Tricyclic compounds can’t be cleared by haemodialysis.

Drugs that can be cleared with haemodialysis include: (BLAST)
– Barbiturate
– Lithium
– Alcohol (inc methanol, ethylene glycol)
– Salicylates
– Theophyllines (charcoal hemoperfusion is preferable)

Drugs which cannot be cleared with haemodialysis include:
– Tricyclics
– Benzodiazepines
– Dextropropoxyphene (Co-proxamol)
– Digoxin
– Beta-blockers

Haemoptysis is a symptom which indicates the worsening of mitral stenosis. It occurs due to the rupture of pulmonary veins or the capillary system due to pulmonary venous hypertension. Elevated serum creatinine is seen in worsening aortic stenosis. Worsening of tricuspid regurgitation causes ascites and a pulsatile liver.

Post-concussion syndrome is a complex disorder in which various symptoms, such as headaches and dizziness, last for weeks and sometimes months after the injury that caused the concussion.

Concussion is a mild traumatic brain injury that usually happens after a blow to the head. It can also occur with violent shaking and movement of the head or body. You don’t have to lose consciousness to get a concussion or post-concussion syndrome. In fact, the risk of post-concussion syndrome doesn’t appear to be associated with the severity of the initial injury.

Post-concussion symptoms include:
Headaches
Dizziness
Fatigue
Irritability
Anxiety
Insomnia
Loss of concentration and memory
Ringing in the ears
Blurry vision
Noise and light sensitivity
Rarely, decreases in taste and smell

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.

Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signalling pathways that activate innate and adaptive immune responses.

In rheumatoid arthritis (RA), clinical symptoms of joint stiffness, pain, and functional disability are commonly most severe in the early morning. These symptoms closely follow the circadian rhythm of the pro-inflammatory cytokine, interleukin (IL)-6. In RA, the increase in nocturnal anti-inflammatory cortisol secretion is insufficient to suppress ongoing inflammation, resulting in the morning symptoms characteristic of RA. Established diagnostic criteria for RA include prolonged morning stiffness that could last up to an hour. Loss of joint mobility, pain, malaise and swelling of finger joints are features that are not specific to rheumatoid arthritis, and are found in many other conditions.

Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis.
Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and for access to invasive monitoring and inotropic support, if necessary.
– Supportive measures
If needed, immediately provide supplemental oxygen, ventilatory support, and intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope with continuously high metabolic demand.
– Correct electrolyte abnormalities.
– Treat cardiac arrhythmia, if necessary.
– Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen (15 mg/kg orally or rectally every 4 hours).
– Antiadrenergic drugs.
– Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs).
High-dose propylthiouracil (PTU) or methimazole may be used for treatment of thyroid storm.
– Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism and improving vasomotor symptoms.
– Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated TH metabolites secreted into bile through the enterohepatic circulation).
– Treat the underlying condition.

Koilonychia, known as spoon nails, is a condition of the nails bending inwards, taking the shape of a spoon. This is a strong indication of iron-deficiency anaemia (IDA). The rest of the patient’s symptoms further indicate IDA.

Most patients with psoriatic arthritis present with monoarthritis or asymmetric oligoarthritis. The most common form of the disease is the one involving a few joints of the peripheral skeleton with a distinct asymmetry of symptoms. Involvement of the smaller joints of the hands and feet, especially distal interphalangeal joints, seems to be a characteristic feature. Arthritis mutilans is a rare and severe complication of psoriatic arthritis.

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. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Dermatomyositis is a long-term inflammatory disorder which affects muscles. Its symptoms are generally a skin rash and worsening muscle weakness in the proximal muscles (for example, the shoulders and thighs) over time. These may occur suddenly or develop over months. Other symptoms may include weight loss, fever, lung inflammation, or light sensitivity. Complications may include calcium deposits in muscles or skin.
The skin rash may manifest as aheliotrope (a purplish color) or lilac, but may also be red. It can occur around the eyes along with swelling, as well as the upper chest or back ( shawl sign) or V-sign above the breasts and may also occur on the face, upper arms, thighs, or hands. Another form the rash takes is called Gottron’s sign which are red or violet, sometimes scaly, slightly raised papules that erupt on any of the finger joints (the metacarpophalangeal joints or the interphalangeal joints)

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.

A study conducted showed that the average post smoking cessation weight gain was about 2 kg.
Withdrawal symptoms usually peak after 1–3 days and then decrease over a period of 3–4 weeks. After this time, the body has expelled most of the nicotine, and the withdrawal effects are mainly psychological.

DGI presents as two syndromes: 1) a bacteremic form that includes a triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis and 2) a septic arthritis form characterized as a purulent arthritis without associated skin lesions. Many patients will have overlapping features of both syndromes. Time from infection to clinical manifestations may range from 1 day to 3 months. There is no travel history and the rash of Lyme disease is not purulent. Reactive arthritis presents with conjunctivitis, urethritis and arthritis usually with a red hot tender and swollen joint.

Risk factors specific to depression:
-Family history of mental disorder.
-History of previous suicide attempts (this includes self-harm).
-Severe depression.
-Anxiety.
-Feelings of hopelessness.
-Personality disorder.
-Alcohol abuse and/or drug abuse.
-Male gender.

Protective Factors for Suicide.
Protective factors buffer individuals from suicidal thoughts and behaviour. To date, protective factors have not been studied as extensively or rigorously as risk factors. Identifying and understanding protective factors are, however, equally as important as researching risk factors.

Protective Factors:
-Effective clinical care for mental, physical, and substance abuse disorders
-Easy access to a variety of clinical interventions and support for help seeking
-Family and community support (connectedness)
-Support from ongoing medical and mental health care relationships
-Skills in problem solving, conflict resolution, and nonviolent ways of handling disputes
-Cultural and religious beliefs that discourage suicide and support instincts for self-preservation

Thrombolytic therapy is indicated in patients with evidence of ST-segment elevation MI (STEMI) or presumably new left bundle-branch block (LBBB) presenting within 12 hours of the onset of symptoms if there are no contraindications to fibrinolysis. STEMI is defined as new ST elevation at the J point in at least two contiguous leads of 2 mm (0.2 mV) or more in men or 1.5 mm (0.15 mV) in women in leads V2-V3 and/or 1 mm (0.1 mV) or more in other contiguous limb leads.

Patients with active cancer are at a continuous risk of having venous thromboembolism (VTE), such as DVT. Therefore, a six-month course of an anticoagulant such as LMWH is recommended. LMWH is the drug of choice since its side effects can be reversed and it can be stopped easily in case of a cancer-related bleed, for example, massive haemoptysis in a patient with lung cancer.

Achondroplasia is a common cause of dwarfism. It is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia can be born to parents that do not have the condition due to spontaneous mutation. It occurs as a sporadic mutation in approximately 80% of cases (associated with advanced paternal age) or it may be inherited as an autosomal dominant genetic disorder.
People with achondroplasia have short stature, with an average adult height of 131 centimeters (52 inches) for males and 123 centimeters (48 inches) for females.

Tumour marker CA 125 is mostly associated with primary peritoneal cancer and ovarian cancer. It can be used to monitor response to chemotherapy, alongside regular CT scans.

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)

Gastrin is released from G cells in the antrum of the stomach after a meal. It stimulates parietal cells to release HCl. Gastrin is stimulated by a number of things: antrum distention, vagal stimulation, peptides (especially amino acids) in the stomach, hypercalcemia. Gastrin release is inhibited by acid, SST, GIP, VIP, secretin, glucagon, and calcitonin.

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.

Androgen deprivation therapy (ADT) for prostate cancer:

Goserelin (Zoladex) is a synthetic gonadotropin-releasing hormone (GnRH) analogue; chronic stimulation of goserelin results in suppression of LH, FSH serum levels thereby preventing a rise in testosterone.

Dosage form: 3.6 mg/10.8mg implants.

Adverse effects include flushing, sweating, diarrhoea, erectile dysfunction, less commonly, rash, depression, hypersensitivity, etc.

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test—It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test—It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

Furosemide is a loop diuretic that is known to have significant ototoxicity side-effects although the mechanism is not fully known.

Elevated haemoglobin A2 level is seen in beta thalassaemia trait, whereas, it is typically low in iron deficiency anaemia unless the patient has received a recent blood transfusion.

Low mean corpuscular volume (MCV) and reduced haematocrit (Ht) are encountered in both conditions. Peripheral blood smear is grossly abnormal in both beta thalassaemia and severe iron deficiency anaemia, showing bizarre morphology, target cells, and a small number of nucleated red blood cells.

There are many possible causes of a red eye. It is important to be able to recognise the causes which require urgent referral to an ophthalmologist. Acute angle closure glaucoma presents with severe pain, decreased visual acuity, patient seeing haloes, semi-dilated pupils, and hazy cornea. Anterior uveitis presents with acute onset pain, blurred vision and photophobia, with small, fixed oval pupils and ciliary flush.

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.

Rifampicin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C.

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.

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.

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.

Finasteride inhibits the formation of dihydrotestosterone.
Finasteride is a 5α-reductase inhibitor and thus, inhibits the conversion of testosterone to dihydrotestosterone (DHT).

DHT is much more active than testosterone and binds more avidly to cytoplasmic receptors. DHT stimulates prostate growth and may be responsible for benign prostatic hyperplasia in the elderly.

Thus, finasteride can cause a reduction in prostatic volume and help in managing a patient with benign prostatic hyperplasia.

PPI will affect the accuracy of the test. In general, most recommend discontinuing PPI therapy for 2 weeks prior to a urea breath test. PPI’s have an anti-H. pylori effect.

The patient presented with sudden-onset headache that is more painful than his usual migraine attacks. This gives a high suspicion of subarachnoid haemorrhage; thus, a CT brain scan should be ordered first to rule this out. However, a normal CT scan is apparent in 30% of patients with subarachnoid haemorrhage and should be referred for lumbar puncture to look for red blood cells.

Confusion and pink mucosae are typical features of CO poisoning.
The patient often presents, most commonly with headaches, and other symptoms like malaise, nausea, and dizziness.

Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Features of carbon monoxide toxicity
– Headache: 90% of cases
– Nausea and vomiting: 50%
– Vertigo: 50%
– Confusion: 30%
– Subjective weakness: 20%
– Severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death

Treatment:
Use of Hyperbaric oxygen therapy (HBOT) for treating mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)

The history is suggestive of hypertrophic obstructive cardiac myopathy. The degree of left ventricular hypertrophy is strongly associated with sudden cardiac death.

The Green Book guidelines report in an active infection (HBeAg+ and HBsAg+) to give the vaccine as well as immunoglobulin. If antibodies are present it is not active infection (anti-Hbe) and then in that case only the vaccine, and no immunoglobulin, would be given. The presence of HBeAg means a person is infectious and can transmit to other people.

The most appropriate intervention in this patient is intravenous hydroxocobalamin.
The clinical scenario provided is suggestive of acute cyanide toxicity secondary to burning plastics in the house fire.
Cyanide ions inhibit mitochondrial cytochrome oxidase, preventing aerobic respiration. This manifests in normal oxygen saturations, a high pO2 and flushing (or ‘brick red’ skin) brought on by the excess oxygenation of venous blood. In the question above it is important to note that the blood gas sample given is venous rather than arterial. His blood gas also demonstrates an increased anion gap, consistent with his high lactate (generated by anaerobic respiration due to the inability to use available oxygen).

The recommended treatment for moderate cyanide toxicity in the UK is one of three options: sodium thiosulfate, hydroxocobalamin or dicobalt edetate.

Among the options given is hydroxocobalamin and this is, therefore, the correct answer. Hydroxocobalamin additionally has the best side-effect profile and speed of onset compared with other treatments for cyanide poisoning.

Other options:
– Intubation would be appropriate treatment in the context of airway burns but this patient has no evidence of these, although close monitoring would be advised.
– High-flow oxygen is the treatment for carbon monoxide poisoning – a sensible differential, but this man’s very high lactate and high venous pO2 fit better with cyanide toxicity. Intravenous dexamethasone would be another treatment for airway oedema once an endotracheal tube had been placed.
– Intravenous sodium nitroprusside is a treatment for high blood pressure that can cause cyanide poisoning, and would, therefore, be inappropriate.

Note:

Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidizing enzymes
Clinical presentation:
Classical features: brick-red skin, the smell of bitter almonds
Acute: hypoxia, hypotension, headache, confusion
Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
Supportive measures: 100% oxygen
Definitive: hydroxocobalamin (intravenously), also a combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously).

Absolute contraindications for fibrinolytic use in STEMI

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

Charles Bonnet syndrome (CBS) involves visual hallucinations due to eye disease, usually associated with a sharp decline in vision. The phenomenon is seen in patients with moderate or severe visual impairment. It can occur spontaneously as the vision declines or it may be precipitated, in predisposed individuals, by concurrent illness such as infections elsewhere in the body.

It is not clear why CBS develops or why some individuals appear to be predisposed to it. It is particularly noted in patients with advanced macular degeneration. It has been suggested that reduced or absent stimulation of the visual system leads to increased excitability of the visual cortex (deafferentation hypothesis). This release phenomenon is compared to phantom limb symptoms after amputation.

CBS is much more common in older patients because conditions causing marked visual loss are more common in older people. However, it can occur at any age and has been described in children.
The prevalence is hard to assess due to considerable under-reporting, perhaps because patients frequently fear that it is a sign of mental illness or dementia. However, it is thought to occur in:
About 10-15% of patients with moderate visual loss.
Possibly up to 50% of people with severe visual loss.
Presentation:
The nature of the hallucination depends on the part of the brain that is activated. The hallucinations may be black and white or in colour. They may involve grids/brickwork/lattice patterns but are typically much more complex:

The hallucinations are always outside the body.
The hallucinations are purely visual – other senses are not involved.
The hallucinations have no personal meaning to the patient.
Hallucinations may last seconds, minutes or hours.
CBS tends to occur in a ‘state of quiet restfulness’. This may be after a meal or when listening to the radio (but not when dozing off).
Symptoms also have a tendency to occur in dim lighting conditions.
Patients may report high levels of distress, with some patients reporting anger, anxiety and even fear associated with the hallucinations.

A high transferrin saturation is seen in hemochromatosis, as well as a high iron level (>30), a high ferritin level, and a LOW TIBC (<20). Think of it like the opposite findings of iron deficiency anaemia which is a low iron, low ferritin, high TIBC.

Polymyositis is an inflammatory disorder causing symmetrical, proximal muscle weakness. It is thought to be a T-cell mediated cytotoxic process directed against muscle fibres. It may be idiopathic or associated with connective tissue disorders. It may also be associated with malignancy for example small cell lung carcinoma.
Dermatomyositis is a variant of the disease where skin manifestations are prominent, for example a purple (heliotrope) rash on the cheeks and eyelids.
It typically affects middle-aged, female: male 3:1. Features include proximal muscle weakness +/- tenderness, Raynaud’s phenomenon, respiratory muscle weakness, interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia, dysphagia, dysphonia. Investigations: elevated creatine kinase, other muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) are also elevated in 85-95% of patients, EMG, muscle biopsy. Anti-Jo-1 antibodies are seen in pattern of disease associated with lung involvement, Raynaud’s and fever. Interstitial lung disease plays a major role in morbidity and mortality in patients with polymyositis and is considered a major risk factor for premature death in patients with myositis.

The most probable diagnosis in this patient is post-traumatic stress disorder (PTSD). The first-line treatment for this patient would be cognitive behavioural therapy or eye movement desensitization and reprocessing therapy.

Post-traumatic stress disorder (PTSD) can develop in people of any age following a traumatic event, for example, a major disaster or childhood sexual abuse. It encompasses what became known as ‘shell shock’ following the first world war. One of the DSM-IV diagnostic criteria is that symptoms have been present for more than one month.

Clinical features:
Re-experiencing: flashbacks, nightmares, repetitive and distressing intrusive images
Avoidance: avoiding people, situations or circumstances resembling or associated with the event
Hyperarousal: hypervigilance for threat, exaggerated startle response, sleep problems, irritability and difficulty concentrating
Emotional numbing – lack of ability to experience feelings, feeling detached from other people
Depression
Drug or alcohol misuse
Anger

Management:
Following a traumatic event single-session interventions (often referred to as debriefing) are not recommended
Watchful waiting may be used for mild symptoms lasting less than 4 weeks
Trauma-focused cognitive-behavioural therapy (CBT) or eye movement desensitization and reprocessing (EMDR) therapy may be used in more severe cases
Drug treatments for PTSD should not be used as a routine first-line treatment for adults.
If drug treatment is used then paroxetine or mirtazapine are recommended.

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.

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.

Impetigo appears more commonly on the face than other exposed areas like the limbs. Its blisters are clustered and may have a fluid discharge.

Cataract is a condition characterized by clouding of the lens of the eye. This condition most frequently occurs due to age-related degenerative processes in the lens, but can also be associated with ocular trauma, metabolic disorders, side-effects of drugs, or congenital infections. The clouding causes distortion of light, as it passes through the lens, resulting in visual impairment and glare. Initially, a cataract presents discretely and may even go unnoticed, but the visual impairment worsens as the cataract grows larger.

Diagnosis is typically established on the basis of a thorough history and direct visualization of the cataract (by means of slit-lamp microscopy). Surgery is indicated with significant visual impairment and involves lens extraction and implantation of an artificial lens. Untreated cataracts eventually lead to complete blindness.

Glioblastoma multiforme, also considered as grade IV astrocytoma, is the most malignant form of the tumour and accounts for about 20% of all cerebral tumours. These often remain clinically silent until they have reached a large enough size. In adults, glioblastoma multiforme usually occurs in the cerebral hemispheres, especially the frontal and temporal lobes of the brain. About half occupy more than one hemisphere at presentation, and some are multicentric. Biopsy shows high cellularity with mitoses, pleomorphism, and vascular hyperplasia. Prognosis is extremely poor, with only 20% surviving beyond 1 year and 10% beyond 2 years.

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.

Extended-spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Extended spectrum beta-lactamase (ESBL) production is the main reason for multi-drug resistance among E.coli. Commonly used medications to treat ESBL-involved infections include carbapenems (imipenem, meropenem, and doripenem), cephamycins (cefoxitin and cefotetan), Fosfomycin, nitrofurantoin, beta-lactamase inhibitors (clavulanic acid, tazobactam, or sulbactam), non-beta-lactamases and colistin (if all other medications have failed.)

Hypotensive effect of streptokinase occurs during the streptokinase infusion which is usually transient. Acute mitral regurgitation due to rupture of papillary muscles, ventricular septal defects and reinfarctions (left or right) are known to cause hypotension after 24 hrs. Pulmonary embolism is less likely but cannot be excluded.

A case–control study (also known as case–referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease (the cases) with patients who do not have the condition/disease but are otherwise similar (the controls).
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B or vice versa.

The frequency of type-1 diabetes is higher in siblings of diabetic parents (e.g., in the UK 6% by age 30) than in the general population (in the U.K. 0.4% by age 30), while disease concordance in monozygotic (identical) twins is about 40% i.e. the risk that the unaffected twin will develop diabetes.

Oesophageal stricture is a complication of systemic sclerosis, think of the oesophagus as sclerosing (fibrosing) leading to stricture and you never forget. Based on the clinical presentation of systemic sclerosis this is more likely than pancreatic dysfunction, PSC, lymphoma, or diverticulitis. Additionally, CREST syndrome stands for: calcinosis cutis, Raynaud’s phenomenon (which the patient has), oesophageal dysmotility, sclerodactyly, and telangiectasias), this is a form of systemic sclerosis you should be familiar with.

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.

Felty syndrome is a severe subtype of seropositive Rheumatoid arthritis. Clinical triad consists of arthritis, splenomegaly, and neutropenia (leads to an increased risk of recurrent bacterial infections). Other symptoms include skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever, and chest pain (indicating pleuritis or pericarditis). It is associated with increased risk of developing non-Hodgkin lymphoma.

The clinical manifestations of Small cell lung cancer (SCLC) can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known.
SIADH is present in 15% of cases and most commonly seen.
Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases.
Ectopic Cushing’s syndrome in SCLC does not usually exhibit the classic signs of Cushing’s syndrome and Cushing’s syndrome could also appear during effective chemotherapy.
Chemotherapy is the treatment of choice in SCLC.

Positive predictive value = TP (true positives) / [TP + FP (false positives)] = 40 / (40 + 20) = 0.66

Deletion of part of chromosome 5 or 7 is a poor prognostic feature for acute myeloid leukaemia (AML).

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 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.

Nail dystrophy (pitting of nails, onycholysis, subungual hyperkeratosis), dactylitis, sausage shaped fingers are most commonly seen with psoriatic arthropathy. There is asymmetric joint involvement most commonly distal interphalangeal joints. Uveitis and sacroiliitis may also occur. Arthritis mutilans may occur but is very rare. Cutaneous lesions may or may not develop. When they do, its usually much after the symptoms of arthritis.

1B: Individual Randomised Control Trial (with narrow confidence intervals)

Patients with varicella zoster infection present with general fatigue and fever along with multiple lesions which do not appear to be identical.

High-resolution CT (HRCT) scanning is more sensitive than standard chest radiography and is highly specific for diagnosing emphysema (outlined bullae are not always visible on a radiograph).

HRCT scanning may provide an adjunct means of diagnosing various forms of COPD (i.e., lower lobe disease may suggest AAT deficiency) and may help the clinician to determine whether surgical intervention would benefit the patient.

COPD is commonly associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favourable effects on pulmonary hemodynamics.

Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD, according to 2 landmark trials, the British Medical Research Council (MRC) study and the US National Heart, Lung and Blood Institute’s Nocturnal Oxygen Therapy Trial (NOTT). Hypoxemia is defined as PaO2 (partial pressure of oxygen in arterial blood) of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used for 15-19 hours per day.

Therefore, specialists recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythaemia, or cor pulmonale. Patients should be evaluated after 1-3 months after initiating therapy, because some patients may not require long-term oxygen.

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.

A very common complication after ERCP is post-ERCP pancreatitis, which based on the clinical scenario , this man has. The treatment for this is pain control, lots of intravenous fluids, and traditionally bowel rest, although more recent evidence suggests early feeding is better.

Distal renal tubular acidosis is due to defective proton secretion from the alpha intercalated cells of the distal tubule caused by dysfunction of the H+/K+ antiporter on the apical membrane. This leads to failure of H+ excretion thereby causing systemic acidosis and potassium depletion. Inability to lower the urine pH below 5.3 in the presence of systemic acidosis is the diagnostic hallmark of type I or distal renal tubular acidosis. Hypercalciuria, hypocitraturia and elevated urinary pH observed in distal renal tubular acidosis can lead to nephrocalcinosis and may cause renal calculi, obstructive uropathy and renal failure necessitating surgical or endoscopic stone extraction.

Charcot arthropathy is a progressive condition of the musculoskeletal system that is characterized by joint dislocations, pathologic fractures, and debilitating deformities. It results in progressive destruction of bone and soft tissues at weight-bearing joints. In its most severe form, it may cause significant disruption of the bony architecture.
Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle. Diabetes is now considered to be the most common aetiology of Charcot arthropathy.

This patient presentation is unlikely to be an L5 nerve root lesion given the results of the MRI scan. Therefore, the most likely diagnosis is a mononeuritis affecting the left common peroneal nerve. This would lead to sensory loss over the dorsum of the foot and anterolateral leg on the left.

Both long-acting calcium channel blockers and beta blockers improve symptoms of patients with SVT. Verapamil does not have adverse maternal or fetal side effects which would suggest that the use of verapamil in the treatment of supraventricular arrhythmias in pregnancy is safe and effective. Beta blockers are associated with intrauterine fetal growth restriction.

This is a low protein level, indicating the fluid is transudative. The only answer choice that is a transudative fluid is in hepatic cirrhosis. Exudative fluid would be seen in tuberculous peritonitis, peritoneal lymphoma, with liver mets, and with intra-abdominal malignancy.

From the given physical findings (the difference in BP between the radial and femoral arteries), the most probable diagnosis is coarctation of the aorta.

Insulinoma is associated with LOW fasting glucose, HIGH insulin level, and HIGH C peptide. Insulin-abuse or overdose will cause HGH insulin levels and a LOW C peptide. If the C peptide is low, be suspicious.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

Chickenpox is a highly communicable viral disease caused by human (alpha) herpesvirus 3 (varicella-zoster virus, VZV). It is transmitted from person to person by direct contact (touching the rash), droplet or air born spread (coughing and sneezing).

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.

Difficulty in initiating movement (bradykinesia), postural instability and unilateral symptoms (initially) are typical of Parkinson’s. Essential tremor symptoms are usually worse if arms are outstretched and eased by rest and alcohol.

Ramipril is an ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II as well as preventing the breakdown of bradykinin, leading to blood vessel dilatation and decreased blood pressure. However, bradykinin also causes smooth muscles in the lungs to contract, so the build-up of bradykinin is thought to cause the dry cough that is a common side-effect in patients that are on ACE inhibitors.

Redness of the eyes can present in all of the conditions. However, the green sticky discharge that causes the eyelids to stick together overnight is characteristic of bacterial conjunctivitis. Bacterial conjunctivitis is an inflammatory condition of the conjunctiva in which bacteria commonly Staphylococcus Aureus invade the conjunctiva. The person experiences a foreign body feeling in the eye and mucopurulent or purulent discharge.

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.

The classic triad of symptoms in patients with aortic stenosis is chest pain, heart failure and syncope. Pulsus parvus et tardus, pulsus alternans, hyperdynamic left ventricle, reversed splitting of the S2, prominent S4 and systolic murmur are some of the common findings of aortic stenosis. A calcified aortic valve is found in almost all adults with hemodynamically significant aortic stenosis.

Hereditary non-polyposis syndrome (HNPCC) is the most common type of inherited colorectal cancer. It often presents in younger and younger generations down a family. FAP presents with 100’s-1000’s of polyps and is less common. Li-Fraumeni syndrome and Fanconi syndrome are rare. For Peutz-Jeghers syndrome, the thing you will look for in the question stem is discoloured spots on the lips, this is classic.

Protein-calorie malnutrition is observed in almost 50% of dialysis patients, contributing to increased morbidity and mortality. All the other complications listed can usually be prevented thanks to modern-day dialysis techniques.

Erythropoietin (EPO) is used to distinguish between primary and secondary polycythaemia. Secondary polycythaemia can be caused by tumours in the kidney that may secrete EPO or EPO-like proteins.

Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases, as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Use of Hyperbaric oxygen therapy (HBOT) for treatment of mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)
Principle of HBOT:
Exposing patients to 100 percent oxygen under supra-atmospheric conditions results in a decrease in the half-life (t1/2) of COHb, from , 90 min in atmospheric air to , 30 minutes. The amount of oxygen dissolved in the blood also rises from , 0.3 to 6 mL/dL, increasing the delivery of non-haemoglobin-bound oxygen to the tissues.

The diagnosis is acute inferior ST elevation myocardial infarction so the most appropriate management is primary angioplasty.

This patient’s symptoms of anaemia, leukopenia, and elevated non-albumin protein concentration with fatigue and weight loss, point to myeloma. Thus plasma protein electrophoresis or Serum Protein Electrophoresis (SPE) is indicated when there is suspicion of myeloma.

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 darkness of the cinema room will have caused halfway dilation of the pupil. This can cause an acute attack of angle closure glaucoma. The appropriate test to diagnose this is applanation tonometry.

Stricturing is associated with Crohn’s disease, and elevated CRP supports this diagnosis in this patient, as well. Infliximab should not yet be started. Acute treatment is steroids (of a flare) however this man needs surgery. Although surgery should be avoided if at all possible in Crohn’s disease, and minimal surgery should occur (resecting as little as possible, given possible need for future resections), including possible stricturoplasty instead of resection. Chronic pancreatitis is unlikely given it would not cause stricture. Patients undergoing surgery should always have informed consent, which always includes risk of a stoma for any bowel surgery. Given the amount of weight he has lost he is at significant risk for refeeding syndrome, which can cause hypokalaemia, hypophosphatemia and hypomagnesemia.

Blood pressure should be routinely measured as leflunomide may cause hypertension and thus an increase in BP. It doesn’t cause changes in blood sugar levels, peak expiratory flow rate or haematuria.

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

Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies. The lungs are the second most frequent site of metastases from extrathoracic malignancies. Twenty percent of metastatic disease is isolated to the lungs. The development of pulmonary metastases in patients with known malignancies indicates disseminated disease and places the patient in stage IV in TNM (tumour, node, metastasis) staging systems.
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis in patients with known malignancies. Chest CT scanning without contrast is more sensitive than CXR.
Breast, colorectal, lung, kidney, head and neck, and uterus cancers are the most common primary tumours with lung metastasis at autopsy. Choriocarcinoma, osteosarcoma, testicular tumours, malignant melanoma, Ewing sarcoma, and thyroid cancer frequently metastasize to lung, but the frequency of these tumours is low.

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

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

A grossly elevated APTT may be caused by heparin therapy, haemophilia, or antiphospholipid syndrome. A normal factor VIIIc activity, however, points towards the diagnosis of haemophilia B, which is the deficiency of factor IX in the blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to the deficiency of clotting factor VIII and is more common than haemophilia B, accounting for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

The patient should be prescribed IV iron and subcutaneous erythropoietin to enhance erythropoiesis to address the dropped haemoglobin.

Urticaria is a group of disorders that share a distinct skin reaction pattern, namely the occurrence of itchy wheals anywhere on the skin. Wheals are short-lived elevated erythematous lesions ranging from a few millimetres to several centimetres in diameter and can become confluent. The itching can be prickling or burning and is usually worse in the evening or night time. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear.

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

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

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.

Postpartum depression may be mistaken for baby blues at first — but the signs and symptoms are more intense and last longer, and may eventually interfere with your ability to care for your baby and handle other daily tasks. Symptoms usually develop within the first few weeks after giving birth, but may begin earlier, during pregnancy or later, up to a year after birth.

The period prevalence of postpartum depression among women is a striking 21.9% the first year after birth, which makes it one of the most common medical complications of childbearing. Sertraline has been identified as an antidepressant of choice for breastfeeding women because infants are unlikely to develop quantifiable serum sertraline levels and very few adverse events associated with sertraline have been reported.

Women with a prior episode of postpartum psychosis have about a 30% risk of having another episode in the next pregnancy.

An atheroma is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.

Clostridium species do not present with an exfoliative skin rash. C. perfringens is a common aetiology in necrotizing infections (gas gangrene) as well as food poisoning, which often also includes diarrhoea. C. difficle causes diarrhoea. C. tetany and C. botulinum have neurotoxins that can lead to paralysis.

In asthma, a reversible increase in residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) may occur. There is a fall in FEV1, FVC and gas transfer.

Obsessive-Compulsive Disorder (OCD) is a common, chronic and long-lasting disorder in which a person has uncontrollable, reoccurring thoughts (obsessions) and behaviours (compulsions) that he or she feels the urge to repeat over and over.
People with OCD may have symptoms of obsessions, compulsions, or both. These symptoms can interfere with all aspects of life, such as work, school, and personal relationships.

Obsessions are repeated thoughts, urges, or mental images that cause anxiety. Common symptoms include:
Fear of germs or contamination
Unwanted forbidden or taboo thoughts involving sex, religion, and harm
Aggressive thoughts towards others or self
Having things symmetrical or in a perfect order

Compulsions are repetitive behaviours that a person with OCD feels the urge to do in response to an obsessive thought. Common compulsions include:
-Excessive cleaning and/or handwashing
-Ordering and arranging things in a particular, precise way
-Repeatedly checking on things, such as repeatedly checking to see if the door is locked or that the oven is off
-Compulsive counting

Research also shows that a type of CBT called Exposure and Response Prevention (ERP) is effective in reducing compulsive behaviours in OCD, even in people who did not respond well to SRI medication. ERP has become the first-line psychotherapeutic treatment for OCD

This case presents with characteristic symptoms of SLE and with her renal biopsy results of focal glomerulonephritis, this is clearly Class III SLE.

Annual incidence of DVT in the general population is about 1 per 1000 adults. So the most suitable answer is about 2 per 1000.

Hemiballismus or hemiballism in its unilateral form is a very rare movement disorder. It is a type of chorea caused in most cases by a decrease in activity of the subthalamic nucleus of the basal ganglia, resulting in the appearance of flailing, ballistic, undesired movements of the limbs. Symptoms may decrease while the patient is asleep. Antidopaminergic agents (e.g. Haloperidol) are the mainstay of treatment.

Cyclophosphamide is a cytotoxic alkylating agent that acts by causing cross-linking of DNA strands. Its major adverse effects include haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma.

Cardiomyopathy is caused by doxorubicin and ototoxicity is caused by cisplatin. Alopecia and weight gain are associated with a variety of chemotherapeutic agents especially those that treat breast cancers (e.g. paclitaxel).

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.

Diagnosis of multiple myeloma (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

Alpha-1-antitrypsin (AAT) is a member of the serine proteinase inhibitor (serpin) family of proteins with a broad spectrum of biological functions including inhibition of proteases, immune modulatory functions, and the transport of hormones.

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus.

Some patients return spontaneously to a euthyroid state within a few months, but most patients experience a phase of hypothyroidism that takes 2 to 6 months to resolve; of this group, some develop permanent hypothyroidism. About 50% of patients, however, will develop permanent hypothyroidism within 5 years of the diagnosis of postpartum thyroiditis.

High titres of anti-TPO antibodies during pregnancy have been reported to have high sensitivity and specificity for postpartum autoimmune thyroid disease.

Intracranial pressure (ICP) is a complex brain modality that determines cerebral perfusion pressure (CPP), which is the difference between arterial blood pressure (ABP), and ICP. Raised ICP reduces CPP and blood delivery to the brain. This jeopardizes cerebral function and organismal survival in many species. A massive rise in ICP is also known to produce an increase in ABP, bradycardia and respiratory irregularities termed Cushing response. This mechanism is generally considered to be an agonal and terminal event occurring in extreme condition of brainstem ischaemia leading to a sympatho-adrenal response.

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.

Methyldopa is the drug of first choice for the control of mild to moderate hypertension in pregnancy. Labetalol is also considered as a first line drug for hypertension in pregnancy. Calcium channel blockers and hydralazine are considered as second line drugs. Beta-blockers (except labetalol), angiotensin receptor blockers, angiotensin-converting enzyme inhibitors and thiazides are not recommended.

The chronic asymptomatic carrier state is thought to be why there is continued appearance of the bacterium in human populations. As shedding of the organism is intermittent and sometimes at low levels, methods to detect it have been limited. The Salmonella typhi may be cultured from intestinal secretions, faeces or urine in chronic carriers and is recommended to confirm the diagnosis. Vi agglutination test can also be high in normal people in areas with typhoid endemic. Full blood count or blood culture would not be helpful to determine carrier status. Widal antigen test is unable to differentiate carriers from people with a hx of prior infection.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder that predominantly affects infants, children, and young adults. CF is the most common life-limiting genetic disorder in whites, with an incidence of 1 case per 3200-3300 new-borns in the United States.

People with CF can have a variety of symptoms, including:
Very salty-tasting skin
Persistent coughing, at times with phlegm
Frequent lung infections including pneumonia or bronchitis
Wheezing or shortness of breath
Poor growth or weight gain in spite of a good appetite
Frequent greasy, bulky stools or difficulty with bowel movements
Male infertility

Signs of bronchiectasis include the tubular shadows; tram tracks, or horizontally oriented bronchi; and the signet-ring sign, which is a vertically oriented bronchus with a luminal airway diameter that is 1.5 times the diameter of the adjacent pulmonary arterial branch.

Bronchiectasis is characterized by parallel, thick, line markings radiating from hila (line tracks) in cylindrical bronchiectasis. Ring shadows represent dilated thick-wall bronchi seen in longitudinal section or on-end or dilated bronchi in varicose bronchiectasis.

Pseudomonas aeruginosa is the key bacterial agent of cystic fibrosis (CF) lung infections, and the most important pathogen in progressive and severe CF lung disease. This opportunistic pathogen can grow and proliferate in patients, and exposure can occur in hospitals and other healthcare settings.

Haemophilus influenzae is regularly involved in chronic lung infections and acute exacerbations of CF patients

The diagnosis for the aforementioned case is thrombotic thrombocytopenic purpura (TTP). TTP is classically characterised as a pentad of thrombocytopaenia, microvascular haemolysis, fluctuating neurological signs, renal impairment, and fever.

The differential diagnosis for severe thrombocytopaenia is immune thrombocytopenic purpura (ITP). ITP is more common than TTP. However, a patient of ITP would not present with the range of symptoms seen in this scenario.

In TTP, there is deficiency of a protease which breaks down large multimers of von Willebrand factor. This leads to abnormally large and sticky multimers of von Willebrand factor which cause platelets to clump within the vessels.

Untreated TTP has a mortality rate of up to 90%. Therefore, rapid plasma exchange (PEX) may be a life-saving intervention. Platelet transfusion in TTP is only indicated if there is an ongoing life-threatening bleed. Intravenous methylprednisolone is indicated after treatment with PEX has been completed. There is no current role of intravenous immunoglobulin in the routine management of TTP. However, there have been reports of its successful use in PEX- and steroid-refractory cases. Intravenous argatroban is indicated in heparin-induced thrombocytopaenia (HIT), but there is no history of recent heparin administration or hospitalisation in this patient nor are the clinical signs consistent with HIT.

Management options for TTP include PEX as the treatment of choice. Steroids and immunosuppressants are also given. Antibiotics are not recommended as they may worsen the outcome of the disease. For cases resistant to PEX and pharmacologic therapy, vincristine is given.

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.

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.

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.

The rationale behind the use of sodium bicarbonate is that it increases the alkalinity of the urine promoting lithium excretion. The preferred treatment in severe cases would be haemodialysis.

Lithium is a mood-stabilizing drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Toxicity may be precipitated by dehydration, renal failure, diuretics (especially Bendroflumethiazide), ACE inhibitors, NSAIDs and metronidazole.

Features of toxicity
Coarse tremor (a fine tremor is seen in therapeutic levels)
Hyperreflexia
Acute confusion
Seizure
Coma

Management
Mild-moderate toxicity may respond to volume resuscitation with normal saline
Haemodialysis may be needed in severe toxicity
Sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion.

The empty boxes indicate that the patient has run out of his medication.
Chronic administration of high doses of glucocorticoids (GCs) (e.g., prednisone or prednisolone) and also other hormones such as oestrogens, progestins, androgens and growth hormone induce varying degrees of tolerance, resulting in a progressively decreased response to the effect of the drug, followed by dependence and rarely addiction.
The glucocorticoid withdrawal syndrome (GWS) has been considered a withdrawal reaction due to established physical dependence on supraphysiological GC levels.
The severity of GWS depends on the genetics and developmental history of the patient, on his environment, and on the phase and degree of dependence the patient has reached. Its management should include a temporary increase in the dose of GCs followed by gradual, slow tapering to a maintenance dose.

Acute, symptomatic hypocalcaemia is treated with 10ml of 10% calcium gluconate over 10 minutes.

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion characterised by the acute onset of non-cardiogenic pulmonary oedema following transfusion of blood products.

TRALI is a more severe manifestation of the febrile non-haemolytic group of transfusion reactions and usually occur in patients who have had multiple previous transfusions. TRALI is related to leucocyte antibodies which are present in the plasma of the blood donor. Multiparous women are the highest-risk donors for TRALI.

For management, leucocyte-depleted blood is now used for transfusion and this is associated with a reduced risk of this type of transfusion reaction.

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.

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.

Hypertrophic cardiomyopathy is an autosomal dominant condition. Patients present with sudden cardiac death, dyspnoea, syncope and presyncope, angina, palpitations, orthopnoea and paroxysmal nocturnal dyspnoea, Congestive heart failure and dizziness. Physical findings include double or triple apical impulse, prominent a wave in the JVP, an ejection systolic crescendo-decrescendo murmur and a holosystolic murmur at the apex and axilla of mitral regurgitation.
ECG shows ST-T wave abnormalities and LVH, axis deviation (right or left), conduction abnormalities (P-R prolongation, bundle-branch block), sinus bradycardia with ectopic atrial rhythm, atrial enlargement, abnormal and prominent Q wave in the anterior precordial and lateral limb leads.
2D echocardiography shows abnormal systolic anterior leaflet motion of the mitral valve, LVH, 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, partial systolic closure of the aortic valve in midsystole

Tumour lysis syndrome (TLS) occurs most notably in patients with haematological malignancies including, Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphocytic Leukaemia (ALL).
Risk factors for TLS include:
• Large tumour burden
• Sensitivity of the tumour to chemotherapy
• Rapid tumour growth rate
TLS is characterized by:
• Hyperuricemia
• Hyperkalaemia
• Hyperphosphatemia
• Hypocalcaemia
Treatment of TLS:
• Allopurinol: It is a xanthine oxidase inhibitor, it reduces the conversion of nucleic acid by-products to uric acid. Thus, it prevents urate nephropathy and subsequent oliguric renal failure. Note: dose reduction is essential in renal failure or if given along with mercaptopurine or azathioprine.
Alternatives to Allopurinol: Febuxostat; Rasburicase are useful in patients with hyperuricemia.
• Hydration
• Diuresis: Should be considered in well hydrated patients with insufficient urine output. Furosemide to be considered in normo-volemic patients with hyperkalaemia. Urine alkalization can be considered for promoting alkaline diuresis.
• Treatment of electrolyte imbalances including hyperkalaemia, hyperphosphatemia, and hypocalcaemia.
• Dialysis can be considered in refractory cases.

This scenario is suggestive of a pancreatic head mass with obstructive jaundice and US showing a ‘double duct’ sign. A CT Scan would be recommended to evaluate for a pancreatic head mass. If a mass was found, the next step would then be to do an ERCP with EUS to obtain a biopsy of the mass for tissue diagnosis. Laparoscopy would not be recommended. CA19-9 would not be diagnostic.

Spinal cord hemisection, also known as Brown-Sequard syndrome, is associated with symptoms affecting one spinothalamic and one corticospinal tract. Symptoms include ipsilateral paralysis, loss of vibration and position sense, and hyperreflexia below the level of the lesion. Contralateral loss of pain and temperature sensation is also seen, usually beginning 2-3 segments below the level of the lesion.

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

Thrombotic thrombocytopenic purpura (TTP) is characterised by the von Willebrand factor (vWF) microthrombi within the vessels of multiple organs. In this condition, the ADAMTS13 metalloprotease enzyme which is responsible for the breakdown of vWF multimer, is deficient, causing its build-up and leading to platelet clots that then decreases the circulating platelets, leading to bleeding in the patient.

Alpha1-antitrypsin (AAT) deficiency, first described in 1963, is one of the most common inherited disorders amongst white Caucasians. Its primary manifestation is early-onset of pan acinar emphysema. In adults, alpha1-antitrypsin deficiency leads to chronic liver disease in the fifth decade. As a cause of emphysema, it is seen in non-smokers in the fifth decade of life and during the fourth decade of life in smokers.

Symptoms of alpha1-antitrypsin (AAT) deficiency emphysema are limited to the respiratory system. Dyspnoea is the symptom that eventually dominates alpha1-antitrypsin deficiency. Similar to other forms of emphysema, the dyspnoea of alpha1-antitrypsin deficiency is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.
The serum levels of some of the common genotypes are:
•PiMM: 100% (normal)
•PiMS: 80% of normal serum level of A1AT
•PiSS: 60% of normal serum level of A1AT
•PiMZ: 60% of normal serum level of A1AT, mild deficiency
•PiSZ: 40% of normal serum level of A1AT, moderate deficiency
•PiZZ: 10–15% (severe alpha 1-antitrypsin deficiency)

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

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.

Angioid retinal streaks are seen on fundoscopy as irregular dark red streaks radiating from the optic nerve head. They are caused by degeneration, calcification and breaks in Bruch’s membrane. They are typically associated with Paget’s disease.

Avascular necrosis (AVN) of the femoral head is a pathological process that results from disruption of the blood supply to the bone and occurs most commonly in the femoral epiphysis. Patients usually present with pain and limited joint motion. The mechanism involves impaired circulation to a specific area that ultimately becomes necrotic. AVN is most frequently associated with high doses of oral and intravenous corticosteroids and prolonged duration of therapy. Cancer patients receiving chemotherapy are usually also treated with corticosteroids.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group)
Experimental event rate, EER = 10 / 200 = 0.05

Control event rate, CER = 12 / 600 = 0.02

Therefore the relative risk = EER / CER = 0.05 / 0.02 = 2.5

Physiological abnormalities in anorexia include:
– Hypokalaemia – from diuretic or laxative use
– Low FSH, LH, oestrogens and testosterone – most consistent endocrine abnormality was low serum luteinizing and follicle stimulating hormone (LH and FSH) levels associated with depressed serum oestradiol levels.
– Raised cortisol and growth hormone
– Impaired glucose tolerance – lack of glucose precursors in the diet or low glycogen stores. Low blood glucose may also be due to impaired insulin clearance
– Hypercholesterolemia
– Hypercarotenaemia
– Low T3

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.

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.

Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. It causes pain, redness, a watering eye (epiphora), and swelling and erythema at the inner canthus of the eye. Management is with systemic antibiotics. IV antibiotics are indicated if there is associated periorbital cellulitis.

The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. In this case the NNT can be calculated as follows: NNT = 1/ Absolute risk reduction (ARR). ARR=(Control event rate expressed per 1000 patient years) – (Experimental event rate expressed per 1000 patient years) = 43.9-37.3 = 6.6/1000 patient years

NNT=(Patient years)/ARR = 1000/ 6.6 = 151.5. The closest to 151.5 is 150, thus it is the correct answer.

Diagnosis of RA is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). Rheumatoid factor is not very specific for this disease and hence has low reliability. X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis.

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.

There is a strong suspicion of Thrombotic Thrombocytopenic Purpura (TTP) in this patient as he presents with neurological changes (from confusion to convulsions and coma), fever, haemolysis, thrombocytopenia, and renal failure. Additionally, TTP cases may present with jaundice, splenomegaly, and hypertension as seen in this patient. With a diagnosis of TTP, recent studies have shown that platelet transfusion is not recommended in this case because it has been shown to increase the risk for arterial thrombosis and mortality possibly due to increased aggregations.

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 Smooth endoplasmic reticulum (ER) is the major site at which membrane lipids are synthesized in eukaryotic cells. Because they are extremely hydrophobic, lipids are synthesized in association with already existing cellular membranes rather than in the aqueous environment of the cytosol. Although some lipids are synthesized in association with other membranes, most are synthesized in the ER. They are then transported from the ER to their ultimate destinations either in vesicles or by carrier proteins.

Classically, pheochromocytoma manifests with the following 4 characteristics:
– Headaches
– Palpitations
– Sweating
– Severe hypertension

The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have released clinical practice guidelines for the diagnosis and management of pheochromocytoma.
Biochemical testing via measurement of plasma free metanephrines or urinary fractionated metanephrines should be performed in patients suspected of having pheochromocytoma.

Catecholamines produced by pheochromocytomas are metabolized within chromaffin cells. Norepinephrine is metabolized to normetanephrine and epinephrine is metabolized to metanephrine. Because this process occurs within the tumour, independently of catecholamine release, pheochromocytomas are best diagnosed by measurement of these metabolites rather than by measurement of the parent catecholamines.

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.

He has a consequence of atherosclerotic disease (MI). The most probable diagnosis is cutaneous cholesterol emboli as it is more common after anticoagulation or thrombolytics, the skin involvement, eosinophilia and raised IgE. It is more common above 60 yrs. of age.

Renal osteodystrophy is a metabolic bone disease often affecting long-term dialysis patients. The kidneys are no longer able to maintain the calcium levels in the blood, thus the PTH increases as the body attempts to raise blood calcium levels. Osteomalacia in these cases is most likely caused by the diminished activity of renal 1-a-hydroxylase that is important for hydroxylation of Calciferol to calcitriol (Vitamin D). This bioactive form of Vitamin D is responsible for increasing intestinal absorption of calcium.

The most likely cause for acute breathlessness is due to papillary muscle rupture which causes mitral regurgitation.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

Prevention of osteoporosis associated with chronic glucocorticoid therapy is done by administrating bisphosphonates. Oral bisphosphonates are indicated for patients aged above 65 who have been on steroid therapy for over 3 months, so as to reduce the risk of steroid induced osteoporosis. HRT is usually done in post menopausal women who have oestrogen related bone resorption.

Lofgren’s syndrome is an acute form of sarcoidosis characterized by erythema nodosum, bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. Other symptoms include anterior uveitis, fever, ankle periarthritis, and pulmonary involvement.

Löfgren syndrome is usually an acute disease with an excellent prognosis, typically resolving spontaneously from 6-8 weeks to up to 2 years after onset. Pulmonologists, ophthalmologists, and rheumatologists often define this syndrome differently, describing varying combinations of arthritis, arthralgia, uveitis, erythema nodosum, hilar adenopathy, and/or other clinical findings.

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.

Bulimia nervosa is a serious, potentially life-threatening eating disorder characterized by a cycle of bingeing and compensatory behaviours such as self-induced vomiting designed to undo or compensate for the effects of binge eating.

According to the DSM-5, the official diagnostic criteria for bulimia nervosa are:
Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
Eating, in a discrete period of time (e.g. within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances.
A sense of lack of control over eating during the episode (e.g. a feeling that one cannot stop eating or control what or how much one is eating).
Recurrent inappropriate compensatory behaviour in order to prevent weight gain, such as self-induced vomiting, misuse of laxatives, diuretics, or other medications, fasting, or excessive exercise.
The binge eating and inappropriate compensatory behaviours both occur, on average, at least once a week for three months.
Self-evaluation is unduly influenced by body shape and weight.
The disturbance does not occur exclusively during episodes of anorexia nervosa.

Antidepressants as a group – particularly selective serotonin reuptake inhibitors (SSRIs) – are the mainstay of pharmacotherapy for bulimia nervosa. These may be helpful for patients with substantial concurrent symptoms of depression, anxiety, obsessions, or certain impulse disorder symptoms. They may be particularly good for patients who have not benefited from or had suboptimal response to suitable psychosocial therapy or who have a chronic, difficult course in combination with other treatments.

Food and Drug Administration (FDA) approved treatments
Fluoxetine (Prozac): Initial dose 20 mg/d with advance over 1–2 weeks to 60 mg/d in the morning as tolerated. Some patients may need to begin at a lower dose if side effects are intolerable. A maximum dose of 80 mg/d may be used in some cases.

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.

Features that affect prognosis are tumour thickness in millimetres (Breslow’s depth – the deeper the Breslow thickness the poorer the prognosis.), depth related to skin structures (Clark level – the level of invasion through the dermis), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumour-infiltrating lymphocytes (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant metastasis. Malignant melanoma tends to grow radially before entering a vertical growth phase. The diameter it reaches has not been found to be a prognostic factor.

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli. The laboratory results will usually include fragmented RBCs, decreased serum haptoglobin, reduced platelet count, nonspecific WBC changes, and normal coagulation tests (PTT included).

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.

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

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

This patient is having vaso-occlusive event/crisis (thrombotic crisis) which is a type of sickle cell crisis. It may be associated with ostealgia.

There is no evidence of an aplastic crisis in this case as the haemoglobin level is reasonable with a good reticulocyte count. Conversely, the haemoglobin is not low enough and reticulocyte count and bilirubin are not high enough for a haemolytic crisis.

Sickle cell anaemia is characterised by periods of good health with intervening crises. The four main types of sickle cell crises are thrombotic crisis (painful or vaso-occlusive crisis), sequestration crisis, aplastic crisis, and haemolytic crisis.

Thrombotic crisis is precipitated by infection, dehydration, alcohol, change in temperature, and deoxygenation. Sequestration crisis is characterised by acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates). Aplastic crisis is characterised by a sudden fall in haemoglobin without marked reticulocytosis. It usually occurs secondary to parvovirus infection. In haemolytic crisis, a fall in haemoglobin occurs secondary to haemolysis. It is a rare type of sickle cell crisis.

Meningiomas are the most common benign tumours of the brain. Their name is derived from the fact that they arise from the dura mater which together with the pia matter and arachnoid mater form the meninges. The chances that a meningioma is benign are almost 98%. They are non-invasive and well delineated, causing sign and symptoms of brain compression.

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (beta-adrenoceptor mediated). ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. The main physiological actions of natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular resistance. It causes a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion.

The most COMMON site of inflammation from ulcerative colitis is the rectum, making this the correct answer. This is simply a fact you need to memorize. In general, ulcerative colitis only occurs in colorectal regions– nothing in the small bowel (unless there is backwash into the terminal ileum) and nothing further up the GI tract. In Crohn’s it can affect the entire GI tract from mouth to anus.

The patient has spinal cord compression until proven otherwise. Urgent assessment is required.

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

Behçet disease is a rare vasculitic disorder that is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. The systemic manifestations can be variable. Ocular disease has the greatest morbidity, followed by vascular disease generally from active vasculitis. Cutaneous manifestations can occur in up 75% of patients with Behcet disease and can range from acneiform lesions, to nodules and erythema nodosum. GI manifestations can be severe. Differentiating Behçet disease from active inflammatory bowel disease can be clinically difficult. Herpes would have ideally responded to acyclovir. Sarcoidosis does not have genital and oral ulcerations.

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.

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

Hypovitaminosis B1, consistent with dry beriberi is crucially a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Dry beriberi or ‘acute nutritional polyneuropathy’ is considered to be rare in the western world. Rapid deterioration can occur, typically with weakness, paraesthesia and neuropathic pain. Striking motor nerve involvement can occur, mimicking Guillain-Barré syndrome (GBS). In the context of increasing alcohol abuse in the western world, it is possible that alcoholic neuropathy associated with abrupt deterioration due to concomitant nutritional hypovitaminosis B1 may be seen increasingly often.

Retinitis pigmentosa is a genetic disorder primarily affecting the peripheral retina resulting in tunnel vision. Night blindness is often the initial sign. Fundoscopy exam reveals black bone spicule-shaped pigmentation in the peripheral retina, and mottling of the retinal pigment epithelium.

Positive predictive value is the probability that subjects with a positive screening test truly have the disease.

Positive predictive value = true positive / ( true positive + false positive)

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).

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.

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli.

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

Drug induced lupus is usually positive for antinuclear and antihistone antibodies, typically without renal or neurologic involvement. However, pulmonary involvement is common. Drugs that can induce lupus include isoniazid, hydralazine, procainamide, chlorpromazine, and other anticonvulsants.

Asthma is a condition characterized by airway hyperresponsiveness, which results in reversible increases in bronchial smooth muscle tone, and variable amounts of inflammation of the bronchial mucosa.
During an acute asthma attack, the already inflamed airways narrow further due to bronchospasm, which leads to increased airway resistance. Because of the increased smooth muscle tone during an asthma attack, the airways also tend to close at abnormally high lung volumes, trapping air behind occluded or narrowed small airways. Thus the acute asthmatic will breathe at high lung volumes, his functional residual capacity will be elevated, and he will inspire close to total lung capacity. The accessory muscles of respiration are often used to maintain the lungs in a hyperinflated state.

During episodes of acute asthma, pulmonary function tests reveal an obstructive pattern. This includes a decrease in the rate of maximal expiratory air flow (a decrease in FEV1 and the FEV1/FVC ratio) due to the increased resistance, and a reduction in forced vital capacity (FVC) correlating with the level of hyperinflation of the lungs. Because these patients breathe at such high lung volumes (near the top of the pressure-volume curve, where lung compliance greatly decreases), they must exert significant effort to create an extremely negative pleural pressure, and consequently fatigue easily. Overinflation also reduces the curvature of the diaphragm, making it less efficient in generating further negative pleural pressure.