Palmar xanthomas are found in type III hyperlipoproteinemia. Her total cholesterol level and triglyceride level support the diagnosis.

Zinc deficiency can present with alopecia, dermatitis, poor growth, increased susceptibility to infection, and cognitive deficiency. Magnesium deficiency can cause fatigue, cramping and an irregular EKG. Copper deficiency can present with fatigue and weakness. Chromium deficiency can present with hyperglycaemia.

Because of the patient’s history of excessive alcohol consumption, there is a strong suspicion of alcoholic peripheral neuropathy. In the UK, alcohol abuse and diabetes are the most common causes of peripheral neuropathy.

Salbutamol stimulates beta-2 adrenergic receptors, which are the predominant receptors in bronchial smooth muscle (beta-2 receptors are also present in the heart in a concentration between 10% and 50%).

Stimulation of beta-2 receptors leads to the activation of enzyme adenyl cyclase that forms cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate). This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations. Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

Increased cyclic AMP concentrations also inhibits the release of bronchoconstrictor mediators such as histamine and leukotriene from the mast cells in the airway.

Primary gout is related more often to underexcretion of uric acid or overproduction.

PCR is a simple, yet elegant, enzymatic assay, which allows for the amplification of a specific DNA fragment from a complex pool of DNA. PCR can be performed using source DNA from a variety of tissues and organisms, including peripheral blood, skin, hair, saliva, and microbes. Only trace amounts of DNA are needed for PCR to generate enough copies to be analysed using conventional laboratory methods. For this reason, PCR is a sensitive assay. Each PCR assay requires the presence of template DNA, primers, nucleotides, and DNA polymerase. The DNA polymerase is the key enzyme that links individual nucleotides together to form the PCR product. The above mentioned components are mixed in a test tube or 96-well plate and then placed in a machine that allows repeated cycles of DNA amplification to occur in three basic steps. The machine is essentially a thermal cycler. It has a thermal block with holes, into which the test tubes or plates holding the PCR reaction mixture are inserted. The machine raises and lowers the temperature of the block in discrete, precise and pre-programmed steps. The reaction solution is first heated above the melting point of the two complementary DNA strands of the target DNA, which allows the strands to separate, a process called denaturation. The temperature is then lowered to allow the specific primers to bind to the target DNA segments, a process known as hybridization or annealing. Annealing between primers and the target DNA occurs only if they are complementary in sequence (e.g. A binding to G). The temperature is raised again, at which time the DNA polymerase is able to extend the primers by adding nucleotides to the developing DNA strand. With each repetition of these three steps, the number of copied DNA molecules doubles.

5–15% of the cases of polycythaemia vera progress to myelofibrosis or acute myeloid leukaemia (AML).

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

After the exposure to chickenpox while pregnant, even if the patient is negative for antibodies she requires immunoglobulin to prevent further issues.

CMV infection is usually asymptomatic in adults. However, if the mother is infected for the first time during pregnancy then there is high chances of this infection passing on to the foetus. CMV infection can cause blindness, deafness, learning difficulties, restricted growth etc. Hepatitis B, herpes simplex, syphilis and HIV do not present with these classical signs of CMV infection in new-borns. It is estimated that 10 stillbirths occur in England and Wales every year due to CMV infection. The foetus is most at risk in early pregnancy. There is no effective prevention.

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

A fasting blood glucose level from 110 to 126 mg/dL (5.5 to 6.9 mmol/L) is considered prediabetes. This result is sometimes called impaired fasting glucose.
Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by plasma glucose. If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.

Biguanides (Metformin):
People who take metformin alone should be able to fast safely given that the possibility of hypoglycaemia is minimal. However, patients should modify its dose and administration timing to provide two-thirds of the total daily dose, which should be taken immediately with the sunset meal, while the other third is taken before the predawn meal.

Thiazolidinediones: No change needed.

Sulfonylurea:
Once-daily sulfonylurea (such as glimepiride or gliclazide MR): the total daily dose should be taken with the sunset meal.
Shorter-acting sulfonylurea (such as gliclazide twice daily): the same daily dose remains unchanged, and one dose should be taken at the sunset meal and the other at the predawn meal.
Long-acting sulfonylurea (such as glibenclamide): these agents should be avoided.

It is important that diabetic patients to eat a healthy balanced diet and choose foods with a low glycaemic index (such as complex carbohydrates), which can help to maintain blood glucose levels during fasting. Moreover, it is crucial to consume adequate fluids to prevent dehydration. Physical activity is encouraged, especially during non-fasting periods.

Giant Cell Arteritis (Temporal Arteritis) is the most probable diagnosis. GCA should always be considered in the differential diagnosis of a new-onset headache in patients 50 years of age or older with an elevated erythrocyte sedimentation rate. Temporal artery biopsy remains the criterion standard for diagnosis of this granulomatous vasculitis. High-dose corticosteroid therapy is the universally accepted treatment.

Lewy body dementia is an increasingly recognised cause of dementia, accounting for up to 20% of cases. The characteristic pathological feature is alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic and neocortical areas. Neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible parkinsonism. Questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent.

The given history is more compatible with spontaneous pneumothorax. Left-sided pneumothoraxes may be associated with a clicking noise, which is heard with each heart-beat and can sometimes be heard by the patient.

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease).
It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.
The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect.
Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile.
Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. A complete oculomotor nerve palsy will result in a characteristic down and out position in the affected eye. This is because the lateral rectus (innervated by the sixth cranial nerve) and superior oblique (innervated by the fourth cranial or trochlear nerve), is unantagonized by the paralyzed superior rectus, inferior rectus and inferior oblique. The affected individual will also have a ptosis, or drooping of the eyelid, and mydriasis (pupil dilation), not miosis.

Criteria for the diagnosis of diabetes

1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is certified and standardized.*
OR
2. Fasting glucose ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*
OR
3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycaemia or hyperglycaemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycaemia, criteria 1–3 should be confirmed by repeat testing.

Normal cerebrospinal fluid (CSF) glucose together with lymphocytosis, an increased opening pressure and raised CSF protein are typical of a viral meningitis.

Vitamin B12 is mostly used in the body for the development of red blood cells and maintenance of the nervous system. It is actively absorbed in the terminal ileum after binding to the intrinsic factor (IF) which is secreted from the parietal cells of stomach. Moreover, a small amount is also passively absorbed without being bound to IF.

Vitamin B12 deficiency is characterised by sore tongue and mouth, mood disturbances, ataxia, and macrocytic anaemia. Its causes include poor diet, impaired absorption (due to disorders of terminal ileum), pernicious anaemia, and post-gastrectomy. While managing this condition, if the person is also deficient in folic acid, then it is important to treat the B12 deficiency first in order to avoid precipitating subacute combined degeneration of the cord.

This is a typical picture of acute chest syndrome (ACS). According to the British Committee for Standards in Haematology (BCSH), ACS is defined as ‘an acute illness characterised by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on chest X-ray’. ACS occurs in sequestration crisis, which is one of the four main types of crises occurring in sickle cell disease.

The fundamentals of initial management are as follows:
1. Oxygen therapy to maintain saturation >95%
2. Intravenous fluids to ensure euvolemia
3. Adequate pain relief
4. Incentive spirometry in all patients presenting with rib or chest pain
5. Antibiotics with cover for atypical organisms
6. Bronchodilators if asthma co-exists with acute chest syndrome, or if there is an evidence of acute bronchospasm on auscultation
7. Early consultation with the critical care team and haematology department

A senior haematologist then makes a decision as to whether a simple or exchange transfusion is necessary in order to achieve a target Hb of 10.0–11.0g/dL in either instance.

Sickle Cell Crises:
Sickle cell anaemia is characterised by periods of good health with intervening crises:
1. Sequestration crisis: acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates)

2. Thrombotic (painful or vaso-occlusive) crisis: precipitated by infection, dehydration, and deoxygenation

3. Aplastic crisis: sudden fall in haemoglobin without marked reticulocytosis, usually occurring secondary to parvovirus infection

4. Haemolytic crisis: fall in haemoglobin secondary to haemolysis, rare type of sickle cell crises

The latest research recommends that simple tooth extraction in patients on warfarin treatment can be performed safely without high risk of bleeding, providing that the INR is equal to or less than 3.5 on the day of extraction. A close follow-up and monitoring of patients taking warfarin is mandatory after dental extraction.

This patient has developed a venous sinus thrombosis peri-partum, resulting in her symptoms. Anticoagulation therapy including Heparin improves outcomes.

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.

Connective-tissue diseases, liver cirrhosis, exposure to anorexigens and likely other alpha-adrenergic stimulants [e.g., cocaine, amphetamines] and HIV infection are associated with primary pulmonary hypertension. Recurrent pulmonary emboli, chronic lung diseases, left heart diseases are causes for secondary pulmonary hypertension. Pulmonary vascular hypertension after use of fenfluramine is rarely reported.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Arnold-Chiari malformation usually presents with symptoms due to brainstem and lower cranial nerve dysfunction such as DBN.

Subcutaneous low molecular weight heparin (LMWH) is the preferred treatment for most patients with acute DVT, including in pregnancy. A large meta-analyses comparing LMWH to unfractionated heparin (UFH) showed that LMWH decreased the risk of mortality, recurrent veno-thrombo embolism (VTE), and haemorrhage compared with heparin. Other advantages of LMWH may include more predictable therapeutic response, ease of administration and monitoring, and less heparin-induced thrombocytopenia. Disadvantages of LMWH include cost and longer half-life compared with heparin.

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. Warfarin crosses the placenta and is teratogenic, causing a constellation of anomalies known as warfarin embryopathy, with greatest risk between the sixth and twelfth week of gestation.
Other options are not indicated for use.

In general, the aim is to keep the homocysteine (Hcy) concentration as close to normal as possible. In patients who are fully-responsive to pyridoxine, standard doses can lead to tHcy levels below 50 μmol/L (and sometimes within the normal range). Some patients who are partially-responsive to pyridoxine may be able to achieve a tHcy level below 50 μmol/L if they are also on a low-Met diet; for others it is not a realistic goal.

Pseudomembranous colitis is caused by a C. difficile infection that causes membranes to form on the colon wall. It is caused most commonly by broad-spectrum antibiotics. This would include cephalosporins, broad-spectrum penicillin, and clindamycin. Macrolides and quinolones have also been reported as potential aetiologies, but much less commonly. This woman would have received antibiotics prophylactically before her surgery, predisposing her to a possible c difficile infection. This is a much better answer choice than pseudo obstruction, abdominal sepsis, bile acid diarrhoea, and campylobacter gastroenteritis simply based on history of present illness.