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.

Silicosis is a common occupational lung disease that is caused by the inhalation of crystalline silica dust. Silica is the most abundant mineral on earth. Workers that are involved for example in construction, mining, or glass production are among the individuals with the highest risk of developing the condition. Acute silicosis causes severe symptoms (e.g., exertional dyspnoea, cough with sputum) and has a very poor prognosis.
Chronic silicosis has a very variable prognosis and affected individuals may remain asymptomatic for several decades. However, radiographic signs are usually seen early on. Typical radiographic findings are calcifications of perihilar lymph nodes, diffuse ground glass opacities, large numbers of rounded, solitary nodules or bigger, confluent opacities. Avoiding further exposure to silica is crucial, especially since the only treatment available is symptomatic (e.g., bronchodilators). Silicosis is associated with an increased risk of tuberculosis and lung cancer. Berylliosis typically affects individuals who are exposed to aerospace industry. Histoplasmosis and tuberculosis do not form eggshell calcifications.

This question describes Charcot’s triad– fever, RUQ pain, and jaundice, which is seen in ascending cholangitis. Reynold’s pentad is a worsened version of this, where you have RUQ pain, fever, jaundice, hypotension, and altered mental status. Risk factors for gallstones are the 4F’s- female, fat, forty, and fertile. You would not have the elevated bilirubin, ALP, transaminases with a kidney stone or in peptic ulcer disease. Hepatitis would not cause elevation of bilirubin.

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%

Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 is considered mild or subclinical hypothyroidism.
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.
The following are symptoms of hypothyroidism:
– Fatigue, loss of energy, lethargy
– Weight gain
– Decreased appetite
– Cold intolerance
– Dry skin
– Hair loss
– Sleepiness
– Muscle pain, joint pain, weakness in the extremities
– Depression
– Emotional lability, mental impairment
– Forgetfulness, impaired memory, inability to concentrate
– Constipation
– Menstrual disturbances, impaired fertility
– Decreased perspiration
– Paraesthesia and nerve entrapment syndromes
– Blurred vision
– Decreased hearing
– Fullness in the throat, hoarseness
Physical signs of hypothyroidism include the following:
– Weight gain
– Slowed speech and movements
– Dry skin
– Jaundice
– Pallor
– Coarse, brittle, straw-like hair
– Loss of scalp hair, axillary hair, pubic hair, or a combination
– Dull facial expression
– Coarse facial features
– Periorbital puffiness
– Macroglossia
– Goitre (simple or nodular)
– Hoarseness
– Decreased systolic blood pressure and increased diastolic blood pressure
– Bradycardia
– Pericardial effusion
– Abdominal distention, ascites (uncommon)
– Hypothermia (only in severe hypothyroid states)
– Nonpitting oedema (myxoedema)
– Pitting oedema of lower extremities
– Hyporeflexia with delayed relaxation, ataxia, or both.

Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath. Patients are typically aged 18-40 years, tall, thin, and, often, are smokers.

In small pneumothoraxes with minimal symptoms, no active treatment is required. These patients can be safely discharged with early outpatient review and should be given written advice to return if breathlessness worsens. Patients who have been discharged without intervention should be advised that air travel should be avoided until a radiograph has confirmed resolution of the pneumothorax.

Glomerulosclerosis is the scarring and hardening of the glomeruli known as diabetic glomerulosclerosis occurring in long-standing diabetes.

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.

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Herpes zoster is a viral disorder in which painful vesicular lesions are present in a specific dermatome area. High-grade fever may present as well due to infection. Varicella zoster, measles, herpes simplex and HIV do not present with tender lesions of a limited area.

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 patient has Klumpke’s paralysis due to damage to the T1 nerve root. This root eventually supplies the median and ulnar nerves. The ulnar nerve supplies all of the intrinsic hand muscles except for those of the thenar eminence and the first and second lumbricals, which are innervated by the median nerve.

Tacrolimus is a calcineurin inhibitor used as an immunosuppressive agent used for prophylaxis of organ rejection post-transplant.

Pharmacology: Calcineurin inhibition leads to reduced T-lymphocyte signal transduction and IL-2 expression. It has a half-life of 12 hours (average).

Other off-label indications for the use of tacrolimus include Crohn disease, graft-versus-host disease (GVHD), myasthenia gravis, rheumatoid arthritis.

Adverse effects of tacrolimus includes:
Cardiovascular: Angina pectoris, cardiac arrhythmias, hypertension
Central nervous system: Abnormal dreams, headaches, insomnia, tremors.
Dermatologic: Acne vulgaris, alopecia, pruritis, rash
Endocrine and metabolic: Decreased serum bicarbonate, decreased serum iron, new-onset diabetes mellitus after transplant (NODAT), electrolyte disturbances.
Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhoea
Genitourinary: Urinary tract infection
Hepatic: Abnormal hepatic function tests
Neuromuscular and skeletal: Arthralgia, muscle cramps
Ophthalmic: Blurred vision, visual disturbance
Otic: Otalgia, otitis media, tinnitus
Renal: Acute renal failure

Other options:
Sirolimus (a macrolide) is an mTOR inhibitor that blocks the response to IL-2 and has a half-life of 12–15 hours.
Azathioprine inhibits purine synthesis, an essential step in the proliferation of white cells and has a half-life of around 5 hours.

The most widely used prognostic predictors for acetaminophen over-ingestion is King’s College Criteria, which is: arterial PH < 7.3 after fluid resuscitation, Cr level > 3.4, PT > 1.8x control or > 100s, or INR > 6.5, and Grave III or IV encephalopathy.

Oxycodone is a safer opioid to use in patients with moderate to end-stage renal failure.
Active metabolites of morphine accumulate in renal failure which means that long-term use is contraindicated in patients with moderate/severe renal failure.
These toxic metabolites can accumulate causing toxicity and risk overdose.
Oxycodone is mainly metabolised in the liver and thus safer to use in patients with moderate to end-stage renal failure with dose reductions.
Adverse effects:
Constipation is the most common overall side effect. Others include: asthenia, dizziness, dry mouth, headache, nausea, pruritus, etc.

Medications in renal failure:
Drugs to be avoided in patients with renal failure
Antibiotics: tetracycline, nitrofurantoin
NSAIDs
Lithium
Metformin
Drugs that require dose adjustment:
Most antibiotics including penicillin, cephalosporins, vancomycin, gentamicin, streptomycin
Digoxin, atenolol
Methotrexate
Sulphonylureas
Furosemide
Opioids
Relatively safe drugs:
Antibiotics: erythromycin, rifampicin
Diazepam
Warfarin

The total daily morphine dose is 30 x 2 = 60 mg. Therefore, the breakthrough dose should be one-sixth of this, 10 mg.

Mitochondrial DNA (mtDNA) is a double-stranded molecule of 16.6 kb (Figure 1, lower panel). The two strands of mtDNA differ in their base composition, with one being rich in guanines, making it possible to separate a heavy (H) and a light (L) strand by density centrifugation in alkaline CsCl2 gradients.

There is a high risk of bleeding due to recent surgery and heparin. So thrombolysis is not an option. The most appropriate management is percutaneous coronary intervention.

According to NICE guidelines (2013) all people who have had an acute MI treatment should be offered with ACE inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), a beta-blocker and a statin.

Dilation of systemic veins is a beneficial effect of nitro-glycerine.

Administration of nitro-glycerine results in the dilation of systemic veins and decrease of myocardial wall tension and oxygen demand. Dilatation of systemic veins can cause reduced systemic vascular resistance leading to reduced cardiac workload thus reducing anginal symptoms secondary to demand ischemia.

This is accompanied by vasodilation of large and medium-sized coronary arteries with increased coronary blood flow to the sub endocardium.

Squamous-cell carcinoma is the most common histological type of lung cancer to cavitate (82% of cavitary primary lung cancer), followed by adenocarcinoma and large cell carcinoma. Multiple cavitary lesions in primary lung cancer are rare, however, multifocal bronchoalveolar cell carcinoma can occasionally have multiple cavitary lesions. Small cell carcinoma is not known to cavitate.

The described rash is the typical rash of erythema migrans of Lyme disease, which is treated by doxycycline PO

Among the above statements, gastric lavage and normal saline IV infusion are the two appropriate interventions for a patient of acute lithium toxicity.

Activated charcoal is not effective after lithium overdose, although gastric lavage should be considered if patients present within 6–8 h.
Where levels are above 3 mmol/l, the use of normal saline to induce diuresis should be considered, although careful monitoring of fluid balance is necessary.
Where levels of lithium are above 4 mmol/l, dialysis is often required. Haemodialysis is preferred, but in a facility where haemodialysis is not possible, peritoneal dialysis may be considered.
Patients should not be discharged until they are asymptomatic and have a serum lithium level less than 1.5 mEq/L.

People with polyarteritis nodosa often exhibit anaemia of chronic disease. Leucocytosis and eosinophilia may also be present. ANCA is only rarely positive. As polyarteritis nodosa affects the kidneys as well, the creatinine is elevated in most cases.

The most probable diagnosis in this patient is conversion disorder.

There may be underlying tension regarding her musical career which could be manifesting as apparent limb weakness.

Conversion disorder typically involves loss of motor or sensory function. The patient doesn’t consciously feign the symptoms (factitious disorder) or seek material gain (malingering). Patients may be indifferent to their apparent disorder – la belle indifference – although this has not been backed up by studies.

Other options:
Unexplained symptoms
There are a wide variety of psychiatric terms for patients who have symptoms for which no organic cause can be found:

Somatization disorder
Multiple physical symptoms present for at least 2 years
the patient refuses to accept reassurance or negative test results

Hypochondriacal disorder
The persistent belief in the presence of an underlying serious disease, e.g. cancer.
The patient again refuses to accept reassurance or negative test results

Dissociative disorder
Dissociation is a process of ‘separating off’ certain memories from normal consciousness
Unlike conversion disorder, it involves psychiatric symptoms e.g. amnesia, fugue, stupor
Dissociative identity disorder (DID) is the new term for multiple personality disorder as is the most severe form of dissociative disorder

Munchausen’s syndrome
Also known as factitious disorder
The intentional production of physical or psychological symptoms

Malingering
Fraudulent simulation or exaggeration of symptoms with the intention of financial or another gain.

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.

There are five prognostic factors which indicate poor prognosis in HOCM:
-family history of HOCM-related sudden cardiac death
-unexplained recent syncope
-large left ventricular wall thickness (MLVWT ≥ 30 mm)
-multiple bursts of nsVT on ambulatory electrocardiography
-hypotensive or attenuated blood pressure response to exercise

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

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)

Of all the listed options, gastric cancer is least likely to be inherited.

The above mentioned tumours are ruled out as explained below:
1. Breast and Ovarian cancers: Between 5%–10% of all breast cancers are thought to be hereditary. Mutation in the BRCA1 and BRCA2 genes also increase the risk of ovarian cancer.

2. Colorectal and Endometrial cancers: About 5% of cases of colorectal cancer are caused by hereditary non-polyposis colorectal carcinoma (HNPCC) and 1% are due to familial adenomatous polyposis. Women who have HNPCC also have a markedly increased risk of developing endometrial cancer—around 5% of endometrial cancers occur in women with this risk factor.

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.