Transposition of the great arteries results in a significant hypoxemic status that is observed clinically by central cyanosis. The bluish discoloration of the skin and mucous membranes is therefore the basic pattern of clinical presentation in transposition. Its onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. Limited intercirculatory mixing, usually present if the ventricular septum is intact or the atrial septal defect is restrictive, is related to progressive and profound central cyanosis evident within the first hours of life. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy. Heart murmurs associated with left outflow tract obstruction, due to a persistent arterial duct or a septal defect may be heard, but they are not a constant finding.

An aspergilloma is a fungus ball (mycetoma) that develops in a pre-existing cavity in the lung parenchyma. Underlying causes of the cavitary disease may include treated tuberculosis or other necrotizing infection, sarcoidosis, cystic fibrosis, and emphysematous bullae. The ball of fungus may move within the cavity but does not invade the cavity wall. Aspergilloma may manifest as an asymptomatic radiographic abnormality in a patient with pre-existing cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes. In patients with HIV disease, aspergilloma may occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia. Of patients with aspergilloma, 40-60% experience haemoptysis, which may be massive and life threatening. Less commonly, aspergilloma may cause cough and fever.

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

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

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.

Renal elimination of a drug has no role in altering the bioavailability of a drug.
The bioavailability of a drug is the proportion of the drug which reaches systemic circulation.
Mathematically, bioavailability is the AUCoral/AUCiv x 100%, where AUC = area under the concentration-time curve following a single (oral or iv) dose.

Other options are true:
By definition, the bioavailability of a drug given intravenously is 100%.
Drugs given orally that undergo high pre-systemic (first-pass) metabolism in the liver or gut wall have a low bioavailability e.g. lidocaine.
Bioavailability is also affected by the degree of absorption from the gut and this can change depending on gut motility and administration of other drugs.

Bronchial carcinoids are uncommon, slow growing, low-grade, malignant neoplasms, comprising 1-2% of all primary lung cancers.
It is believed to be derived from surface of bronchial glandular epithelium. Mostly located centrally, they produce symptoms and signs of bronchial obstruction such as localized wheeze, non resolving recurrent pneumonitis, cough, chest pain, and fever. Haemoptysis is present in approximately 50% of the cases due to their central origin and hypervascularity.
Central bronchial carcinoids are more common than the peripheral type and are seen as endobronchial nodules or hilar/perihilar mass closely related to the adjacent bronchus. Chest X-ray may not show the central lesion depending on how small it is.

Corticosteroids are well known for their ocular complications such as glaucoma and cataracts.

The most probable diagnosis is Marfan’s syndrome because of a family history of cardiac death and heart murmurs. A characteristic feature is pain which radiates to the back. A wide pulse pressure and a diastolic heart murmur is suggestive of aortic dissection.

The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8 to 3.0 mmol/L has been suggested for treatment of eclamptic convulsions. Maternal toxicity is rare when MgSO4 is carefully administered and monitored. The first warning of impending toxicity in the mother is loss of the patellar reflex at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at 5 to 6.5 mmol/L. Cardiac conduction is altered at greater than 7.5 mmol/L, and cardiac arrest can be expected when concentrations of magnesium exceed 12.5 mmol/L. Careful attention to the monitoring guidelines can prevent toxicity. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most commonly monitored parameters.

Ataxic telangiectasia is an inherited combined immunodeficiency disorder that is characterised by cerebellar ataxia and telangiectasia as seen in this child, as well as frequent infections as noted in this child’s history. The other differentials would not present with this clinical picture:

Friedreich’s ataxia and Infantile-onset spinocerebellar ataxia do not present with immune problems, whereas Cerebral palsy and Di-George Syndrome do not present with ataxia.

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti–sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.

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

The 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.

A typical attack may last less than an hour but can also persist for longer. In primary Raynaud’s, attacks are more likely symmetric, episodic, and without evidence of peripheral vascular disease. Patients more commonly have a negative ANA and normal inflammatory markers. There should be no evidence of tissue gangrene, digital pitting, or tissue injury in primary Raynaud’s. In contrast, patients with secondary Raynaud’s will describe attacks that are more frequent, painful, often asymmetric and may lead to digital ulcerations.

Secretin is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Secretin helps regulate the pH of the duodenum by
1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and
(2) stimulating the production of bicarbonate from the ductal cells of the pancreas.
G cells in the antrum of the stomach release gastrin
I cells in upper small intestine release CCK
D cells in the pancreas & stomach secrete somatostatin
K cells secrete gastric inhibitory peptide, an incretin, which also promotes triglyceride storage.

Sodium cromoglycate principally acts by inhibiting the degranulation of mast cells triggered by the interaction of antigen and IgE.
The inhibitory effect on mast cells appears to be cell-type specific since cromoglycate has little inhibitory effect on mediator release from human basophils.
Thus, it inhibits the release of histamine, leukotrienes, and slow-reacting substance of anaphylaxis from mast cells by inhibiting degranulation following exposure to reactive antigens.

Adverse effects include cough, flushing, palpitation, chest pain, nasal congestion, nausea, fatigue, migraine, etc.

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.

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

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

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

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

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

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

The best next step is to try a dairy-free diet, many patients may develop this in their lifetime. IBS is a diagnosis of exclusion, and one would need to rule lactose intolerance out as a potential aetiology first. She is only 28, and without overt bleeding or signs/sxs/labs suggestive of obstruction or inflammation; colonoscopy, flex sig and a barium enema are not indicated.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

Chronic hepatitis B patients have an increased risk of hepatocellular carcinoma. In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have+HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, +anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. It is important to remember these serologies, it will get you a lot of points on the test.

Clubbing of the fingers can be present in many clinical conditions like CLD, bronchiectasis, lung abscess, Ulcerative colitis and Crohn’s Disease.

Koilonychia or spoon shaped nails are a typical finding in iron deficiency anaemia.

Splinter haemorrhages are pin point haemorrhages found in infective endocarditis and secondary to trauma.

Yellow nails are present in pulmonary and renal disease.

Though a common community pathogen, Staphylococcus Aureas is found twice as frequently in pneumonias in hospitalized patients. It often attacks the elderly and patients with CF and arises as a co-infection with influenza viral pneumonia. The clinical course is characterized by high fevers, chills, a cough with purulent bloody sputum, and rapidly progressing dyspnoea. The gross pathology commonly reveals an acute bronchopneumonia pattern that may evolve into a necrotizing cavity with congested lungs and airways that contain a bloody fluid and thick mucoid secretions.

The patient has acute promyelocytic leukaemia (APML) with associated disseminated intravascular coagulation (DIC). Although
the platelet count is high, platelet function is ineffective.

Patients may present, as in this case, with severe bleeding, and the most appropriate emergency treatment would be administration of fresh frozen plasma (FFP).

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Chiari Type I malformation usually presents with symptoms due to brain stem and lower cranial nerve dysfunction, which includes DBN.

Narrow complex tachycardia with hypotension is a medical emergency. Immediate synchronized cardioversion is the ideal management.

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

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

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

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

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

Cefalexin should be avoided in this patient.
This patient is known to have a severe penicillin allergy. None of the above antibiotics are penicillin based. However, 0.5 – 6.5% of patients who are proven to have an IgE mediated penicillin allergy will also be allergic to cephalosporins, including cefalexin.

Penicillin, cephalosporins, and carbapenems are all members of the beta-lactam group of antibiotics and share a common beta-lactam ring. There is, therefore, a small risk of allergy cross-over between all these antibiotics. The rates of allergy cross-over are lower with second and third-generation cephalosporins than first-generation cephalosporins such as cefalexin.

It is important to question the patient carefully to ascertain what symptoms they had on exposure to penicillin. Symptoms such as an urticarial rash or itching make it more likely that they have an IgE mediated allergy.