The oedema is an effect of the a decreased cardiac output that increases renin release which leads to vasoconstriction and sodium and water retention.

Triamterene is a potassium-sparing diuretic that can cause hyperkalaemia, therefore, it was stopped in this patient. With all other lab results returning normal values and a normal ECG, management will simply require repeating the U & E after one week since the Triamterene has already be stopped.

The patient’s chronic renal failure causes decreased renal hydroxylation of vitamin D which leads to decreased calcium absorption in the gut. Simultaneously, there is also decreased renal excretion of phosphate, and this combination of factors results in increased PTH levels.

Specificity (negative in health)
The ability of a test to correctly classify an individual as disease- free is called the test′s specificity. [Table 2]

Specificity = d / b+d

= d (true negative) / b+d (true negative + false positive)

= Probability of being test negative when disease absent.

Example: One hundred persons with normal angles (diagnosed by ′gold standard′: gonioscopy) are examined by peripheral angle chamber depth examination. Eighty-five persons had normal peripheral angle chamber depth [Table 3]. The specificity of the peripheral angle chamber depth examination to PACG is therefore –

85 / 100 = 85%.

The most probable diagnosis of this patient is Cotard syndrome.

Cotard syndrome is a rare mental disorder where the affected patient believes that they (or in some cases just a part of their body) is either dead or non-existent. This delusion is often difficult to treat and can result in significant problems due to patients stopping eating or drinking as they deem it not necessary. Cotard syndrome is often associated with severe depression and psychotic disorders.

Other options:
– Othello syndrome is a delusional belief that a patients partner is committing infidelity despite no evidence of this. It can often result in violence and controlling behaviour.
– De Clerambault syndrome (otherwise known as erotomania), is where a patient believes that a person of higher social or professional standing is in love with them. Often this presents with people who believe celebrities are in love with them.
– Ekbom syndrome is also known as delusional parasitosis and is the belief that they are infected with parasites or have ‘bugs’ under their skin. This can vary from the classic psychosis symptoms in narcotic use where the user can ‘see’ bugs crawling under their skin or can be a patient who believes that they are infested with snakes.
– Capgras delusion is the belief that friends or family members have been replaced by an identical-looking imposter.

Among the given anti-epileptics the best drug that can be given in this patient is lamotrigine.
Topiramate, carbamazepine, phenytoin, and phenobarbital are all hepatic enzyme inducers and are associated with decreased effectiveness of the oral contraceptive (OCP) due to acceleration of the metabolism of oestrogens and progestogens.
If she is planning on pregnancy then registry studies suggest that lamotrigine would also be the best choice.
Other hepatic enzyme inducers include rifampicin, spironolactone, griseofulvin, etc.

The patients high morning blood sugar levels are suggestive to Somogyi Phenomenon which suggests that hypoglycaemia during the late evening induced by insulin could cause a counter regulatory hormone response that produces hyperglycaemia in the early morning.
Substitution of regular insulin with an immediate-acting insulin analogue, such as Humulin lispro, may be of some help.

The patient presented with sudden-onset headache that is more painful than his usual migraine attacks. This gives a high suspicion of subarachnoid haemorrhage; thus, a CT brain scan should be ordered first to rule this out. However, a normal CT scan is apparent in 30% of patients with subarachnoid haemorrhage and should be referred for lumbar puncture to look for red blood cells.

In mild-to-moderate heroin overdoses, arterial blood gas (ABG) analysis reveals respiratory acidosis. In more severe overdoses, tissue hypoxia is common, leading to mixed respiratory and metabolic acidosis.

The normal range for PaCO2 is 35-45 mmHg (4.67 to 5.99 kPa). Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range (i.e., >45 mm Hg) with an accompanying academia (i.e., pH < 7.35). In chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range, with a normal or near-normal pH secondary to renal compensation and an elevated serum bicarbonate levels (i.e., >30 mEq/L).

Arterial blood gases with pH = 7.31; pCO2 = 7.4 kPa; pO2 = 8.1 kPa would indicate respiratory acidosis.

Historically, high rates of maternal and fetal death have been reported for pregnant women with pulmonary hypertension (30–56% and 11–28%, respectively). The causes of poor maternal outcomes are varied and include risk of death from right heart failure and stroke from intracardiac shunting. Furthermore, there is a high peri-/post-partum risk due to haemodynamic stress, bleeding complications and the use of general anaesthesia, which can all lead to right heart failure.
The most common risk to the foetus is death, with premature birth and growth retardation being reported in successfully delivered children.
CXR is not contraindicated in pregnancy. D-dimers are not used as a diagnostic aid as they are almost always elevated in pregnancy. Nifedipine, although contraindicated in pregnant women may be used judiciously if the need arises.

Turner syndrome (TS) is one of the most common genetic disorders; occurs with an incidence of I: 2,500 female live births. It results from complete or partial chromosome X monosomy. TS is associated with abnormalities of the X chromosome and characteristic clinical features of short stature, gonadal dysgenesis, sexual developmental deficiencies, cardiac and/or renal defects, webbed neck, low-set ears, skeletal deformities including cubitus valgus, a propensity to ear infections and hearing deficits.

The level of haemoglobin A1c (HbA1c), also known as glycated haemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8–12 weeks. Recent studies have been made to correlate between HbA1c and average glucose level.
Using the following formula: Average blood glucose (mmol/l) = (1.98 x 1 HbA1c) – 4.29

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

According to NICE guidelines (2013) all people who have had an acute MI treatment should be offered with ACE inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), a beta-blocker and a statin.

Because the medical history included tonsillitis followed by haematuria and hypertension, there is a strong suspicion of a case of post-streptococcal glomerulonephritis (PSGN). Patients with PSGN usually have serological findings showing depressed serum haemolytic component CH50 and serum concentrations of C3. Sometimes depressed C4 levels are also apparent, but not always, therefore, the answer to this question is: depressed CH50 level.

Hypertension and haematuria are not common presentations in minimal change glomerulonephritis, all other statements are correct.

The dendritic ulceration seen on fluorescein staining of the eye is pathopneumonic for keratitis caused by HSV (herpes simplex virus). Presentation is that of blepharoconjunctivitis. Treatment is required, the treatment is typically topical acyclovir. Topical steroids can make the infection worse. The other answer choices would not have this dendritic pattern seen on fluorescein staining.

The patient is AMA+ and weakly + for anti-dsDNA, suggesting an autoimmune process. She also has gritty eyes, which makes you think Sjogren’s syndrome. She has an elevated ALP and normal AST/ ALT. All of these factors, in addition to her middle age and the fact that she is a woman, make the diagnosis of primary biliary cirrhosis (PBC) most likely. It is associated with conditions (autoimmune) such as Sjogren’s syndrome. The treatment for this disease initially is ursodeoxycholic acid. Liver transplantation is the definitive treatment for end-stage disease.

Results of a randomized trial confirm that the antidepressant sertraline can be used safely in patients with recent MI or unstable angina and is effective in relieving depression in these patients.

There are theoretical reasons for believing that selective serotonin reuptake inhibitors (SSRIs), widely used to treat depression, might increase the risk of gastrointestinal bleeding. Gastroprotective drugs are advocated for high risk patients taking non-steroidal anti-inflammatory drugs, another class of drug that causes gastrointestinal bleeding.

Serotonin is released from platelets in response to vascular injury and promotes vasoconstriction and a change in the shape of the platelets that leads to aggregation. Platelets cannot themselves synthesise serotonin. SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability to form clots and a subsequent increase in the risk of bleeding.

The well established association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding is estimated to result in 700-2000 deaths/year in the UK. This has led to the recommendation that patients in high risk groups should receive gastroprotection in the form of an H2 antagonist, proton pump inhibitor (lansoprazole), or misoprostol.

Proton pump inhibitors have been shown to reduce endoscopically diagnosed mucosal damage and heal ulcers induced by non-steroidal anti-inflammatory drugs but not to reduce the incidence of severe gastrointestinal bleeds.

Intracranial pressure (ICP) is a complex brain modality that determines cerebral perfusion pressure (CPP), which is the difference between arterial blood pressure (ABP), and ICP. Raised ICP reduces CPP and blood delivery to the brain. This jeopardizes cerebral function and organismal survival in many species. A massive rise in ICP is also known to produce an increase in ABP, bradycardia and respiratory irregularities termed Cushing response. This mechanism is generally considered to be an agonal and terminal event occurring in extreme condition of brainstem ischaemia leading to a sympatho-adrenal response.

Hydroxychloroquine is used in the management of SLE as it prevents disease progression and has relatively mild side effects, for instance headache, nausea etc. Its use reduces the usage of corticosteroids. It is particularly effective when the disease is less severe and there is no organ involvement. Cyclophosphamide and prednisolone are indicated in cases of renal, neurological and lung involvement.

Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in the small intestinal endocrine I-cells and cerebral neurons.

Apraclonidine eye drops are initially used to confirm a Horner’s pupil. Apraclonidine stimulates both alpha-1 and alpha-2 receptors. When added to the affected eye, it causes pupil dilation by >2mm because of the relative super sensitivity of this pupil to alpha-1 receptor activity. In a normal pupil, however, it causes constriction due to the more potent activity at the alpha-2 receptor which triggers re-uptake of noradrenaline in the synaptic cleft.

Hydroxy amphetamine is then used to distinguish between first/second or third order neurones. In other words, it will distinguish either a lesion in the brainstem, cervical cord, chest or neck and one affecting above the superior cervical ganglion at the carotid bifurcation. In a normal pupil or a first/second order Horner’s, the pupil will dilate secondary to increased levels of noradrenaline released from the post-synaptic neurones. In a third order neurone, this will not occur. There is no fourth or fifth order neurone.

Bulimia nervosa is a serious, potentially life-threatening eating disorder characterized by a cycle of bingeing and compensatory behaviours such as self-induced vomiting designed to undo or compensate for the effects of binge eating.

According to the DSM-5, the official diagnostic criteria for bulimia nervosa are:
Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
Eating, in a discrete period of time (e.g. within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances.
A sense of lack of control over eating during the episode (e.g. a feeling that one cannot stop eating or control what or how much one is eating).
Recurrent inappropriate compensatory behaviour in order to prevent weight gain, such as self-induced vomiting, misuse of laxatives, diuretics, or other medications, fasting, or excessive exercise.
The binge eating and inappropriate compensatory behaviours both occur, on average, at least once a week for three months.
Self-evaluation is unduly influenced by body shape and weight.
The disturbance does not occur exclusively during episodes of anorexia nervosa.

Antidepressants as a group – particularly selective serotonin reuptake inhibitors (SSRIs) – are the mainstay of pharmacotherapy for bulimia nervosa. These may be helpful for patients with substantial concurrent symptoms of depression, anxiety, obsessions, or certain impulse disorder symptoms. They may be particularly good for patients who have not benefited from or had suboptimal response to suitable psychosocial therapy or who have a chronic, difficult course in combination with other treatments.

Food and Drug Administration (FDA) approved treatments
Fluoxetine (Prozac): Initial dose 20 mg/d with advance over 1–2 weeks to 60 mg/d in the morning as tolerated. Some patients may need to begin at a lower dose if side effects are intolerable. A maximum dose of 80 mg/d may be used in some cases.

Transposition of the great arteries results in a significant hypoxemic status that is observed clinically by central cyanosis. The bluish discoloration of the skin and mucous membranes is therefore the basic pattern of clinical presentation in transposition. Its onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. Limited intercirculatory mixing, usually present if the ventricular septum is intact or the atrial septal defect is restrictive, is related to progressive and profound central cyanosis evident within the first hours of life. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy. Heart murmurs associated with left outflow tract obstruction, due to a persistent arterial duct or a septal defect may be heard, but they are not a constant finding.

The history gives you a woman who is on inhaled steroid therapy. It is always a good idea for patients to rinse their mouths well after using inhaled steroids. Odynophagia (pain on swallowing) is a symptom of oesophageal candidiasis, which is the most likely answer given the steroids. Typically, you might see this in someone who is immunocompromised (classically, in HIV+ patients).

Henoch-Schönlein purpura (HSP) rashes are commonly found on the legs, feet, and buttocks while Immune thrombocytopenia (ITP) rashes manifest predominantly on the lower legs. HSP happens following a sore throat while ITP usually happens following an URTI or Flu. HSP is an inflammation of a blood vessel (vasculitis) while ITP is immune mediated insufficiency of platelets.

After renal transplantation, cytomegalovirus has been identified to affect 1/4 of the post-op patients. It is the most common viral infection causing morbidity and mortality in post-op patients in the first 3 months.

Scabies is an infection caused by a microscopic mite known as Sarcoptes scabies. The chief presenting complaint is itching especially in skin folds and mostly during night. It spreads from one person to another through skin contact, and therefore it is more prevalent in crowded areas like hospitals, hostels and even at homes where people live in close contact with each other. Treatment options include benzyl benzoate, ivermectin, sulphur and permethrin.

Patients with compressive neuropathy of the ulnar nerve typically describe numbness and tingling of the ulnar-sided digits of the hand, classically in the small finger and ulnar aspect of the ring finger. Among the general population, symptoms usually begin intermittently and are often worse at night, particularly if the elbow is flexed while sleeping. As the disease progresses, paraesthesia may occur more frequently and during the daytime.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

The NICE 2017 guidelines state that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Inhaled corticosteroid e.g. Beclomethasone), a leukotriene receptor antagonist (LTRA) should be added.
If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks.

This recommendation is also stated in NICE 2019 guidelines.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes.

In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC). However, LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.

This patient has developed a venous sinus thrombosis peri-partum, resulting in her symptoms. Anticoagulation therapy including Heparin improves outcomes.

The risk factors for bladder cancer are:

1. Smoking
2. Exposure to aniline dyes in the printing and textile industry
3. Exposure to rubber manufacturing
4. Cyclophosphamides
5. Schistosomiasis.

Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum and specifically transported through the Golgi apparatus to the trans-Golgi network, from which transport vesicles bud to deliver them to the endosomal/lysosomal compartment. The explanation of how the lysosomal enzymes are accurately recognized and selected over many other proteins in the trans-Golgi network relies on them being tagged with a unique marker: the mannose-6-phosphate (M6P) group, which is added exclusively to the N-linked oligosaccharides of lysosomal soluble hydrolases, as they pass through the cis-Golgi network. Generation of the M6P recognition marker depends on a reaction involving two different enzymes: UDP-N-acetylglucosamine 1-phosphotransferase and α-N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase.

Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

The number needed to treat (NNT) is valuable information in treatment decisions. NNT is the inverse of the absolute risk reduction (1/ARR) between two treatment options.

The most probable diagnosis of this patient is Cotard syndrome.

Cotard syndrome is a rare mental disorder where the affected patient believes that they (or in some cases just a part of their body) is either dead or non-existent. This delusion is often difficult to treat and can result in significant problems due to patients stopping eating or drinking as they deem it not necessary. Cotard syndrome is often associated with severe depression and psychotic disorders.

Other delusional syndromes:
– Othello syndrome is a delusional belief that a patients partner is committing infidelity despite no evidence of this. It can often result in violence and controlling behaviour.
– De Clerambault syndrome (otherwise known as erotomania), is where a patient believes that a person of higher social or professional standing is in love with them. Often this presents with people who believe celebrities are in love with them.
– Capgras syndrome is characterised by a person believing their friend or relative had been replaced by an exact double.
– Couvade syndrome is also known as ‘sympathetic pregnancy’. It affects fathers, particularly during the first and third trimesters of pregnancy, who suffer the somatic features of pregnancy.
– Ekbom syndrome is also known as delusional parasitosis and is the belief that they are infected with parasites or have ‘bugs’ under their skin. This can vary from the classic psychosis symptoms in narcotic use where the user can ‘see’ bugs crawling under their skin or can be a patient who believes that they are infested with snakes.

The patient (known case of acromegaly) seems to have developed cholelithiasis (presenting with right upper quadrant pain) probably due to octreotide.

It is a long-acting analogue of somatostatin which is released from D cells of the pancreas and inhibits the release of growth hormone, glucagon, and insulin.

Uses
– Acute treatment of variceal haemorrhage
– Acromegaly
– Carcinoid syndrome
– Prevent complications following pancreatic surgery
– VIPomas
– Refractory diarrhoea

Adverse effects
Gallstones (secondary to biliary stasis)

Other options:
– Bromocriptine – a dopamine agonist with side effects arising from its stimulation of the brain vomiting centre.
– Desmopressin – predominantly used in patients with diabetes insipidus by increasing the presence of aquaporin channels in the distal collecting duct to increase water reabsorption from the kidneys. The main side effects include headache and facial flushing due to hypertension.
– Metformin – mainly reduces hepatic gluconeogenesis in patients with type 2 diabetes, common side effects include diarrhoea, vomiting, and lactic acidosis
– Levothyroxine – synthetic thyroxine used in patients with hypothyroidism, common side effects result from incorrect dosing and mimic the symptoms of hyperthyroidism.

Throughout pregnancy the tubular reabsorption of glucose is less effective than in the non-pregnant state, this leads to glycosuria.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

After the exposure to chickenpox while pregnant, even if the patient is negative for antibodies she requires immunoglobulin to prevent further issues.

The patient has presented with signs of small cell lung cancer. The associated proximal muscle weakness is most probably due to dermatomyositis which occurs as a paraneoplastic syndrome associated with lung carcinoma. In most cases, the first symptom is a distinctive skin rash on the face, eyelids, chest, nail cuticle areas, knuckles, knees or elbows. The rash is patchy and usually a bluish-purple colour. Corticosteroids are helpful in the management of the cutaneous changes and muscle weakness.

Chicken pox in adults may manifest with acute encephalitis, causing the confusional syndrome known as delirium. Blisters on the trunk favour the diagnosis. The trip to Italy however seems unimportant since the incubation period of chicken pox is 10 to 21 days.

Psoriasis is a long-lasting autoimmune disease which is characterized by patches of abnormal skin. These skin patches are typically red, itchy, and scaly commonly on the extensor surfaces. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn’s disease, and depression. Psoriatic arthritis affects up to 30% of individuals with psoriasis. Psoriasis is mediated by type 1 helper T cells which are involved in the cell mediated response, rather than type 2 helper T cells

There are many possible causes of a red eye. It is important to be able to recognise the causes which require urgent referral to an ophthalmologist. Acute angle closure glaucoma presents with severe pain, decreased visual acuity, patient seeing haloes, semi-dilated pupils, and hazy cornea. Anterior uveitis presents with acute onset pain, blurred vision and photophobia, with small, fixed oval pupils and ciliary flush.

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Arthrocentesis should be performed, especially in acute cases.
Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals.
Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils.
X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis).
Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group). The relative risk is mistaken by some, with the odds ratio and absolute risk. Relative risk is the ratio of the probability of an event occurring with an exposure versus the probability of the event occurring without the exposure. Thus to calculate the relative risk, we must know the exposure status of all individuals (either exposed or not exposed). This implies that relative risk is only appropriate for cases where the exposure status and incidence of disease can be accurately determined such as prospective cohort studies.

The patient is most likely suffering from Waldenström’s macroglobulinemia in which IgM paraproteinemia is found. Hyperviscosity syndrome can occur in the patients accounting for 10–15% of the cases.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Prednisolone although has many undesirable side effects it may be considered relatively safe compared to the drugs that are provided here. Prolonged treatment with sulphasalazine may depress semen quality and cause irreversible infertility. Methotrexate and leflunomide both inhibit purine/pyrimidine synthesis (the former by inhibiting folate metabolism) and are contraindicated in pregnancy or while trying to conceive. In males, a temporary or permanent decrease in sperm count may occur with cyclophosphamide. Because the recovery of fertility after cyclophosphamide therapy is variable, sperm banking should be considered before treatment is begun.

Haemoptysis is a symptom which indicates the worsening of mitral stenosis. It occurs due to the rupture of pulmonary veins or the capillary system due to pulmonary venous hypertension. Elevated serum creatinine is seen in worsening aortic stenosis. Worsening of tricuspid regurgitation causes ascites and a pulsatile liver.

Methadone and cocaine can cause QT prolongation through the direct effects on the resting membrane potential. Methadone can increase QT dispersion in addition to QT interval. Methadone inhibits the Human Ether-a-go-go Related Gene (hERG) and causes QTc prolongation and development of Torsades de point. Brugada-like syndrome is another condition found in methadone users which predisposes the users to life-threatening ventricular tachycardia and sudden cardiac death.

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.
DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of thoracic aortic aneurysm.

Thoracic aortic aneurysms are usually asymptomatic however chest pain is most commonly reported symptom. Left hemidiaphragm paralysis, because of left phrenic nerve palsy, is a very rare presentation of thoracic aortic aneurysm.
Thoracic aortic aneurysm may present atypical symptoms such as dysphagia due to compression of the oesophagus; hoarseness due to vocal cord paralysis or compression of the recurrent laryngeal nerve; superior vena cava syndrome due to compression of the superior vena cava; cough, dyspnoea or both due to tracheal compression; haemoptysis due to rupture of the aneurysm into a bronchus; and shock due to rupture of the aneurysm.
Common causes of phrenic nerve palsy include malignancy such as bronchogenic carcinoma, as well as mediastinal and neck tumours. Phrenic nerve palsy can also occur due to a penetrating injury or due to iatrogenic causes arising, for example, during cardiac surgery and central venous catheterization. Many cases or phrenic nerve palsy are idiopathic.

This patient is having a myasthenic crisis. Opinions vary as to whether plasmapheresis or intravenous immunoglobulins should be given first-line. Plasmapheresis usually works much faster, but is more costly due to equipment.
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases. Myasthenia gravis is more common in women (2:1).

The most common type of Hodgkin’s lymphoma (HL) is nodular sclerosing.

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

According to the histological classification, there are four types of HL:

1. Nodular sclerosing: most common (around 70%), more common in women, associated with lacunar cells, good prognosis

2. Mixed cellularity: Around 20%, associated with a large number of Reed-Sternberg cells, good prognosis

3. Lymphocyte-predominant: Around 5%, Reed-Sternberg cells with nuclei surrounded by a clear space found, best prognosis

4. Lymphocyte-depleted: rare, worst prognosis

This woman has a history that is suggestive of Guillain– Barré syndrome. This may be precipitated by Campylobacter, and her history of recent diarrhoeal illness is pointing towards that. Certain features point to a poor prognosis, including rapidity of onset, reduced vital capacity or respiratory failure, age >40 and reduced amplitude of compound muscle action potential. Her inability to perform spirometry and desaturating whilst lying flat are suggestive of impending respiratory muscle weakness. Review for consideration of ventilation is recommended. Further management of choice for Guillain-Barre syndrome is IV immunoglobulins. Steroids have no value in the treatment of the condition.

A prominent A wave is observed in the jugular venous pulse and this indicates the presence of established pulmonary hypertension. In addition the pulmonic component of the second heart sound (P2) may be increased and the P2 may demonstrate fixed or paradoxical splitting. The signs of right ventricular failure include a high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral oedema.

Cyclophosphamide is a cytotoxic alkylating agent that acts by causing cross-linking of DNA strands. Its major adverse effects include haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma.

Cardiomyopathy is caused by doxorubicin and ototoxicity is caused by cisplatin. Alopecia and weight gain are associated with a variety of chemotherapeutic agents especially those that treat breast cancers (e.g. paclitaxel).

The water deprivation test (i.e., the Miller-Moses test), is a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis. It is typically performed in patients with more chronic forms of Diabetes Insipidus (DI). The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality will be above 750 mOsm/kg after water deprivation.
A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

The most COMMON site of inflammation from ulcerative colitis is the rectum, making this the correct answer. This is simply a fact you need to memorize. In general, ulcerative colitis only occurs in colorectal regions– nothing in the small bowel (unless there is backwash into the terminal ileum) and nothing further up the GI tract. In Crohn’s it can affect the entire GI tract from mouth to anus.

Brugada syndrome is an autosomal dominant disorder characterized by sudden cardiac death. The positive family history and characteristic ECG findings are in favour of Brugada syndrome. Usually the physical findings are normal.

Peroneal nerve injury is also known as foot drop. The common peroneal nerve supplies the ankle and toe extensor muscle groups as well as sensation over the dorsum of the foot; thus, there is also loss of sensation in these cases.

The patient is presenting with symptoms of lateral medullary syndrome also known as Wallenberg’s syndrome or posterior inferior cerebellar artery syndrome, where the symptoms are due to an ischemia in the brainstem. The classical symptoms include contralateral sensory deficits of the trunk region paired with ipsilateral facial sensory deficits.

Acute, symptomatic hypocalcaemia is treated with 10ml of 10% calcium gluconate over 10 minutes.

The diagnosis is Refsum’s disease. This is an autosomal recessive disorder that causes a sensorimotor peripheral neuropathy. It is caused by defective alpha oxidation of phytanic acid leading to its accumulation in tissues. Cardiac conduction abnormalities and cardiomyopathies may also occur.
Epiphyseal dysplasia causes a characteristic shortening of the fourth toe. Serum phytanic acid levels are elevated. Treatment is by dietary restriction of foods containing phytanic acid (dairy products, fish, beef and lamb).

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms of bronchiectasis include:
– a persistent productive cough
– breathlessness.

The 3 most common causes in the UK are:
– a lung infection in the past, such as pneumonia or whooping cough, that damages the bronchi
– underlying problems with the immune system (the body’s defence against infection) that make the bronchi more vulnerable to damage from an infection
– allergic bronchopulmonary aspergillosis (ABPA) – an allergy to a certain type of fungi that can cause the bronchi to become inflamed if spores from the fungi are inhaled

In restless leg syndrome (RLS), males and females are thought to be equally affected. RLS is a syndrome of spontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population and a family history may be present.

The classic history in this high risk patient is suggestive of a dissecting aortic aneurysm. His transoesophageal echocardiogram confirms the diagnosis. ST elevation in ECG is probably due to the extension of the dissection of the aorta which results in compromised coronary blood supply.

Drug induced lupus typically presents with pulmonary involvement and no renal or neurological involvement. Hence glomerulonephritis would be highly unlikely in this case. Rash and arthralgias are classic presentations. Pleurisy can be present as pulmonary involvement may occur with DILE.

The patient has Meigs syndrome. Meigs syndrome is defined as a triad of benign ovarian tumour with ascites and pleural effusion that resolves after resection of the tumour. Ovarian fibromas constitute the majority of the benign tumours seen in Meigs syndrome.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

The farmer has most likely ingested an organophosphate insecticide.
Organophosphorus compounds are used widely as:
• Insecticides – Malathion, parathion, diazinon, dichlorvos
• Nerve gases – Soman, sarin, tabun, VX
• Ophthalmic agents – Echothiophate
• Antihelmintics – Trichlorfon
• Herbicides – merphos
• Industrial chemical (plasticizer) – Tricresyl phosphate
Signs and symptoms of Organophosphorus Poisoning (OPP) can be classified as:
• Muscarinic effects:
o Cardiovascular – Bradycardia, hypotension
o Respiratory – Rhinorrhoea, bronchorrhea, bronchospasm, cough, severe respiratory distress
o Gastrointestinal – Hypersalivation, nausea and vomiting, abdominal pain, diarrhoea, faecal incontinence
o Genitourinary – Incontinence
o Ocular – Blurred vision, miosis
o Glands – Increased lacrimation, diaphoresis
• Nicotinic effects:
o Muscle fasciculation, weakness, cramping, diaphragmatic failure, and autonomic side effects include: hypertension, tachycardia, and mydriasis.
• Central nervous system (CNS) effects:
o Anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, coma, apnoea
Mainstay Treatment:
• Decontamination
• Securing Airway, Breathing and Circulation
• Atropine
• Pralidoxime
• Benzodiazepines

Tetracycline is not recommended in pregnancy because of the risk to fetal development (bones, teeth!). Metronidazole in pregnancy: currently not thought to be an increased risk in pregnancy; however this is not effective against chlamydia. Amoxicillin is shown to be an adequate treatment for chlamydia, so this is the correct answer.

Koilonychia, known as spoon nails, is a condition of the nails bending inwards, taking the shape of a spoon. This is a strong indication of iron-deficiency anaemia (IDA). The rest of the patient’s symptoms further indicate IDA.

Lithium acts by:
– I inhibiting postsynaptic D2 receptor super sensitivity
– Altering cation transport in nerve and muscle cells and influencing reuptake of serotonin or norepinephrine
– Inhibiting phosphatidylinositol cycle second messenger systems

The NICE guidelines for depression and bipolar disorder both recommend Lithium as an effective treatment; patients who take lithium should have regular blood tests to monitor the amount of lithium in their blood (every 3 months), and to make sure the lithium has not caused any problems with their kidneys or thyroid (every 6 months).

Lithium adverse effects include:
– Leucocytosis (most patients) which is when the white cells are above the normal range in the blood.
– Polyuria/polydipsia (30-50%)
– Dry mouth (20-50%)
– Hand tremor (45% initially, 10% after 1 year of treatment)
– Confusion (40%)
– Decreased memory (40%)
– Headache (40%)
– Muscle weakness (30% initially, 1% after 1 year of treatment)
– Electrocardiographic (ECG) changes (20-30%)
– Nausea, vomiting, diarrhoea (10-30% initially, 1-10% after 1-2 years of treatment)
– Hyperreflexia (15%)
– Muscle twitch (15%)
– Vertigo (15%)

First and foremost, the patient should be put on ECG monitoring to identify the cardiac state, and because of the markedly raised serum potassium, a calcium gluconate bolus will have the immediate effect of moderating the nerve and muscle performance.

Bivalirudin is a competitive, direct thrombin inhibitor. It inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade. So inhibition of fibrinogen conversion to fibrin inhibits thrombus development.

SIGN produced guidelines in 2008 on the management of migraines. Key points include that if patients have migraines with aura then the combined oral contraceptive (COC) is absolutely contraindicated due to an increased risk of stroke (relative risk 8.72).

According to the updated GMC guidelines, patient safety is more important than anything else, thus the correct thing to do is inform your colleague’s employing body.

This case is most likely tumour lysis syndrome, often occurring immediately after starting chemotherapy because the tumour cells are killed and their contents are released into the bloodstream. After treating lymphomas or leukaemia, there is a sudden hypocalcaemia, hyperphosphatemia, and hyperkalaemia

HIV-associated nephropathy (HIVAN) show typical findings of scarring called focal segmental glomerulosclerosis (FSGS) and microcystic tubular dilatation, prominent podocytes, and collapsing capillary loops.

Chronic hepatitis B patients have an increased risk of hepatocellular carcinoma. In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have+HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, +anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. It is important to remember these serologies, it will get you a lot of points on the test.

Lesions in the optic radiation can cause a homonymous hemianopia with macular sparing, as a result of collateral circulation offered to macular tracts by the middle cerebral artery.
Lesions in the optic tract also cause a homonymous hemianopia, but without macular sparing.
Lesions in the optic chiasm, optic nerve, and temporal lobe cause bitemporal hemianopia, ipsilateral complete blindness, and superior homonymous quadrantanopia respectively.

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. In Mallory-Weiss tear, they typically present as a hemodynamically stable patient after a night of binge drinking and excessive resultant vomiting. Given his EGD did not show any other pathology and he is now stable, he can be discharged home.

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

Normal distribution describes the spread of many biological and clinical measurements. Usually, 68.3% lies within 1 standard deviation (SD) of the mean, 95.4% lies within 2 SD of the mean and 99.7% lies within 3 SD of the mean.

Renal biopsy in this patient will most likely show thickened glomerular basement membrane with deposits of IgG and C3 as a result of membranous glomerulonephritis that has caused the nephrotic syndrome in this patient. Membranous glomerulonephritis in this case is most likely associated with an underlying bronchial carcinoma, consistent with the patient’s smoking history and physical presentation.

Carbon monoxide has high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. There are approximately 50 deaths per year from accidental carbon monoxide poisoning in the UK. In these circumstances, antidotal therapy to block alcohol dehydrogenase with ethanol or 4-MP alone is insufficient to treat the poisoning. Data suggest that a severe lactic acidosis needs initial correction and in this patient the most appropriate treatment would be IV fluids with bicarbonate to correct the metabolic acidosis. Haemodialysis may be required thereafter.

Infection of chickenpox in the first half of pregnancy can result in congenital varicella syndrome. It presents as cerebral, cortical and cerebellar hypoplasia with convulsions and rudimentary digits. Prevention is by administering varicella vaccine, even before pregnancy. Varicella immunoglobulin is administered to pregnant women who are exposed to infection. Infection during pregnancy is treated with acyclovir.

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Behçet disease is a rare vasculitic disorder that is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. The systemic manifestations can be variable. Ocular disease has the greatest morbidity, followed by vascular disease generally from active vasculitis. Cutaneous manifestations can occur in up 75% of patients with Behcet disease and can range from acneiform lesions, to nodules and erythema nodosum. GI manifestations can be severe. Differentiating Behçet disease from active inflammatory bowel disease can be clinically difficult. Herpes would have ideally responded to acyclovir. Sarcoidosis does not have genital and oral ulcerations.

Burkitt lymphoma is a germinal centre B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer.

Diabetes is a risk factor for hepatocellular carcinoma. Screening has been shown to be effective. Bevacizumab is not used for advanced cases. The incidence is higher in men. Alcohol is not the most common underlying cause worldwide; this is from cirrhosis from diseases like hepatitis B and C.

Tinea manum is a superficial fungal infection of the hands characterised by dry scaly rash and also involves the interdigital spaces of the hands.

Tinea pedis is a fungal infection of feet, whereas onychomycosis represents a fungal infection of the nails, characterised by nail dystrophy, hyperkeratosis.

Kerion is the name given to secondarily infected tinea capitis leading to a soft boggy swelling over the scalp.

Psoriasis presents as silvery scales over the extensors of the body and it may involve the nails, scalp and joints.

Deletion of part of chromosome 5 or 7 is a poor prognostic feature for acute myeloid leukaemia (AML).

AML is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly.

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

Acute promyelocytic leukaemia (APL) is an aggressive form of AML.

Intestinal phosphate absorption is mediated by both transcellular and paracellular routes. The 1,25(OH)2D increases intestinal transcellular phosphate absorption at least in part by enhancing expression of type 2b sodium–phosphate cotransporter, thus increasing plasma phosphate.

This patient is a case of chronic myeloid leukaemia (CML) and should be started on imatinib as the first-line drug of choice.

Retinitis pigmentosa is a genetic disorder primarily affecting the peripheral retina resulting in tunnel vision. Night blindness is often the initial sign. Fundoscopy exam reveals black bone spicule-shaped pigmentation in the peripheral retina, and mottling of the retinal pigment epithelium.

Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT.