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In both types sociated with paraesthesia purchase levitra extra dosage with american express erectile dysfunction treatment in singapore, numbness discount levitra extra dosage 40mg with mastercard erectile dysfunction red 7, cramps and motion buy generic levitra extra dosage 40mg erectile dysfunction treatment drugs, particularly of the head, can exacerbate the sen- tetany. With a chronic lesion such as a tumour, adaptive Hysteria may lead to non-epileptic attacks (pseudo- mechanisms reduce the sensation of dizziness over a pe- seizures) with or without feigned loss of consciousness. The patient will drop to the ground in front of witnesses, withoutsustaininganyinjuryandhaveafluctuatinglevel Labyrinth disorders (peripheral lesions) of consciousness for some time with unusual seizure- Peripherallesionstendtocauseaunidirectionalhorizon- like movements such as pelvic thrusting and forced eye tal nystagmus enhanced by asking the patient to look in closure. This is a diagnosis they tend to veer to one side, but walking is generally of exclusion and should be made with caution. Symptoms last days to weeks and can be is the sensation experienced when getting off a round- reduced with vestibular sedatives (useful only in the about and as part of alcohol intoxication. Positional testing with the Hallpike appears after a few seconds (latency), lasts less than manoeuvre is diagnostic. It tient’seyesarecloselyobservedfornystagmusforupto responds poorly to vestibular sedatives. This test can Central lesions provoke intense nausea, vertigo and even vomiting, Acentral lesion due to disease of the brainstem, cere- particularly in peripheral lesions. For ex- ample, risk factors for cerebrovascular disease, previous history of migraine, demyelination, or the presence of any other neurology. Altered sensation or weakness in the limbs Altered sensation in the limbs is often described as numbness, pins and needles (‘paraesthesiae’), cold or hot sensations. Painful or unpleasant sensations may be felt, such as shooting pains, burning pain, or increased sensitivity to touch (dysaesthesia). There may be a pre- cipitating cause, such as after trauma, or exacerbating features. The distribution of the sensory symptoms, and any associated pain (such as radicular pain, back pain or neck pain) can help to determine the cause. Depending on the level of the lesion the weak- r Can you get up from a chair easily? Signs to use your arms to help you get up from a include: chair or to climb up stairs? Glove and stocking sensory loss in all modalities (pain, temperature, vibration and joint position sense) occurs in peripheral neuropathies. They may have peripheral muscle weakness, which is also bilateral, symmetrical and distal. Bilateral symmetrical loss of all modalities of sensation occurs with a transverse section of the cord. These lesions are characteristically associated with lower motor neurone signs at the level of transection and upper motor neurone signs below the level. There are also ipsilateral upper motor neurone signs below the level of the lesion and lower motor neurone signs at the level of the lesion. Depending on the severity, the weakness may be de- r Anterior horn cell lesions occur as part of motor neu- scribed as a ‘plegia’ = total paralysis, or a ‘paresis’ = rone disease, polio or other viral infections, and can partial paralysis, but these terms are often used inter- affect multiple levels. Common causes are st- will cause weakness and wasting of the small muscles rokes(vascularocclusionorhaemorrhage)andtumours. Ask the patient to say r Decreased power in the distribution of the affected ‘British Constitution’ or ‘West Register Street’. Usually due to a cervical spinal cord lesion, occasionally bilateral cerebral lesions. Hemiplegia Weakness of one half of the body (sometimes including the face) caused be a contralateral cerebral hemisphere lesion, a brainstem lesion or ipsilateral spinal cord lesion (unusual). Paraplegia Affecting both lower limbs, and usually caused by a thoracic or lumbar spinal cord lesion e. Bilateral hemisphere (anterior cerebral artery) lesions can cause this but are rare. Monoplegia Contralateral hemisphere lesion in the motor cortex causing weakness of one limb, usually the arm. Test the abil- r Bradykinesia (slowness in movements) is noticeable ity of the patient to sit on the edge of the bed with their when doing alternate hand tapping movements, or arms crossed. Micro- r Gait:Wide-basedgait,withatendencytodrifttowards graphia (small, spidery handwriting). Even a mild cerebellar problem makes tiation of movement is impaired (hesitancy) with the this very difficult. A festinating gait is Causes include the following: r when the patient looks as though they are shuffling in Multiple sclerosis r order to keep up with their centre of gravity, and then Trauma r has difficulty in stopping and turning round. The three groups of tremor are distinguished by obser- r Metabolic: Alcohol (acute, reversible or chronic de- vation (see Table 7. If unilateral, the leg is swung out to the side to move it forwards (circumduction). If bilateral, the Extrapyramidal signs (Parkinsonism) pelvis has to alternately tilt and the gait often becomes r Appearance: Expressionless face. Thepatientcanstandontip-toe,butoften Resting tremor which is slow and classically pill- not on their heels. Even if mildly affected the patient is unable to strating whether seizure activity is suppressed by walk heel-toe in a straight line. In or encephalitis, as well as occurring in focal status Parkinson’s disease, this pattern tends to be asym- epilepticus. They are useful in the di- agnosis of muscle disease, diseases of the neuromuscular Electroencephalography junction, peripheral neuropathies and anterior horn cell disease. It is obtained by placing electrodes on the scalp, using a jelly to reduce electrical Electromyography resistance. A recording of at least half an hour is usually Aneedleelectrodeisplacedintomusclesandinsertional, needed, to maximise the chances of picking up tran- resting and voluntary electrical activity is studied, using sient abnormalities. Its main use is for the classification of epilepsy, but is r Peripheral neuropathies and anterior horn cell disease it may also be useful in the diagnosis of other brain dis- lead to a reduced number of motor units, which fire orders such as encephalitis. Surface electrodes or occasionally needles are used both r Suspected spinal cord compression. The knees are drawn up as far as possible and uation of brachial and lumbosacral plexus and nerve the neck flexed, to open up the spinous processes of the roots. The lumbar puncture needle is inserted in the midline Lumbar puncture with its stylet in place aiming slightly towards the um- bilicus. If the needle encounters firm resistance, it Indications should be withdrawn and another approach tried. When any of the following are suspected: Sometimes the patient will feel a pain radiating into r Infection (meningitis, encephalitis, fungal infections the leg or back – this is due to the needle touching a or neurosyphilis). A simultaneous blood diagnosis of idiopathic (benign) intracranial hyperten- sample for glucose should be sent. Chapter 7: Cerebrovascular disease 295 Bleeding, infection, arachnoiditis, exacerbation of spinal various processing which may be performed on the data. Thereisadiffer- in the case of sick patients, is relatively unaccessible – ence in healthy tissue and infarcted, infected or oedema- although some units have facilities for ventilation in the tous tissue. Cerebrovascular disease Faster scans are now possible – particularly helpful for patients unwilling or unable to lie flat for long, although in some cases general anaesthetic may be necessary for Stroke unco-operative patients.

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Increased osteoclast activity Increased excretion resorbing bone of phosphate Raised Serum Calcium Figure 11 buy generic levitra extra dosage on line erectile dysfunction at age of 20. The parathyroids Complications Fractures order discount levitra extra dosage online erectile dysfunction protocol scam or real, complications of urinary stones purchase levitra extra dosage no prescription erectile dysfunction latest medicine, seizures, are exposed by a transverse neck incision. Dehydration of the thyroid is mobilised and the parathyroids iden- occurs secondary to hypercalcaemia, which can cause a tified. Bisphosphonates may also be used, although periosteal erosions, ‘brown tumours’ which are areas they can take some time to act. For renal patients alfacalcidol and calcitriol are suitable forms of Secondary hyperparathyroidism vitamin D, as they do not require hydroxylation by the Definition kidney to become active. Tertiary hyperparathyroidism Incidence/prevalence Definition Increasing because of survival of renal patients on dial- Development of parathyroid hyperplasia or adenomas ysis. Aetiology Common causes of chronic hypocalcaemia are chronic Aetiology renal failure and vitamin D deficiency. Any cause of chronic secondary hyperparathyroidism, in particular chronic renal failure. Clinical features This condition is usually asymptomatic and chronic, Complications although hyperparathyroidism may cause vague bone Acuteseverehypercalcaemiamaycauseseizures,abdom- pains. Complications Tertiary hyperparathyroidism (hypercalcaemia due to Investigations autonomous parathyroids). Chapter 11: Disorders of the parathyroids 449 Management Clinical features Total parathyroidectomy possibly with autotransplanta- Hypocalcaemiaandalkalosiscauseincreasedneuromus- tion of parathyroid tissue equivalent to a normal gland cularexcitability:paraesthesiasofthefingertipsandtoes, into the arm, where it can be readily accessed for further tetany (spasms of muscles of extremities and face) treatment. Aetiology Most commonly occurs following surgery with removal of abnormal parathyroid glands or removal of neck ma- Management lignancies. Serum and urinary calcium must Idiopathic hypoparathyroidism: be measured, as hypercalcaemia and hypercalciuria can r Genetic abnormalities are usually autosomal recessive occur. Thiazide diuretics which increase renal tubular tibodies specific for parathyroid and adrenal tissue. Prognosis r Late onset idiopathic hypoparathyroidism occurs Lifelong treatment and follow-up. Other features are the same 450 Chapter 11: Endocrine system as those of hypoparathyroidism. Definition Multiple endocrine neoplasia is a group of inherited syn- Incidence/prevalence dromes characterised by multiple tumours of endocrine Rare in infancy but rises to 2 per 1000 at age 16. Most present aged less than 20 years (peaks at suggested that susceptible individuals inherit a gene 3–4 years and around puberty). HighinNorthernEu- r Tumours occur within the parathyroids in 90% (re- rope, low in Japan. Type Chroniccomplicationscanbeconsideredasmicrovas- 1 diabetes presents most commonly in autumn and cular or macrovascular. Type 1 diabetes is the culmination of an diabetic retinopathy, diabetic nephropathy and the occult process of β-cell destruction. In type 1 diabetes, there is hyperglycaemia due to fail- Investigations ure of glucose uptake and uncontrolled gluconeogenesis, Diagnosis is made on finding symptoms of diabetes (i. If there are no symptoms diagnosis should not be based r Patients should be regularly assessed for the develop- onasingleglucosedetermination. Immunosuppression itself may prevent quire an oral glucose tolerance test to exclude diabetes. This is a risk factor for the Definition development of diabetes and cardiovascular disease. Type 2 diabetes mellitus is a chronic disorder of carbohy- Other investigations that may be of value include C- drate, fat and protein metabolism with hyperglycaemia peptide measurement (the cleavage product when pro- as its principal feature. It is characterised by impaired insulin is converted to insulin) and detection of autoan- insulin secretion and insulin resistance. These tests are useful in distinguishing patients r Type 2 diabetes used to be called non-insulin depen- with type 1 from type 2 diabetes. Diabetes requires a combination of education, dietary advice, insulin regimens and careful monitoring and Incidence/prevalence follow-up. Normally the liver immediately takes up 50% of Sex insulin output of the pancreas. Most patients are man- M = F aged on a twice-daily regimen or basal bolus regimen (see page 454). Geography Good control of blood glucose reduces small ves- Wide geographic variation. Trial has shown that only 12% of intensively monitored and treated patients developed retinopathy after 9 years, compared to >50% of the conventionally treated pa- Aetiology tients. Acombination of genetic and environmental factors Monitoring: both in the development of insulin resistance and im- r Regular capillary blood glucose measurement often paired insulin secretion. The overall concordance in pre-meals, two hours post meals and during the night monozygotic twins is up to 90%. Once include diet both in relation to obesity, lack of exercise a patient is stabilised on a particular regimen moni- andtheepidemiologicalevidencethatonce‘westernised’ toring may be less frequent. Loss of weight by an obese patient can lead to normal- Pathophysiology isation of blood glucose levels and resolution of symp- r Insulin resistance in the liver, skeletal muscle and adi- toms. However,thereissufficient biguanides in patients with moderate renal or hepatic insulin to suppress lipolysis and ketogenesis, so that failure. These increase Clinical features levels of plasma insulin and may result in more weight Type 2 diabetes may be diagnosed on routine blood test- gain, insulin resistance and a higher risk of compli- ing (this may follow detection of glycosuria). Symp- cations, they are often avoided in the early treatment, tomatic patients have an insidious onset of polyuria, unless symptoms are severe. Diabetes causes an in- r Thiazolidinediones (glitazones) increase peripheral creased predisposition to infections, such as abscesses, insulin sensitivity. Complications r α−glucosidaseinhibitors(acarbose)whichreducethe r Acute complications: Hyperglycaemic coma which is activity of the enzyme responsible for digesting carbo- usually hyperosmolar non-ketotic coma and com- hydrates in the intestine, thus delaying and reducing plications of therapy such as hypoglycaemia due to postprandial blood glucose peaks. Macrovascular (large vessel) disease: Atherosclerosis which leads to complications such as myocardial Secondary diabetes mellitus infarction, strokes, gangrene of the legs and mesenteric artery occlusion. Definition Chronichyperglycaemiaandothermetabolicabnormal- Investigations ities seen in diabetes mellitus due to another identifiable The diagnostic criteria are as for type 1 diabetes. Causes include chronic pancreatitis, post- duced numbers of insulin receptors due to muta- pancreatectomy, pancreatic cancer, cystic fibrosis or tions in the allele for the receptor gene. Older patients with antibodies to insulin receptors Insulin counter-regulatory hormones inhibit insulin reducing their affinity for insulin. Various insulins have been r Glucagon (glucagonoma) ‘designed’ with different pharmacokinetic effects (see r Catecholamines (phaeochromocytoma) Table 11. Drugs may inhibit insulin secretion or cause damage to r Abolus of short or immediate acting insulin given the pancreatic islets. Instead, lower amounts Long acting should be used with careful monitoring, or the patient will need to be admitted for intravenous glucose and insulin to avoid either diabetic ketoacidosis or hyperos- molar non-ketotic coma. Complications of diabetes Diabetic microvascular disease Definition Microvascular diabetic complications includes diabetic retinopathy, nephropathy and the neuropathies. Aetiology It is thought that microvascular complications are sec- ondary to the metabolic derangements of diabetes, in particular hyperglycaemia.

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The analysis confirmed that patients buy generic levitra extra dosage 60mg on line causes of erectile dysfunction young males, whether diabetic or not order 60mg levitra extra dosage overnight delivery erectile dysfunction suction pump, benefit from lipid-lowering in accordance with their absolute cardiovascular risk order levitra extra dosage 60 mg impotence trials france. The evidence for efficacy of other lipid-lowering agents in primary prevention is weak. This was a mixed primary and secondary prevention study, which randomly assigned 2131 patients with previ- 48 Prevention of cardiovascular disease ous cardiovascular disease and 7664 without to receive either fenofibrate or a placebo. At 5 years follow-up, fenofibrate did not significantly reduce the risk of coronary events. While statins and resins had a significant lipid-lowering effect, n-3 fatty acids did not significantly affect cholesterol levels. Although there is little reason to believe that the effects would be different in non-Europeans with similar baseline risks of cardiovascular disease and similar lipid profiles, research is needed to examine the effects of lipid-lowering treatment in other racial groups. Risks There is no evidence from the large studies that cholesterol-lowering therapy increases the risk of death from other causes (333, 337, 338). Meta-analysis of data from statin trials has not shown an excess of adverse symptoms, including muscle pain and various gastrointestinal symptoms, in the treated group. Rhabdomyolysis (indicated by serum creatine kinase ≥10 times the upper limit of normal) was reported in 55 treated patients (0. The incidence of rhabdomyolysis is estimated to be about one per million person–years of use. Hepatitis (indicated by alanine aminotransferase ≥3 times the upper limit of normal) was reported in 449 treated patients (1. Data from randomized trials of cholesterol reduction and disease events have not provided evi- dence that a low serum cholesterol concentration increases mortality from any cause, other than possibly haemorrhagic stroke. Too few haemorrhagic strokes were observed in the randomized trials to resolve the uncertainty related to this condition. Further, the risk of haemorrhagic stroke affected only people with a very low cholesterol concentration and, even in this group, the risk was outweighed by the benefits from the reduced risk of coronary heart disease. In the Cholesterol Treatment Trialists Collaboration meta-analysis, there was no evidence of an effect on cancer deaths. The reduction in major vascular events was as marked in these elderly patients as in those aged under 65 years. However, there was an apparent excess of non-melanoma skin cancer in the simvastatin-treated group, compared with the placebo group (2. In the Scandinavian Simvastatin Survival Study (342), 21 patients in the statin group developed non-melanoma skin cancer, compared with seven in the placebo group. Overall, there is no statistically significant evidence that statin therapy increases the incidence of cancer. Treatment of those most at risk will bring the most benefit; treatment of patients not at high risk of cardiovascular disease may expose them to adverse effects without much benefit. As the side-effects of liver and muscle damage are dose- dependent (340), the high-dose statin regimens evaluated in some of the trials (344) will have a worse side-effects profile when applied to patients treated in everyday clinical practice. Fibrates reduced the risk of major coronary events by 25% and niacin by 27% (349). However, recent studies have not found a cholesterol level below which there is no benefit, suggesting that taking a trial-validated dose of a statin is more important than aiming for a particular target cholesterol level (321). Thus, continued moni- toring of blood lipids may not be necessary in settings with limited resources. Primary prevention trials (320, 322, 323) have demonstrated that patients at highest total risk of cardiovascular events obtain the greatest benefit from statin therapy. Treatment should therefore be targeted at the group with highest total risk, rather than simply those with highest lipid levels. Cost-effectiveness, feasibility and resource implications of antihypertensive and statin therapy The cost-effectiveness of a treatment is determined by the relationship between the benefits obtained and the expenditure. The prevalence of a condition and the total cost of treating it in a specific setting, on the other hand, determine affordability. Because resources are limited, even a cost-effective treatment may not be affordable. The two main determinants of cost-effectiveness are the cost of drug therapy and the initial cardiovascular risk of the patient. In the case of antihypertensive treatment, the major classes of antihypertensive drugs are largely equivalent in terms of efficacy. However, diuretics and beta-blockers, singly or in combination, are associated with an increased incidence of diabetes; thus, in populations with an increasing burden of diabetes, other classes of antihypertensive therapies may be preferable. In most parts of the world, a diuretic is the cheapest option and is, therefore, generally most cost-effective. However, for certain compelling indications, other classes will provide additional benefits; even if they are more expensive, they may be more cost-effective. There is no evidence to support claims of superior performance of any particular drug within each of the major drug classes. As popula- tions age, increasing numbers of elderly people are being diagnosed as hypertensive and requiring treatment. For this group, diuretic-based therapy is the most cost-effective; therapy that includes either atenolol or low-dose reserpine has been shown to be a relatively inexpensive approach to prevention of cardiovascular events in older adults with isolated systolic hypertension (351). Although people over the age of 75 years get less benefit from statin therapy, such therapy is cost-effective for people in all age groups with a 10-year cardiovascular risk of 20% or more (352, 353 ). Thus, if the decision is made to initiate statin therapy, the least expensive statin should usually be chosen. Control of glycaemia Issue Does control of glycaemia reduce cardiovascular risk in patients with diabetes? Evidence Cardiovascular disease accounts for about 60% of all mortality in people with diabetes. The risk of cardiovascular events is 2–3 times higher in people with type 1 or type 2 diabetes (354, 355) and the risk is disproportionately higher in women (354, 356). Patients with diabetes also have a poorer prognosis after cardiovascular events compared with non-diabetics (357, 358). Epidemiological evidence also suggests that the association between blood glucose and cardiovas- cular disease begins before diabetes manifests itself (357–361). In a meta-analysis of non-diabetic subjects, those with the highest blood glucose levels had a relative risk for cardiovascular disease events of 1. This suggests that cardiovas- cular risk increases as glucose tolerance becomes impaired and then progresses to diabetes (362). However, the difference in the number of events in the two groups was not significant. Each 1% increase in HbA1c level was associated with a 14% increase in the incidence of fatal or nonfatal myocardial infarction (368). However, intensive treatment of patients with newly diagnosed type 2 diabetes, with sulfonylureas or insulin, resulted in a 16% reduction (P = 0. There was no “threshold” of glycaemia at which there was a significant change in risk for any of the clinical outcomes examined.

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