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

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.

The wedged hepatic venous pressure is a reflection of the portal venous pressure in the hepatic sinusoids. This is a fact to remember. Here is a great but concise explanation as to why: https://www.ncbi.nlm.nih.gov/pubmed/18695309

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.

Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses.

The clinical presentation is suggestive of congenital rubella syndrome. The classic triad of presenting symptoms includes sensorineural hearing loss, ocular abnormalities (cataract, infantile glaucoma, and pigmentary retinopathy) and congenital heart disease (patent ductus arteriosus and pulmonary artery stenosis). Other findings in congenital rubella syndrome include CNS abnormalities (mental retardation, behavioural disorders, encephalographic abnormalities, hypotonia, meningoencephalitis, and microcephaly), hepatosplenomegaly, and jaundice.

Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes. Necrosis, inflammation, and haemorrhage occur within lung tissue, sometimes producing a thick, bloody, mucoid sputum described as currant jelly sputum.
The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. An increased tendency exists toward abscess formation, cavitation, empyema, and pleural adhesions.

Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
The most recent update to the NICE guidelines for management of neuropathic pain occurred in 2013: first-line treatment* includes amitriptyline. If the first-line drug treatment does not work then move on to one of the other 3 drugs: duloxetine, gabapentin or pregabalin. Tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain. Topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia). Pain management clinics may be useful in patients with resistant problems.

*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia.

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.

Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is the enzyme responsible for the conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway.
Statins are usually well tolerated with myopathy, rhabdomyolysis, hepatotoxicity, and diabetes mellitus being the most common adverse reactions.
This is the rate-limiting step in cholesterol synthesis, that leads to increased hepatic low-density lipoprotein (LDL) receptors and reduced hepatic VLDL synthesis coupled with increased very-low-density lipoprotein (VLDL) clearance.

The most common causes of a sudden painless loss of vision are:
– ischaemic optic neuropathy
– occlusion of central retinal vein or artery
– vitreous haemorrhage
– retinal detachment.
Central retinal artery occlusion is due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis). Features include afferent pupillary defects, and a ‘cherry red’ spot on a pale retina.

Frequent change of eye glasses, scotoma, and mild cupping are suggestive of primary open angle glaucoma. This means that the anterior angle of the eye is normal but there is a problem in the trabecular meshwork, where the Schlemm’s Canal is not allowing the drainage of the aqueous humor. Pilocarpine should be given to the patient because it is a parasympathomimetic agent. It causes the ciliary muscle of the eye to contract, causing the trabecular meshwork to open up, allowing the aqueous humor to drain again.

Idiopathic hypercalciuria presents with excess calcium in the urine without an apparent cause. Dietary modification is the first step in addressing this condition, however, because hypercalciuria increases the risk of developing renal stones and bone demineralisation, thiazide diuretics should be prescribed to increase calcium reabsorption when these symptoms are also present.

Because Charcot-Marie-Tooth disease (type 1) is an autosomal dominant condition; therefore, there is a 50% chance that the children of this patient will be affected.

PCR is a simple, yet elegant, enzymatic assay, which allows for the amplification of a specific DNA fragment from a complex pool of DNA. PCR can be performed using source DNA from a variety of tissues and organisms, including peripheral blood, skin, hair, saliva, and microbes. Only trace amounts of DNA are needed for PCR to generate enough copies to be analysed using conventional laboratory methods. For this reason, PCR is a sensitive assay. Each PCR assay requires the presence of template DNA, primers, nucleotides, and DNA polymerase. The DNA polymerase is the key enzyme that links individual nucleotides together to form the PCR product. The above mentioned components are mixed in a test tube or 96-well plate and then placed in a machine that allows repeated cycles of DNA amplification to occur in three basic steps. The machine is essentially a thermal cycler. It has a thermal block with holes, into which the test tubes or plates holding the PCR reaction mixture are inserted. The machine raises and lowers the temperature of the block in discrete, precise and pre-programmed steps. The reaction solution is first heated above the melting point of the two complementary DNA strands of the target DNA, which allows the strands to separate, a process called denaturation. The temperature is then lowered to allow the specific primers to bind to the target DNA segments, a process known as hybridization or annealing. Annealing between primers and the target DNA occurs only if they are complementary in sequence (e.g. A binding to G). The temperature is raised again, at which time the DNA polymerase is able to extend the primers by adding nucleotides to the developing DNA strand. With each repetition of these three steps, the number of copied DNA molecules doubles.

Stopping smoking is the single most effective non-pharmacological intervention which will reduce future ischaemic events. But the rest of the responses are also important interventions with regards to reducing future ischaemic events.

Among the above statements, gastric lavage and normal saline IV infusion are the two appropriate interventions for a patient of acute lithium toxicity.

Activated charcoal is not effective after lithium overdose, although gastric lavage should be considered if patients present within 6–8 h.
Where levels are above 3 mmol/l, the use of normal saline to induce diuresis should be considered, although careful monitoring of fluid balance is necessary.
Where levels of lithium are above 4 mmol/l, dialysis is often required. Haemodialysis is preferred, but in a facility where haemodialysis is not possible, peritoneal dialysis may be considered.
Patients should not be discharged until they are asymptomatic and have a serum lithium level less than 1.5 mEq/L.

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

The most likely diagnosis is idiopathic Parkinson’s disease because of the unilateral presentation. In addition, cogwheel rigidity is a classic presenting symptom. Neuroleptic-induced parkinsonism is usually bilateral and symmetrical. Essential tremors do not cause rest tremors.

Mechanism of action of low molecular weight heparin (LMWH):
It inhibits coagulation by activating antithrombin III. Antithrombin III binds to and inhibits factor Xa. In doing so it prevents activation of the final common path; Xa inactivation means that prothrombin is not activated to thrombin, thereby not converting fibrinogen into fibrin for the formation of a clot.

LMHW is a small fragment of a larger mucopolysaccharide, heparin. Heparin works similarly, by binding antithrombin III and activating it. Heparin also has a binding site for thrombin, so thrombin can interact with antithrombin III and heparin, thus inhibiting coagulation.
Heparin has a faster onset of anticoagulant action as it will inhibit not only Xa but also thrombin, while LMWH acts only on Xa inhibition.

Compared to heparin, LMWHs have a longer half-life, so dosing is more predictable and can be less frequent, most commonly once per day.

Dosage and uses:
LMWH is administered via subcutaneous injection. This has long-term implications on the choice of anticoagulant for prophylaxis, for example, in orthopaedic patients recovering from joint replacement surgery, or in the treatment of DVT/PE.

Adverse effects:
The main risk of LMWH will be bleeding. The specific antidote for heparin-induced bleeding is protamine sulphate.
Less commonly it can cause:
Heparin-induced thrombocytopenia (HIT)
Osteoporosis and spontaneous fractures
Hypoaldosteronism
Hypersensitivity reactions

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

Herpes zoster ophthalmicus (HZO) describes the reactivation of the varicella zoster virus in the area supplied by the ophthalmic division of the trigeminal nerve. It accounts for around 10% of case of shingles. Features include a vesicular rash around the eye, which may or may not involve the actual eye itself, and Hutchinson’s sign: a rash on the tip or side of the nose, indicating nasociliary involvement and is a strong risk factor for ocular involvement.

Among the given options the most appropriate management in this patient would be ethanol and haemodialysis.

Ethanol competes with ethylene glycol for alcohol dehydrogenase and thus, helps manage a patient with ethylene glycol toxicity.

Ethylene glycol is a type of alcohol used as a coolant or antifreeze
Features of toxicity are divided into 3 stages:
Stage 1: (30 min to 12 hours after exposure) Symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness (CNS depression)
Stage 2: (12 – 48 hours after exposure) Metabolic acidosis with a high anion gap and high osmolar gap. Also tachycardia, hypertension
Stage 3: (24 – 72 hours after exposure) Acute renal failure

Management has changed in recent times:
Fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol.
Ethanol has been used for many years works by competing with ethylene glycol for the enzyme alcohol dehydrogenase this limits the formation of toxic metabolites (e.g. glycolaldehyde and glycolic acid) which are responsible for the hemodynamic/metabolic features of poisoning.
Haemodialysis has a role in refractory cases.

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test).

The cardiovascular alterations which occur during pregnancy are for the optimal growth and development of the foetus and help to protect the mother from the risks of delivery, such as haemorrhage. The changes are characterized by an increased vascular volume, cardiac output, and heart rate, with a marked fall in vascular resistance and reduction in blood pressure.

In patients with factor V Leiden, inactivation of the active factor V (a clotting factor) by active protein C occurs 10x more slowly than normal. Therefore, this condition is also called activated protein C resistance.

Factor V Leiden is the most commonly inherited thrombophilia, being present in around 5% of the UK’s population. It occurs due to gain-of-function mutation in the Factor V Leiden protein.

This case describes Zollinger-Ellison syndrome. It is characterized by refractory peptic ulcer disease, often multiple ulcers. This is typically caused by secretion of gastrin from a gastrinoma, a neuroendocrine tumour. The most common site of ulceration is the duodenum. A symptom of a pancreatic gastrinoma may be steatorrhea from the hypersecretion of gastrin. Serum gastrin levels > 1000 and a pH < 2 are diagnostic of pancreatic gastrinoma. None of the other answer choices are a better answer than this. CT abdomen may potentially show a tumour, but this is not diagnostic for type.

Insulin is produced by the beta-cells in the islets of Langerhans in the pancreas while Glucagon is secreted from the alpha cells of the pancreatic islets of Langerhans.
Type 1 diabetes mellitus is the culmination of lymphocytic infiltration and destruction of the beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycaemia develops and diabetes may be diagnosed.

The main symptom of dermatomyositis include skin rash and symmetric proximal muscle weakness (in over 90% of patients) which may be accompanied by pain and tenderness. It occurs more commonly in females. Skin findings include:
Gottron’s sign – an erythematous, scaly eruption occurring in symmetric fashion over the MCP and interphalangeal joints
Heliotrope or lilac rash – a violaceous eruption on the upper eyelids and in rare cases on the lower eyelids as well, often with itching and swelling
Shawl (or V-) sign is a diffuse, flat, erythematous lesion over the back and shoulders or in a V over the posterior neck and back or neck and upper chest, which worsens with UV light.
Erythroderma is a flat, erythematous lesion similar to the shawl sign but located in other areas, such as the malar region and the forehead.
Periungual telangiectasias and erythema occur.

Acute cord compression is a medical emergency. Typically, signs of segmental damage at the level of compression are usually combined with corticospinal tract dysfunction (e.g., hyperreflexia, Babinski’s sign and weakness) and sensory deficits below the level of compression. Symptoms include spinal pain that precedes the development of weak legs and sensory loss. There may be loss of bladder (and anal) sphincter control, manifesting as hesitancy, frequency and, finally, painless retention.
Spinal X-rays are rarely diagnostic. MRI is usually the investigation of choice and should not be delayed, but if not available consider doing a CT scan and myelography to confirm cord compression and fully define the level and extent of the lesion. If malignancy is the cause, it is important to give dexamethasone (oral or intravenous) while considering therapy more specific to the cause.

Gastrin is released by G cells in the antrum of the stomach. It stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and also aids in gastric motility. It is released in response to the following stimuli: vagal stimulation, antrum distention, hypercalcemia. It is inhibited by the following: presence of acid in stomach, SST, secretion, GIP, VIP, glucagon, calcitonin.

HIV can cause strictures in the biliary tract (see source for details of the disease). This makes the diagnosis of primary sclerosing cholangitis most likely given the clinical presentation and lab values. Due to its association with HIV this is more likely than all of the other answer choices. Know this association.

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.

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

Cubital Tunnel Syndrome is a condition that involves pressure or stretching of the ulnar nerve (also known as the “funny bone” nerve), which can cause numbness or tingling in the 4th and 5th digit, pain in the forearm, and/or weakness in the hand. Epicondylitis of the elbow is a condition associated with repetitive forearm and elbow activities. Both lateral epicondylitis (commonly known as tennis elbow) and medial epicondylitis (commonly known as golfer’s elbow) are characterized by elbow pain during or following elbow flexion and extension. Radial tunnel syndrome is a set of symptoms that include fatigue or a dull, aching pain at the top of the forearm with use. Although less common, symptoms can also occur at the back of the hand or wrist.

Clozapine can cause neutropenia or agranulocytosis.

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics.

It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.

Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.

Other side effects include:
Hypotension, tachycardia
Fever, sedation, seizures (with high doses)
Appetite increase
Constipation
Heartburn
Weight gain
Extrapyramidal symptoms
Agranulocytosis
Neuroleptic malignant syndrome

Hereditary C1 inhibitor deficiency leads to recurrent angioedema without urticaria or pruritus. Physical triggers include dental work, surgery or intubation. Medical triggers include angiotensin-converting enzyme (ACE) inhibitor, tamoxifen, oestrogen-containing medications (e.g., hormone replacement therapy and oral contraceptives). It is diagnosed on the basis of low levels of C1 esterase inhibitor or elevated levels of dysfunctional C1 esterase inhibitor. C4 levels are low between attacks. IgE levels, eosinophils, skin prick tests and RASTs are helpful in other allergic conditions and asthma but not of use in this case.

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

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

This is a typical picture of acute chest syndrome (ACS). According to the British Committee for Standards in Haematology (BCSH), ACS is defined as ‘an acute illness characterised by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on chest X-ray’. ACS occurs in sequestration crisis, which is one of the four main types of crises occurring in sickle cell disease.

The fundamentals of initial management are as follows:
1. Oxygen therapy to maintain saturation >95%
2. Intravenous fluids to ensure euvolemia
3. Adequate pain relief
4. Incentive spirometry in all patients presenting with rib or chest pain
5. Antibiotics with cover for atypical organisms
6. Bronchodilators if asthma co-exists with acute chest syndrome, or if there is an evidence of acute bronchospasm on auscultation
7. Early consultation with the critical care team and haematology department

A senior haematologist then makes a decision as to whether a simple or exchange transfusion is necessary in order to achieve a target Hb of 10.0–11.0g/dL in either instance.

Sickle Cell Crises:
Sickle cell anaemia is characterised by periods of good health with intervening crises:
1. Sequestration crisis: acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates)

2. Thrombotic (painful or vaso-occlusive) crisis: precipitated by infection, dehydration, and deoxygenation

3. Aplastic crisis: sudden fall in haemoglobin without marked reticulocytosis, usually occurring secondary to parvovirus infection

4. Haemolytic crisis: fall in haemoglobin secondary to haemolysis, rare type of sickle cell crises

All of the aforementioned listed tumours, except brain tumours, can metastasise to lungs and produce the typical CXR picture consisting of hilar lymphadenopathy with either diffuse multinodular shadows resembling miliary disease or multiple large well-defined masses (canon balls). Occasionally, cavitation or calcification may also be seen.

Most brain tumours, however, do not metastasise. Some, derived form neural elements, do so but in these cases, intraparenchymal metastases generally precede distant haematogenous spread.

The history and ECG findings are adequate to begin cardiac revascularization of this patient. There is no need for cardiac markers to confirm the diagnosis. Further delay in starting definite treatment is not recommended.

L4 dermatome distribution includes the kneecaps.

The most likely diagnosis is acute atrial fibrillation (AF) precipitated by acute pneumonia. History of fever, cough and the auscultation findings support it. So the most appropriate management is treating the pneumonia with antibiotics. Treating the underlying cause will reduce the heart rate. Other responses are helpful in the management of chronic AF.

Aortic dissection is defined as separation of the layers within the aortic wall. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space. This can be caused as a result of both congenital or acquired factors like chronic uncontrolled hypertension. This patient shows no sign of hypertension but his physical examination hints towards Marfan Syndrome. Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting the microfibrils and elastin in connective tissue throughout the body. MFS is associated with pathological manifestations in the cardiovascular system (e.g., mitral valve prolapse, aortic aneurysm, and dissection), the musculoskeletal system (e.g., tall stature with disproportionately long extremities, joint hypermobility), and the eyes (e.g., subluxation of the lens of the eye). Decreased collagen production occurs in ageing, hydroxylation defects are present in vitamin C deficiency, copper deficiency affecting lysyl oxidase enzyme occurs in Menke’s disease.

Bilateral occipital cortex infarction will produce varying degrees of cortical blindness, wherein the patient has no vision but fundoscopy findings are normal. When there are extensive lesions, patients my present with denial of their condition, known as Anton’s Syndrome, and begin to describe objects that they have never seen before.

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.

An overall concordance rate in monozygotic twins was documented to be 25% as compared to dizygotic twins with 3%. First degree relatives have a chance of around 3% of developing the disease. Caucasians show an increase frequency of HLA-B8. The Japanese lupus patients had a stronger association with HLA-DR2.

Hepatitis B full vaccine and Ig should be given to babies born to hepatitis B positive mothers. Hepatitis B vaccine alone or Ig alone is not sufficient to prevent the infection in the new-born baby.

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.

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 presents with a combination of akinetic rigid syndrome, cerebellar signs and the suggestion of autonomic features. This is most indicative of a diagnosis of multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia.

Catatonia is a state of apparent unresponsiveness to external stimuli and apparent inability to move normally in a person who is apparently awake. Catatonia can be acute and occur in severely ill patients with underlying psychiatric or other medical disorders.

A history of behavioural responses to others usually includes the presence of the following:
– Mutism (absence of speech)
– Negativism (performing actions contrary to the commands of the examiner)
– Echopraxia (repeating the movements of others)
– Echolalia (repeating the words of others)
– Waxy flexibility (slight, even resistance to positioning by examiner)
– Withdrawal (absence of responses to the environment).

In the presence of a catatonic state, both first and second generation antipsychotics (SGA) may contribute to maintaining or worsening the catatonic state and increase the risk of developing NMS (neuroleptic malignant syndrome).

Electroconvulsive therapy (ECT) is effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient’s medical condition.

Electroconvulsive therapy (ECT) is a procedure, done under general anaesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions.

Pregnant patient in a third world country with hepatitis: The answer is most likely Hepatitis E. The mortality for Hepatitis E in pregnant women is very high. It is transmitted faecal-orally. There is no hepatitis G. Hepatitis C, B, A are less likely to be the correct answer than E given it’s classic association with pregnancy and poor living conditions.

Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%.

The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.

This patient has a dendritic corneal ulcer. Herpes simplex keratitis most commonly presents with a dendritic corneal ulcer. Topical acyclovir and ophthalmology review is required. Giving a topical steroid in this situation could be disastrous as it may worsen the infection.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by stressful, frightening or distressing events.

PTSD is a lasting consequence of traumatic ordeals that cause intense fear, helplessness, or horror, such as a sexual or physical assault, the unexpected death of a loved one, an accident, war, or natural disaster. Families of victims can also develop PTSD, as can emergency personnel and rescue workers.

PTSD is diagnosed after a person experiences symptoms for at least one month following a traumatic event. However symptoms may not appear until several months or even years later. The disorder is characterized by three main types of symptoms:
-Re-experiencing the trauma through intrusive distressing recollections of the event, flashbacks, and nightmares.
-Emotional numbness and avoidance of places, people, and activities that are reminders of the trauma.
-Increased arousal such as difficulty sleeping and concentrating, feeling jumpy, and being easily irritated and angered.

The goal of PTSD treatment is to reduce the emotional and physical symptoms, to improve daily functioning, and to help the person better cope with the event that triggered the disorder. Treatment for PTSD may involve psychotherapy (a type of counselling), medication, or both.

Certain antidepressant medications are used to treat PTSD and to control the feelings of anxiety and its associated symptoms including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Mood stabilizers such are sometimes used.

Afferent pupillary defect is simply a delayed pupillary response to light. Accommodation is otherwise unaffected.

The upper motor neurone signs in this patient point towards a diagnosis of spinal cord compression above the level of L1 and rules out cauda equina syndrome.

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. One of the most common causes of spinal cord compression is osteoarthritis. It is also more commonly seen in patients with lung, breast, or prostate cancer.

Clinical features include:
1. Back pain: the earliest and most common symptom, may worsen on lying down or coughing
2. Lower limb weakness
3. Sensory changes: sensory loss and numbness
4. Neurological signs: depending on the level of the lesion.
Lesions above L1 usually result in upper motor neurone signs in the legs. Lesions below L1 usually cause lower motor neurone signs in the legs and perianal numbness. Tendon reflexes are increased below the level of the lesion and absent at the level of the lesion.

Management options are:
1. High-dose oral dexamethasone
2. Urgent MRI for consideration of radiotherapy or surgery

Proton pump inhibitors can reduce gastric acid secretion by up to 99%. Acid production resumes following the normal renewal of gastric parietal cells.

One of the questions the therapist poses himself while informing a patient is: whom shall I inform about the diagnosis, treatment and prognosis? If we unconditionally accepted the view that information belongs to the patient from an ethical and legal standpoint, we would automatically exclude the partner and the family. Therefore, the therapist should raise another question: what is the benefit to the patient? To answer the question and the resulting dilemma, we have to leverage the long experience of family therapy and tailor it to the cases we are dealing with. It should be taken into consideration that patient and family are a dynamic system which was balanced before the onset of the disease, but is now disrupted, entering into crisis. Therefore, the denial mechanisms and personality characteristics we have previously elaborated on, and communication among members play a crucial role in determining the information strategy and the way family should be approached. In this particular case, the most appropriate person to inform the patient is the consultant, meaning the one currently responsible for the patient’s care. The patient most probably has already developed some form of close and trustful relationship with his consultant.

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.

The presentation of the patient is typical of chronic lithium toxicity (due to the presence of mainly neurological manifestations). Additional to the blood investigations mentioned, urine analysis, electrolyte levels, and renal function should also be performed. A low urine Anion gap and a low urine specific gravity are highly suggestive of lithium toxicity.
ECG obtained in this patient is likely to show: nonspecific, diffuse ST segment depression with T wave inversion.
Acute lithium toxicity presents with more GI manifestations while, the clinical features of chronic lithium toxicity are mainly neurological and can include:
Coarse tremors (fine tremors are seen in therapeutic levels), hyperreflexia, acute confusion, seizures, and coma.
The management of lithium toxicity is as follows:
Immediate GI decontamination with gastric lavage (in case of acute intoxication)
Saline Administrations: the goal of saline administration is to restore GFR, normalize urine output and enhance lithium clearance.
Haemodialysis remains the mainstay treatment for lithium toxicity as lithium is readily dialyzed because of water solubility, low volume of distribution, and lack of protein binding.
The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP Workgroup) recommendations for dialysis (extracorporeal treatment) in lithium toxicity include:
• Impaired kidney function and lithium levels > 4.0 mEq/L
• Decreased consciousness, seizures, or life-threatening dysrhythmias, regardless of lithium levels
• Levels are > 5.0 mEq/L, significant confusion is noted, or the expected time to reduce levels to < 1.0 mEq/L is more than 36 hours
As post-dialysis rebound elevations in lithium levels have been documented, continuous veno-venous hemofiltration (CVVH) has been advocated.

There are five prognostic factors which indicate poor prognosis in HOCM:
-family history of HOCM-related sudden cardiac death
-unexplained recent syncope
-large left ventricular wall thickness (MLVWT ≥ 30 mm)
-multiple bursts of nsVT on ambulatory electrocardiography
-hypotensive or attenuated blood pressure response to exercise

Osteomalacia is a marked softening of the bones that can present in both type I and type II Renal Tubular Acidosis (RTA) and will thus not differentiate the two types in any case. The other measures will allow differentiation of the two types.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. Symmetric lower limb arthropathy and a sterile joint aspirate points towards reactive arthropathy.

Cerebral venous sinus thrombosis (CVST) is associated with headache (>90% of cases), seizures, focal weakness (40%) and papilledema (40%), all seen in this patient.
Risk factors for CVST include genetic or acquired prothrombotic disorders, pregnancy, the oral contraceptive pill, vasculitis, malignancy, dehydration and infection. However, there are multiple other associated factors.
Diagnosis is normally confirmed with magnetic resonance venography (MRV). Treatment is with anticoagulation, initially with heparin and subsequently with warfarin.

Varicose eczema is a common problem, particularly in elderly patients due to stasis or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins. It is often mistaken for cellulitis, but cellulitis is rarely bilateral and is painful rather than itchy.

The most likely diagnosis is Wernicke’s encephalopathy. This presents in a long time alcoholic from vitamin BI deficiency. Symptoms include confusion and confabulation, oculomotor symptoms/signs, and ataxia.

The foramen rotundum is one of the several circular apertures (the foramina) located in the base of the skull, in the anterior and medial part of the sphenoid bone. The maxillary branch (V2) of the trigeminal nerve (CN V) passes through and exits the skull via the pterygopalatine fossa and the foramen rotundum.

Ankylosing spondylitis (spondylarthritis) is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease.
The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumour necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. The spine adopts a bamboo shape, not lordosis. The pain usually improves as the day progresses. leg raise test causes pain in cases of meningitis etc not in this case.

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.

Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas (rare), and primary thyroid sarcomas (rare).
Hürthle cell carcinoma is a rare thyroid malignancy that is often considered a variant of follicular carcinoma.
– Papillary and Follicular carcinoma are slow-growing tumours
– Sporadic cases of Medullary thyroid carcinoma also typically manifest with painless solitary thyroid nodules in the early stages.
– Anaplastic thyroid carcinoma has the most aggressive biologic behaviour of all thyroid malignancies and has one of the worst survival rates of all malignancies in general. It manifests as a rapidly growing thyroid mass in contrast to a well-differentiated carcinoma, which are comparatively slow-growing. Patients commonly present with associated symptoms due to local invasion. Hoarseness and dyspnoea resulting from the involvement of the recurrent laryngeal nerve and airway occur in as many as 50% of patients.
– Almost all patients with primary thyroid lymphoma have either a clinical history or histological evidence of chronic lymphocytic thyroiditis. The risk of primary thyroid lymphoma increases 70-fold in patients with chronic lymphocytic thyroiditis compared with the general population. Regional and distant lymphadenopathy is common.

The most common location for a duodenal ulcer bleed is the posterior duodenum (remember: posterior bleeds, anterior perforates). The perfusion to this area is most specifically from the posterior superior pancreaticoduodenal artery.

The anterior superior pancreaticoduodenal artery supplies the anterior region. The gastroepiploic artery supplies mostly the stomach. The splenic artery goes, obviously, toward the spleen, in the other direction. The gastroduodenal artery is a branch of the celiac artery, and it’s branches are the anterior superior pancreaticoduodenal artery and posterior superior pancreaticoduodenal artery.

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.

People with Systemic Juvenile Idiopathic Arthritis (also known as Stills disease) can have recurrent fevers, a macular rash, joint pain, joint deformities, an enlarged liver and/or spleen, and can occasionally have polyserositis, lung involvement or pericardial effusions. Rheumatoid factor and antinuclear antibodies are usually negative. Treatment is with non-steroidal anti-inflammatory drugs (NSAIDs) and the prognosis is better than for adult rheumatoid arthritis.
In pauciarticular Still’s disease, antinuclear antibodies are present. Large joints are affected and most patients develop classic features of seronegative spondylarthritis.

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.

The history is suggestive of leptospirosis. This is a zoonotic infection caused by a spirochete. As the patient is in shock, resuscitation with IV fluids is the first step in the management. IV antibiotics should be started (Doxycycline or Penicillin) as soon as possible. Other investigations mentioned are important during the management to rule out other possible diagnoses.

TNF-alpha inhibitors are known to ameliorate the symptoms and disease activity of Arthritis mutilans (a rare and severe form of psoriatic arthritis), by disabling the cytokines that are involved in inflammation and joint destruction. From the mentioned choices, this would be the most effective option. Methotrexate is the most commonly used DMARD, followed by sulfasalazine used in mild to moderate forms of psoriatic arthritis but has not shown much efficacy in arthritis mutilans. Phototherapy, narrowband UVB light therapy can be very effective in clearing skin lesions.

The C8 nerve forms part of the radial and ulnar nerves via the brachial plexus, and therefore has motor and sensory function in the upper limb. It originates from the spinal column from below the cervical vertebra 7 (C7).
The C8 nerve receives sensory afferents from the C8 dermatome. This consists of all the skin on the little finger, and continuing up slightly past the wrist on the palmar and dorsal aspects of the hand and forearm.
The other options available correspond to the C6 or C7 roots and these are unaffected as evidenced by normal elbow flexion and thumb sensation (C6) and normal sensation over the middle finger (C7). Elbow extension is weak as it has roots from both C7 and C8 and so cannot be used alone to decide between the two levels clinically.
The C8 nerve contributes to the motor innervation of many of the muscles in the trunk and upper limb. Its primary function is the flexion of the fingers, and this is used as the clinical test for C8 integrity, in conjunction with the finger jerk reflex.

Trunk:
– Pectoralis major – Medial and lateral pectoral nerves (C5, C6, C7, C8, T1)
– Pectoralis minor – Medial pectoral nerve (C5, C6, C7,C8, T1)
– Latissimus dorsi – Thoracodorsal nerve (C6, C7, C8)
Upper arm:
– Triceps brachii – Radial nerve (C6, C7,C8)
Forearm
– Flexor carpi ulnaris – Ulnar nerve (C7, C8, T1)
– Palmaris longus – Median nerve (C7,C8)
– Flexor digitorum superficialis – Median nerve (C8, T1)
– Flexor digitorum profundus – Median and Ulnar nerves (C8, T1)
– Flexor pollicis longus – Median nerve (C7,C8)
– Pronator quadratus – Median nerve (C7,C8)
– Extensor carpi radialis brevis – Deep branch of the radial nerve (C7,C8)
– Extensor digitorum – Posterior interosseous nerve (C7,C8)
– Extensor digiti minimi – Posterior interosseous nerve (C7,C8)
– Extensor carpi ulnaris – Posterior interosseous nerve (C7,C8)
– Anconeus – Radial nerve (C6, C7,C8)
– Abductor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor pollicis brevis – Posterior interosseous nerve (C7,C8)
– Extensor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor indicis – Posterior interosseous nerve (C7,C8)
Hand
– Palmaris brevis – Superficial branch of ulnar nerve (C8, T1)
– Dorsal interossei – Deep branch of ulnar nerve (C8, T1)
– Palmar interossei – Deep branch of ulnar nerve (C8, T1)
– Adductor pollicis – Deep branch of ulnar nerve (C8, T1)
– Lumbricals – Deep branch of ulnar, Digital branches of median nerve
– Opponens pollicis – Recurrent branch of median nerve (C8, T1)
– Abductor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Flexor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Opponens digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Abductor digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Flexor digiti minimi brevis – Deep branch of ulnar nerve (C8, T1)

The patient likely has celiac’s disease, but if she has been avoiding gluten, a biopsy may be negative. Even though a biopsy is the gold standard for diagnosis, she will need to re-introduce gluten into her diet prior to undergoing the biopsy.

The normal partial pressure reference values are: oxygen PaO2 more than 80 mmHg (11 kPa), and carbon dioxide PaCO2 lesser than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 of 6.8kPa which exceeds the normal value of less than 6.0kPa.
The pH is also lower than 7.35 at 7.32

In any patient with asthma, an increasing PaCO2 indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

According to the British Thoracic Society guidelines:
Indications for admission to intensive care or high-dependency units include
patients requiring ventilatory support and those with acute severe or life-threatening asthma who are failing to respond to therapy, as evidenced by:
• deteriorating PEF
• persisting or worsening hypoxia
• hypercapnia
• arterial blood gas analysis showing fall in pH or rising hydrogen concentration
• exhaustion, feeble respiration
• drowsiness, confusion, altered conscious state
• respiratory arrest

Transfer to ICU accompanied by a doctor prepared to intubate if:
• Deteriorating PEF, worsening or persisting hypoxia, or hypercapnia
• Exhaustion, altered consciousness
• Poor respiratory effort or respiratory arrest

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to
patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy.
Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

The most probable cause for diarrhoea is pseudomembranous colitis which is caused by Clostridium difficile. Pseudomembranous colitis is an inflammatory disease of the colon where the antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile. Any antibiotic can cause this but the chances are higher with ampicillin, clindamycin, fluoroquinolones, and cephalosporins.

The main cardiovascular manifestations associated with Marfan’s syndrome are aortic dilatation and mitral valve prolapse.

The tumour has only invaded the visceral pleura and measures 3cm in the greatest dimension. Hence it is designated at T2. Ipsilateral peribronchial and/or hilar lymph node involvement would make it N1. There is no distal metastasis so M would be 0.

Polycythaemia vera (PV) is associated with a low ESR.

PV, also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance. PV is associated with a low ESR.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or acute myeloid leukaemia (AML). The risk of having AML is increased with chemotherapy treatment.

Most new moms experience postpartum baby blues after childbirth, which commonly include mood swings, crying spells, anxiety and difficulty sleeping. Baby blues typically begin within the first two to three days after delivery, and may last for up to two weeks.

Signs and symptoms of baby blues may include:
Mood swings
Anxiety
Sadness
Irritability
Feeling overwhelmed
Crying
Reduced concentration
Appetite problems
Trouble sleeping

The exact cause of the “baby blues” is unknown at this time. It is thought to be related to the hormone changes that occur during pregnancy and again after a baby is born. These hormonal changes may produce chemical changes in the brain that result in depression.
Although the experience of baby blues is unpleasant, the condition usually subsides within two weeks without treatment. All the mom needs is reassurance and help with the baby and household chores.

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.

The patient has paroxysmal nocturnal haemoglobinuria (PNH). The classic sign of the disease is red discolouration of the urine due to the presence of haemoglobin and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the colour is most pronounced.

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combinations of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

Lead can be absorbed through the skin and by inhalation. It is associated with iron deficiency and a microcytic anaemia. The most common gastrointestinal symptoms are abdominal colic and constipation.

In patients with polycystic ovarian syndrome (PCOS), FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Women with PCOS have abnormalities in the metabolism of androgens and oestrogen and in the control of androgen production. PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism. Other signs and symptoms of PCOS may include the following:
– Hirsutism
– Infertility
– Obesity and metabolic syndrome
– Diabetes
– Obstructive sleep apnoea

Androgen excess can be tested by measuring total and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess. Other androgens, such as dehydroepiandrosterone sulphate (DHEA-S), may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS). Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one-third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. Absolute risk reduction = (Control event rate) – (Experimental event rate) = 0.15 = 15%

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

Diabetic peripheral neuropathy usually goes in parallel with retinopathy and nephropathy. It is also slowly progressive and affects mainly the spinothalamic pathway.
Alcohol induced peripheral neuropathy is also slowly progressive and affects mainly the spinothalamic pathway.
Vitamin B 12 deficiency usually causes a more rapidly progressive neuropathy with dorsal column involvement (joint position and vibration involvement with sensory ataxia and pseudoathetosis of upper limbs).

If steroid is applied first, applying an emollient after could spread it from where it had been applied. If steroid is applied immediately after the emollient then it cannot be absorbed, this is why there should be a time interval of around thirty minutes between these two treatments in order for them to be effective.

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.

The correct course of action after giving terlipressin and resuscitating with IV fluids is to perform an EGD with endoscopic variceal band ligation. According to NICE: ‘Offer endoscopic variceal band ligation for the primary prevention of bleeding for people with cirrhosis who have medium to large oesophageal varices. There are serious complications of a TIPS procedure and it is not the first line treatment.

Activated charcoal is useful if given within one hour of the paracetamol overdose. Liver function tests, INR and prothrombin time will be normal, as liver damage may not manifest until 24 hours or more after ingestion.

The antidote of choice is intravenous N-acetylcysteine, which provides complete protection against toxicity if given within 10 hours of the overdose.

Lidocaine is an example of class IB antiarrhythmics.

The Vaughan-Williams classification of antiarrhythmics
I: Membrane stabilizing agents
IA: Quinidine, Procainamide, Disopyramide
IB: Lidocaine, Mexiletine
IC: Propafenone, Flecainide
II: β blockers – Propranolol, Esmolol
III: Agents widening AP – Amiodarone, Dronedarone, Dofetilide, Ibutilide, Sotalol
IV: Calcium channel blockers – Verapamil, Diltiazem
V: Miscellaneous – Digoxin, adenosine, magnesium

The classes refer to the WHO classification of glomerulonephritis in SLE patients.
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis

Class IV: diffuse proliferative glomerulonephritis is the most common and the most severe form, where more than 50% of the glomeruli are involved.

One of the most important complications in patients with PKD is being affected by berry aneurysms that may burst, causing a subarachnoid haemorrhage, which seems to be the case in this patient.

Central chemoreception refers to the detection of changes in CO2/H+ within the brain and the associated effects on breathing. In the conscious animal the response of ventilation to changes in the brain’s interstitial fluid (ISF) pH is very sensitive. Note that a small change in cerebrospinal fluid (CSF) pH from 7.30 to 7.25 is associated with a doubling of alveolar ventilation; it is a very sensitive reflex response. Note also that the relationship of alveolar ventilation to ISF pH is essentially the same for both types of stimulation, metabolic acid-base disorders and primary CO2 stimulation.

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

Hypogammaglobulinemia occurs due to a variety of underlying primary or secondary immunodeficient states, including HIV which is suspected in this case. The most commonly recognised clinical feature is recurrent infection.

Based on the given clinical scenario, the most probable diagnosis in this patient is acute paranoid schizophrenia.

Schizophrenia is a functional psychotic disorder characterized by the presence of delusional beliefs, hallucinations, and disturbances in thought, perception, and behaviour.

Clinical features:
Schneider’s first-rank symptoms may be divided into auditory hallucinations, thought disorders, passivity phenomena, and delusional perceptions:

Auditory hallucinations of a specific type:
Two or more voices discussing the patient in the third person
Thought echo
Voices commenting on the patient’s behaviour

Thought disorder:
Thought insertion
Thought withdrawal
Thought broadcasting

Passivity phenomena:
Bodily sensations being controlled by external influence
Actions/impulses/feelings – experiences which are imposed on the Individual or influenced by others

Other features of schizophrenia include
Impaired insight (a feature of all psychoses)
Incongruity/blunting of affect (inappropriate emotion for circumstances)
Decreased speech
Neologisms: made-up words
Catatonia
Negative symptoms: incongruity/blunting of affect, anhedonia (inability to derive pleasure), alogia (poverty of speech), avolition (poor motivation).

Treatment:
For the initial treatment of acute psychosis, it is recommended to commence an oral second-generation antipsychotics such as aripiprazole, olanzapine, risperidone, quetiapine, etc.
Once the acute phase is controlled, switching to a depot preparation like aripiprazole, paliperidone, zuclopenthixol, fluphenazine, haloperidol, pipotiazine, or risperidone is recommended.
Cognitive-behavioural therapy (CBT) and the use of art and drama therapies help counteract the negative symptoms of the disease, improve insight, and assist relapse prevention.
Clozapine is used in case of treatment resistance.

Drug metabolism can be broadly classified into:
Phase I (functionalization) reactions: also termed non-synthetic reactions, they include oxidation, reduction, hydrolysis, cyclization and de-cyclization. The most common and vital reactions are oxidation reactions. (Of the given enzymes only Alcohol dehydrogenase is involved in phase I drug metabolism. Succinate dehydrogenase, is a vital enzyme involved in the Kreb’s cycle and the mitochondrial electron transport chain). They are mainly catalysed by Cytochrome P-450 enzyme.

Phase II (conjugation) reactions: occur following phase I reactions, they include reactions: glucuronidation and sulphate conjugation, etc. They are mostly catalysed by UDP-glucuronosyltransferase enzyme. Other phase II enzymes include: sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases.

Gaucher’s disease is characterized by hepatosplenomegaly, cytopenia, sometimes severe bone involvement and, in certain forms, neurological impairment. The variability in the clinical presentations of GD may be explained by the continuum of phenotypes. However, three major phenotypic presentations can usually be distinguished. Type-1 GD is usually named non-neuronopathic GD; type-2 and type-3 are termed neuronopathic-GD. Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages.

According to the history the patient has cardiogenic shock and pulmonary oedema. On-going ischaemia is indicated by persisting symptoms. So the most appropriate management is coronary angiography and rescue PCI. There are no indications for blood transfusion at this moment and it will aggravate the pulmonary oedema. Haemodialysis, beta blockers and furosemide cannot be given due to low blood pressure.

The most appropriate treatment in this patient would be to stop warfarin therapy and keep the patient under observation.

The drugs that lead to enhanced potency of warfarin include: disulfiram, trimethoprim-sulphamethoxazole, metronidazole, phenylbutazone, aspirin, heparin, and clofibrate.
Liver disease, thrombocytopenia, hyperthyroidism also increase the oral anticoagulant potency.
If the patient has minor bleeding and the international normalized ratio (INR) is >6.0, warfarin should be stopped; the INR should be rechecked daily and in addition to the stoppage of warfarin, vitamin K 2.5 mg oral or 0.5 mg intravenously should also be administered.
In a patient with INR of 2.0 or 3.0, it takes two or three times longer for that individual’s blood to clot than someone who is not taking any anticoagulants. Most patients on warfarin have an INR goal of 2 to 3.

If there is major bleeding then prothrombin complex concentrates 50 u/kg or fresh-frozen plasma 15 ml/kg may be considered.

To describe how often a disease or another health event occurs in a population, different measures of disease frequency can be used. The prevalence reflects the number of existing cases of a disease. In contrast to the prevalence, the incidence reflects the number of new cases of disease and can be reported as a risk or as an incidence rate. Prevalence and incidence are used for different purposes and to answer different research questions.

Speaking to your consultant is the most appropriate first action to take in this scenario. They are best placed to be able to take action to try and amend the situation. The consultant is also ultimately responsible for patient care and hterefore have a right to know if you are struggling, as this may affect patient care.
Arriving early and taking time off sick do not address the problem.

The patient has primary Hypogonadism.
Since he already had two children, Klinefelter syndrome is excluded and the patient does not need karyotyping.
His lab results are normal indicating normal pituitary gland functions.
So the next step is testicular ultrasound as testicular tumour, infiltration or idiopathic failure is suspected.

Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin.

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.

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome

The best treatment for a colovesicular fistula is surgery. This is the only definitive treatment. If the patient is a poor surgical candidate, there can be an attempt to manage them non-operatively, but this is absolutely NOT the MOST EFFECTIVE therapy.

A history of ischaemic heart disease in a contraindication for prescribing triptans because they act by constricting cerebral and also coronary vessels, increasing the risk of stroke.

To differentiate ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrant conduction the following electrocardiographic features should be looked for:

Evidence of preceding atrial activity for SVT. Oesophageal leads are helpful if P waves are hidden in the QRS complex.
QRS duration more than 140 ms for VT.
QRS morphology: Features of QRS morphology that favour SVT are RBBB or triphasic patterns like rSR in V1 and qRS in V6. Monophasic pattern like R or qR in V1 and rS or QS in V6 or multiple morphology QRS complexes favour VT.
AV dissociation for VT.

The most probable diagnosis is Herpes Simplex infection. Topical Acyclovir can be used in early stages.

Infective causes of hair loss include:
Dissecting cellulitis
Fungal infections (such as tinea capitis)
Folliculitis
Secondary syphilis
Demodex folliculorum
Lupus erythematosus (hair loss may be permanent due to scarring of the hair follicles).
Psoriasis and seborrheic dermatitis commonly involve the scalp but do not produce hair loss.

The patient’s history of recent weight loss and malaise, paired with enlarged kidneys and renal failure, as well as a suspected central pelvic mass on ultrasound, gives a suspicion of cervical carcinoma.

CHA₂DS₂-VASc score is used for atrial fibrillation stroke risk calculation.
Congestive heart failure – 1 point
Hypertension – 1 point
Age ≥75 years – 2 points
Diabetes mellitus – 1 point
Stroke/Transient Ischemic Attack/Thromboembolic event – 2 points
Vascular disease (prior MI, PAD, or aortic plaque) – 1 point
Age 65 to 74 years – 1 point
Sex category (i.e., female sex) – 1 point
A score of 2 or more is considered as high risk and anticoagulation is indicated. This patient’s score is 3, so he needs life long warfarin to prevent stroke.

Benign Prostatic Enlargement or Hyperplasia (BPE/BPH) is the most probable diagnosis of the patient in question. It is a histological diagnosis characterized by proliferation of the cellular elements of the prostate.
The initial treatment modality of choice is selective alpha 1 antagonists (such as Prazosin, Alfuzosin and Indoramin, and long acting agents like, Terazosin, Doxazosin, etc.) as they provide immediate relief from the bothersome lower urinary tract symptoms (LUTS).
Other treatment modalities include:
• Non-selective alpha blockers: no longer used due to severe adverse effects and the availability of selective alpha 1 blockers.
• 5 alpha reductase inhibitors: Finasteride and Dutasteride, they target the underlying disease process and reduce the overall prostate volume. Thus, reduce the urinary retention and the lower urinary tract symptoms. (They do not provide immediate relief from LUTS and thus are not preferred as first line drugs over alpha 1 antagonists)
• PDE-5 Inhibitors: The long-acting tadalafil has proven to be useful.
• Surgical Treatment modalities: TURP, Prostatectomy, etc.

It has been determined that HPV infection is the most powerful epidemic factor. This virus is needed, but not sufficient for the development of cervical cancer.
The WHO’s International Agency for Research on Cancer (IARC) classified HPV infection as carcinogenic to humans (HPV types 16 and 18), probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11).
Tobacco smoking, the use of contraceptives, and the number of births are factors that showed no statistically significant deviations in the studied population compared to other countries in the region, as well as European countries. They have an equal statistical significance in all age groups.

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

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.

Hashimoto thyroiditis is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is an inadequate dietary intake of iodine. This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, comparing two independent samples from the same population.

In central and nephrogenic diabetes insipidus (DI), urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI.

In primary polydipsia, water deprivation results in an increase in urine osmolality, anywhere between 300 – 800 mOsm/Kg (usually up to 600 – 700 mOsm/Kg), without a substantial increase in plasma osmolality, but the increase in urine osmolality is not as substantial as in a normal response.

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.

Early morning waking is a highly suggestive feature of depression in this patient.

NICE use the DSM-IV criteria to grade depression:
1. Depressed mood most of the day, nearly every day
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
3. Significant weight loss or weight gain when not dieting or decrease or increase in appetite nearly every day
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day
8. Diminished ability to think or concentrate, or indecisiveness nearly every day
9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Subthreshold depressive symptoms: Fewer than 5 symptoms
Mild depression: Few, if any, symptoms over the 5 required to make the diagnosis, and symptoms result in only minor functional impairment
Moderate depression: Symptoms or functional impairment are between ‘mild’ and ‘severe’
Severe depression: Most symptoms and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms.

Treatment of depression:
Psychotherapy (in the form of cognitive behavioural therapy or interpersonal therapy) alone or in combination with medications such as:
– Selective serotonin reuptake inhibitors (SSRIs)
– Serotonin/norepinephrine reuptake inhibitors (SNRIs)
– Atypical antidepressants
– Serotonin-Dopamine Activity Modulators (SDAMs)
– Tricyclic antidepressants (TCAs)

There is also empirical support for the ability of CBT to prevent relapse.

Electroconvulsive therapy is a useful treatment option for patients with severe depression refractory to medication or those with psychotic symptoms. The only absolute contraindications is raised intracranial pressure.

Side-effects:
Headache
Nausea
Short term memory impairment
Memory loss of events before ECT
Cardiac arrhythmia
Long-term side-effects: Impaired memory

Hepatitis C is a single-stranded positive sense RNA virus. It is variable because of the high rate of error of RNA-dependent RNA polymerase and the pressure from the host immune system has caused HCV to evolve and develop seven genetic lineages.

Methotrexate lung disease (pneumonitis and fibrosis) is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given as disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy. Methotrexate withdrawal is indicated in such cases.

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.

This girl most probably has Turner’s syndrome, which is caused by the absence of one set of genes from the short arm of one X chromosome.
Turner syndrome is a lifelong condition and needs lifelong oestrogen replacement therapy. Oestrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose oestrogens. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months; progestin can be added later.

In childhood, growth hormone therapy is standard to prevent short stature as an adult.

Fetal ovarian development seems to be normal in Turner syndrome, with degeneration occurring in most cases around the time of birth so pulsatile GnRH and luteinising hormone would be of no use.

Streptococcus pneumonia is the chief causative organism for lobar pneumonia in this age group patients. Typically patients present with rusty coloured sputum and a cough. Pneumocystis jiroveci is responsible for causing pneumocystis pneumonia among immunocompromised patients.

The duration of these cell cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 phase might last about 11 hours, S phase about 8 hours, G2 about 4 hours, and M about 1 hour. The proliferation of most animal cells is similarly regulated in the G1 phase of the cell cycle. In particular, a decision point in late G1, called the restriction point in animal cells, is the point at which the cell becomes committed to the cell cycle and after which extracellular proliferation stimulants are no longer required.. Although the proliferation of most cells is regulated primarily in G1, some cell cycles are instead controlled principally in G2.

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.

The oxygen saturation in the pulmonary artery is higher than that of the right ventricle. The pressure of the pulmonary artery and of the PCWP are also high. So patent ductus arteriosus is highly suggestive.

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

Alveolar haemorrhage (AH) is a rare, but serious manifestation of SLE. It may occur early or late in disease evolution. Extrapulmonary disease may be minimal and may be masked in patients who are already receiving immunosuppressants for other symptoms of SLE.

DLCO or TLCO (diffusing capacity or transfer factor of the lung for carbon monoxide (CO)) is the extent to which oxygen passes from the air sacs of the lungs into the blood.
Factors that can increase the DLCO include polycythaemia, asthma (can also have normal DLCO) and increased pulmonary blood volume as occurs in exercise. Other factors are left to right intracardiac shunting, mild left heart failure (increased blood volume) and alveolar haemorrhage (increased blood available for which CO does not have to cross a barrier to enter).

The differential diagnosis of bilateral exercise-induced pain would include metabolic muscle disease, lumbar canal stenosis and intermittent claudication. The patient’s age, history and lack of other risk factors make the latter two options unlikely.

The syndrome described is in fact McArdle’s disease (myophosphorylase deficiency). This is a disorder of carbohydrate metabolism. Clinical features of pain and fatigue are precipitated in early exercise, as carbohydrates cannot be mobilized to provide an energy substrate to the muscle. With prolonged exercise, fatty acid metabolism provides energy, and symptoms lessen. The dark urine described is likely to represent myoglobinuria following rhabdomyolysis. Definitive diagnosis of most metabolic muscle diseases relies on muscle biopsy and enzyme analysis.

The given history is more compatible with spontaneous pneumothorax. Left-sided pneumothoraxes may be associated with a clicking noise, which is heard with each heart-beat and can sometimes be heard by the patient.

Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally). These shifts result from hormonal and metabolic changes and may cause serious clinical complications. The hallmark biochemical feature of refeeding syndrome is hypophosphatemia. However, the syndrome is complex and may also feature abnormal sodium and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency; hypokalaemia; and hypomagnesaemia.

Polymyalgia rheumatica, a syndrome characterized by proximal muscle pain and stiffness in older persons, generally is treated with prednisone. Dosages of 15 to 25 mg of prednisone per day can reduce inflammation considerably, although many patients relapse when therapy is tapered. Long-term (18 to 36 months) steroid treatment has been recommended by several studies, but this can result in multiple side effects, including osteoporosis, hypertension, cataracts, and hyperglycaemia. Methotrexate has been used to reduce inflammation in rheumatoid arthritis, systemic vasculitis, and giant cell arteritis, and in some studies has been combined with prednisone to treat polymyalgia rheumatica, decreasing the duration of treatment.

The principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Paget disease is a localized disorder of bone remodelling that typically begins with excessive bone resorption followed by an increase in bone formation. This osteoclastic over activity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:
– Bone pain (the most common symptom)
– Secondary osteoarthritis (when Paget disease occurs around a joint)
– Bony deformity (most commonly bowing of an extremity)
– Excessive warmth (due to hypervascularity)
– Neurologic complications (caused by the compression of neural tissues)
Measurement of serum alkaline phosphatase—in some cases, bone-specific alkaline phosphatase (BSAP)—can be useful in the diagnosis of Paget disease. Elevated levels of urinary markers, including hydroxyproline, deoxypyridinoline, C-telopeptide, and N -telopeptide, may help identify patients with Paget disease.
Serum calcium and phosphate levels should be within the reference range in patients with Paget disease.

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

The blood investigations in this patient reveal hyponatremia as well as hypokalaemia. Among the options provided, Bendroflumethiazide therapy can cause the above presentation with the electrolyte disturbances.
Note:
– Spironolactone is a potassium-sparing diuretic that is associated with hyperkalaemia.
– Enalapril therapy can cause side effects of dizziness, hypotension, cough, and rarely a rash.
– Felodipine therapy can cause side effects of dizziness, headache, cough, and palpitations.

The a wave indicates atrial contraction. The c wave indicates ventricular contraction and resulting bulging of the tricuspid valve into the right atrium during isovolumetric systole. The v wave indicates venous filling. The x descent indicates the atrium relaxation and the movement of tricuspid valve downward. The y descent indicates the filling of the ventricle after the opening of the tricuspid valve.

B-type natriuretic peptide (BNP) is secreted mainly from the left ventricle and it is secreted as a response to stretching caused by increased ventricular blood volume.

The a wave indicates atrial contraction. The c wave indicates ventricular contraction and the resulting bulging of tricuspid valve into the right atrium during isovolumetric systole. The v wave indicates venous filling. The x descent indicates the atrium relaxation and the movement of the tricuspid valve downward. The y descent indicates the filling of the ventricle after tricuspid opening.

Anti–Mi-2 antibodies are highly specific for dermatomyositis, but sensitivity is low; only 25% of patients with dermatomyositis demonstrate these antibodies. A positive antinuclear antibody (ANA) finding is common in patients with dermatomyositis, but is not necessary for diagnosis. Anti-Jo-1 antibodies are mostly associated with polymyositis. Anti Scl-70 antibodies and anti centromere antibodies are most commonly found in systemic scleroderma.

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 normal partial pressure reference values are:
– PaO2 more than 80 mmHg (11 kPa)
– PaCO2 less than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 (7.4kPa)
Hypoxemia (PaO2 <8kPa) with hypercapnia (PaCO2 >6.0kPa).
The pH is also lower than 7.35 at 7.3

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the build-up of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include:
– Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)
– Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
– A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
– Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)
– Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

Oestrogen therapy reduces plasma levels of LDL cholesterol and increases levels of HDL cholesterol. It can improve endothelial vascular function, however, it also has adverse physiological effects, including increasing the plasma levels of triglycerides (small dense LDL particles). Therefore, although HRT may have direct beneficial effects on cardiovascular outcomes, these effects may be reduced or balanced by the adverse physiological effects.

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 vas deferens is a long tube that connects the epididymis to the ejaculatory ducts. It acts as a canal through which mature sperm may pass through the penis during ejaculation.

Most men with CF (97-98 percent) are infertile because of a blockage or absence of the vas deferens, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never makes it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. The absence of sperm in the semen can also contribute to men with CF having thinner ejaculate and lower semen volume.

Supraspinatus tendinopathy is a common and disabling condition that becomes more prevalent after middle age and is a common cause of pain in the shoulder. A predisposing factor is resistive overuse. This patient has the classic painful arc that is a sign of shoulder impingement characteristic of supraspinatus tendonitis.

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.

Indications for permanent pacemaker implantation

-Sinus node dysfunction
-Acquired Atrioventricular(AV) block (Complete third-degree AV block with or without symptoms, Symptomatic second degree AV block, Mobitz type I and II, Exercise-induced second or third degree AV block in the absence of myocardial infarction, Mobitz II with widened QRS complex)
-Chronic bifascicular block
-After acute phase of myocardial infarction
-Neurocardiogenic syncope and hypersensitive carotid sinus syndrome
-Post cardiac transplantation
-Hypertrophic cardiomyopathy
-Pacing to detect and terminate tachycardia
-Cardiac resynchronization therapy in patients with severe systolic heart failure
-Patients with congenital heart disease

Myoglobinuria is the condition when there is degeneration of necrosed muscle that it is excreted in the urine. This condition would then cause acute tubular damage leading to renal failure.

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.

With a clinical history of weight loss, smoking, drinking alcohol, and hematemesis, the most likely answer is gastric carcinoma (also a mass). Based on symptomatology alone this is more likely than gastric lymphoma, as she has many risk factors for adenocarcinoma and/or squamous cell carcinoma. Helicobacter gastritis would not likely present with the severity of symptoms, neither would benign gastric ulcers.

When statistically comparing data sets, researchers estimate the population of each sample and examine them to see whether they are identical. The standard error of the mean (SEM) – not the standard deviation (SD), which represents the variation in the sample – is used to estimate the population mean. Via this process, researchers conclude that the sample used in their studies appropriately represents the population within the error range specified by the pre-set significance level.
The SEM is smaller than the SD, as the SEM is estimated usually with the SD divided by the square root of the sample size. For this reason, researchers are tempted to use the SEM when describing their samples. It is acceptable to use either the SEM or SD to compare two different groups if the sample sizes of the two groups are equal; however, the sample size must be stated in order to deliver accurate information. For example, when a population has a large amount of variation, the SD of an extracted sample from this population must be large. However, the SEM will be small if the sample size is deliberately increased.

The history of diabetes, complete loss of vision in the affected eye and inability to visualise the retina, suggest a diagnosis of vitreous haemorrhage (VH). 3 conditions cause 59 to 88.5% of VH cases: proliferative diabetic retinopathy, posterior vitreous detachment (PVD), and ocular trauma

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.

The sciatic neve originates in the sacral plexus, mainly from spinal segments L5-S2. It supplies muscles that cause extension of the thigh and flexion of the leg. It divides into two main branches, the tibial nerve and common peroneal nerve, which are responsible for all foot movements. Anterior thigh and medial leg sensory loss is typical of a femoral nerve lesion. The femoral nerve also mediates flexion of the hip.

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

Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer’s disease and other neurodegenerative diseases.

Drug interactions:
When given concomitantly with other NMDA-receptor antagonists (e.g., ketamine, amantadine) increase the risk of psychosis.
Dopamine agonists, L-dopa, and anticholinergics enhance effects of memantine.
Antispasmodics (e.g., baclofen)  enhance effects, as memantine has some antispasmodic effects.
Drugs excreted by cationic transporters in the kidney (e.g. quinine, cimetidine, ranitidine) reduce excretion.

Common adverse effects include dizziness, headache, confusion, diarrhoea, and constipation.

5–15% of the cases of polycythaemia vera progress to myelofibrosis or acute myeloid leukaemia (AML).

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

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.

The patient presents with worsened renal condition from the last consultation when he was started on enalapril (an ACE inhibitor) so this medication should be stopped. Because there is also no fluid overload; furosemide, a diuretic, should also be stopped.

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.

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

People aged 16 or over are entitled to consent to their own treatment. This can only be overruled in exceptional circumstances. Children under the age of 16 can consent to their own treatment if they’re believed to have enough intelligence, competence and understanding to fully appreciate what’s involved in their treatment. This is known as being Gillick competent.

Otherwise, someone with parental responsibility can consent for them.
This could be:
the child’s mother or father
the child’s legally appointed guardian
a person with a residence order concerning the child
a local authority designated to care for the child
a local authority or person with an emergency protection order for the child.
Giving the blood transfusion is therefore both clinically and ethically the right course of action.
Jehovah’s Witnesses frequently carry a signed and witnessed Advance Decision Document listing the blood products and autologous procedures that are, or are not, acceptable to them It is appropriate to have a frank, confidential discussion with the patient about the potential risks of their decision and the possible alternatives to transfusion, but the freely expressed wish of a competent adult must always be respected.

Cyanide poisoning:
Aetiology:
Smoke inhalation, suicidal ingestion, and industrial exposure (specific industrial processes involving cyanide include metal cleaning, reclaiming, or hardening; fumigation; electroplating; and photo processing) are the most frequent sources of cyanide poisoning. Treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source.
Cyanide exposure most often occurs via inhalation or ingestion, but liquid cyanide can be absorbed through the skin or eyes. Once absorbed, cyanide enters the blood stream and is distributed rapidly to all organs and tissues in the body. 

Pathophysiology:
Inside cells, cyanide attaches itself to ubiquitous metalloenzymes, rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores.

Presentation:
• ‘Classical’ features: brick-red skin, smell of bitter almonds
• Acute: hypoxia, hypotension, headache, confusion
• Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
• Supportive measures: 100% oxygen, ventilatory assistance in the form of intubation if required.
• Definitive: Hydroxocobalamin (iv) is considered the drug of choice and is approved by the FDA for treating known or suspected cyanide poisoning.
• Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergistic effect on detoxification.
Mechanism of action of hydroxocobalamin:
• Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.
• Alternatively, cyanocobalamin may dissociate from cyanide at a slow enough rate to allow for cyanide detoxification by the mitochondrial enzyme rhodanese.

This patient has Klumpke’s paralysis due to damage to the T1 nerve root. This root eventually supplies the median and ulnar nerves. The ulnar nerve supplies all of the intrinsic hand muscles except for those of the thenar eminence and the first and second lumbricals, which are innervated by the median nerve.

The patient is asymptomatic but matches the diagnostic criteria for multiple myeloma (MM). Therefore, the underlying diagnosis of this condition is smouldering multiple myeloma (SMM). SMM is an early precursor to MM. Its treatment is typically to watch and wait.

MM is a neoplasm of the bone marrow plasma cells. Peak incidence is in patients aged 60–70 years.

Clinical features of MM include:
1. Ostealgia, osteoporosis, pathological fractures (typically vertebral), and osteolytic lesions
2. Lethargy
3. Infections
4. Hypercalcaemia
5. Renal failure
6. Other features: amyloidosis e.g. macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

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

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

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.