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.

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

A high transferrin saturation is seen in hemochromatosis, as well as a high iron level (>30), a high ferritin level, and a LOW TIBC (<20). Think of it like the opposite findings of iron deficiency anaemia which is a low iron, low ferritin, high TIBC.

Rheumatoid Scleritis is a painful inflammatory condition of the sclera in patients with rheumatoid arthritis. It might be diffuse, nodular, or necrotizing in nature. This occurs mostly in the sixth decade of life and mostly when the rheumatoid disease is in remission. Sclera is the first ocular manifestation in a patient of rheumatoid arthritis. This inflammation might later spread to the adjacent ocular structures like the cornea, causing keratitis, the uveal tract causing uveitis and the lens causing cataracts.

The clinical picture points to Lambert– Eaton myasthenic syndrome (LEMS) which often presents with weakness of the arms and legs. In LEMS, antibodies against voltage-gated calcium channels (VGCC) decrease the amount of calcium that can enter the nerve ending, causing autonomic symptoms like dry mouth and slurring of speech, as seen in this patient.

Myoglobinuria is the condition when there is degeneration of necrosed muscle that it is excreted in the urine. This condition would then cause acute tubular damage leading to renal failure.

When a patient presents with an illness (unrelated to the liver) or a stressful event on the body, and develops asymptomatic jaundice, think Gilbert’s syndrome. It is autosomal dominant. It is an unconjugated hyperbilirubinemia from impaired glucuronyl transferase. Classically, Crigler-Najjar would be in infants, and it would be symptomatic. It is also an unconjugated hyperbilirubinemia.

The patient has acute promyelocytic leukaemia (APML) with associated disseminated intravascular coagulation (DIC). Although
the platelet count is high, platelet function is ineffective.

Patients may present, as in this case, with severe bleeding, and the most appropriate emergency treatment would be administration of fresh frozen plasma (FFP).

It is proven that spironolactone has survival benefits and loop diuretics only give symptomatic relief. Beta blockers are however, known to improve exercise tolerance, left ventricular function and reduce symptoms. They also reduce the mortality associated with heart failure. So administration of beta blockers will reduce the time spent in hospital by improving symptoms.

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion characterised by the acute onset of non-cardiogenic pulmonary oedema following transfusion of blood products.

TRALI is a more severe manifestation of the febrile non-haemolytic group of transfusion reactions and usually occur in patients who have had multiple previous transfusions. TRALI is related to leucocyte antibodies which are present in the plasma of the blood donor. Multiparous women are the highest-risk donors for TRALI.

For management, leucocyte-depleted blood is now used for transfusion and this is associated with a reduced risk of this type of transfusion reaction.

When closure of the pulmonary valve occurs before the aortic valve, reversed splitting occurs. The causes of reversed splitting are aortic stenosis, hypertrophic cardiomyopathy, left bundle branch block (LBBB), and a ventricular pacemaker.

Insulinoma is associated with LOW fasting glucose, HIGH insulin level, and HIGH C peptide. Insulin-abuse or overdose will cause HGH insulin levels and a LOW C peptide. If the C peptide is low, be suspicious.

Northern blotting’s purpose is to measure the size and amount of RNA transcribed from a specific gene of interest.

Lewy body dementia is the second most common cause of dementia in the elderly after Alzheimer’s disease. The core feature is a progressive dementia, but other characteristic features include Parkinsonism, visual hallucinations, fluctuating cognitive abilities and executive function, and an increased risk of falls or autonomic failure.

The blood gas analysis provided above is suggestive of a mixed respiratory alkalosis and metabolic acidosis characteristic of salicylate overdose.

Pathophysiology:
The direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis.
As it is metabolized, it causes an uncoupling of oxidative phosphorylation in the mitochondria.
Lactate levels then increase due to the increase in anaerobic metabolism. This, along with a slight contribution from the salicylate metabolites result in metabolic acidosis.

Tinnitus is characteristic and salicylate ototoxicity may produce deafness. Other neurological sequelae include encephalopathy and agitation, seizures and CNS depression and coma. Cardiovascular complications include tachycardia, hypotension, and dysrhythmias (VT, VF, and asystole).

According to the latest research, beta blockers are associated with higher incidence of fatal and non-fatal strokes, all cardiovascular events, and cardiovascular mortality. New-onset diabetes also associates with beta blockers.

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.

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.

Different Oral Hypoglycaemic Agents (OHAs) and their respective mechanism(s) of action include:
• Sulfonylureas (such as, glipizide, gliclazide, glimepiride) – bind to ATP sensitive Potassium channels (K – ATP channels) in the ? cells of the islets of the pancreas. Inhibition of these channels lead to an altered resting membrane potential in these cells causing an influx of calcium which increases insulin secretion.
• Meglitinides (like Repaglinide) through a different receptor, they similarly regulate K – ATP channels thereby causing an increase in insulin secretion.
• Biguanides (e.g., Metformin) increase the hepatic AMP-activated protein kinase activity leading to reduced gluconeogenesis and lipogenesis and increased insulin-mediated uptake of glucose in muscles. (it doesn’t increase insulin secretion)
• Thiazolidinediones (rosiglitazone, pioglitazone) bind to PPAR-? and increase peripheral uptake of glucose and decrease hepatic glucose production.
• α-Glucosidase inhibitors (such as acarbose, miglitol, voglibose) competitively inhibit α-glucosidase enzymes in the intestine that digest the dietary starch thus, inhibiting the polysaccharide reabsorption as well as metabolism of sucrose to glucose and fructose.
• DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin) prolong the action of glucagon-like peptide. This leads to inhibition of glucagon release, increase in insulin secretion and a decrease in gastric emptying leading to a decrease in blood glucose levels.
• SGLT2 inhibitors (dapagliflozin and canagliflozin) inhibit glucose reabsorption in the proximal tubules of the renal glomeruli leading to glycosuria which in-turn reduces blood glucose levels.
Note: Side effects of pioglitazone are weight gain, pedal oedema, bone loss and precipitation of congestive cardiac failure.

The patient’s presentation with slurred speech, intention tremor and past pointing, as well as ataxia and nystagmus, paired with a history of vertigo suggest the cerebellum as the site of cerebrovascular accident (CVA) or stroke.

Anti–Mi-2 antibodies are highly specific for dermatomyositis, but sensitivity is low; only 25% of patients with dermatomyositis demonstrate these antibodies. A positive antinuclear antibody (ANA) finding is common in patients with dermatomyositis, but is not necessary for diagnosis. Anti-Jo-1 antibodies are mostly associated with polymyositis. Anti Scl-70 antibodies and anti centromere antibodies are most commonly found in systemic scleroderma.

Mania is a state of extreme physical and emotional elation. A person experiencing mania or a manic episode may present with the following symptoms:
-Elevated mood. The person feels extremely ‘high’, happy and full of energy; he or she may describe the experience as feeling on top of the world and invincible. The person may shift rapidly from an elevated,
happy mood to being angry and irritable if they perceive they have been obstructed.
-Increased energy and overactivity. The person may have great difficulty remaining still.
-Reduced need for sleep or food. The person may be too active to eat or sleep.
-Irritability. The person may become angry and irritated with those who disagree with or dismiss his or her sometimes unrealistic plans or ideas.
-Rapid thinking and speech. The person’s thoughts and speech are more rapid than usual.
-Grandiose plans and beliefs. It is quite common for a person in a hypomanic or manic state to believe that he or she is unusually talented or gifted or has special friends in power. For example, the person may believe that he or she is on a special mission from God.
-Lack of insight. A person in a hypomanic or manic state may understand that other people see his or her ideas and actions as inappropriate, reckless or irrational. However, he or she is unlikely to personally accept that the behaviour is inappropriate, due to a lack of insight.
– Distractibility. The person has difficulty maintaining attention and may not be able to filter out external stimuli.

Careful assessment to rule out organic conditions is an important first step in the management of mania. Often hospitalisation is required for someone who is experiencing acute mania. Both mood-stabilising agents such as lithium carbonate or sodium valproate and an antipsychotic may be needed to treat psychotic symptoms, agitation, thought disorder and sleeping difficulties. Benzodiazepines may be useful to reduce hyperactivity. Treatment with lithium alone may have a relatively slow response rate (up to two weeks after a therapeutic blood level is established), so that adjunctive medication such as sodium valproate is usually required. Regular monitoring of blood levels for lithium and valproate is essential because of the potential for toxicity.

The symptoms of hypomania are similar to those of mania: elevated mood, inflated self-esteem, decreased need for sleep, etc. except that they don’t significantly impact a person’s daily function and never include any psychotic symptoms.

Koilonychia, known as spoon nails, is a condition of the nails bending inwards, taking the shape of a spoon. This is a strong indication of iron-deficiency anaemia (IDA). The rest of the patient’s symptoms further indicate IDA.

Indapamide is a mild thiazide-like diuretic with hypotensive effect, and compared to other thiazides, it is reported to also have less metabolic derangements. However, it may have beneficial hypo-calciuric effects that are often associated with thiazides, thus, in this case, we would recommend prescribing this to the patient.

Specificity (negative in health)
The ability of a test to correctly classify an individual as disease- free is called the test′s specificity. [Table 2]

Specificity = d / b+d

= d (true negative) / b+d (true negative + false positive)

= Probability of being test negative when disease absent.

Example: One hundred persons with normal angles (diagnosed by ′gold standard′: gonioscopy) are examined by peripheral angle chamber depth examination. Eighty-five persons had normal peripheral angle chamber depth [Table 3]. The specificity of the peripheral angle chamber depth examination to PACG is therefore –

85 / 100 = 85%.

Hypertension and haematuria are not common presentations in minimal change glomerulonephritis, all other statements are correct.

Primary gout is related more often to underexcretion of uric acid or overproduction.

In patients with acute renal tubular necrosis, infection in the form of gram-negative septicaemia is the most common cause of death, especially while the patient is awaiting spontaneous recovery of their renal function.

The given history suggests a small fibre painful peripheral sensory neuropathy, the most common cause of which is diabetes. Joint position sense and vibratory sensation are carried through large fibres, and therefore are not currently affected. Sensory nerves are affected more often than motor, so reflexes usually remain in tact.

Vitamin B12 deficiency causes impairment of joint position and vibratory sensation.

Chronic inflammatory demyelinating polyneuropathy (CIPD) causes a large fibre peripheral neuropathy with areflexia.

In syringomyelia there is impaired pain and temperature noted in the upper limbs.

Finally, with alcoholic polyneuropathy, all fibre types are affected (sensory and motor loss). It is usually gradual with long term alcohol abuse and may be accompanied by a nutritional deficiency. In addition, pain is a more dominant feature.

Osteomalacia is a marked softening of the bones that can present in both type I and type II Renal Tubular Acidosis (RTA) and will thus not differentiate the two types in any case. The other measures will allow differentiation of the two types.