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Pathophysiology r Injointsanacutesynovitismayoccurwhenuratecrys- Age tals have been phagocytosed order aurogra 100mg amex. Sex r If chronic buy aurogra 100mg otc, the crystals accumulate in the synovium 10M:1F and sites such as the ear cartilage forming lumps termed tophi. Theresultof urate damage is either tubulointerstitial disease (urate Aetiology nephropathy) or acute tubular necrosis. High levels of uric acid cause gout but not all individuals with hyperuricaemia will develop gout. Hyperuricaemia Clinical features is associated with increasing age, male sex and obesity, In 70–90% the initial attack of gout affects the big toe. These features ratesofuricacid production or decreased uric acid make it difficult to distinguish from a septic arthritis. Other joints affected include ankles, knees, fingers, el- r Increased uric acid production may be idiopathic or bowsandwrists. Chronicgoutisunusualbutmaycausea secondary to excessive intake or high turnover as seen chronic polyarthritis with destructive joint damage with in malignancy (especially with chemotherapy). Chapter 8: Metabolic bone disorders 373 Investigations Management Urate levels are often high, although they may fall during The pain of pseudogout is relieved by nonsteroidal anti- an acute attack. Metabolic bone disorders Management Acute gout is managed with high dose nonsteroidal anti- inflammatory drugs. Hyperuricaemia is treated only if Osteoporosis associated with recurrent gout attacks. Definition r Non-pharmacological: Weight loss, high-fluid intake, A disease characterised by low bone mass and microar- low alcohol, low-purine diet, avoid thiazides and as- chitectural disruption. Excess purines are excreted as xan- thine rather than uric acid, and the therapy is lifelong. Overall 30% of individuals will have a pathological frac- ture due to osteoporosis. It is thought that osteoporosis rophosphate production leads to local crystal formation. The risk of fractures increases with bone shed from the cartilage in which they have formed. Factors that can affect the re- modelling balance are as follows: r Sex: Females have a lower bone mass and a high rate of Clinical features bone loss in the decade following the menopause. This Chondrocalcinosis may be detected on X-ray in cartilage is largely oestrogen-dependent, early menopause and without joint disease. Acute joint inflammation resem- ovariectomy without hormone replacement therapy bles gout most commonly affecting the knee and other predisposes. Examination of the joint fluid will demonstrate posi- r Genetic factors implicated include the vitamin D re- tively birefringent crystals. Aetiology Pathophysiology Osteomalacia is usually due to a lack of vitamin D or its Although there is low bone mass it is normally min- activemetabolites,butitmaybecausedbyseverecalcium eralised. The structural integrity of the bone is During bone remodelling vitamin D deficiency results in reduced, causing skeletal fragility. Clinical features Osteoporosis is not itself painful; however, the fractures that result are. Typical sites include the vertebrae, distal Clinical features radius(Colles’fracture)andtheneckofthefemur. Other Onset is insidious with bone pain, backache and weak- symptomsofvertebralinvolvementarelossofheightand ness that may be present for years before the diagnosis is increasing kyphosis. Vertebral compression and pathological fractures may occur; a biochemical diagnosis may be made prior Investigations to onset of clinical disease. Investigations r X-rayinvestigationshowsfractures,abonescancanbe r X-ray investigation shows generalised bone rarefac- used to demonstrate recent fractures. Looser’s zones bone density is difficult to assess as the appearance is may be seen in which there is a band of severe rarefac- dependent on the X-ray penetration. Maleswith A disorder of bone remodelling with accelerated rate of gonadal failure benefit from androgens. Chapter 8: Genetic musculoskeletal disorders 375 Prevalence calcium level may rise dramatically. Asymptomatic Paget’s disease requires no treatment, patients with persistent bone pain, repeated fractures, Sex neurological complications or high cardiac output are M = F treated with calcitonin and/or bisphosphonates, which suppress bone turnover.

Sutherland and Shephered (2001) have shown that drug use is associated with academic difficulties buy 100 mg aurogra fast delivery, absenteeism and dropping out of school best 100 mg aurogra. For example cannabis use, which is a drug of choice among South Africa youth has been shown that it generally interferes with learning, short-term memory and psychomotor skills. Melisa et al (2014) reported that methamphetamine (“tik”) had “adverse effects on mental, physical, and economic well-being, and limited future opportunities through school drop-out and incarceration” of drug users in the Western Cape Province. The same study implicated tik use to household conflict, with negative consequences on children, “including neglect and poor birth outcomes”. At a community level, respondents linked tik use to increased rates of crime, violence and corruption, which undercut community cohesion. Consequences to Society Substance abuse certainly means the energies, creativity and talents of the youths are not harnessed. Substance abuse is linked to unemployment, crime, physical inactivity and even premature deaths. The National Drug Master Plan (2012-2016) estimates the costs of illicit drugs to the South African economy at 6. Other major costs such as drug related violence, injuries, deaths, disease, law enforcement and lost productivity remain largely unquantified. Melisa et al (2014) noted that at the community level, tik use was 23 associated with “increased rates of crime, violence and corruption, which undercut community cohesion”. Although these statistics do not directly speak to the youth; they point to a serious national burden. Missing connections in Literature Other than the above, literature in South Africa is silent on the harm substance abuse has on others (friends, and colleagues) (Ramsoomar, 2015). Further research is required to establish the effects of substance abuse by young people on the quality of family life, pressures on family finances, family stress levels, family or friend disruptions, emotional and psychological impacts on families, divorces, theft from family and friends, etc 24 Section 6 Approaches to combating drug use among Youth The above review of literature shows that youth substance abuse is a multidimensional challenge that requires a multifaceted and integrated gamut of interventions. Bronfenbrenner’s socio-ecological framework becomes handy when analysing interventions as it allows the targeting of interventions to all risk factors at all levels: be it individual, micro, mesosystem and exosystem. Thwala (2005) has noted that for any intervention to be successful, it should be underpinned by the following set of principles:  Principle 1: Interventions should promote protective factors and seek to lessen risk factors. Individual Measures At the individual level, literature proposes many strategies for dealing with substance abuse. According to Brook, (2012) effective strategies at this level target the youth directly and also take into account peer influence. Brook observes “that combating substance use should involve reversing positive attitudes to drugs and dealing with personality dispositions that predispose them to drug use, and addressing symptoms of mental health problems that may cause and/or exacerbate the abuse of substances…. Young people should be trained on how to resist peer pressure as this is the single most important risk factor for the youth. Harker, at al (2008) also suggests that it is 25 important to have prevention programmes that attempt to engage the minds of the youth to avoid boredom. Such activities include life skills programmes, vocational training services, youth sport and recreational activities. Thwala (2005), highlights the following key elements for successful prevention programmes:  Balancing negative and positive effects of substance abuse  Improve social skills,  Provide healthy alternatives to drugs,  Focusing on harm reduction to those already affected,  Emphasise quality of life changes  Have interactive programmes and include peers and parents. As young people spend most their time at school, school-based programmes are essential. At school Harker, Myers and Parry (2008) caution against once-off training sessions by specialists as these may have perverse outcomes. They note that once off lectures have proved to be ineffective and instead stimulate more interests on substance abuse. Scare tactics, where inducing fear among substance abusers and immediate families by exaggerating the risks and relative dangers of illegal drugs, or misusing statistics to drive scare messages home, should also be avoided as they have rarely influenced behaviours in a positive way (United Nations Office on Drugs and Crime for Southern Africa 2004). When adolescents discover that they have been misled they subsequently reject any information on drugs from official channels Microsystem: Literature is clear that successful interventions are those that target the youth concurrently with their peers, parents and families. Improving parenting skills and behaviours is essential when trying to address a youth’s immediate toxic environment. The training for parents should ideally focus on  The importance of nurturing one’s children. This could be done through regulatory interventions; decreasing access to alcohol via increased taxes; brief interventions for high risk drinkers; regulation of unlicensed outlets, and removing outlets from residential areas; advertisement restrictions; community mobilisation; and product related strategies such as appropriate labelling. A study by Griffin and Botvin, (2011) has documented various evidence based successful approaches to dealing with youth drug abuse problems.

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Moreover purchase aurogra 100mg mastercard, the constituent amino acids of protein act as precursors of many coenzymes 100mg aurogra free shipping, hormones, nucleic acids, and other molecules essential for life. Thus an adequate supply of dietary protein is essential to maintain cellular integrity and function, and for health and reproduction. Proteins in both the diet and body are more complex and variable than the other energy sources, carbohydrates and fats. The defining char- acteristic of protein is its requisite amino (or imino) nitrogen group. The average content of nitrogen in dietary protein is about 16 percent by weight, so nitrogen metabolism is often considered to be synonymous with protein metabolism. Carbon, oxygen, and hydrogen are also abundant elements in proteins, and there is a smaller proportion of sulfur. The structures for the common L-amino acids found in typical dietary proteins are shown in Figure 10-1. In the protein molecule, the amino acids are joined together by peptide bonds, which result from the elimination of water between the carboxyl group of one amino acid and the α-amino (or imino in the case of proline) group of the next in line. In biological systems, the chains formed might be anything from a few amino acid units (di, tri, or oligopeptide) to thousands of units long (polypeptide), corresponding to molecular weights ranging from hundreds to hundreds of thousands of Daltons. Polypeptide chains do not exist as long straight chains, nor do they curl up into random shapes, but instead fold into a definite three- dimensional structure. The chains of amino acids tend to coil into helices (secondary structure) due to hydrogen bonding between side chain residues, and sections of the helices may fold on each other due to hydrophobic interactions between nonpolar side chains and, in some proteins, to disulfide bonds so that the overall molecule might be globular or rod-like (tertiary structure). Their exact shape depends on their function and for some proteins, their interaction with other molecules (quaternary structure). The most important aspect of a protein from a nutritional point of view is its amino acid composition, but the protein’s structure may also influ- ence its digestibility. Some proteins, such as keratin, are highly insoluble in water and hence are resistant to digestion, while highly glycosylated proteins, such as the intestinal mucins, are resistant to attack by the proteolytic enzymes of the intestine. Amino Acids The amino acids that are incorporated into mammalian protein are α-amino acids, with the exception of proline, which is an α-imino acid. This means that they have a carboxyl group, an amino nitrogen group, and a side chain attached to a central α-carbon (Figure 10-1). Functional differences among the amino acids lie in the structure of their side chains. In addition to differences in size, these side groups carry different charges at physiological pH (e. These side chains have an important bearing on the ways in which the higher orders of protein structure are stabilized and are intimate parts of many other aspects of protein function. Attractions between positive and negative charges pull different parts of the molecule together. Hydrophobic groups tend to cluster together in the center of globular proteins, while hydrophilic groups remain in contact with water on the periphery. The ease with which the sulfhydryl group in cysteine forms a disulfide bond with the sulfhydryl group of another cysteine in a polypeptide chain is an important factor in the stabilization of folded structures within the poly- peptide and is a crucial element in the formation of inter-polypeptide bonds. The hydroxyl and amide groups of amino acids provide the sites for the attachment of the complex oligosaccharide side chains that are a feature of many mammalian proteins such as lactase, sucrase, and the mucins. Histidine and amino acids with the carboxyl side chains (glutamic acid and aspartic acid) are critical features in ion-binding proteins, such as the calcium-binding proteins (e. Some amino acids in protein only achieve their final structure after their precursors have been incorporated into the polypeptide. The former hydroxylated amino acids are critical parts of the cross-linking of collagen chains that lead to rigid and stable structures. Nutritional and Metabolic Classification of Amino Acids Older views of the nutritional classification of amino acids categorized them into two groups: indispensable (essential) and dispensable (non- essential). The nine indispensable amino acids (Table 10-1) are those that have carbon skeletons that cannot be synthesized to meet body needs from simpler molecules in animals, and therefore must be provided in the diet.

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Research suggests that both of these are involved in the disease process cheap 100mg aurogra with amex, but the exact sequence of events is still not understood 100 mg aurogra with amex. We still need to learn more about why these proteins build up in the brain and how they damage nerve cells. Research is underway to understand more about what happens in the brain during Alzheimer’s. Someone’s risk of developing Alzheimer’s is made up of a number of different elements. The biggest risk factor for developing late-onset Alzheimer’s is age – the older you are the more likely you are to develop it. While we can’t change our age or our genes, research is underway to learn more about ways we might help prevent Alzheimer’s or lower our risk. Lifestyle Some of the risk factors for Alzheimer’s are the same as for cardiovascular disease (like heart disease and stroke). By leading a healthy lifestyle and taking regular exercise you will be helping to keep your heart healthy. To keep healthy: be active and exercise regularly keep cholesterol at a healthy level don’t smoke maintain a healthy weight eat a healthy balanced diet only drink alcohol within recommended limits. Some research has suggested that if you have a parent or grandparent with Alzheimer’s and they developed Alzheimer’s over the age of 65, then your risk of developing Alzheimer’s may be slightly higher than someone with no family history. Research has identifed some genes that may be associated with a higher risk of late-onset Alzheimer’s in some people. In these cases, many members of the same side of the family are affected, often in their 30s, 40s or 50s. If you want to know more about the genetics of Alzheimer’s, ask us for our ‘Genes and dementia’ leafet. People with Down’s syndrome are at increased risk of developing Alzheimer’s, and are more likely to develop the disease at an earlier age. Through the research we fund into the causes of Alzheimer’s, our scientists are building a detailed picture of what happens in the brain in the disease. This is essential for improving diagnosis and developing new treatments to stop it. Thanks to the generosity of our supporters, we continue to support scientists who will take us one step closer to a cure. Find out more If you have questions about dementia research or want to fnd out more about how to get involved in research, contact our Dementia Research Infoline on 0300 111 5 111 or email infoline@alzheimersresearchuk. Calls cost no more than national rate calls to 01 or 02 numbers and should be included in any free call packages. You can drop it straight in a post box or put it in an envelope labelled with the freepost address overleaf. I would like to know more about Early-onset Alzheimer’s Treatments for dementia Genes and dementia Caring for someone with dementia: organisations that can help The latest dementia research Title Name Address We would like to keep you informed about our research and our progress in defeating dementia. You can let us know what you think about this booklet by contacting us using the details below. Although symptoms can vary widely, the first problem many people notice is forgetfulness severe enough to affect their ability to function at home or at work, or to enjoy hobbies. The disease may cause a person to become confused, get lost in familiar places, misplace things or have trouble with language. It can be easy to explain away unusual behavior as part of normal aging, especially for someone who seems physically healthy. That includes 11 percent of those age 65 and older and one-third of those 85 and older. The disease also impacts more than 15 million family members, friends and caregivers. Dementia Dementia is a general term for the loss of memory and other cognitive abilities serious enough to interfere with daily life. Other types of dementia » Vascular dementia is a decline in thinking skills caused by conditions that block or reduce blood flow to the brain, depriving brain cells of vital oxygen and nutrients. These changes sometimes occur suddenly following strokes that block major brain blood vessels.

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Subject to statutory exception and to the provisions of relevant collective licensing agreements discount 100 mg aurogra visa, no reproduction of any part may take place without the written permission of Cambridge University Press aurogra 100mg amex. First published 2010 Printed in the United Kingdom at the University Press, Cambridge A catalog record for this publication is available from the British Library Library of Congress Cataloging in Publication data Mayer, Dan. To the extent permitted by applicable law, Cambridge University Press is not liable for direct damages or loss of any kind resulting from the use of this product or from errors or faults contained in it, and in every case Cambridge University Press’s liability shall be limited to the amount actually paid by the customer for the product. Every effort has been made in preparing this publication to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors, and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors, and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this publication. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use. However, the publisher has no responsibility for the websites and can make no guarantee that a site will remain live or that the content is or will remain appropriate. Kaplan v vi Contents 17 Applicability and strength of evidence 187 18 Communicating evidence to patients 199 Laura J. Henry Pohl, then Associate Dean for Aca- demic Affairs, asked me to develop a course to teach students how to become lifelong learners and how the health-care system works. The first syllabus was based on a course in critical appraisal of the medical literature intended for inter- nal medicine residents at Michigan State University. The basis for the orga- nization of the book lies in the concept of the educational prescription proposed by W. The goal of the text is to allow the reader, whether medical student, resident, allied health-care provider, or practicing physician, to become a critical con- sumer of the medical literature. This textbook will teach you to read between the lines in a research study and apply that information to your patients. For reasons I do not clearly understand, many physicians are “allergic” to mathematics. It seems that even the simplest mathematical calculations drive them to distraction. Although the math content in this book is on a pretty basic level, most daily interaction with patients involves some understanding of mathematical processes. We may want to determine how much better the patient sitting in our office will do with a particular drug, or how to interpret a patient’s concern about a new finding on their yearly physical. Far more commonly, we may need to interpret the information from the Internet that our patient brought in. The math is limited to simple arithmetic, and a handheld calculator is the only computing ix x Preface instrument that is needed. The layout of the book is an attempt to follow the process outlined in the edu- cational prescription. You will be given information about the answer after pressing “submit” if you get the question wrong. When you press “submit,” you will be shown the correct or suggested answer for that question and can proceed to the next question. After finishing, a sample of correct and acceptable answers will be shown for you to compare with your answers. Decisions are made by language and the language includes both words and numbers, but before evidence-based decision-making came along, relatively little consideration was given to the types of statement or proposi- tion being made. Hospital Boards and Chief Executives, managers and clinicians, made statements but it was never clear what type of statement they were mak- ing. Was it, for example, a proposition based on evidence, or was it a proposition based on experience, or a proposition based on values? All these different types of propositions are valid but to a different degree of validity. This language was hard-packed like Arctic ice, and the criteria of evidence- based decision-making smash into this hard-packed ice like an icebreaker with, on one side propositions based on evidence and, on another, propositions based on experience and values. As with icebreakers, the channel may close up when the icebreaker has moved through but usually it stays open long enough for a decision to be made. We use a simple arrows diagram to illustrate the different components of a decision, each of which is valid but has a different type of validity.

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