Acute alcohol intoxication presents with pupillary dilation, thus, this is ruled out in this patient. All the other listed causes present with small pupils bilaterally.

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.

Osteoblastic (or sclerotic) bone metastases, characterized by deposition of new bone, present in prostate cancer, carcinoid, small cell lung cancer, Hodgkin lymphoma or medulloblastoma.

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

Philadelphia translocation, t(9;22), is a marker of poor prognosis in acute lymphoblastic leukaemia (ALL).

ALL is the malignancy of lymphoid progenitor cells affecting B or T cell lineage. This results in the arrest of lymphoid cell maturation and proliferation of immature blast cells (lymphoblasts), leading to bone marrow and tissue infiltration.

ALL is the most common type of childhood cancers. Its peak incidence is between two to three years of age.

Acute B lymphoblastic leukaemia (B-ALL) is the most common type of ALL, involving overproduction of B-cell lymphoblasts. It is manifested by low initial WCC and is associated with a good prognosis.

Poor prognostic factors for ALL include:
1. Pre-B cell or T-cell ALL (T-ALL)
2. Philadelphia translocation, t(9;22)
3. Age <2 years or >10 years
4. Male sex
5. CNS involvement
6. High initial WBC (e.g. >100 x 10^9/L)
7. non-Caucasian

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before age 40 and various patterns of disease are recognised, including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.
Non-invasive ventilation (usually BIPAP) is used at night, with studies having shown a survival benefit of around 7 months. Riluzole prevents stimulation of glutamate receptors, used mainly in amyotrophic lateral sclerosis and has been shown to prolong life by about 3 months.

Normal pO2 but decreased oxygen saturation is characteristic of methemoglobinemia.

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Inclusion body myositis (IBM) is a progressive muscle disorder characterized by muscle inflammation, weakness, and atrophy (wasting). It is a type of inflammatory myopathy. IBM develops in adulthood, usually after age 50. The symptoms and rate of progression vary from person to person. The most common symptoms include progressive weakness of the legs, arms, fingers, and wrists. Some people also have weakness of the facial muscles (especially muscles controlling eye closure), or difficulty swallowing (dysphagia). Muscle cramping and pain are uncommon, but have been reported in some people. The underlying cause of IBM is poorly understood and likely involves the interaction of genetic, immune-related, and environmental factors. Some people may have a genetic predisposition to developing IBM, but the condition itself typically is not inherited. Elevated creatine kinase (CK) levels in the blood (at most ,10 times normal) are typical in IBM. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

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

Different Oral Hypoglycaemic Agents (OHAs) and their respective mechanism(s) of action include:
• Sulfonylureas (such as, glipizide, gliclazide, glimepiride) – bind to ATP sensitive Potassium channels (K – ATP channels) in the ? cells of the islets of the pancreas. Inhibition of these channels lead to an altered resting membrane potential in these cells causing an influx of calcium which increases insulin secretion.
• Meglitinides (like Repaglinide) through a different receptor, they similarly regulate K – ATP channels thereby causing an increase in insulin secretion.
• Biguanides (e.g., Metformin) increase the hepatic AMP-activated protein kinase activity leading to reduced gluconeogenesis and lipogenesis and increased insulin-mediated uptake of glucose in muscles. (it doesn’t increase insulin secretion)
• Thiazolidinediones (rosiglitazone, pioglitazone) bind to PPAR-? and increase peripheral uptake of glucose and decrease hepatic glucose production.
• α-Glucosidase inhibitors (such as acarbose, miglitol, voglibose) competitively inhibit α-glucosidase enzymes in the intestine that digest the dietary starch thus, inhibiting the polysaccharide reabsorption as well as metabolism of sucrose to glucose and fructose.
• DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin) prolong the action of glucagon-like peptide. This leads to inhibition of glucagon release, increase in insulin secretion and a decrease in gastric emptying leading to a decrease in blood glucose levels.
• SGLT2 inhibitors (dapagliflozin and canagliflozin) inhibit glucose reabsorption in the proximal tubules of the renal glomeruli leading to glycosuria which in-turn reduces blood glucose levels.
Note: Side effects of pioglitazone are weight gain, pedal oedema, bone loss and precipitation of congestive cardiac failure.

Colonoscopy screening should begin 10 years after the first diagnosis in ulcerative colitis, given the increased risk for colon cancer. Given that she has developed primary sclerosing cholangitis, her risk of colon cancer is even higher. Colonoscopy screening should occur at 3 year intervals in the second decade, 2 year intervals in the third decade, and 1 year intervals by the first decade, making A the correct answer choice.

Tumour marker CA 15-3 is mostly associated with breast cancer.

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

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

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

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

Relief of symptoms with food suggests duodenal ulceration, for which the pain gets worse on an empty stomach. In chronic pancreatitis, you would expect worsening of symptoms with food.

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

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.

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 fact that he has recently stopped taking his valganciclovir, anti-viral, is key to the answer to this question. This makes the answer quite plainly donor-acquired CMV infection over all of the other answer choices. He needs to stay on prophylaxis against this, particularly in the first 3 months after transplant. Symptoms and presentations of CMV infection can include fever, abdominal pain, diarrhoea, pneumonitis, hepatitis, hematologic abnormalities, retinitis, and esophagitis.

The given clinical scenario is suggestive of myo-neuropathy and is most likely to be caused by colchicine toxicity.
It gives rise to subacute proximal muscle weakness and on occasions can lead to an acute necrotizing myopathy. Creatine phosphokinase may be normal or may be elevated.
Weakness resolves when the drug is discontinued but the neuropathic features remain.
Death is usually a result of respiratory depression and cardiovascular collapse.
Treatment is symptomatic and supportive, and the treatment for colchicine poisoning includes lavage and measures to prevent shock.

When you have abnormal liver function tests after a cardiac arrest, the most likely aetiology, barring history that is known or given excluding this diagnosis, would be ischemia. Chronic alcohol abuse would not see an acute elevation like this. Hepatitis B is just unlikely given the clinical picture, ischemia is much more likely. The same is for Budd-Chiari syndrome (venous thrombosis) and Wilson’s disease.