Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.

Contraindications:
– Patients taking nitrates and related drugs such as nicorandil
– Hypotension
– Recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Side-effects:
Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic Neuropathy
Nasal congestion
Flushing
Gastrointestinal side-effects
Headache

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)

Immune thrombocytopenic purpura (ITP) refers to thrombocytopaenia occurring in the absence of toxic exposure or other diseases associated with low platelets and involves IgG-type antibodies. It is characterised by normal or increased marrow megakaryocytes, shortened platelet survival, and the absence of splenomegaly. Autoimmune haemolytic anaemia (AIHA) occurs commonly in association with ITP. Leukemic transformation, however, does not occur in ITP.

In neonatal ITP, IgG antibodies are passively transferred across the placenta. The infant platelet count may be normal at birth but decreases within 12–24 hours. It is rarely severe enough to induce bleeding diathesis in the infant.

Beckwith-Wiedemann syndrome is a inherited condition associated with organomegaly, macroglossia, abdominal wall defects, Wilm’s tumour and neonatal hypoglycaemia. Wilm’s tumour is a kidney cancer that usually occurs in children. The causes are unknown, however, risk factors include race and family history. Of note, Wilm’s tumour can occur as part of the following syndromes: WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedmann syndrome and not the other listed options in this question.

In many Western countries and health plans in the United States, patients have a primary care physician who acts as a formal gatekeeper for medical specialist care and thereby determines together with the patient whether or not a patient requires medical specialist care. Ideally in such systems, patients are treated in primary care if possible, and referred to medical specialist care if necessary. For the gatekeeper system to be effective, it is vital that adequate decisions are made about when and who to refer. But it is also important that referred patients comply with the referral by consulting a medical specialist. In this case, the GP should discuss with the patient the reasons why she cannot follow the treatment plan. In other words, the GP should detect why the patient is being non-compliant.

First and foremost, the patient should be put on ECG monitoring to identify the cardiac state, and because of the markedly raised serum potassium, a calcium gluconate bolus will have the immediate effect of moderating the nerve and muscle performance.

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.

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

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.

The most likely diagnosis is acute atrial fibrillation (AF) precipitated by acute pneumonia. History of fever, cough and the auscultation findings support it. So the most appropriate management is treating the pneumonia with antibiotics. Treating the underlying cause will reduce the heart rate. Other responses are helpful in the management of chronic AF.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include weight loss and lethargy; monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Avascular necrosis (AVN) of the femoral head is a pathological process that results from disruption of the blood supply to the bone and occurs most commonly in the femoral epiphysis. Patients usually present with pain and limited joint motion. The mechanism involves impaired circulation to a specific area that ultimately becomes necrotic. AVN is most frequently associated with high doses of oral and intravenous corticosteroids and prolonged duration of therapy. Cancer patients receiving chemotherapy are usually also treated with corticosteroids.

Acute dacryocystitis presents as inflammation of the lacrimal sac and is typically caused by infection. Symptoms of acute dacryocystitis can be pain, redness of the eye and swelling of the nasal aspect of the eye. The eye is usually watery and discharge can be expressed through the lacrimal punctum which is generally mucoid but can also be purulent. Patient can also present with fever.

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

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.

The most common location for a duodenal ulcer bleed is the posterior duodenum (remember: posterior bleeds, anterior perforates). The perfusion to this area is most specifically from the posterior superior pancreaticoduodenal artery.

The anterior superior pancreaticoduodenal artery supplies the anterior region. The gastroepiploic artery supplies mostly the stomach. The splenic artery goes, obviously, toward the spleen, in the other direction. The gastroduodenal artery is a branch of the celiac artery, and it’s branches are the anterior superior pancreaticoduodenal artery and posterior superior pancreaticoduodenal artery.

Uhthoff’s phenomenon is worsening of vision following a rise in body temperature.
Lhermitte’s sign describes paraesthesia in the limbs on neck flexion.
Oppenheim’s sign is seen when scratching of the inner side of leg leads to extension of the toes. It is a sign of cerebral irritation and is not related to multiple sclerosis.
Werdnig-Hoffman’s disease is also known as spinal muscular atrophy.

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

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

Depressive disorders require long-term treatment with antidepressants, psychotherapy, or both. The goal of antidepressant therapy is complete remission of symptoms and return to normal daily functioning. Studies have shown that achieving remission and continuing antidepressant therapy long after the acute symptoms remit can protect against the relapse or recurrence of the psychiatric episode. Many patients, however, inadvertently or intentionally skip doses of their antidepressant, and even discontinue it, if their symptoms improve or if they experience side effects. Antidepressant discontinuation may increase the risk of relapse or precipitate certain distressing symptoms such as gastrointestinal complaints, dizziness, flu-like symptoms, equilibrium disturbances, and sleep disorders.

Pharmacologic therapy should be continued long enough to sustain remission and avoid relapses and recurrences. Recurrence refers to a return of depression at a time beyond the expected duration of the index episode (> 9 months after remission). This means that physicians and patients alike should not be too eager to discontinue medication prematurely. An interval of 6 months has been thought to be the usual duration of antidepressant therapy. New recommendations, however, suggest that treatment should continue for up to 9 months after symptoms have resolved (continuation phase) to prevent relapse and for longer to help prevent recurrence (maintenance phase).

SSRI discontinuation symptoms are similar to those of the TCAs, with dizziness, gastrointestinal symptoms, and sleep disorders common. Anecdotal reports have included complaints of “electric shock–like” sensations, flashes, and “withdrawal buzz.” The type and severity of the symptoms correlate with the relative affinities of the agents for the serotonin reuptake sites and with secondary effects on other neurotransmitters; with SRIs that also affect cholinergic systems, the symptoms possibly correlate with cholinergic rebound.

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.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

In the PCR, DNA amplification is performed by thermostable enzymes; invariably either family A DNA polymerases from thermophilic and hyperthermophilic Bacteria or family B DNA polymerases from hyperthermophilic Archaea. Family Y DNA polymerase from the hyperthermophilic archaeon Sulfolobus solfataricus, Sso-polY, is also an enzyme marketed for PCR, but with specialist applications. Each thermostable DNA polymerases has different characteristics and to achieve optimal results, the choice of a PCR enzyme depends on the application itself.

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

Sevelamer is a phosphate-binding drug that can lower raised serum phosphate levels in chronic kidney disease. Because of its aluminium-related side-effects, aluminium hydroxide is no longer the drug of choice.
The other options are calcium-containing salts that may increase risks of tissue calcification.

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli.

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.

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

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

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

The prognosis of breast cancer depends chiefly on the extent of nodal metastases.

The breast cancer TNM staging system is the most common way that doctors use to stage breast cancer. TNM stands for Tumour, Node, Metastasis. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero), which is non-invasive ductal carcinoma in situ (DCIS), and stages I through IV (1 through 4), which are used for invasive breast cancer.

Staging can be clinical or pathological. Clinical staging is based on the results of tests done before surgery, which may include physical examinations, mammogram, ultrasound, and MRI scans. Pathologic staging is based on what is found during surgery to remove breast tissue and lymph nodes. In general, pathological staging provides the most information to determine a patient’s prognosis.

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
Thus, ethanol’s inhibitory effect helps to explain the increased diuresis experienced during intoxicated states as well as increased free water loss; without appropriate ADH secretion, more water is excreted by the kidneys.

Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre.
Following a particularly severe episode of alcohol excess, people may experience tremors due to increased glutamate production by neurons to compensate for the previous inhibition by ethanol.

Management of alcoholism:
Nutritional support:
– Alcoholic patients should receive oral thiamine if their ‘diet may be deficient’.
Pharmacological management:
– Benzodiazepines for acute withdrawal
– Disulfiram promotes abstinence – alcohol intake causes a severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis.
– Acamprosate reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo-controlled trials.