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

Tumour lysis syndrome (TLS), triggered by the introduction of chemotherapy, has resulted in the aforementioned symptoms in this patient.

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.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.

In many Western countries and health plans in the United States, patients have a primary care physician who acts as a formal gatekeeper for medical specialist care and thereby determines together with the patient whether or not a patient requires medical specialist care. Ideally in such systems, patients are treated in primary care if possible, and referred to medical specialist care if necessary. For the gatekeeper system to be effective, it is vital that adequate decisions are made about when and who to refer. But it is also important that referred patients comply with the referral by consulting a medical specialist. In this case, the GP should discuss with the patient the reasons why she cannot follow the treatment plan. In other words, the GP should detect why the patient is being non-compliant.

Hepatitis B full vaccine and Ig should be given to babies born to hepatitis B positive mothers. Hepatitis B vaccine alone or Ig alone is not sufficient to prevent the infection in the new-born baby.

After renal transplant, asymptomatic patients can still have graft dysfunction as an early complication, with rising serum creatinine; therefore, urine and blood cultures should be ordered first. This should be followed by measuring the Tacrolimus levels, as this drug can be directly nephrotoxic. Next, a Doppler ultrasound of the transplant site should be ordered, to check for any obstructions or occlusions.

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

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

Anticholinergic syndrome occurs following overdose with drugs that have prominent anticholinergic activity including tricyclic antidepressants, antihistamines and atropine. Features include dry, warm, flushed skin, urinary retention, tachycardia, mydriasis (dilated pupils) and agitation.

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.

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.

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.

Graves’ disease is the most common cause of thyrotoxicosis in pregnancy.

– Poor control of thyrotoxicosis is associated with pregnancy loss, pregnancy-induced hypertension, prematurity, low birth weight, intrauterine growth restriction, stillbirth, thyroid storm, and maternal congestive heart failure.

– Antithyroid drugs are the treatment of choice of hyperthyroidism during pregnancy. The lowest dose of ATD needed to maintain TT4 1.5× the upper limit of the non-pregnant reference range or FT4 at the upper limit of the reference range should be used.
Two different antithyroid drug (ATD) regimens are in common use for Grave’s disease: i) Titration method and ii) Block-and-replace method.
In the titration method, the usual starting dose is 15–30 mg/day methimazole (or equivalent doses of other thionamides); further to periodic thyroid status assessment, daily dose is tapered down to the lowest effective dose (avoiding both hyper- and hypothyroidism).
The block-and-replace method uses persistently high ATD doses in association with L-thyroxine replacement to avoid hypothyroidism; treatment lasts 6 months. This method has advantages and disadvantages over the titration method. Higher doses of ATDs may have a greater immunosuppressive action useful for a permanent remission of hyperthyroidism, but this effect remains to be demonstrated.
Avoidance of hypothyroidism or ‘escape’ of hyperthyroidism seems easier than with the titration method; treatment is shorter, and the number of visits lower. On the other hand, the much higher number of tablets taken every day may create problems of poor compliance. The block-and-replace method should not be used during pregnancy.

– Breastfeeding has been shown to be safe in mothers taking ATDs in appropriate doses.

Immunoglobulin should be given to all seronegative women within 4 days. However, it is strongly advised to seek medical care immediately if the disease develops.

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.

Thioridazine has a quinidine-like action on the heart and is known to cause cardiac arrhythmias including prolonged PR and QT intervals and widening of QRS complexes. Intravenous magnesium sulphate is regarded as the treatment of choice for this arrhythmia.

HIV-associated nephropathy (HIVAN) show typical findings of scarring called focal segmental glomerulosclerosis (FSGS) and microcystic tubular dilatation, prominent podocytes, and collapsing capillary loops.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Given her history of bowel resections, the most likely answer in this case is short bowel syndrome. IBS is a diagnosis of exclusion and less likely. Bacterial overgrowth does not relate to resection history, so unlikely. Celiac disease or a flare of IBD are also less likely than short bowel syndrome in this case, simply given the history. Also her labs are normal making these unlikely. History, history, history!

Lithium acts by:
– I inhibiting postsynaptic D2 receptor super sensitivity
– Altering cation transport in nerve and muscle cells and influencing reuptake of serotonin or norepinephrine
– Inhibiting phosphatidylinositol cycle second messenger systems

The NICE guidelines for depression and bipolar disorder both recommend Lithium as an effective treatment; patients who take lithium should have regular blood tests to monitor the amount of lithium in their blood (every 3 months), and to make sure the lithium has not caused any problems with their kidneys or thyroid (every 6 months).

Lithium adverse effects include:
– Leucocytosis (most patients) which is when the white cells are above the normal range in the blood.
– Polyuria/polydipsia (30-50%)
– Dry mouth (20-50%)
– Hand tremor (45% initially, 10% after 1 year of treatment)
– Confusion (40%)
– Decreased memory (40%)
– Headache (40%)
– Muscle weakness (30% initially, 1% after 1 year of treatment)
– Electrocardiographic (ECG) changes (20-30%)
– Nausea, vomiting, diarrhoea (10-30% initially, 1-10% after 1-2 years of treatment)
– Hyperreflexia (15%)
– Muscle twitch (15%)
– Vertigo (15%)

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.

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.

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.

The ECG findings are suggestive of anterior myocardial infarction and the most likely artery affected is the left anterior descending artery. Occlusion of the right coronary artery will be shown by ST elevation in lead II, III, aVF and occlusion of the circumflex artery will show changes in leads I, aVL, V5 and V6. To have ST elevation, there should be complete occlusion of the artery.

Hyperthermia (Temperature 39.5 C) points towards the use of ecstasy.

MDMA (3,4 – methylenedioxymethamphetamine), or more commonly known as Molly or Ecstasy, is a synthetic psychoactive substance.
Patients who consumed MDMA may present in a tachycardic, hypertensive, hyperthermic, and agitated state.
Adverse effects, even at minor recreational doses, include increased muscle activity (such as bruxism, restless legs, and jaw clenching), hyperactivity, insomnia, difficulty concentrating and feelings of restlessness.

Treatment of MDMA overdose:
Emphasis should be on maintaining the airway along with the stabilization of breathing and circulation.
Patients may present obtunded due to hyponatremia requiring endotracheal intubation.
For the hyperthermic patient, evaporative cooling along with ice packs to the groin and axilla are beneficial.
Patients who present in severe toxicity within one hour of ingestion can receive activated charcoal PO or via an NG tube.
Antipyretics, such as acetaminophen, should be avoided as they have no role and can worsen an already compromised liver.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. Absolute risk reduction = (Control event rate) – (Experimental event rate) = 0.05 = 5% reduction

Given she is not showing signs of systemic illness, you do not need to treat for an acute flair (which would be steroids), but you need to put her on maintenance medication. Oral ASA would be the best option for this, it is first line. You cannot give rectal ASA because the location of her disease is in the ascending colon and the enema will not reach.

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

The duration of these cell cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 phase might last about 11 hours, S phase about 8 hours, G2 about 4 hours, and M about 1 hour. The proliferation of most animal cells is similarly regulated in the G1 phase of the cell cycle. In particular, a decision point in late G1, called the restriction point in animal cells, is the point at which the cell becomes committed to the cell cycle and after which extracellular proliferation stimulants are no longer required.. Although the proliferation of most cells is regulated primarily in G1, some cell cycles are instead controlled principally in G2.

Cyanide poisoning:
Aetiology:
Smoke inhalation, suicidal ingestion, and industrial exposure (specific industrial processes involving cyanide include metal cleaning, reclaiming, or hardening; fumigation; electroplating; and photo processing) are the most frequent sources of cyanide poisoning. Treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source.
Cyanide exposure most often occurs via inhalation or ingestion, but liquid cyanide can be absorbed through the skin or eyes. Once absorbed, cyanide enters the blood stream and is distributed rapidly to all organs and tissues in the body. 

Pathophysiology:
Inside cells, cyanide attaches itself to ubiquitous metalloenzymes, rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores.

Presentation:
• ‘Classical’ features: brick-red skin, smell of bitter almonds
• Acute: hypoxia, hypotension, headache, confusion
• Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
• Supportive measures: 100% oxygen, ventilatory assistance in the form of intubation if required.
• Definitive: Hydroxocobalamin (iv) is considered the drug of choice and is approved by the FDA for treating known or suspected cyanide poisoning.
• Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergistic effect on detoxification.
Mechanism of action of hydroxocobalamin:
• Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.
• Alternatively, cyanocobalamin may dissociate from cyanide at a slow enough rate to allow for cyanide detoxification by the mitochondrial enzyme rhodanese.

Gamma delta T cells are of low abundance in the body, are found in the gut mucosa, skin, lungs and uterus, and are involved in the initiation and propagation of immune responses. Their ligands are not known in detail, but the gamma delta T cell receptors recognise intact proteins rather than MHC-presented peptides. Like alpha beta T cells, they develop in the thymus.