By D. Georg. University of New Haven.

She has had three episodes of cough silvitra 120mg low price erectile dysfunction at 20, fever and purulent sputum over the last 6 months buy silvitra 120 mg without prescription erectile dysfunction remedies pump. Recently she has had trouble with regurgitation and vomiting of recognizable food purchase 120 mg silvitra free shipping erectile dysfunction protocol list. She lived in the north-west coast of the United States for 4 years up until 10 years ago cheap silvitra 120mg otc erectile dysfunction australian doctor. She has always tended to be constipated and this has been a little worse recently. There are no abnormalities to find in the cardiovascular system, abdomen or other systems. The X-ray shows a dilated fluid-filled oesophagus with no visible gastric air bubble. The oesophagus has now dilated and there has been spill-over of stagnant food into the lungs giving her the episodes of repeated respiratory infections. Such aspiration is most likely to affect the right lower lobe because of the more vertical right main bronchus, although the result of aspiration at night may depend on the position of the patient. It tends to be present for all foods, indicating a motility problem, and there may initially be some relief from the mechanical load as the oesophagus fills. The diagnosis can be made at this stage by a barium swallow showing the dilated oesopha- gus. Earlier it may require careful cine-radiology with a bolus of food impregnated with barium, or oesophageal motility studies using a catheter fitted with a number of pressure sensors to detect the abnormal motility of the oesophageal muscle. A similar condition can be produced by the protozoan parasite Trypanosoma cruzi (Chagas’ disease), but this is limited to South and Central America and would not be relevant to her stay in the north-west United States. Other common causes of dysphagia are benign oesophageal structures from acid reflux, malignant structures, external compression or an oesophageal pouch. Achalasia may be managed by muscle relaxants when mild, but often requires treatment to disrupt the lower oesophageal muscle by dilatation or surgery. In his abdomen the only abnormality is that his spleen is palpable 4 cm below the left costal margin. This is due to abnormal proliferation of red cell precursors derived from a single haematopoietic progenitor cell with the capacity for differentiation down red cell, white cell and platelet lines. As a result, there is an increase in haemoglobin, white cell count and platelet level. Patients may present with a throm- botic event or with symptoms due to increased blood viscosity such as headaches, tinni- tus and blurred vision. Severe pruritus is characteristic and is particularly related to warmth occurring on getting into a warm bed or bath. Conditions associated with generalized pruritus without a rash • Obstructive jaundice due to bile salt retention • Iron deficiency • Lymphoma • Carcinoma, especially bronchial • Chronic renal failure, partially due to phosphate retention This patient should be referred to a haematology unit for investigation. It is important to exclude relative polycythaemia due to dehydration from diuretic and alcohol use. The red cell mass will be raised in polcythaemia rubra vera, but normal in relative polycythaemia. The following causes of secondary polycythaemia must be excluded: • chronic lung disease with hypoxia • cyanotic congenital heart disease • renal cysts, tumours, renal transplants • hepatoma, cerebellar haemangioblastoma, uterine fibroids • Cushing’s disease. The erythropoietin level is low in polycythaemia rubra vera and high in secondary poly- cythaemia. The leucocyte alkaline phosphatase level is also raised in polycythaemia rubra vera. The patient should be venesected until the haematocrit is within the normal range. A var- iety of agents can be used to keep the haematocrit down: 32P, hydroxyurea and busulphan. The symptoms have been present for 2 months and have increased slightly over that time. He had noticed some skin lesions on the edge of the hairline and around his nostrils. Previously he had been well apart from an appendicec- tomy at the age of 17 years. Examination There is no deformity of the joints and no evidence of any acute inflammation. In the skin there are some slightly raised areas on the edge of the hairline posteriorly and at the ala nasae. The age is typical and sarcoidosis is more common in those of African-Caribbean origin. The blood results show a slightly raised calcium level which is related to vitamin D sensi- tivity in sarcoidosis where the granulomas hydroxylate 25-hydroxycholecalciferol to 1,25- dihydroxycholecalciferol. The skin lesions at the hairline and the nostrils are typical sites for sarcoid skin problems. The eye trouble 6 weeks earlier might also have been a manifesta- tion of sarcoidosis, which can cause both anterior and posterior uveitis. Tuberculosis can also cause hypercalcaemia although this is much less common than in sarcoid. Tumours, especially lymphoma, might give this X-ray appearance but would not explain the other findings. The arthralgia (pains with no evidence of acute inflammation or deformity on examination) can occur in sarcoid or tuberculosis but again they are commoner in sarcoid. The serum level of angiotensin-converting enzyme would be raised in over 80 per cent of cases of sarcoidosis but often in tuberculosis also; the granuloma cells secrete this enzyme. A bronchial or transbronchial lung biopsy at fibreoptic bron- choscopy would be another means of obtaining diagnostic histology. In patients with a cough and sarcoidosis the bronchial mucosa itself often looks abnormal, and biopsy will provide the diagnosis. Steroid treatment would not be necessary for the hilar lymphadenopathy alone, but would be indicated for the hypercalcaemia and possibly for the systemic symptoms. She also has a persist- ent frontal headache associated with early morning nausea. Eight years previously she had a left mastectomy and radiother- apy for carcinoma of the breast. She is a retired civil servant who is a non-smoker and drinks 10 units of alcohol per week. Her pulse rate is 72/min, blood pressure 120/84 mmHg, jugular venous pressure is not raised, heart sounds are normal and she has no peripheral oedema. It is more likely that she has polyuria due to neurogenic diabetes insipidus as a result of secondary metastases in her hypothalamus.

These headaches have been present in previous years but have now become more intense cheap 120mg silvitra visa erectile dysfunction natural treatment reviews. She also complains of loss of appetite and difficulty sleeping generic 120 mg silvitra with mastercard erectile dysfunction at 55, with early morning wak- ing discount 120 mg silvitra otc impotence urologist. She has had eczema and irritable bowel syndrome diagnosed in the past but these are not giving her problems at the moment 120mg silvitra free shipping impotence losartan potassium. Examination of the cardiovascular, respiratory and gastrointestinal systems, breasts and reticuloendothelial system is normal. The headache is usually bilateral, often with diffuse radiation over the vertex of the skull, although it may be more localized. Patients may show symp- toms of depression (this woman has biological symptoms of loss of appetite and disturbed sleep pattern). Sufferers may reveal sources of stress such as bereavement or difficulty with work. There may be an element of suggestion as in this case, with concern that she may have inherited a brain tumour from her mother. Major differential diagnoses of chronic headaches • Classic migraine: characterized by visual symptoms followed within 30 min by the onset of severe hemicranial throbbing, headache, photophobia, nausea and vomiting lasting for several hours. The onset is usually in early adult life and a positive family history may be present. It characteristically occurs 1–2h after sleeping, and lasts 1–2h and recurs nightly for 6–8 weeks. There will often be other signs, including personality change and focal neurological signs. It is important to come to a clear diagnosis and to address the patient’s beliefs and con- cerns about the symptoms. The question of depression needs to be explored further and may need treating with antidepressants. Two months earlier he had been admitted with a productive cough and acid-fast bacilli had been found in the sputum on direct smear. He was found a place in a local hostel for the homeless and sent out after 1 week in hospital on antituberculous treatment with rifampicin, isoniazid, ethambutol and pyrazinamide together with pyridoxine. His chest X-ray at the time was reported as showing probable infiltration in the right upper lobe. This might have occurred because he had a resistant organism or, more likely, because he had not taken his treatment as prescribed. Other possi- bilities would be liver damage from the antituberculous drugs and the alcohol, although clinical jaundice would be expected, or electrolyte imbalance. If these are not present a lumbar puncture would be indicated, provided that there is no sign to suggest raised intracranial pressure. It is now 2 months since the initial finding of acid-fast bacilli in the sputum and the cul- tures and sensitivities of the organism should now be available. These should be checked to be sure that the organism was Mycobacterium tuberculosis and that it was sensitive to the four antituberculous drugs which he was given. The urine will be coloured orangy-red by metabolites of rifampicin taken in the last 8 h or so. Comparison with his old chest X-rays showed extension of the right upper-lobe shadow- ing. It is difficult to be sure about activity from a chest X-ray but extension of shadow- ing is obviously suspicious. A direct smear of the sputum showed that acid-fast bacilli were still present on direct smear. The breathlessness persisted over the 4 h from its onset to her arrival in the emergency department. There is no relevant previous medical history except asthma controlled on salbutamol and beclometa- sone. She works as a driving instructor and had returned from a 3-week holiday in Australia 3 weeks previously. The phys- ical signs of tachypnoea, tachycardia, raised jugular venous pressure and pleural rub would fit with a diagnosis of a pulmonary embolus. The peak flow of 410 L/min indicates that asthma does not explain her breathlessness. The differential diagnosis would include pneumonia, pneumothorax and pulmonary embolism. Possible predis- posing factors for pulmonary embolism are the history of a long aeroplane journey 3 weeks earlier, oral contraception and her work involving sitting for prolonged periods. Other signs such as transient right ventricular hypertrophy features, P pulmonale and T-wave changes may also occur. A ventilation–perfusion lung scan could be done looking for a typical mismatch with an area which is ventilated but not perfused. A pulmonary arteriogram has been the ‘gold standard’ for the diagnosis of embolism but is a more invasive test. In cases with a normal chest X-ray and no history of chronic lung disease, equivocal results are less common and it is not usually necessary to go further than the lung scan. This showed a filling defect typical of an embolus in the right lower lobe pulmonary artery. A search for a source of emboli with a Doppler of the leg veins may help in some cases, and the finding of negative D-dimers in the blood makes intravascular thrombosis and embolism unlikely. The anticoagulation can then transfer to warfarin, continued in a case like this for 6 months. Alternative modes of contraception should be discussed and advice given on alternating walking or other leg movements with her seated periods at work. Thrombolysis should be considered when there is haemodynamic compromise by a large embolus. The pain is in the centre of the chest and has lasted for 3 h by the time of his arrival in the emergency department. He has been treated with aspirin and with beta-blockers regularly for the last 2 years and has been given a glyceryl trinitrate spray to use as needed. His father died of a myocardial infarction aged 66 years and his 65-year-old brother had a coronary artery bypass graft 4 years ago. Examination He was sweaty and in pain but had no abnormalities in the cardiovascular or respiratory systems. He was given analgesia and thrombolysis intravenously and his aspirin and beta-blocker were continued. On examination, now his jugular venous pressure is raised to 6 cm above the manubrioster- nal angle. On auscultation of the heart, there is a loud systolic murmur heard all over the praecordium. In the respiratory system, there are late inspiratory crackles at the lung bases and heard up to the mid-zones. The late inspiratory crackles are typical of pulmonary oedema and the chest X-ray confirms this showing hilar flare with some alveo- lar filling, Kerley B lines at the lung bases and blunting of the costophrenic angles with small pleural effusions.

They are a major advance in treating various immune proteinuria in 30% of patients generic silvitra 120mg amex erectile dysfunction vacuum pump reviews. The drug should be diseases (see Chapter 50) cheap 120 mg silvitra with amex erectile dysfunction at 65, including rheumatoid arthritis discount silvitra 120 mg mastercard erectile dysfunction vyvanse, but stopped until proteinuria resolves and treatment then have serious adverse effects trusted silvitra 120mg impotence trials, including infusion reactions and resumed at a lower dose. They are currently used by rheumatologists • Other symptoms include hypersensitivity reactions with for adults with active disease which has not responded to two urticaria. They are not continued if a response has not gravis-like syndromes can also be involved. Combinations of these proteins with methotrexate are being investigated for refractory disease, Contraindications with encouraging results. Penicillamine is contraindicated in patients with systemic lupus erythematosus, and should be used with caution, if at all, in individuals with renal or hepatic impairment. A number of hepatic metab- and gives rise to problems because of its limited solubility. Adverse effects Xanthine oxidase Adverse effects include the following: Figure 26. The final enzymatic • peripheral neuropathy; reactions in the production of uric acid are shown in Figure 26. It is more soluble in Colchicine is well absorbed from the gastro-intestinal tract. Plasma uric acid concentration is is partly metabolized, and a major portion is excreted via the lowered either by increasing renal excretion or, more often, by bile and undergoes enterohepatic circulation, contributing to inhibiting synthesis. Hyperuricaemia often occurs in the setting of obesity and excessive ethanol consumption. Hyperuricaemia also Allopurinol is used as long-term prophylaxis for patients occurs when excretion is decreased, for example, in renal fail- with recurrent gout, especially tophaceous gout, urate renal ure or when tubular excretion is diminished by diuretics, pyraz- stones, gout with renal failure and acute urate nephropathy, inamide (Chapter 44) or low doses of salicylate (Chapter 25). It The acute attack is treated with anti-inflammatory analgesic must not be commenced till several weeks after an acute agents (e. Allopurinol is a xanthine oxidase inhibitor and decreases the production of uric acid (Figure 26. It is also used in patients with familial Adverse effects Mediterranean fever and Behçet’s disease. A low dose can be used pro- rashes and life-threatening hypersensitivity reactions (includ- phylactically. It is relatively contraindicated in the elderly and ing Stevens Johnson syndrome) can occur. There is a history of essential hypertension, and he has had a similar but less Drug interactions severe attack three months previously which settled sponta- • Allopurinol decreases the breakdown of 6-mercaptopurine neously. Following this, serum urate concentrations were determined and found to be within the normal range. His (the active metabolite of azathioprine) with a potential for toe is now inflamed and exquisitely tender. He therefore prescribes cocodamol for Use the pain and repeated the serum urate measurement. Review Their main effect on the handling of uric acid by the kidney is his medication (is he on a diuretic for his hypertension? Despite his occupation, the patient does not drink alcohol and he was receiving ben- precipitate an acute attack of gout. The patient should period of poor antihypertensive control in this setting is not drink enough water to have a urine output of 2L/day during of great importance. After the pain has settled and ibuprofen the first month of treatment and a sodium bicarbonate or stopped, the patient’s blood pressure decreases further to 140/84mmHg on amlodipine. He did not have any recurrence potassium citrate mixture should be given to keep the urinary of gout. The coxibs, selective inhibitors of cyclooxy- • Gout is caused by an inflammatory reaction to genase-2. Risk of acute myocardial infarction • Always consider possible contributing factors, including and sudden cardiac death in patients treated with cyclo-oxygenase drugs (especially diuretics) and ethanol. Medication use and the risk of Stevens- alternative when allopurinol causes severe adverse Johnson syndrome or toxic epidermal necrolysis. Since these are the major causes of morbidity and mortality among adults in industrialized societies, its prevention is of great importance. An important practical distinction is made between prevent- ive measures in healthy people (called ‘primary prevention’) and measures in people who have survived a stroke or a heart attack, or who are symptomatic, e. The absolute risk per unit time is greatest in those with clinical evidence of established disease, so secondary prevention is especially worthwhile (and cost-effective, since the number needed to treat to pre- Figure 27. Primary prevention inevitably involves larger populations who are at relatively low absolute risk per unit time, so inter- These plaques are rich in both extracellular and intracellular ventions must be inexpensive and have a low risk of adverse cholesterol. Epidemiological ulcerate, in which event the subintima acts as a focus for observations, including the rapid change in incidence of coron- thrombosis: platelet-fibrin thrombi propagate and can occlude ary disease in Japanese migrants from Japan (low risk) to the artery, causing myocardial infarction or stroke. Approximately two-thirds of cholesterol circu- intima and progress to proliferative fibro-fatty growths that lating in the blood is synthesized in the liver. Low-density lipoprotein that enters arterial walls ticles by lipoprotein lipase, an enzyme on the surface of at sites of endothelial damage can be remobilized in the form endothelial cells. Chylomicron and be taken up by macrophages as part of atherogenesis remnants are taken up by hepatocytes to complete the exoge- (see below). Intimal enrichment of the particles with cholesterol, with an increase injury initiates atherogenesis, which is a chronic inflammatory in their density through intermediate-density to low-density process. The injury may initially be undetectable morphologi- cally, but results in focal endothelial dysfunction. Blood Modifiable risk factors are potentially susceptible to therapeutic monocytes adhere to adhesion molecules expressed by injured intervention. These include smoking, obesity, sedentary habits, endothelium and migrate into the vessel wall, where they dyslipidaemia, glucose intolerance (Chapter 37) and hyperten- become macrophages. Lymphocytes and platelets adhere to matous disease were disproved by randomized controlled trials the injured intima and secrete growth factors and cytokines, (Figure 27. The plasma concentration of Lp(a) varies over attempts to give up are often unsuccessful. Most tine, bupropion and varenicline (partial agonist at the nico- drugs have little effect (nicotinic acid is an exception). Apo(a) tinic receptor) in conjunction with counselling in smoking contains multiple repeats of one of the kringles of plasminogen cessation programmes are covered in Chapter 53. Obesity is increasingly common and is a strong risk factor, partly via its associations with hypertension, diabetes and dyslipidaemia. Secondary forms of dyslipidaemia cells (including macrophages and endothelial cells). Dietary advice focuses on chemical messengers are released by lipid-laden reducing saturated fat and correcting obesity rather than macrophages (‘foam cells’), T-lymphocytes and reducing cholesterol intake per se. These interleukins and growth factors cause evidence of atheromatous disease, the decision as to whether the migration and proliferation of vascular smooth to initiate drug treatment at any given level of serum lipids muscle cells and fibroblasts, which form a fibro-fatty plaque. This is cal- • Cigarette smoking promotes several of these processes culated from cardiovascular risk prediction charts (e.