal relationships, and thus the ecology of disease properly embraces both epidemiologic and pathologic theory. The classic epidemiologic triad of 'agent-host-environment' is integrated into hierarchical, natural historical frameworks embracing both disease causation and course. Within these ecologic frameworks and based upon discipline-related concepts of causation, it is possible to derive conceptual/operational criteria of causality applicable to both infectious and neoplastic diseases. As approaches to the comprehension of infectious and neoplastic disease share considerable conceptual common ground, it follows that approaches to their control share considerable operational common ground. Indeed, insofar as actions follow ideas, the ecology of disease provides the basis for medical ecology and the planning, conduct and evaluation of overall operational approaches to the control of disease, to include both preventive and therapeutic interventions. From these perspectives, contemporary approaches to the control of neoplastic diseases seem to be derived largely from clinical-pathologic viewpoints of effectual disease process and emphasize non-specific (agent-unrelated) therapeutic interventions. Those general approaches most successful in controlling infectious diseases (i.e. preventive interventions and agent/defect-specific therapeutic interventions) need greater emphasis and application in approaches to controlling neoplastic diseases.
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A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses.
Recently there has been a confusing and somewhat frustrating difference of opinion in epidemiology concerning the relative merit and utility of descriptive versus mechanistic knowledge in approaching the comprehension and control of human cancer. This distinction has both historical and evolutionary rationale; it generally being necessary to know something of WHAT is happening before one can be legitimately concerned with HOW it is happening. As outlined below, however, there is little justification for making value judgements based on this distinction, and the situation is more one in which descriptive approaches and mechanistic approaches are equally essential in the development of a systematic viewpoint, a viewpoint providing guidance to meaningful intervention.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Guinea pigs were observed to be refractory to carcinogenesis by 3 different carcinogenic 5-nitrofurans administered at 0.1% of the diet for 50 weeks followed by 74 weeks of control diet. In view of the evidenced involvement of nitroreduction in the metabolic activation of 5-nitrofurans, it is of interest that guinea pig refractoriness is not due to a quantitative nitroreductase deficiency in guinea pig liver.
The failure of 13-cis-retinoic acid to inhibit either the incidence or severity of bladder carcinoma in female Fischer rate initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) suggests that inhibition of bladder carcinogenesis by natural and synthetic retinoids is carcinogen-class specific, and adds an element of complexity to approaches in chemoprevention.
For some time, there has been a confusing and often frustrating difference of opinion amongst molecular pathologists and biologists regarding the relative involvement of somatic mutation vs. altered differentiation (neodifferentiation) in human carcinogenesis. This distinction, however, has led to opposing biological viewpoints which have a found alignment with opposing political viewpoints. While this distinction may have historical rationale, it has little biological basis, and it is possible to construct an integrative viewpoint which reconciles the "very different points of view and styles of argument" resulting from its use. The general evidence available suggests that most human epithelial cancers are caused by chemicals and radiations capable of inducing local mutations in regulatory sequences of genomic DNA, leading, perhaps through genetic transposition, to a mis-programming of natural genomic information expression. In this viewpoint, somatic mutation and altered differentiation are not mutually exclusive mechanisms as often implied, but, in all likelihood, are temporally related mechanisms; and human cancer thus becomes fundamentally a disease of cellular differentiation caused by somatic mutations.
An analysis of the effects of natural (vitamin A) and synthetic retinoids on experimental carcinogenesis of the urinary bladder indicates that inhibitory activity is carcinogen- or carcinogen-class-specific. These findings suggest that there may be more than one pathway for the neo-differentiation of urothelial cells to frank carcinoma and that these pathways may be related to both carcinogen class and dietary vitamin A status.