Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes.

In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC). However, LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.

The human immunodeficiency virus (HIV) is grouped to the genus Lentivirus within the family of Retroviridae, subfamily Orthoretrovirinae. The HIV genome consists of two identical single-stranded RNA molecules that are enclosed within the core of the virus particle. The genome of the HIV provirus, also known as proviral DNA, is generated by the reverse transcription of the viral RNA genome into DNA, degradation of the RNA and integration of the double-stranded HIV DNA into the human genome.

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 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.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

According to echocardiography findings pulmonary pressure is closer to systemic blood pressure and it is evidence of pulmonary hypertension. Because of the reversal of shunt due to pulmonary hypertension, cyanosis and clubbing have developed. So the most probable diagnosis is Eisenmenger’s syndrome.

Palmar xanthomas and tuberoeruptive xanthomas are found in type III hyperlipoproteinemia (dysbetalipoproteinemia,broad-beta disease, remnant removal disease)

The most sensitive test for detecting Hepatitis C infection (acute) is HCA RNA; it can be detected 1-2 weeks after infection. Anti-HCV antibodies take at least 6 weeks to develop and be positive.

Fundoscopy findings of cotton wool spots and retinal tears, accompanied by a history of blurred vision, are characteristic of retinitis. Cytomegalovirus is known to cause retinitis.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. Symmetric lower limb arthropathy and a sterile joint aspirate points towards reactive arthropathy.

Maternal and fetal toxoplasma infection may be avoided by advising pregnant women to wear gloves when gardening or handling cat litter and to cook meat thoroughly. Affected babies are treated with pyrimethamine, sulfadiazine, and folic acid.

The most probable diagnosis for this patient is delirium tremens due to alcohol withdrawal, which should be treated as a medical emergency. 
Delirium tremens is a hyperadrenergic state and is often associated with tachycardia, hyperthermia, hypertension, tachypnoea, tremor, and mydriasis.
Treatment:
– The most common and validated treatment for alcohol withdrawal is benzodiazepine: first-line treatment includes oral lorazepam.
– If the symptoms persist, or the medication is refused, parenteral lorazepam, haloperidol or olanzapine should be given.
– Central-acting, alpha-2 agonists such as clonidine and dexmedetomidine should not be used alone for the treatment of alcohol withdrawal.
– It is also recommended to avoid using alcohol, antipsychotics, anticonvulsants, beta-adrenergic receptor blockers, and baclofen for the treatment of alcohol withdrawal as there are not enough studies to support the safety of these.

Asthma is a condition characterized by airway hyperresponsiveness, which results in reversible increases in bronchial smooth muscle tone, and variable amounts of inflammation of the bronchial mucosa.
During an acute asthma attack, the already inflamed airways narrow further due to bronchospasm, which leads to increased airway resistance. Because of the increased smooth muscle tone during an asthma attack, the airways also tend to close at abnormally high lung volumes, trapping air behind occluded or narrowed small airways. Thus the acute asthmatic will breathe at high lung volumes, his functional residual capacity will be elevated, and he will inspire close to total lung capacity. The accessory muscles of respiration are often used to maintain the lungs in a hyperinflated state.

During episodes of acute asthma, pulmonary function tests reveal an obstructive pattern. This includes a decrease in the rate of maximal expiratory air flow (a decrease in FEV1 and the FEV1/FVC ratio) due to the increased resistance, and a reduction in forced vital capacity (FVC) correlating with the level of hyperinflation of the lungs. Because these patients breathe at such high lung volumes (near the top of the pressure-volume curve, where lung compliance greatly decreases), they must exert significant effort to create an extremely negative pleural pressure, and consequently fatigue easily. Overinflation also reduces the curvature of the diaphragm, making it less efficient in generating further negative pleural pressure.

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
Thus, ethanol’s inhibitory effect helps to explain the increased diuresis experienced during intoxicated states as well as increased free water loss; without appropriate ADH secretion, more water is excreted by the kidneys.

Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre.
Following a particularly severe episode of alcohol excess, people may experience tremors due to increased glutamate production by neurons to compensate for the previous inhibition by ethanol.

Management of alcoholism:
Nutritional support:
– Alcoholic patients should receive oral thiamine if their ‘diet may be deficient’.
Pharmacological management:
– Benzodiazepines for acute withdrawal
– Disulfiram promotes abstinence – alcohol intake causes a severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis.
– Acamprosate reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo-controlled trials.

Acute breathlessness in SLE can be due to a pericardial effusion or a pulmonary embolism. Normal peripheral oxygen saturation and normal ECG, make the diagnosis of pulmonary embolism less likely. To exclude pericardial effusion, an urgent transthoracic echocardiogram is needed.

Anti-TNF-α therapy is effective for patients with arthritis but it can oftentimes lead to the reactivation of latent TB. Hence it should be used with great caution in patients with a past history of TB or current infection.

Diagnosis of RA is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). Rheumatoid factor is not very specific for this disease and hence has low reliability. X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis.

Insulin/dextrose infusion will increase the activity of the sodium-potassium pump in the cells, which will in turn decrease serum potassium levels.

In Wilson’s disease, serum caeruloplasmin is decreased. Skin pigmentation is not increased, but may become jaundiced. 24 hour urine copper excretion is increased. Hepatic copper concentration is increased. Serum copper level is also increased. Key point: high copper. Remember Kayser-Fleisher rings for the eyes in Wilson’s disease.

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles and thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which will result in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

The history and ECG findings are adequate to begin cardiac revascularization of this patient. There is no need for cardiac markers to confirm the diagnosis. Further delay in starting definite treatment is not recommended.

Sarin acts by inhibiting acetylcholinesterase.

Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase
Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase. This results in high levels of acetylcholine (ACh).

The effects of excessive ACh can be remembered by the mnemonic DUMBELLS:
Diarrhoea
Urination
Miosis/muscle weakness
Bronchorrhea/Bradycardia
Emesis
Lacrimation
Salivation/sweating

Organophosphate insecticide poisoning:
One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase
Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)
Salivation
Lacrimation
Urination
Defecation/diarrhoea
cardiovascular: hypotension, bradycardia
miosis, muscle fasciculation.

Organophosphate poisoning is treated with the anti-muscarinic atropine.

The patient is presenting with symptoms of lateral medullary syndrome also known as Wallenberg’s syndrome or posterior inferior cerebellar artery syndrome, where the symptoms are due to an ischemia in the brainstem. The classical symptoms include contralateral sensory deficits of the trunk region paired with ipsilateral facial sensory deficits.

The patient most likely has Klinefelter’s syndrome.
Klinefelter syndrome (KS) refers to a group of chromosomal disorders in which the normal male karyotype, 46,XY, has at least one extra X chromosome. XXY aneuploidy, the most common human sex chromosome disorder. It is also the most common chromosomal disorder associated with male hypogonadism and infertility.
Klinefelter syndrome is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia), gynecomastia in late puberty, hyalinization and fibrosis of the seminiferous tubules, elevated urinary gonadotropin levels, and behavioural concerns.

Although this patient’s left ventricular function is normal at the time of examination, there is chance of deterioration of it due to aortic regurgitation. It is found that ACE inhibitors slow the development of left ventricular dysfunction. So this patient should be started on an ACE inhibitor.

St John’s wort interferes with warfarin by increasing its breakdown and decreasing its effectiveness. This leads to the need for adjustment in the dose of warfarin and careful attention to monitoring if the patient decides to continue with the drug. Ideally, an alternative antidepressant should also be considered.

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals. This would be the most likely option as it is the only disease that can affect both liver and lung functions.
People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema. Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.
About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and sclera (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing hepatocellular carcinoma.

Elderly patients with severe hypothyroidism often present with variable symptoms that may be masked or potentiated by co-morbid conditions. Characteristic symptoms may include fatigue, weight gain, cold intolerance, hoarseness, constipation, and myalgias. Neurologic symptoms may include ataxia, depression, and mental status changes ranging from mild confusion to overt dementia.
Clinical findings that may raise suspicion of thyroid hormone deficiency include hypothermia, bradycardia, goitrous enlargement of the thyroid, cool dry skin, myxoedema, delayed relaxation of deep tendon reflexes, a pericardial or abdominal effusion, hyponatremia, and hypercholesterolemia.

The patient has a greatly reduced free T4 concentration, is hypothermic, unconscious and has evidence of associated heart failure. All of those support the diagnosis of profound hypothyroidism.

The given clinical scenario is highly suggestive of a borderline personality disorder.

Borderline personality disorder is marked out by instability in moods, behaviour, and relationships. The diagnosis is confirmed by the presence of at least 5 of the following symptoms;
1) Extreme reactions including panic, depression, rage, or frantic actions to abandonment, whether real or perceived
2) A pattern of intense and stormy relationships with family, friends, and loved ones, often veering from extreme closeness and love to extreme dislike or anger
3) Distorted and unstable self-image or sense of self, which can result in sudden changes in feelings, opinions, values, or plans and goals for the future (such as school or career choices)
4) Impulsive and often dangerous behaviours, such as spending sprees, unsafe sex, substance abuse, reckless driving, and binge eating
5) Recurring suicidal behaviours or threats or self-harming behaviour, such as cutting, intense and highly changeable moods, with each episode lasting from a few hours to a few days
6) Chronic feelings of emptiness and/or boredom
7) Inappropriate, intense anger or problems controlling anger
8) Having stress-related paranoid thoughts or severe dissociative symptoms, such as feeling cut off from oneself, observing oneself from outside the body, or losing touch with reality.

Other options:
There are no features consistent with endogenous depression, such as early morning wakening or loss of appetite.
There are also no features consistent with hypomania such as pressure of speech, a flight of ideas, or over-exuberant behaviour.
The lack of history of drug abuse rules out drug-induced psychosis.
An anti-social personality disorder is characterized by a failure to conform to social norms and repeated lawbreaking. There is consistent irresponsibility, impulsivity, and disregard for both their safety and that of others. This is not the case in the given scenario.