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%.

Impetigo appears more commonly on the face than other exposed areas like the limbs. Its blisters are clustered and may have a fluid discharge.

Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled.

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.

The incubation periods of disorders is extremely important to diagnose, treat, prevent or attenuate a disease.

• Chickenpox: 7-21 days.
• Whooping cough: 10-14 days.
• Hand, foot and mouth disease: 2-6 days.
• German measles: 14-21 days.
• Mumps: 14-18 days.

The clinical manifestations of Small cell lung cancer (SCLC) can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known.
SIADH is present in 15% of cases and most commonly seen.
Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases.
Ectopic Cushing’s syndrome in SCLC does not usually exhibit the classic signs of Cushing’s syndrome and Cushing’s syndrome could also appear during effective chemotherapy.
Chemotherapy is the treatment of choice in SCLC.

This patient meets the diagnostic criteria for neutropenic sepsis, which is a relatively common complication of cancer therapy – usually chemotherapy occurring 7–14 days after. It is defined as a neutrophil count of <0.5 x 10^9/L in a patient undergoing anticancer treatment and who has either a temperature higher than 38°C or has other features consistent with clinically significant sepsis. Management approach is the same as mentioned in this case. However, if the patient still remains unwell, then an antifungal such as amphotericin B is started after risk-stratifying the patient and carrying out investigations (e.g. HRCT and Aspergillus PCR) to determine the likelihood of systemic fungal infection.

Favus is a fungal infection of the scalp, resulting in the formation of a yellowish crusted plaque over the scalp and leads to scar formation with alopecia. Tinea capitus is a fungal infection of the scalp resulting in scaling and non scarring hair loss. Folliculitis presents with multiple perifollicular papules which can be caused by both bacteria and fungi. Cradle cap usually affects infants where the whole scalp is involved. It can lead to hair loss and responds to topical antifungals and keratolytics.

Neutrophilia is also commonly associated with polycythaemia vera.

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

To differentiate ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrant conduction the following electrocardiographic features should be looked for:

Evidence of preceding atrial activity for SVT. Oesophageal leads are helpful if P waves are hidden in the QRS complex.
QRS duration more than 140 ms for VT.
QRS morphology: Features of QRS morphology that favour SVT are RBBB or triphasic patterns like rSR in V1 and qRS in V6. Monophasic pattern like R or qR in V1 and rS or QS in V6 or multiple morphology QRS complexes favour VT.
AV dissociation for VT.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

The farmer has most likely ingested an organophosphate insecticide.
Organophosphorus compounds are used widely as:
• Insecticides – Malathion, parathion, diazinon, dichlorvos
• Nerve gases – Soman, sarin, tabun, VX
• Ophthalmic agents – Echothiophate
• Antihelmintics – Trichlorfon
• Herbicides – merphos
• Industrial chemical (plasticizer) – Tricresyl phosphate
Signs and symptoms of Organophosphorus Poisoning (OPP) can be classified as:
• Muscarinic effects:
o Cardiovascular – Bradycardia, hypotension
o Respiratory – Rhinorrhoea, bronchorrhea, bronchospasm, cough, severe respiratory distress
o Gastrointestinal – Hypersalivation, nausea and vomiting, abdominal pain, diarrhoea, faecal incontinence
o Genitourinary – Incontinence
o Ocular – Blurred vision, miosis
o Glands – Increased lacrimation, diaphoresis
• Nicotinic effects:
o Muscle fasciculation, weakness, cramping, diaphragmatic failure, and autonomic side effects include: hypertension, tachycardia, and mydriasis.
• Central nervous system (CNS) effects:
o Anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, coma, apnoea
Mainstay Treatment:
• Decontamination
• Securing Airway, Breathing and Circulation
• Atropine
• Pralidoxime
• Benzodiazepines

Extended-spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Extended spectrum beta-lactamase (ESBL) production is the main reason for multi-drug resistance among E.coli. Commonly used medications to treat ESBL-involved infections include carbapenems (imipenem, meropenem, and doripenem), cephamycins (cefoxitin and cefotetan), Fosfomycin, nitrofurantoin, beta-lactamase inhibitors (clavulanic acid, tazobactam, or sulbactam), non-beta-lactamases and colistin (if all other medications have failed.)

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.

Patients with varicella zoster infection present with general fatigue and fever along with multiple lesions which do not appear to be identical.

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.

The cardiovascular alterations which occur during pregnancy are for the optimal growth and development of the foetus and help to protect the mother from the risks of delivery, such as haemorrhage. The changes are characterized by an increased vascular volume, cardiac output, and heart rate, with a marked fall in vascular resistance and reduction in blood pressure.

ACE inhibitors are known to cause a dry cough and they should be stopped, to settle the cough. The next drug of choice is an angiotensin receptor blocker such as candesartan.

In a patient with chronic alcoholism, one can expect confabulations, which point towards a diagnosis of Korsakoff’s syndrome.

Korsakoff’s is characterized by confabulation and amnesia, typically occurring in alcoholics secondary to chronic vitamin B1 (thiamine) deficiency.

Other options:
Dysthymia refers to mild depression.
Hydrophobia is a feature of rabies
Lilliputians may be observed in delirium tremens.
Perseveration is repetitive speech patterns, commonly seen after traumatic brain injury.

According to the Caine criteria, the presence of any two among the four following criteria can be used to clinically diagnose Wernicke’s Encephalopathy:
Dietary deficiency
Oculomotor abnormalities
Cerebellar dysfunction
Either altered mental status or mild memory impairment
Korsakoff psychosis:
Altered mental status – disorientation, confabulations
Oculomotor findings – most often horizontal nystagmus, ophthalmoplegia, cranial nerve IV palsy, conjugate gaze
Ataxia – wide-based gait

Treatment:
The mainstay of treatment in an acute presentation is thiamine replacement.
Electrolyte abnormalities should be corrected and fluids replaced.
In particular, magnesium requires replacement, as thiamine-dependent enzymes cannot operate in a magnesium-deficient state.
After the acute phase of vitamin and electrolyte replacement, memory rehabilitation is beneficial in Korsakoff syndrome.

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.

The major endocrine functions of adrenal gland are to produce catecholamines and steroids. Catecholamine, synthesized by the adrenal medulla, is responsible for blood pressure and blood flow regulation whereas steroids produced by the cortex control energy and water homeostasis and immune responses. Glucocorticoids, a major group of adrenal steroids, have a stimulatory effect on catecholamine synthesis in the medulla.

The CD15 antigen, also known as Lewis (hapten)X, serves as an immuno-phenotypic marker for Reed-Sternberg cells and its expression has diagnostic, but also prognostic significance in Hodgkin Lymphoma.

The antithrombotic action of aspirin is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX) at the functionally important amino acid serine529. This prevents the access of the substrate (arachidonic aid) to the catalytic site of the enzyme at tyrosine385 and results in an irreversible inhibition of platelet-dependent thromboxane formation.

Uric acid stones will most likely be found in this case because of the patient’s long history of gout. Additionally, studies have shown that ileostomy patients have an increased risk for the development of uric acid stones.

The combination of frequent infections, eczema, and thrombocytopaenia are characteristic of Wiskott-Aldrich syndrome, which is due to an abnormality in the WASP gene. It is an X-linked recessive disorder that causes primary immunodeficiency owing to a combined B- and T-cell dysfunction.

The other listed options are:
1. PKD1: polycystic kidney disease
2. CFTR: cystic fibrosis
3. HFE1: haemochromatosis
4. RET: multiple endocrine neoplasia, Hirschsprung’s disease

The main cardiovascular manifestations associated with Marfan’s syndrome are aortic dilatation and mitral valve prolapse.

Syringomyelia is a development of a cavity (syrinx) within the spinal cord. Signs and symptoms include loss of feeling, paralysis, weakness, and stiffness in the back, shoulders, and extremities. Syringomyelia may also cause a loss of the ability to feel extremes of hot or cold, especially in the hands. Symptoms typically vary depending on the extent and, often more critically, on the location of the syrinx within the spinal cord.

Hereditary non-polyposis syndrome (HNPCC) is the most common type of inherited colorectal cancer. It often presents in younger and younger generations down a family. FAP presents with 100’s-1000’s of polyps and is less common. Li-Fraumeni syndrome and Fanconi syndrome are rare. For Peutz-Jeghers syndrome, the thing you will look for in the question stem is discoloured spots on the lips, this is classic.

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.

Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.

In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.

Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.

Management:
– Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.
– Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline).
– On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.
– Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

Haemoptysis is a symptom which indicates the worsening of mitral stenosis. It occurs due to the rupture of pulmonary veins or the capillary system due to pulmonary venous hypertension. Elevated serum creatinine is seen in worsening aortic stenosis. Worsening of tricuspid regurgitation causes ascites and a pulsatile liver.