B-cells (20% of lymphocytes) mature in the bone marrow and circulate in the peripheral blood until they undergo recognition of antigen. B-cell immunoglobulin molecules synthesised in the cell are exported and bound to the surface membrane to become the B-cell receptor (BCR) which can recognise and bind to a specific antigen (either free or presented by APCs). The BCR is also important for antigen internalisation, processing and presentation to T helper cells. Most antibody responses require help from antigen-specific T helper cells (although some antigens such as polysaccharide can lead to T-cell independent B-cell antibody production). When the B-cell is activated, the receptor itself is secreted as free soluble immunoglobulin and the B-cell matures into a memory B-cell or a plasma cell (a B-cell in its high-rate immunoglobulin secreting state). Plasma cells are non-motile and are found predominantly in the bone marrow or spleen. Most plasma cells are short-lived (1 – 2 weeks) but some may survive much longer. A proportion of B-cells persist as memory cells, whose increased number and rapid response underlies the augmented secondary response of the adaptive immune system.

The NICE guidelines for women with lower UTIs who are not pregnant are:
1. Consider prescribing a different antibiotic if symptoms do not improve within 48 hours or worsen at any time
2. If the urine culture and susceptibility test results are available, review the choice of antibiotic according to the results and change the antibiotic accordingly if symptoms are not improving or bacteria is resistant to the prescribed antibiotic

The first choice of antibiotics for non-pregnant women aged 16 years and over is:
1. Nitrofurantoin
100 mg modified-release PO BD for 3 days – if eGFR >45 ml/minute
2. Trimethoprim
200 mg PO BD for three days

The second-choice (no improvement in lower UTI symptoms on first-choice for at least 48 hours, or when first-choice is not suitable) are:
1. Nitrofurantoin
100 mg modified-release PO BD for three days – if eGFR >45 ml/minute
2. Pivmecillinam
400 mg PO initial dose, then 200 mg PO TDS for three days
3. Fosfomycin 3 g single sachet dose

Gastric emptying is decreased by the presence of fats in the duodenum (by stimulating release of cholecystokinin). Mixing of the food with gastric secretions takes place in the distal body and antrum of the stomach where the muscularis externa layer is thicker. The stomach has an additional inner oblique smooth muscle layer (in addition to the inner circular layer and outer longitudinal layer). Gastric emptying is increased by a low gastric pH and decreased by a low duodenal pH.

Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+from the cell by inhibiting the membrane Na+pump (Na+/K+ATPase) which generates the Na+gradient required for driving the export of Ca2+by Na+/Ca2+exchange; consequently the removal of Ca2+from the myocyte is slowed and more Ca2+is available for the next contraction.

Cellulitis is most commonly caused by bacteria from the group Aß-hemolytic streptococcus.

Cellulitis can be caused by animal bites. For uncomplicated cellulitis, flucloxacillin is the first-line antibiotic. Because it is beta-lactamase stable, it is efficient against Staphylococcus aureus.

Entonox is a mixture of 50% Oxygen and 50% nitrous oxide and is given in an inhaled form as a quick form of analgesia. Entonox causes non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors, which are a subtype of the glutamate receptor.

It is stored in blue and white cylinders and administered via a pressure regulator and demand valve. The administration of this medicine reduces pain and anxiety in paediatric and dental procedures ands during labour.

Effects are apparent after 20 seconds, and peak action occurs after 3 to 5 minutes as it is a drug with a rapid onset and the patient will also recover rapidly from its effects. Entonox is widely used as it does not accumulate in the body and does not cause many side effects. However, a notable side effect is the inhibition of Vitamin B12 synthesis.

Pulmonary oedema causes stimulation of the Juxtacapillary receptors (J receptors) leading to a reflex increase in breathing rate. These receptors are also thought to be involved in the sensation of dyspnoea. The J receptors are sensory cells and are located within the alveolar walls in juxtaposition to the pulmonary capillaries.

Aortic baroreceptor are involved in detecting blood pressure

Central chemoreceptors detect changes in CO2 and hydrogen ion within the brain

Atrial volume receptors regulate plasma volume

The p value is statistically significant when it is less than 0.05 (5% or 1 in 20).

Statistical significance is not the same as clinical significance.

The null hypothesis states that there is no difference between the groups.

The power of a study is the probability of correctly rejecting the null hypothesis when it is false.

A type I error occurs when the null hypothesis has been rejected when it is true. A type II error occurs when the null hypothesis has been accepted when it is actually false.

Extensor pollicis brevis is a short and slender muscle located in the posterior compartment of the forearm, extending from the posterior surface of radius to the proximal phalanx of thumb. It is one of the deep extensors of the forearm, together with supinator, abductor pollicis longus, extensor pollicis longus and extensor indicis muscles.

Extensor pollicis brevis is a deep extensor of the thumb that lies deep to extensor digitorum muscle. It sits directly medial to abductor pollicis longus and posterolateral to extensor pollicis longus muscle. Just above the wrist, extensor pollicis brevis obliquely crosses the tendons of extensor carpi radialis brevis and extensor carpi radialis longus muscles.

Extensor pollicis brevis is innervated by posterior interosseous nerve which is a continuation of a deep branch of radial nerve (root value C7 and C8).

Extensor pollicis brevis receives its blood supply by posterior interosseous artery and perforating branches from the anterior interosseous artery, which are the branches of common interosseous artery. The common interosseous artery arises immediately below the tuberosity of radius from the ulnar artery.

Together with extensor pollicis longus, extensor pollicis brevis is in charge of extension of the thumb in the first metacarpophalangeal joint. It also extends the thumb in the carpometacarpal joint of the thumb. This movement is important in the anatomy of the grip, as it enables letting go of an object. As it crosses the wrist, extensor pollicis brevis also participates in the extension and abduction of this joint.

Adverse effects include:
Drowsiness and lightheadedness
Confusion and ataxia (especially in the elderly), amnesia, muscle weakness
Headache, vertigo, tremor, dysarthria, hypotension, decreased libido, erectile dysfunction, gynaecomastia, urinary retention
Paradoxical effects such as talkativeness, excitement, irritability, aggression, anti-social behaviour, and suicidal ideation
Withdrawal symptoms, for example anxiety, depression, anorexia, impaired concentration, insomnia, abdominal cramps, palpitations, tremor, tinnitus and perceptual disturbances
Tolerance and dependence (people who use benzodiazepines longer term can develop tolerance and eventual dependence)

The oculomotor nerve is the third cranial nerve. It is the main source of innervation to the extraocular muscles and also contains parasympathetic fibres which relay in the ciliary ganglion. Damage to the third cranial nerve may cause diplopia, pupil mydriasis, and/or upper eyelid ptosis. The clinical manifestations of third cranial nerve dysfunction reflect its constituent parts.

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.

The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.

A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Ipratropium bromide is an antimuscarinic drug used in the management of acute asthma and COPD. It can provide short-term relief in chronic asthma, but short-acting β2agonists act more quickly and are preferred.

The BTS guidelines recommend that nebulised ipratropium bromide (0.5 mg 4-6 hourly) can be added to β2agonist treatment for patients with acute severe or life-threatening asthma or those with a poor initial response to β2 agonist therapy.
The aerosol inhalation of ipratropium can be used for short-term relief in mild chronic obstructive pulmonary disease in patients who are not already using a long-acting antimuscarinic drug (e.g. tiotropium).

Its maximum effect occurs 30-60 minutes after use; its duration of action is 3-6 hours, and bronchodilation can usually be maintained with treatment three times per day.
The commonest side effect of ipratropium bromide is dry mouth. It can also trigger acute closed-angle glaucoma in susceptible patients. Tremor is commonly seen with β2agonists but not with antimuscarinics. Ipratropium bromide should be used with caution in: Men with prostatic hyperplasia and bladder-outflow obstruction (worsened urinary retention has been reported in elderly men), People with chronic kidney disease (CKD) stages 3 and above (because of the risk of drug toxicity), People with angle-closure glaucoma (nebulised mist of antimuscarinic drugs can precipitate or worsen acute angle-closure glaucoma)

Because the anatomical position of the penis is erect, the paired corpora cavernosa are defined as dorsal in the body of the penis and the single corpus spongiosum as ventral. The nerves and vessels lie superficial to the corpus cavernosum. The urethra lies within the corpus spongiosum.

Beta-2 agonists should be used with caution in people with:
Cardiovascular disease, including arrhythmias and hypertension (beta-2 agonists may cause an increased risk of arrhythmias and significant changes to blood pressure and heart rate)
Diabetes(risk of hyperglycaemia and ketoacidosis, especially with intravenous use)
Hyperthyroidism(beta-2 agonists may stimulate thyroid activity)
Hypokalaemia(potentially serious hypokalaemia may result from beta-2 agonist therapy; this effect may be potentiated in severe asthma by concomitant treatment with theophylline, corticosteroids, diuretics and by hypoxia)
Susceptibility to QT-interval prolongation
Convulsive disorders

Cholera is a severe diarrheal illness caused by the Vibrio cholerae bacteria infecting the bowel. Ingesting cholera-infected food or drink is the a way to contract the disease. In the intestinal crypt cells, the toxigenic bacterium Vibrio cholera activates adenylate cyclase and raises cyclic adenosine monophosphate (cAMP).

cAMP stimulates the Cl-secretory channels in crypt cells, resulting in the secretion of chloride with sodium ions and water. The toxin it produces causes the body to secrete massive amounts of water, resulting in diarrhoea and significant fluid and electrolyte loss.

The following drugs have been linked to impaired glucose tolerance:
Thiazide diuretics, e.g. Bendroflumethiazide
Loop diuretics, e.g. furosemide
Steroids, e.g. prednisolone
Beta-blockers, e.g. atenolol

Lidocaine is a class 1B antidysrhythmic; combines with fast Na channels and thereby inhibits recovery after repolarization, resulting in decreasing myocardial excitability and conduction velocity. However, in ischaemic areas, where anoxia causes depolarisation and arrhythmogenic activity, many Na+ channels are inactivated and therefore susceptible to lidocaine.

Synthesis of platelets occurs in the bone marrow by fragmentation of megakaryocytes cytoplasm, derived from the common myeloid progenitor cell. The average time for differentiation of the human stem cell to the production of platelets is about 10 days. The major regulator of platelet formation is thrombopoietin and 95% of this is produced by the liver. Normal platelet count is 150 – 450 x 109/L and the normal lifespan of a platelet is about 10 days. Usually about one-third of the marrow output of platelets may be trapped at any one time in the normal spleen.

A single dose of IV benzodiazepine will terminate the seizure in 60 to 80 percent of patients who present with seizures.

Because benzodiazepines are lipid-soluble, they cross the blood-brain barrier quickly. This explains their quick onset of action.

As a first-line treatment, IV lorazepam should be given. If IV lorazepam is not available, IV diazepam can be used instead, and buccal midazolam can be used if intravenous access cannot be established quickly. Lorazepam can be administered via the rectal route, but it is less reliable and has a lower absorption rate and bioavailability.

Pronator quadratus is a deep-seated, short, flat, and quadrilateral muscle with fibres running in a parallel direction.

It arises from the oblique ridge on the anterior surface of the distal fourth of the Ulna. It is inserted in lateral border and anterior surface of the distal fourth of the radius. It is innervated by the anterior interosseous nerve, a branch of the median nerve (C8-T1). It is vascularized by the anterior interosseous artery.

The action of the pronator quadratus muscle along with the pronator teres result in the pronation of the radioulnar joint. Contraction of this muscle pulls the distal end of the radius over the ulna, resulting in the pronation of the radioulnar joint

A nominal variable is a type of variable that is used to name, label or categorize particular attributes that are being measured. It takes qualitative values representing different categories, and there is no intrinsic ordering of these categories.
A nominal variable is one of the 2 types of categorical variables and is the simplest among all the measurement variables. Some examples of nominal variables include gender, name, phone, etc.

A nominal variable is qualitative, which means numbers are used here only to categorize or identify objects. They can also take quantitative values. However, these quantitative values do not have numeric properties. That is, arithmetic operations cannot be performed on them. If the variable is nominal, the mode is the only measure of central tendency to use.

Anti-HBc IgM antibodies are diagnostic for acute hepatitis B infection. Anti-HBc IgG antibodies indicate previous exposure, either chronic state or cleared infection. HBsAg is also positive in acute infection but is not diagnostic as this remains positive in chronic infection.

CSF fills the ventricular system, a series of interconnected spaces within the brain, and the subarachnoid space directly surrounding the brain. The intraventricular CSF reflects the composition of the brain’s extracellular space via free exchange across the ependyma, and the brain “floats” in the subarachnoid CSF to minimize the effect of external mechanical forces. The volume of CSF within the cerebral ventricles is approximately 30 mL, and that in the subarachnoid space is about 125 mL. Because about 0.35 mL of CSF is produced each minute, CSF is turned over more than three times daily. Approximately 500 mL of CSF is produced per day, at a rate of about 25 mL per hour.

CSF is a filtrate of capillary blood formed largely by the choroid plexuses, which comprise pia mater, invaginating capillaries, and ependymal cells specialized for transport. The choroid plexuses are located in the lateral, third, and fourth ventricles. The lateral ventricles are situated within the two cerebral hemispheres. They each connect with the third ventricle through one of the interventricular foramina (of Monro). The third ventricle lies in the midline between the diencephalon on the two sides. The cerebral aqueduct (of Sylvius) traverses the midbrain and connects the third ventricle with the fourth ventricle. The fourth ventricle is a space defined by the pons and medulla below and the cerebellum above. The central canal of the spinal cord continues caudally from the fourth ventricle, although in adult humans the canal is not fully patent and continues to close with age.

The clinical effects of Warfarin occur after a dose of greater than 0.5 mg/kg, and they will be observable 8-10 hours after consumption of the drug. The antidote used for Warfarin is Vitamin K.

1. In low-risk cases with no apparent bleeding:
an oral dose of 10 mg vitamin K

2. If there is clinically significant bleeding
an intravenous dose of 250-300 mcg/kg

Activated charcoal:
in cases of warfarin ingestion
binds to it and reduces the absorption of warfarin
the ingestion must have occurred within the last hour
There is, however, rarely a need for the use of activated charcoal because vitamin K is such as safe and effective antidote.

Clotting studies, including an INR, can be performed, but small children who have ingested warfarin do not require INRs or follow up if they have been treated with 10 mg vitamin K. This dose of vitamin will completely reverse the anticoagulative effects of warfarin.

Perform INR if any of the following are present:
1. Delayed presentation (>6 hours)
2. Patients with symptoms or signs of anticoagulation
3. Possible massive ingestion

The most common cause of drug-induced anaphylaxis is penicillin.

The second commonest cause are NSAIDs. Other drugs associated with anaphylaxis are ACE inhibitors and aspirin.

Amiodarone is a class III potassium channel blocker used to treat multiple types of arrhythmias.

Side effects include:
1. pulmonary fibrosis
2. blue discolouration of the skin
3. phototoxicity
4. corneal deposits
5. hepatic necrosis
6. thyroid dysfunction
7. sleep disturbances
8. peripheral neuropathy.

Xanthopsia is a condition where the patient complains of seeing yellow lines and is seen in digoxin overdose.

Ketamine is a dissociative anaesthetic with analgesic, amnesic, and hypnotic effects. It is the only anaesthetic agent which causes all three of these effects.

Ketamine exerts its action by non-competitive antagonism at the NMDA (N-methyl-D-aspartate) receptor. Due to its analgesic property, Ketamine is given so that patients do not retain memories of short term procedures. Ketamine is used for the induction and maintenance of anaesthesia in general surgery and for treating burn wounds, battlefield injuries, and children who cannot tolerate other anaesthetic or analgesic agents.

It can be given by both intravenous and intramuscular routes. Ketamine causes cardiac stimulation by increasing the sympathetic tone. The major side effect is increased intracranial pressure as an increase in the sympathetic tone causes vasoconstriction and an increase in the MAP.

Bias is the term used to describe an error at any stage of the study that was not due to chance. Bias leads to the systematic difference between the results from a study and the true states of affair. Bias may be introduced at all stages of the research process, from study design, through to analysis and publication. Bias can create a spurious association or mask a real association.Good research design can reduce the effect of bias (e.g. blinding, randomisation) but they cannot eliminate it completely. Increasing the sample size does not reduce bias.