Methadone and cocaine can cause QT prolongation through the direct effects on the resting membrane potential. Methadone can increase QT dispersion in addition to QT interval. Methadone inhibits the Human Ether-a-go-go Related Gene (hERG) and causes QTc prolongation and development of Torsades de point. Brugada-like syndrome is another condition found in methadone users which predisposes the users to life-threatening ventricular tachycardia and sudden cardiac death.

The patient has a history of:
1 – Balance and gait disturbance – falls and broad based clumsy gait
2 – Dementia – strange behaviour and disorientation to time and place
3 – Urinary incontinence – episodes of enuresis.
All of the symptoms constitute the classic triad of normal pressure hydrocephalus.

Beta-blockers are drugs of choice for patients with LQTS. The protective effect of beta-blockers is related to their adrenergic blockade, which diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.

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.

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.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

Erythropoietin (EPO) is used to distinguish between primary and secondary polycythaemia. Secondary polycythaemia can be caused by tumours in the kidney that may secrete EPO or EPO-like proteins.

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.

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.

The symptoms and signs of carbon monoxide poisoning are variable and nonspecific. The most common symptoms of CO poisoning are headache, dizziness, weakness, nausea, vomiting, chest pain, and altered mental status.

The clinical presentation of CO poisoning is the result of its underlying systemic toxicity. Its effects are caused not only by impaired oxygen delivery but also by disrupting oxygen utilization and respiration at the cellular level, particularly in high-oxygen demand organs (i.e., heart and brain).

Symptoms of severe CO poisoning include malaise, shortness of breath, headache, nausea, chest pain, irritability, ataxia, altered mental status, other neurologic symptoms, loss of consciousness, coma, and death; signs include tachycardia, tachypnea, hypotension, various neurologic findings including impaired memory, cognitive and sensory disturbances; metabolic acidosis, arrhythmias, myocardial ischemia or infarction, and noncardiogenic pulmonary edema, although any organ system might be involved.

Photosensitivity is a common adverse effect of cardiology drugs including amiodarone and thiazide diuretics. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin 2 receptor blockers (A2RBs) commonly also cause rashes only some of which appear to be photosensitive.

Among the following hypertensives, lisinopril (an ACE inhibitor) is contraindicated in patients who are planning for pregnancy.

Per the NICE guidelines, when treating the woman in question, she should be treated as if she were pregnant given the absence of effective contraception.
ACE inhibitors such as lisinopril are known teratogens and most be avoided.

Drugs contraindicated in pregnancy:
Antibiotics
Tetracyclines
Aminoglycosides
Sulphonamides and trimethoprim
Quinolones

Other drugs:
ACE inhibitors, angiotensin II receptor antagonists
Statins
Warfarin
Sulfonylureas
Retinoids (including topical)
Cytotoxic agents
The majority of antiepileptics including valproate, carbamazepine, and phenytoin are known to be potentially harmful.

Ebstein’s anomaly is characterised by apical displacement and adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium, thereby displacing the functional tricuspid orifice apically and dividing the right ventricle into two portions. The main haemodynamic abnormality leading to symptoms is tricuspid valve incompetence. The clinical spectrum is broad; patients may be asymptomatic or experience right-sided heart failure, cyanosis, arrhythmias and sudden cardiac death (SCD). Many Ebstein’s anomaly patients have an interatrial communication (secundum atrial septal defect (ASD II) or patent foramen ovale). Other structural anomalies may also be present, including a bicuspid aortic valve (BAV), ventricular septal defect (VSD), and pulmonary stenosis. The morphology of the tricuspid valve in Ebstein anomaly, and consequently the clinical presentation, is highly variable. The tricuspid valve leaflets demonstrate variable degrees of failed delamination (separation of the valve tissue from the myocardium) with fibrous attachments to the right ventricular endocardium.
The displacement of annular attachments of septal and posterior (inferior) leaflets into the right ventricle toward the apex and right ventricular outflow tract is the hallmark finding of Ebstein anomaly.

Signs and symptoms of haemolytic uremic syndrome can include bloody diarrhoea, low urine output, nausea, vomiting, abdominal pain and general fatigue. Increased values of urea and creatinine are also typical.

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

The history is suggestive of gastric carcinoma with dysphagia, vomiting, weight loss and lymphatic metastasis to the supraclavicular node, known as Virchow’s node.

Steps required in performing the Wilcoxon signed rank test:

1 State the null hypothesis and, in particular, the hypothesized value for comparison
2 Rank all observations in increasing order of magnitude, ignoring their sign. Ignore any observations that are equal to the hypothesized value. If two observations have the same magnitude, regardless of sign, then they are given an average ranking
3 Allocate a sign (+ or -) to each observation according to whether it is greater or less than the hypothesized value (as in the sign test)
4 Calculate:
R+ = sum of all positive ranks
R- = sum of all negative ranks
R = smaller of R+ and R-
5 Calculate an appropriate P value What makes this test the most appropriate for this study is that the data is non-parametric, paired and comes from the same population.

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.

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

The age of the patient, one sided headache and loss of vision on that side suggest temporal arteritis, also known as giant cell arteritis. The laboratory hallmark of this condition is a raised ESR.

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).

Methotrexate is also known as a DMARD (Disease Modifying Anti Rheumatic Drug). It reduces inflammation and suppresses the immune system, and is thought to cause folic acid deficiency leading to megaloblastic anaemia.
NSAIDS and Sulfasalazine are known to cause haemolytic but not megaloblastic anaemia.
Chronic disease might be accompanied with normocytic or microcytic anaemia as opposed to the macrocytic anaemia this patient is suffering from.
Steroids are not known to cause anaemia.

A head CT scan is the best step to rule out a mass lesion or bleed. Since the patient has symptoms that may suggest elevated intracranial pressure (ICP), a lumbar puncture should be consulted first with a neurologist since it is contraindicated in this case due to raised ICP and risk of coning.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

Candida albicans is the most common cause of candidiasis and appears almost universally in low numbers on healthy skin, in the oropharyngeal cavity, and in the gastrointestinal and genitourinary tracts. In immunocompetent individuals, C. albicans usually causes minor localized infections, including thrush (affecting the oral cavity), vaginal yeast infections (if there is an underlying pH imbalance), and infections of the intertriginous areas of skin (e.g., the axillae or gluteal folds). More widespread and systemic infections may occur in immunocompromised individuals (e.g., neonates, diabetics, and HIV patients), with the oesophagus most commonly affected (candida esophagitis). Localized cutaneous candidiasis infections may be treated with topical antifungal agents (e.g., clotrimazole). More widespread and systemic infections require systemic therapy with fluconazole or caspofungin.

Baclofen is used to treat spastic movement symptoms such as those seen in cerebral palsy and multiple sclerosis. It is known to be associated with a withdrawal syndrome similar to alcohol withdrawal; thus, gradual withdrawal is necessary to avoid this.

The most pertinent diagnosis suspected in this case would be a pulmonary embolism considering the recent surgical history and acute onset of breathlessness. A CT pulmonary angiogram (CTPA) is a medical diagnostic test that employs computed tomography (CT) angiography to obtain an image of the pulmonary arteries. Its main use is to diagnose pulmonary embolism (PE).

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.

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-Barre syndrome, motor neuron disease)
– Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

Type I pneumocyte: The cell responsible for the gas (oxygen and carbon dioxide) exchange that takes place in the alveoli. It is a very thin cell stretched over a very large area. This type of cell is susceptible to a large number of toxic insults and cannot replicate itself.
Type II pneumocyte: The cell responsible for the production and secretion of surfactant (the molecule that reduces the surface tension of pulmonary fluids and contributes to the elastic properties of the lungs). The type 2 pneumocyte is a smaller cell that can replicate in the alveoli and will replicate to replace damaged type 1 pneumocytes. Alveolar macrophages are the primary phagocytes of the innate immune system, clearing the air spaces of infectious, toxic, or allergic particles that have evaded the mechanical defences of the respiratory tract, such as the nasal passages, the glottis, and the mucociliary transport system. The main role of goblet cells is to secrete mucus in order to protect the mucous membranes where they are found. Goblet cells accomplish this by secreting mucins, large glycoproteins formed mostly by carbohydrates.