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V. Felipe. University of Tennessee, Knoxville.

They provided a comprehensive and consistent theoretical framework for re- search and understanding of the human body order 100mg kamagra effervescent otc protein shakes erectile dysfunction, its structure cheap 100 mg kamagra effervescent with amex what causes erectile dysfunction treatment, workings and failings and its reactions to foods, drinks, drugs and the environment. They further provided fruitful methods and concepts by means of which medical knowledge could be acquired, interpreted, systematised and com- municated to scientific communities and wider audiences. And through their development of historiographical and doxographical discourse, they placed medicine in a historical setting and thus made a major contribu- tion to the understanding of how medicine and science originated and developed. Aristotle himself was the son of a distinguished court physician and had a keen interest in medicine and biology, which was further developed by the members of his school. Aristotle and his followers were well aware of earlier and contemporary medical thought (Hippocratic Corpus, Diocles of Carystus) and readily acknowledged the extent to which doctors con- tributed to the study of nature. This attitude was reflected in the reception of medical ideas in their own research and in the interest they took in the historical development of medicine. It was further reflected in the extent to which developments in Hellenistic and Imperial medicine (especially the Alexandrian anatomists and Galen) were incorporated in the later history of Aristotelianism and in the interpretation of Aristotle’s works in late anti- quity. Aristotelianism in turn exercised a powerful influence on Hellenistic and Galenic medicine and its subsequent reception in the Middle Ages and early modern period. Introduction 15 Yet although all the above may seem uncontroversial, the relationship between Aristotelianism and medicine has long been a neglected area in scholarship on ancient medicine. The medical background of Aristotle’s biological and physiological theories has long been underestimated by a majority of Aristotelian scholars – and if it was considered at all, it tended to be subject to gross simplification. These attitudes appear to have been based on what I regard as a misun- derstanding of the Aristotelian view on the status of medicine as a science and its relationship to biology and physics, and on the erroneous belief that no independent medical research took place within the Aristotelian school. Aristotle’s distinction between theoretical and practical sciences is sometimes believed to imply that, while doctors were primarily concerned with practical application, philosophers only took a theoretical interest in medical subjects. It is true that Aristotle was one of the first to spell out the differences between medicine and natural philosophy; but, as I argue in chapters 6 and 9, it is often ignored that the point of the passages in which he does so is to stress the substantial overlap that existed between the two areas. And Aristotle is making this point in the context of a theoretical, physicist account of psycho-physical functions, where he is wearing the hat of the phusikos, the ‘student of nature’; but this seems not to have prevented him from dealing with more specialised medical topics in different, more ‘practical’ contexts. That such more practical, specialised treatments existed is suggested by the fact that in the indirect tradition Aristotle is credited with several writings on medical themes and with a number of doctrines on rather specialised medical topics. And as I argue in chapter 9, one of those medical works may well be identical to the text that survives in the form of book 10 of his History of Animals. Such a project would first of all have to cover the reception, transformation and further development of medical knowledge in the works of Aristotle and the early Peripatetic school. This would comprise a study of Aristotle’s views on the status of medicine, his characterisation of medicine and medical practice, and his use and further development of medical knowledge in the areas of anatomy, physiology and embryology; and it would also have to comprise the (largely neglected) medical works of the early Peripatos, such as the medical sections of the Problemata and the treatise On Breath, as well as the works of Theophrastus and Strato on human physiology, pathology and embryology. It would further have to examine the development of medical thought in the Peripatetic school in the Hellenistic period and the reception of Aristotelian thought in the major Hellenistic medical systems of Praxago- ras, Herophilus, Erasistratus and the Empiricists. Thirdly, it would have to cover the more striking aspects of Galen’s Aristotelianism, such as the role of Aristotelian terminology, methodology, philosophy of science, and tele- ological explanation in Galen’s work; and finally, it would have to consider the impact of developments in medicine after Aristotle – for example the Alexandrian discoveries of the nervous system and of the cognitive function of the brain, or the medical theories of Galen – on later Aristotelian thought and on the interpretation of Aristotle’s biological, physiological and psy- chological writings in late antiquity by the ancient commentators, such as Alexander of Aphrodisias, Themistius, Simplicius and John Philoponus, or by authors such as Nemesius of Emesa and Meletius of Sardes. This is a very rich and challenging field, in which there still is an enormous amount of work to do, especially when artificial boundaries between medicine and philosophy are crossed and interaction between the two domains is con- sidered afresh. It is concerned with what I claim to be an Aristotelian discussion 24 In addition to older studies by Flashar (1962) and (1966) and Marenghi (1961), see the more recent titles by King, Manetti, Oser-Grote, Roselli, Fortenbaugh and Repici listed in the bibliography. Introduction 17 of the question of sterility, a good example of the common ground that connected ‘doctors’ and ‘philosophers’, in which thinkers like Anaxagoras, Empedocles, Democritus and Aristotle himself were pursuing very much the same questions as medical writers like the author of the Hippocratic embryological treatise On Generation/On the Nature of the Child/On Diseases 4 or Diocles, and their methods and theoretical concepts were very similar. But Aristotle’s medical and physiological interests are also reflected in non-medical contexts, in particular in the fields of ethics and of psycho- physiological human functions such as perception, memory, thinking, imagination, dreaming and desire. In the case of Aristotle’s theory of sleep and dreams, too, there was a medical tradition preceding him, which he explicitly acknowledges; but as we will see in chapter 6, his willingness to accommodate the phenomena observed both by himself and by doctors and other thinkers before him brings him into difficulties with his own theoretical presuppositions. A similar picture is provided by the psychology and pathology of rational thinking (ch. And, moving to the domain of ethics, there is a very in- triguing chapter in the Eudemian Ethics, in which Aristotle tries to give an explanation for the phenomenon of ‘good fortune’ (eutuchia), a kind of luck which makes specific types of people successful in areas in which they have no particular rational competence (ch. Aristotle tackles here a phe- nomenon which, just like epilepsy in On the Sacred Disease, was sometimes attributed to divine intervention but which Aristotle tries to relate to the human soul and especially to that part of the soul that is in some sort of intuitive, instinctive way connected with the human phusis – the peculiar psycho-physical make-up of an individual. Thus we find a ‘naturalisation’ very similar to what we get in his discussion of On Divination in Sleep (see chapter 6). Yet at the same time, and again similar to what we find in On the Sacred Disease, the divine aspect of the phenomenon does not completely disappear: eutuchia is divine and natural at the same time. This is a remarkable move for Aristotle to make, and it can be better understood against the background of the arguments of the medical writers. Moreover, 18 Medicine and Philosophy in Classical Antiquity the phenomenon Aristotle describes has a somewhat peculiar, ambivalent status: eutuchia is natural yet not fully normal, and although it leads to success, it is not a desirable state to be in or to rely on – and as such it is comparable to the ‘exceptional performances’ (the peritton) of the melan- cholic discussed in chapter 5. We touch here on yet another major theme that has been fundamental to the development of European thought and in which ancient medicine has played a crucial role: the close link be- tween genius and madness, which both find their origin in the darker, less controllable sides of human nature. The fact that many of these writers and their works have, in the later tradition, been associated with Hippocrates and placed under the rubric of medicine, easily makes one forget that these thinkers may have had rather different conceptions of the disciplines or contexts in which they were working. Thus the authors of such Hippocratic works as On the Nature of Man, On Fleshes, On the Nature of the Child, On Places in Man and On Regimen as well as the Pythagorean writer Alcmaeon of Croton emphatically put their investigations of the human body in a physicist and cosmological framework. Some of them may have had very little ‘clinical’ or therapeutic interest, while for others the human body and its reactions to disease and treatment were just one of several areas of study. Thus it has repeatedly been claimed (though this view has been disputed) that the Hippocratic works On the Art of Medicine and On Breaths were not written by doctors or medical people at all, but by ‘sophists’ writing on technai (‘disciplines’, fields of systematic study with practical application) for whom medicine was just one of several intellectual pursuits. Be that as it may, the authors of On Regimen and On Fleshes, for instance, certainly display interests and methods that correspond very neatly to the agendas of people such as Anaxagoras and Heraclitus, and the difference is of degree rather than kind. A further relevant point here is that what counted as medicine in the fifth and fourth centuries bce was still a relatively fluid field, for which rival definitions were continuously being offered. There was very considerable diversity among Greek medical people, not only between the ‘rational’, Introduction 19 philosophically inspired medicine that we find in the Hippocratic writings on the one hand and what is sometimes called the ‘folk medicine’ practised by drugsellers, rootcutters and suchlike on the other, but even among more intellectual, elite physicians themselves.

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The genes coding for dopamine receptors purchase kamagra effervescent 100mg on line depression and erectile dysfunction causes, serotonin transporters purchase kamagra effervescent 100mg on-line erectile dysfunction treatment sydney, and dehydroge- nases represent susceptibility loci for addictive behavior. The presence of the L versus the S allele on a serotonin transporter gene has been found to influence responses to ondansetron. Alcoholics with the L-allele have greater alcohol craving than those with the S-allele, and polymorphisms in another receptor result in differences in sensitivity to benzodiazepines used to treat early stage alcohol withdrawal systems. Alcoholism is a complex psychiatric disorder caused by multiple factors, both genetic and environmental. Furthermore, there are probably different subtypes of alcoholism each with a distinct genetic background, which require different thera- peutic approaches. However, gene polymorphisms are not only responsible for a predisposition to alcoholism, but also for the way an individual responds to treat- ment. Because of the genetic heterogeneity between alcoholics there is no one drug that works in all patients, which has made it necessary to provide multiple treatment options that clinicians can use to find which ones work. A personalized treatment that matches specific interventions to the individual, particularly to an individual’s genetic profile, is more efficient. Topiramate has been shown to reduce drinking and heavy drinking in individuals with alcohol dependence whose goal is to stop drinking. A randomized study has evaluated the efficacy and tolerability of topiramate in heavy drinkers whose treat- ment goal is to reduce drinking to safe levels (Kranzler et al. The moderator effect of rs2832407, if validated, would facilitate the identification of heavy drinkers who are likely to respond well to topiramate treatment and provide an important Universal Free E-Book Store Personalized Approach to Addiction 475 Table 13. New treatment strategies focusing on genes contribut- ing to drug and alcohol dependence (such as gene therapy) have been examined in animal models and clinical trials have been conducted with drugs. However, further research is required before these developments will consider- ably change today’s clinical handling of alcoholism on an individual basis. Various human and animal studies can help to determine the full range of genetic variation affecting the pharmacodynamic and pharmacokinetic parameters that result in altered drug efficacy and toxicity. Sequencing technologies to identify variations in candidate genes that may play a role in drug responses, use of pharmacogenetic testing to examine genetic variability in side effects from medi- cation, and use of gene expression profiling to determine transcriptomics changes associated with drug response. Personalized Therapy for Smoking Cessation The evidence to date is very consistent with respect to the significance of genetic contributions to smoking behavior. Variants in the genes encoding the α5-α3-β4 nico- tinic receptor subunits most strongly contribute to differences in the risk for develop- ing nicotine dependence among smokers and a differential response to pharmacologic treatment for smoking cessation (Bierut et al. As the field of genetics and smoking research progresses, increasing attention is being devoted to gene-environ- ment interactions, with particular attention to the identification of genetic variants that may modify the effects of pharmacological treatment for smoking. Universal Free E-Book Store 476 13 Personalized Management of Psychiatric Disorders With advances in molecular biology and genomics technology, individualization of smoking cessation therapy according to genotype is within our grasp. Such research has the potential to improve treatment outcome, thereby reducing morbid- ity and mortality from smoking-related disease. A dopamine receptor gene polymorphism appears to influence the response of cigarette smokers to smoking cessation therapy that includes an antidepressant medicine − venlafaxine. A clinical trial showed no significant difference between the active and placebo treatments for the smokers with the A1 allele in terms of reduction in negative affect during their attempt to quit but those with the A2 allele receiving venlafaxine have 25 % lower score on testing for negative affect. This demonstrates the value of genotyping in designing a spe- cific smoking cessation therapy for a subgroup of patients. Effectiveness of Nicotine Patches in Relation to Genotype In women the effectiveness of nicotine patches seems to be related to genotype. The increased effectiveness reflected a tendency to a higher quit rate with the active patches and a lower quit rate with placebo patches. The overall effectiveness of nicotine replacement therapy could be greater if the therapy were targeted at those most likely to respond. Future Prospects of Personalized Psychiatry Limited number of applications of personalized medicine approach in psychiatry has shown the usefulness of this approach and identified this as an area for further development. Pre-emptive approaches are an important part of personalized medi- cine and preventive psychiatry requires predictive tools that are currently not ade- quate. Biomarkers are needed to develop a clinical staging model for psychiatric disorders. The staging model also facilitates integration of data on the biological, social and environmental factors that influence mental illness into existing clinical and diagnostic infrastructure, which will provide a major step forward in the devel- opment of a truly pre-emptive psychiatry (McGorry et al. Universal Free E-Book Store References 477 References Alemi F, Zargoush M, Erdman H, et al. Toward personalized medicine in the pharmacotherapy of alcohol use disorder: targeting patient genes and patient goals. The antidepressant treatment response index as a predictor of reboxetine treatment outcome in major depressive disorder. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics: part I. Neurophysiologic correlates of side effects in normal subjects randomized to venlafaxine or placebo. Pharmacogenetic approach at the serotonin trans- porter gene as a method of reducing the severity of alcohol drinking. A micro opioid receptor gene polymorphism (A118G) and nal- trexone treatment response in adherent Korean alcohol-dependent patients. A double-blind, randomized trial of sertraline for alcohol dependence: moderation by age of onset [corrected] and 5-hydroxytryptamine transporter- linked promoter region genotype. Functional polymorphism of the dopamineβ-hydroxylase gene is associated with increased risk of disulfiram-induced adverse effects in alcohol-depen- dent patients. Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users.

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Although study of the phosphoprotein network is usually associated with oncology buy 100 mg kamagra effervescent with mastercard impotence yeast infection, such a technology might be useful for other diseases for which multiple treatment options exist and competing technologies have not been able to adequately predict the optimal treatment for individual patients best 100mg kamagra effervescent impotence from stress. Diseases Due to Misfolding of Proteins Taking on the right shape is vital to a protein’s action. To help make sure this hap- pens correctly, cells contain chaperone proteins devoted to helping newly made pro- teins fold. Other proteins, the ubiquitins, bind to proteins that have failed the shape test and mark them for destruction. Prion diseases are associated with misfolding of proteins and this is linked to the pathogenesis of neu- rodegenerative disorders such as Alzheimer’s disease. Disturbance of protein fold- ing system leads to spinocerebellar ataxia – a fatal movement disorder of childhood. Mutations in the gene create an enlarged portion in ataxin1 containing multiple copies of the amino acid glutamine. This stops the protein from folding Universal Free E-Book Store 162 6 Pharmacoproteomics normally, causing them to clump together and form toxic deposits in neurons. The disease can also arise if neurons make too much of the normal protein, pushing the protein folding capacity of chaperones beyond their normal limits. Other genes counteract the effects of misfolded ataxin and provide potential targets for future human therapies. In many cases, the mutations are not so severe as to render the protein biologi- cally inactive. A number of low-molecular-weight compounds, all of which are known to stabilize proteins in their native conformation, are effective in rescuing the folding and/or processing defects associated with different mutations that often lead to human disease. Recent reports have suggested that some of the major neuro- degenerative pathologies could be gathered under a unifying theory stating that all diseases linked to protein misfolding could be due to the inherent toxicity associated with protein aggregates. Therapies for Protein Misfolding A number of low-molecular-weight compounds, all of which are known to stabilize proteins in their native conformation, are effective in rescuing the folding and/or processing defects associated with different mutations that often lead to human dis- ease. The small compounds being developed to correct the misfolding of proteins are called chemical chaperones, pharmacological chaperones or pharmacoperones. Promising results have been achieved in a small clinical trial to treat nephrogenic diabetes insipidus, and trials are under way of patients with emphysema and chronic liver disease, conditions that can be caused by the same misfolded protein. Encouraging in vitro results have been reported for cystic fibrosis, Fabry disease, hypercholesterolemia, and the aggregation of prions in spongiform encephalopathy. Potential also exists to correct misfolding in retinitis pigmentosa, sickle cell disease, thalassemia, cataracts, and hypertrophic cardiomyopathy. Antagonist can be removed after the correctly folded protein reaches the cell surface and the receptor will function normally, as measured by its participation in activating the production of inositol phosphate and release of intracellular calcium. This suggests that the drug need not interact at the same site as the native ligand; it can stabilize the protein allosterically. The pharmacoperone Universal Free E-Book Store Proteomic Technologies for Drug Discovery and Development 163 acts as a scaffolding or template for folding rather than as a competitive antagonist. A synthetic antagonist has been used successfully in clinical trials to rescue receptor protein misfoldings in nephrogenic diabetes insipi- dus, in which improper reabsorption of water in the kidneys leads to various meta- bolic disorders. When the mutant protein is retained in the liver cells rather than secreted into the blood and body fluids, it is thought to become toxic to the liver. Its depletion in the lung causes emphysema via failure to block an enzyme that hydrolyzes the connective tissue elastin. Proteomic Technologies for Drug Discovery and Development Proteomic technologies are now being integrated into the drug discovery process as complimentary to genomic approaches. By focusing on protein activity levels, or expres- sion levels, researchers are able to learn more about the role proteins play in causing and treating disease. Proteomics also aids in deciphering the mechanisms of disease and increasing both the opportunity to develop drugs with reduced side effects and an increased probability of clinical trial success. Proteomics has the potential to increase substantially the number of drug targets and thereby the number of new drugs. Automation of proteomics on a scale similar to that used for genome sequenc- ing may be needed and this is feasible by adapting the many tools already developed for genomics for application to proteomic technologies. Application of proteomic technologies has enabled the prediction of all possible protein-coding regions and to choose the best candidates among novel drug targets. By helping to elucidate the pathomechanism of diseases, proteomics will help the discovery of rational medications that will fit in with the future concept of personalized medicines. A detailed description of various pro- teomic technologies for drug discovery is given in a special report on proteomics (Jain 2015). Pharmacoproteomics helps to determine the mechanisms of action of bioactive molecules in a systems pharmacology context. In contrast to traditional drug dis- covery, pharmacoproteomics integrates the mechanism of a drug’s action, its side effects including toxicity, and the discovery of new drug targets in a single approach (Hess 2013). This class of microarray can be used to interrogate cellular sam- ples, serum or body fluids. Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized ther- apy. Kinases are important drug targets as such kinase network information could become the basis for development of therapeutic strategies for improving treatment outcome. An urgent clinical goal is to identify functionally important molecular networks associated with subpopulations of patients that may not respond to con- ventional combination chemotherapy. Dynamic Proteomics for Targeting Disease Pathways Dynamic proteomics is the study of dynamics (synthesis, breakdown, transport, storage, etc. Advantages of this approach are: • Focus on causes rather than symptoms: generating pivotal knowledge for devel- oping blockbuster drugs, by targeting underlying biochemical causes. Target Identification and Validation The genomics revolution has led to a flood of potential targets but genomic data, by itself, is not be sufficient for validating drug targets. Even the most useful disease biomarkers such as prostate-specific antigen, are proteins.

I was looking to - 191 - staying healthy in the fast lane simplify all this self-improvement stuff I was working on buy kamagra effervescent 100 mg low price erectile dysfunction 43, and Marc Allen made it so simple! It was perfect for me to “laser down” my focus on my dreams discount 100mg kamagra effervescent with mastercard erectile dysfunction drugs and melanoma, goals, and plans, which seemed to be scat- tered all over the place. I drove to the beach, sat in a little coffee shop, and two hours later had writ- ten my “five-year ideal scene” down to precise detail on just two pages. That was twenty-five years of scattered goals and dreams consolidated and refined. The point is this: I had been asking with all my heart for the last four or five years to really get my life’s path together. The works of these two wonderful teachers (Canfield and Allen) came at the exact right time. Most importantly, my quiet time is better, so I can “see” (hear) the messages God is giving me quicker and more clearly, and I have more confidence that I am being led. Some Thoughts on the Validity of Imagery Some might say that this imagery and picturing what you want is all “hocus pocus. During the Beijing Olympics in 2008 and the Vancouver Olympics in 2010, you probably heard more than one athlete say they pictured or visualized winning the race or their event over and over to perfection in their minds. If you believe imagery can be used for athletic performance, then it is not a far-fetched notion to believe that imagery can help us achieve a state of wellness with the physical body and abilities we want. Just thinking - 192 - the triad mind-body program about yourself being whole and vibrant has to create something positive physically instead of living in fear that your body is “falling apart. Ulti- mately, if they resonate with you, they are really from God, lovingly guiding you to take the next step to fulfilling your true passions and walking your path on this planet, which is true health—to be able to live your life purpose with vibrancy, energy, passion, com- passion, and most importantly love! That said, any way you get positive momentum going or tighten a few spokes, whether you start with your mind first or physical changes from diet and exercise, moving positively is the key. Ideally, you do it all at once, tightening a couple of mental and physical spokes at the same time. You marry positive mental practices with good lifestyle practices, and wonderful things happen! These changes in dietary intake have been facilitated by improvements in worldwide transportation, marketing, and manufacturing. In ad- dition, people are less physically active in their daily jobs and get- ting to those jobs. These modern lifestyle factors lead to unhealthy weight gain and body inflammation that initiate and propagate all chronic diseases (i. Medical research over the last thirty to forty years has shown that we can reverse chronic diseases, such as heart disease and diabetes, with simple but aggressive lifestyle practices involving diet and exercise. If done with consistency, lifestyle changes by far exceed anything that medication, hormones, or nutritional supple- ments can do for chronic disease management. We have been afraid to use the word “reverse” for the major killers such as heart disease, diabetes, and obesity. These diseases can be reversed with very low-cost, low-technolo- gy approaches, and minimal medical resources—but you have to be educated, you have to choose, you have to be committed, and you have to act! Other chronic diseases—such as cancer, hyperten- sion, stroke, bone loss, bone fractures, and degenerative eye and brain disorders—can be dramatically reduced or delayed and, in some cases, reversed as well. The problem I see is too many compromises with industries and institutions that have to be drastically changed if we are to be a truly healthy society. The whole medical industrial complex has to be downsized, and the pharmaceutical industry must become a second or third option to medical treatment, not the primary approach. Industries that produce unhealthy, highly processed foods and not whole, healthy foods will have to become much smaller. I don’t want these chang- es occurring from government mandate, but from smart and edu- cated consumers. If we simply make good choices with the food we eat and practice these 9 Simple Steps to Optimal Health, we will change these industries and institutions literally overnight with- out “firing a shot! If the government does anything, I want them to disseminate good, credible health information and give economic incentives to individuals, busi- nesses, and industries that help us stay well and use fewer medical services. I hope you can see that through your understanding of the prob- lem of disease care and chronic diseases, and living the lifestyle practices it takes to prevent and reverse most of these conditions, this is the greatest healthcare reform possible. You have to get off your behind and go do it, and healthcare reform is a moot issue! It is harder to be a single mom of three kids, start a new business, take care of an ailing or aging fam- ily member or spouse, or figure out the stock market. My hope is that by now you believe you can live in a world where people are healthy and all people are living their passion and sharing their gifts with the world. My Last Pitch There are two bold sections of my “Life Purpose Statement” that I truly wish for all of you: “I, Kirkham Hamilton, use my energy and honesty to teach and inspire the people of the world to be confidently healthy and to joyfully encourage individuals to follow their life’s pas- sions to the fullest, while they encourage others to do the same in a spirit of peace, joy, respect, and cooperation between people, animals, and the environment. I realize that sometimes my belief in them is stronger than their belief in themselves. Sometimes my enthusiasm and challenge to them can be misunderstood as cocky, pushy, hard, not compassionate, or just plain overwhelming. But - 197 - staying healthy in the fast lane I think most of my patients—not all—know how much I love and care about them and want them to be in charge of their own health. I see you right now stronger, more energetic, spending more time doing what you love to do, and fired up and confident that you can do this. From the depth of my total being, in the words of my ever-present and be- loved mother, I say to you, “You can do it! You may re-introduce reactive foods into your diet after one month on a non-daily basis (ev- ery three to four days). Get clearance from your physician before beginning this restricted diet for one to four weeks.

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