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.

The chronic asymptomatic carrier state is thought to be why there is continued appearance of the bacterium in human populations. As shedding of the organism is intermittent and sometimes at low levels, methods to detect it have been limited. The Salmonella typhi may be cultured from intestinal secretions, faeces or urine in chronic carriers and is recommended to confirm the diagnosis. Vi agglutination test can also be high in normal people in areas with typhoid endemic. Full blood count or blood culture would not be helpful to determine carrier status. Widal antigen test is unable to differentiate carriers from people with a hx of prior infection.

Blue tinge of vision/cyanopsia is caused due to the intake of sildenafil citrate.

Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction.
It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.

Uses:
It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.

Adverse effects:
Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.
It can also cause hypotension, dizziness, and rhinitis.

Note: Xanthopsia (yellow-green vision) may occur secondary to treatment with digoxin.

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.

From the given answers, complete heart block with a narrow complex QRS complex is associated with the least risk of asystole. Transvenous pacing is indicated by the other given responses.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

CMV is the best answer . Weight loss is mostly caused by HIV, which commonly presents with retinal haemorrhage and retinopathy when associated with CMV.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. The other factors that are mentioned do not play a key prognostic role.

Haemophilia B (Christmas disease), is the deficiency of clotting factor IX and is inherited in an X-linked recessive pattern. The factor IX level dictates the disease severity and established arthropathy is usually seen in those with severe disease.

The aforementioned patient’s history and presentation is consistent with the development of hemarthrosis. Joint aspiration is not recommended. The treatment, therefore, should be intravenous replacement of the deficient clotting factor with plasma-derived factor IX concentrate.

The other listed options are ruled out because:
1. Joint aspiration is not preferred over the administration of clotting factor as the first step of management.
2. DDAVP (desmopressin) can increase factor VIII levels transiently in those with mild haemophilia A and is useful prior to minor surgical procedures in such patients.
3. Cryoprecipitate is rich in fibrinogen, factor VIII, and von Willebrand factor and is used in the treatment of haemophilia A.

Traditionally two forms of macular degeneration are seen:
– Dry (geographic atrophy) macular degeneration is characterized by drusen – yellow round spots in Bruch’s membrane.
– Wet (exudative, neovascular) macular degeneration is characterized by choroidal neovascularization. Leakage of serous fluid and blood can subsequently result in a rapid loss of vision. This carries the worst prognosis.

This patient has a poorly controlled T2DM with an underlying diabetic nephropathy. The histological findings are Kimmelstiel-Wilson lesions (nodular glomerulosclerosis) and hyaline arteriosclerosis. This is due to nonenzymatic glycosylation.

Diabetic nephropathy is the chronic loss of kidney function occurring in those with diabetes mellitus. Protein loss in the urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) and result in the nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD). It usually is slowly progressive over years.

The most common causes of a sudden painless loss of vision are as follows:
– Ischaemic optic neuropathy (e.g. temporal arteritis or atherosclerosis)
– Occlusion of central retinal vein
– Occlusion of central retinal artery
– Vitreous haemorrhage
– Retinal detachment

Retinal detachment is a cause of sudden painless loss of vision. It is characterised by a dense shadow starting peripherally and progressing centrally.

Vitreous haemorrhage usually presents with dark spots.

Central retinal artery and central retinal vein occlusion do not usually present with progressing dense shadow.

This man’s lack of ischaemic risk factors makes ischaemic optic neuropathy less likely.

A lucid interval, in which the patient portrays a temporary improvement in condition after a traumatic brain injury, is especially indicative of an epidural haematoma.

Type I pneumocyte: The cell responsible for the gas (oxygen and carbon dioxide) exchange that takes place in the alveoli. It is a very thin cell stretched over a very large area. This type of cell is susceptible to a large number of toxic insults and cannot replicate itself.
Type II pneumocyte: The cell responsible for the production and secretion of surfactant (the molecule that reduces the surface tension of pulmonary fluids and contributes to the elastic properties of the lungs). The type 2 pneumocyte is a smaller cell that can replicate in the alveoli and will replicate to replace damaged type 1 pneumocytes. Alveolar macrophages are the primary phagocytes of the innate immune system, clearing the air spaces of infectious, toxic, or allergic particles that have evaded the mechanical defences of the respiratory tract, such as the nasal passages, the glottis, and the mucociliary transport system. The main role of goblet cells is to secrete mucus in order to protect the mucous membranes where they are found. Goblet cells accomplish this by secreting mucins, large glycoproteins formed mostly by carbohydrates.

Fundoscopy reveals flame-shaped haemorrhages which are specific to central retinal vein occlusion (CRVO). In CRA thrombosis, fundoscopy would show a cherry-red spot. A patient with retinal detachment would give a characteristic history of seeing flashes of light and floaters. Background retinopathy is associated with diabetes.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.

Contraindications:
– Patients taking nitrates and related drugs such as nicorandil
– Hypotension
– Recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Side-effects:
Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic Neuropathy
Nasal congestion
Flushing
Gastrointestinal side-effects
Headache

The patient’s presentation is consistent with diabetes insipidus: eunatreaemia, high serum osmolality, and inappropriately dilute urine, which leads to the suspicion of lithium-induced diabetes insipidus.

The question describes a patient who has had an ileal resection. Bile acids are reabsorbed in the distal ileum. Since this has been resected in this patient, one would expect her to have malabsorption of bile acids, causing her diarrhoea. This is a more likely correct answer than a Crohn’s flare, bacterial overgrowth, gastroenteritis, or tropical sprue, given the details included in the question prompt.

Patients who have autonomously functioning nodules should be treated definitely with radioactive iodine or surgery.
Na131 I treatment – In the United States and Europe, radioactive iodine is considered the treatment of choice for Toxic Nodular Goitre. Except for pregnancy, there are no absolute contraindications to radioiodine therapy.

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Blood tests are used to look for signs of an allergic reaction. This includes evaluating your immunoglobulin E (IgE) level. This level is increased with any type of allergy. Many people with asthma have higher than normal IgE levels. In ABPA however, the IgE level is extremely high (more than 1000 ng/ml or 417 IU/ml). In addition to total IgE, all patients with ABPA have high levels of IgE that is specific to Aspergillus. A blood test can be done to measure specific IgE to Aspergillus. A blood or skin test for IgE antibodies to Aspergillus can be done to see if a person is sensitized (allergic) to this fungus. If these skin tests are negative (i.e. does not show a skin reaction) to Aspergillus fumigatus, the person usually does not have ABPA.
Therefore, there should be no change in medication since this patient does not have ABPA.

Betahistine is a histamine analogue that has been the mainstay treatment drug for Meniere’s disease.

In statistical hypothesis testing there are 2 types of errors:
– type I: the null hypothesis is rejected when it is true – i.e. Showing a difference between two groups when it doesn’t exist, a false positive.
– type II: the null hypothesis is accepted when it is false – i.e. Failing to spot a difference when one really exists, a false negative.

This is a low protein level, indicating the fluid is transudative. The only answer choice that is a transudative fluid is in hepatic cirrhosis. Exudative fluid would be seen in tuberculous peritonitis, peritoneal lymphoma, with liver mets, and with intra-abdominal malignancy.

Normal distribution, also known as the Gaussian distribution, is a probability distribution that is symmetric about the mean. The normal distribution has the following properties:
– It is symmetric around the mode, the median and the mean of the distribution.
– It is unimodal
– The area under the curve and over the x-axis is unity (i.e. equal to one).
– Its density has two inflection points.
– Its density is log-concave.
The standard deviation (SD) is a measure of how much dispersion exists from the mean. SD = square root (variance)

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles, thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which results in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

Achondroplasia is the most common type of short-limb disproportionate dwarfism. A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. All people with achondroplasia have a short stature.
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Examination of the infant after birth shows increased front-to-back head size. There may be signs of hydrocephalus. It may be diagnosed radiographically at birth, or becomes obvious within the first year with disparity between a large skull, normal trunk length and short limbs.

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.

Synacthen test interpretation:
– Basal Cortisol level should be greater than 180nmol/L
– 30min or 60min Cortisol should be greater than 420nmol/L (whatever the basal level)
– The increment should be at least 170nmol/L, apart from in severely ill patients where adrenal output is already maximal.
The patient’s results show that she has Acute Adrenal Insufficiency
The guidelines include the following recommendations for emergency treatment:
Administer hydrocortisone: Immediate bolus injection of 100 mg hydrocortisone intravenously or intramuscularly followed by continuous intravenous infusion of 200 mg hydrocortisone per 24 hours (alternatively, 50 mg hydrocortisone per intravenous or intramuscular injection every 6 h)
Rehydrate with rapid intravenous infusion of 1000 mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4-6 L in 24 h; monitor for fluid overload in case of renal impairment and elderly patients)
Contact an endocrinologist for urgent review of the patient, advice on further tapering of hydrocortisone, and investigation of the underlying cause of the disease, including the diagnosis of primary versus secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an endocrinologist; in patients with primary adrenal insufficiency, mineralocorticoid replacement must be initiated (starting dose 100 μg fludrocortisone once daily) as soon as the daily glucocorticoid dose is below 50 mg of hydrocortisone every 24 hours

Drug induced lupus is usually positive for antinuclear and antihistone antibodies, typically without renal or neurologic involvement. However, pulmonary involvement is common. Drugs that can induce lupus include isoniazid, hydralazine, procainamide, chlorpromazine, and other anticonvulsants.

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.

An atheroma is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.

Digoxin acts by inhibiting the Na+/K+ ATPase pump.
Digoxin is a cardiac glycoside now mainly used for rate control in the management of atrial fibrillation. As it has positive inotropic properties it is sometimes used for improving symptoms (but not mortality) in patients with heart failure.

Mechanism of action:
It decreases the conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and atrial flutter.
It increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. It also stimulates the vagus nerve.

Digoxin toxicity:
Plasma concentration alone does not determine whether a patient has developed digoxin toxicity. The likelihood of toxicity increases progressively from 1.5 to 3 mcg/l.
Clinical feature of digoxin toxicity include a general feeling of unwell, lethargy, nausea & vomiting, anorexia, confusion, xanthopsia, arrhythmias (e.g. AV block, bradycardia), and gynaecomastia

Precipitating factors:
Hypokalaemia
Increasing age
Renal failure
Myocardial ischemia
Hypomagnesaemia, hypercalcemia, hypernatremia, acidosis
Hypoalbuminemia
Hypothermia
Hypothyroidism
Drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in the distal convoluted tubule, therefore, reduce excretion), ciclosporin. Also, drugs that cause hypokalaemia e.g. thiazides and loop diuretics.

Management of digoxin toxicity:
Digibind
Correct arrhythmias
Monitor and maintain potassium levels within the normal limits.

Anti-TNF-α therapy is effective for patients with arthritis but it can oftentimes lead to the reactivation of latent TB. Hence it should be used with great caution in patients with a past history of TB or current infection.

Finasteride inhibits the formation of dihydrotestosterone.
Finasteride is a 5α-reductase inhibitor and thus, inhibits the conversion of testosterone to dihydrotestosterone (DHT).

DHT is much more active than testosterone and binds more avidly to cytoplasmic receptors. DHT stimulates prostate growth and may be responsible for benign prostatic hyperplasia in the elderly.

Thus, finasteride can cause a reduction in prostatic volume and help in managing a patient with benign prostatic hyperplasia.

Osteoblastic (or sclerotic) bony metastases, characterized by deposition of new bone, present in prostate cancer, carcinoid, small cell lung cancer, Hodgkin lymphoma or medulloblastoma. The other cancers listed in the options are osteolytic.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

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.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

This patient shows classic symptoms of autosomal-dominant polycystic kidney disease (ADPKD). The abdominal pain and early satiety is caused by the enlarged kidneys that were apparent from the physical examination. Additionally, hypertension is a common symptom along with the systolic murmur that was heard, suggesting mitral valve involvement. In ADPKD cases, the most common extra-renal manifestation is the development of liver cysts which are associated with hepatomegaly.

The pons is above the level of decussation of the corticospinal tracts so a pontine lesion would cause a contralateral limb weakness.
The facial motor nucleus is located in the pons and supplies the ipsilateral facial muscles.
A right cerebral lesion would give left upper and lower limb weakness. It would also cause a left sided facial weakness.
A left cerebral lesion would give right upper and lower limb weakness with right facial weakness.
Finally, a cervical spinal cord lesion would not cause a facial weakness.

Hyperchylomicronaemia is an increase (markedly) in chylomicrons, and this can cause acute pancreatitis, as well as xanthomas. It can be seen in familial lipoprotein lipase (LPL) deficiency, primary type V hyperlipoproteinemia, idiopathic hyperchylomicronaemia, and familial apolipoprotein CII deficiency. Treatment is dietary fat restriction in order to avoid pancreatitis attacks.

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.

Palmar xanthomas are found in type III hyperlipoproteinemia. Her total cholesterol level and triglyceride level support the diagnosis.

Given that the patient has had large amount, high volume watery diarrhoea in an acute period of time, from the answer choices given, this narrows the diagnosis down to VIPoma or carcinoid syndrome. You would expect with carcinoid syndrome for there to be periodic episodes of diarrhoea, though, with a description of flushing, additionally, associated with these episodes. Thus, VIPoma is the most likely answer here. VIPomas are known to cause hypokalaemia from this large amount of watery diarrhoea. Stool volume should be > 700 ml/day.

The combination of APTT and low platelets with recurrent DVTs make antiphospholipid syndrome the most likely diagnosis.

Secretin is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Secretin helps regulate the pH of the duodenum by
1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and
(2) stimulating the production of bicarbonate from the ductal cells of the pancreas.
G cells in the antrum of the stomach release gastrin
I cells in upper small intestine release CCK
D cells in the pancreas & stomach secrete somatostatin
K cells secrete gastric inhibitory peptide, an incretin, which also promotes triglyceride storage.

Excessive sweating points towards a morphine overdose.

Morphine is considered the classic opioid analgesic with which other painkillers are compared. Like other medications in this class, morphine has an affinity for delta, kappa, and mu-opioid receptors.
Most commonly used in pain management, morphine provides major relief to patients afflicted with pain.

Among the more common adverse effects of morphine use is constipation. Other side effects include nausea, vomiting, drowsiness, and confusion. Psychological and physical dependence may occur.

Other side effects include bronchospasm, angioedema, urinary retention, ureteric or biliary spasm, dry mouth, sweating, rash, facial flushing, vertigo, tachycardia, bradycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, mood change, hallucinations, seizures (adults and children) and miosis, headache and allergic reactions (including anaphylaxis) and decreased libido or potency.

Raised intracranial pressure occurs in some patients. Muscle rigidity may occur with high doses. Elevated liver enzymes may occur due to biliary sphincter constriction. Large doses can lead to respiratory depression, circulatory failure, and coma.

Treatment of opioid overdose:
Initial treatment of overdose begins with supportive care.
Naloxone is a pure competitive antagonist of opiate receptors and has no agonistic activity. The drug is relatively safe and can be administered intravenous, intramuscular, subcutaneous or via the endotracheal tube.
Alternatively, nalmefene and naltrexone maybe considered.

The patient is in a suitable age for developing temporal arteritis and the fact that she’s unable to comb her hair indicates scalp tenderness or proximal muscle weakness. A high ESR together with increased CRP supports the diagnosis. Temporal artery biopsy is also useful to establish the diagnosis.

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.

This is a classical picture of graft versus host disease (GVHD) following bone marrow transplant. Acute GVHD occurs in the first 100 days post transplant with chronic GVHD occurring 100-300 days after transplant. GVHD is graded according to the Seattle system, and each organ involved is scored (skin, liver, and gut).

The standard initial treatment in the acute setting is high-dose methylprednisolone started immediately. If there is no response, a more intensive immunosuppressive agent such as alemtuzumab or antilymphocyte globulin is needed.

In acute angle closure glaucoma (AACG) there is a rise in IOP secondary to an impairment of aqueous outflow. Management options include reducing aqueous secretions with acetazolamide and inducing pupillary constriction with topical pilocarpine.

1B: Individual Randomised Control Trial (with narrow confidence intervals)

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent – 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes. Another way of expressing this is the number needed to treat (NNT). If 8 children out of 100 benefit from treatment, the NNT for one child to benefit is about 13 (100 ÷ 8 = 12.5). CER = 20 / 400 = 1 / 20 = 0.05, EER = 10 / 400 = 0.025, ARR =CER – EER = 0.025

5-ASA is not an acute treatment; it is for maintenance therapy for ulcerative colitis and/or Crohn’s. The most benefit is seen in patients with ulcerative colitis.

The presence of tinnitus, fever and hyperventilation are clues for aspirin (salicylate) toxicity.
Clinical Presentation of salicylate toxicity can include:
• Pulmonary manifestations include: Hyperventilation, hyperpnea, severe dyspnoea due to noncardiogenic pulmonary oedema, fever and dyspnoea due to aspiration pneumonitis
• Auditory symptoms caused by the ototoxicity of salicylate poisoning include: Hard of hearing and deafness, and tinnitus (commonly encountered when serum salicylate concentrations exceed 30 mg/dL).
• Cardiovascular manifestations include: Tachycardia, hypotension, dysrhythmias – E.g., ventricular tachycardia, ventricular fibrillation, multiple premature ventricular contractions, asystole – with severe intoxication, Electrocardiogram (ECG) abnormalities – E.g., U waves, flattened T waves, QT prolongation may reflect hypokalaemia.
• Neurologic manifestations include: CNS depression, with manifestations ranging from somnolence and lethargy to seizures and coma, tremors, blurring of vision, seizures, cerebral oedema – With severe intoxication, encephalopathy
• GI manifestations include: Nausea and vomiting, which are very common with acute toxicity, epigastric pain, GI haemorrhage – More common with chronic intoxication, intestinal perforation, pancreatitis, hepatitis – Generally in chronic toxicity; rare in acute toxicity, Oesophageal strictures – Reported as a very rare delayed complication
• Genitourinary manifestations include: Acute kidney injury (NSAID induced Nephropathy) is an uncommon complication of salicylate toxicity, renal failure may be secondary to multisystem organ failure.
• Hematologic effects may include prolongation of the prothrombin and bleeding times and decreased platelet adhesiveness. Disseminated intravascular coagulation (DIC) may be noted with multisystem organ failure in association with chronic salicylate toxicity.
• Electrolyte imbalances like: Dehydration, hypocalcaemia, acidaemia, Syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalaemia
Management of these patients should be done in the following manner:
• Secure Airway, Breathing, and Circulation
• Supportive therapy
• GI decontamination
• Urinary excretion and alkalization
• Haemodialysis

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals. This would be the most likely option as it is the only disease that can affect both liver and lung functions.
People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema. Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.
About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and sclera (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing hepatocellular carcinoma.

All of the aforementioned options may be important however cytogenetics, for detecting chromosomal abnormalities, is the single most important test to determine her disease prognosis.

Acute myeloid leukaemia (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 a 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.

Pneumonitis is a serious and unpredictable side-effect of treatment with methotrexate (MTX) that may become life-threatening. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields. Pulmonary function tests show a restrictive pattern with diminished diffusion capacity. Lung biopsy reveals cellular interstitial infiltrates, granulomas or a diffuse alveolar damage pattern accompanied by perivascular inflammation. Most patients present in the first few months of starting methotrexate. It is important that all patients receiving methotrexate be educated concerning this potential adverse reaction and instructed to contact their physicians should significant new pulmonary symptoms develop while undergoing therapy. If methotrexate pneumonitis is suspected, methotrexate should be discontinued, supportive measures instituted and careful examination for different causes of respiratory distress conducted. This may be treated with corticosteroids once underlying infection has been excluded.

The somatostatin-secreting D-cells comprise ,5% of the cells of the pancreatic islets. The D-cells have a complex morphology and may, via cellular process, interact with many more islet cells than suggested by their low number. D-cells are equipped with ATP-sensitive potassium channels (KATP channels).

Bradycardia and miosis should be anticipated following the administration of anticholinesterases.

Anticholinesterase agents include the following medications:
– Pyridostigmine, neostigmine, and edrophonium which play a significant role in the diagnosis and the management of myasthenia gravis.
– Rivastigmine, galantamine and donepezil are cholinesterase inhibitors found to be significantly useful in the management of Alzheimer’s disease.

Mechanism of action and pharmacological effects:
Inhibition of cholinesterase increases the level and the duration of action of acetylcholine within the synaptic cleft.

Thus, cholinergic effects such as a reduction in heart rate (bradycardia), miosis (pupillary constriction), increased secretions, increased gastrointestinal motility and reduction in BP may occur with anticholinesterases.

Toxins such as organophosphates and carbamates also are primarily anticholinergic and cause the following typical SLUDGE symptoms:
– Salivation
– Lacrimation
– Urination
– Diaphoresis
– Gastrointestinal upset
– Emesis

Tumour lysis syndrome (TLS), triggered by the introduction of chemotherapy, has resulted in the aforementioned symptoms in this patient.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.