Contact Dr. Ronald B. Keys at (718) 460-3966 or e-mail at rkeysphd@brainlink.com.
After all, it's only your life.
Lao Tzu, The Tao De Ching, Book II, LXXI
The purpose of a functional assessment is to identify and profile altered states of metabolism with particular changes in the metabolic and biochemical pathways as a result of disease or dysfunction. A proper diagnosis still, always, guides a rational treatment. This is even more important in primary practice where patients tend to present with more subtle, varied and multi-system, poly-organ involvement than in subspecialty practices. The object of this work is to aid the clinician in the selection of the appropriate routine or newest diagnostic tools based upon current technologies.
For purposes of this book, disease may be defined as the slow but progressive loss of function, organ reserve, until compromise is so accumulated causing an onset of a diagnosable set of conditions called a disease. Within the context of prevention and and the application of life extension technologies, disease is a question of degree where levels of dysfunction are reached at certain planned, predetermined threshold levels.
The conceptual framework for this book for the recognition, assessment and treatment of levels of dysfunction including disease is a "Patient-Centered Diagnosis (PCD) Model recently advanced by Dr. Leo Galland, a practicing physician in New York City, and respected teacher and lecturer in Functional Medicine It is a comprehensive diagnostic model that assesses bio-psycho-social factors with a detailed, comprehensive patient-databasing. In bio assessments, the idea is to correlate psycho-social factors in a patient's personal and family history with laboratory results that include patient-appropriate molecular diagnostics.
Patient-Centered Diagnosis and Treatment (Galland, 1993) is a single, functional medicine model that integrates behavioral, metabolic, constitutional and environmental factors with fundamental differential diagnosis in medicine first published in French's Index of Differential Diagnosis in 1912. The problem with differential diagnosis, alone, is that it treats the disease rather then the patient. It requires an answer to "What disease does this patient have?". Signs and symptoms are matched to the disease. Competing treatment methodologies are selected under the disease category and the disease is treated rather than the patient, thereby isolating the patient from his psychosocial context (Engel, 1977). This system treats "disease," merely a label, and fails to treat the "illness" as a dynamic process in which the individual characteristics of patients influence their prognosis (Fessel, 1983; Feinstein, 1987).
It is both a theoretical and practical framework that emphasizes cost containment by applying an individualized, tailored, treatment protocol rather then a public health approach. The concept of "mind" versus "body," the separation of which is an artifact of our western cultural heritage, does not exist in this model. The austere, Spartan, experimental method of science is combined with the art of diagnosis. While the scientific method embodies the reproducibility and replicability of experimental findings, the dynamics of art moves in quite an opposite direction in favor of adopting a "perspective" which creates individual works that are unique which derive their value from being irreproducible. The creativity and originality of an original are what is valued in art. Similarly, in diagnosis and treatment, each treatment plan or strategy recognizes the patient or client who is an "original" who is not "reproducible" or "replicable" (Galland, 1993).
The word "diagnosis," derived from Greek, meant "to know through" or "to know thoroughly," is consistent with the PCD model that is more comprehensive then mere differential diagnosis.
It is important to recognize that a "disease" does not exist by itself but only phenomenologically as a label reflecting a combination of
(1) What are the mediators of this patient's illness? The goal is (a) to avoid only adverse mediator activation (b) and to restore the adaptive control of mediator activation rather then total mediator suppression. Individual patient requirements will govern either the requirements (the "when" and the "how") to either "downregulate" or "upregulate" any particular metabolic or biochemical pathway as a mediator, and its various cascades, circuits and loops. The challenge is to identify all mediators of the patient's illness, cognitive or otherwise, and not focus on a single class of mediators, alone. Physical measures to control mediator malfunction must include all other relevant mediators such as social support for patient compliance. Treatment under the PCD model requires treatment tailored to the individual characteristics of the patient rather then the characteristics of the disease, syndrome or deficiency state (Galland, 1993).
(2) What triggers for activation of these mediators can be identified? There is sufficient individuality in the evolution of disease or metabolic dysfunction to realize that a malfunction in a metabolic pathway, circuit or loop may be the result of individual responses to a variety of triggers.
(3) What is there in this patient's personal and familial background that permitted or determined the evolution or development of the illness, or, metabolic derangements? This antecedent of illness with metabolic dysrefulation and malfunction in key biochemical pathways may be genetic in origin with focal, pivotal, major histocompatability locus determinants within the regions of the patient's DNA and therefore, a specific diathesis in this patient. The extent to which this patient's illness is influenced by still other antecedents of illness including the patient's behavior, other constitutional or other environmental factors must still be assessed.
Using a PCD model, it is imperative to identify all of the mediators that may be responsible. The identification of all primary and secondary mediators to disturbances in biochemical pathways is necessary to tailor a more effective and individual treatment strategy. It is highly unlikely that a single substance deficiency model of treatment can account for all of the observed phenomena concerning a patient. Environmental factors such as poor lighting (Parry et al., 1993; Midwinter et al., 1991), poor personal sleep hygiene and emotional states including abandonment due to death of a loved one, fear, denial or anger (Galland, 1993) or any other cognitive state which would induce sleeplessness as an example of a symptom
Mediators are organized into response patterns that subserve homeostasis. They do not exist to cause disease but rather to maintain equilibrium and stability in the face of internal malfunction and external threat (Galland, 1993). The common approach has been to suppress all mediator function that serves to interrupt or block homeodynamic circuits and the interacting cascades of other mediators. Mediators are multifunctional. For example, basic regulatory functions have been shown which describes the pineal gland, acting through pineal melatonin, its principal hormone, as responsible for fine tuning and integrating various neural and endocrine functions (Sandyk, 1990). Lack of nocturnal plasma melatonin is responsible for internal desynchronization and circadian disorganization (Aschoff, 1969; Bartsch et al., 1993). The goal of therapy is to restore adaptive control of mediator activation (Galland, 1993) which in this case is to restore a robust, nocturnal hormone melatonin amplitude to restore homeostasis. Other mediators, and their interaction with and affect upon nocturnal melatonin amplitudes, such as poor lighting, poor personal sleep hygiene or abstention from drugs that may impair endogenous nocturnal, melatonin output must be considered in each patient.
The activities of mediators are profoundly affected by common components of life such as thoughts, diet, exercise or sunlight (Galland, 1993). For example, strenuous and prolonged exercise, at least in trained athletes, has been shown to increase plasma melatonin levels (Stressman et al., 1989). The time of day and the light/dark cycle may profoundly affect melatonin rhythm and amplitude, causing high nocturnal plasma melatonin during a dark cycle and low daylight plasma melatonin during daylight hours. These components of everyday life themselves such as the light/dark cycle are secondary mediators that feed into the daily melatonin cycles, cascades and loops that determine the amplitude of nocturnal melatonin secretion. Many mediators are involved in maintaining homeostasis in a complex biological system. All important regulatory functions rely upon multiple mediators and more than one circuit. However, the total number of important mediator cascades or loops is relatively small in relation to the total number of diseases that numbers into the thousands. The focus on mediators, such as melatonin, should be liberating as a creative, dynamic endeavor, rather then enslavement into a mechanical, differential diagnosis, because the emphasis is on "process," interactions and relationships among systems--"regulation" versus "dysregulation." This is very important when interpreting laboratory findings in molecular pathology.
The clinician must learn how to recognize, understand and respond to the impact of the common components of life (e.g. the influence of institutional lighting on nocturnal melatonin amplitude in assessing melatonin deficiency states in the elderly) on illness. This challenge has been called a paradigm shift for many physicians today (Baron, 1986). Unfortunately, most of them are not prepared for this shift, frequently failing to recognize psychological or psychosocial problems in their patients (Brody, 1980). Many of them fail to meet basic competence in clinical nutrition (Levine et al., 1993). Findings in laboratory medicine require its proper connection and correlation with the life of the patient.
Certain behaviors may be relevant to the illness or condition of a patient. These behaviors include the decision to seek medical care or help, compliance with a treatment or dosing regimen, self-care practices, engagement in high-risk activities. Poor sleep hygiene, eating or sleeping habits may disrupt melatonin rhythm and amplitude, independent of developmental secretory declines. Cognitive-behavioral intervention and education of patients (biobbehavioral modification) in sleep hygiene and sleeping habits may enhance patients' perceived self-efficacy and may improve treatment outcome (O'Leary, 1985; Galland, 1993).
In reviewing and assessing various biochemical pathways, questions include what are the triggers that induce their production, regulation and activation or deficiency states within individual patients? If there is an illness for which a particular metabolic pathway is a critical mediator, what are the multiple triggers that may vary its plasma or tissue levels and, or, amplitudes unique to this particular patient, using a client centered or PCD model? In people with specific metabolic deficiency states, the recognition and identification of still, other triggers as well as other mediators is necessary for a successful treatment strategy. There is much individuality in the evolution of illness in each patient with different entrained catecholamine and many neuropeptide network, receptor and alarm functions. And yes, certain enzyme systems, their circuits, cascades and loops among various systems can make it a mediator as well as a trigger of other conditions within an illness. Cyclical enzyme production or its failure to produce or impaired production within the patient's DNA may also be part of the antecedents of illness because, as previously stated, it may be both "cause" and "effect" in the management of "wellness" and "illness."
Such advanced laboratory technologies must exist within a patient and treatment management context. It is hoped that clinicians will become more familiar with various assays to help their patients within a patient-centered context that will include, amino acid analyses, organic acid analyses, the full range of functional liver and other organ challenge tests, HPLC, Northern and Southern Analyses, Elisa; dot-blot, cDNA library screening, confocal laser scanning microscopy, capillary column gas chromatography, lectin affinity chromatography, lectin binding, transduction, western-blot, radioimmunoprecipitation, one- and two dimensional SDS Page, polyclonal and monoclonal antibody production, metabolic labeling, in vitro transcription and translation, PCR, DNA sequencing and plasmid cloning.
Contact Dr. Ronald B. Keys at (718) 460-3966 or e-mail at rkeysphd@brainlink.com.
After all, it's only your life.