The use of nitrates and nicorandil concomitantly with sildenafil citrate is contraindicated.

Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.

Contraindications
– Patients taking nitrates and related drugs such as nicorandil
– Hypotension
– Recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Side-effects:
Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic Neuropathy
Nasal congestion
Flushing
Gastrointestinal side-effects
Headache

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.

Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.

In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.

Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.

Management:
– Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.
– Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline).
– On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.
– Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

Melanocytic naevi are skin tumours produced by melanocytes. They usually present in childhood but increase during puberty. The mnemonic A-B-C-D, is used by institutions to assess for suspicion of malignancy. The letters stand for asymmetry, border, colour, and diameter. If a mole starts changing in size, colour, shape or, especially, if the border of a mole develops ragged edges or becomes larger than a pencil eraser, it would be an appropriate time to consult with a physician. Other warning signs include if it begins to crust over, bleed, itch, or become inflamed.

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%)

Renal biopsy in this patient will most likely show thickened glomerular basement membrane with deposits of IgG and C3 as a result of membranous glomerulonephritis that has caused the nephrotic syndrome in this patient. Membranous glomerulonephritis in this case is most likely associated with an underlying bronchial carcinoma, consistent with the patient’s smoking history and physical presentation.

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.

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.

The clinical picture points to Lambert– Eaton myasthenic syndrome (LEMS) which often presents with weakness of the arms and legs. In LEMS, antibodies against voltage-gated calcium channels (VGCC) decrease the amount of calcium that can enter the nerve ending, causing autonomic symptoms like dry mouth and slurring of speech, as seen in this patient.

Liddle’s Syndrome is an autosomal dominant disorder that presents with hypertension usually in young patients, that do not respond to anti-hypertensive therapy and is later associated with hypokalaemia, low renin plasma, and low aldosterone levels as well. The other conditions listed do not present with hypertension and associated hypokalaemia.

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.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include weight loss and lethargy; monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Nerve conduction velocity is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Ultimately, conduction velocities are specific to each individual and depend largely on an axon’s diameter and the degree to which that axon is myelinated.
The cardiac action potential is a brief change in voltage (membrane potential) across the cell membrane of heart cells. Conduction speed varies:
Atrial conduction spreads along ordinary atrial myocardial fibres at 1 m/sec
AV node conduction 0.05 m/sec
Ventricular conduction Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec (this allows a rapid and coordinated contraction of the ventricles.

Rheumatoid factor is an IgM antibody that targets the Fc portion of IgG.

Squamous-cell skin cancer usually presents as a hard lump with a scaly top but can also form an ulcer. Onset is often over months and it is more likely to spread to distant areas than basal cell cancer vie the lymphatics. The greatest risk factor is high total exposure to ultraviolet radiation from the Sun. Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen’s disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection. While prognosis is usually good, if distant spread occurs five-year survival is ,34%

A lucid interval, in which the patient portrays a temporary improvement in condition after a traumatic brain injury, is especially indicative of an epidural haematoma.

Herpes zoster ophthalmicus (HZO) describes the reactivation of the varicella zoster virus in the area supplied by the ophthalmic division of the trigeminal nerve. It accounts for around 10% of case of shingles. Features include a vesicular rash around the eye, which may or may not involve the actual eye itself, and Hutchinson’s sign: a rash on the tip or side of the nose, indicating nasociliary involvement and is a strong risk factor for ocular involvement.

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003.
In general, SARS begins with a high fever (temperature greater than 38.0°C). Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also have mild respiratory symptoms at the outset. About 10 to 20 percent of patients have diarrhoea. After 2 to 7 days, SARS patients may develop a dry cough. Most patients develop pneumonia. 

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.

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.

Patients with a VTE within the previous three months, patients with AF and previous stroke or TIA or multiple other risk factors, and patients with a mitral valve replacement should be considered for bridging therapy.

The most appropriate bridging therapy in this case would be low-molecular-weight heparin (LMWH), with the last dose given not less than 24 hours prior to the procedure. Warfarin should be discontinued 5 days prior to the procedure. If the INR is still above 3 on the day prior to the procedure, vitamin K should be administered.

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

Superior vena cava (SVC) obstruction is an oncological emergency caused by compression of the SVC and is most commonly associated with lung cancer.

Some causes of the condition include:
1. Common malignancies: non small cell lung cancer, lymphoma
2. Other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
3. Aortic aneurysm
4. Mediastinal fibrosis

Clinical features of SVC obstruction include:
1. Dyspnoea: most common
2. Swelling of the face, neck, and arms: conjunctival and periorbital oedema may be seen
3. Headache: often worse in the morning
4. Visual disturbances
5. Pulseless jugular venous distension

Management options are:
1. General: dexamethasone, balloon venoplasty, stenting
2. Small cell lung cancer: chemotherapy and radiotherapy
3. Non small cell lung cancer: radiotherapy

DIAGNOSIS:
A consensus definition for hemodynamically significant PDA is lacking. The diagnosis is often suspected clinically, when an infant demonstrates signs of excessive shunting from the arterial to pulmonary circulation. Continuous or a systolic murmur; note, a “silent” PDA may also occur when the ductus shunt is large enough that nonturbulent flow fails to generate a detectible murmur.
A low diastolic blood pressure (due to runoff into the ductus during diastole, more frequent in the most premature infants).
A wide pulse pressure (due to ductus runoff or steal)Hypotension (especially in the most premature infants)
Bounding pulses
Increased serum creatinine concentration or oliguria
Hepatomegaly

Melanoma is more common in men than women. Reasons for the disease includes: UV light and genetic predisposition or mutations. Diagnosis is by biopsy and analysis of any skin lesion that has signs of being potentially cancerous.
Early warning signs of melanoma ABCDE:
Asymmetry
Borders (irregular with edges and corners)
Colour (variegated)
Diameter (greater than 6 mm)
Evolving over time

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. Because of the history, that makes this more likely than haemorrhagic gastritis, duodenal ulceration, or oesophagitis (also oesophagitis would not bleed a cupful). Oesophageal varices would present with copious amounts of hematemesis and most likely hemodynamic instability as a result of the amount of blood loss. In Mallory-Weiss tear they are typically presented as a hemodynamically stable patient.

Carbon monoxide (CO) poisoning:
It is 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%.

Clinical features of carbon monoxide toxicity:
Headache: 90% of cases (most common clinical feature)
Nausea and vomiting: 50%
Vertigo: 50%
Confusion: 30%
Subjective weakness: 20%
Severe toxicity: ‘pink’ skin and mucosa, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
Cherry red skin is a sign of severe toxicity and is usually a post-mortem finding.
Management
• 100% oxygen
• Hyperbaric oxygen therapy (HBOT)

The use of Hyperbaric oxygen therapy (HBOT) for treatment 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 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.

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.

The majority of patients with primary open-angle glaucoma are managed with eye drops. These aim to lower intra-ocular pressure which in turn has been shown to prevent progressive loss of visual field. A prostaglandin analogue should be used first-line in patients with a history of asthma.

The patient has hyperprolactinaemia with otherwise normal oestradiol, FSH and LH. This is highly suggestive of Prolactinoma rather than a non functioning tumour.
In polycystic ovaries, there is increase in the level of LH while FSH is normal or low.