The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. There is poor genotype:phenotype correlation. Within a tissue or cell there can be different mitochondrial populations (this is known as heteroplasmy).
Examples of mitochondrial diseases include:
– Leber’s optic atrophy
– MELAS syndrome (mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes)
– MERRF syndrome (myoclonus epilepsy with ragged-red fibres)
– Kearns-Sayre syndrome (more severe syndromic variant of chronic progressive external ophthalmoplegia, onset in patients < 20 years old)

Hereditary C1 inhibitor deficiency leads to recurrent angioedema without urticaria or pruritus. Physical triggers include dental work, surgery or intubation. Medical triggers include angiotensin-converting enzyme (ACE) inhibitor, tamoxifen, oestrogen-containing medications (e.g., hormone replacement therapy and oral contraceptives). It is diagnosed on the basis of low levels of C1 esterase inhibitor or elevated levels of dysfunctional C1 esterase inhibitor. C4 levels are low between attacks. IgE levels, eosinophils, skin prick tests and RASTs are helpful in other allergic conditions and asthma but not of use in this case.

Pulmonary alveolar proteinosis (PAP) is a lung condition that is caused by a build-up of proteins and other substances in the alveoli. The alveoli are the part of the lungs that contain air. PAP has the following symptoms:
Shortness of breath, also called dyspnoea
Chest pain or tightness
Fever
Weight loss
Cough (sometimes, but not always)
Low levels of oxygen in the blood
Nail clubbing (abnormal growth of toenails or fingernails)

Serologic studies are generally not useful for PAP. Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF. Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as crazy paving.

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material.

To confirm the diagnosis, especially in patients with negative anti-Ro or anti-La antibodies, labial gland biopsy is done. In performing a labial biopsy, the surgeon typically makes a shallow 1/2 inch wide incision on either side of the inner lip after numbing the area with a local anaesthetic. Schirmer’s test determines whether the eye produces enough tears to keep it moist. This test can be done for ocular symptoms of Sjogren syndrome but is of no diagnostic importance as it can be positive with many other diseases.

Methadone and cocaine can cause QT prolongation through the direct effects on the resting membrane potential. Methadone can increase QT dispersion in addition to QT interval. Methadone inhibits the Human Ether-a-go-go Related Gene (hERG) and causes QTc prolongation and development of Torsades de point. Brugada-like syndrome is another condition found in methadone users which predisposes the users to life-threatening ventricular tachycardia and sudden cardiac death.

The diagnosis is acute inferior ST elevation myocardial infarction so the most appropriate management is primary angioplasty.

West Nile virus is an RNA virus transmitted by the Culex species of mosquitoes. It is mostly prevalent in South America, Africa and some parts of Europe. Clinically it presents with high grade fever, headache, abdominal pain, anorexia and a morbilliform rash over the body. It can also lead to meningitis, encephalitis and flaccid paralysis by affecting the anterior horn cells, a process suggesting similarity to poliomyelitis. It can be fatal if not treated abruptly. Studies suggest that it can be transferred from mother to offspring. New-borns may present with encephalitis, chorioretinitis and wide spread brain damage. Patients suffering from West Nile virus can be effectively treated with interferon, IV immunoglobulin and Ribavirin.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by stressful, frightening or distressing events.

PTSD is a lasting consequence of traumatic ordeals that cause intense fear, helplessness, or horror, such as a sexual or physical assault, the unexpected death of a loved one, an accident, war, or natural disaster. Families of victims can also develop PTSD, as can emergency personnel and rescue workers.

PTSD is diagnosed after a person experiences symptoms for at least one month following a traumatic event. However symptoms may not appear until several months or even years later. The disorder is characterized by three main types of symptoms:
-Re-experiencing the trauma through intrusive distressing recollections of the event, flashbacks, and nightmares.
-Emotional numbness and avoidance of places, people, and activities that are reminders of the trauma.
-Increased arousal such as difficulty sleeping and concentrating, feeling jumpy, and being easily irritated and angered.

The goal of PTSD treatment is to reduce the emotional and physical symptoms, to improve daily functioning, and to help the person better cope with the event that triggered the disorder. Treatment for PTSD may involve psychotherapy (a type of counselling), medication, or both.

Certain antidepressant medications are used to treat PTSD and to control the feelings of anxiety and its associated symptoms including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Mood stabilizers such are sometimes used.

The dendritic ulceration seen on fluorescein staining of the eye is pathopneumonic for keratitis caused by HSV (herpes simplex virus). Presentation is that of blepharoconjunctivitis. Treatment is required, the treatment is typically topical acyclovir. Topical steroids can make the infection worse. The other answer choices would not have this dendritic pattern seen on fluorescein staining.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Melanocytic nevi are benign neoplasms or hamartomas composed of melanocytes. Melanocytes are derived from the neural crest and migrate during embryogenesis to selected ectodermal sites (primarily the skin and the CNS), but also to the eyes and the ears.
They tend to appear during early childhood and during the first 30 years of life. They may change slowly, becoming raised, changing color or gradually fading.. Pregnancy can increase the number of naevi as well as the degree of hyperpigmentation.
They may become malignant and this should be suspected if the naevus increases in size, develops an irregular surface or becomes darker, itches or bleeds.

Retinitis pigmentosa primarily affects the peripheral retina resulting in tunnel vision. Night blindness is often the initial sign. Tunnel vision occurs due to loss of the peripheral retina (occasionally referred to as funnel vision).
Fundoscopy exam reveals black bone spicule-shaped pigmentation in the peripheral retina, and mottling of the retinal pigment epithelium.

The classic history in this high risk patient is suggestive of a dissecting aortic aneurysm. His transoesophageal echocardiogram confirms the diagnosis. ST elevation in ECG is probably due to the extension of the dissection of the aorta which results in compromised coronary blood supply.

The main mechanism of fibrate drugs is activation of gene transcription factors known as PPARs, particularly PPAR-α, which regulate the expression of genes that control lipoprotein metabolism. There are several consequences of PPAR-α activation, which reduce circulating LDL cholesterol and triglycerides and increase HDL cholesterol.

Myasthenia gravis (MG) is an organ-specific autoimmune disease caused by an antibody-mediated assault on the muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Binding of antibodies to the AChR leads to loss of functional AChRs and impairs the neuromuscular signal transmission, resulting in muscular weakness.

The level of haemoglobin A1c (HbA1c), also known as glycated haemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8–12 weeks. Recent studies have been made to correlate between HbA1c and average glucose level.
Using the following formula: Average blood glucose (mmol/l) = (1.98 x 1 HbA1c) – 4.29

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

Benign Prostatic Enlargement or Hyperplasia (BPE/BPH) is the most probable diagnosis of the patient in question. It is a histological diagnosis characterized by proliferation of the cellular elements of the prostate.
The initial treatment modality of choice is selective alpha 1 antagonists (such as Prazosin, Alfuzosin and Indoramin, and long acting agents like, Terazosin, Doxazosin, etc.) as they provide immediate relief from the bothersome lower urinary tract symptoms (LUTS).
Other treatment modalities include:
• Non-selective alpha blockers: no longer used due to severe adverse effects and the availability of selective alpha 1 blockers.
• 5 alpha reductase inhibitors: Finasteride and Dutasteride, they target the underlying disease process and reduce the overall prostate volume. Thus, reduce the urinary retention and the lower urinary tract symptoms. (They do not provide immediate relief from LUTS and thus are not preferred as first line drugs over alpha 1 antagonists)
• PDE-5 Inhibitors: The long-acting tadalafil has proven to be useful.
• Surgical Treatment modalities: TURP, Prostatectomy, etc.

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

The commonest time for bacterial meningitis is in the 1st month of life and group B Streptococcus is the commonest organism. The anterior fontanelle is full, but does not bulge with normal flexion. Neurological manifestations include seizures, irritability, poor tone, lethargy and tremors, however no findings of sensorineural deafness have been noted. One of the risk factors for introduction of meningeal infection is Meningomyelocele.

Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

Infections of the superficial skin around the eyes are called periorbital, or preseptal, cellulitis. It is predominantly a paediatric disease. Erysipelas is a bacterial skin infection involving the upper dermis which extends into the superficial cutaneous lymphatics. Sinusitis is in sinuses. Orbital infections and conjunctivitis are within the eye.

Sun burn reactions usually occur after individuals with a light skin tone have prolonged exposure to the sun. The usual symptoms are redness and itching of the skin. The best treatment plan would be further avoidance of sun exposure and the topical application of emollients. These are Ist degree burns and aggressive therapy is not required in such cases.

Because of the patient’s presentation with flank pain that radiates to the groin, we are suspecting renal colic. We should follow guidelines for acute renal management and prescribe IM diclofenac for immediate relief of pain.

Thrombolytic therapy is indicated in patients with evidence of ST-segment elevation MI (STEMI) or presumably new left bundle-branch block (LBBB) presenting within 12 hours of the onset of symptoms if there are no contraindications to fibrinolysis. STEMI is defined as new ST elevation at the J point in at least two contiguous leads of 2 mm (0.2 mV) or more in men or 1.5 mm (0.15 mV) in women in leads V2-V3 and/or 1 mm (0.1 mV) or more in other contiguous limb leads.

The main symptom of dermatomyositis include skin rash and symmetric proximal muscle weakness (in over 90% of patients) which may be accompanied by pain and tenderness. It occurs more commonly in females. Skin findings include:
Gottron’s sign – an erythematous, scaly eruption occurring in symmetric fashion over the MCP and interphalangeal joints
Heliotrope or lilac rash – a violaceous eruption on the upper eyelids and in rare cases on the lower eyelids as well, often with itching and swelling
Shawl (or V-) sign is a diffuse, flat, erythematous lesion over the back and shoulders or in a V over the posterior neck and back or neck and upper chest, which worsens with UV light.
Erythroderma is a flat, erythematous lesion similar to the shawl sign but located in other areas, such as the malar region and the forehead.
Periungual telangiectasias and erythema occur.

The dose is calculated, using the conversion factor, as follows:

(Conversion factor used to convert oral morphine to subcutaneous diamorphine = Divide the total daily dose of oral morphine by 3)
Hence,
60mg*2 = 120mg
120mg/3 = 40mg

The side effects of opioids can be transient or persistent, and these include constipation, nausea, and drowsiness. Therefore, all patients taking opioids should also be prescribed a laxative and an anti-emetic (if the nausea is persistent). Dose-adjustment may be necessary in cases of persistent drowsiness. Moreover, strong opioids can also provide quick relief from metastatic bone pain, as compared to NSAIDs, bisphosphonates, and radiotherapy.

The history is consistent with carpal tunnel syndrome (CTS) arising as a result of pressure on the median nerve in the carpal tunnel. The median nerve supplies the muscles of the thenar eminence: the abductor pollicis (C7, C8), flexor pollicis brevis and opponens pollicis, and the lateral two lumbricals. The nerve conduction studies confirm marked denervation and absent sensory potentials within the median nerve territory.

Exposure to excessive androgens is usually accompanied by premature epiphyseal maturation and closure, resulting in a final adult height that is typically significantly below that expected from parental heights.

congenital adrenal hyperplasia (CAH) is associated with precocious puberty caused by long term exposure to androgens, which activate the hypothalamic-pituitary-gonadal axis. Similarly, CAH is associated with hyperpigmentation and hyperreninemia due to sodium loss and hypovolaemia.

First and foremost, the patient should be put on ECG monitoring to identify the cardiac state, and because of the markedly raised serum potassium, a calcium gluconate bolus will have the immediate effect of moderating the nerve and muscle performance.