Insulin is produced by the beta-cells in the islets of Langerhans in the pancreas while Glucagon is secreted from the alpha cells of the pancreatic islets of Langerhans.
Type 1 diabetes mellitus is the culmination of lymphocytic infiltration and destruction of the beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycaemia develops and diabetes may be diagnosed.

Exogenous thyroid hormone use has been associated with episodes of thyroid storm as well as thyrotoxic periodic paralysis.
It presents with marked proximal muscle weakness in both upper and lower limbs, hypokalaemia and signs of hyperthyroidism.
Hyperthyroidism generally presents with tachycardia, hypertension, hyperthermia, and cardiac arrhythmias

Laxatives and diuretics can result in electrolyte abnormalities.
Medical complications associated with laxatives include chronic diarrhoea which disrupts the normal stool electrolyte concentrations that then leads to serum electrolyte shifts; acutely, hypokalaemia is most typically seen. The large intestine suffers nerve damage from the chronic laxative use that renders it unable to function properly. The normal peristalsis and conduction are affected; the disorder is thought to be secondary to a degeneration of Auerbach’s Plexi. However, it does not cause muscle weakness.

Insulin tends to cause weight gain, not weight loss.
Metformin does not cause muscle weakness but can cause headaches.

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

Whilst asthma and COPD are different diseases they cause similar symptoms, which can present a challenge in identifying which of the two diseases a patient is suffering from. COPD causes chronic symptoms and narrowed airways which do not respond to treatment to open them up. In the case of asthma the constriction of the airways through inflammation tends to come and go and treatment to reduce inflammation and to open up the airways usually works well.

COPD is more likely than asthma to cause a chronic cough with phlegm and is rare before the age of 35 whilst asthma is common in under-35s. Disturbed sleep caused by breathlessness and wheeze is more likely in cases of asthma, as is a history of allergies, eczema and hay fever. Differentiating between COPD and asthma requires a history of both symptoms and spirometry. The spirometry history should include post bronchodilator measurements, the degree of reversibility and, ideally, home monitoring which gives a history of diurnal variation.

Airflow Obstruction: Both asthma and COPD are characterised by airflow obstruction. Airflow obstruction is defined as a reduced FEV1 and a reduced FEV1/FVC ratio, such that FEV1 is less than 80% of that predicted, and FEV1/FVC is less than 0.7.

These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

COPD: COPD is a chronic, slowly progressive disorder characterised by airflow obstruction (reduced FEV1 and FEV1/VC ratio) that does not change markedly over several months. The airflow obstruction is not fully reversible.

Spirometry COPD Asthma
VC Reduced Nearly normal
FEV1 Reduced Reduced in attack
FVC (or FEV6) Reduced Nearly normal
FEV1 Ratio
(of VC/FVC/FEV6) Reduced in attack

This man has a low FEV1 and FVC. His diffusions capacity is also low despite having a normal total lung capacity. These values confirm a diagnosis of COPD.

Primary hyperaldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension (HTN).
The common clinical scenarios in which the possibility of primary hyperaldosteronism should be considered include the following:
– Patients with spontaneous or unprovoked hypokalaemia, especially if the patient is also hypertensive
– Patients who develop severe and/or persistent hypokalaemia in the setting of low to moderate doses of potassium-wasting diuretics
– Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalaemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalaemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.

This case has hypercalcaemia most likely associated with the bony metastases from her pre-existing breast carcinoma. The most appropriate next step is to give Pamidronate 60mg intravenously, a bisphosphonate, to immediately inhibit bone resorption and formation.

Urea breath test is the most sensitive test to determine if there has been RESOLUTION/ERADICATION of the infection with H. pylori. The best test for initial diagnosis would be EGD with biopsy.

Annual incidence of DVT in the general population is about 1 per 1000 adults. So the most suitable answer is about 2 per 1000.

Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath. Patients are typically aged 18-40 years, tall, thin, and, often, are smokers.

In small pneumothoraxes with minimal symptoms, no active treatment is required. These patients can be safely discharged with early outpatient review and should be given written advice to return if breathlessness worsens. Patients who have been discharged without intervention should be advised that air travel should be avoided until a radiograph has confirmed resolution of the pneumothorax.

Mechanism of action of low molecular weight heparin (LMWH):
It inhibits coagulation by activating antithrombin III. Antithrombin III binds to and inhibits factor Xa. In doing so it prevents activation of the final common path; Xa inactivation means that prothrombin is not activated to thrombin, thereby not converting fibrinogen into fibrin for the formation of a clot.

LMHW is a small fragment of a larger mucopolysaccharide, heparin. Heparin works similarly, by binding antithrombin III and activating it. Heparin also has a binding site for thrombin, so thrombin can interact with antithrombin III and heparin, thus inhibiting coagulation.
Heparin has a faster onset of anticoagulant action as it will inhibit not only Xa but also thrombin, while LMWH acts only on Xa inhibition.

Compared to heparin, LMWHs have a longer half-life, so dosing is more predictable and can be less frequent, most commonly once per day.

Dosage and uses:
LMWH is administered via subcutaneous injection. This has long-term implications on the choice of anticoagulant for prophylaxis, for example, in orthopaedic patients recovering from joint replacement surgery, or in the treatment of DVT/PE.

Adverse effects:
The main risk of LMWH will be bleeding. The specific antidote for heparin-induced bleeding is protamine sulphate.
Less commonly it can cause:
Heparin-induced thrombocytopenia (HIT)
Osteoporosis and spontaneous fractures
Hypoaldosteronism
Hypersensitivity reactions

Immunoglobulin should be given to all seronegative women within 4 days. However, it is strongly advised to seek medical care immediately if the disease develops.

When you hear painless jaundice and weight loss in the same sentence, the first thing you should think is cancer. Likely cholangiocarcinoma here or some other biliary tract obstructing cancer. The first line imaging for this would be MRCP because you’re looking for obstruction– the dilatation of the intra and extrahepatic ducts suggests this. This is less invasive than an ERCP or a liver biopsy. CT C/A/P will likely be needed for staging later but it is asking for the initial test.

The case presents with an underlying ovarian tumour, associated with psychiatric symptoms; thus, an organic illness must first be ruled out before considering the other conditions listed which often present with psychiatric features without an underlying organic disease. Among the listed conditions Anti-NMDA receptor encephalitis is the only condition that presents with psychiatric features including agitation, hallucinations, delusions and disordered thinking that is associated with tumours 50% of the time.

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.

Biguanides (Metformin):
People who take metformin alone should be able to fast safely given that the possibility of hypoglycaemia is minimal. However, patients should modify its dose and administration timing to provide two-thirds of the total daily dose, which should be taken immediately with the sunset meal, while the other third is taken before the predawn meal.

Thiazolidinediones: No change needed.

Sulfonylurea:
Once-daily sulfonylurea (such as glimepiride or gliclazide MR): the total daily dose should be taken with the sunset meal.
Shorter-acting sulfonylurea (such as gliclazide twice daily): the same daily dose remains unchanged, and one dose should be taken at the sunset meal and the other at the predawn meal.
Long-acting sulfonylurea (such as glibenclamide): these agents should be avoided.

It is important that diabetic patients to eat a healthy balanced diet and choose foods with a low glycaemic index (such as complex carbohydrates), which can help to maintain blood glucose levels during fasting. Moreover, it is crucial to consume adequate fluids to prevent dehydration. Physical activity is encouraged, especially during non-fasting periods.

As the patient has early menopause, hormone replacement therapy (HT) is considered to be the first line of choice for prevention of bone loss and fracture in the early postmenopausal period for 5 years.

Ezetimibe is a cholesterol-lowering agent that acts to prevent cholesterol absorption by directly inhibiting cholesterol receptors on enterocytes.
It does not affect the absorption of drugs (e.g. digoxin, thyroxine) or fat-soluble vitamins (A, D and K) as the anion-exchange resins do. It does not affect the cytochrome P450 enzyme system.
The increased risk of myositis associated with the statins is not seen with ezetimibe.
The most common adverse effects include headache, runny nose, and sore throat.
Less common reactions include body aches, back pain, chest pain, diarrhoea, joint pain, fatigue, and weakness.

The duration of these cell cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 phase might last about 11 hours, S phase about 8 hours, G2 about 4 hours, and M about 1 hour. The proliferation of most animal cells is similarly regulated in the G1 phase of the cell cycle. In particular, a decision point in late G1, called the restriction point in animal cells, is the point at which the cell becomes committed to the cell cycle and after which extracellular proliferation stimulants are no longer required.. Although the proliferation of most cells is regulated primarily in G1, some cell cycles are instead controlled principally in G2.

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.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Arnold-Chiari malformation usually presents with symptoms due to brainstem and lower cranial nerve dysfunction such as DBN.

Acute cord compression is a medical emergency. Typically, signs of segmental damage at the level of compression are usually combined with corticospinal tract dysfunction (e.g., hyperreflexia, Babinski’s sign and weakness) and sensory deficits below the level of compression. Symptoms include spinal pain that precedes the development of weak legs and sensory loss. There may be loss of bladder (and anal) sphincter control, manifesting as hesitancy, frequency and, finally, painless retention.
Spinal X-rays are rarely diagnostic. MRI is usually the investigation of choice and should not be delayed, but if not available consider doing a CT scan and myelography to confirm cord compression and fully define the level and extent of the lesion. If malignancy is the cause, it is important to give dexamethasone (oral or intravenous) while considering therapy more specific to the cause.

The size of the kidneys on ultrasound would differentiate chronic from acute renal failures. Chronic renal failure is more associated with small-sized kidneys.

The normal partial pressure reference values are:
– PaO2 more than 80 mmHg (11 kPa)
– PaCO2 less than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 (7.4kPa)
Hypoxemia (PaO2 <8kPa) with hypercapnia (PaCO2 >6.0kPa).
The pH is also lower than 7.35 at 7.3

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the build-up of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include:
– Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)
– Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
– A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
– Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)
– Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

The woman seems to have a chancroid, which may or may not drain to the lymph nodes of the groin. These nodes are the superficial inguinal lymph nodes.

Patients who have autonomously functioning nodules should be treated definitely with radioactive iodine or surgery.
Na131 I treatment – In the United States and Europe, radioactive iodine is considered the treatment of choice for Toxic Nodular Goitre. Except for pregnancy, there are no absolute contraindications to radioiodine therapy.

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2–3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

Major depression (MD) often occurs after MI and has been shown to be an independent predictor of poor cardiovascular (CV) outcome.

Results of a randomized trial confirm that the antidepressant sertraline can be used safely in patients with recent MI or unstable angina and is effective in relieving depression in these patients.

Adverse effects to note:
Sertraline – Diarrhoea (13-24%), Nausea (13-30%), Headache (20-25%),
Insomnia (12-28%)
Imipramine – ECG changes, orthostatic hypotension, tachycardia
Confusion, extrapyramidal symptoms (EPS), dizziness, paraesthesia, tinnitus
Flupentixol – seizures, irregular/fast heartbeat, increased sweating
Paroxetine – Hypertension, Tachycardia, Emotional lability, Pruritus
Venlafaxine – Abnormal vision (4-6%), Hypertension (2-5%), Paraesthesia (2-3%), Vasodilation (2-6%), Aneurism, Deep vein thrombophlebitis, Takotsubo cardiomyopathy

Scleroderma renal crisis (SRC) is a rare but severe complication in patients with systemic sclerosis (SSc). It is characterized by malignant hypertension, microangiopathic haemolytic anaemia with schistocytes and oligo/anuric acute renal failure. SRC occurs in 5% of patients with systemic scleroderma, particularly in the first years of disease evolution and in the diffuse form. Patients may develop symptoms of fluid overload.

The immunological changes in HIV include depletion in CD4+ T cell, cytokine dysregulation and immune dysfunction. The dominant immunologic feature of HIV infection is progressive depletion of the helper T cell (CD4+ T cell), which reverses the normal CD4:CD8 ratio and subsequently lead to immunodeficiency. Other imuunological changes include:
increased B2-microglobulin
decreased IL-2 production
polyclonal B-cell activation
decreased NK cell function
reduced delayed hypersensitivity responses

The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8(+) T-cell lymphocytosis associated with a CD8(+) T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also manifest itself independently of CD4(+) T-cell counts. The syndrome may present as a Sjögren-like disease that generally associates sicca signs with bilateral parotiditis, lymphadenopathy, and extra glandular organ involvement. The latter may affect the lungs, nervous system, liver, kidneys, and digestive tract. Anomalies of the respiratory system are often identified as lymphocytic interstitial pneumonia. Facial nerve palsy, aseptic meningitis or polyneuropathy are among the more frequent neurological features. Hepatic lymphocytic infiltration, lymphocytic interstitial nephropathy and digestive tract lymphocytic infiltration account for more rarely noted complications. Sicca syndrome, organomegaly and/or organ dysfunction associated with polyclonal CD8(+) T-cell organ-infiltration are greatly suggestive of DILS in people living with HIV.

The most probable diagnosis in this patient is conversion disorder.

There may be underlying tension regarding her musical career which could be manifesting as apparent limb weakness.

Conversion disorder typically involves loss of motor or sensory function. The patient doesn’t consciously feign the symptoms (factitious disorder) or seek material gain (malingering). Patients may be indifferent to their apparent disorder – la belle indifference – although this has not been backed up by studies.

Other options:
Unexplained symptoms
There are a wide variety of psychiatric terms for patients who have symptoms for which no organic cause can be found:

Somatization disorder
Multiple physical symptoms present for at least 2 years
the patient refuses to accept reassurance or negative test results

Hypochondriacal disorder
The persistent belief in the presence of an underlying serious disease, e.g. cancer.
The patient again refuses to accept reassurance or negative test results

Dissociative disorder
Dissociation is a process of ‘separating off’ certain memories from normal consciousness
Unlike conversion disorder, it involves psychiatric symptoms e.g. amnesia, fugue, stupor
Dissociative identity disorder (DID) is the new term for multiple personality disorder as is the most severe form of dissociative disorder

Munchausen’s syndrome
Also known as factitious disorder
The intentional production of physical or psychological symptoms

Malingering
Fraudulent simulation or exaggeration of symptoms with the intention of financial or another gain.

The first line treatment for ascites that is symptomatic is paracentesis. If it is not symptomatic, treatment could be with salt and fluid restriction as well as spironolactone. If spironolactone maximum dosage is reached, you can use furosemide additionally. Amiloride is not a diuretic that is recommended in this case.

Nerve conduction velocity is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Ultimately, conduction velocities are specific to each individual and depend largely on an axon’s diameter and the degree to which that axon is myelinated.
The cardiac action potential is a brief change in voltage (membrane potential) across the cell membrane of heart cells. Conduction speed varies:
Atrial conduction spreads along ordinary atrial myocardial fibres at 1 m/sec
AV node conduction 0.05 m/sec
Ventricular conduction Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec (this allows a rapid and coordinated contraction of the ventricles.

Speaking to your consultant is the most appropriate first action to take in this scenario. They are best placed to be able to take action to try and amend the situation. The consultant is also ultimately responsible for patient care and hterefore have a right to know if you are struggling, as this may affect patient care.
Arriving early and taking time off sick do not address the problem.

Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases, as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Use of Hyperbaric oxygen therapy (HBOT) for treatment of mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)
Principle of HBOT:
Exposing patients to 100 percent oxygen under supra-atmospheric conditions results in a decrease in the half-life (t1/2) of COHb, from , 90 min in atmospheric air to , 30 minutes. The amount of oxygen dissolved in the blood also rises from , 0.3 to 6 mL/dL, increasing the delivery of non-haemoglobin-bound oxygen to the tissues.

This girl most probably has Turner’s syndrome, which is caused by the absence of one set of genes from the short arm of one X chromosome.
Turner syndrome is a lifelong condition and needs lifelong oestrogen replacement therapy. Oestrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose oestrogens. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months; progestin can be added later.

In childhood, growth hormone therapy is standard to prevent short stature as an adult.

Fetal ovarian development seems to be normal in Turner syndrome, with degeneration occurring in most cases around the time of birth so pulsatile GnRH and luteinising hormone would be of no use.

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

The best treatment for a colovesicular fistula is surgery. This is the only definitive treatment. If the patient is a poor surgical candidate, there can be an attempt to manage them non-operatively, but this is absolutely NOT the MOST EFFECTIVE therapy.

Supraspinatus tendinopathy is a common and disabling condition that becomes more prevalent after middle age and is a common cause of pain in the shoulder. A predisposing factor is resistive overuse. This patient has the classic painful arc that is a sign of shoulder impingement characteristic of supraspinatus tendonitis.

The positive family history and the smoking make him an ideal candidate for a myocardial infarction. The chest pain is also a suggestive symptom. So troponin is needed to rule out MI.

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.

Again, remember the Hepatitis B serologies: In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have +HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, + anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. IN THIS CASE, the person is HBsAg+ for 6 months and everything else is negative, normal transaminase. They do not need antiviral therapy, but their serology should be monitored serially. There would be no reason to do a liver biopsy.

Ostium secundum atrial septal defects are known to cause stroke due to the passage of emboli from the right sided circulation to the left sided circulation. ECG shows tall, peaked P waves (usually best seen in leads II and V2) and prolongation of the PR interval, rSR pattern in leads V3 R and V1 as well as right axis deviation.

Zinc deficiency can present with alopecia, dermatitis, poor growth, increased susceptibility to infection, and cognitive deficiency. Magnesium deficiency can cause fatigue, cramping and an irregular EKG. Copper deficiency can present with fatigue and weakness. Chromium deficiency can present with hyperglycaemia.

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test—It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test—It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

Current guidelines recommend the use of ambrisentan, Bosentan (recommendation I, level of evidence A) and macitentan (I, B) in patients with PAH and WHO functional class II and III. In WHO functional class IV, the first-line drug is Epoprostenol and the recommendation for Endothelin receptor antagonists is weaker (IIb, C).

The patient is most likely to have Medullary Thyroid Carcinoma (MTC).
Sporadic, or isolated MTC accounts for 75% of cases and inherited MTC constitutes the rest.
Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.
A 24-hour urinalysis for catecholamine metabolites (e.g., vanillylmandelic acid [VMA], metanephrine) has to be done to rule out concomitant pheochromocytoma in patients with MEN type 2A or 2B, as Pheochromocytoma must be treated before MTC.

There are two main reasons for using combinations of chemotherapeutic agents rather than single agents. First, different drugs exert their effects through different mechanisms, therefore, carefully combining them will increase the number of tumour cells killed in each cycle as well as decrease their chances of developing drug resistance. Second, there may be an even greater effect with drugs that are synergistic.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumours: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumours, adrenocortical carcinoma (ACC), and leukaemia. LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history.

In asthma, a reversible increase in residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) may occur. There is a fall in FEV1, FVC and gas transfer.

The symptoms of ataxia, slurred speech and blurred vision are all suggestive of phenytoin toxicity. Cimetidine increases the efficacy of phenytoin by reducing its hepatic metabolism.

Phenytoin has a narrow therapeutic index (10-20 mg/L) and its levels are monitored by measuring the total phenytoin concentration.
Cimetidine is an H2 receptor antagonist used in the treatment of peptic ulcers. It acts by decreasing gastric acid secretion.
Cimetidine also has an inhibitory effect on several isoforms of the cytochrome enzyme system including the CYP450 enzymatic pathway. Phenytoin is metabolized by the same cytochrome P450 enzyme system in the liver.
Thus, the simultaneous administration of both these medications leads to an inhibition of phenytoin metabolism and thus increases its circulating levels leading to phenytoin toxicity.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

Bilateral median nerve dysfunction is suggestive of degenerative cervical myelopathy (DCM) rather than bilateral carpal tunnel syndrome. DCM should be suspected in elderly patients presenting with limb neurology. This patient’s twitches are probably fibrillations, a sign of lower motor neuron dysfunction.
Degenerative cervical myelopathy is associated with a delay in diagnosis. It is most commonly misdiagnosed as carpal tunnel syndrome. In one study, 43% of patients who underwent surgery for degenerative cervical myelopathy had been initially diagnosed with carpal tunnel syndrome.
Management of these patients should be by specialist spinal services (neurosurgery or orthopaedic spinal surgery). Decompressive surgery is the mainstay of treatment and has been shown to stop disease progression. Physiotherapy and analgesia do not replace surgical opinion, though they may be used alongside. Nerve root injections do not have a role in management.

Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in smooth muscle cells and maintains vascular function by inducing vasorelaxation in nearby blood vessels. GC-1 converts guanosine 5′-triphosphate (GTP) into cyclic guanosine 3′,5′-monophosphate (cGMP), which acts as a second messenger to improve blood flow.

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

Among the given options the most appropriate management in this patient would be ethanol and haemodialysis.

Ethanol competes with ethylene glycol for alcohol dehydrogenase and thus, helps manage a patient with ethylene glycol toxicity.

Ethylene glycol is a type of alcohol used as a coolant or antifreeze
Features of toxicity are divided into 3 stages:
Stage 1: (30 min to 12 hours after exposure) Symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness (CNS depression)
Stage 2: (12 – 48 hours after exposure) Metabolic acidosis with a high anion gap and high osmolar gap. Also tachycardia, hypertension
Stage 3: (24 – 72 hours after exposure) Acute renal failure

Management has changed in recent times:
Fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol.
Ethanol has been used for many years works by competing with ethylene glycol for the enzyme alcohol dehydrogenase this limits the formation of toxic metabolites (e.g. glycolaldehyde and glycolic acid) which are responsible for the hemodynamic/metabolic features of poisoning.
Haemodialysis has a role in refractory cases.

Mumps presents with a prodromal phase of general malaise and fever. On examination there is usually painful parotid swelling which has high chances of becoming bilateral. In OM with effusion there are no signs of infection and the only symptom is usually hearing loss. Acute otitis externa produces otalgia as well as ear discharge and itching. Acute OM produces otalgia and specific findings upon otoscopy. In acute mastoiditis the patient experiences ear discharge, otalgia, headache, hearing loss and other general signs of inflammation.

Hepatorenal syndrome is renal vasoconstriction that cannot overcome the effects of splanchnic vasodilation. Vasoactive mediators cause this splanchnic vasodilation, reducing SVR, which is sensed by the juxtaglomerular apparatus, activating the RAAS system, leading to renal vasoconstriction. However, the overall splanchnic vasodilation effect is greater than this renal vasoconstriction effect.

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having “non-ketotic diabetic acidosis.
It is most commonly associated with tissue hypoperfusion and states of acute circulatory failure.
Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source, early antimicrobial intervention, and resection of any potential ischemic regions. Reassessment of lactate levels for clearance assists ongoing medical management.

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.

Approximately one third of patients treated with radioiodine therapy develop transient hypothyroidism. Unless a patient is highly symptomatic, thyroxine replacement may be withheld if hypothyroidism occurs within the first 2 months of therapy. If it persists for longer than 2 months, permanent hypothyroidism is likely and replacement with T4 should be initiated.

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.

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.

Clozapine can cause neutropenia or agranulocytosis.

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics.

It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.

Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.

Other side effects include:
Hypotension, tachycardia
Fever, sedation, seizures (with high doses)
Appetite increase
Constipation
Heartburn
Weight gain
Extrapyramidal symptoms
Agranulocytosis
Neuroleptic malignant syndrome

This is most likely describing irritable bowel syndrome (IBS). Symptoms are either diarrhoea, constipation, or both, abdominal pain, bloating, with various durations. It is a functional, not organic, problem, as far as research shows at this point. It is essentially a diagnosis of exclusion. Treatment is a high fibre diet with fluids. Caffeine should be avoided as this can worsen symptoms. Full colonoscopy is not warranted at this time, neither is a barium enema. A wheat-free diet is not likely to help as there is no evidence they have an allergy to this.

Myotonic dystrophy is the most likely diagnosis here.
It is a multisystem disorder causing cognitive impairment, cataracts, cardiac problems and testicular atrophy, as well as affecting the muscles. Patients have muscle weakness, normally worse distally, and/or myotonia (which is worse in cold weather).
On examination, patients may also have frontal balding, a myopathic facies, bilateral ptosis, an ophthalmoplegia and wasting of facial muscles and other limb muscles. Myotonic dystrophy is associated with diabetes mellitus and pituitary dysfunction.
Diagnosis is normally based on clinical features with a characteristic electromyogram (EMG) of myotonic discharges. Creatine kinase is generally normal and muscle biopsy is non-specific.

Erythromycin is a bacteriostatic antibiotic. This means it stops the further growth of bacteria rather than directly destroying it. This is achieved by inhibiting protein synthesis. Erythromycin binds to the 23S ribosomal RNA molecule in the 50S subunit of the bacterial ribosome. This causes a blockage in the exiting of the peptide chain that is growing. Given that humans have 40S and 60S subunits, and do not have 50S subunits, erythromycin does not affect protein synthesis in human tissues.

Drug induced lupus is usually positive for antinuclear and antihistone antibodies, typically without renal or neurologic involvement. However, pulmonary involvement is common. Drugs that can induce lupus include isoniazid, hydralazine, procainamide, chlorpromazine, and other anticonvulsants.

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)

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti–sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors.

A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. Tumor suppressor genes can be grouped into categories including caretaker genes, gatekeeper genes, and landscaper genes; the classification schemes are continually evolving.
Examples include:
Gene Associated cancers
p53 Common to many cancers, Li-Fraumeni syndrome
APC Colorectal cancer
BRCA1 Breast and ovarian cancer
BRCA2 Breast and ovarian cancer
NF1 Neurofibromatosis
Rb Retinoblastoma
WT1 Wilm’s tumour

Spironolactone is an aldosterone antagonist which acts in the distal convoluted tubule. It is a potassium-sparing diuretic that prevents the body from absorbing too much salt and keeps the potassium levels from getting too low. Spironolactone is used to treat heart failure, high blood pressure (hypertension), or hypokalaemia (low potassium levels in the blood).

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis.

The carotid body consists of chemosensitive cells at the bifurcation of the common carotid artery that respond to changes in oxygen tension and, to a lesser extent, pH. In contrast to central chemoreceptors (which primarily respond to PaCO2) and the aortic bodies (which primarily have circulatory effects: bradycardia, hypertension, adrenal stimulation, and also bronchoconstriction), carotid bodies are most sensitive to PaO2. At a PaO2 of approximately 55-60 mmHg, they send their impulses via CN IX to the medulla, increasing ventilatory drive (increased respiratory rate, tidal volume, and minute ventilation). Thus, patients who rely on hypoxic respiratory drive will typically have a resting PaO2 around 60 mm Hg.

Chicken pox in adults may manifest with acute encephalitis, causing the confusional syndrome known as delirium. Blisters on the trunk favour the diagnosis. The trip to Italy however seems unimportant since the incubation period of chicken pox is 10 to 21 days.

The most probable diagnosis in this patient is post-traumatic stress disorder (PTSD). The first-line treatment for this patient would be cognitive behavioural therapy or eye movement desensitization and reprocessing therapy.

Post-traumatic stress disorder (PTSD) can develop in people of any age following a traumatic event, for example, a major disaster or childhood sexual abuse. It encompasses what became known as ‘shell shock’ following the first world war. One of the DSM-IV diagnostic criteria is that symptoms have been present for more than one month.

Clinical features:
Re-experiencing: flashbacks, nightmares, repetitive and distressing intrusive images
Avoidance: avoiding people, situations or circumstances resembling or associated with the event
Hyperarousal: hypervigilance for threat, exaggerated startle response, sleep problems, irritability and difficulty concentrating
Emotional numbing – lack of ability to experience feelings, feeling detached from other people
Depression
Drug or alcohol misuse
Anger

Management:
Following a traumatic event single-session interventions (often referred to as debriefing) are not recommended
Watchful waiting may be used for mild symptoms lasting less than 4 weeks
Trauma-focused cognitive-behavioural therapy (CBT) or eye movement desensitization and reprocessing (EMDR) therapy may be used in more severe cases
Drug treatments for PTSD should not be used as a routine first-line treatment for adults.
If drug treatment is used then paroxetine or mirtazapine are recommended.

The diagnosis of Hodgkin disease requires the identification of Reed-Sternberg cells in a characteristic cellular background. The normal cell of origin for the Reed-Sternberg cells remains unclear, with the predominance of evidence indicating a B or T lymphocyte.

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

Thalassaemias are a group of genetic disorders characterised by decreased production of either alpha or beta chains of haemoglobin (Hb). Beta thalassaemia trait is an autosomal recessive condition in which a disproportionate hypochromic, microcytic anaemia occurs—microcytosis is disproportionate to the Hb level. It is usually asymptomatic.

Microcytic anaemia in a female should raise the possibility of either gastrointestinal blood loss or menorrhagia. However, there is no history to suggest this in the aforementioned patient. This, combined with characteristic disproportionate microcytosis and raised HbA2 levels ( >3.5%), point towards beta thalassaemia trait.

Basophilic stippling is also seen in lead poisoning but the raised HbA2 levels cannot be explained in such a case.

Leaking of cerebrospinal fluid from the dura is the most likely explanation for post-lumbar puncture headaches. It is thought that ongoing leak of cerebrospinal fluid (CSF) through the puncture site causes ongoing CSF loss, leading to low pressure. A post-LP headache is typically frontal or occipital and occurs within three days. It is normally associated with worsening on standing and improvement when lying down. Treatment in severe cases includes an epidural blood patch, but most resolve on their own.

The definition of negative predictive value is the probability that the individuals with truly negative screening test don’t have Chlamydia. The equation is the following: Negative predictive value = Truly negative/(truly negative + false negative) = 172 / (172 + 5) = 172 / 177

Among the given options, an addiction to opiates is considered the strongest risk factor for committing suicide.

Other options:
Being a female – Being male is one of the most significant risk factors for suicide.
Being married – Having family support is an important protective factor for suicide.
Having five children – Having children at home is thought to be a protective factor.
Having never seen a general practitioner – Having a chronic mental or physical condition is however a risk factor for suicide.

Risk factors of suicide:
There are several factors shown to be associated with an increased risk of suicide:
Male sex
History of deliberate self-harm
Alcohol or drug misuse
History of mental illness (depression, schizophrenia)
History of chronic disease
Advancing age
Unemployment or social isolation/living alone
Being unmarried, divorced or widowed
Previous attempt to commit suicide.

Signs pointing towards suicidal intension:
Efforts to avoid discovery
Planning
Leaving a written note
Final acts such as sorting out finances
Violent method

Protective factors against suicide:
Family support
Having children at home
Religious belief

The most likely diagnosis is idiopathic Parkinson’s disease because of the unilateral presentation. In addition, cogwheel rigidity is a classic presenting symptom. Neuroleptic-induced parkinsonism is usually bilateral and symmetrical. Essential tremors do not cause rest tremors.

Osteoblastic (or sclerotic) bone metastases, characterized by deposition of new bone, present in prostate cancer, carcinoid, small cell lung cancer, Hodgkin lymphoma or medulloblastoma.

Giardiasis also known as travellers diarrhoea is caused by Giardia lamblia, which is an anaerobic parasite affecting the small intestine. It can lead to diarrhoea, flatulence, abdominal cramps, malodourous greasy stools and intestinal malabsorption. It can also cause bloody diarrhoea. The investigation of choice is stool examination for trophozoites and cysts. It is treated by metronidazole and tinidazole as first line therapies.

Diagnosis of multiple myeloma (MM) is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

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.

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.

A Mongolian spot can be present in new born babies which usually appears over the back and fades with time. There is nothing to worry about.

Synacthen test interpretation:
– Basal Cortisol level should be greater than 180nmol/L
– 30min or 60min Cortisol should be greater than 420nmol/L (whatever the basal level)
– The increment should be at least 170nmol/L, apart from in severely ill patients where adrenal output is already maximal.
The patient’s results show that she has Acute Adrenal Insufficiency
The guidelines include the following recommendations for emergency treatment:
Administer hydrocortisone: Immediate bolus injection of 100 mg hydrocortisone intravenously or intramuscularly followed by continuous intravenous infusion of 200 mg hydrocortisone per 24 hours (alternatively, 50 mg hydrocortisone per intravenous or intramuscular injection every 6 h)
Rehydrate with rapid intravenous infusion of 1000 mL of isotonic saline infusion within the first hour, followed by further intravenous rehydration as required (usually 4-6 L in 24 h; monitor for fluid overload in case of renal impairment and elderly patients)
Contact an endocrinologist for urgent review of the patient, advice on further tapering of hydrocortisone, and investigation of the underlying cause of the disease, including the diagnosis of primary versus secondary adrenal insufficiency
Tapering of hydrocortisone can be started after clinical recovery guided by an endocrinologist; in patients with primary adrenal insufficiency, mineralocorticoid replacement must be initiated (starting dose 100 μg fludrocortisone once daily) as soon as the daily glucocorticoid dose is below 50 mg of hydrocortisone every 24 hours

Infective causes of hair loss include:
Dissecting cellulitis
Fungal infections (such as tinea capitis)
Folliculitis
Secondary syphilis
Demodex folliculorum
Lupus erythematosus (hair loss may be permanent due to scarring of the hair follicles).
Psoriasis and seborrheic dermatitis commonly involve the scalp but do not produce hair loss.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Chiari Type I malformation usually presents with symptoms due to brain stem and lower cranial nerve dysfunction, which includes DBN.

Though a common community pathogen, Staphylococcus Aureas is found twice as frequently in pneumonias in hospitalized patients. It often attacks the elderly and patients with CF and arises as a co-infection with influenza viral pneumonia. The clinical course is characterized by high fevers, chills, a cough with purulent bloody sputum, and rapidly progressing dyspnoea. The gross pathology commonly reveals an acute bronchopneumonia pattern that may evolve into a necrotizing cavity with congested lungs and airways that contain a bloody fluid and thick mucoid secretions.

This patient has hypercalcaemia due to hyperparathyroidism. However, the intestinal absorption of calcium is mainly controlled by 1,25 dihydroxy-vitamin D. Under the influence of calcitriol (active form of vitamin D), intestinal epithelial cells increase their synthesis of calbindin (calcium-binding carrier protein) necessary for active calcium ion absorption.

Given she is not showing signs of systemic illness, you do not need to treat for an acute flair (which would be steroids), but you need to put her on maintenance medication. Oral ASA would be the best option for this, it is first line. You cannot give rectal ASA because the location of her disease is in the ascending colon and the enema will not reach.

Three classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.

Fibrate is used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more. Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not.

Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (>4 g/d), triglycerides are reduced.

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

The question describes a patient who has had an ileal resection. Bile acids are reabsorbed in the distal ileum. Since this has been resected in this patient, one would expect her to have malabsorption of bile acids, causing her diarrhoea. This is a more likely correct answer than a Crohn’s flare, bacterial overgrowth, gastroenteritis, or tropical sprue, given the details included in the question prompt.

Fc Receptors include the IgG receptors (FcγR), high-affinity IgE receptor (FcεRI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcγRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Fc receptors, the receptors for the Fc region of immunoglobulins, play an essential role in antibody-dependent immune responses. Fc receptors are detected on many types of hematopoietic cells including macrophages, neutrophils, dendritic cells, eosinophils, basophils, mast cells, and NK cells. Plasma cells produce five classes of antibodies, IgA, IgD, IgE, IgG and IgM. Fc receptors with an Ig superfamily related structure exist that correspond to each of these classes of immunoglobulins.

Live virus vaccines include: Vaccinia (smallpox), Measles, Mumps, Rubella (MMR combined vaccine), Varicella (chickenpox), Influenza (nasal spray), Rotavirus, Zoster (shingles) and Yellow fever. Inactivated vaccines are Polio (IPV), Hepatitis A and Rabies.

Vestibular damage is a neurological side effect of streptomycin.

Streptomycin is an aminoglycoside bactericidal antibiotic. It is used in the treatment of tularaemia and resistant mycobacterial infections.
The most common neurological side-effect is vestibular damage leading to vertigo and vomiting.
Cochlear damage is less frequent and results in deafness.
Other side-effects include rashes, angioneurotic oedema, and nephrotoxicity.

The following are conditions commonly associated with pyoderma gangrenosum:
Inflammatory bowel disease:
– Ulcerative colitis
– Crohn’s disease
Arthritides:
– Rheumatoid arthritis
– Seronegative arthritis
Haematological disease:
– Myelocytic leukaemia[8]
– Hairy cell leukaemia
– Myelofibrosis
– Myeloid metaplasia
– Monoclonal gammopathy
Autoinflammatory disease:
– Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)
– Granulomatosis with polyangiitis

B-type natriuretic peptide (BNP) is secreted mainly from the left ventricle and it is secreted as a response to stretching caused by increased ventricular blood volume.

Chronic hepatitis B patients have an increased risk of hepatocellular carcinoma. In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have+HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, +anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. It is important to remember these serologies, it will get you a lot of points on the test.

Palmar xanthomas are found in type III hyperlipoproteinemia. Her total cholesterol level and triglyceride level support the diagnosis.

Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas (rare), and primary thyroid sarcomas (rare).
Hürthle cell carcinoma is a rare thyroid malignancy that is often considered a variant of follicular carcinoma.
– Papillary and Follicular carcinoma are slow-growing tumours
– Sporadic cases of Medullary thyroid carcinoma also typically manifest with painless solitary thyroid nodules in the early stages.
– Anaplastic thyroid carcinoma has the most aggressive biologic behaviour of all thyroid malignancies and has one of the worst survival rates of all malignancies in general. It manifests as a rapidly growing thyroid mass in contrast to a well-differentiated carcinoma, which are comparatively slow-growing. Patients commonly present with associated symptoms due to local invasion. Hoarseness and dyspnoea resulting from the involvement of the recurrent laryngeal nerve and airway occur in as many as 50% of patients.
– Almost all patients with primary thyroid lymphoma have either a clinical history or histological evidence of chronic lymphocytic thyroiditis. The risk of primary thyroid lymphoma increases 70-fold in patients with chronic lymphocytic thyroiditis compared with the general population. Regional and distant lymphadenopathy is common.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive chronic lung disease. Typically, COPD includes emphysema and chronic bronchitis. COPD is characterized by the restriction of airflow into and out of the lungs. The obstruction of airflow makes breathing difficult. The causes of COPD include smoking, long-term exposure to air pollutants and a rare genetic disorder.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) developed the GOLD Staging System. In the GOLD System, the forced expiratory volume in one second (FEV1) measurement from a pulmonary function test is used to place COPD into stages. Often, doctors also consider your COPD symptoms.

COPD has four stages. The stages of COPD range from mild to very severe. COPD affects everyone differently. Because COPD is a progressive lung disease, it will worsen over time.
The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 63 which falls within the stage 2 or moderate COPD.

Illness anxiety disorder (IAD) is a recent term for what used to be diagnosed as hypochondriasis, or hypochondrial disorder. People diagnosed with IAD strongly believe they have a serious or life-threatening illness despite having no, or only mild, symptoms.

Symptoms of IAD may include:
-Excessive worry over having or getting a serious illness.
-Physical symptoms are not present or if present, only mild. If another illness is present, or there is a high risk for developing an illness, the person’s concern is out of proportion.
-High level of anxiety and alarm over personal health status.
-Excessive health-related behaviours (e.g., repeatedly checking body for signs of illness) or shows abnormal avoidance (e.g., avoiding doctors’ appointments and hospitals).
-Fear of illness is present for at least six months (but the specific disease that is feared may change over that time).
-Fear of illness is not due to another mental disorder.

Spinal cord hemisection, also known as Brown-Sequard syndrome, is associated with symptoms affecting one spinothalamic and one corticospinal tract. Symptoms include ipsilateral paralysis, loss of vibration and position sense, and hyperreflexia below the level of the lesion. Contralateral loss of pain and temperature sensation is also seen, usually beginning 2-3 segments below the level of the lesion.

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.

Patients with diabetes often develop ophthalmic complications, the most common and potentially most blinding of these complications is diabetic retinopathy.
The following are the 5 stages in the progression of diabetic retinopathy:
1. Dilation of the retinal venules and formation of retinal capillary microaneurysms.
2. Increased vascular permeability.
3. Vascular occlusion and retinal ischemia.
4. Proliferation of new blood vessels on the surface of the retina.
5. Vitreous haemorrhage and contraction of the fibrovascular proliferation.
The first 2 stages of diabetic retinopathy are known as background or nonproliferative retinopathy. Initially, the retinal venules dilate, then microaneurysms (tiny red dots on the retina that cause no visual impairment) appear. As the microaneurysms or retinal capillaries become more permeable, hard exudates appear, reflecting the leakage of plasma.

Mild nonproliferative diabetic retinopathy (NPDR) or background diabetic retinopathy is indicated by the presence of at least 1 microaneurysm, while neovascularization is the hallmark of Proliferative Diabetic Retinopathy (PDR).

Causes for ST segment elevation other than myocardial infarction
Natural variants
-Early repolarization
-Left ventricular hypertrophy and hypertrophic cardiomyopathy
-Left bundle branch block
Artefacts
-Leads mispositioning
-Electrical cardioversion
Cardiovascular diseases
-Pericarditis/ Myocarditis
-Aortic dissection
-Prinzmetal’s angina
-Takotsubo Cardiomyopathy
-Brugada Syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia
Pulmonary diseases
-Pulmonary thromboembolism
-Pneumothorax
-Atelectasis and pulmonary metastases
Gastrointestinal diseases
-Acute pancreatitis
-Acute cholecystitis
Other conditions
-Hyperkalaemia
-Drug induced ST segment elevation (e.g. – clozapine)
-Haemorrhagic cerebrovascular disease

Coronary artery disease and myocardial infarction can be excluded with a negative angiogram and a slightly elevated troponin. Hypertrophic cardiomyopathy can be excluded with cardiovascular MR findings. Left ventricular aneurysm usually occurs following a myocardial infarction, but there is no positive history for that. The characteristic findings on cardiovascular MR confirms the diagnosis of Takotsubo cardiomyopathy.

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.

Nitric oxide, known as an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes and is a signaling molecule in many physiological and pathological processes in humans.
One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron.

Vincristine is part of the antimitotic agents, cell cycle specific (M phase). It binds to microtubules in the spindle apparatus and prevents their proper function, finally arresting mitosis.

A very common complication after ERCP is post-ERCP pancreatitis, which based on the clinical scenario , this man has. The treatment for this is pain control, lots of intravenous fluids, and traditionally bowel rest, although more recent evidence suggests early feeding is better.

Klinefelter syndrome (KS), the most common human sex chromosome disorder 47,XXY. It is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia) and gynecomastia in late puberty. If Klinefelter syndrome is not diagnosed prenatally, a patient with 47,XXY karyotype may demonstrate various subtle, age-related clinical signs that would prompt diagnostic testing. These include the following:
Infants: Hypospadias, small phallus, cryptorchidism.
Toddlers: Developmental delay (especially expressive language skills), hypotonia.
Older boys and adolescent males: Tall stature; delayed or incomplete pubertal development with eunuchoid body habitus; gynecomastia; small, firm testes; sparse body hair.

From childhood with progression to early puberty, the pituitary-gonadal function observed is within normal limits for 47,XXY males.
At mid puberty and later, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations rise to hyper-gonadotropic levels, inhibin B levels fall until they are undetectable, and testosterone levels are at low or low-normal levels after an initial increase.

Fragile X syndrome, also termed Martin-Bell syndrome or marker X syndrome, is the most common cause of inherited mental retardation, intellectual disability, and autism.
However, the patient here does not have any mental disabilities as he already works as a clerk, and that too would make Down’s Syndrome less likely.

Classic Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) are rare genetic conditions that encompass the spectrum of isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. Hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome, in contrast to patients with idiopathic hypogonadotropic hypogonadism, whose sense of smell is normal.

Scleritis, or inflammation of the sclera, is usually painful whereas episcleritis is not painful.

Keratoconjunctivitis sicca is usually bilateral and associated more with dryness, burning and itching.

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms of bronchiectasis include:
– a persistent productive cough
– breathlessness.

The 3 most common causes in the UK are:
– a lung infection in the past, such as pneumonia or whooping cough, that damages the bronchi
– underlying problems with the immune system (the body’s defence against infection) that make the bronchi more vulnerable to damage from an infection
– allergic bronchopulmonary aspergillosis (ABPA) – an allergy to a certain type of fungi that can cause the bronchi to become inflamed if spores from the fungi are inhaled

Primary aldosteronism now is considered one of the more common causes of secondary hypertension (HTN).
Individuals with primary aldosteronism may present with hypokalaemia metabolic alkalosis; however, as many as 38% of patients with primary aldosteronism may be normokalaemia at presentation.
Routine laboratory studies can show hypernatremia, hypokalaemia, and metabolic alkalosis resulting from the action of aldosterone on the renal distal convoluted tubule (DCT) (i.e., enhancing sodium reabsorption and potassium and hydrogen ion excretion).
Plasma aldosterone/plasma renin activity ratio is used for screening because it is fairly constant over many physiologic conditions.

The patient is clinically free, so Cushing diseases can be exclude.

Chvostek and Trousseau signs can be elicited in patients with hypocalcaemia. Chvostek sign is the twitching of the upper lip with tapping on the cheek 2 cm anterior to the earlobe, below the zygomatic process overlying the facial nerve. Trousseau sign (a more reliable sign present in 94% of hypokalaemic individuals and only 1% to 4% of healthy people) is the presence of carpopedal spasm observed following application of an inflated blood pressure cuff over systolic pressure for 3 minutes in hypokalaemic patients.

Barrett’s oesophagus is the transformation of the normal squamous epithelium of the oesophagus to columnar, intestinal type epithelium. It is often seen in patients with reflux and there is a 50-100 fold increased risk of oesophageal adenocarcinoma in patients with Barrett’s oesophagus.

The most probable diagnosis is Herpes Simplex infection. Topical Acyclovir can be used in early stages.

Blurring of vision and dry mouth are antimuscarinic side-effects that are more common with imipramine than other types of tricyclic antidepressants.

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

Mechanism of action: Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (this, may give rise to seizures).

Common side-effects:
Drowsiness
Dry mouth
Blurred vision
Constipation
Urinary retention

Low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headaches (both tension and migraine).
Lofepramine has a lower incidence of toxicity in overdose
Amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose.

After renal transplantation, cytomegalovirus has been identified to affect 1/4 of the post-op patients. It is the most common viral infection causing morbidity and mortality in post-op patients in the first 3 months.

A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing a cross-section at intervals through time.
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Relative risk is used in the statistical analysis of the data of experimental, cohort and cross-sectional studies, to estimate the strength of the association between treatments or risk factors, and outcomes.

This patient’s symptoms of anaemia, leukopenia, and elevated non-albumin protein concentration with fatigue and weight loss, point to myeloma. Thus plasma protein electrophoresis or Serum Protein Electrophoresis (SPE) is indicated when there is suspicion of myeloma.

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.

Methotrexate lung disease (pneumonitis and fibrosis) is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given as disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy. Methotrexate withdrawal is indicated in such cases.

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.

Gram-staining of the blood cultures of this patient will show gram-positive cocci. Gram-negative bacilli used to be the most common pathogen isolated in neutropenic sepsis, but currently, the most common pathogens are gram-positive organisms. Staphylococcus epidermidis is the most frequent causative agent, and following this are other staphylococci and streptococci species.

Neutropenic sepsis is a relatively common complication of cancer therapy—usually chemotherapy. It most commonly occurs 7-14 days after the treatment and is usually 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 includes starting empirical antibiotic therapy (piperacillin with tazobactam—Tazocin) immediately. Following this initial treatment, the patient is usually assessed by a specialist and risk-stratified to see if outpatient treatment may be possible. However, if the patient remains febrile and unwell after 48 hours, an alternative antibiotic such as meropenem is often prescribed with or without vancomycin. If patient is still not responding after 4-6 days, then an antifungal, such as amphotericin B, is started after carrying out investigations (e.g. HRCT and Aspergillus PCR) to determine the likelihood of systemic fungal infection.

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.

The most common type of Hodgkin’s lymphoma (HL) is nodular sclerosing.

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

According to the histological classification, there are four types of HL:

1. Nodular sclerosing: most common (around 70%), more common in women, associated with lacunar cells, good prognosis

2. Mixed cellularity: Around 20%, associated with a large number of Reed-Sternberg cells, good prognosis

3. Lymphocyte-predominant: Around 5%, Reed-Sternberg cells with nuclei surrounded by a clear space found, best prognosis

4. Lymphocyte-depleted: rare, worst prognosis

Characteristic findings on patients suffering from diphtheria are the grey membrane on the uvula and tonsils together with the low grade fever and dyspnoea. It’s of great importance that the patient has recently been to India where there is a know prevalence.

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.)

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.

The best option would be the combination of ampicillin and gentamycin. Changing to IV amoxicillin+gentamycin is however the best among the given choices here.

This patient has a combination of right cerebellar dysfunction with right-sided cranial nerve palsies (VI, VII, and VIII). The magnetic resonance imaging (MRI) shows a calcified meningioma within the right cerebellar pontine area, which would account for these findings. The cerebrospinal fluid (CSF) analysis shows oligoclonal bands, however, these are matched in the serum, which reflects a systemic inflammatory response from his rheumatoid arthritis.

The MRI scan and CSF analysis would not be consistent with progressive multiple sclerosis. The progressive nature of her symptoms would be against a diagnosis of brainstem infarct, and one would expect more pyramidal signs in the peripheral nervous system.

The classic triad of symptoms in patients with aortic stenosis is chest pain, heart failure and syncope. Pulsus parvus et tardus, pulsus alternans, hyperdynamic left ventricle, reversed splitting of the S2, prominent S4 and systolic murmur are some of the common findings of aortic stenosis. A calcified aortic valve is found in almost all adults with hemodynamically significant aortic stenosis.

Campylobacter is the most likely cause of diarrheal illness often due to undercooked meat being ingested. It is also a major cause of traveller’s diarrhoea. Sufficient fluid replacement and anti-emetics are indicated first followed by the antibiotic, Erythromycin although antibiotic treatment in adults is still in question. Ciprofloxacin and Tetracycline may also be effective.

Moxonidine and alpha-methyl dopa are centrally acting antihypertensives and modify blood pressure through modifying sympathetic activity.

Other options:
Verapamil is a calcium antagonist.
Minoxidil and hydralazine are both vasodilators.
Phenoxybenzamine is an alpha-blocker.

Adverse effects:
Dry mouth and somnolence were the most frequently reported adverse events, followed by headache, dizziness, nausea and allergic skin reactions.

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).

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 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.

A grossly elevated APTT may be caused by heparin therapy, haemophilia, or antiphospholipid syndrome. A normal factor VIIIc activity, however, points towards the diagnosis of haemophilia B, which is the deficiency of factor IX in the blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to the deficiency of clotting factor VIII and is more common than haemophilia B, accounting for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

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.

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.

This clinical scenario describes pernicious anaemia. Anti-intrinsic factor (IF) antibodies are most specific for pernicious anaemia. Antigastric parietal cell antibodies have a higher sensitivity but are less specific for pernicious anaemia. The other antibodies listed are not related to pernicious anaemia. Anti-TTG is seen with Celiac’s disease, anti-TPO is seen with thyroid disease, GAD is seen with type I diabetes, but this does not explain her anaemia.

Glioblastoma multiforme, also considered as grade IV astrocytoma, is the most malignant form of the tumour and accounts for about 20% of all cerebral tumours. These often remain clinically silent until they have reached a large enough size. In adults, glioblastoma multiforme usually occurs in the cerebral hemispheres, especially the frontal and temporal lobes of the brain. About half occupy more than one hemisphere at presentation, and some are multicentric. Biopsy shows high cellularity with mitoses, pleomorphism, and vascular hyperplasia. Prognosis is extremely poor, with only 20% surviving beyond 1 year and 10% beyond 2 years.

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.

COPD is commonly associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favourable effects on pulmonary hemodynamics.

Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD, according to 2 landmark trials, the British Medical Research Council (MRC) study and the US National Heart, Lung and Blood Institute’s Nocturnal Oxygen Therapy Trial (NOTT). Hypoxemia is defined as PaO2 (partial pressure of oxygen in arterial blood) of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used for 15-19 hours per day.

Therefore, specialists recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythaemia, or cor pulmonale. Patients should be evaluated after 1-3 months after initiating therapy, because some patients may not require long-term oxygen.

Achondroplasia is the most common type of short-limb disproportionate dwarfism. A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. All people with achondroplasia have a short stature.
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Examination of the infant after birth shows increased front-to-back head size. There may be signs of hydrocephalus. It may be diagnosed radiographically at birth, or becomes obvious within the first year with disparity between a large skull, normal trunk length and short limbs.

Vasopressin, also called antidiuretic hormone (ADH), regulates the tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels.. An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume. In high concentrations may also raise blood pressure by inducing moderate vasoconstriction.

This question describes Charcot’s triad– fever, RUQ pain, and jaundice, which is seen in ascending cholangitis. Reynold’s pentad is a worsened version of this, where you have RUQ pain, fever, jaundice, hypotension, and altered mental status. Risk factors for gallstones are the 4F’s- female, fat, forty, and fertile. You would not have the elevated bilirubin, ALP, transaminases with a kidney stone or in peptic ulcer disease. Hepatitis would not cause elevation of bilirubin.

The most widely used prognostic predictors for acetaminophen over-ingestion is King’s College Criteria, which is: arterial PH < 7.3 after fluid resuscitation, Cr level > 3.4, PT > 1.8x control or > 100s, or INR > 6.5, and Grave III or IV encephalopathy.

The patient’s history of a blood transfusion and lab results showing a markedly low C4 (with normal C3), elevated rheumatoid factor, and elevated serum IgM is highly suggestive of hepatitis C-associated cryoglobulinaemic vasculitis. Testing for Cryoglobulins will confirm this suspicion.

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols.

SIGN produced guidelines in 2008 on the management of migraines. Key points include that if patients have migraines with aura then the combined oral contraceptive (COC) is absolutely contraindicated due to an increased risk of stroke (relative risk 8.72).

The combination of Insulinoma and Parathyroid diseases is suggestive of MEN 1 syndrome.
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumour syndrome inherited in an autosomal dominant manner and characterized by a predisposition to a multitude of endocrine neoplasms primarily of parathyroid, entero-pancreatic, and anterior pituitary origin, as well as non-endocrine neoplasms.
Other endocrine tumours in MEN1 include foregut carcinoid tumours, adrenocortical tumours, and rarely pheochromocytoma. Nonendocrine manifestations include meningiomas and ependymomas, lipomas, angiofibromas, collagenomas, and leiomyomas.

Primary hyperparathyroidism (PHPT), due to parathyroid hyperplasia is the most frequent and usually the earliest expression of MEN-1, with a typical age of onset at 20–25 years.

The cause of Vitiligo is typically unknown. It is believed to be due to genetic susceptibility that is triggered by an environmental factor such that an autoimmune disease occurs. This results in the destruction of skin pigment cells. Risk factors include a family history of the condition or other autoimmune diseases, such as hyperthyroidism, alopecia areata, and pernicious anaemia. Vitiligo is classified into two main types: segmental and non-segmental. Most cases are non-segmental meaning they affect both sides and typically get worse with time. The prevalence of vitiligo is 0.5-1% of populations worldwide. Typical sites include backs of hands, wrists, knees, neck and around body orifices. The Koebner phenomenon refers to skin lesions appearing on lines of trauma. This occurs in vitiligo secondary to scratching.

CMV is a common viral infection that can be transmitted from a pregnant woman to her unborn child, leading to congenital CMV infection. Congenital CMV infection can result in a range of symptoms and complications in newborns, including deafness. In fact, CMV is one of the leading causes of non-genetic sensorineural hearing loss in children.

Given the mother’s history of symptoms during pregnancy and the concern for deafness in the infant, CMV should also be considered as a potential cause.

Silicosis is a common occupational lung disease that is caused by the inhalation of crystalline silica dust. Silica is the most abundant mineral on earth. Workers that are involved for example in construction, mining, or glass production are among the individuals with the highest risk of developing the condition. Acute silicosis causes severe symptoms (e.g., exertional dyspnoea, cough with sputum) and has a very poor prognosis.
Chronic silicosis has a very variable prognosis and affected individuals may remain asymptomatic for several decades. However, radiographic signs are usually seen early on. Typical radiographic findings are calcifications of perihilar lymph nodes, diffuse ground glass opacities, large numbers of rounded, solitary nodules or bigger, confluent opacities. Avoiding further exposure to silica is crucial, especially since the only treatment available is symptomatic (e.g., bronchodilators). Silicosis is associated with an increased risk of tuberculosis and lung cancer. Berylliosis typically affects individuals who are exposed to aerospace industry. Histoplasmosis and tuberculosis do not form eggshell calcifications.

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.

Renal biopsy in this patient will most likely show thickened glomerular basement membrane with deposits of IgG and C3 as a result of membranous glomerulonephritis that has caused the nephrotic syndrome in this patient. Membranous glomerulonephritis in this case is most likely associated with an underlying bronchial carcinoma, consistent with the patient’s smoking history and physical presentation.

The most likely diagnosis is chronic tophaceous gout, which is classically associated with chronic renal impairment or long term diuretic therapy. There is tophus formation due to urate crystal deposition in and around the joint. These tophi can also form in the bones and soft tissues. Renal manifestations with uric acid include nephrolithiasis and uric acid nephropathy. Whenever there is an acute on chronic attack of gout, the inciting cause must be established and in case of diuretic use, they should be immediately replaced with another medication. Allopurinol is never started during an acute episode. it is first allowed to settle before administration of allopurinol. Although dietary restriction must be observed in people with a propensity of gout, this scenario clearly presents diuretics as the cause.

If the INR in the range of 2-3 has still resulted in thrombosis, the target INR is increased to 3-4. However, because the risk of bleeding increases as the INR rises, the INR is closely monitored and adjustments are made as needed to maintain the INR within the target range.

Relief of symptoms with food suggests duodenal ulceration, for which the pain gets worse on an empty stomach. In chronic pancreatitis, you would expect worsening of symptoms with food.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.

MDMA commonly known as ecstasy or molly, is a psychoactive drug primarily used as a recreational drug. The desired effects include altered sensations, increased energy, empathy, and pleasure. Features of MDMA abuse include hyponatraemia, tachycardia, hyperventilation, and hyperthermia.

The sciatic neve originates in the sacral plexus, mainly from spinal segments L5-S2. It supplies muscles that cause extension of the thigh and flexion of the leg. It divides into two main branches, the tibial nerve and common peroneal nerve, which are responsible for all foot movements. Anterior thigh and medial leg sensory loss is typical of a femoral nerve lesion. The femoral nerve also mediates flexion of the hip.

A patient with a gradual onset of schizophrenia is to be associated with a poor prognosis.

Schizophrenia is a functional psychotic disorder characterized by the presence of delusional beliefs, hallucinations, and disturbances in thought, perception, and behaviour.

Clinical features:
Schneider’s first-rank symptoms may be divided into auditory hallucinations, thought disorders, passivity phenomena, and delusional perceptions:

Auditory hallucinations of a specific type:
Two or more voices discussing the patient in the third person
Thought echo
Voices commenting on the patient’s behaviour

Thought disorder:
Thought insertion
Thought withdrawal
Thought broadcasting

Passivity phenomena:
Bodily sensations being controlled by external influence
Actions/impulses/feelings – experiences which are imposed on the Individual or influenced by others

Other features of schizophrenia include
Impaired insight (a feature of all psychoses)
Incongruity/blunting of affect (inappropriate emotion for circumstances)
Decreased speech
Neologisms: made-up words
Catatonia
Negative symptoms: incongruity/blunting of affect, anhedonia (inability to derive pleasure), alogia (poverty of speech), avolition (poor motivation).

Treatment:
For the initial treatment of acute psychosis, it is recommended to commence an oral second-generation antipsychotics such as aripiprazole, olanzapine, risperidone, quetiapine, etc.
Once the acute phase is controlled, switching to a depot preparation like aripiprazole, paliperidone, zuclopenthixol, fluphenazine, haloperidol, pipotiazine, or risperidone is recommended.
Cognitive-behavioural therapy (CBT) and the use of art and drama therapies help counteract the negative symptoms of the disease, improve insight, and assist relapse prevention.
Clozapine is used in case of treatment resistance.

The patient’s chronic renal failure causes decreased renal hydroxylation of vitamin D which leads to decreased calcium absorption in the gut. Simultaneously, there is also decreased renal excretion of phosphate, and this combination of factors results in increased PTH levels.

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.

One of the questions the therapist poses himself while informing a patient is: whom shall I inform about the diagnosis, treatment and prognosis? If we unconditionally accepted the view that information belongs to the patient from an ethical and legal standpoint, we would automatically exclude the partner and the family. Therefore, the therapist should raise another question: what is the benefit to the patient? To answer the question and the resulting dilemma, we have to leverage the long experience of family therapy and tailor it to the cases we are dealing with. It should be taken into consideration that patient and family are a dynamic system which was balanced before the onset of the disease, but is now disrupted, entering into crisis. Therefore, the denial mechanisms and personality characteristics we have previously elaborated on, and communication among members play a crucial role in determining the information strategy and the way family should be approached. In this particular case, the most appropriate person to inform the patient is the consultant, meaning the one currently responsible for the patient’s care. The patient most probably has already developed some form of close and trustful relationship with his consultant.

Because the patient has chronic kidney disease, we need to consider the associated adverse effects of trying to maintain normal haemoglobin levels (14-18g/dl in this patient) and instead only instigate therapy when the level falls below 11 g/dl. Thus, in this case we should just monitor the haemoglobin levels and not initiate therapy just yet.

Studies have shown that benefits of Long-tern oxygen therapy (LTOT) include improved exercise tolerance, with improved walking distance, and ability to perform daily activities, reduction of secondary polycythaemia, improved sleep quality and reduced sympathetic outflow, with increased sodium and water excretion, leading to improvement in renal function.

Protein-calorie malnutrition is observed in almost 50% of dialysis patients, contributing to increased morbidity and mortality. All the other complications listed can usually be prevented thanks to modern-day dialysis techniques.

Pseudomembranous colitis is caused by a C. difficile infection that causes membranes to form on the colon wall. It is caused most commonly by broad-spectrum antibiotics. This would include cephalosporins, broad-spectrum penicillin, and clindamycin. Macrolides and quinolones have also been reported as potential aetiologies, but much less commonly.

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.

Tuberculous lymphadenitis is a chronic, specific granulomatous inflammation of the lymph node with caseation necrosis, caused by infection with Mycobacterium tuberculosis or a related bacteria. The characteristic morphological element is the tuberculous granuloma (caseating tubercle).

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.

According to NICE guidelines (2013) all people who have had an acute MI treatment should be offered with ACE inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), a beta-blocker and a statin.

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.