The blood gas analysis provided above is suggestive of a mixed respiratory alkalosis and metabolic acidosis characteristic of salicylate overdose.

Pathophysiology:
The direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis.
As it is metabolized, it causes an uncoupling of oxidative phosphorylation in the mitochondria.
Lactate levels then increase due to the increase in anaerobic metabolism. This, along with a slight contribution from the salicylate metabolites result in metabolic acidosis.

Tinnitus is characteristic and salicylate ototoxicity may produce deafness. Other neurological sequelae include encephalopathy and agitation, seizures and CNS depression and coma. Cardiovascular complications include tachycardia, hypotension, and dysrhythmias (VT, VF, and asystole).

Difficulty in initiating movement (bradykinesia), postural instability and unilateral symptoms (initially) are typical of Parkinson’s. Essential tremor symptoms are usually worse if arms are outstretched and eased by rest and alcohol.

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).

When you hear painless jaundice and weight loss in the same sentence, the first thing you should think is cancer. Likely cholangiocarcinoma here or some other biliary tract obstructing cancer. The first line imaging for this would be MRCP because you’re looking for obstruction– the dilatation of the intra and extrahepatic ducts suggests this. This is less invasive than an ERCP or a liver biopsy. CT C/A/P will likely be needed for staging later but it is asking for the initial test.

Psoriasis is a long-lasting autoimmune disease characterized by patches of skin typically red, dry, itchy, and scaly. Psoriasis can affect the nails and produces a variety of changes in the appearance of finger and toe nails including pitting and onycholysis. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin and has a lifetime incidence of 80–90% in those with psoriatic arthritis. Psoriasis is mediated by type 1 helper T cells which are involved in the cell mediated response.

A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. There are six antimuscarinic drugs currently marketed for the treatment of urge incontinence: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin.

Malignant mesothelioma is a type of cancer that occurs in the thin layer of tissue that covers the majority of the internal organs (mesothelium).
Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumour of the pleura and peritoneum. Aetiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen.

Thoracoscopically guided biopsy should be performed if mesothelioma is suggested; the results are diagnostic in 98% of cases. No specific treatment has been found to be of benefit, except radiotherapy, which reduces seeding and invasion through percutaneous biopsy sites.

Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal.

The given clinical scenario is highly suggestive of a borderline personality disorder.

Borderline personality disorder is marked out by instability in moods, behaviour, and relationships. The diagnosis is confirmed by the presence of at least 5 of the following symptoms;
1) Extreme reactions including panic, depression, rage, or frantic actions to abandonment, whether real or perceived
2) A pattern of intense and stormy relationships with family, friends, and loved ones, often veering from extreme closeness and love to extreme dislike or anger
3) Distorted and unstable self-image or sense of self, which can result in sudden changes in feelings, opinions, values, or plans and goals for the future (such as school or career choices)
4) Impulsive and often dangerous behaviours, such as spending sprees, unsafe sex, substance abuse, reckless driving, and binge eating
5) Recurring suicidal behaviours or threats or self-harming behaviour, such as cutting, intense and highly changeable moods, with each episode lasting from a few hours to a few days
6) Chronic feelings of emptiness and/or boredom
7) Inappropriate, intense anger or problems controlling anger
8) Having stress-related paranoid thoughts or severe dissociative symptoms, such as feeling cut off from oneself, observing oneself from outside the body, or losing touch with reality.

Other options:
There are no features consistent with endogenous depression, such as early morning wakening or loss of appetite.
There are also no features consistent with hypomania such as pressure of speech, a flight of ideas, or over-exuberant behaviour.
The lack of history of drug abuse rules out drug-induced psychosis.
An anti-social personality disorder is characterized by a failure to conform to social norms and repeated lawbreaking. There is consistent irresponsibility, impulsivity, and disregard for both their safety and that of others. This is not the case in the given scenario.

The patient has hyperprolactinaemia with otherwise normal oestradiol, FSH and LH. This is highly suggestive of Prolactinoma rather than a non functioning tumour.
In polycystic ovaries, there is increase in the level of LH while FSH is normal or low.

Erythropoietin (EPO) is used to distinguish between primary and secondary polycythaemia. Secondary polycythaemia can be caused by tumours in the kidney that may secrete EPO or EPO-like proteins.

The given history suggests a small fibre painful peripheral sensory neuropathy, the most common cause of which is diabetes. Joint position sense and vibratory sensation are carried through large fibres, and therefore are not currently affected. Sensory nerves are affected more often than motor, so reflexes usually remain in tact.

Vitamin B12 deficiency causes impairment of joint position and vibratory sensation.

Chronic inflammatory demyelinating polyneuropathy (CIPD) causes a large fibre peripheral neuropathy with areflexia.

In syringomyelia there is impaired pain and temperature noted in the upper limbs.

Finally, with alcoholic polyneuropathy, all fibre types are affected (sensory and motor loss). It is usually gradual with long term alcohol abuse and may be accompanied by a nutritional deficiency. In addition, pain is a more dominant feature.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Connective-tissue diseases, liver cirrhosis, exposure to anorexigens and likely other alpha-adrenergic stimulants [e.g., cocaine, amphetamines] and HIV infection are associated with primary pulmonary hypertension. Recurrent pulmonary emboli, chronic lung diseases, left heart diseases are causes for secondary pulmonary hypertension. Pulmonary vascular hypertension after use of fenfluramine is rarely reported.

Thioridazine has a quinidine-like action on the heart and is known to cause cardiac arrhythmias including prolonged PR and QT intervals and widening of QRS complexes. Intravenous magnesium sulphate is regarded as the treatment of choice for this arrhythmia.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

The most probable diagnosis of this patient is Cotard syndrome with major depressive disorder.

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 (like schizophrenia).

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.

It is a metabolic bone disease caused by defective osteoclastic resorption of immature bone. Osteopetrosis is also known as marble bone disease. Osteoclasts are unable to adequately acidify bone matrix. Impaired bone resorption leads to overly dense bone that is more likely to fracture. It is usually treated with bone marrow transplant and high dose calcitriol.

The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 37 which falls within the stage 3 or severe COPD.
During stage 3 COPD, you will likely experience significant lung function impairment. Many patients will experience an increase in COPD flare-ups or exacerbations. For some people, the increase in flare-ups means they could need to be hospitalized at times as well.

Inhaled corticosteroid (ICS) use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma–COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.

The Towards a Revolution in COPD Health (TORCH) trial was a pivotal, double-blind, placebo-controlled, randomized study comparing salmeterol plus fluticasone propionate (50 and 500 µg, respectively, taken twice daily) with each component alone and placebo over 3 years.26 Patients with COPD were enrolled if they had at least a 10-pack-year smoking history, FEV1 <60% predicted, and an FEV1:FVC ratio ≤0.70.26 Among 6,184 randomized patients, the risk of death was reduced by 17.5% with the ICS-LABA combination vs placebo (P=0.052). ICS-LABA significantly reduced the rate of exacerbations by 25% compared with placebo (P<0.001) and improved health status and FEV1 compared with either component alone or placebo.

A case–control study (also known as case–referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease (the cases) with patients who do not have the condition/disease but are otherwise similar (the controls).
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B or vice versa.

Gilles de la Tourette syndrome is the most severe and rare of the tic syndromes, consisting of multiple tics involving both motor actions and vocalisation. Onset is usually in childhood. Symptoms include utterance of obscenities (coprolalia); echolalia (repetition of another person’s spoken words) and palilalia (involuntary repetition of words, phrases, or sentences).
The underlying cause is unknown, with no particular imaging or standard histopathological abnormalities having been identified. The EEG shows non-specific abnormalities in about half of patients. However, more recent immunocytochemical studies have suggested altered dopamine uptake in the striatal system.
Risperidone is an effective therapeutic option without the effects associated with chlorpromazine and haloperidol.

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli causing diarrhoea in these cases as well.

Major depression (MD) often occurs after MI and has been shown to be an independent predictor of poor cardiovascular (CV) outcome.

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.

Adverse effects to note:
Sertraline – Diarrhoea (13-24%), Nausea (13-30%), Headache (20-25%),
Insomnia (12-28%)
Imipramine – ECG changes, orthostatic hypotension, tachycardia
Confusion, extrapyramidal symptoms (EPS), dizziness, paraesthesia, tinnitus
Flupentixol – seizures, irregular/fast heartbeat, increased sweating
Paroxetine – Hypertension, Tachycardia, Emotional lability, Pruritus
Venlafaxine – Abnormal vision (4-6%), Hypertension (2-5%), Paraesthesia (2-3%), Vasodilation (2-6%), Aneurism, Deep vein thrombophlebitis, Takotsubo cardiomyopathy

Café-au-lait spots is hyperpigmented lesions that vary in colour from light brown to dark brown, with borders that may be smooth or irregular. Causes include:
Neurofibromatosis type I
McCune–Albright syndrome
Legius syndrome
Tuberous sclerosis
Fanconi anaemia
Idiopathic
Ataxia-telangiectasia
Basal cell nevus syndrome
Benign congenital skin lesion
Bloom syndrome
Chediak-Higashi syndrome
Congenital nevus
Gaucher disease
Hunter syndrome
Maffucci syndrome
Multiple mucosal neuroma syndrome
Noonan syndrome
Pulmonary Stenosis
Silver–Russell syndrome
Watson syndrome
Wiskott–Aldrich syndrome

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

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.

The typical “rheumatoid effusion” is a sterile exudative fluid with low pH (<7.3), low glucose (<60 mg. dL−1) and elevated lactate dehydrogenase (may be >700 IU). It should initially be treated with NSAIDs. Decortication should be reserved in patients with thickened pleura who have symptomatic dyspnoea.

In asthma, a reversible increase in residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) may occur. There is a fall in FEV1, FVC and gas transfer.

Hypopyon can be seen in anterior uveitis, however the combination of a normal pupillary reaction and contact lens use make a diagnosis of keratitis more likely. Keratitis describes inflammation of the cornea, and features include red eye with pain and erythema, photophobia, and foreign body/gritty sensation.

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon. GLP-1 is released in response to meal intake.
The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the ileal brake mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake.
Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycaemia.

The rationale behind the use of sodium bicarbonate is that it increases the alkalinity of the urine promoting lithium excretion. The preferred treatment in severe cases would be haemodialysis.

Lithium is a mood-stabilizing drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Toxicity may be precipitated by dehydration, renal failure, diuretics (especially Bendroflumethiazide), ACE inhibitors, NSAIDs and metronidazole.

Features of toxicity
Coarse tremor (a fine tremor is seen in therapeutic levels)
Hyperreflexia
Acute confusion
Seizure
Coma

Management
Mild-moderate toxicity may respond to volume resuscitation with normal saline
Haemodialysis may be needed in severe toxicity
Sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion.

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

The most probable diagnosis in this patient is serotonin syndrome.

The serotonin syndrome is a cluster of symptoms and signs (range from barely perceptible tremor to life-threatening hyperthermia and shock).
It may occur when SSRIs such as citalopram, escitalopram, fluoxetine, fluoxetine, paroxetine, and sertraline that impair the reuptake of serotonin from the synaptic cleft into the presynaptic neuron are taken in combination with monoamine oxidase inhibitors or tricyclic antidepressants. It has also been reported following an overdose of selective serotonin reuptake inhibitors (SSRIs) alone.

Treatment:
Most cases of serotonin syndrome are mild and will resolve with removal of the offending drug alone.
After stopping all serotonergic drugs, management is largely supportive and aimed at preventing complications.
Patients frequently require sedation, which is best facilitated with benzodiazepines.
Antipsychotics should be avoided because of their anticholinergic properties, which may inhibit sweating and heat dissipation.

Hypovitaminosis B1, consistent with dry beriberi is crucially a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Dry beriberi or ‘acute nutritional polyneuropathy’ is considered to be rare in the western world. Rapid deterioration can occur, typically with weakness, paraesthesia and neuropathic pain. Striking motor nerve involvement can occur, mimicking Guillain-Barré syndrome (GBS). In the context of increasing alcohol abuse in the western world, it is possible that alcoholic neuropathy associated with abrupt deterioration due to concomitant nutritional hypovitaminosis B1 may be seen increasingly often.

Pneumonia is the predominant clinical manifestation of Legionnaires disease (LD). After an incubation period of 2-10 days, patients typically develop the following nonspecific symptoms:
Fever
Weakness
Fatigue
Malaise
Myalgia
Chills

Respiratory symptoms may not be present initially but develop as the disease progresses. Almost all patients develop a cough, which is initially dry and non-productive, but may become productive, with purulent sputum and, (in rare cases) haemoptysis. Patients may experience chest pain.
Common GI symptoms include diarrhoea (watery and non bloody), nausea, vomiting, and abdominal pain.

Fever is typically present (98%). Temperatures exceeding 40°C occur in 20-60% of patients. Lung examination reveals rales and signs of consolidation late in the disease course.

Males are more than twice as likely as females to develop Legionnaires disease.

Age
Middle-aged and older adults have a high risk of developing Legionnaires disease while it is rare in young adults and children. Among children, more than one third of reported cases have occurred in infants younger than 1 year.

Situations suggesting Legionella disease:
-Gram stains of respiratory samples revealing many polymorphonuclear leukocytes with few or no organisms

-Hyponatremia

-Pneumonia with prominent extrapulmonary manifestations (e.g., diarrhoea, confusion, other neurologic symptoms)

Specific therapy includes antibiotics capable of achieving high intracellular concentrations (e.g., macrolides, quinolones, ketolides, tetracyclines, rifampicin).
Clarithromycin, a new macrolide antibiotic, is at least four times more active in vitro than erythromycin against Legionella pneumophila. In this study the safety and efficacy of orally administered clarithromycin (500 to 1,000 mg bid) in the treatment of Legionella pneumonia were evaluated.
Clarithromycin is a safe effective treatment for patients with severe chest infections due to Legionella pneumophila.

Exogenous thyroid hormone use has been associated with episodes of thyroid storm as well as thyrotoxic periodic paralysis.
It presents with marked proximal muscle weakness in both upper and lower limbs, hypokalaemia and signs of hyperthyroidism.
Hyperthyroidism generally presents with tachycardia, hypertension, hyperthermia, and cardiac arrhythmias

Laxatives and diuretics can result in electrolyte abnormalities.
Medical complications associated with laxatives include chronic diarrhoea which disrupts the normal stool electrolyte concentrations that then leads to serum electrolyte shifts; acutely, hypokalaemia is most typically seen. The large intestine suffers nerve damage from the chronic laxative use that renders it unable to function properly. The normal peristalsis and conduction are affected; the disorder is thought to be secondary to a degeneration of Auerbach’s Plexi. However, it does not cause muscle weakness.

Insulin tends to cause weight gain, not weight loss.
Metformin does not cause muscle weakness but can cause headaches.

Post-concussion syndrome is a complex disorder in which various symptoms, such as headaches and dizziness, last for weeks and sometimes months after the injury that caused the concussion.

Concussion is a mild traumatic brain injury that usually happens after a blow to the head. It can also occur with violent shaking and movement of the head or body. You don’t have to lose consciousness to get a concussion or post-concussion syndrome. In fact, the risk of post-concussion syndrome doesn’t appear to be associated with the severity of the initial injury.

Post-concussion symptoms include:
Headaches
Dizziness
Fatigue
Irritability
Anxiety
Insomnia
Loss of concentration and memory
Ringing in the ears
Blurry vision
Noise and light sensitivity
Rarely, decreases in taste and smell

Poor prognostic factors for breast cancer include:
1. Young age (<40 years)
2. Premenopausal at the time of diagnosis
3. Increased tumour size
4. High-grade tumour
5. Oestrogen and progesterone receptor-negative tumour
6. Positive lymph node status

Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. It causes pain, redness, a watering eye (epiphora), and swelling and erythema at the inner canthus of the eye. Management is with systemic antibiotics. IV antibiotics are indicated if there is associated periorbital cellulitis.

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

The patient has Acromegaly.
Acromegaly is a chronic disorder characterised by growth hormone (GH) hypersecretion, predominantly caused by a pituitary adenoma.

Random GH level testing is not recommended for diagnosis given the pulsatile nature of secretion. Stress, physical exercise, acute critical illness and fasting state can cause a physiological higher peak in GH secretion.

Pegvisomant is a US Food and Drug Administration-approved treatment for use after surgery. In a global non-interventional safety surveillance study, pegvisomant normalised IGF-1 in 67.5% of patients after 5 years (most likely due to lack of dose-up titration), and also improved clinical symptoms. Pegvisomant improves insulin sensitivity, and long-term follow-up showed significantly decreased fasting glucose over time, while the first-generation SRL only have a marginal clinical impact on glucose homeostasis in acromegaly. Pegvisomant does not have any direct anti-proliferative effects on pituitary tumour cells, but tumour growth is rare overall.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

The most widely used prognostic predictors for acetaminophen over-ingestion is King’s College Criteria, which is: arterial PH < 7.3 after fluid resuscitation, Cr level > 3.4, PT > 1.8x control or > 100s, or INR > 6.5, and Grave III or IV encephalopathy.

N-acetylcysteine depletes glutathione reserves by providing cysteine, which is an essential precursor in glutathione production.

Glutathione within the liver can normally detoxify these minuscule quantities of NAPQI and prevent tissue damage.
N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity.

Paracetamol overdose:
The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose, the conjugation system becomes saturated leading to oxidation by cytochrome P450 (predominately CYP2E1) mixed-function oxidases. This produces a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).

Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death.

Other uses: In COPD, cystic fibrosis, and other lung conditions, nebulized NAC has mucolytic, anti-inflammatory, and antioxidant properties.

Seasonal affective disorder (SAD) is a type of depression that’s related to changes in seasons. SAD begins and ends at about the same time every year. For most people with SAD, the symptoms start in the fall and continue into the winter months, sapping the person’s energy and making him feel moody. Less often, SAD causes depression in the spring or early summer.

Treatment for SAD may include light therapy (phototherapy), medications and psychotherapy.

Signs and symptoms of SAD may include:
Feeling depressed most of the day, nearly every day
Losing interest in activities you once enjoyed
Having low energy
Having problems with sleeping
Experiencing changes in your appetite or weight
Feeling sluggish or agitated
Having difficulty concentrating
Feeling hopeless, worthless or guilty
Having frequent thoughts of death or suicide.

Seasonal affective disorder is diagnosed more often in women than in men. And SAD occurs more frequently in younger adults than in older adults.

Factors that may increase your risk of seasonal affective disorder include:
Family history. People with SAD may be more likely to have blood relatives with SAD or another form of depression.
Having major depression or bipolar disorder. Symptoms of depression may worsen seasonally if you have one of these conditions.
Living far from the equator. SAD appears to be more common among people who live far north or south of the equator. This may be due to decreased sunlight during the winter and longer days during the summer months.

The prognosis of breast cancer depends chiefly on the extent of nodal metastases.

The breast cancer TNM staging system is the most common way that doctors use to stage breast cancer. TNM stands for Tumour, Node, Metastasis. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero), which is non-invasive ductal carcinoma in situ (DCIS), and stages I through IV (1 through 4), which are used for invasive breast cancer.

Staging can be clinical or pathological. Clinical staging is based on the results of tests done before surgery, which may include physical examinations, mammogram, ultrasound, and MRI scans. Pathologic staging is based on what is found during surgery to remove breast tissue and lymph nodes. In general, pathological staging provides the most information to determine a patient’s prognosis.

This man is likely suffering from a subarachnoid haemorrhage or intracerebral bleed. The priority is to prevent a secondary brain injury. Important first steps include ensuring a secure airway, normalizing cardiovascular function, and treating seizures. His airway is likely to be protected with a GCS of 9, although he may benefit from a nasal or oral airway, and close attention should be paid to his airway if going for a CT scan. He should receive high flow oxygen and his blood pressure should not be treated acutely, as i is often appropriate to compensate for a rise in intracranial pressure. Nimodipine should be given if a subarachnoid haemorrhage is proven. Attention should also be given to maintaining a normal blood sugar, as hyperglycaemia worsens outcomes.

If the INR in the range of 2-3 has still resulted in thrombosis, the target INR is increased to 3-4. However, because the risk of bleeding increases as the INR rises, the INR is closely monitored and adjustments are made as needed to maintain the INR within the target range.

Charles Bonnet syndrome (CBS) involves visual hallucinations due to eye disease, usually associated with a sharp decline in vision. The phenomenon is seen in patients with moderate or severe visual impairment. It can occur spontaneously as the vision declines or it may be precipitated, in predisposed individuals, by concurrent illness such as infections elsewhere in the body.

It is not clear why CBS develops or why some individuals appear to be predisposed to it. It is particularly noted in patients with advanced macular degeneration. It has been suggested that reduced or absent stimulation of the visual system leads to increased excitability of the visual cortex (deafferentation hypothesis). This release phenomenon is compared to phantom limb symptoms after amputation.

CBS is much more common in older patients because conditions causing marked visual loss are more common in older people. However, it can occur at any age and has been described in children.
The prevalence is hard to assess due to considerable under-reporting, perhaps because patients frequently fear that it is a sign of mental illness or dementia. However, it is thought to occur in:
About 10-15% of patients with moderate visual loss.
Possibly up to 50% of people with severe visual loss.
Presentation:
The nature of the hallucination depends on the part of the brain that is activated. The hallucinations may be black and white or in colour. They may involve grids/brickwork/lattice patterns but are typically much more complex:

The hallucinations are always outside the body.
The hallucinations are purely visual – other senses are not involved.
The hallucinations have no personal meaning to the patient.
Hallucinations may last seconds, minutes or hours.
CBS tends to occur in a ‘state of quiet restfulness’. This may be after a meal or when listening to the radio (but not when dozing off).
Symptoms also have a tendency to occur in dim lighting conditions.
Patients may report high levels of distress, with some patients reporting anger, anxiety and even fear associated with the hallucinations.

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.

The major endocrine functions of adrenal gland are to produce catecholamines and steroids. Catecholamine, synthesized by the adrenal medulla, is responsible for blood pressure and blood flow regulation whereas steroids produced by the cortex control energy and water homeostasis and immune responses. Glucocorticoids, a major group of adrenal steroids, have a stimulatory effect on catecholamine synthesis in the medulla.

Citalopram is an antidepressant medication that works in the brain. It is approved for the treatment of major depressive disorder (MDD). Stopping citalopram abruptly may result in one or more of the following withdrawal symptoms: irritability, nausea, feeling dizzy, vomiting, nightmares, headache, and/or paraesthesia (prickling, tingling sensation on the skin).

When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (e.g., over 2 to 4 weeks) to minimize withdrawal symptoms and detect re-emerging symptoms. Reasons for a slower titration (e.g., over 4 weeks) include use of a drug with a half-life <24 hours (e.g., paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants.

Current guidelines recommend the use of ambrisentan, Bosentan (recommendation I, level of evidence A) and macitentan (I, B) in patients with PAH and WHO functional class II and III. In WHO functional class IV, the first-line drug is Epoprostenol and the recommendation for Endothelin receptor antagonists is weaker (IIb, C).

Guillain-Barre syndrome is an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni). Characteristic features include progressive weakness of all four limbs, and it is classically ascending, affecting the lower extremities first. Sensory symptoms tend to be mild.

Functional neurological syndrome can be discounted due to presence of hard neurological signs. Multiple sclerosis can be excluded because of the presence of lower motor neuron signs and absence of upper motor neuron signs. Chronic inflammatory demyelinating polyneuropathy is the chronic form of Guillain-Barre syndrome.

Tumour lysis syndrome (TLS) occurs most notably in patients with haematological malignancies including, Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphocytic Leukaemia (ALL).
Risk factors for TLS include:
• Large tumour burden
• Sensitivity of the tumour to chemotherapy
• Rapid tumour growth rate
TLS is characterized by:
• Hyperuricemia
• Hyperkalaemia
• Hyperphosphatemia
• Hypocalcaemia
Treatment of TLS:
• Allopurinol: It is a xanthine oxidase inhibitor, it reduces the conversion of nucleic acid by-products to uric acid. Thus, it prevents urate nephropathy and subsequent oliguric renal failure. Note: dose reduction is essential in renal failure or if given along with mercaptopurine or azathioprine.
Alternatives to Allopurinol: Febuxostat; Rasburicase are useful in patients with hyperuricemia.
• Hydration
• Diuresis: Should be considered in well hydrated patients with insufficient urine output. Furosemide to be considered in normo-volemic patients with hyperkalaemia. Urine alkalization can be considered for promoting alkaline diuresis.
• Treatment of electrolyte imbalances including hyperkalaemia, hyperphosphatemia, and hypocalcaemia.
• Dialysis can be considered in refractory cases.

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.

Obsessive-Compulsive Disorder (OCD) is a common, chronic and long-lasting disorder in which a person has uncontrollable, reoccurring thoughts (obsessions) and behaviours (compulsions) that he or she feels the urge to repeat over and over.
People with OCD may have symptoms of obsessions, compulsions, or both. These symptoms can interfere with all aspects of life, such as work, school, and personal relationships.

Obsessions are repeated thoughts, urges, or mental images that cause anxiety. Common symptoms include:
Fear of germs or contamination
Unwanted forbidden or taboo thoughts involving sex, religion, and harm
Aggressive thoughts towards others or self
Having things symmetrical or in a perfect order

Compulsions are repetitive behaviours that a person with OCD feels the urge to do in response to an obsessive thought. Common compulsions include:
-Excessive cleaning and/or handwashing
-Ordering and arranging things in a particular, precise way
-Repeatedly checking on things, such as repeatedly checking to see if the door is locked or that the oven is off
-Compulsive counting

Research also shows that a type of CBT called Exposure and Response Prevention (ERP) is effective in reducing compulsive behaviours in OCD, even in people who did not respond well to SRI medication. ERP has become the first-line psychotherapeutic treatment for OCD

Hypersegmented neutrophils in the peripheral blood film is suggestive of megaloblastic changes in bone marrow.

Arthritis mutilans is a rare (occurs in only 5% of the patients) and extremely severe form psoriatic arthritis characterized by resorption of bones and the consequent collapse of soft tissue. When this affects the hands, it can cause a phenomenon sometimes referred to as ‘telescoping fingers.’ The associated nail changes are also characteristic of arthritis.

Anti ds-DNA antibodies are very specific for SLE and their presence most often indicates systemic spread of the disease. These antibodies are present in about 30 percent of the total cases of SLE.

Indapamide is a mild thiazide-like diuretic with hypotensive effect, and compared to other thiazides, it is reported to also have less metabolic derangements. However, it may have beneficial hypo-calciuric effects that are often associated with thiazides, thus, in this case, we would recommend prescribing this to the patient.

The following drugs should be used as normal during pregnancy:
short acting β2 -agonists
long acting β2- agonists
inhaled corticosteroids
oral and intravenous theophyllines

Use steroid tablets as normal when indicated during pregnancy for severe asthma. Steroid tablets should never be withheld because of pregnancy.
If leukotriene receptor antagonists are required to achieve adequate control of asthma then they should not be withheld during pregnancy.

Class I indications (i.e., the benefit greatly outweighs the risk, and the treatment should be administered): -Structural heart disease, sustained VT
-Syncope of undetermined origin, inducible VT or VF at electrophysiologic study (EPS)
-Left ventricular ejection fraction (LVEF) ≤35% due to prior MI, at least 40 days post-MI, NYHA class II or III
-LVEF ≤35%, NYHA class II or III
-LVEF ≤30% due to prior MI, at least 40 days post-MI
-LVEF ≤40% due to prior MI, inducible VT or VF at EPS

Class IIa indications (i.e., the benefit outweighs the risk and it is reasonable to administer the treatment):
-Unexplained syncope, significant LV dysfunction, nonischaemic cardiomyopathy
-Sustained VT, normal or near-normal ventricular function
-Hypertrophic cardiomyopathy with 1 or more major risk factors
-Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) with 1 or more risk factors for sudden cardiac death (SCD)
-Long QT syndrome, syncope or VT while receiving beta-blockers
-Nonhospitalized patients awaiting heart transplant
-Brugada syndrome, syncope or VT
-Catecholaminergic polymorphic VT, syncope or VT while receiving beta-blockers
-Cardiac sarcoidosis, giant cell myocarditis, or Chagas disease

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

Glioblastoma multiforme, also considered as grade IV astrocytoma, is the most malignant form of the tumour and accounts for about 20% of all cerebral tumours. These often remain clinically silent until they have reached a large enough size. In adults, glioblastoma multiforme usually occurs in the cerebral hemispheres, especially the frontal and temporal lobes of the brain. About half occupy more than one hemisphere at presentation, and some are multicentric. Biopsy shows high cellularity with mitoses, pleomorphism, and vascular hyperplasia. Prognosis is extremely poor, with only 20% surviving beyond 1 year and 10% beyond 2 years.

Liver flap is pathognomonic for liver failure. Paracetamol (also known as acetaminophen) overdose usually presents with symptoms including liver failure, resulting in confusion, jaundice, and coagulopathy a few days after overdose. The first 24 hours, people usually have minimal symptoms. Diagnosis is based on blood levels of acetaminophen at specific times after it was taken (see reference). If she took it a few days ago, levels may indeed be undetectable. The hepatitis B serology suggests prior vaccination. Wilson’s disease is not the most likely diagnosis given her presentation. The AST:ALT ratio would be expected to be reversed in alcohol induced liver failure.

Among the given options, an addiction to opiates is considered the strongest risk factor for committing suicide.

Other options:
Being a female – Being male is one of the most significant risk factors for suicide.
Being married – Having family support is an important protective factor for suicide.
Having five children – Having children at home is thought to be a protective factor.
Having never seen a general practitioner – Having a chronic mental or physical condition is however a risk factor for suicide.

Risk factors of suicide:
There are several factors shown to be associated with an increased risk of suicide:
Male sex
History of deliberate self-harm
Alcohol or drug misuse
History of mental illness (depression, schizophrenia)
History of chronic disease
Advancing age
Unemployment or social isolation/living alone
Being unmarried, divorced or widowed
Previous attempt to commit suicide.

Signs pointing towards suicidal intension:
Efforts to avoid discovery
Planning
Leaving a written note
Final acts such as sorting out finances
Violent method

Protective factors against suicide:
Family support
Having children at home
Religious belief

Hereditary non-polyposis syndrome (HNPCC) is the most common type of inherited colorectal cancer. It often presents in younger and younger generations down a family. FAP presents with 100’s-1000’s of polyps and is less common. Li-Fraumeni syndrome and Fanconi syndrome are rare. For Peutz-Jeghers syndrome, the thing you will look for in the question stem is discoloured spots on the lips, this is classic.

Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. A complete oculomotor nerve palsy will result in a characteristic down and out position in the affected eye. This is because the lateral rectus (innervated by the sixth cranial nerve) and superior oblique (innervated by the fourth cranial or trochlear nerve), is unantagonized by the paralyzed superior rectus, inferior rectus and inferior oblique. The affected individual will also have a ptosis, or drooping of the eyelid, and mydriasis (pupil dilation), not miosis.

B2-microglobulin is a useful marker of prognosis in multiple myeloma (MM). Raised levels imply a poorer prognosis. Low levels of albumin are also associated with a poor prognosis.

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols.

Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). It significantly helps in reducing pulmonary hypertension associated with COPD and treating underlying pathology of future heart failure. There is little to no benefit of oxygen therapy for less than 15 hours.

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines. Prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. NICE advises either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives.

Leaking of cerebrospinal fluid from the dura is the most likely explanation for post-lumbar puncture headaches. It is thought that ongoing leak of cerebrospinal fluid (CSF) through the puncture site causes ongoing CSF loss, leading to low pressure. A post-LP headache is typically frontal or occipital and occurs within three days. It is normally associated with worsening on standing and improvement when lying down. Treatment in severe cases includes an epidural blood patch, but most resolve on their own.

Breast feeding has not been shown to increase the risk of transmission of HCV from mother to baby. This is simply a fact to memorize. The other answer choices are not the most accurate as there is no evidence-proven way to decrease the chance that baby will get HCV from the mother during the birth. About 5 out of every 100 infants born to HCV infected mothers become infected.

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

Beckwith-Wiedemann syndrome is a inherited condition associated with organomegaly, macroglossia, abdominal wall defects, Wilm’s tumour and neonatal hypoglycaemia. Wilm’s tumour is a kidney cancer that usually occurs in children. The causes are unknown, however, risk factors include race and family history. Of note, Wilm’s tumour can occur as part of the following syndromes: WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedmann syndrome and not the other listed options in this question.

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), beta-blocker and a statin.

Rheumatoid arthritis is an inflammatory systemic disease associated with some extraarticular manifestations. Keratoconjunctivitis sicca, episcleritis, scleritis, corneal changes, and retinal vasculitis are the most common ocular complications among extraarticular manifestations of RA. The overall prevalence of keratoconjunctivitis sicca also known as dry eye syndrome among patients of RA is 21.2% and is the most common with sense of grittiness in the eyes.

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.

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. There is poor genotype:phenotype correlation. Within a tissue or cell there can be different mitochondrial populations (this is known as heteroplasmy).
Examples of mitochondrial diseases include:
– Leber’s optic atrophy
– MELAS syndrome (mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes)
– MERRF syndrome (myoclonus epilepsy with ragged-red fibres)
– Kearns-Sayre syndrome (more severe syndromic variant of chronic progressive external ophthalmoplegia, onset in patients < 20 years old)

The symptoms of ataxia, slurred speech and blurred vision are all suggestive of phenytoin toxicity. Cimetidine increases the efficacy of phenytoin by reducing its hepatic metabolism.

Phenytoin has a narrow therapeutic index (10-20 mg/L) and its levels are monitored by measuring the total phenytoin concentration.
Cimetidine is an H2 receptor antagonist used in the treatment of peptic ulcers. It acts by decreasing gastric acid secretion.
Cimetidine also has an inhibitory effect on several isoforms of the cytochrome enzyme system including the CYP450 enzymatic pathway. Phenytoin is metabolized by the same cytochrome P450 enzyme system in the liver.
Thus, the simultaneous administration of both these medications leads to an inhibition of phenytoin metabolism and thus increases its circulating levels leading to phenytoin toxicity.

The patient has acute promyelocytic leukaemia (APML) with associated disseminated intravascular coagulation (DIC). Although
the platelet count is high, platelet function is ineffective.

Patients may present, as in this case, with severe bleeding, and the most appropriate emergency treatment would be administration of fresh frozen plasma (FFP).

Chvostek and Trousseau signs can be elicited in patients with hypocalcaemia. Chvostek sign is the twitching of the upper lip with tapping on the cheek 2 cm anterior to the earlobe, below the zygomatic process overlying the facial nerve. Trousseau sign (a more reliable sign present in 94% of hypokalaemic individuals and only 1% to 4% of healthy people) is the presence of carpopedal spasm observed following application of an inflated blood pressure cuff over systolic pressure for 3 minutes in hypokalaemic patients.

Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies. The lungs are the second most frequent site of metastases from extrathoracic malignancies. Twenty percent of metastatic disease is isolated to the lungs. The development of pulmonary metastases in patients with known malignancies indicates disseminated disease and places the patient in stage IV in TNM (tumour, node, metastasis) staging systems.
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis in patients with known malignancies. Chest CT scanning without contrast is more sensitive than CXR.
Breast, colorectal, lung, kidney, head and neck, and uterus cancers are the most common primary tumours with lung metastasis at autopsy. Choriocarcinoma, osteosarcoma, testicular tumours, malignant melanoma, Ewing sarcoma, and thyroid cancer frequently metastasize to lung, but the frequency of these tumours is low.

Tumour marker CA 125 is mostly associated with primary peritoneal cancer and ovarian cancer. It can be used to monitor response to chemotherapy, alongside regular CT scans.

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 combination of frequent infections, eczema, and thrombocytopaenia are characteristic of Wiskott-Aldrich syndrome, which is due to an abnormality in the WASP gene. It is an X-linked recessive disorder that causes primary immunodeficiency owing to a combined B- and T-cell dysfunction.

The other listed options are:
1. PKD1: polycystic kidney disease
2. CFTR: cystic fibrosis
3. HFE1: haemochromatosis
4. RET: multiple endocrine neoplasia, Hirschsprung’s disease

Varicella zoster virus (VZV) presents in this way and the rash transforms from macules to vesicles. Pneumonitis is a common complication of VZV infection.

Oxycodone is a safer opioid to use in patients with moderate to end-stage renal failure.
Active metabolites of morphine accumulate in renal failure which means that long-term use is contraindicated in patients with moderate/severe renal failure.
These toxic metabolites can accumulate causing toxicity and risk overdose.
Oxycodone is mainly metabolised in the liver and thus safer to use in patients with moderate to end-stage renal failure with dose reductions.
Adverse effects:
Constipation is the most common overall side effect. Others include: asthenia, dizziness, dry mouth, headache, nausea, pruritus, etc.

Medications in renal failure:
Drugs to be avoided in patients with renal failure
Antibiotics: tetracycline, nitrofurantoin
NSAIDs
Lithium
Metformin
Drugs that require dose adjustment:
Most antibiotics including penicillin, cephalosporins, vancomycin, gentamicin, streptomycin
Digoxin, atenolol
Methotrexate
Sulphonylureas
Furosemide
Opioids
Relatively safe drugs:
Antibiotics: erythromycin, rifampicin
Diazepam
Warfarin

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.

Infections of the superficial skin around the eyes are called periorbital, or preseptal, cellulitis. It is predominantly a paediatric disease. Erysipelas is a bacterial skin infection involving the upper dermis which extends into the superficial cutaneous lymphatics. Sinusitis is in sinuses. Orbital infections and conjunctivitis are within the eye.