The water deprivation test (i.e., the Miller-Moses test), is a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis. It is typically performed in patients with more chronic forms of Diabetes Insipidus (DI). The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality will be above 750 mOsm/kg after water deprivation.
A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

Guillain-Barre syndrome is an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni). Characteristic features include progressive weakness of all four limbs, and it is classically ascending, affecting the lower extremities first. Sensory symptoms tend to be mild.

Functional neurological syndrome can be discounted due to presence of hard neurological signs. Multiple sclerosis can be excluded because of the presence of lower motor neuron signs and absence of upper motor neuron signs. Chronic inflammatory demyelinating polyneuropathy is the chronic form of Guillain-Barre syndrome.

Anti ds-DNA antibodies are very specific for SLE and their presence most often indicates systemic spread of the disease. These antibodies are present in about 30 percent of the total cases of SLE.

NICE now recommends the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Memantine is reserved for patients with moderate to severe Alzheimer’s.

The patient presents with sudden onset of alexia (the inability to read) WITHOUT agraphia (inability to write) which is consistent with lesions of the corpus callosum where there is a disconnect syndrome and the patient’s language and visual centres are actually in tact, but are unable to communicate between hemispheres. In this case, the damage due to the stroke is most likely in the left visual cortex, leaving visual processing to the intact right hemisphere which unfortunately cannot communicate the information to the language centres (Broca and Wernicke’s) in the left hemisphere, hence the alexia. Alternatively, the speech and writing are unaffected as the language centres can still communicate with the primary motor cortex.

Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism.

Lead poisoning is characterised by abdominal pain, fatigue, constipation, peripheral neuropathy (mainly motor), and blue lines on gum margin in 20% of the adult patients (very rare in children).

For diagnosis, the level of lead in blood is usually considered with levels greater than 10 mcg/dL being significant. Furthermore, the blood film shows microcytic anaemia and basophilic stippling of red blood cells. Urinary coproporphyrin is increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased). Raised serum and urine levels of delta-aminolaevulinic acid may also be seen, making it sometimes difficult to differentiate from acute intermittent porphyria.

In patients with polycystic ovarian syndrome (PCOS), FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Women with PCOS have abnormalities in the metabolism of androgens and oestrogen and in the control of androgen production. PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism. Other signs and symptoms of PCOS may include the following:
– Hirsutism
– Infertility
– Obesity and metabolic syndrome
– Diabetes
– Obstructive sleep apnoea

Androgen excess can be tested by measuring total and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess. Other androgens, such as dehydroepiandrosterone sulphate (DHEA-S), may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS). Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one-third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age.

Finasteride inhibits the formation of dihydrotestosterone.
Finasteride is a 5α-reductase inhibitor and thus, inhibits the conversion of testosterone to dihydrotestosterone (DHT).

DHT is much more active than testosterone and binds more avidly to cytoplasmic receptors. DHT stimulates prostate growth and may be responsible for benign prostatic hyperplasia in the elderly.

Thus, finasteride can cause a reduction in prostatic volume and help in managing a patient with benign prostatic hyperplasia.

The oxygen saturation in the pulmonary artery is higher than that of the right ventricle. The pressure of the pulmonary artery and of the PCWP are also high. So patent ductus arteriosus is highly suggestive.

Reduced conduction velocity is associated with demyelinating neuropathies. An abnormally slow response is associated with very proximal disease, i.e. radiculopathies. Delayed P100 latency is a feature of performing visual evoked potentials in those with optic nerve disease. Conduction block is usually associated with certain types of demyelinating neuropathy.

Leptin, a 167–amino acid hormone, was discovered in 1994 and is secreted mainly by adipocytes. Plasma leptin levels are significantly correlated with body mass index (BMI) and the total amount of body fat.

There are number of diseases that have to be notified to relevant authorities to prevent or reduce their spread. Those conditions include Cholera, Diphtheria, Food poisoning, Infectious bloody diarrhoea, Malaria, Measles, Meningococcal septicaemia, Mumps, Plague, Rabies and Rubella.

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

Pulsus alternans is the alternation of one strong and one weak beat without a change in the cycle length. It occurs most commonly in heart failure due to increased resistance to LV ejection, as occurs in hypertension, aortic stenosis, coronary atherosclerosis, and dilated cardiomyopathy. Pulsus alternans is usually associated with an S3 gallop, which is associated with a poor prognosis. It usually disappears with treatment of the heart failure.

The patient is displaying signs and symptoms of hyperviscosity syndrome, secondary to the Waldenström’s macroglobulinemia. Treatment of choice is plasmapheresis.

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 monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%.

The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.

Before the initiation of trastuzumab, an echocardiography is a must to rule out any pre-existing cardiac abnormalities as trastuzumab is cardiotoxic.

Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.

Adverse effects include:
Flu-like symptoms and diarrhoea are common.
Cardiotoxicity:
– Risk increases when anthracyclines are used concomitantly.
– Trastuzumab-induced cardiac dysfunctions are regarded as less severe and largely reversible because primary cardiomyocyte do not show ultrastructure changes unlike those associated with anthracycline-induced cardiotoxicity.
– Primary myocyte injury does not occur in patients who were treated with trastuzumab.

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.

Both fibrates and nicotinic acid have been associated with myositis, especially when combined with a statin. However, the Committee on Safety of Medicines has produced guidance which specifically warns about the concomitant prescription of fibrates with statins concerning muscle toxicity.

Bezafibrate: It is a fibric acid derivative (fibrate) that has been used as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels.
Pharmacological effects:
– Increases VLDL catabolism by increasing lipoprotein and hepatic triglyceride lipase.
– Decreases triglyceride synthesis by inhibiting acetyl-CoA reductase.
– Decreases cholesterol synthesis by inhibiting HMG-CoA reductase.

Side effects:
– Hypersensitivity
– Primary biliary cirrhosis
– Pre-existing gallbladder disease
– Concurrent use with HMG-CoA inhibitors (statins) can produce myopathy
– Hepatic/renal impairment in a patient warrants dose adjustment as this drug is primarily excreted via the renal mechanism.

Contraindications: Concurrent use of MAO inhibitors, hypersensitivity, pre-existing cholestasis, and pregnancy.

Use: It can be used to treat Barth syndrome (characterized by dilated cardiomyopathy, neutropenia (presenting with recurrent infections), skeletal myopathy and short stature)

Narrow complex tachycardia with hypotension is a medical emergency. Immediate synchronized cardioversion is the ideal management.

A couple of papers written by the same authors indicate that children and adolescents taking an SSRI definitely experience discontinuation reactions that can be mild, moderate or severe when the medication is stopped suddenly or high doses are reduced substantially. Among the SSRIs paroxetine seems to be the worst offender and fluoxetine the least while sertraline and fluvoxamine tend to be intermediate. The rate of discontinuation syndrome varies with the particular SSRI involved. It is generally quoted as 25% but is higher for SSRIs with shorter half-lives. Paroxetine has been associated with more frequent discontinuation symptoms than the other SSRIs.

The use of fluoxetine with its long half-life appears safer in this respect than paroxetine and venlafaxine causing the most concerns.

Paroxetine has the shortest half-life with 21 hours of all listed SSRIs and as such it would be expected to have a higher incidence or severity (greater number of symptoms) and fluoxetine would have the least since it has a half life of 96 hours. Citalopram has a half-life of 35 hours while escitalopram has a half-life of 30 hours.

The most common symptoms reported are: dizziness, light-headedness, drowsiness, poor concentration, nausea, headache and fatigue.
Another common symptom in adults is paraesthesia described as burning, tingling, numbness or electric shock feelings usually in the upper half of the body or proximal lower limbs.

Measles and chickenpox are spread by droplets. Thus, patients should be isolated.
Rheumatic fever and post-streptococcal glomerulonephritis are immune mediated diseases that don’t require isolation.
Herpetic gingivostomatitis spreads by direct transmission of infected secretions to the stratified squamous epithelium.
HSP is not an infectious disease.

The rationale behind the use of sodium bicarbonate is that it increases the alkalinity of the urine promoting lithium excretion. The preferred treatment in severe cases would be haemodialysis.

Lithium is a mood-stabilizing drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Toxicity may be precipitated by dehydration, renal failure, diuretics (especially Bendroflumethiazide), ACE inhibitors, NSAIDs and metronidazole.

Features of toxicity
Coarse tremor (a fine tremor is seen in therapeutic levels)
Hyperreflexia
Acute confusion
Seizure
Coma

Management
Mild-moderate toxicity may respond to volume resuscitation with normal saline
Haemodialysis may be needed in severe toxicity
Sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion.

Increased WBC count and CRP suggest infection. But with the fluctuating hard neurological signs, there is suspicion of the presence of a cerebral mass, which is an indication for requesting for a CT scan with contrast, to rule out an abscess or haematoma. The lumbar puncture can be considered after the CT scan.

The patient is most likely to have Bulimia nervosa. A young girl with a low body mass contributes to the low urea. Hypokalaemia and hyponatraemia are due to vomiting. Her urine sodium is also low.
– In Addison’s diseases, there are low levels of sodium and high levels of potassium in the blood. In acute adrenal crisis: The most consistent finding is elevated blood urea nitrogen (BUN) and creatinine. Urinary and sweat sodium also may be elevated.
– In Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) there is hyponatremia with corresponding hypo-osmolality, continued renal excretion of sodium, urine less than maximally dilute and absence of clinical evidence of volume depletion.

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.

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

Malingering is not considered a mental illness. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), malingering receives a V code as one of the other conditions that may be a focus of clinical attention. The DSM-5 describes malingering as the intentional production of false or grossly exaggerated physical or psychological problems. Motivation for malingering is usually external (e.g., avoiding military duty or work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs).

Malingering should be strongly suspected if any combination of the following factors is noted to be present: (1) medicolegal context of presentation; (2) marked discrepancy between the person’s claimed stress or disability and the objective findings; (3) lack of cooperation during the diagnostic evaluation and in complying with the prescribed treatment regimen; and (4) the presence in the patient of antisocial personality disorder (ASPD).

This patient is be pretending to be sick in order to get morphine.

The QT interval is the time from the start of the Q wave to the end of the T wave. It represents the time taken for ventricular depolarisation and repolarisation. The QT interval should be measured in either lead II or V5-6.