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By Z. Jorn. University of Advancing Technology. 2018.

For all of these acknowledge that what they know concerning medical practice they know by means of reasoning in conjunction with experience atorlip-10 10mg free shipping cholesterol levels genetic factors. In particular discount atorlip-10 10mg with amex best cholesterol lowering foods recipes, Diogenes and Diocles argue at length that it is not possible in the case of food and drink to ascertain their ultimate effects but by way of experience. In this testimony, the view of Diocles and the other ancient authorities is obviously referred to in order to support Galen’s argument against an exclusively theoretical approach to medicine. And although we should not assign much independent value to this testimony – which, apart from its vagueness, is a typical example of Galen’s bluffing with the aid of one of his lists of Dogmatic physicians – it is compatible both with the picture of Diocles’ general medical outlook that emerges from the collection of fragments as a whole and with his approach to dietetics as reflected in our fragment 176. Diogenes and Diocles are mentioned by Galen in particular trofaª m»non e«s©n, oÉ f†rmaka, mžqì Ëp†gonta gast”ra... This reference to the ‘ultimate effects’58 is in accordance with the in- terpretation of section 8 given above: this ultimate effect does not admit of further causal explanation; we can only make sure what it is by experience, by applying the foodstuff in a given case and seeing how it works out. Postscript Discussions of this fragment that came out after the original publication of this paper can be found in Hankinson (1998a), (1999) and (2002), in van der Eijk (2001a) 321–34, and in Frede (forthcoming). But a re-examination of the Arabic would seem to make this interpretation less plausible. A literal translation of the Arabic would read as follows: ‘It is not possible to ascertain in the case of food and drink where their last things (akhiriyatuha? The idea is then that although a Dogmatist might speculate theoretically about the power (dÅnamiv)ofa particular foodstuff, e. Thus the position attributed to Diocles here corresponds closely with that attributed to him by Galen in fr. This would suggest that Galen is referring to how foods and drinks are ultimately disposed of; but this would seem to be quite inappropriate to the context. Principles and practices of therapeutics in the Hippocratic Corpus and in the work of Diocles of Carystus 1 introduction In a well-known passage from the Hippocratic Epidemics, the doctor’s duties are succinctly characterised as follows: [The doctor should] declare what has happened before, understand what is present, and foretell what will happen in the future. As to diseases, he should strive to achieve two things: to help, or to do no harm. The (medical) art consists of three components: the disease, the patient, and the doctor. It is succinctly summarised here in the words ‘to help, or to do no harm’ (Ýfele±n £ mŸ bl†ptein), a formula which is often quoted or echoed both in the Hippocratic Corpus and in later Greek and Roman medical literature. The Hippocratic Oath, which explicitly mentions the well-being of the patient as the doctor’s This chapter was first published in slightly different form in I. Thus, according to the Oath, the doctor is not allowed to give a woman an abortive, nor to administer a lethal poison, not even when being asked to do so; and the doctor is instructed to refrain from every kind of abuse of the relation of trust that exists between him and the patient. Yet it is also possible – as the word ‘or’ suggests – to take the formula in the sense of unintended harm: ‘To help, or at least to cause no harm’, that is to say, the doctor should be careful when treating the patient not to aggravate the patient’s condition, for example in cases that are so hopeless that treatment will only make matters worse, or in cases which are so difficult that the doctor may fail in the execution of his art; and as we shall see, there is evidence that Greek doctors considered this possibility too. In this chapter I will examine how this principle ‘to help, or to do no harm’ is interpreted in Greek medical practice and applied in cases where it is not immediately obvious what ‘helping’ or ‘causing harm’ consists in. I will study this question by considering the therapeutic sections of a number of Hippocratic writings (most of which date from the period 425–350 bce) and in the fragments of the fourth-century bce medical writer Diocles of Carystus. This passage has received ample attention in scholarship, and it is not my in- tention to give a detailed interpretation or an assessment of its historical reliability. By this I mean the position and relative importance of therapeutics within the field of medicine as a whole, which gives rise to 3 ‘I will use dietetic measures to the benefit of the patients... I will keep them from harm and injustice’ (diaitžmas© te cržsomai –pì Ýfele©h€ tän kamn»ntwn... For more general assessments of Celsus as a source for the history of medicine see Smith (1979) 226–30 and (1989) 74–80; von Staden (1994b) 77–101 and (1999b); Stok (1994) 63–75; Temkin (1935) 249–64. To help, or to do no harm 103 questions such as the following: Are therapeutics and medicine identical? Or is therapeutics a part of medicine, or perhaps an aim (or even the aim) of medicine?

But it would no doubt refrain from worked-out nosological descriptions and from extended and detailed prescriptions on prognostics and therapeutics cheap atorlip-10 10 mg fast delivery which cholesterol medication is best. He obviously approves of doctors who build their practice on principles of natural science buy atorlip-10 10mg overnight delivery cholesterol ratio in human body, but he also acknowledges that more empirically minded doctors often have greater therapeutic suc- cess. He further praises those liberal-minded students of nature (among whom he implicitly counts himself) who deal with the principles of health and disease. He obviously prefers the study of nature rather than medicine, because the former is concerned with universals, the latter with particu- lars, and because the former reaches a higher degree of accuracy, but he quoted above Aristotle credits the liberal-minded student of politics with a similar awareness of a limited degree of accuracy in his interest in psychology: one might say that this implies a comparable awareness with the distinguished doctors with regard to their use of principles derived from the study of nature. Aristotle on sleep and dreams 197 also recognises that even medicine may contribute to the study of na- ture (a fact he hardly could ignore, given the large amount of anatomi- cal and physiological information preserved in the Hippocratic writings). Having considered his theoretical position on the relationship between medicine and the study of nature, let us now turn to the practice of the ‘inquisitive non-specialist’ Aristotle in his discussion of the prognostic value of dreams. For although the distinguished doctors’ opinion is a reputable view and as such an important indication that there are, in fact, dreams which play the part of signs of bodily events, the rational justification (eulogon) for the natural scientist’s sharing this view does not lie in the doctors’ authority, but in the fact that he can give an explanation for it. The explanation which follows makes use of empirical claims but is also based on Aristotle’s own theory of dreams. For the fact is that movements occurring in the daytime, if they are not very great and powerful, escape our notice in comparison with greater movements occurring in the waking state. But in sleep the opposite happens: then it is even the case that small movements appear to be great. This is evident from what often happens during sleep: people think that it is lightning and thundering, when there are only faint sounds in their ears, and that they are enjoying honey and sweet flavours when a tiny bit of phlegm is running down their throats, and that they go through a fire and are tremendously hot when a little warmth is occurring around certain parts of the body. But when they wake up, they plainly recognise that these things are of this nature. Consequently, since of all things the beginnings are small, it is evident that also of diseases and of other affections which are going to occur in the body, the beginnings are small. It is obvious, then, that these are necessarily more clearly visible in sleep than in the waking state. If the dream is correctly interpreted, it can be reduced to its cause, which can be recognised as the cause of an imminent disease. Aristotle pays no attention to the rules for such a correct interpretation of dreams; he only analyses the causal structure of the relationship between the dream and the event foreseen in it. The first is one of the corner stones of his theory of dreams as set out in On Dreams (460 b 28ff. This principle is demonstrated by means of a number of examples derived from common experience (no. The second principle is that the origins of all things (including diseases) are small and therefore belong to the category of small movements. The two principles are combined in the form of a syllogism at the end of the paragraph. These points are most relevant for an assessment of what Aristotle is do- ing in the passage under discussion. It has, of course, long been recognised by commentators that the sentence 463 a 4–5 may very well be a reference to the Hippocratic treatise On Regimen, the fourth book of which deals with dreams and which I quoted at the beginning of this chapter. Although the Hippocratic Corpus contains several examples of the use of dreams as prognostic or diagnostic clues,49 we nowhere find such an explicit theoret- ical foundation of this as in this book. It is chronologically possible and plausible that Aristotle knew this treatise, because other places in the Parva naturalia show a close similarity of doctrine to On Regimen. Moreover, the author’s approach must have appealed to Aristotle for the very fact that the interest of dreams is that they reveal the causes of diseases. However, these similarities should not conceal the fundamental differ- ence of approach between the medical writer and Aristotle. This difference not only manifests itself in that Aristotle, as a natural scientist, is only inter- ested in the causal relationship between the dream and the event, whereas On Regimen is primarily a text about regimen (both from a preventive and from a therapeutic point of view), which explains the great amount of de- tailed attention paid to the interpretation of the contents of dreams and to prescriptions about preventive dietetic measures.

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The strategy included data preprocessing order atorlip-10 10mg line cholesterol lowering foods omega 3, data analysis buy atorlip-10 10mg on-line cholesterol upper limit, and validation of sta- tistical models. Univariate plots of potential biomarkers were used to obtain insight in up- or down-regulation. Pharmacometabonomics A major factor underlying inter-individual variation in drug effects is variation in metabolic phenotype, which is influenced not only by genotype but also by environ- mental factors such as nutritional status, the gut microbiota, age, disease and the co- or pre-administration of other drugs. Thus, although genetic variation is clearly important, it seems unlikely that personalized drug therapy will be enabled for a wide range of major diseases using genomic knowledge alone. Metabolite patterns Universal Free E-Book Store Metabonomic Technologies for Toxicology Studies 175 that are characteristic of the individual can be used to diagnose diseases, predict an individual’s future illnesses, and their responses to treatments. The principle of pharmacometabonomics has been demonstrated in humans by showing a clear connection between an individual’s metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen (Clayton et al. The predose spectra were statistically analyzed in relation to drug metabolite excre- tion to detect predose biomarkers of drug fate and a human-gut microbiome come- tabolite predictor was identified. Thus, the investigators found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. They conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acet- aminophen. Given that acetaminophen is such a widely used and seemingly well- understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, many other sulfonation reactions are expected to be similarly affected by competition with p-cresol and these finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. It is proposed that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, gut bacterial populations might be deliberately manipulated to improve drug effi- cacy and to reduce adverse drug reactions. Pharmacometabonomics could be used to preselect volunteers at key stages of the clinical trials. This would enable stratifi- cation of subjects into cohorts, which could minimize the risk of adverse events, or focus on those individuals with a characteristic disease phenotype for assessment of efficacy. Metabonomic Technologies for Toxicology Studies Metabonomics studies demonstrate its potential impact in the drug discovery pro- cess by enabling the incorporation of safety endpoints much earlier in the drug discovery process, reducing the likelihood (and cost) of later stage attrition. Global metabolic profiling (metabonomics/metabolomics) has shown particular promise in the area of toxicology and drug development. A metabolic profile need not be a comprehensive survey of composition, nor need it be completely resolved and assigned, although these are all desirable attributes. For the profile to be useful across a range of problems, however, it must be amenable to quantitative interpreta- tion and it should be relatively unbiased in its scope. A further requirement for the Universal Free E-Book Store 176 7 Role of Metabolomics in Personalized Medicine platform used to generate profiles is that the analytical variation introduced postcol- lection be less than the typical variation in the normal population of interest, so as not to reduce significantly the opportunity to detect treatment/group-related differ- ences. Fulfilling this condition is very dependent on the actual system and question in hand and is probably best tested in each new application. In both preclinical screening and mechanistic exploration, metabolic profiling can offer rapid, noninvasive toxicological information that is robust and reproduc- ible, with little or no added technical resources to existing studies in drug metabo- lism and toxicity. Extended into the assessment of efficacy and toxicity in the clinic, metabonomics may prove crucial in making personalized therapy and pharmacoge- nomics a reality. The company believes that it is possible to profile metabolic diseases before symptoms appear. Metabonomic testing is important in obesity/metabolic syndromes, in which several metabolic pathways interact to produce symptoms and could be an important guide to select diets and exercise programs tailored to metabolic states. It is considered desirable to establish a human “metabonome” parallel to human genome and proteome but it will be a formidable undertaking requiring analysis of at least half a million people.

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