Alpha-1-antitrypsin (AAT) is a member of the serine proteinase inhibitor (serpin) family of proteins with a broad spectrum of biological functions including inhibition of proteases, immune modulatory functions, and the transport of hormones.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14).

Burkitt lymphoma is a rare high-grade non-Hodgkin lymphoma endemic to west Africa and the mosquito belt. It has a close association with the contraction of Epstein-Barr virus (EBV). Burkitt lymphoma often presents with symmetrical painless lymphadenopathy, systemic B symptoms (fever, sweats, and weight loss), central nervous system involvement, and bone marrow infiltration. Classically in the textbooks, the patient also develops a large jaw tumour.

Other aforementioned options are ruled out because:
1. t(9;22)—Chronic myeloid leukaemia
2. t(15;17)—Acute promyelocytic leukaemia
3. t(14;18)—Follicular Lymphoma
4. t(11;14)—Mantle Cell Lymphoma

Protein-calorie malnutrition is observed in almost 50% of dialysis patients, contributing to increased morbidity and mortality. All the other complications listed can usually be prevented thanks to modern-day dialysis techniques.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

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.

Chloride channels are involved in a diverse set of functions in normal physiology and acquired diseases. Additionally, there are genetic diseases caused by mutations in chloride channels (channelopathies) — the most common being cystic fibrosis, which has a prevalence of 1 in 2,000 Caucasians.

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

Depending on the level of SCI, patients experience paraplegia or tetraplegia. Paraplegia is defined as the impairment of sensory or motor function in lower extremities. Patients with incomplete paraplegia generally have a good prognosis in regaining locomotor ability (,76% of patients) within a year. Complete paraplegic patients, however, experience limited recovery of lower limb function if their NLI is above T9. The spinothalamic tract is the one responsible for sensory information such as pain or temperature. However, it decussates at the same level the nerve root enters the spinal cord, meaning that the sensory loss will be contralateral. However, the dorsal column carries sensory fibres for fine touch and vibration and it decussates at the medulla which means that the sensory loss will be ipsilateral. The corticospinal tract is responsible for motor functions and it decussates at the medulla, meaning that the motor function loss will be ipsilateral.

In hyperkalaemia the ECG will show tall, tented T waves as well as small P waves and widened QRS complexes. 

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

J waves in an ECG is associated with hypothermia, hypercalcemia, the Brugada syndrome, and idiopathic ventricular fibrillation. The other responses are all associated with atrial myxoma

Nail dystrophy (pitting of nails, onycholysis, subungual hyperkeratosis), dactylitis, sausage shaped fingers are most commonly seen with psoriatic arthropathy. There is asymmetric joint involvement most commonly distal interphalangeal joints. Uveitis and sacroiliitis may also occur. Arthritis mutilans may occur but is very rare. Cutaneous lesions may or may not develop. When they do, its usually much after the symptoms of arthritis.

The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. In this case the NNT can be calculated as follows: NNT = 1/ Absolute risk reduction (ARR). ARR=(Control event rate expressed per 1000 patient years) – (Experimental event rate expressed per 1000 patient years) = 43.9-37.3 = 6.6/1000 patient years

NNT=(Patient years)/ARR = 1000/ 6.6 = 151.5. The closest to 151.5 is 150, thus it is the correct answer.

Serial Peak Expiratory Flow measurement at work and home is a feasible, sensitive, and specific test for the diagnosis of occupational asthma. For a diagnosis of occupational asthma, it is important to establish a relationship objectively between the workplace exposure and asthma symptoms and signs. Physiologically, this can be achieved by monitoring airflow limitation in relation to occupational exposure(s). If there is an effect of a specific workplace exposure, airflow limitation should be more prominent on work days compared with days away from work (or days away from the causative agent). Airflow limitation can be measured by spirometry, with peak expiratory flow (PEF) and/or forced expiratory volume in 1 s(FEV1) being the most useful for observing changes in airway calibre. Other tests mentioned are less reliable and would not help in establishing a satisfactory diagnosis of occupational asthma.

Hashimoto thyroiditis is part of the spectrum of autoimmune thyroid diseases (AITDs) and is characterized by the destruction of thyroid cells by various cell- and antibody mediated immune processes. It usually presents with hypothyroidism, insidious in onset, with signs and symptoms slowly progressing over months to years.

The diagnosis of Hashimoto thyroiditis relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features.

Post-concussion syndrome is a complex disorder in which various symptoms, such as headaches and dizziness, last for weeks and sometimes months after the injury that caused the concussion.

Concussion is a mild traumatic brain injury that usually happens after a blow to the head. It can also occur with violent shaking and movement of the head or body. You don’t have to lose consciousness to get a concussion or post-concussion syndrome. In fact, the risk of post-concussion syndrome doesn’t appear to be associated with the severity of the initial injury.

Post-concussion symptoms include:
Headaches
Dizziness
Fatigue
Irritability
Anxiety
Insomnia
Loss of concentration and memory
Ringing in the ears
Blurry vision
Noise and light sensitivity
Rarely, decreases in taste and smell

Gaucher’s disease is characterized by hepatosplenomegaly, cytopenia, sometimes severe bone involvement and, in certain forms, neurological impairment. The variability in the clinical presentations of GD may be explained by the continuum of phenotypes. However, three major phenotypic presentations can usually be distinguished. Type-1 GD is usually named non-neuronopathic GD; type-2 and type-3 are termed neuronopathic-GD. Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages.

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.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

For medical management of carcinoid syndrome, there are two somatostatin analogues available, Octreotide and Lanreotide. Somatostatin is an amino acid peptide which is an inhibitory hormone, which is synthesized by paracrine cells located ubiquitously throughout the gastrointestinal tract. Both somatostatin analogues provide symptom relief in 50% to 70% of patients and biochemical response in 40% to 60% patients. Many studies have shown that Octreotide and Lanreotide also inhibit the proliferation of tumour cells.

Cabergoline, an ergot derivative, is a long-acting dopamine agonist. It is usually better tolerated than Bromocriptine (BEC), and its efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline.

The most probable diagnosis of this patient is Cotard syndrome.

Cotard syndrome is a rare mental disorder where the affected patient believes that they (or in some cases just a part of their body) is either dead or non-existent. This delusion is often difficult to treat and can result in significant problems due to patients stopping eating or drinking as they deem it not necessary. Cotard syndrome is often associated with severe depression and psychotic disorders.

Other options:
– Othello syndrome is a delusional belief that a patients partner is committing infidelity despite no evidence of this. It can often result in violence and controlling behaviour.
– De Clerambault syndrome (otherwise known as erotomania), is where a patient believes that a person of higher social or professional standing is in love with them. Often this presents with people who believe celebrities are in love with them.
– Ekbom syndrome is also known as delusional parasitosis and is the belief that they are infected with parasites or have ‘bugs’ under their skin. This can vary from the classic psychosis symptoms in narcotic use where the user can ‘see’ bugs crawling under their skin or can be a patient who believes that they are infested with snakes.
– Capgras delusion is the belief that friends or family members have been replaced by an identical-looking imposter.

Activated charcoal is useful if given within one hour of the paracetamol overdose. Liver function tests, INR and prothrombin time will be normal, as liver damage may not manifest until 24 hours or more after ingestion.

The antidote of choice is intravenous N-acetylcysteine, which provides complete protection against toxicity if given within 10 hours of the overdose.

Hepatitis C is a single-stranded positive sense RNA virus. It is variable because of the high rate of error of RNA-dependent RNA polymerase and the pressure from the host immune system has caused HCV to evolve and develop seven genetic lineages.

Most patients with psoriatic arthritis present with monoarthritis or asymmetric oligoarthritis. The most common form of the disease is the one involving a few joints of the peripheral skeleton with a distinct asymmetry of symptoms. Involvement of the smaller joints of the hands and feet, especially distal interphalangeal joints, seems to be a characteristic feature. Arthritis mutilans is a rare and severe complication of psoriatic arthritis.

When you have a patient with HIV and diarrhoea on the exam, think Cryptosporidium. In those who are immunocompetent this organism doesn’t usually cause symptoms, but in immunocompromised people like those with HIV, it causes infection and diarrhoea. Typically those with CD4 counts of <100 cells/µL1 have the greatest risk for prolonged, severe, or extraintestinal cryptosporidiosis.

Blue tinge of vision/cyanopsia is caused due to the intake of sildenafil citrate.

Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction.
It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.

Uses:
It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.

Adverse effects:
Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.
It can also cause hypotension, dizziness, and rhinitis.

Note: Xanthopsia (yellow-green vision) may occur secondary to treatment with digoxin.

Secretin stimulates bicarbonate secretion from the pancreas and liver. VIP induces relaxation of the stomach and gallbladder, secretion of water into pancreatic juice/ bile, and inhibits gastric acid secretion/absorption. CCK classically stimulates gallbladder contraction and relaxation of the sphincter of Oddi. Gastrin stimulates the secretion of HCl by parietal cells in the stomach. Motilin, as the name suggests, increases motility.

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.

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 diseases.