Pulsus paradoxus is defined as the exaggerated fall in systolic blood pressure during inspiration by greater than 10 mmHg. Cardiac tamponade is the classic cause of pulsus paradoxus. Kussmaul’s sign (a rise in the jugular venous pressure on inspiration) is mostly seen in constrictive pericarditis. Hypotension, muffled heart sounds and raised JVP can be seen in both conditions.

Aprepitant is an anti-emetic which blocks the neurokinin 1 (NK1) receptor and acts as a substance P antagonist. It is licensed for chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting.

Nausea and vomiting are the common side effects of chemotherapy. Risk factors for the development of these symptoms include age<50 years, anxiety, concurrent use of opioids, and the type of chemotherapy administered.

The immunological changes in HIV include depletion in CD4+ T cell, cytokine dysregulation and immune dysfunction. The dominant immunologic feature of HIV infection is progressive depletion of the helper T cell (CD4+ T cell), which reverses the normal CD4:CD8 ratio and subsequently lead to immunodeficiency. Other imuunological changes include:
increased B2-microglobulin
decreased IL-2 production
polyclonal B-cell activation
decreased NK cell function
reduced delayed hypersensitivity responses

Deep vein thrombosis (DVT) is a serious condition in which a blood clot forms in a deep vein, usually in the leg.

Subcutaneous low molecular weight heparin (LMWH) is the preferred treatment for most patients with acute DVT, including in pregnancy. A large meta-analyses comparing LMWH to unfractionated heparin (UFH) showed that LMWH decreased the risk of mortality, recurrent veno-thrombo embolism (VTE), and haemorrhage compared with heparin. Other advantages of LMWH may include more predictable therapeutic response, ease of administration and monitoring, and less heparin-induced thrombocytopenia. Disadvantages of LMWH include cost and longer half-life compared with heparin.

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. Warfarin crosses the placenta and is teratogenic, causing a constellation of anomalies known as warfarin embryopathy, with greatest risk between the sixth and twelfth week of gestation.
Other options are not indicated for use.

Indications for surgery for the treatment of primary hyperparathyroidism:
1. Symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation
2. End-organ disease (renal stones, fragility fractures or osteoporosis)
3. An albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

The principal mechanism of action of taxanes (e.g. docetaxel) is the prevention of microtubule disassembly.

Other aforementioned options are ruled out because:

1. Doxorubicin: stabilizes DNA topoisomerase II complex and inhibits DNA and RNA synthesis.

2. Vincristine, vinblastine: inhibits formation of microtubules.

3. Cisplatin: causes cross-linking in DNA.

Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease as the anti-Ro and anti-La antibodies cross the placenta and lead to various life threatening complications. Studies show a high incidence of poor fetal outcomes for these patients. Congenital heart block, neonatal lupus, congestive cardiac failure, hydrops fetalis can all be caused as a result of Sjogren syndrome.

In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by nuchal rigidity (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness). Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises).
In the United Kingdom empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone. In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended. Penicillins, cephalosporins, carbapenems and monobactams all act via inhibition of cell wall synthesis.

The dose is calculated, using the conversion factor, as follows:

(Conversion factor used to convert oral morphine to subcutaneous diamorphine = Divide the total daily dose of oral morphine by 3)
Hence,
60mg*2 = 120mg
120mg/3 = 40mg

The side effects of opioids can be transient or persistent, and these include constipation, nausea, and drowsiness. Therefore, all patients taking opioids should also be prescribed a laxative and an anti-emetic (if the nausea is persistent). Dose-adjustment may be necessary in cases of persistent drowsiness. Moreover, strong opioids can also provide quick relief from metastatic bone pain, as compared to NSAIDs, bisphosphonates, and radiotherapy.

The chance of two carriers of a recessive gene having a child that is homozygous for that disease (that is both genes are transmitted to the child) is 25%. Therefore, the chances of this couple having a child with CF are 25%(1/4) x 1/20 = 1/80.

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.

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients however, there is a combination of clinical patterns. In progressive bulbar palsy there is palsy of the tongue and muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei. This carries the worst prognosis.

The patient’s underlying arthritis has most likely led to Renal tubular acidosis RTA type 1, which presents with the following symptoms consistent with the presentation of the patient: Normal anion gap metabolic acidosis/acidaemia, hypokalaemia and hyperchloremia. Comparatively, the other conditions are ruled out because Aspirin and diabetic ketoacidosis is associated with a raised anion gap, Conn’s syndrome explains hypokalaemia but not the metabolic acidosis, and RTA type 4 is associated with hyperkalaemia.

This case presents with sensorimotor neuropathy secondary to his DM. The progression of the neuropathy, known dying-back neuropathy, is a distal axonopathy or axonal degeneration as where the sensorimotor loss begins distally and travels proximally.

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.

Temazepam is a medication that is often prescribed for the treatment of short-term insomnia. It belongs to the benzodiazepine family of drugs and is classed as intermediate-acting, meaning that it can take between six and twenty-four hours for the drug to take effect.

Although it is known that shorter-acting benzodiazepines are more harmful and more likely to cause addiction, temazepam is, nevertheless, a highly addictive drug. It should not be taken for longer than four weeks.

-Adverse effects associated with the use of benzodiazepine hypnotics (to which the elderly are most vulnerable) include confusion, over sedation, increased risks of falls and consequent fractures

-Withdrawal from a benzodiazepine hypnotic must be agreed between the clinician and the patient – patients should never be forced or threatened. The risks of continued benzodiazepine use should be explained. An agreed schedule for reduction of and gradual withdrawal from the benzodiazepine hypnotic should also be agreed. This will involve substitution of the hypnotic with a long-acting benzodiazepine (e.g. diazepam) and a subsequent gradual reduction in dose of the substituted benzodiazepine -the substituted benzodiazepine can then be withdrawn in steps of about one-eighth to one-tenth every fortnight
Example: withdrawal schedule for patient on temazepam 20mg nocte
week 1 – temazepam 10mg, diazepam 5mg
week 2 – stop temazepam, diazepam 10mg
week 4 – diazepam 9mg
week 6 – diazepam 8mg
continue reducing dose of diazepam by 1mg every fortnight – tapering of dose may be slower if necessary

From the given history the patient has NYHA grade III heart failure. He can be safely started on an ACE inhibitor as his serum potassium was towards the lower limit. As there an impairment of renal function, his urea, creatinine and serum electrolytes should be closely monitored after commencing an ACE inhibitor. Adding atenolol will not have any clinical benefit. Increasing the digoxin dose is not needed as the patient is in sinus rhythm. Increasing furosemide will only have symptomatic relief.

Absolute contraindications for fibrinolytic use in STEMI

Prior intracranial haemorrhage (ICH)
Known structural cerebral vascular lesion
Known malignant intracranial neoplasm
Ischemic stroke within 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed head trauma or facial trauma within 3 months
Intracranial or intraspinal surgery within 2 months
Severe uncontrolled hypertension (unresponsive to emergency therapy)
For streptokinase, prior treatment within the previous 6 months

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.

Many drugs are responsible for causing drug induced lupus. However, it is most commonly associated with hydralazine, procainamide and quinidine.

This patient has a high risk of sudden cardiac death due to a strong family history and non sustained VT. So the most appropriate management is implantable cardiovertor defibrillator.

Over consumption of fluids, prolonged race duration and inadequate training all can predispose to acute hyponatraemia.
Mild symptoms include a decreased ability to think, headaches, nausea, and an increased risk of falls. Severe symptoms include confusion, seizures, and coma. Normal serum sodium levels are 135 – 145 mEq/liter (135 – 145 mmol/L). Hyponatremia is generally defined as a serum sodium level of less than 135 mEq/L and is considered severe when the level is below 120 mEq/L.
The correct treatment to give is hypertonic saline. Decompressive craniotomy would help alleviate raised intracranial pressure due to cerebral oedema however is not an appropriate first line treatment. Demeclocycline is used for SIADH and mannitol is more likely to be used in the context of traumatic brain injury.
Hyponatremia is corrected slowly, to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. During treatment of hyponatremia, the serum sodium (salt level in the blood) should not rise by more than 8 mmol/L over 24 hours.

Pulsus alternans is the alternation of one strong and one weak beat without a change in the cycle length. It occurs most commonly in heart failure due to increased resistance to LV ejection, as occurs in hypertension, aortic stenosis, coronary atherosclerosis, and dilated cardiomyopathy. Pulsus alternans is usually associated with an S3 gallop, which is associated with a poor prognosis. It usually disappears with treatment of the heart failure.

Fc Receptors include the IgG receptors (FcγR), high-affinity IgE receptor (FcεRI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcγRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Fc receptors, the receptors for the Fc region of immunoglobulins, play an essential role in antibody-dependent immune responses. Fc receptors are detected on many types of hematopoietic cells including macrophages, neutrophils, dendritic cells, eosinophils, basophils, mast cells, and NK cells. Plasma cells produce five classes of antibodies, IgA, IgD, IgE, IgG and IgM. Fc receptors with an Ig superfamily related structure exist that correspond to each of these classes of immunoglobulins.

The power of a test is defined as 1 − the probability of Type II error. The Type II error is concluding at no difference (the null is not rejected) when in fact there is a difference, and its probability is named β. Therefore, the power of a study reflects the probability of detecting a difference when this difference exists. It is also very important to medical research that studies are planned with an adequate power so that meaningful conclusions can be issued if no statistical difference has been shown between the treatments compared. More power means less risk for Type II errors and more chances to detect a difference when it exists.

The diagnosis is inferior ST elevation myocardial infarction. As the right coronary artery supplies the SA and AV nodes and bundle of His, conduction abnormalities are more common with inferior MIs. The most immediate drug management is high dose Aspirin. Definite treatment is urgent cardiac revascularization.

This patient has a combination of right cerebellar dysfunction with right-sided cranial nerve palsies (VI, VII, and VIII). The magnetic resonance imaging (MRI) shows a calcified meningioma within the right cerebellar pontine area, which would account for these findings. The cerebrospinal fluid (CSF) analysis shows oligoclonal bands, however, these are matched in the serum, which reflects a systemic inflammatory response from his rheumatoid arthritis.

The MRI scan and CSF analysis would not be consistent with progressive multiple sclerosis. The progressive nature of her symptoms would be against a diagnosis of brainstem infarct, and one would expect more pyramidal signs in the peripheral nervous system.

The use of nitrates and nicorandil concomitantly with sildenafil citrate is contraindicated.

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

This patient has Wilson’s disease. They Kayser-Fleischer ring (ring that encircles the iris) is diagnostic of this. Low serum copper is seen in Wilson’s disease. With the Kayser-Fleischer ring, this makes all of the other answer choices incorrect.

The patient has bloody diarrhoea that sounds like a food poisoning in the clinical scenario. Campylobacter is the most common cause of this in the United Kingdom. This is then followed by Salmonella and Shigella. The symptoms are usually self limiting. This is more likely to be bacterial from the food than a viral gastroenteritis.