The most likely diagnosis is hypertrophic obstructive cardiomyopathy which is suggestive by the history, positive family history and ECG findings. Two-dimensional echocardiography is diagnostic for hypertrophic cardiomyopathy. In general, a summary of echocardiography findings includes abnormal systolic anterior leaflet motion of the mitral valve, LV hypertrophy, left atrial enlargement, small ventricular chamber size, septal hypertrophy with septal-to-free wall ratio greater than 1.4:1, mitral valve prolapse and mitral regurgitation, decreased midaortic flow, and partial systolic closure of the aortic valve in midsystole.

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.

If a pleural effusion is present, a diagnostic thoracentesis may be performed and analysed for pH, lactate dehydrogenase, glucose levels, specific gravity, and cell count with differential. Pleural fluid may also be sent for Gram stain, culture, and sensitivity. Acid-fast bacillus testing may also be considered and the fluid may be sent for cytology if cancer is suspected.

The following findings are suggestive of an empyema or parapneumonic effusion that will likely need a chest tube or pigtail catheter for complete resolution:
-Grossly purulent pleural fluid
-pH level less than 7.2
-WBC count greater than 50,000 cells/µL (or polymorphonuclear leukocyte count of 1,000 IU/dL)
-Glucose level less than 60 mg/dL
-Lactate dehydrogenase level greater than 1,000 IU/mL
-Positive pleural fluid culture

The most often used golden criteria for empyema are pleural effusion with macroscopic presence of pus, a positive Gram stain or culture of pleural fluid, or a pleural fluid pH under 7.2 with normal peripheral blood ph.

Methadone and cocaine can cause QT prolongation through the direct effects on the resting membrane potential. Methadone can increase QT dispersion in addition to QT interval. Methadone inhibits the Human Ether-a-go-go Related Gene (hERG) and causes QTc prolongation and development of Torsades de point. Brugada-like syndrome is another condition found in methadone users which predisposes the users to life-threatening ventricular tachycardia and sudden cardiac death.

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

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

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)

It is proven that spironolactone has survival benefits and loop diuretics only give symptomatic relief. Beta blockers are however, known to improve exercise tolerance, left ventricular function and reduce symptoms. They also reduce the mortality associated with heart failure. So administration of beta blockers will reduce the time spent in hospital by improving symptoms.

A couple of papers written by the same authors indicate that children and adolescents taking an SSRI definitely experience discontinuation reactions that can be mild, moderate or severe when the medication is stopped suddenly or high doses are reduced substantially. Among the SSRIs paroxetine seems to be the worst offender and fluoxetine the least while sertraline and fluvoxamine tend to be intermediate. The rate of discontinuation syndrome varies with the particular SSRI involved. It is generally quoted as 25% but is higher for SSRIs with shorter half-lives. Paroxetine has been associated with more frequent discontinuation symptoms than the other SSRIs.

The use of fluoxetine with its long half-life appears safer in this respect than paroxetine and venlafaxine causing the most concerns.

Paroxetine has the shortest half-life with 21 hours of all listed SSRIs and as such it would be expected to have a higher incidence or severity (greater number of symptoms) and fluoxetine would have the least since it has a half life of 96 hours. Citalopram has a half-life of 35 hours while escitalopram has a half-life of 30 hours.

The most common symptoms reported are: dizziness, light-headedness, drowsiness, poor concentration, nausea, headache and fatigue.
Another common symptom in adults is paraesthesia described as burning, tingling, numbness or electric shock feelings usually in the upper half of the body or proximal lower limbs.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive chronic lung disease. Typically, COPD includes emphysema and chronic bronchitis. COPD is characterized by the restriction of airflow into and out of the lungs. The obstruction of airflow makes breathing difficult. The causes of COPD include smoking, long-term exposure to air pollutants and a rare genetic disorder.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) developed the GOLD Staging System. In the GOLD System, the forced expiratory volume in one second (FEV1) measurement from a pulmonary function test is used to place COPD into stages. Often, doctors also consider your COPD symptoms.

COPD has four stages. The stages of COPD range from mild to very severe. COPD affects everyone differently. Because COPD is a progressive lung disease, it will worsen over time.
The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 63 which falls within the stage 2 or moderate COPD.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent – 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes. Another way of expressing this is the number needed to treat (NNT). If 8 children out of 100 benefit from treatment, the NNT for one child to benefit is about 13 (100 ÷ 8 = 12.5). CER = 20 / 400 = 1 / 20 = 0.05, EER = 10 / 400 = 0.025, ARR =CER – EER = 0.025

Cervical radiculopathy is usually due to compression or injury to a nerve root by a herniated disc or degenerative changes. Levels C5 to T1 are the most commonly affected. It is usually, but not always, accompanied by cervical radicular pain, a sharp and shooting pain that travels from the neck and down the upper limb and may be severe. This needs to be differentiated from pain referred from the musculoskeletal (somatic) structures in the neck, which may be aching rather than sharp, and is more severe in the neck than in the upper limb. The neurological signs of cervical radiculopathy depend on the site of the lesion. The patient may have motor dysfunction, sensory deficits or alteration in tendon reflexes. While pain is a common presenting symptom, not all radiculopathies are painful (i.e. only motor deficits may be obvious). CT scanning cannot accurately demonstrate the commonest cause for cervical radiculopathy (disc herniation) without myelography, which requires hospital admission, lumbar puncture and the use of contrast. In patients with cervical radiculopathy, MRI is the imaging technique of choice for the detection of root compression by disc herniation and osteophytes. MRI allows the nerve roots to be directly visualised. Nerve conduction studies are also useful in determining the nerve roots that are involved.

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.

Nitric oxide, known as an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes and is a signaling molecule in many physiological and pathological processes in humans.
One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron.

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

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

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

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

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

All the above side-effects, with the exception of alopecia, may be seen in patients taking lithium.

Common lithium side effects may include:
– dizziness, drowsiness;
– tremors in your hands;
– trouble walking;
– dry mouth, increased thirst or urination;
– nausea, vomiting, loss of appetite, stomach pain;
– cold feeling or discoloration in your fingers or toes;
– rash; or.
– blurred vision.

Elderly patients with severe hypothyroidism often present with variable symptoms that may be masked or potentiated by co-morbid conditions. Characteristic symptoms may include fatigue, weight gain, cold intolerance, hoarseness, constipation, and myalgias. Neurologic symptoms may include ataxia, depression, and mental status changes ranging from mild confusion to overt dementia.
Clinical findings that may raise suspicion of thyroid hormone deficiency include hypothermia, bradycardia, goitrous enlargement of the thyroid, cool dry skin, myxoedema, delayed relaxation of deep tendon reflexes, a pericardial or abdominal effusion, hyponatremia, and hypercholesterolemia.

The patient has a greatly reduced free T4 concentration, is hypothermic, unconscious and has evidence of associated heart failure. All of those support the diagnosis of profound hypothyroidism.

Retinitis pigmentosa is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreased peripheral vision. Onset of symptoms is generally gradual.
– In keratitis, there will be pain, redness and photophobia but vision is not affected
– In macular degeneration, near blindness does not occur rather the inability to identify faces or read small print
– Cataracts are more common in elderly
– It is not angle closure glaucoma as angle closure glaucoma occurs usually after the age of 50; In open angle glaucoma visual loss is not gradual but rather occurs suddenly following progression

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

Huntington’s disease is an autosomal inherited condition characterized by progressive dementia and worsening choreiform movements. Symptoms typically appear between ages 30 and 50. Ultimately the weakened individual succumbs to pneumonia, heart failure, or other complications.

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 hypersecretion of gastrin. Serum gastrin levels > 1000 and a pH < 2 are diagnostic of pancreatic gastrinoma. The secretin test is a test that can differentiate gastrinoma from other causes of high gastrin levels. Gastrin will rise after secretin injection if the patient has a gastrinoma.

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles, thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which results in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

Infection of chickenpox in the first half of pregnancy can result in congenital varicella syndrome. It presents as cerebral, cortical and cerebellar hypoplasia with convulsions and rudimentary digits. Prevention is by administering varicella vaccine, even before pregnancy. Varicella immunoglobulin is administered to pregnant women who are exposed to infection. Infection during pregnancy is treated with acyclovir.

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.

Synacthen test interpretation:
– Basal Cortisol level should be greater than 180nmol/L
– 30min or 60min Cortisol should be greater than 420nmol/L (whatever the basal level)
– The increment should be at least 170nmol/L, apart from in severely ill patients where adrenal output is already maximal.
The patient’s results show that she has Acute Adrenal Insufficiency
The guidelines include the following recommendations for emergency treatment:
Administer hydrocortisone: Immediate bolus injection of 100 mg hydrocortisone intravenously or intramuscularly followed by continuous intravenous infusion of 200 mg hydrocortisone per 24 hours (alternatively, 50 mg hydrocortisone per intravenous or intramuscular injection every 6 h)
Rehydrate with rapid intravenous infusion of 1000 mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4-6 L in 24 h; monitor for fluid overload in case of renal impairment and elderly patients)
Contact an endocrinologist for urgent review of the patient, advice on further tapering of hydrocortisone, and investigation of the underlying cause of the disease, including the diagnosis of primary versus secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an endocrinologist; in patients with primary adrenal insufficiency, mineralocorticoid replacement must be initiated (starting dose 100 μg fludrocortisone once daily) as soon as the daily glucocorticoid dose is below 50 mg of hydrocortisone every 24 hours

Porphyria cutanea tarda (PCT) is the most common of the porphyries. It is characterised by fragility and blistering of exposed skin. Typically, patients who are ultimately diagnosed with PCT first seek treatment following the development photosensitivities in the form of blisters and erosions on commonly exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. It heals slowly and with scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations like hyperpigmentation (as if they are getting a tan) and hypertrichosis (mainly on top of the cheeks) also occur. Risk factors for the development of PCT include alcohol and sun.

There are number of diseases that have to be notified to relevant authorities to prevent or reduce their spread. Those conditions include Cholera, Diphtheria, Food poisoning, Infectious bloody diarrhoea, Malaria, Measles, Meningococcal septicaemia, Mumps, Plague, Rabies and Rubella.

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

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

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

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.

Urobiligen is produced by the action of bacteria on bilirubin in the intestine. As a reminder, unconjugated bilirubin becomes conjugated in the hepatocyte. Conjugated bilirubin goes through enterohepatic circulation. About half of the urobiligen is reabsorbed and excreted by the kidneys in the urine. The rest is converted to stercobilinogen –> stercobilin, which is excreted in stool, giving it its brown colour.