Mark Corson

By H. Kayor. Houston Baptist University.

Many of them may stem from factors other than a true association with disease risk (McClellan and King 2010) order 50 mg viagra super active otc erectile dysfunction medications for sale. Current sequencing technologies offer the possibility of finding rare disease-causing mutations and the genes that harbor them discount 50 mg viagra super active otc buy generic erectile dysfunction drugs. Genetic testing will eventually improve predictions about what diseases we are predisposed to viagra super active 50 mg line erectile dysfunction gif, the timing of their onset, their extent and eventual severity as well as which treatments or medications are likely to be efficacious or deadly. Genotyping, however, does not necessarily correlate with response to medications and other fac- tors such as environmental have to be taken into consideration in personalizing treatment. Pharmacogenomics and pharmacogenetics are providing the basis for the devel- opment of molecular diagnostics to improve drug selection, identify optimal dos- ing, maximize drug efficacy or minimize the risk of toxicity. Rapid advances in basic research have identified many opportunities for the development of personal- ized treatments for individuals and/or subsets of patients defined by genetic and/or genomic tests. However, the integration of these tests into routine clinical practice remains a major multidisciplinary challenge. Although physicians and patients are optimistic about the health benefits that genetic testing might provide, neither group is well informed, and there are likely too few experts available to meet growing demands for genetic testing. Attempts to integrate genomic medicine into clinical practice are still in the early stages, and as a result, many questions sur- round the current state of this translation. There is a need for a large-scale effort to educate both health professionals and the public about genomic medicine, and to develop and evaluate new ways to deliver genetic services. Genomics-based molecular profiling and related technologies may impact on the delivery of healthcare even before genomics-based drugs hit the market. Identification of genetic factors affecting the prognosis of disease is likely to be of most clinical relevance. Greatest progress will be made in understanding the genetic contribution to the intermediate phenotypes linking genes and disease, and thus the biology of the disorder, as in atherosclerotic disease. The greatest impact of personalized medicine will be in the treatment of cancer, cardiovascular diseases, infections and neurological disorders. The emerging fields of metabonomics (metabolite profiling to identify genotype- phenotype associations) and phenomics might offer solutions for anticipating and decreasing risk of adverse drug reactions in each individual patient, but tests based on these approaches are not expected to become generally available to the practicing clinician for at least the next 5 years. Genetic Testing and Concerns About Equality of Healthcare There is a concern genomics and associated technologies may exacerbate dispari- ties at multiple levels because of unequal application among human populations. Genomic tech- nologies will provide new opportunities and their translation into healthcare appli- cations should not be held back because of this concern. Genetic data collection should be extended to as many diverse populations as possible. It is also critical to assess nongenetic factors, which vary substantially among populations and may interact in important ways with genetic risk factors. Analyses of these effects and interactions can be especially powerful in the context of large, long-term prospec- tive studies. To make the best use of genomic data, physicians and the public should be educated about its benefits as well as limitations. Pharmacotyping Pharmacotyping is individualized drug selection and dosage profiling by the phy- sician based on clinical evaluation of the patient’s genotyping and haplotyping data for genes involved in the pharmacokinetics and pharmacodynamics of drugs in the body (Vizirianakis 2007). Pharmacotyping could be a new dimension of pharmacogenetics/pharmacogenomics and its application in routine clinical prac- tice in the post-genomic era could better depict drug selection and dosage. This means a transition from a drug-selection process mainly based on the physician’s own experience, into a more, highly integrated, information-based and computer- aided pharmacotherapy-based decision, thus making drug delivery digitized, more efficient and safer. Progress in nanomedicine with nano-based systems for targeted drug deliv- ery and pharmacogenomics are moving the drug-prescription process toward phar- macotyping, but the utility of this approach needs to be demonstrated by cost-effectiveness analysis (Vizirianakis 2011). In order to achieve major benefits for all patients worldwide, a multidisciplinary technological infrastructure should be organized in the healthcare system to address issues affecting regulatory environ- ment, clinical pharmacology guidelines, education, bioethics and genomics data dissemination. However, by supporting comparative studies it might counteract the criticism that there is a paucity of studies comparing personal- ized with conventional care, and may help in promoting further acceptance of per- sonalized medicine. For example, large observational databases and pooled trial results can be used to learn more about the subgroups of patients who benefit from therapy. An initiative to advance our knowledge about the effective- ness of clinical strategies can hasten the day when personalized medicine trans- forms health care. Medicine in the Year 2025 Medicine is evolving rapidly in the postgenomic era and some of the general advances anticipated by the year 2025 are: • Pathomechanism of most of the currently known major diseases will be under- stood at the molecular level. Universal Free E-Book Store Medicine in the Year 2025 705 • Marked increase in the number of validated biomarkers and their use for monitoring therapy. Companies that do not use pharmacogenomic testing in drug development will lose out to the ones that do so. Although some of the pharmacogenomic-based new drugs being discov- ered now may not have completed the development by this time, use of some of the older drugs is being individualized and several components of personalized medi- cine are being put into place now. Molecular and diagnostic tests have a shorter time to approval than drugs and some are already in the market. Integration of diagnostics and therapeutics is also taking place and it is anticipated that personalized medicine will develop parallel with the introduction of pharmacogenomic-based medicines. Genotyping will be for twenty-first century medicine what the x-rays were for twenty-first century clinical practice. Genetic testing will eventually improve pre- dictions about what diseases we are predisposed to, the timing of their onset, their extent and eventual severity as well as which treatments or medications are likely to be efficacious or deadly. Genotyping, however, does not necessarily correlate with response to medications and other factors such as environmental have to be taken into consideration in personalizing treatment. Universal Free E-Book Store 706 24 Future of Personalized Medicine Concluding Remarks About the Future of Personalized Medicine In the year 1998, when the first monograph with the title (“Personalized Medicine” was published, there was little interest in this topic (Jain 1998). Some of them have backgrounds in pharmacogenetics and pharmacogenom- ics, but had not made any efforts to integrate other emerging technologies into per- sonalized medicine. Others accept that personalized medicine will come but try to put the date off into the distant future. This conclusion was disputed even though the Royal Society claims to have consulted a broad spectrum of persons and organizations involved in personalized medicine, because they ignored the most important play- ers, the biopharmaceutical industry (Jain 2006).

Distracters such as videotaped cartoons and stories have been used to help children cope with dental treatment order 50 mg viagra super active fast delivery erectile dysfunction drugs recreational use. The results have been somewhat equivocal and the threat to switch off the video was needed to maintain co-operation best viagra super active 50mg erectile dysfunction causes relationship problems. As the techniques require the presence of a trained therapist buy viagra super active 25mg fast delivery erectile dysfunction latest treatments, the potential value in general paediatric dentistry has still to be assessed. This technique relies on the use of a trained therapist and in most instances a simple dentally based acclimatization programme should be tried first. Hosey (2002) and Manley (2004) note that in the United Kingdom the use of physical restraint is presently unacceptable. In this section other options to restraint have been suggested and, although time consuming, are likely to provoke less of a nervous reaction and avoid associating dental care with an unpleasant experience. For those readers who wish to study the topic in more detail, comprehensive clinical guidelines collated by The American Academy of Paediatric Dentistry have been published in the Journal of Paediatric Dentistry (2002). Non-verbal communication is the reinforcement and guidance of behaviour through appropriate contact, posture, and facial expression. Objectives: (i) To enhance the effectiveness of other communicative management techniques. Tell-show-do is a technique of behaviour shaping used with both verbal and non- verbal communication. Objectives: (i) To teach the patient important aspects of the dental visit and familiarize the patient with the dental setting. Positive reinforcement is the process of establishing desirable patient behaviour through appropriate feedback. Parental presence/absence involves either allowing or removing the parent(s) from the dental surgery in order to gain cooperation. Hand over mouth exercise is a technique for managing unsuitable behaviour that cannot be modified by the more straightforward techniques. Indications: (i) A healthy child who is able to understand and co-operate, but who exhibits obstreperous or hysterical avoidance behaviours. Contraindications: (i) In children who, due to age, disability, medication, or emotional immaturity are unable to verbally communicate, understand, and co-operate. Other techniques such as sedation in all its forms and general anaesthesia are described elsewhere. To prevent the development of anxiety it is more important to maintain trust than concentrate on finishing a clinical task. The reduction in dental caries means that children with special psychological, medical, and physical needs can be offered the oral health care they require. The care of children who are very anxious can be improved by using the techniques described in this chapter. Preventing dental disease should always be given the same status as clinical intervention. However, it is important to ensure that preventive care is appropriate and relevant. The key messages are outlined in The scientific basis of oral health education (Levine and Stillman-Lowe, 2004). Strap him down or knock him out: is conscious sedation with restraint an alternative to general anaesthesia? High on the list of challenges is the need to devise a comprehensive yet realistic treatment plan for these young patients. Successful outcomes are very unlikely in the absence of thorough short- and long- term treatment planning. Furthermore, decision-making for children has to take into account many more factors than is the case for adults. This chapter aims to highlight how history-taking, examination, and risk assessment are all critical stages in the treatment planning process. The most important element of the consent procedure is ensuring that the patient/parent understands the nature and purpose of the proposed treatment, together with any alternatives available, and the potential benefits and risks. In this context, where clinician and patient/parent do not share a common language, the assistance of an interpreter is essential. Key Point A signature on a consent form is not consent if the patient/parent has not been given and understood the relevant information. In the United Kingdom, for the purposes of medical and dental treatment, a child is defined as being less than 16 years of age. If a child is subjected to examination, investigation, or treatment without the consent of an individual who has parental responsibility, this can constitute an assault, actionable in civil or criminal law as a breach of the human right. While most children will attend the dental surgery accompanied by an adult, it is important to bear in mind that this individual will not always have parental responsibility (the Children Act 1989 sets out the persons who may have parental responsibility for a child). Key Point It is essential to establish what relationship exists between the child and the accompanying adult at the outset. In circumstances where a child is a ward of Court, the prior consent of the Court is required for significant interventions. In an emergency, it is justifiable to treat a child without the consent of the person with parental responsibility if the treatment is vital to the health of the child. For example, while it may be acceptable to replant an avulsed permanent incisor, the parent should be contacted before proceeding to other forms of treatment.

Such a ‘medicalisation’ of daily life was strengthened by the intellectual cachet and rhetorical elegance of medicine which Celsus refers to purchase viagra super active 100mg on line impotence at 33, and to which the extant fragments of Diocles’ works certainly testify; but it is easy to see how it may have met with resistance – an unease which is reflected buy 50 mg viagra super active erectile dysfunction injections, as far as the application of dietetic principles to the treatment of diseases is concerned buy 25mg viagra super active with visa erectile dysfunction 9 code, by Plato’s well-known attack on dietetics in the Republic. This is illustrated by the fragment of Diocles’ contemporary Mnesitheus just quoted, and also by a fragment of Erasistra- tus,70 in which a distinction between medicine («atrikž) and the care for health (t‡ Ëgiein†) is connected with a distinction between two different practitioners: the ‘healer’ («atr»v) and the ‘health specialist’ (Ëgiein»v). It is also illustrated five centuries later by Galen’s treatise Thrasybulus, which deals with the question ‘Whether the care for the healthy body belongs to medicine or to gymnastics’. But this specialisation, or indeed compart- mentalisation, of medical care meant that the unity of therapeutics which the Hippocratic doctors had insisted on, was gradually lost: the distance between patient and doctor steadily increased – a development that has continued up to the present day, and which clearly goes against what I would still call the spirit of Hippocratic medicine. His main reason for doing so is to show the contrast between his own and only correct treatment of the disease and the general confusion among other doctors: What part [of the body] is affected in phrenitis? This question has been raised particularly by leaders of other sects so that they may apply their treatments ac- cording to the different parts affected and prepare local remedies for the places in question. Now some say that the brain is affected, others its fundus or base, which we may translate sessio [‘seat’], others its membranes, others both the brain and its membranes, others the heart, others the apex of the heart, others the mem- brane which incloses the heart, others the artery which the Greeks call aorte, others the thick vein (Greek phleps pacheia), others the diaphragm. But why continue in this way when we can easily clarify the matter by stating what these writers really had in mind? For in every case they hold that the part affected in phrenitis This chapter was first published in Dutch in Gewina 18 (1995) 214–29. The epistemological principles of the Methodists are discussed by Frede (1983) and by Lloyd (1983) 182–200. Now we hold that in phrenitis there is a general affection of the whole body, for the whole body is shaken by fever. And fever is one of the signs that make up the general indication of phrenitis, and for that reason we treat the whole body. We do hold, however, that the head is more particularly affected, as the antecedent symptoms indicate, e. But there are those who argue as follows: ‘We determine the part affected on the basis of the theory of nature (Greek phusiologia), for we know in advance that the ruling part of the soul is located in the head, and conclude that that must be the source of mental derangement. But the number and variety of symptoms occurring in the head have shown us that this organ is more particularly affected than the rest of the body. This discussion was to a certain extent determined by a lack of clarity about the evidential value of the etymological relation between the name of the disease and the Greek word phrenes, which had been used since Homer to indicate the midriff (later, the common term for this became diaphragm, as used here by Caelius). Some advocates of the location in the diaphragm appealed to this etymology,4 others were of the opinion that the name of the disease should not be related to any part of the body (be it affected or not), but to the faculty that was affected (phronein, phronesis¯ , standard terms in Greek for what we would call ‘intelligence’ or ‘consciousness’). Another significant fact is that Caelius Aurelianus criticises his predeces- sors’ strong desire to locate the condition in one particular place in the body, and their presupposition that this place should also be the seat of the mind (the faculty affected in the case of phrenitis). Heart, brain, blood, pneuma 121 any particular place, but that the entire body is ill and therefore the entire body requires treatment. Another characteristic of the Methodists is that speculations on the location of the mind are rejected for being pointless, as it is impossible to reach conclusions on the matter on empirical grounds, and the doctor should abstain from expressing any opinions (‘first of all it is still uncertain which part of the body is the leading part’). This attitude is inspired by the close connection between the epistemological views of the Methodists and those of the philosophical school of the Sceptics, who on principle refuse to express opinions on any non-perceptible matters. In addition, the Methodists consider such questions irrelevant to therapeutic practice, which they regard as the focus of medical science. Whether Caelius Aurelianus does justice to all his medical predecessors by presenting matters as he does is very much the question. Recent research into the principles and methods of doxography (the description of the doxai, the characteristic doctrines of authorities in a certain subject) has revealed that the question ‘What is the leading principle in man and where is it located? It became a favourite subject for practising argumentation techniques (comparable to questions such as ‘Is an embryo a living being? Such ‘dialectic’ staging of a debate bears little relation to a historically faithful rendition of a debate that actually took place in the past. It is most probable that Caelius Aurelianus’ summary of views as quoted above is part of such a doxographical tradition, and therefore highly schema- tised. In his presentation, the views of those to whom he refers – without mentioning their names8 – imply a number of presuppositions regarding empirical evidence and theoretical concepts in respect of which it is ques- tionable whether the authorities concerned actually held them. A question like ‘What is the leading principle of the soul and where is it located? The debate to which Caelius 7 On this see Mansfeld (1990), and for embryology Tieleman (1991). Further down in the same book Caelius Aurelianus discusses the therapeutic views on phrenitis held by Diocles, Erasistratus, Asclepiades, Themison and Heraclides. The use of this term implies the possibility of grading various psychic parts or faculties, some of which are subordinate to others, and presupposes an anatomical and physiological relationship underlying such a hierarchy. On the one hand such a presen- tation presupposes a rather elaborate psychological theory, free from the difficulties and obscurities that, for instance, Aristotle points out when he discusses the psychological views of his predecessors in the first book of his On the Soul (De anima ). It will be clear that a presentation such as that by Caelius Aurelianus, in which all doctors and philosophers are called to the fore to express their views on the matter, puts opinions in their mouths that many of them (probably) never phrased in these terms. On the other hand, such a presentation does not do justice to thinkers such as Aris- totle and some authors of the Hippocratic Corpus, as it often obscures the subtle differences in meaning between the various terms used for psychic faculties by these thinkers. We will see below that as early as the fifth and fourth centuries bce, doctors and philosophers carefully differentiated be- tween cognitive faculties such as ‘practical’, ‘theoretical’, and ‘productive thinking’; ‘insight’; ‘understanding’; ‘opinion’; and ‘judgement’. Thus Aristotle was credited in late antiquity with the view that ‘the soul’, or at least its leading principle (the arche¯), is seated in the heart. We will see that this is a mis- representation of Aristotle’s views, which, strictly speaking, leave no room for location of the highest psychic faculty, the nous. Similarly, the author of the Hippocratic work On Regimen (at the start of the fourth century bce) presupposes a view of the soul that does not specify where exactly it is located in the body; he even appears to assume that the location may vary. In short, this doxographic distortion attributes to doctors and philosophers answers to questions which some of them would not even be able or willing to answer as a matter of principle.