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G enetic syndrom es 1 Patterns of inheritance cheap 20 mg vasodilan overnight delivery, 516 Incidence Patterns of inheritance Rises with increasing maternal age (1 in 3000 when mother is less than 30 years to 1 in 300 when mother Autosomal dominant:Mendelian pattern of inheritance is 35 40 years and 1 in 30 in women above 45 years) cheap vasodilan 20 mg online. Be- where the presence of a single abnormal allele is able cause of the high birth rate in mothers below 35 vasodilan 20 mg sale, half to produce the disease. There may be reduced expres- of all Down syndrome children are born to mothers sion of the condition if the condition does not have full below 35. Autosomal recessive: Mendelian pattern in which Age both genes must be defective to produce the clinical phe- Congenital. M = F There is no male-to-male transmission, daughters of an affected male will be obligate carriers. In X linked domi- Geography nant conditions, females may also demonstrate the clin- All ethnic communities. The additional chromosome 21 is usually follow normal Mendelian patterns of inheritance. In this (94% of cases) the result of non-disjunction of chromo- set of conditions males and females may be affected, but some 21 during the formation of the maternal ovum. In about 3% of cases there is mosaicism with some cells demonstrating a normal Down syndrome karyotype. Denition Pathophysiology Down syndrome is the clinical condition usually result- The Alzheimer s disease seen with Down syndrome is ing from a trisomy of chromosome 21 rst described by thought to be due to the presence of three copies of the Langdon Down in 1865. Chronic granulomatous Recessive Cytochrome Neutrophils can phagocytose material, but are unable disease b245 to generate respiratory burst and hence kill bacteria. Duchenne muscular dystrophy Recessive Dystrophin Progressive proximal muscle weakness with calf psuedohypertrophy. Causes progressive intellectual deterioration, loss of purposeful use of hands and jerky truncal ataxia. Leber optic atrophy Multiple loci Sudden onset adult blindness, cardiomyopathy, cardiac conduction defects. Short into adult life, but by 40 almost all have Alzheimer s middle phalynx of little nger, single horizontal pal- disease. Klinefelter syndrome r Congenitalheartdiseasein30%,mostcommonlyatri- Denition oventricular septal defects. Tracheo-oesophageal stula, duodenal atresia, annu- lar pancreas, Hirschsprung s disease. Denitive diagnosis is made by chori- more X chromosomes the more severe the phenotype. All appear normal until puberty when hypogo- tions for testing include maternal age and a Down nadism becomes prominent. As there is nor- mally only one copy of the X chromosome, females Incidence suffer from X linked recessive conditions such as 1in5000 live births. O verdose, poisoning 1 and addiction Alcohol and drugs of abuse, 521 Overdose and poisoning, 526 r Alcohol dependence is dened as a maladaptive pat- Alcohol and drugs of abuse tern of use associated with tolerance and withdrawal syndrome despite signicant physical and psycholog- Alcohol abuse and dependence ical problems. Patients often exhibit a stereotyped drinking pattern with alcohol consumption taking Denition preference over other activities. Regular or binge consumption of alcohol sufcient to A history of alcohol consumption should be taken from cause physical, neuropsychiatric or social damage. In addi- Incidence/prevalence tion signs of chronic liver disease and other complica- 3 4%ofthepopulationreportalcohol-relatedproblems. Health care professionals Blood alcohol levels are of limited value, a persistently with access to opiates may abuse drugs like fentanyl. Incidence/prevalence Heroin abuse fell during the late 1990s, but rose again Management rapidly in 2000 and 2001. A fall in use since then has 1 Identication and advice at an early stage may be been attributed to the fall in supply after the Taliban enough to avert serious medical, neuropsychiatric banned production in Afghanistan. Precipitating fac- numbers of users, the number of heroin-induced deaths tors should be identied and psychological sup- has remained static. Abusers and diazepam or lorazepam in the treatment of repeatedly take the drug to achieve the euphoric effect; seizures. Withdrawal in acetaldehyde accumulation resulting in ushing, symptoms also occur, and so further doses are taken to headache, anxiety and nausea. Heroincanbesmoked( chasingthedragon ),snorted, or injected into a vein ( shooting up or mainlining ), or subcutaneously ( skin popping ) or intramuscularly. Opium contains morphine and A history should be taken of recent and previous codeine. Itisnormallyboughtasawhitepowder, Withexcessivedoses,comaanddeathfromrespiratory which is usually snorted or smoked. This combusts more readily making the when tolerance is reduced, or if other drugs or alcohol cocaine more potent. Social problems include loss of job, deterioration in The street term freebasing means smoking cocaine, ei- relationships and criminal activities to obtain money ther as the salt or base. Cocaine and crack can also be to buydrugs,includingstealing,prostitutionanddrug injected, although this is far less common. Incidence/prevalence Investigations 7% of 20 24 year olds have tried cocaine, mainly snort- These depend on the presentation of the individual. About 10 15% of those who try snorting cocaine vestigations may be needed for possible complications become abusers. Crack is linked with areas of social depending on the history and clinical diagnosis. Heroin intoxication is treated by ensuring airway pro- tection, and giving the opiate antagonist naloxone. Tolerance does seem to occur to some not cause euphoria, is used as a method of programmed extent. Baseformsofcocaine, Supportive therapy is needed to prevent the patient from including crack, have a more rapid onset but a much seeking increased doses (either of heroin, other drugs or shorter duration of action. In alcohol, its effects are increased by an active metabolite, some cases, patients stay on long-term methadone at which only forms in the presence of alcohol. Within half an 2 Agitation and hypertension often respond to di- hour of the last dose of a binge, there is a crash when the azepam. Haloperidol and phenothiazines should be user feels intense cravings, depression and anxiety. Long-term users coronary vasoconstriction due to unopposed alpha may become persistently restless, with anorexia, weight effects). Smok- physical effects from withdrawal so sedatives or a re- ing can cause granulomas and pulmonary oedema. Other medical tension or myocardial ischaemia) and antidepressants complications include hypertension, myocardial in- may be indicated. Denition r Social: The most common reason for a cocaine ad- Amphetamines were originally widely used for medical dict to present for treatment of dependency is run- reasons such as appetite suppressants and for insom- ning out of money, as a cocaine or crack binge can nia, but are now recreationally used. Other prob- phetamine (and derivatives) is now limited to selected lems include loss of job and criminal activities such as cases of narcolepsy and attention decit hyperactivity stealing, prostitution and drug dealing. There are several derivatives of amphetamine, such Investigations as methamphetamine, which can be smoked, and there- These depend on the presentation of the individual. Co- fore became popular for their increased speed of on- caine use can be tested for using a urine screen. Amphetamines can be taken gations may be needed for possible complications such orally, intranasally, smoked or injected. Management Cocaine intoxication: Initial management includes en- Incidence/prevalence suring a clear airway and ventilation if needed. Amphetamineandderivatives(includingecstasy)arethe 1 Seizures are treated with diazepam or lorazepam. The excre- tion of amphetamine depends on urine pH acid urine increases its clearance. Ecstasy abuse Denition Clinical features Ecstasy is a semi-synthetic derivative of amphetamine Physical effects of an amphetamine-intoxicated state in- with hallucinogenic properties. A history should be taken of re- usually comes in tablets or capsules, which may have centandpreviousrecreationaldruguse,includingmeth- logos or pictures on them. Occasionally it is and social history should be taken, as well as a medical found in a powder form that is smoked or snorted.

Service delivery Organization of services for delivery of neurological care has an important bearing on their effec- tiveness 20mg vasodilan visa. Because of their different social discount 20mg vasodilan amex, cultural buy vasodilan 20 mg otc, political and economic contexts, countries have various forms of service organization and delivery strategies. The differing availability of nancial and human resources also affects the organization of services. Certain key issues, however, need to be taken into account for structuring services to provide effective care to people with neurologi- cal disorders. Depending upon the health system in the country, there is a variable mix of private and public provision of neurological care. The three traditional levels of service delivery are primary, secondary and tertiary care. Primary care includes treatment and preventive and promotional interventions conducted by primary care professionals. These vary from a general practitioner, nurse, other health-care staff and non- medical staff to primary care workers based in rural areas. Primary care represents the point of entry for most people seeking care and is the logical setting where neurological disorders should begin to be addressed. Users of primary care are more likely to seek early help because of the wide availability of facilities, their easy accessibility, cultural acceptability and reduced cost, thus leading to early detection of neurological disorders and better clinical outcome. Integration of neurological services into the primary care system needs to be a signicant policy objective in both developing and developed countries. Providing neurological care through primary care requires signicant investment in training primary care professionals to detect and treat neurological disorders. Such training should meet the specic practical training needs of different groups of primary care professionals such as doctors, nurses and community health workers. Preferably, ongoing training is needed to provide subsequent support for reinforcing new skills. In many countries, this has not been possible and thus suboptimal care is provided (18). Primary care centres are limited in their ability to adequately diagnose and treat certain neuro- logical disorders. For the management of severe cases and patients requiring access to diagnostic and technological expertise, a secondary level of care is necessary. A number of neurological services may be offered in district or regional hospitals that form part of the general health system. Common facilities include inpatient beds in general medicine, specialist beds, emergency depart- ments and outpatient clinics. These services require adequate numbers of general as well as specialist profes- sionals who can also provide supervision and training in neurology to primary care staff. In some countries, there are also other public or private facilities offering various types of neurological services in inpatient wards and outpatient clinics. These facilities are not expected to deliver primary neurological care but act as second- ary and tertiary referral services. They also serve as facilities for clinical research, collection of epidemiological data, and the creation and distribution of health educational materials. Neurologi- cal specialist services require a large complement of trained specialist staff. Shortages of such staff are a serious problem in low income countries, as are the lack of nancial resources and infrastructure. Even within countries, signicant geographical disparities usually exist between regions. Little concerted ef- fort has been made to use primary care as the principal vehicle of delivery of neurological services. Some countries have good examples of intersectoral collaboration between nongovernmental organizations, academic institutions, public sector health services and informal community-based health services. At present, such activities are limited to small populations in urban areas; most rural populations have no access to such services. Even in developed countries, more emphasis is placed on providing specialist services than on approaches to integrate neurological services into primary care. Such disorders are better managed by services that adopt a continuing care approach, emphasizing the long-term nature of these neurological disorders and the need for ongoing care. The emphasis is on an inte- grated system of service delivery that attempts to respond to the needs of people with neurological disorders. Integrated and coordinated systems of service delivery need to be developed where services based in primary, secondary and tertiary care complement each other. In order to address the needs of persons with neurological disorders for health care and social support, a clear referral and linkage system needs to be in place. Management of the disability is aimed at cure or the individual s adjustment and behaviour change. The social model of disability sees the issue mainly as a socially created problem and a matter related to the full integration of individuals into society. According to the social model, disability is not an attribute of the individual, but rather a complex col- lection of conditions, many of which are created by the social environment: the approach to disability requires social action and is a responsibility of society. Rehabilitation is one of the key components of the primary health-care strategy, along with promotion, preven- tion and treatment. While promotion and prevention primarily target risk factors of disease and public health principles and neurological disorders 17 treatment targets ill-health, rehabilitation targets human functioning. As with other key health strategies, it is of varying importance and is relevant to all other medical specialities and health professions. Though rooted in the health sector, rehabilitation is also relevant to other sectors including education, labour and social affairs. For example, building of ramps and other facilities to improve access by disabled people falls beyond the purview of the health sector but is neverthe- less very important for the comprehensive management of a person with a disability. As a health-care strategy, rehabilitation aims to enable people who experience or are at risk of disability to achieve optimal functioning, autonomy and self-determination in the interaction with the larger physical, social and economic environment. It is based on the integrative model of human functioning, disability and health, which understands human functioning and disability both as an experience in relation to health conditions and impairments and as a result of interaction with the environment. Rehabilitation involves a coordinated and iterative problem-solving process along the continuum of care from the acute hospital to the community. It is based on four key approaches integrating a wide spectrum of interventions: 1) biomedical and engineering approaches; 2) approaches that build on and strengthen the resources of the person; 3) approaches that provide for a facilitating envi- ronment; and 4) approaches that provide guidance across services, sectors and payers. Rehabilitation services are like a bridge between isolation and exclusion often the rst step towards achieving fundamental rights. Health is a fundamental right, and rehabilitation is a powerful tool to provide personal empowerment. Rehabilitation strategy Because of the complexity of rehabilitation based on the above-mentioned integrative model, re- habilitation services and interventions applying the rehabilitation strategy need to be coordinated along the continuum of care across specialized and non-specialized services, sectors and payers. The rst refers to the guidance along the continuum of care and the second to the provision of a specic service. The assignment step refers to the assignment to a service and an intervention programme. The Evaluation Assignment evaluation step refers to service and the achievement of the intervention goal. The assignment step refers to the as- signment of health professionals and interventions to the intervention targets. The intervention step refers to the specication of the intervention techniques, the denition of indicator measures to follow the progress of the intervention, and the denition of target values to be achieved within a 18 Neurological disorders: public health challenges predetermined time period. It also includes the decision regarding the need for another intervention cycle based on a reassessment. Rehabilitation of neurological disorders Rehabilitation should start as soon as possible after the diagnosis of a neurological disorder or condition and should focus on the community rehabilitation perspective. The type and provision of services is largely dependent on the individual health-care system. Therefore no generally agreed principles currently exist regarding the provision of rehabilitation and related services. Rehabilitation is often exclusively associated with well-established and coordinated multi- disciplinary efforts by specialized rehabilitation services. While availability and access to these specialized inpatient or outpatient services are at the core of successful rehabilitation, a need also exists for rehabilitation service provision, from the acute settings through the district hospital and the community, often by health professionals not specialized in rehabilitation but working closely with the rehabilitation professionals. It is important to recognize that rehabilitation efforts in the community can be delivered by professionals outside the health sector, ideally in collaboration with rehabilitation professionals.

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This reduces the portal pressure gradient purchase vasodilan 20 mg online, the azygos blood Investigations ow and variceal pressure proven vasodilan 20mg, which reduces the likeli- These are aimed at discovering the cause of the por- hood of variceal bleeding generic vasodilan 20 mg otc. The in patients with signicant varices who are unable to severity of liver disease may be graded A C by means tolerate -blockers. Ultrasound of the liver and spleen is performed traindicated isosorbide mononitrate has been shown to assess size and appearance. Liver biopsy may be re- ascites (see page 188), bleeding varices (see page 199) quired. There are various r Portal hypertension is signicantly improved by ab- techniques, for example connecting the: stinence from alcohol in cases of alcohol-induced dis- 1 Portal vein to inferior vena cava. A transjugu- lar approach is used to pass a guidewire through the Management hepatic vein piercing the wall to the intrahepatic Resuscitation: branches of the portal vein, a stent is then passed r At least two large bore peripheral cannulae should over the guidewire. Packed red blood cells the same as for other shunts, but operative morbid- should be given as soon as possible, O ve blood may ity and mortality is improved. Oesophageal varices are dilated vessels at the junction r Elective intubation may be required in severe uncon- between the oesophagus and the stomach and occur in trolled variceal bleeding, severe encephalopathy, in portal hypertension. They may rupture and cause an patients unable to maintain oxygen saturation above acute and severe upper gastrointestinal bleed. Incidence/prevalence Further management: 30 50% of patients with portal hypertension will bleed r An upper gastrointestinal endoscopy should be per- from varices. Aetiology If banding is not possible, the varices should be in- Varicesresult from portal hypertension, the most com- jected with a sclerosant. All patients should receive a course of features of portal hypertension may be seen. Secondary prophylaxis following a variceal bleed in cir- Investigations rhosis: The diagnostic investigation is endoscopy, which may r Following control of active bleeding the varices also be therapeutic during an acute bleed. The varices should be eradicated using endoscopic band liga- must be conrmed to be the source of bleeding, because tion (sclerotherapy if banding unavailable). Following up to 20% of patients with varices also have peptic ulcers successful eradication of the varices repeated upper and/orgastritis. Thevaricesareseenastortuouscolumns gastrointestinal endoscopy is required to screen for in the lower third of the oesophagus. If they are used alone, it is recommended that childhood being common and adults universally im- hepatic venous pressure gradient is measured to con- mune. It is infec- Prognosis tious from 2 weeks before clinical symptoms until a few There is a 50% mortality in patients presenting for the days after the onset of jaundice. Prognosis atocyte necrosis is unclear; the virus is not cytopathic in is worse in patients with high Child Pugh grading (see tissue culture. Without treatment to prevent recurrence two thirds of patients re-bleed whilst in hospital and 90% Clinical features re-bleed within a year. A history of contact/travel abroad may be found, al- Viral hepatitis thoughmanyasymptomaticcasesoccur. Patientspresent with a prodromal phase (malaise, anorexia, nausea, aver- Denition sion to fatty foods and cigarettes) lasting about a week. The term viral hepatitis usually refers specically to the Jaundice appears after the prodromal phase and lasts diseases of the liver caused by the hepatotropic viruses, about 2 weeks. Other viruses such as the Epstein Barr virus and cy- Complications tomegalovirus may cause acute hepatitis. Very occasionally fulminant hepatic The hepatotrophic viruses can cause a range of failure occurs. Prognosis Post exposure prophylaxis has reduced this transmis- Case fatality rate less than 1 per 1000. Nosocomial infections may Geography occur due to needle stick injuries or contaminated in- More common in the developing world with highest lev- struments. The virus is not cytopathic, the liver damage is immune- r Vertical transmission is the most common route in mediated by the cytotoxic T lymphocytes response to high endemic areas. It occurs at or after birth and is viral antigen expressed on the surface of liver cells dur- mostcommoninbabiesofe-antigenpositivemothers. The complete virion or Dane particle is spheri- Hepatitis B is diagnosed and followed using serological cal, 42 nm in diameter (see Fig. It has also sAg made in yeast cells) is given to at risk individuals been noted that patients who present with jaundice including health-care workers and in areas of high during the acute infection rarely convert to a carrier prevalence. The likelihood of these conditions depends on also used as post-exposure prophylaxis for needlestick the age of the patient: injuries. Less than 10% of patients have an acute u-like illness with jaundice, the remainder are asymptomatic at the time of infection. Followinginfectionmostpatients developchronichepatitisC,whichpredisposestocirrho- Denition sis and hepatocellular carcinoma. Chronic hepatitis C is Hepatitis C is one of the hepatotrophic viruses, which oftenasymptomaticbutmaycausefatigue,myalgia,nau- predominantly causes a chronic hepatitis. Symptoms and signs of chronic liver disease occur years after initial Incidence/prevalence infection. Five per cent carrier rate in Far East; 1 2% in Mediter- Fatty change is seen in the hepatocytes, with little active ranean. Quantication of the viral load may be of ing to an increased risk of rapidly developing cirrhosis use in tailoring treatment. Com- bination therapy with pegylated interferon and rib- Management avirin is recommended for the treatment of people aged There is no vaccine for hepatitis D; however, vaccination 18yearsandoverwithmoderatetoseverechronichepati- against hepatitis B will prevent hepatitis D infection. In- tis C (histological evidence of signicant scarring and/or terferon can be used to treat patients with chronic signicant necrotic inammation). There is no Recovery from hepatitis B leads to clearance of hepatitis available vaccine. Any patient at risk of Geography hepatitis B is at risk of hepatitis D, particularly intra- Cause of water-borne epidemics in the Indian subconti- venous drug users. Hepatitis r WhenhepatitisBandDsimultaneouslyinfectthehost E, like hepatitis A, is transmitted via the faecal oral route aco-infectionoccurs. It causes a able severity, but is more likely to cause fulminant self-limiting acute hepatitis, with no chronic or carrier hepatic failure. Liver cell membranes may become immunogenic resulting in a lymphocyte-mediated cytotoxic response against Other liver diseases the liver cells. Alcohol-induced liver disease Clinical features Denition Differing patterns are seen: r Acute alcoholic hepatitis resembles acute viral hepati- Liver disease caused by alcohol range from a fatty liver to hepatitis and cirrhosis. Characteristically Mallory s bodies composed of cytoskeletal fragments Pathophysiology andubiquitin,aheatshockproteinthatlabelsproteins r Any alcohol ingestion causes changes in liver cells, as being damaged and targets them for breakdown. Alcoholic It appears as bright eosinophilic amorphous globules hepatitis refers to alcohol-induced liver injury visible within hepatocytes. This form of change is seen in those ingesting more than 80 g alcohol per day (6 units, 1 bottle of wine or 3 pints of beer). Steatosis r Cirrhosis: Repeated damage has led to brosis, with damage to the normal architecture upon which func- Steatohepatitis tion is dependent. Up to 10% of patients with cirrhosis, secondary to Cirrhosis alcohol use, develop hepatocellular carcinoma. Ultra- sound may show signicant cholestasis and be mistaken liver injury, occurring in patients with little or no his- for extra-hepatic obstructive jaundice. In late stages patients ranges from fat accumulation in hepatocytes (hepatic maybeconsideredforlivertransplantiftheyhaveproved steatosis) to hepatic steatosis with hepatic inamma- abstinence. The pathogenesis of nonalcoholic fatty liver disease is r Fatty liver is reversible, with complete recovery. However, if they abstain from drinking 90% acid entering the liver, decreased free fatty acid leav- have a full recovery. Insulin resistance appears to be important in the acute episode of hepatitis have the poorest prognosis development of hepatic steatosis and steatohepatitis. Hepatomegaly is a frequent nd- atotoxicity may be subdivided into predictable (dose- ing. Most cases are found on incidental abnormal liver dependent) and idiosyncratic, although more than one function tests.

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You don t realize it purchase vasodilan 20mg free shipping, but your own (c) The G protein passes the hormone s message to the cell by switching on body sent this substance a hormone called a cell enzyme (purple) that triggers epinephrine to protect you buy vasodilan 20 mg amex, telling you to a response vasodilan 20 mg free shipping. Your body reacts, whipping up the familiar, spine-tingling, ght-or-ight response that gears you to respond quickly to potentially threatening situations such as this one. Getting into a cell is a challenge, a strictly guarded process kept in control by a protective gate called the plasma membrane. Figuring out how molecular triggers like epinephrine communicate important messages to the inner parts of cells earned two scientists the Nobel Prize in physiology or medicine in 1994. Getting a cellular message across the membrane is called signal transduction, and it the world have focused on these signaling occurs in three steps. Research on G proteins and on all epinephrine) encounters the outside of a cell aspects of cell signaling has prospered, and as Got It? In the fall of 2000, Gilman embarked on transducer, or switch molecule, passes the a groundbreaking effort to begin to untangle What is a liposome? The group has a big dream: to understand One of the Nobel Prize winners, pharma everything there is to know about signaling cologist Alfred G. According to Gilman, Alliance Describe how Texas Southwestern Medical Center at Dallas, researchers focus lots of attention on G G proteins work. As with any switch, G proteins must be revolution in biomedical turned on only when needed, then shut off. Some illnesses, including fatal diseases like cholera, occur when a G protein is errantly left on. In the case of cholera, the poisonous weaponry of the cholera bacterium freezes in place one particular type of G protein that controls water balance. In the few decades since Gilman and the other Nobel Prize winner, the late National Institutes of Health scientist Martin Rodbell, made their fundamental discovery about G protein switches, pharmacologists all over 48 National Institute of General Medical Sciences Medicines for the Future he advances in drug development and T delivery described in this booklet reect scientists growing knowledge about human biology. This knowledge has allowed them to develop medicines targeted to specic molecules or cells. In the future, doctors may be able to treat or prevent diseases with drugs that actually repair cells or protect them from attack. No one knows which of the techniques now being developed will yield valuable future medicines, but it is clear that thanks to pharmacology research, tomorrow s doctors will have an unprecedented array of weapons to ght disease. Medicines By Design I Medicines for the Future 49 Careers in Pharmacology Wanna be a pharmacologist? These cology as a career, here are some of the places you scientists often work with patients and spend a might nd yourself working: lot of time trying to understand issues relating College or University. Most basic biomedical to drug dosage, including side effects and research across the country is done by scientists drug interactions. Pharmacologists and cologists perform research to determine how toxicologists play key roles in formulating drug medicines interact with living systems. Agonist | A molecule that triggers a cellular Bioinformatics | A eld of research that relies response by interacting with a receptor. Analgesic | A medicine s ability to relieve pain, or a drug that alleviates pain; the term comes from Biotechnology | The industrial use of living the Greek word algos, which means pain. Antagonist | A molecule that prevents the action of other molecules, often by competing Biotransformation | The conversion of a for a cellular receptor; opposite of agonist. Antibiotic | A substance that can kill or inhibit the growth of certain microorganisms. Blood-brain barrier | A blockade consisting of cells and small blood vessels that limits the Antibody | A protein of the immune system, movement of substances from the bloodstream produced in response to an antigen (a foreign, into the brain. Carcinogen | Any substance that, when exposed Anti-inammatory | A drug s ability to to living tissue, may cause cancer. Cell | The basic subunit of any living organism; the simplest unit that can exist as an independent Antipyretic | Fever-reducing; the term comes living system. Central nervous system | The brain and Arachidonic acid | A molecule that synthesizes spinal cord. Bacterium | One-celled organism without Chemical genetics | A research approach a nucleus that reproduces by cell division; can resembling genetics in which scientists custom- infect humans, plants, or animals. Medicines By Design I Glossary 51 Cholesterol | A lipid unique to animal cells that Dose-response curve | A graph drawn to is used in the construction of cell membranes and show the relationship between the dose of a drug as a building block for some hormones. Chromosome | A structure in the cell nucleus Enzyme | A molecule (usually a protein) that that contains hereditary material (genes); humans speeds up, or catalyzes, a chemical reaction with have 23 pairs of chromosomes in each body cell, out being permanently altered or consumed. G protein | One of a group of switch proteins Combinatorial genetics | A research process involved in a signaling system that passes incoming in which scientists remove the genetic instructions messages across cell membranes and within cells. Genomics | The study of all of an organism s Cytochrome P450 | A family of enzymes genetic material. Neurotransmitter | A chemical messenger that allows neurons (nerve cells) to communicate with Lipid | A fatty, waxy, or oily molecule that each other and with other cells. Nucleus | The membrane-bound structure within a cell that contains most of the cell s Liposome | Oily, microscopic capsules designed genetic material. Organelle | A specialized, membrane-bound structure that has a dened cellular function; Membrane | A thin covering surrounding a cell for example, the nucleus. Pharmacodynamics | The study of how drugs Metabolism | All enzyme-catalyzed reactions act at target sites of action in the body. Pharmacokinetics | The study of how the Metabolite | A chemical intermediate in body absorbs, distributes, breaks down, and metabolic reactions; a product of metabolism. Sepsis | A clinical condition in which infectious Prostaglandins | Any of a class of hormone- agents (bacteria, fungi) or products of infection like, fat-soluble, regulatory molecules made from (bacterial toxins) enter the blood and profoundly fatty acids such as arachidonic acid; prostaglandins affect body systems. Steroid | A type of molecule that has a multiple ring structure, with the rings sharing molecules Receptor | A specialized molecule that receives of carbon. Toxicology | The study of how poisonous substances interact with living organisms. X-ray crystallography | A technique used to determine the detailed, three-dimensional structure of molecules based on the scattering of X rays through a crystal of the molecule. It aims to advance access to medicine in low- and middle-income countries by stimulating and guiding the pharmaceutical industry to play a greater role in improving access to medicine. For ten years, the Foundation has been building consensus on the role for the pharmaceutical industry in improving access to medicine and vaccines. It published its frst benchmark of industry activity in this area in 2008, in the frst Access to Medicine Index, now in its ffth iteration. In 2017, the Foundation will publish the frst Access to Vaccines Index, funded by the Dutch National Postcode Lottery. The Foundation is1 grateful for their time and expertise, and would like to thank them for providing valuable insights throughout the development of the 2016 Index. Iyer Warren Kaplan Danny Edwards Jillian Kohler Anna Massey Niranjan Konduri Emma Ross Prashant Yadav 1 This acknowledgement does not infer that the individuals and institutions mentioned above endorse the Access to Medicine Index analyses or results. Decisions regarding the inclusion of feedback were made by the Access to Medicine Foundation. We continue to make progress toward pany is best, overall, at mobilising to reach the major public health goals: polio is close to being poor. Importantly, the Index is also a book of eradicated, as is guinea worm; more than 45% of potential solutions. Which means important vaccines for malaria and dengue fever there is plenty companies can achieve without are being implemented. But at the same time, our going back to the drawing board by expanding models for providing healthcare are leaving people good company practices to more products, coun- behind. The challenge is the medicine they need, most of whom live hand to ensure this knowledge benefts those with the to mouth. Pharmaceutical companies, as the innovators There is a social contract between pharmaceutical and producers of life-saving medicine, act early companies and the people who need their prod- in the value chain. Our research suggests that many people in the impact on access can be huge with signif- the industry are committed to fulflling this con- cant savings for healthcare budgets, and of course, tract. But progress is slower than many of us in terms of improving human life and wellbeing. At the Access to Medicine Foundation, we have been tracking the world s largest research-based pharmaceutical companies for ten years now, look- ing at how they bring medicine within reach of people in low- and middle-income countries. Iyer held their top spots over the years by asking the Executive Director right questions, reviewing their paths and challeng- Access to Medicine Foundation ing themselves to keep improving, against a chang- ing backdrop of stakeholder expectations and competing priorities. For and diagnostics more accessible in low- and mid- the 2016 Index, the weight of the performance pillar was increased to dle-income countries.

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