Chloride channels are involved in a diverse set of functions in normal physiology and acquired diseases. Additionally, there are genetic diseases caused by mutations in chloride channels (channelopathies) — the most common being cystic fibrosis, which has a prevalence of 1 in 2,000 Caucasians.

Breast cancer has a lower incidence in HIV positive patients. Seminoma, Hodgkin’s disease, anal cancer, and non-small cell lung cancer are all increased incidence. Memorize this breast cancer fact.

Lymphedema is most commonly the result of removal or damage to lymph nodes.

The cytochrome p450 3A4 enzyme system in the liver is affected by grapefruit juice.

Patients taking antihistamines should be advised to avoid drinking grapefruit juice. This is because constituents of grapefruit juice such as naringin and bergamottin inhibit CYP3A4 in the liver, particularly at high doses, leading to decreased drug elimination via hepatic metabolism and can increase potential drug toxicities.

Inhibition of this enzyme system leads to reduced metabolism of antihistamines leading to an increased incidence of side effects like excessive drowsiness and nausea as in this patient.

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.

Aprepitant is an anti-emetic which blocks the neurokinin 1 (NK1) receptor and acts as a substance P antagonist. It is licensed for chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting.

Nausea and vomiting are the common side effects of chemotherapy. Risk factors for the development of these symptoms include age<50 years, anxiety, concurrent use of opioids, and the type of chemotherapy administered.

Depending on the level of SCI, patients experience paraplegia or tetraplegia. Paraplegia is defined as the impairment of sensory or motor function in lower extremities. Patients with incomplete paraplegia generally have a good prognosis in regaining locomotor ability (,76% of patients) within a year. Complete paraplegic patients, however, experience limited recovery of lower limb function if their NLI is above T9. The spinothalamic tract is the one responsible for sensory information such as pain or temperature. However, it decussates at the same level the nerve root enters the spinal cord, meaning that the sensory loss will be contralateral. However, the dorsal column carries sensory fibres for fine touch and vibration and it decussates at the medulla which means that the sensory loss will be ipsilateral. The corticospinal tract is responsible for motor functions and it decussates at the medulla, meaning that the motor function loss will be ipsilateral.

Carbon monoxide (CO) poisoning:
It is 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%.

Clinical features of carbon monoxide toxicity:
Headache: 90% of cases (most common clinical feature)
Nausea and vomiting: 50%
Vertigo: 50%
Confusion: 30%
Subjective weakness: 20%
Severe toxicity: ‘pink’ skin and mucosa, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
Cherry red skin is a sign of severe toxicity and is usually a post-mortem finding.
Management
• 100% oxygen
• Hyperbaric oxygen therapy (HBOT)

The use of Hyperbaric oxygen therapy (HBOT) for treatment 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)

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

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

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.

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.

There are theoretical reasons for believing that selective serotonin reuptake inhibitors (SSRIs), widely used to treat depression, might increase the risk of gastrointestinal bleeding. Gastroprotective drugs are advocated for high risk patients taking non-steroidal anti-inflammatory drugs, another class of drug that causes gastrointestinal bleeding.

Serotonin is released from platelets in response to vascular injury and promotes vasoconstriction and a change in the shape of the platelets that leads to aggregation. Platelets cannot themselves synthesise serotonin. SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability to form clots and a subsequent increase in the risk of bleeding.

The well established association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding is estimated to result in 700-2000 deaths/year in the UK. This has led to the recommendation that patients in high risk groups should receive gastroprotection in the form of an H2 antagonist, proton pump inhibitor (lansoprazole), or misoprostol.

Proton pump inhibitors have been shown to reduce endoscopically diagnosed mucosal damage and heal ulcers induced by non-steroidal anti-inflammatory drugs but not to reduce the incidence of severe gastrointestinal bleeds.

The pons is above the level of decussation of the corticospinal tracts so a pontine lesion would cause a contralateral limb weakness.
The facial motor nucleus is located in the pons and supplies the ipsilateral facial muscles.
A right cerebral lesion would give left upper and lower limb weakness. It would also cause a left sided facial weakness.
A left cerebral lesion would give right upper and lower limb weakness with right facial weakness.
Finally, a cervical spinal cord lesion would not cause a facial weakness.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, comparing two independent samples from the same population.

The history is suggestive of acute gingivostomatitis, which is a manifestation of primary HSV-1 infection. Patients present with gingivitis and vesicular lesions which develop on the oral mucosa, tongue, and lips and later rupture and coalesce, leaving ulcerated plaques.

The wedged hepatic venous pressure is a reflection of the portal venous pressure in the hepatic sinusoids. This is a fact to remember. Here is a great but concise explanation as to why: https://www.ncbi.nlm.nih.gov/pubmed/18695309

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

Renal elimination of a drug has no role in altering the bioavailability of a drug.
The bioavailability of a drug is the proportion of the drug which reaches systemic circulation.
Mathematically, bioavailability is the AUCoral/AUCiv x 100%, where AUC = area under the concentration-time curve following a single (oral or iv) dose.

Other options are true:
By definition, the bioavailability of a drug given intravenously is 100%.
Drugs given orally that undergo high pre-systemic (first-pass) metabolism in the liver or gut wall have a low bioavailability e.g. lidocaine.
Bioavailability is also affected by the degree of absorption from the gut and this can change depending on gut motility and administration of other drugs.

Triamterene is a potassium-sparing diuretic that can cause hyperkalaemia, therefore, it was stopped in this patient. With all other lab results returning normal values and a normal ECG, management will simply require repeating the U & E after one week since the Triamterene has already be stopped.

The most probable diagnosis in this patient is De Clerambault’s syndrome, also known as erotomania, which is a form of paranoid delusion with an amorous quality. The patient, often a single woman, believes that a famous person is in love with her.

Other options:
– Bouffée délirante is an acute psychotic disorder in which hallucinations, delusions or perceptual disturbances are obvious but markedly variable, changing from day to day or even from hour to hour.
– Fregoli delusion is the mistaken belief that some people currently present in the deluded person’s environment (typically a stranger) is a familiar person in disguise.
– Capgras delusion is the belief that significant others have been replaced by impostors, robots or aliens.
– Couvade is the common but poorly understood phenomenon whereby the expectant father experiences somatic symptoms during the pregnancy for which there is no recognized physiological basis.

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy. Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

CD8+ T cells recognize antigens in the form of short peptide fragments bound to major histocompatibility complex class I (MHCI) molecules on the target cell surface.1 Specific engagement of peptide-MHCI (pMHCI) complexes via the clonotypically expressed αβ T-cell receptor (TCR) triggers a range of effector functions that play a critical role in protective immunity against intracellular infections and various malignancies.

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

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Treatment of ABPA aims to control inflammation and prevent further injury to your lungs. ABPA is a hypersensitivity reaction that requires treatment with oral corticosteroids. Inhaled steroids are not effective. ABPA is usually treated with a combination of oral corticosteroids and anti-fungal medications. The corticosteroid is used to treat inflammation and blocks the allergic reaction. Examples
of corticosteroids include: prednisone, prednisolone or methylprednisolone. Inhaled corticosteroids alone – such as used for asthma treatment – are not effective in treating ABPA. Usually treatment with an oral corticosteroid is needed for months.

The second type of therapy used is an anti-fungal medication, like itraconazole and voriconazole. These medicines help kill Aspergillus so that it no longer colonizes the airway. Usually one of these drugs is given for at least 3 to 6 months. However, even this treatment is not curative and can have side effects.

Normal cerebrospinal fluid (CSF) glucose together with lymphocytosis, an increased opening pressure and raised CSF protein are typical of a viral meningitis.

The oedema is an effect of the a decreased cardiac output that increases renin release which leads to vasoconstriction and sodium and water retention.

Increased WBC count and CRP suggest infection. But with the fluctuating hard neurological signs, there is suspicion of the presence of a cerebral mass, which is an indication for requesting for a CT scan with contrast, to rule out an abscess or haematoma. The lumbar puncture can be considered after the CT scan.

Most new moms experience postpartum baby blues after childbirth, which commonly include mood swings, crying spells, anxiety and difficulty sleeping. Baby blues typically begin within the first two to three days after delivery, and may last for up to two weeks.

Signs and symptoms of baby blues may include:
Mood swings
Anxiety
Sadness
Irritability
Feeling overwhelmed
Crying
Reduced concentration
Appetite problems
Trouble sleeping

The exact cause of the “baby blues” is unknown at this time. It is thought to be related to the hormone changes that occur during pregnancy and again after a baby is born. These hormonal changes may produce chemical changes in the brain that result in depression.
Although the experience of baby blues is unpleasant, the condition usually subsides within two weeks without treatment. All the mom needs is reassurance and help with the baby and household chores.

If a pleural effusion is present, a diagnostic thoracentesis may be performed and analysed for pH, lactate dehydrogenase, glucose levels, specific gravity, and cell count with differential. Pleural fluid may also be sent for Gram stain, culture, and sensitivity. Acid-fast bacillus testing may also be considered and the fluid may be sent for cytology if cancer is suspected.

The following findings are suggestive of an empyema or parapneumonic effusion that will likely need a chest tube or pigtail catheter for complete resolution:
-Grossly purulent pleural fluid
-pH level less than 7.2
-WBC count greater than 50,000 cells/µL (or polymorphonuclear leukocyte count of 1,000 IU/dL)
-Glucose level less than 60 mg/dL
-Lactate dehydrogenase level greater than 1,000 IU/mL
-Positive pleural fluid culture

The most often used golden criteria for empyema are pleural effusion with macroscopic presence of pus, a positive Gram stain or culture of pleural fluid, or a pleural fluid pH under 7.2 with normal peripheral blood ph.

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.

Because of the patient’s history of chronic analgesic use of daily paracetamol intake, the most likely diagnosis of this case is Analgesic misuse headache. In these cases, the headache is only temporarily relieved by analgesics. Treatment involves gradual withdrawal of analgesics.

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

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.

Apex beat displacement is caused by mitral regurgitation and because it is not found in mitral stenosis, it is suggestive of mixed mitral disease. The other given responses occur in mitral stenosis.

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

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 number needed to treat (NNT) is valuable information in treatment decisions. NNT is the inverse of the absolute risk reduction (1/ARR) between two treatment options. Control event rate = 10 / 50 = 0.2
Experimental event rate = 18 / 120 = 0.15

Absolute risk reduction = 0.2 – 0.15 = 0.05
Number needed to treat = 1 / 0.05 = 20

Senile cataract is an age-related, vision-impairing disease characterized by gradual progressive clouding and thickening of the lens of the eye. Patients with senile cataracts often present with a history of gradual progressive visual deterioration and disturbance in night and near vision.

Anti ds-DNA antibodies are very specific for SLE and their presence most often indicates systemic spread of the disease. These antibodies are present in about 30 percent of the total cases of SLE.

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)

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.

Most patients with psoriatic arthritis present with monoarthritis or asymmetric oligoarthritis. The most common form of the disease is the one involving a few joints of the peripheral skeleton with a distinct asymmetry of symptoms. Involvement of the smaller joints of the hands and feet, especially distal interphalangeal joints, seems to be a characteristic feature. Arthritis mutilans is a rare and severe complication of psoriatic arthritis.

Confusion in the patient refers to neurological symptoms that are more associated with thrombotic thrombocytopenic purpura than with haemolytic uremic syndrome. All the other symptoms present in both conditions similarly.

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.

Most new moms experience postpartum baby blues after childbirth, which commonly include mood swings, crying spells, anxiety and difficulty sleeping. Baby blues typically begin within the first two to three days after delivery, and may last for up to two weeks.

Postpartum depression may be mistaken for baby blues at first — but the signs and symptoms are more intense and last longer, and may eventually interfere with your ability to care for your baby and handle other daily tasks. Symptoms usually develop within the first few weeks after giving birth, but may begin earlier, during pregnancy or later, up to a year after birth.

The period prevalence of postpartum depression among women is a striking 21.9% the first year after birth, which makes it one of the most common medical complications of childbearing. Sertraline has been identified as an antidepressant of choice for breastfeeding women because infants are unlikely to develop quantifiable serum sertraline levels and very few adverse events associated with sertraline have been reported.

Women with a prior episode of postpartum psychosis have about a 30% risk of having another episode in the next pregnancy.

CURB Pneumonia Severity Score estimates the mortality of community-acquired pneumonia to help determine inpatient vs. outpatient treatment.
Select Criteria:
Confusion (abbreviated Mental Test Score <=8) (1 point)
Urea (BUN > 19 mg/dL or 7 mmol/L) (1 point)
Respiratory Rate > 30 per minute (1 point)
Blood Pressure: diastolic < 60 or systolic < 90 mmHg (1 point) The CURB-65 scores range from 0 to 5. Clinical management decisions can be made based on the score:
Score Risk Disposition
0 or 1 – 1.5% mortality – Outpatient care
2 – 9.2% mortality – Inpatient vs. observation admission
≥ 3 – 22% mortality – Inpatient admission with consideration for ICU admission with score of 4 or 5

Fundoscopy findings of cotton wool spots and retinal tears, accompanied by a history of blurred vision, are characteristic of retinitis. Cytomegalovirus is known to cause retinitis.

The classes refer to the WHO classification of glomerulonephritis in SLE patients.
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis

Class IV: diffuse proliferative glomerulonephritis is the most common and the most severe form, where more than 50% of the glomeruli are involved.

Among the given options, cognitive-behavioural therapy is the most likely to benefit a patient with schizophrenia.

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.

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.

He has a consequence of atherosclerotic disease (MI). The most probable diagnosis is cutaneous cholesterol emboli as it is more common after anticoagulation or thrombolytics, the skin involvement, eosinophilia and raised IgE. It is more common above 60 yrs. of age.