Example of cancer The fight against cancer is one of the greatest chal- prevention: early intesti- lenges facing modern medicine generic 200mg nizoral. According to an nal cancer detection estimate by the International Agency for Research on Cancer 200 mg nizoral with visa,part of the World HealthOrganization 200mg nizoral otc, over 1. Al- though screening programs are in place in most industrialised countries, people do not avail themselves of them to the neces- sary extent. Yet up to 90 percent of all fatal cases of intestinal cancer, says the German Felix Burda Foundation, could be pre- vented in the space of ten years by instituting a program of reg- ular endoscopic checks. The major misgiving is that although intestinal endoscopy is effective, it is also unpleasant and, being invasive,not without its risks. To date there is no screening meth- od that is able to identify high-risk patients simply and safely. The early detection of intestinal cancer still relies for the most part on the results of an occult blood test, which detects hidden (occult) blood in the stool. Depending on the study con- cerned, however, this test fails to identify up to half of positive cases. In addition, one in five patients proves to be healthy after subsequent endoscopy. Given the large number of patients with intestinal cancer, medical researchers are therefore working in- tensively on alternatives to the occult blood test. Suitable screen- ing tests based on protein biomarkers could become available within just a few years. It is now known that over 100 different disorders some degenerative, some inflammatory are sub- sumed under the umbrella term rheumatism. That alone shows to what extent doctors have to depend on modern diag- nostic testing, especially since the right treatment often depends on the actual cause of the pain symptoms. Patients usually have to con- tend with severe pain and considerable impairment of move- ment. The causes of the disease are still unknown, but it appears certain that genetic predisposition, previous diseases and prob- ably also lifestyle are all factors. The best marker combinations searchers look for an optimum combination of markers therefore do not necessarily contain the best individual which together describe as many disease factors as markers. Treatment begins with diagnosis 63 The fact that diverse factors contribute to the development and progression of rheumatoid arthritis is also reflected in the search for suitable biomarkers. Not a single protein is known which can be used to diagnose a disease with absolute reliability a fact that has become increasingly clear in recent years. All the molecular candidates so far tested either do not occur in all pa- tients or occur also in other inflammatory diseases. Biologists have therefore teamed up with mathematicians to develop a model to help in the search for an optimum combination of multiple markers (see box, p. Prospects: diagnostics Biotechnology has made key contributions not and treatment only to therapy but also to diagnostics. Armed evolve together with molecular diagnostic tests at the gene and protein levels, doctors can already search much more effectively for the causes of a patients illness and adapt the treatment accordingly, and not just in the early phases. Diagnostics, treatment and treatment monitoring are evolving together, and research in this area is being inten- sively pursued. The reasons for this are varied, ranging from differences in the immune re- sponse between individuals to significant variations in the ge- nome of the virus. Modern molecular diagnostic methods are there- fore needed not only at the start of the therapeutic process but throughout treatment. The more specifically a drug is directed against the cause of a disease, the more important it is for doctors to identify the cause accurately. For pharmaceutical companies that are active in both areas, this development has opened up a unique opportunity: Now diagnosis and therapy can be con- sidered together to help patients individually. Progress in the treatment of complex diseases in particular shows that molecular diagnostics holds new promises for med- Treatment begins with diagnosis 65 ical science. In this area, biotech drugs and diagnostic agents are not competing with conventional therapies but in many cases permit specific therapy for the first time where before the aim of treatment was merely to relieve unspecific symptoms a real blessing for patients. Spektrum Akademischer Verlag, Heidelberg, 6th edition 2003 Presentations at a media conference: The Roche Group one of the worlds leaders in bio- tech. It works at the limit of science bringing the highest levels of human knowledge and skill to save lives and improve health. It touches our lives at times of basic human need, when care and compassion are what matters most. Across the world, we are witnessing a healthcare revolution driven by scientifc and technological advances in genomics, informatics and bio nanotechnology to name but a few which are enhancing our ability to more precisely diagnose illnesses and target treatment of disease. Britain has the opportunity to be at the forefront of this new era of medicine, delivering 21st century healthcare. As the single biggest integrated healthcare system, combined with our world leading science base and global reputation for innovation, we have the opportunity and capability to transform the way we deliver healthcare to secure benefts for our patients, our society and our economy. We will create a healthcare system focused on improving health, not just treating illness, able to accurately predict disease and tailor treatments, with shared decision making at its heart. It will only be possible to achieve this if we continue to work with people across the entire health and care system. These are just a few of the breakthroughs that have been made by British clinicians and scientists for the beneft of patients. Whole Genome Sequencing provides a huge step forward in the diagnostic information available. When analysed with other information about our health and the way people live their lives, it provides much richer information about the complex interactions within a person, and between them and their environment. It offers a greater understanding of the underlying causes, triggers and drivers of disease as well as the likely success or failure of drugs and interventions. Clinicians have been working to personalise care, tailored to peoples individual health needs, throughout the history of medicine. But never before has it been possible to predict how each of our bodies will respond to specifc interventions, or identify which of us is at risk of developing an illness. New possibilities are now emerging as we bring together novel approaches, such as whole genome sequencing, data and informatics, and wearable technology. It is the interconnections between these innovations that make it possible to move to truly personalised care. Technological and scientifc advances are already here and will continue to develop and improve medical practice; change is inevitable. Personalised medicine is important not only for the 1 in 17 people who have a rare disease, or for those living with cancer, but also for the many others who have or are at risk of developing other common diseases. Personalised medicine: Personalised medicine: a move away from a one size fts all approach to the treatment and care of patients with a particular condition, to one which uses new approaches to better manage patients health and target therapies to achieve the best outcomes in the management of a patients disease or predisposition to disease. Our health is determined by our inherited genetic differences combined with our lifestyles and other environmental factors. By combining and analysing information about our genome, with clinical and diagnostic information and then comparing that with data from others, patterns can be identifed. In the early 20th century we saw the frst connection between genetic inheritance and susceptibility to disease. It recognises that complex diseases should no longer be considered as a single entity. One disease may have many different forms, or subtypes, resulting from the complex interaction of our biological make-up and the diverse pathological and physiological processes in our bodies. These will not only vary between patients who have the same disease but also within an individual patient as they get older and their body changes. As we integrate and analyse genomic and other data, we can fnd common factors and causes of variation, resulting in the discovery of new pathways of disease, changing how diseases are thought of and treated. All patients with the same condition receive the same frst line treatment even though it may be only 30 to 60% effective. This can be used for a wide range of cancers such as melanoma (skin cancer), leukaemia, colon, brain and breast cancers. It may also mean that patients with different types of cancer may, on the basis of the genomic diagnosis, receive similar treatments. It will create the opportunity to fnd new purposes for, and better use of, existing medicines including generics and biosimilars. It will also help us to use other non-pharmacological treatments, and even, in some patients, simple dietary or lifestyle interventions.

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The murmur is order 200mg nizoral with visa, however order nizoral 200mg amex, causes a loud pulmonary component to the second quieter as there is less turbulent ow nizoral 200mg generic. Initially increased pulmonary blood ow does not cause arise in pressures within the pulmonary circulation Investigations due to the vascular compliance. If, however, there is a r Chest X-ray: Abnormalities are only seen with large defects when cardiomegaly and prominent pul- monary vasculature may be seen. Measurement of the size of the defect and the blood ow allows prediction of the outcome. The shunting of blood from left to right increases the volume of blood passing through the right side of the Incidence heart leading to right ventricular volume overload and 10% of congenital heart defects. Prolongedhigh volume blood ow through lungs can occasionally lead Sex to pulmonary hypertension due to changes in the pul- F > M monary vasculature similar to ventricular septal defects (see page 84). Aetiology Defects in the ostium primum occur in patients with Clinical features Down syndrome often as part of an atrioventricular sep- Atrialseptaldefectsareoftenasymptomaticinchildhood tal defect. On examination Pathophysiology there is a xed widely split second heart sound due to the The atrial septum is embryologically made up of two high volumes owing through the right side of the heart parts: the ostium primum and the ostium secundum, and the equalisation of right and left pressures during which forms a ap over the defect in the ostium pri- respiration. A diastolic murmur may through the fossa ovalis and hence shunts blood away also occur due to ow across the tricuspid valve. In normal individuals Rarely patients may present with paradoxical emboli at birth the vasculature within the lungs dilate at birth (where thrombus from a deep vein thrombosis crosses and hence the right heart pressures fall. Once the left the atrial septal defect and causes stroke or peripheral atrial pressure exceeds the right, the ostium secundum arterial occlusion). Eighty per cent of cases occur in association with a Management bicuspid aortic valve. The defect may be closed using an umbrella-shaped Clinical features occluder placed at cardiac catheterisation. Traditional Proximal hypertension may cause headache and dizzi- open surgical repair requires cardiopulmonary bypass ness, distal hypotension results in weakness and poor pe- and may use a pericardial or Dacron patch to close the ripheral circulation. Surgicalinterventioninostiumprimumdefectsis are weak or absent and there is radiofemoral delay. Four- morecomplexduetoinvolvementoftheatrioventricular limb blood pressure measurement will demonstrate the valves. Coarctation of the aorta Investigations Denition r Chest X-ray may show left ventricular hypertrophy Localised narrowing of the descending aorta close to the and rib notching due to dilated intercostal arteries site of the ductus arteriosus. Pathophysiology Coarctation of the aorta tends to occur at the site of the ductus/ligamentus arteriosus, which is usually opposite Management the origin of the left subclavian artery (see Fig. The Surgical treatment is used in the majority of cases and left ventricle hypertrophies to overcome the obstruction is an emergency in coarctation complicated by a patent and cardiac failure may occur. The chest is opened by left lateral tho- develops with hypotension in the lower body. Prognosis Without treatment 50% of patients die within the rst year of life from cardiac failure and complications of hypertension such as intracranial bleeds. This reduces the right to left intracardiac shunt and provides some symptomatic relief. On auscultation there is initially a long systolic murmur across the pulmonary valve, which shortens as cyanosis develops. Spasm of the infundibular muscle in the right ven- tricular outow tract results in further compromises the right cardiac outow causing worsening cyanosis and often loss of consciousness. Investigations ChestX-rayoftenshowsaheartofnormalsizebuttheleft heartborderisconcave(bootshape)duetothesmallpul- r Right ventricular outow obstruction (pulmonary monary trunk. Aetiology Embryological hypoplasia of the conus, which gives rise tothemembranousventricularseptum. OccursinDown Management r Symptomatic infants may require a BlalockTaussig syndrome and as part of fetal alcohol syndrome. This provides a left to The pulmonary stenosis results in high right ventricular rightshunt replacing the duct as it closes. The degree of pulmonary stenosis isvariable(rangingfrommildtoatresia),thustheclinical picture ranges in severity. The right ventricular outow Cardiovascular oncology tract obstruction is often progressive. Clinical features Atrial myxoma In rare severe cases cyanosis develops within days as the Denition pulmonary circulation is dependent on a patent ductus An atrial myxoma is a benign primary tumour of the arteriosus. More commonly presentation is later with heart most commonly arising in the left atrium. Initially it may only be present on exertion, but as the right ventricu- lar outow obstruction is progressive cyanosis becomes Incidence evident at rest, and the characteristic squatting position Primarytumoursoftheheartarerare,butatrialmyxoma may be adopted. Denition Tumour arising from chemoreceptors at the bifurcation Pathophysiology of the carotid artery. The tumour is usually located on a pedicle arising from the atrial septum, and can grow up to about 8 cm Incidence across. The pedicle allows the tumour to move within Rare the atrium resulting in various symptom complexes. If the tumour obstructs the mitral valve a picture similar to Aetiology mitral stenosis will occur. If the tumour passes through More common in people living at high altitude; it is the mitral valve, mitral regurgitation will occur. The tumour may also give rise to thrombosis due to altered Pathophysiology ow patterns and resultant systemic embolisation. Local Carotid body tumours are hormonally inactive chemod- invasion and distant metastasis do not occur. The tu- by features of mitral stenosis with variable cardiac mur- mour tends to grow upwards towards the skull base. Thromboembolism may result from the abnor- Patients present with a pulsatile swelling in the upper mal ow pattern through the atrium. It occurs in 40% neck at the medial border of the sternocleidomastoid and is a common presenting feature. Classically on palpation the lump is mobile from side to side but not up and down, and there may be an associated overlying carotid bruit. Echocardiography demonstrates common metastatic lymph node from a head and neck the mass lesion within the atrium. Macroscopy The tumour is usually a polypoid mass on a stalk, its sur- Microscopy face covered with thrombus. It is composed of is made up of connective tissue, with a variety of cell chief cells with clear cytoplasm and a round nucleus en- typessurrounded by extracellular matrix. Investigations Management Angiography shows a splaying of the carotid bifurcation The tumour is surgically removed under cardiopul- (lyre sign). Management Prognosis Surgical excision may be performed especially in young Five per cent local recurrence within 5 years. Inelderlypatientssurgicalremovalmay up with regular echocardiography is therefore indicated not be necessary. Patients may complain of breathlessness, dif- culty in catching their breath, a feeling of suffocation, Cough and sputum or tightness in the chest. Dyspnoea should be graded by the exertional capability of the patient and the impact Acough is one of the most common presentations of on their lifestyle. In general dyspnoea arises from either the respira- The most common patterns are shown in Table 3. It is usu- thopnoea and paroxysmal nocturnal dyspnoea suggests ally streaky, rusty coloured and mixed with sputum. It a cardiovascular cause, patients with lung disease may should be distinguished from haematemesis (vomiting experience orthopnoea due to abdominal contents re- of blood) which may appear bright red or like coffee stricting the movement of the diaphragm. For diagnosis, respiratory dyspnoea is best considered 1 The most common cause is acute infection, particu- according to the speed of onset and further differenti- larly with underlying chronic obstructive airways dis- ated by a detailed history and clinical examination (see ease. Wheeze and stridor 3 Pulmonary oedema in cardiac failure causes pink, frothy sputum and pulmonary infarction such as pul- Wheeze and stridor are respiratory sounds caused by air- monary embolism may cause haemoptysis. Massive haemoptysis may be caused by bronchiectasis, Awheeze is described according to where it is best bronchial carcinoma or tuberculosis. Recent Smoker, weight Haemoptysis Carcinoma until proved (weeks) loss, occasionally otherwise (often dull chest pain associated pneumonia) specic size of airway usually one bronchus) or poly- creased airway pressure opens the valve, so expiratory phonic (widespread airway limitation). Chest pain can arise from the cardiovascular system, the respiratory system, the oesophagus or the musculoskele- talsystem. Respiratorychestpainisusuallyverydifferent Signs fromischaemicchestpain,asitischaracteristicallysharp, and worse on inspiration.

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