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Fibroadenomas are under hormonal Incidence control discount 5 mg glyburide with amex,theymayenlargeduringpregnancyandinvolute Palpable cysts occur in 7% of women in Western coun- at menopause best 2.5 mg glyburide. Clinical features Aetiology/pathophysiology Patients (normally young women) present with a Breast cysts are a very common nding in the years lead- smooth buy discount glyburide 5 mg on-line, rm, painless nodule that is well-demarcated ing up to the menopause and are thought to arise due to and freely mobile (breast mouse). Juvenile broadenoma is a rare subtype that occurs in femaleadolescentsandgrowsrapidly. Macroscopy/microscopy An encapsulated rubbery white lesion with a glisten- Investigations ing cut surface. It consists of a brous connective tissue Patients require a triple assessment consisting of clinical component and abnormally proliferated ducts and acini examination (see page 409), imaging using ultrasound (adenoma) in varying proportions. Investigations Investigation of any breast lump involves a triple assess- Management ment consisting of clinical examination (see page 409), Patients with a single cyst do not need to be reviewed fol- imaging normally by ultrasound as patients are young lowing an otherwise normal ultrasound and successful and sampling by core biopsy or ne needle aspiration neneedleaspiration. Indications for surgical biopsy in- Management clude bloody uid detected on ne needle aspiration, If conrmed as a broadenoma on triple assessment, aresidual mass following aspiration, or multiple recur- small lesions may be left unless the patient requests rence at the same site. This is Denition associated with an increased risk of developing breast Abenign breast disorder with dilation (ectasia) of the cancer. Clinical features Most patients present with a bloody or serous nipple Age discharge. It is often possible to identify the discharge Most common in women approaching the menopause. There may be a small Aetiology/Pathophysiology swelling at the areolar margin (30%), which if pressed The dilated ducts are lled with inspissated secretions may produce discharge. Macroscopy/microscopy One to two centimetres sized papilloma within a di- Clinical features lated duct with secretions collected behind it. The le- Duct ectasia may be asymptomatic or may cause nipple sion usually consists of fronds of vascular tissue covered discharge (often green) and localised tenderness around byadouble layer of cells resembling ductal epithelium. Investigations Macroscopy/microsopy Mammography and/or ductography show the dilated The ducts may be dilated as much as 1 cm in diam- duct and lling defect. Awire is often passed into the responsible duct, which is excised as a microdochectomy with the breast segment Investigations that drains into it. Although ductography or duc- toscopy are possible, they are not routine investigations. Fat necrosis Denition Management An uncommon condition in which there is death of fat Once the diagnosis is conrmed surgery may be required cellswithin the breast. Treatment is by subareolar excision Aetiology/pathophysiology of the affected ducts. The aetiology is unclear, it is suggested that the death of fat cells may result from trauma. There is an acute inammatory response, which in some cases progresses Duct papilloma to chronic inammation and organisation with brous Denition tissue. The result may be a hard, irregular mass, which Abenign proliferation of the epithelium within large can mimic carcinoma. Clinical features Aetiology pathophysiology Patients present with a hard mass, which may also have Papillomas usually arise less than 1 cm from the nipple skin tethering; often in an obese patient with large and obstruct the natural secretions from the gland. Breast-feeding should be encouraged as this aids drainage of the affected segment of the breast. Lipid-laden macrophages breast-feeding, the baby should be fed from the non- (foam cells/lipophages) may form multinucleate giant infected breast and expression of milk used to drain cells. An alternative is daily ultrasound-guided aspiration with antibiotics until the infection has resolved. Infections of the breast Acute mastitis Breast cancer Denition Acute bacterial inammation of the breast is related to Denition lactation in most cases. Aetiology/pathophysiology r Incidence Breast-feeding predisposes to infection by the devel- Approximately 2/1000 p. Peak 50 60 years Periductal non-lactating mastitis is associated with smoking in 90%. It has been suggested that smok- ing may damage the subareolar ducts, predisposing Sex to infection. Clinical features Patients present with painful tender enlargement of the Aetiology breast, often with a history of a cracked nipple. If left In most cases it appears to be multifactorial with a strong untreated an abscess may form after a few days. Increased risk Investigations with early menarche, late menopause, nulliparity, low Swab any pus and send breast milk (where appropriate) parity and late rst pregnancy. The woman (or rarely, a man) usually presents with a This gene is particularly associated with male breast painless lump in the breast or after routine mammo- cancer. Itmostoftenoccursintheupperouter 3 Mutations in the p53 tumour suppressor gene are quadrant of the breast. Occasionally the lump aches or also associated with an increased risk of developing has an unpleasant prickling sensation. Most tumours of the breast are adenocarcinomas, r Palpable lymph nodes in the axilla, hard in texture, which develop from the epithelial cells of the terminal which may be discrete or matted together or to over- duct/lobular unit. These tu- Some patients present with metastatic disease and a hid- mours form approximately 20% of carcinomas of the den primary. Weight loss and malaise are also nuclear grade and the presence or absence of necro- late symptoms. This grading helps to guide Macroscopy/microscopy management allowing conservative surgery with or The macroscopy of invasive tumours is largely deter- without radiotherapy, whereas previously all pa- mined by the stromal reaction around the cells. It is r Invasive ductal carcinoma: The majority of these identied as a coexistent nding during micro- have no special histological features, reecting scopic examination of breast tissue samples taken their lack of differentiation. Tumourscanbestainedforoestrogenreceptors,which 3 Breast tissue sampling using needle core biopsy or affects response to treatment. This also allows In Paget s disease of the nipple, the skin of the nip- staining for hormone receptors, which guides man- ple and areola is reddened and thickened, mimicking agement. It is a form of ductal carcinoma arising from Ifamalignancy is conrmed patients may undergo thelargeexcretoryducts. Theepidermidisisinltrated achest X-ray, full blood count and liver function tests by large pale vacuolated epithelial cells, and there is al- for staging. Ninety to Early or operable breast cancer (Up to T2, N1, M0 breast ninety-ve per cent of the breast drains to the axillary cancer with or without mobile lymph nodes on the same Table10. Postmenopausal women receive either tamoxifen or Local treatment: an aromatase inhibitor, which reduces the peripheral r Breast conservation surgery involves a wide local ex- conversion of androgens to oestrogen. Conservative breast surgery with hibitors appear to be as effective as tamoxifen with radiotherapy has been shown to be as effective as mas- fewer side effects. Anewclass Lymph node treatment: ofchemotherapeuticagentscalledtaxaneshasresulted r Assessment of the presence of spread to the lymph from yew tree-derived products, e. Trastuzumab nodes may be identied by intraoperative injection of (Herceptin) has been shown to prolong survival in atraceraround the tumour site. Locally advanced disease: Patients are treated with pre- N: Nodal involvement reduces 5-year survival from 80 operativesystemictherapyandtheniftheybecomeoper- to 60%. In more than 65% of women, M: Haematogenous spread has a much poorer progno- the tumour shrinks by more than 50%, which makes it sis (5-year survival is only 10%). Average survival is more likely that the whole tumour is excised at surgery 14 18 months with chemotherapy. Treatments include radiotherapy, systemic treatment Females aged 50 69 years are invited every 3 years for and surgery to debulk the primary tumour, which may screening by a craniocaudal and a mediolateral oblique be ulcerating through the skin and alleviate symptoms mammogram (see also page 412). If identied, a stereotactic needle core biopsy can used depends on whether patients are pre- or post- be performed to obtain tissue for histology. The lump can then be iden- effect of screening on mortality, but as the range of mor- tied and either undergo excision biopsy or wide local talityratesexceedthereductionofmortalitybyscreening excision with the removal of a margin of surrounding it is difcult to demonstrate a statistical benet. If the histology demonstrates malignancy it appears that one woman in every 1000 who under- further treatments for breast cancer may be required (see goes breast screening may be prevented from dying from page 417). This must be balanced against false pos- The evidence of the breast cancer screening pro- itive screening results and unnecessary biopsies, which gramme is difcult to assess. The endocrine system is the mechanism by which in- Endocrine dysfunction generally results in over or un- formation is communicated around the body using der functioning of a gland. For example, hypothy- secreted by glands and may be transported through the roidismmayresultfromafailureoftheanteriorpituitary bloodstream to a distant target organ (endocrine ac- gland or a failure of the thyroid gland. Endocrine test- tivity) or may act directly on local tissue (paracrine ing is used to both identify the lack of hormone and to activity). For example, tides, glycoproteins, steroids or amines such as cate- r measurement of thyroid hormones is used to detect cholamines.

Roche does not provide evidence that strengthening healthcare infrastructure; increas- includes the description of cases where conficts it shared its intellectual property with research ing awareness; and supporting patients purchase 2.5 mg glyburide otc. It tai- of interest may arise order 5mg glyburide overnight delivery, and actions employees are institutions or neglected disease drug discovery lors its approach depending on local health- expected to take order glyburide 2.5 mg amex. In 2015, it rolled out the Access close information related to the political contri- in April 2016, the company did review its posi- Planning Framework, aiming to identify spe- butions it may make in countries within scope. Roche falls 9 places to 20th, Low transparency regarding stakeholder actions taken in response. R&D commitments not clearly linked to needs Targets needs to a degree through equitable Roche engages with local stakeholders on an ad within the scope of the Index. It publishes only general information, to R&D that addresses unmet product needs vant products have pricing strategies that target and provides no evidence that it incorporates within the scope of the Index. Roche makes no priority countries, reaching 70% of correspond- the outcomes of these activities into its opera- commitment to meeting the specifc needs of ing priority countries (disease-specifc sub-sets tions and strategies. Roche has policies in place is due to improvements in the structure of its and takes measures to ensure its in-house and No disease-specifc registration targets. Roche compliance system and to its public transpar- outsourced clinical trials are conducted ethically does not report disease-specifc registration tar- ency regarding lobbying activities and enforce- gets. Does not fully publish trial results; has system registration decisions, nor does it reveal where for making patient-level data available. Roche does not specify a timeframe for publishing has a code of conduct that includes ethical mar- the results of its clinical trials. Roche does not report keting provisions and that also applies to third provide scientifc researchers with access to having a drug recall policy. Roche does not pub- 154 Access to Medicine Index 2016 lish whether it has issued drug recalls during the considers fnancial sustainability and includes ters to measure blood sugar levels for all chil- period of analysis. In 2014, Roche adapted the packaging Phelophepa mobile health clinic in South Africa. Roche partners with information about several ad hoc donations, Roche supplied glucometers and testing strips 50 universities globally, but focuses on coun- including the outcome and impact reports. The company did not disclose any relevant partnerships with local Involved in donations following natural disas- research organisations to build R&D capacity in ters. Roche makes donated more than 180,000 vials of ceftriax- Commits to waiving patent rights in poor coun- a general commitment to build manufacturing one (Rocephin ), an antibiotic that treats a wide tries. Roche contributed to at least Roche Annual Report 2015; Roche corporate signifcant medical need be identifed. It has granted licences for the pro- ples of safety label updates for its medicines or duction of oseltamivir (Tamifu ) in order to pharmacovigilance-related information-sharing support increased production. Roche makes a public statement on Does not take a public position on the Doha counterfeiting, committing to cooperate with Declaration. Roche has not made a public state- authorities whenever a Roche product is con- ment about its position on the Doha Declaration cerned. Roche has not been found to have breached casting) regarding supply chain management competition law during the period of analysis. Roche is The company supports capacity building activi- involved in humanitarian aid donations, and has ties in countries in scope, such as training labo- a clear public commitment to engaging in prod- ratory technicians in sub-Saharan Africa through uct donations. In R&D, it commits to maintaining its investment in equitable pricing strategy for a disease in scope, and has no R&D overall at over 17% of net sales, and has clear targets to relevant registration targets. Its approach ing and lobbying is low, and it was found to have acted unethi- to intellectual property has improved, with a pledge not to fle cally twice. It is one of the biggest risers in Astellas does not donate products for diseases in scope. Transfer knowledge of equitable pricing strate- access to these medicines, while ensuring their Astellas can make specifc access plans for each gies. Biotechnology and Diagnostics Industries on ting, during late stages of clinical development, Combating Antimicrobial Resistance. Astellas can expand this stakeholder Leverage R&D expertise in product adapta- engagement programme to low- and middle-in- tion for more diseases. Through partnerships, Build lasting improvements in local R&D capac- come countries where it has operations. Astellas can draw on its existing R&D activi- could lead to a structured approach to stake- ing products to meet specifc needs (as exhib- ties in countries in scope to build local research holder engagement. Americas Japan *Due to a change in company reporting practices, the numbers from 2011 are incomparable with following reporting years. Astellas has two R&D pro- Astellas portfolio is mainly focused on infectious jects that target high-priority product gaps with diseases, and includes seven broad-spectrum low commercial incentive: for Chagas disease 5 antibiotics registered for the treatment of multi- and schistosomiasis. This includes nilvadipine (Nivadil ), doxycycline and includes plans for access, e. Lags behind without a clear strategy for and for failing to provide accurate information. Has objectives for improving access, but they countries that the company has operations with. Astellas has dropped four places to 19th posi- are not aligned with the core business strategy. Maintains its performance while others drop Nevertheless, it does not report having an access behind. Astellas rises three positions in R&D: No eforts to facilitate its products rational strategy, nor does it explain how its objectives overall it has maintained its performance, and use. Astellas does not have dedicated incen- Astellas commits to conducting R&D for dis- from countries in scope. Such measures help tive structures in place for rewarding its employ- eases that have been neglected for commer- ensure products are used as intended. Nor does it have measures for track- ing its R&D commitments requires long-term Pricing guidelines provided to sales agents. The company does not have a structured Poor policy and transparency in collaborations. However, it does have some ad access-oriented terms (such as pricing or supply tion. Astellas does not set disease-specifc tar- hoc engagement activity, such as those related commitments) are systematically included in gets for registering new products within a set to its Fistula Project in Kenya, in which the com- its research partnerships. It has not fled to register any of pany engages with local non-governmental publish such terms and conditions in relation to its newest products in any of their correspond- organisations. As a result, it is unclear Drops eight positions following low transpar- does not provide evidence of how it takes dis- how the company considers where and when to ency and compliance. Astellas transparency ciplinary action if ethical violations occur in its make its products available for sale. It was found to have breached Transparency around clinical trial data set to ally consistent guidelines for issuing drug recalls industry codes of conduct multiple times. Astellas is revising its global policy for in all countries relevant to the Index where its transparency of its clinical trial data. Astellas has not recalled Low transparency in ethical marketing and rently slated to include the disclosure of the a product for a relevant disease in a country in anti-corruption. Its sales agents In a new step, the company provides scientifc does not have a policy of disclosing recalls on its are only assigned performance-linked incentives, researchers with access to patient-level data website. Astellas commits to assessing needs and building capacity in countries in scope for Rises six places through transparent new in-house manufacturers. After consecutive Indices at the pany undertakes a number of capacity building tail end of the ranking in Patents & Licensing, activities, including with third parties, e. Astellas new philanthropic policy is rel- New commitment not to fle for or enforce pat- atively strong it aims to deliver sustainable ents in the poorest countries. Astellas makes improvements and includes impact evaluation a new, public commitment not to fle for or but it does not clearly target local needs. The enforce its patents in select Least Developed company discloses one relevant initiative to build Countries or in low-income countries. Astellas does not publish whether and/or where Limited approach to building R&D capacity. However, it did not disclose any relevant partnerships with local Committed to considering requests to license. Astellas ranks last: it has not made ments, fnes or judgements relating to competi- any structured or ad hoc donations during the tion law during the period of analysis. The company has improved in capacity building outside the phar- maceutical value chain, and supply chain man- agement. However, it disclosed no relevant R&D capacity building initiatives, and does not have a clear focus on local needs.

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The exact number of people who die from asthma is not known purchase glyburide 2.5mg without prescription, but increases in death rates in patients aged 5 to 34 years had been noted in the 1980s ( 87) generic glyburide 2.5mg free shipping. The fatality rate among nonwhites remains higher than among whites proven 2.5 mg glyburide, with death rates of 3. A disturbing finding that blacks received or filled fewer prescriptions for inhaled corticosteroids and oral steroids was reported in the Detroit area ( 88) in a managed care setting in which physician prescribing and advice (referral to an asthma specialist) appeared to be different depending on the ethnicity of the patient. All the patients in this study were enrolled in the same large health maintenance organization; thus, lack of insurance or access to medications were not issues seemingly. The costs of asthma include direct costs of medications, hospitalizations, and physician charges in addition to indirect costs for time lost from work and loss of worker productivity. Some 20% of the patients used 80% of the resources ($2,584, compared with $140 per patient) (89). Some patients have been labeled as the $100,000 asthmatic patients because of repeated hospitalization and emergency department visits (90). Emotional costs of asthma are great for the sufferer and the family if asthma is managed ineffectively or if the patient refuses to adhere to appropriate medical advice. The death of a family member from asthma is shocking; the person may be young, and the fatal attack may not have been anticipated by others or even the patient. It must be kept in mind that with current understanding and treatment of asthma, all fatalities should be avoidable and asthma need not be a fatal disease. This finding has led some physicians to conclude that emergency medical services should be improved. One cannot dispute such an argument, but it is advisable for the physician managing the patient with asthma to have an emergency plan available for the patient or family so that asthma is not managed from a crisis orientation but rather on a preventive basis. Further, an education program or patient instructions can identify what patients should do when their medications are not effective, such as with a flare of asthma. Substantial increases in cromolyn by metered-dose inhaler had occurred as well as increases in inhaled corticosteroids. The sales of inhaled corticosteroids increased 12-fold from 1976 to 1991, whereas sales of b-adrenergic agonist inhalers increased threefold ( 91). At that time, there was little combined use of inhaled corticosteroids and b-adrenergic agonists. In a study of more than 25,000 patients with asthma in four health maintenance organizations, there was an inverse relationship between pharmaceutical costs and acute care charges, as one might expect ( 93). The hospitalization rates and fatality rates have increased, as have medication prescriptions. The lung is an immunologic organ and has endocrine and drug-metabolizing properties that affect respiration. The lung consists of an alveolar network with capillaries passing near and through alveolar walls and progressively larger intrapulmonary airways, including membranous bronchioles (1 mm or smaller noncartilaginous airways) and larger cartilaginous bronchi and upper airways. The first 16 airway divisions of the lung are considered the conducting zone, whereas subsequent divisions from 17 to 23 are considered transitional and respiratory zones. The conducting zone consists of trachea, bronchi, bronchioles, and terminal bronchioles and produces what is measured as airway resistance. Respiratory bronchioles, alveolar ducts, and sacs compose the transitional and respiratory zones ( 94) and are the sites of gas exchange. The structures of bronchi and trachea are similar, with cartilaginous rings surrounding the bronchi completely until the bronchi enter the lungs, at which point there are cartilage plates that surround the bronchi. When bronchioles are about 1 mm in diameter, the cartilage plates are not present. Smooth muscle surrounds bronchi and is present until the end of the respiratory bronchioles. The lining mucous membrane of the trachea and bronchi is composed of pseudostratified ciliated columnar epithelium ( Fig. Goblet cells are mucin-secreting epithelial cells and are present in airways until their disappearance at the level of terminal bronchioles. The cilia move in a watery lining layer proximally to help remove luminal material (debris, cells, mucus) by the ciliary mucus escalator. Submucosal glands produce either mucous or serous material depending on their functional type. Mast cells can be identified in the bronchial lumen or between the basement membrane and epithelium. Mast cell heterogeneity has been recognized based on contents and functional properties ( 97). Briefly, mucosal mast cells are not recognized in a formalin-fixed specimen, but connective tissue mast cells are. Mucosal mast cells are present in the lung and contain tryptase, whereas connective tissue mast cells contain tryptase and chymotryptase. Mast cells may participate in airway remodeling because they activate fibroblasts (98), and mast cell derived tryptase is a mitogen for epithelial cells and stimulates synthesis of collagen ( 98). The numbers were increased in patients with severe asthma (53%) compared with moderate (49%) and mild (35%) asthma. Neutrophils have been identified in some ( 100) but not all (101) patients with sudden (<3 hours) death from asthma. Macrophages serve as accessory cells presenting antigens and are present in patients with asthma but are found in greater numbers in patients with chronic bronchitis (98). Macrophages have been detected during both early and late bronchial responses to allergens. These cells are metabolically active in that they can generate prostaglandins and leukotrienes, cytokines, free radicals, and mucus secretagogues ( 98). Alveolar macrophages from asthma patients have been found to release increased quantities of transforming growth factor-b, which could contribute to remodeling and fibrosis. Increased numbers of eosinophils in bronchial biopsy specimens ( 98) and sputum (99) can be expected in patients with asthma. It has been estimated that for every 1 eosinophil in peripheral blood, there are 1,000 in the tissue. Patients with mild asthma have eosinophils detected in bronchial biopsy samples, and eosinophils can be found in postmortem histologic sections ( 100,101). Eosinophils are proinflammatory cells that likely participate in the pathogenesis of airway remodeling in patients with persistent asthma. Epithelial cells are shed especially in patients with severe asthma but also in patients with mild asthma. There are many recognized functions of epithelial cells ( 98), but because they produce neutral endopeptidase, which degrades substance P, the loss of functioning epithelium could lead to potentiated effects of this neuropeptide. Similarly, epithelial cells generate smooth muscle relaxing factors that could be decreased in amount as epithelium is denuded ( 98). Mechanically ventilated patients with asthma were found to have very high quantities of a 92-kDa gelatinase, compared with patients with mild asthma and with ventilated, nonasthmatic subjects ( 102). This enzyme may damage collagen and elastin and the subepithelial basal lamina region ( 102). In this study, mechanically ventilated patients with status asthmaticus had increased numbers of eosinophils and neutrophils, compared with nonventilated patients with mild asthma ( 102). Innervation The nervous system and various muscle groups participate in respiration. Efferent parasympathetic (vagal) nerves innervate smooth muscle cells and bronchial glands. The vagus nerve also provides for afferent innervation of three types of sensory responses. The irritant (cough) reflex is rapidly adapting and originates in the trachea and main bronchi. Pulmonary stretch or slowly adapting afferents are also located in the trachea and main bronchi, whereas C fibers are located in small airways and alveolar walls. Afferent stimulation occurs through the carotid body (sensing oxygen tension) and nervous system chemoreceptors in the medulla (sensing hypercapnia). Examples of innervation, muscles, and respiratory responses Efferent respiratory responses include cervical and thoracic nervous system innervation of respiratory muscles, such as those listed in Table 22. Fortunately, not all respiratory muscles are essential for respiration should a spinal cord injury occur. In addition to efferent parasympathetic innervation of smooth muscle cells and bronchial glands, another source of efferent stimulation is through the nonadrenergic, noncholinergic epithelial sensory nerves. Stimulation of these nerves by epithelial cell destruction that occurs in asthma can trigger release of bronchospastic agonists, such as substance P and neurokinins (A and B), through an antidromic axon reflex.

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Urgent biopsy confirmed a carcinoma and she was referred to an oncologist for further management buy discount glyburide 5mg on line. Review of the first X-ray after the lesion was seen on the second film still failed to iden- tify a lesion quality 5mg glyburide, emphasizing the need to repeat an investigation if there is sufficient clinical suspicion of an abnormality 2.5mg glyburide, even if an earlier investigation is normal. Examination of the breasts in women should be part of the routine examination, particu- larly after the age of 40 years, when carcinoma of the breast becomes common. Fifteen years earlier the patient had had a cadaveric renal transplant for renal failure due to chronic glomerulonephritis caused by immunoglobulin A (IgA) nephropathy. Originally this was with prednisolone and azathioprine, but later it was converted to ciclosporin. His only other medication is propranalol for hyper- tension which he has taken for 20 years. Examination The lesion is as described on the right forearm and there are several solar hyperkeratoses on his cheeks, forehead and scalp (he is bald). No other abnormalities are found apart from the transplant kidney in the right iliac fossa. The risk factors are his age, the many years exposure to sunlight as farmer, and the chronic immunosuppression. There is an increased risk of several different types of malignancy in patients on chronic immunosuppression, and skin cancer is now well recognized as a fre- quent complication of chronic immunosuppression unless preventative measures are used. With improving survival rates for transplant patients in general, there is a potential increase in the incidence and prevalence of skin malignancy. Patients on long-term immunosuppres- sion for whatever reason should be strongly advised to avoid direct exposure to sunlight as much as possible, and certainly not to sunbathe, and to use high-factor barrier creams. They should cover their skin in the lighter months (April to September inclusive in the northern hemisphere) no shorts, sleeveless tops or shirts, and a hat to protect the scalp and forehead. This is particularly irksome but even more important for children and young adults who have a potentially longer period of exposure to sunlight ahead of them. The damage caused to skin by sunlight is cumulative and irreversible, and when transplanted at the age of 50 years this patient had already had over 30 years occupational exposure to ultraviolet radi- ation. His immunosuppression needs to continue and should be kept at as low a dose as is compatible with preventing rejection of his transplant. The diagnosis of the lesion was made by biopsy, which showed a squamous cell cancer. An essential part of the follow-up is regular review, at least 6-monthly, of the skin to detect any recurrence, any new lesions or malig- nant transformation of the solar hyperkeratoses. Her appetite is normal, she has no nausea or vomiting and she has not lost weight. Physical examination at this time was completely normal, with a blood pres- sure of 128/72 mmHg. Investigations showed normal full blood count, urea, creatinine and electrolytes, and liver function tests. An H2 antagonist was prescribed and follow-up advised if her symptoms did not resolve. There was slight relief at first, but after 1 month the pain became more frequent and severe, and the patient noticed that it was relieved by sitting forward. Despite the progressive symptoms she and her husband went on a 2-week holiday to Scandinavia which had been booked long before. During the second week her husband remarked that her eyes had become slightly yellow, and a few days later she noticed that her urine had become dark and her stools pale. Examination She was found to have yellow sclerae with a slight yellow tinge to the skin. The pain has two typical features of carcinoma of the pancreas: relief by sitting forward and radiation to the back. As with obstruction of any part of the body the objective is to define the site of obstruc- tion and its cause. The initial investigation was an abdominal ultrasound which showed a dilated intrahepatic biliary tree, common bile duct and gallbladder but no gallstones. The pancreas appeared normal, but it is not always sensitive to this examination owing to its depth within the body. It showed a small tumour in the head of the pancreas causing obstruction to the common bile duct, but no extension outside the pancreas. The patient underwent partial pancreatectomy with anastamosis of the pancreatic duct to the duodenum. Follow-up is necessary not only to detect any recurrence but also to treat any possible development of diabetes. During the singing of a hymn she suddenly fell to the ground without any loss of consciousness and told the other members of the congregation who rushed to her aid that she had a complete par- alysis of her left leg. She has no relevant past or family history, is on no medication and has never smoked or drunk alcohol. She works as a sales assistant in a bookshop and until recently lived in a flat with a partner of 3 years standing until they split up 4 weeks previously. Examination She looks well, and is in no distress; making light of her condition with the staff. The left leg is completely still during the examination, and the patient is unable to move it on request. Superficial sensation was completely absent below the margin of the left buttock and the left groin, with a clear transition to normal above this circumference at the top of the left leg. There was normal withdrawal of the leg to nociceptive stimuli such as firm stroking of the sole and increasing compression of Achilles tendon. The superficial reflexes and tendon reflexes were normal and the plantar response was flexor. The clues to this are the cluster of: the bizarre complex of neurological symptoms and signs which do not fit neuroanatom- ical principles, e. None of these on its own is specific for the diagnosis but put together they are typical. In any case of dissociative disorder the diagnosis is one of exclusion; in this case the neuro- logical examination excludes organic lesions. It is important to realize that this disorder is distinct from malingering and factitious disease. The condition is real to patients and they must not be told that they are faking illness or wasting the time of staff. The management is to explain the dissociation in this case it is between her will to move her leg and its failure to respond as being due to stress, and that there is no underlying serious disease such as multiple sclerosis. A very positive attitude that she will recover is essential, and it is important to reinforce this with appropriate physical treatment, in this case physiotherapy. The prognosis in cases of recent onset is good, and this patient made a complete recovery in 8 days. Dissociative disorder frequently presents with neurological symptoms, and the commonest of these are convulsions, blindness, pain and amnesia. Clearly some of these will require full neurological investigation to exclude organic disease. She lives alone but one of her daughters, a retired nurse, moves in to look after her. The patient has a long history of rheumatoid arthritis which is still active and for which she has taken 7 mg of prednisolone daily for 9 years. For 5 days since 2 days before starting the antibiotics she has been feverish, anorexic and confined to bed. On the fifth day she became drowsy and her daughter had increasing difficulty in rousing her, so she called an ambulance to take her to the emergency department. Examination She is small (assessed as 50 kg) but there is no evidence of recent weight loss. Her pulse is 118/min, blood pressure 104/68 mmHg and the jugular venous pressure is not raised. Her joints show slight active inflammation and deformity, in keeping with the history of rheumatoid arthritis. This is a common problem in patients on long-term steroids and arises when there is a need for increased glucocorticoid output, most frequently seen in infections or trauma, including surgery, or when the patient has prolonged vomiting and therefore cannot take the oral steroid effect- ively. It is probably due to a combination of reduced intake of sodium owing to the anorexia, and dilution of plasma by the fluid intake. In secondary hypoaldosteronism the renin angiotensin aldosterone system is intact and should operate to retain sodium.

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