Spironolactone is an aldosterone antagonist which acts in the distal convoluted tubule. It is a potassium-sparing diuretic that prevents the body from absorbing too much salt and keeps the potassium levels from getting too low. Spironolactone is used to treat heart failure, high blood pressure (hypertension), or hypokalaemia (low potassium levels in the blood).

The patient has a recent history of bleeding peptic ulcer disease, which is an absolute contraindication for thrombolysis. So he should be offered primary angioplasty.

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 cause for bone marrow suppression in this patient is most probably mercaptopurine toxicity.
Azathioprine is metabolized to 6-mercaptopurine (6-MP), which itself is metabolized by xanthine oxidase.
Xanthine oxidase inhibition by allopurinol leads to the accumulation of 6-MP which then precipitates bone marrow failure.
This may be potentially fatal if unrecognized.
Clinical presentation:
Toxicity symptoms include gastrointestinal symptoms, bradycardia, hepatotoxicity, myelosuppression.

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

Mania is a state of extreme physical and emotional elation. A person experiencing mania or a manic episode may present with the following symptoms:
-Elevated mood. The person feels extremely ‘high’, happy and full of energy; he or she may describe the experience as feeling on top of the world and invincible. The person may shift rapidly from an elevated,
happy mood to being angry and irritable if they perceive they have been obstructed.
-Increased energy and overactivity. The person may have great difficulty remaining still.
-Reduced need for sleep or food. The person may be too active to eat or sleep.
-Irritability. The person may become angry and irritated with those who disagree with or dismiss his or her sometimes unrealistic plans or ideas.
-Rapid thinking and speech. The person’s thoughts and speech are more rapid than usual.
-Grandiose plans and beliefs. It is quite common for a person in a hypomanic or manic state to believe that he or she is unusually talented or gifted or has special friends in power. For example, the person may believe that he or she is on a special mission from God.
-Lack of insight. A person in a hypomanic or manic state may understand that other people see his or her ideas and actions as inappropriate, reckless or irrational. However, he or she is unlikely to personally accept that the behaviour is inappropriate, due to a lack of insight.
– Distractibility. The person has difficulty maintaining attention and may not be able to filter out external stimuli.

Careful assessment to rule out organic conditions is an important first step in the management of mania. Often hospitalisation is required for someone who is experiencing acute mania. Both mood-stabilising agents such as lithium carbonate or sodium valproate and an antipsychotic may be needed to treat psychotic symptoms, agitation, thought disorder and sleeping difficulties. Benzodiazepines may be useful to reduce hyperactivity. Treatment with lithium alone may have a relatively slow response rate (up to two weeks after a therapeutic blood level is established), so that adjunctive medication such as sodium valproate is usually required. Regular monitoring of blood levels for lithium and valproate is essential because of the potential for toxicity.

The symptoms of hypomania are similar to those of mania: elevated mood, inflated self-esteem, decreased need for sleep, etc. except that they don’t significantly impact a person’s daily function and never include any psychotic symptoms.

Apraclonidine eye drops are initially used to confirm a Horner’s pupil. Apraclonidine stimulates both alpha-1 and alpha-2 receptors. When added to the affected eye, it causes pupil dilation by >2mm because of the relative super sensitivity of this pupil to alpha-1 receptor activity. In a normal pupil, however, it causes constriction due to the more potent activity at the alpha-2 receptor which triggers re-uptake of noradrenaline in the synaptic cleft.

Hydroxy amphetamine is then used to distinguish between first/second or third order neurones. In other words, it will distinguish either a lesion in the brainstem, cervical cord, chest or neck and one affecting above the superior cervical ganglion at the carotid bifurcation. In a normal pupil or a first/second order Horner’s, the pupil will dilate secondary to increased levels of noradrenaline released from the post-synaptic neurones. In a third order neurone, this will not occur. There is no fourth or fifth order neurone.

Peak Expiratory Flow (PEF), also called Peak Expiratory Flow Rate (PEFR) is a person’s maximum speed of expiration, as measured with a peak flow meter. Measurement of PEFR requires some practise to correctly use a meter and the normal expected value depends on a patient’s gender, age and height.
It is classically reduced in obstructive lung disorders, such as Asthma, COPD or Cystic Fibrosis.

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

The majority of patients with primary open-angle glaucoma are managed with eye drops. These aim to lower intra-ocular pressure which in turn has been shown to prevent progressive loss of visual field. A prostaglandin analogue should be used first-line in patients with a history of asthma.

In Wilson’s disease, serum caeruloplasmin is decreased. Skin pigmentation is not increased, but may become jaundiced. 24 hour urine copper excretion is increased. Hepatic copper concentration is increased. Serum copper level is also increased. Key point: high copper. Remember Kayser-Fleisher rings for the eyes in Wilson’s disease.

Confusion in the patient refers to neurological symptoms that are more associated with thrombotic thrombocytopenic purpura than with haemolytic uremic syndrome. All the other symptoms present in both conditions similarly.

Arterial ischemia ulcers present with many of the symptoms observed in this patient: ulcer on the lower extremities, pain, swelling, yellow sores, a punched-out appearance, the foot turning red when dangling from a bed. Smoking a lot is also known to be a causative factor here. This type of ulcer develops due to damage to the arteries caused by a lack of blood flow to the tissue – they are also deep wounds. Venous ischemic ulcers usually form in the knee or inner ankle area as opposed to the foot.

Sarin acts by inhibiting acetylcholinesterase.

Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase
Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase. This results in high levels of acetylcholine (ACh).

The effects of excessive ACh can be remembered by the mnemonic DUMBELLS:
Diarrhoea
Urination
Miosis/muscle weakness
Bronchorrhea/Bradycardia
Emesis
Lacrimation
Salivation/sweating

Organophosphate insecticide poisoning:
One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase
Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)
Salivation
Lacrimation
Urination
Defecation/diarrhoea
cardiovascular: hypotension, bradycardia
miosis, muscle fasciculation.

Organophosphate poisoning is treated with the anti-muscarinic atropine.

The SEM is an indicator of how close the sample mean is to the population mean. In reality, however, only one sample is extracted from the population. Therefore, the SEM is estimated using the standard deviation (SD) and a sample size (Estimated SEM). The SEM computed by a statistical program is an estimated value calculated via this process.

Estimated Standard Error of the Mean (SEM)=SDn√

Here, the patient seems to be intolerant to standard metformin. In such cases, modified-release preparations is considered as the most appropriate next step.
There is some evidence that these produce fewer gastrointestinal side-effects in patients intolerant of standard-release metformin.

Metformin is a biguanide and reduces blood glucose levels by decreasing the production of glucose in the liver, decreasing intestinal absorption and increasing insulin sensitivity.
Metformin decreases both the basal and postprandial blood glucose.
Other uses: In Polycystic Ovarian Syndrome (PCOS), Metformin decreases insulin levels, which then decreases luteinizing hormone and androgen levels. Thus acting to normalize the menstruation cycle.

Note:
Metformin is contraindicated in patients with severe renal dysfunction, which is defined as a glomerular filtration rate (GFR) less than 30 ml/min/1.732m2.
Metformin overdose has been associated with hypoglycaemia and lactic acidosis, for this reason, it has a black box warning for lactic acidosis.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

Occupational asthma (OA) could be divided into a nonimmunological, irritant-induced asthma and an immunological, allergy-induced asthma. In addition, allergy-induced asthma can be caused by two different groups of agents: high molecular weight proteins (>5,000 Da) or low molecular weight agents (<5,000 Da), generally chemicals like the isocyanates.
Isocyanates are very reactive chemicals characterized by one or more isocyanate groups (–N=C=O). The main reactions of this chemical group are addition reactions with ethanol, resulting in urethanes, with amines (resulting in urea derivates) and with water. Here, the product is carbamic acid which is not stable and reacts further to amines, releasing free carbon dioxide.

Diisocyanates and polyisocyanates are, together with the largely nontoxic polyol group, the basic building blocks of the polyurethane (PU) chemical industry, where they are used solely or in combination with solvents or additives in the production of adhesives, foams, elastomers, paintings, coatings and other materials.

The complex salts of platinum are one of the most potent respiratory sensitising agents having caused occupational asthma in more than 50% of exposed workers. Substitution of ammonium hexachlor platinate with platinum tetra amine dichloride in the manufacture of catalyst has controlled the problem in the catalyst industry. Ammonium hexachlorplatinate exposure still occurs in the refining process.

Rosin based solder flux fume is produced when soldering. This fume is a top cause of occupational asthma.

Bakeries, flour mills and kitchens where flour dust and additives in the flour are a common cause of occupational asthma.

Cadmium was not found to cause occupational asthma.

Acute angle closure glaucoma is associated with hypermetropia, whereas primary open-angle glaucoma is associated with myopia. Glaucoma is a group of eye disorders characterised by optic neuropathy due, in the majority of patients, to raised intraocular pressure (IOP). It is now recognised that a minority of patients with raised IOP do not have glaucoma and vice versa.

Retinal and cerebellar haemangiomas are key features of Von Hippel-Lindau syndrome. Retinal haemangiomas are bilateral in 25% of patients and may lead to vitreous haemorrhage. Von Hippel-Lindau (VHL) syndrome is an autosomal dominant condition predisposing to neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3.

Scabies is an infection caused by a microscopic mite known as Sarcoptes scabies. The chief presenting complaint is itching especially in skin folds and mostly during night. It spreads from one person to another through skin contact, and therefore it is more prevalent in crowded areas like hospitals, hostels and even at homes where people live in close contact with each other. Treatment options include benzyl benzoate, ivermectin, sulphur and permethrin.

Arthrocentesis should usually be done when there is a suspicion of pseudogout or septic arthritis as in this case which leads to an early diagnosis and prompt treatment. Polarized microscopy demonstrates weakly positively birefringent rhomboid crystals which are blue when parallel to light and yellow when perpendicular to light. Elevated serum uric acid levels that cause gout are usually found after large consumption of alcohol or meat, or post surgery. Autoimmune diseases like SLE, RA etc require an autoimmune screen.

Warfarin is contraindicated during pregnancy due to its teratogenic effects. She should be given heparin throughout her pregnancy. It can be converted to warfarin if necessary after the delivery.

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.

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.

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.

Vesicoureteral reflux is the condition when the urine flows backwards from the bladder into the kidneys, which is the most common cause of UTI in patients this age.

Dapagliflozin works by inhibiting sodium glucose cotransporter 2 (SGLT2) and blocking resorption of glucose in the kidney, leading to an increase in urinary glucose excretion and lowering of both plasma glucose levels and body weight.
All studies with SGLT2 inhibitors have found significant reductions in BP, with greater reductions seen in systolic (1.66 to 6.9mmHg) than diastolic (0.88 to 3.5mmHg) BP.
While some trials have shown no change in lipid parameters, others have shown a modest but statistically significant increase in both HDL and LDL cholesterol with no effect on triglycerides or the LDL/HDL ratio.

When a patient fails treatment with metronidazole (Flagyl) treatment, the next course of action is to change to oral vancomycin, which is shown to be effective in the treatment of c diff colitis. Oral rifampicin is not a treatment for c diff. Oral metronidazole is not resolving her symptoms so is not the correct answer. clindamycin is a cause of c diff colitis, not a treatment. IV Vanc is not active in the gut so is not the treatment; oral is active in the gut.

The classic history in this high risk patient is suggestive of a dissecting aortic aneurysm. His transoesophageal echocardiogram confirms the diagnosis. ST elevation in ECG is probably due to the extension of the dissection of the aorta which results in compromised coronary blood supply.