Psychoneuroimmunology: The Science Connecting Body and Mind

The Torah gave the world an understanding of the reciprocal connections between body and soul. Until recently, many scientists rejected the concept that psychological factors and well-being can affect health and disease. In part, this may been caused by a lack of technological tools to prove these links. During the last decade, new methods and findings in neuroscience, neuroimaging, and molecular biology have discovered connections between emotions and disease, between the brain and the immune system, the mind and the body. Science and medicine are beginning to become aware of this interplay. The psycho-neuro-immunology (PNI) revolution uplifts science from a mechanistic, dualistic, reductionistic Descartian view of the human state to a more integrative perception of the complexity and beauty of human existence. PNI deals with the interactions among the mind, human behavior, the nervous system, the immune system, and the endocrine system. Understanding these complex interactions is essential for gaining a better understanding on how to maintain health and to prevent and treat disease. PNI guides science to the holistic view of body and soul interaction found in the Torah.

Yakir Kaufman was born in Haifa and received his MD from the Hebrew University Hadassah Faculty of Medicine in 1994. In 1995 he become a resident doctor at the department of neurology of the Hadassah University Hospital in Jerusalem. Dr. Kaufman is a member of the Israeli Neurological Society and a junior member of the American Academy of Neurology. With his wife and children, he is currently in Toronto, Canada, where he has been appointed a Fellow in the Behavioural Neurology Program at the Baycrest Centre for Geriatric Care and the Rotman Institute. His areas of research include psychoneuroimmunology and the link between spirituality and health.

Mind-Body Unity: Science Is Catching Up with the Torah

The Torah gave the world an understanding of the reciprocal connections between body and soul. Genesis describes the creation of Adam as the implant of a heavenly soul into an earthly body. Throughout the Torah the human interaction between heavenly soul and animal body is an overriding theme. This interaction is a cornerstone of the Torah perception of life.

Moses Maimonides, the great Torah authority and physician, states in the third chapter of his Regime of Health that his medical system is based on the Torah concept of a “healthy soul in a healthy body.”1 Maimonides expanded the Latin aphorism of “a healthy mind in a healthy body.” Whereas Greek and Roman medicine, as formulated by Galen, tried to treat the psyche as an isolated system in cases of mental illness, Maimonides emphasized the necessity of treating the spiritual aspect of every condition of every patient. He understood that the physical well-being of a person is dependent on mental well-being, and reciprocally, that mental well-being is dependent on physical well-being. Furthermore, in the Mishneh Torah, Hilkhot Deot 4:1 Maimonides states that health is necessary in order to know G-d, which is the highest purpose in life.

Throughout the generations, similar concepts have been expressed by numerous Torah commentators. In the past century, the Baal Shem Tov and his hasidic followers emphasized and revitalized this approach. The Maggid of Mazritch says, “A small hole in the body is a big hole in the soul.”

In our generation, the Lubavitcher Rebbe, Rabbi Menachem Mendel Schneerson, wrote to a conference of Torah observant physicians in New York in 1992, “physical health depends upon the health of the nefesh (soul)…the more healthy the nefesh is, the more it can guide the body to mend its deficiencies” (Igrot Kodesh, volume 11, page 202).

Science and medicine are beginning to awaken from a long unawareness concerning the interplay between bodily factors and the mind and soul. In this sense, we are lucky to be living in an exciting era, when the discipline of psycho-neuro-immunology (PNI) is pioneering a revolution in elevating medicine from a mechanistic, dualistic Descartian perception of the human condition to a new paradigm embracing the complexity and beauty of human existence.

The old reductionistic perception of the human being as the sum of many separate biological systems is rooted in ancient Greek philosophy. The difficulty of Western medicine in effectively treating many disease states, especially chronic diseases, may be related to this narrow, non-integrative concept. This attitude also incurs dissatisfaction from health service clients. Patients feel they are looked upon by ultra-specialists as a compilation of systems and not as an integrated human being.

In contrast to the view that body systems function separately, technological development in neuroimaging and molecular biology show that systems continuously interact among themselves. Understanding these complex interactions is essential for gaining a better perception on how to maintain health and prevent and treat disease.2 This perception may lead to the remodeling health-care.

New and Ancient

Today’s exponential growth in technology has allowed us to perceive and understand the human body and brain as we have never done before. We can now “see” the brain while it is engaged in the most delicate tasks. Technological breakthroughs in neuroimaging, such as positron emission tomography (PET), functional magnetic resonance (FMRI), and single photon emission computerized tomography (SPECT), give us a first-time opportunity to pinpoint areas of the brain that are responsible for the generation of emotions, thoughts, and even higher abilities of the mind, such as meditation and prayer.3,4

Another area of technological advancement that has boosted the understanding of the connection between body and mind is molecular biology. Molecular biology has given us the opportunity to track down minute quantities of substances traveling through the human body and interacting with different systems of the body. Of great significance are the molecules found interacting in the brain, especially the limbic system responsible for our emotions, with other bodily systems. The increasing ability to track the pathways of minute amounts of molecules and monitor their effect on different systems has enhanced our knowledge of how mental, emotional, or spiritual changes can alter the molecular profile of the immune or hormonal system and thus affect the body.5,6

Today, PNI through molecular biology techniques provides evidence that behavioral/psychological factors—primarily stress—can impair immunological reactivity.7,8,9,10,11 Conversely, studies in PNI have demonstrated that reduction of stress can enhance immune function in its task of protecting the body from infections, cancer, and other disease states.12,13,14,15,16,17,18

Hence, as more interactions between bodily systems are being discovered, science better understands how changes in a person’s mental, emotional, or spiritual state can change the molecular profile of his or her immune or hormonal system, and thus affect the body.

Thus, science today is approaching the Torah understanding that state of mind affects physical health and disease.

Torah, PNI, and the Definition of Health

You will then serve G-d your L-rd, and he will bless your bread and your water. I will remove sickness from among you…. I will make you live out full lives. (Exodus 23: 25-26)

The ancient but vital Torah concept of health expressed by Maimonides as a “healthy soul in a healthy body” has been recognized by science only in the last century. According to the modern definition of health, as defined by the World Health Organization:

Health is a complete state of physical, social, and mental well-being and the mere absence of disease or infirmity.19

“Mental well-being” means both psychological and spiritual well-being. Health by this definition is considered primarily an outcome of a person’s state of well-being. Spiritual well-being is an important component of general well-being.20 Whereas a deterioration of well-being may bring disease, enhancement of well-being may prevent disease or augment cure. Thus, the concept of the mind-body relationship as defined in the Torah and rediscovered by PNI is embedded in the current definition of health.

Stress and Disease

Psychoneuroimmunology deals with the interactions among the mind, behavior, the nervous system, the immune system, and the endocrine system.

 


One of the foci of PNI is the study of the stress phenomenon and its harmful influence on the body, resulting in disease. Chronic stress, and its ill effects is an example of the connection between body and mind. The cause of disease is multi-factorial. It has been established that chronic stress is a risk factor in the leading causes of morbidity and mortality. Chronic stress has been shown to be a risk factor in heart disease, stroke, cancer,21,22,23 infection, 24,25,26 wound healing,27 autoimmune disease,28,29 depression,30,31,32 infertility,33,34,35,36,37,38 pain, and many other disease states.

Stress has many definitions. A relevant one for our discussion is that stress is an extraordinary demand on physiological and psychological defenses and adaptation mechanisms with concomitant neuro-immuno-endocrine responses.

Stress elicits a “fight or flight” (Hans Selye) reaction. This reaction is essential in animals and humans for survival, particularly when encountered by danger. The confronted organism can quickly recruit tremendous energy to overcome danger either by fighting or fleeing the source of danger.

The stress response mechanism is manifested in two major pathways (see Figure 2). First, the endocrine pathway causes secretion of several stress hormones, including CRH, ACTH, and cortisol. Cortisol has a potent, wide range effect on many organs. After being secreted, it is distributed throughout the body via the bloodstream. It enters the cells and affects the DNA within the cellular nucleus, thus changing the functioning of the cells, organs, and bodily systems.

The second pathway is the autonomic pathway, involving activation of the sympathetic nervous system that stimulates the adrenal gland to secrete adrenaline. Adrenaline, like cortisol, has a large array of effects on several systems.

The significant changes following stress, although favorable on the short term, have a high cost when repeatedly activated on the long run (i.e., chronic stress). The stress response weakens the immune system’s ability to resist disease. Thus, stress exposes us to reduced resistance. An ever-increasing scientific database reveals that chronic stress is a risk factor for many disease processes. Various studies indicate that stress events or breakdown of psychological defenses are related to the onset of allergic, autoimmune, infectious, neoplastic, gastrointestinal, cardiovascular, and other illnesses. Other studies tie stress with myocardial infarctions (heart attacks), stroke, cancer, hypertension, diabetes, arthritis, infertility, depression, obesity, and many more problems. The first three illnesses listed above are the main cause of morbidity and mortality in Western societies today. This means that stress, by causing a “negative” mind-body interaction, is a significant factor in morbidity and mortality.

The cause of disease is multi-factorial. Why is it that while individuals within a group of people (e.g., a family) may have a common genetic tendency to develop a disease, only some of them will actually develop the illness while others won’t? And why is it that virulent bacteria can be found in certain people, of whom only a few will actually become infected and sick? These two examples show us that diseases are caused by factors other than just a certain genetic background or the mere presence of an infective agent (e.g., bacteria or virus). The decline of immune function through stress may be responsible for the ability of the bacteria to cause infection or of a genetic trait to become expressed as an actual disease.

Stress and Health: A Two-Way Street

Rebbe Nahman of Breslov said, “If you believe you can damage, then believe you can mend.”

Studies have repeatedly demonstrated that stress reduction can boost the immune system, enhance well-being, and reduce morbidity and mortality risk.

Rebbe Nahman’s counsel that we can mend as well as damage ourselves is paralleled in the functioning of the stress mechanism. Amazingly, the same mind-body mechanism that causes disease can work in the reverse direction and enhance health. Numerous studies have shown that stress reduction and the enhancement of well-being can boost the immune system and prevent disease. This means that the same physiological mechanism connecting body and mind can work both ways. The same mechanism can either cause disease through chronic stress or reverse its harmful effects through reducing stress and augmenting well-being.

We can better appreciate this two-way process by acknowledging the placebo phenomenon. A placebo drug is a substance that has no pharmaceutical impact but nonetheless may actually cause a desired effect quite like that of a “real” drug. Most drugs have been approved for use through a process proving that its “sister” placebo drug actually had an effect. During the process of developing new drugs the placebo effect becomes a “problem” because there may not be a significant difference between the clinical effect of the “real” drug and that of the placebo. Some scientists argue that certain medications (e.g., anti-depressants) are effective mainly because of their placebo effect.

What underlies the placebo phenomenon? How can a mere “nothing” pill cure? The placebo phenomenon seems to reveal the power of suggestion. Is it a trigger for the mind to actualize an internal potential mechanism to cure the body? Does it show an intrinsic ability of the mind to heal the body? The placebo is an example of how it is possible for the mind to initiate a curing process from within. The placebo phenomenon is an extraordinary illustration of the therapeutic potential of the mind-body relationship when directed in a constructive direction. With the right set of mind a person can improve his or her physical condition. Numerous studies have shown this. Reduction of stress through a wide range of strategies and techniques can reduce morbidity and enhance the immune function to provide protection from disease.

Is Modern Medicine Targeted to Enhance Health?

The big question is: If health is an outcome of well-being, then shouldn’t the primary goal of any health system be the enhancement of well-being? Wouldn’t a preventive medical policy through enhancement of physical, social, and mental well-being be cost-effective? Is modern medicine inducing well-being? And if not, why not? Many modern medicine patients feel that their well-being decreases after an encounter with medical services.

There seems to be an unwritten, silent agreement between patients and physicians saying: When the patient comes to the physician with a complaint of a symptom, the physician gives the patient a drug or surgery to relieve the symptom. Although this relative relief of the symptom has its benefit, it does not address the true underlying process that caused the disease to surface. Studies have shown that certain medications that improved laboratory test results in certain patients are liable to reduce well-being and on the whole diminish health outcomes.39,40

Modern medical research has a tremendous mass of data on how to prevent disease and to enhance health. Much more could be done to enhance well-being and prevent disease (primary and secondary prevention). We lag behind in educating the public about risk factors such as stress and its adverse effects. The public should know that stressful lifestyles may be risk factors for disease. Contemporary medicine is not primarily focused on preventing disease but on treating disease after it has appeared. This focus makes the treatment more costly and incomplete. Western health policy is building the proverbial hospital under a broken bridge instead of fixing the bridge.

The West could learn from China. In the past, the Chinese government paid subsidies to health professionals if the community for which they were medically responsible was physically well. This economic incentive actively enhanced preventive medicine. In our society, physicians are usually financially rewarded if they have more patients (and sometimes rewarded if they treat their patients with more drugs and surgical procedures). This causes a reversed incentive. Physicians today have a “heroic” role to save patients suffering from life-threatening maladies. Preventive care to avoid disease in the first place is considered much less heroic. It is also less financially rewarding.

How to Reduce Stress and Enhance Health

What is the best, most long-lasting way to reduce stress and thus to enhance health? It is clear that any symptomatic or superficial solution will be short-acting and will have side effects (such as those given by anxiolytic drugs and benzodiazepines).

When new findings concerning the mind-body connection are acknowledged, then we may conclude that the most profound way to reduce stress is through changing our state of mind. To do this calls for deep, thorough, long-term introspective work. It takes serious and consistent effort to change a state of mind that has produced stress for many years into a different state of mind, but it is possible to succeed.

Of course, appropriate guidance is needed to go through such a complex, profound but gradual change. If the mind is in constant turmoil and internal conflict, the body also will not be at peace, and disease might eventually appear. If anxiety, sadness, anger, dissatisfaction persist, these eventually will take their toll on the immune, nervous, and endocrine (hormonal) systems and bring about either mental or physical disease.

A profound solution for this common situation is a conscious continuous learning process of how to restore psychological, social, and spiritual well-being. It is possible to learn how to restore long-lasting and true inner peace and happiness. It takes dedication and time, but it’s definitely worth the while. The body will benefit from this mindful effort. Our Talmud sages said, “As the effort, so is the reward.”

When the Maggid of Mazritch says, “A small hole in the body is a big hole in the soul,” he is teaching us that to mend the body, we must first mend the soul. Health comes about through a continuous quest to improve psychological and spiritual well-being.

New Model for Health Care

Healthcare systems and physicians can easily integrate these new understandings in their practice. Actually, good medicine based on mind-body interactions is cost-effective and can save society tremendous unnecessary expenses. Public money is wasted by building hospitals under broken bridges. A society that places top priority on enhancing the well-being of its population, rather than on waging technological wars against advanced stages of disease, can dramatically cut its medical budget and create a healthier society.

Physicians and other health professionals should discuss issues of well-being with their patients. By both assessing well-being and stress factors in the clients and prescribing therapies and strategies to reduce stress, doctors can enhance the physical, social, psychological, and spiritual well-being of their clients. Physical and mental disease can be prevented.

From Treating Symptoms to Achieving Health: Where Mind and Matter Meet

If we acknowledge the evidence showing the connection between mind and body, we can then understand that inner stress, turmoil, or conflict is the source of many maladies. Therefore, only by addressing these issues can the healing process be complete. Only then is the solution a profound cure and not merely symptomatic or superficial temporary measures. This more inclusive approach demands the active participation of the patient. The therapist can offer guidance, but it’s the patient who does the work (in contrast to surgery or medication, where the patient is more passive).

As Jews we have the merit and obligation to bring the light of G-d and the Torah down into every aspect of this world. The Torah guides every aspect of our lives—action, ethics, and morals. If we dwell deeply in the Torah, we can find guidance for our search for a better health care system and optimize our medical practice and our own well-being and health. We must take advantage of the great opportunity brought by the new profound scientific understanding of the physiology of mind-body interactions to remodel our practice of medicine. The advancement in scientific understanding, aided by the enormous progress made in medical technology, brings science closer to the Torah paradigm of the connection between mind and body. The reciprocal mind-body connection is the core of physical, social, psychological, and spiritual well-being in health.

There is a long called for need for quality medical professionals who have a complex integrative understanding of mind-body interactions. There is a need for healthcare workers dedicated to enhancing the well-being of their clients. A responsible medical system can guide the individual and society to physical, social, psychological, and spiritual well-being.

Part Two will discuss spiritual well-being and health

Notes

1 Maimonides, Regimen of Health (1198) chapter 3. See Fred Rosner, Medical Encyclopedia of Moses Maimonides (Northvale, NJ: Jason Aronson, 1998) item “Psychosomatic Medicine” pp. 183-184.

2 E.M. Sternberg, “Does Stress Make You Sick and Belief Make You Well? The Science Connecting Body and Mind” in Ann NY Acad Sci (vol. 917, 2000) pp. 1-3.

3 A.B. Newberg and J. Iversen, “The Neural Basis of the Complex Mental Task of Meditation: Neurotransmitter and Neurochemical Considerations” in Med Hypotheses (vol. 61, 2003) pp. 282-291.

4 A. Newberg, A. Alavi, M. Baime, M. Pourdehnad, J. Santanna, E. d’Aquili, “The Measurement of Regional Cerebral Blood Flow during the Complex Cognitive Task of Meditation: A Preliminary SPECT Study” in Psychiatry Res (vol. 106, 2001) pp. 113-122.

5 J.K. Kiecolt-Glaser, L. McGuire, T.F. Robles, and R. Glaser, “Psychoneuroimmunology and Psychosomatic Medicine: Back to the Future” in Psychosom Med (vol. 64:1, 2002) pp. 15-28.

6 J.K. Kiecolt-Glaser and R. Glaser, “Psychoneuroimmunology and Health Consequences: Data and Shared Mechanisms” in Psychosom Med (vol. 57:3, 1995) pp. 269-274.

7 J.K. Kiecolt-Glaser, L. McGuire, T.F. Robles, and R. Glaser, “Psychoneuroimmunology and Psychosomatic Medicine: Back to the Future” in Psychosom Med (vol. 64:1, 2002) pp. 15-28.

8 W.B. Malarkey, J.K. Kiecolt-Glaser, D. Pearl, and R. Glaser, “Hostile Behavior during Marital Conflict Alters Pituitary and Adrenal Hormones” in Psychosom Med (vol. 56:1, 1994) pp. 41-51.

9 J.K. Kiecolt-Glaser, J.T. Cacioppo, W.B. Malarkey, and R. Glaser, “Acute Psychological Stressors and Short-Term Immune Changes: What, Why, for Whom, and to What Extent?” Psychosom Med (vol. 54:6, 1992) pp. 680-685.

10 J.K. Kiecolt-Glaser, R. Glaser, E.C. Shuttleworth, C.S. Dyer, P. Ogrocki, and C.E. Speicher, “Chronic Stress and Immunity in Family Caregivers of Alzheimer’s Disease Victims” in Psychosom Med (vol. 49:5, 1987) pp. 523-535.

11 J.K. Kiecolt-Glaser, L.D. Fisher, P. Ogrocki, J.C. Stout, C.E. Speicher, and R. Glaser, “Marital Quality, Marital Disruption, and Immune Function” in Psychosom Med (vol. 49:1, 1987) pp. 13-34.

12 B.A. Esterling, J.K. Kiecolt-Glaser, and R. Glaser, “Psychosocial Modulation of Cytokine-Induced Natural Killer Cell Activity in Older Adults” in Psychosom Med (vol. 58:3, 1996) pp. 264-272.

13 J.K. Kiecolt-Glaser, W. Garner, C. Speicher, G.M. Penn, J. Holliday, and R. Glaser, “Psychosocial Modifiers of Immunocompetence in Medical Students” in Psychosom Med (vol. 46:1, 1984) pp. 7-14.

14 G.F. Solomon, “Physiological Responses to Environmental Design: Understanding Psychoneuroimmunology (PNI) and Its Application for Healthcare” in J. Health Des (vol. 8, 1996) pp. 79-83.

15 G.F. Solomon, “Whither Psychoneuroimmunology? A New Era of Immunology, of Psychosomatic Medicine, and of Neuroscience” in Brain Behav Immun (vol. 7:4, 1993) pp. 352-366.

16 G.F. Solomon and A.A. Amkraut, “Psychoneuroendocrinological Effects on the Immune Response” in Annu Rev Microbiol (vol. 35, 1981) pp. 155-184.

17 G.F. Solomon and R.H. Moos, “Psychologic Aspects of Response to Treatment in Rheumatoid Arthritis” in GP (vol. 32:6, 1965) pp. 113-119.

18 R.H. Moos and G.F. Solomon, “Personality Correlates of the Degree of Functional Incapacity of Patients with Physical Disease” in J. Chronic Dis (vol. 18:10, 1965) pp. 1019-1038.

19 Preamble to the Constitution of the World Health Organization, as adapted by the International Health Conference, New York, 19-22 Jun 1946, signed on 22 Jul 1946 by the representatives of sixty-one states (Official Records of the World Health Organization, no. 2, p. 100) and entered into force on 7 Apr 1948.

20 E.L. Idler and S.V. Kasl, “Religion among Disabled and Nondisabled Persons I: Cross-Sectional Patterns in Health Practices, Social Activities, and Well-Being” in J Gerontol B Psychol Sci Soc Sci (vol. 52:6, 1997) S294-S305.

21 S. Ben Eliyahu, G.G. Page, R. Yirmiya, and G. Shakhar, “Evidence that Stress and Surgical Interventions Promote Tumor Development by Suppressing Natural Killer Cell Activity’ in Int J Cancer (vol. 80:6, 1999) pp. 880-888.

22 S. Ben Eliyahu, R. Yirmiya, J.C. Liebeskind, A.N. Taylor, and R.P. Gale, “Stress Increases Metastatic Spread of a Mammary Tumor in Rats: Evidence for Mediation by the Immune System” in Brain Behav Immun (vol. 5:2, 1991) pp. 193-205.

23 S. Ben Eliyahu, R. Yirmiya, Y. Shavit, and J.C. Liebeskind, “Stress-Induced Suppression of Natural Killer Cell Cytotoxity in the Rat: A Naltrexone-Insensitive Paradigm” in Behav Neurosci (vol. 104:1, 1990) pp. 235-238.

24 G.F. Solomon, “Psychoneuroimmunology and Human Immunodeficiency Virus Infection” in Psychiatr Med (vol. 7:2, 1989) pp. 47-57.

25 S. Cohen, D.A. Tyrrell, and A.P. Smith, “Psychological Stress and Susceptibility to the Common Cold” in N Engl J Med (vol. 325: 9) pp. 606-612.

26 G.F. Solomon, “Emotions, Stress, the Central Nervous System, and Immunity” in Ann NY Acad Sci (vol. 164:2, 1969) pp. 335-343.

27 P.T. Marucha, J.K. Kiecolt-Glaser, and M. Favagehi, “Mucosal Wound Healing Is Impaired by Examination Stress” in Psychosom Med (vol. 60:3, 1998) pp. 362-365.

28 M.S. Harbuz, “Chronic Inflammatory Stress” in Baillieres Best Pract Res Clin Endocrinal Metab (vol. 13:4, 1999) pp. 555-565.

29 G.F. Solomon, G.H. Ironson, and E.G. Balbin, “Psychoneuroimmunology and HIV/AIDS” in Ann NY Acad Sci (vol. 917, 2000) pp.500-504.

30 M. Irwin, “Immune Correlates of Depression” in Adv Exp Med Biol (vol. 461:1) pp. 1-24.

31 S. Zisook, S.R. Shuchter, M. Irwin, D.F. Darko, P. Sledge, and K. Resovsky, “Bereavement, Depression, and Immune Function” in Psychiatry Res (vol. 52:1) pp. 1-10.

32 M. Irwin, T. Patterson, T.L. Smith, C. Caldwell, S.A. Brown, J.C. Gillin et al., “Reduction of Immune Function in Life Stress and Depression” in Biol Psychiatry (vol. 27:1, 1990) pp. 22-30.

33S.R. Lindheim and M.V. Sauer, “Stress and Infertility: ‘The Chicken or the Egg?’” in Fertil Steril (vol. 68:2, 1997) pp. 384-385.

34 M.M. Seibel, “Infertility: The Impact of Stress, the Benefit of Counseling” in J Assist Reprod Genet (vol. 14:4, 1997) pp. 181-183.

35L.R. Schover, “Recognizing the Stress of Infertility” in Cleve Clin J Med (vol. 64:4, 1997) pp. 211-214.

36 H. Chiba, E. Mori, Y. Morioka, M. Kashiwaskura, T. Nadaoka, H. Saito et al., “Stress of Female Infertility: Relations to Length of Treatment” in Gynecol Obstet Invest (vol. 43:3, 1997) pp. 171-177.

37S.K. Wasser, G. Sewall, and M.R. Soules, “Psychosocial Stress as a Cause of Infertility” in Fertil Steril (vol. 59:3, 1993) pp. 685-689.

38 J. Shepherd, “Stress Management and Infertility” in Aust NZ J Obstet Gynaecol (vol. 32:4, 1992) pp. 353-356.

39 M.W. Nortvedt, T. Riise, K.M. Nyland, and B.R. Hanestad, “Type I Interferons and the Quality of Life of Multiple Sclerosis Patients. Results from a Clinical Trial on Interferon Alfa-2a” in Mult Scler (vol. 5, Oct 1999) pp. 317-322.

40 T. Vial and J. Descotes, “Clinical Toxicity of the Interferons” in Drug Saf (vol. 10:2, Feb 1994) pp. 115-150.


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