The suprascapular nerve (C5-C6) innervates the infraspinatus. It originates at the superior trunk of the brachial plexus. It runs laterally across the lateral cervical region to supply the infraspinatus and also the supraspinatus.

E.Colistrain 0157 causes enterohaemorrhagic diarrhoea and can be followed by haemolytic uraemic syndrome (renal failure, haemolytic anaemia and thrombocytopenia).

Treponema pallidum is an obligate pathogen. Obligate pathogens are almost always associated with disease and usually cannot survive outside of the body for long periods of time. Examples include and HIV.

Staphylococcus aureus and Bacteroides fragilis are conditional pathogens. These are pathogens that usually cause disease only if certain conditions are met.

Pneumocystis jiroveci and Pseudomonas aeruginosa, are opportunistic pathogens. These are pathogens that can only cause disease in an immunocompromised host or under unusual circumstances.

Damage to the tibial nerve results in loss of plantarflexion of the ankle and weakness of inversion of the foot resulting in a shuffling gait, clawing of the toes and loss of sensation in its cutaneous distribution.

The causes of AKI can be divided into pre-renal, intrinsic renal and post-renal causes. Majority of AKI developing in the community is due to a pre-renal causes (90% of cases).

Pre-renal causes: Haemorrhage, severe vomiting or diarrhoea, burns, cardiac failure, liver cirrhosis, nephrotic syndrome, hypotension, severe cardiac failure, NSAIDs, COX-2 inhibitors, ACE inhibitors or ARBs, Abdominal aortic aneurysm, renal artery stenosis, hepatorenal syndrome,

Intrinsic (renal) causes:
Eclampsia, glomerulonephritis, thrombosis, haemolytic-uraemic syndrome, acute tubular necrosis (ATN), acute interstitial nephritis, drugs ( NSAIDs), infection or autoimmune diseases, vasculitis, polyarteritis nodosa, thrombotic microangiopathy, cholesterol emboli, renal vein thrombosis, malignant hypertension

Post-renal causes: Renal stones, Blood clot, Papillary necrosis, Urethral stricture, Prostatic hypertrophy or malignancy, Bladder tumour, Radiation fibrosis, Pelvic malignancy, Retroperitoneal fibrosis

Maculopapular rashes are commonly seen with ampicillin and amoxicillin. However they are not usually related to true penicillin allergy. Very often, they occur in patients with glandular fever and so, broad-spectrum penicillins should not be used blindly, for management and treatment of a sore throat. There is also an increased risk of rash in patients with acute or chronic lymphocytic leukaemia or in cytomegalovirus infection.

A median nerve block is a simple, safe, and effective method of obtaining anaesthesia to the palmar aspect of the thumb, index finger, middle finger, radial portion of the palm and ring finger. The median nerve lies deep to the flexor retinaculum and about one centimetre under the skin of the volar wrist.
The palmaris longus tendon lies superficial to the retinaculum and is absent in up to 20% of patients.
The median nerve is located slightly lateral (radial) to the palmaris longus tendon and medial (ulnar) to the flexor carpi radialis tendon.

The procedure is as follows:
– Check sensation and motor function of the median nerve. Wear gloves and use appropriate barrier precautions.
– Locate the flexor carpi radialis and palmaris longus tendons, which become prominent when the patient flexes the wrist against resistance. The palmaris longus tendon is usually the more prominent of the two tendons.
– Needle-entry site: The needle will be inserted adjacent to the radial (lateral) border of the palmaris longus tendon just proximal to the proximal wrist crease. If the palmaris longus tendon is absent, the needle-entry site is about 1 cm ulnar to the flexor carpi radialis tendon.
– Cleanse the site with antiseptic solution. Place a skin wheal of anaesthetic, if one is being used, at the needle-entry site.
– Insert the needle perpendicularly through the skin and advance it slowly until a slight pop is felt as the needle penetrates the flexor retinaculum. When paraesthesia in the distribution of the median nerve confirms proper needle placement, withdraw the needle 1 to 2 mm.
– Aspirate to exclude intravascular placement and then slowly (i.e., over 30 to 60 seconds) inject about 3 mL of anaesthetic. If the patient does not feel paraesthesia, redirect the needle in an ulnar direction, under the palmaris longus tendon. If paraesthesia is still not felt, slowly inject 3 to 5 mL of anaesthetic in the proximity of the nerve 1 cm deep to the tendon.
– Allow about 5 to 10 minutes for the anaesthetic to take effect.

Relative risk (RR) is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group.

RR can be computed as the absolute risk of events in the treatment group (ART), divided by the absolute risk of events in the control group (ARC).

RR = ART/ARC
RR = (30/300) / (20/500)
RR = 2.5

Recall that:

If RR < 1, then the intervention reduces the risk of the outcome.
If RR = 1, then the treatment has no effect on the outcome.
If RR > 1, then the intervention increases the risk of the outcome.

Paracetamol is predominantly metabolized in the liver by three main metabolic pathways:
1. Glucuronidation (45-55%)
2. Sulphate conjugation (30-35%)
3. N-hydroxylation via the hepatic cytochrome P450 enzyme system (10-15%)

Cytochrome P450 enzymes catalyse the oxidation of acetaminophen to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI primarily contributes to the toxic effects of acetaminophen. NAPQI is an intermediate metabolite that is further metabolized by fast conjugation with glutathione. The conjugated metabolite is then excreted in the urine as mercapturic acid. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to depleting glutathione and high binding levels of reactive metabolite (NAPQI) to important parts of liver cells.

Antispasmodics, such as antimuscarinics, may be used in the management of irritable bowel syndrome. Other antispasmodics used include direct-acting smooth muscle relaxants such as mebeverine, alverine, and peppermint oil. Antispasmodics are contraindicated in bowel obstruction and severe inflammatory bowel disease. Antispasmodics are occasionally of value in treating abdominal cramp associated with diarrhoea but they should not be used for primary treatment. Antispasmodics should be avoided in young children with gastroenteritis because they are rarely effective and have troublesome side effects. Antimuscarinics are contraindicated in urinary retention.

Clostridium difficile, a Gram-positive, anaerobic, spore forming bacteria is present in the gut of approximately 3% of healthy adults (2012 UK HPA estimates). Following use of broad spectrum antibiotics, which alter normal gut flora, Clostridium difficile associated diarrhoea (CDAD) occurs.

About 80% of Clostridium difficile infections are seen in people over the age of 65 and its main clinical features are:
Abdominal cramps, severe bloody and/or watery diarrhoea, offensive smelling diarrhoea, and fever.

The stomach produces gastric acid, which is a digesting fluid. The stomach secretes about 2-3 litres every day. It is involved in tissue breakdown, the conversion of pepsinogen to active pepsin, and the creation of soluble salts with calcium and iron, and has a pH range of 1.5-3.5. It also serves as an immune system by destroying microbes.

The following substances are found in gastric acid:
Water
Acid hydrochloride
Pepsinogen
mucous
Intrinsic factor

The parietal cells in the proximal 2/3 (body) of the stomach release gastric acid. The concentration of hydrogen ions in parietal cell secretions is 1-2 million times that of blood. Chloride is released against both a concentration and an electric gradient, and active transport is required for the parietal cell to produce acid.

The following is how stomach acid is secreted:

1. Gastric acid secretion is dependent on the H+/K+ ATPase (proton pump) situated in the canalicular membrane. The breakdown of water produces hydrogen ions within the parietal cell. The hydroxyl ions produced in this reaction mix quickly with carbon dioxide to generate bicarbonate ions. Carbonic anhydrase is the enzyme that catalyses this process.

2. In return for chloride, bicarbonate is carried out of the basolateral membrane. The ‘alkaline tide’ occurs when bicarbonate is released into the bloodstream, resulting in a modest rise in blood pH. The parietal cell’s intracellular pH is maintained by this procedure. Conductance channels carry chloride and potassium ions into the lumen of canaliculi.

3. Through the action of the proton pump, hydrogen ions are pushed out of the cell and into the lumen in exchange for potassium; potassium is thus efficiently recycled.

4. The canaliculi accumulate osmotically active hydrogen ions, which creates an osmotic gradient across the membrane, allowing water to diffuse outward.

Gas exchange between alveolar air and blood in the pulmonary capillaries takes place by diffusion across the alveolar-capillary membrane. Diffusion occurs from an area of high partial pressure to an area of low partial pressure, thus the driving force for diffusion is the alveolar-capillary partial pressure gradient. Diffusion occurs until equilibrium is reached, but random movement of particles continues to occur and this is known as dynamic equilibrium. The diffusing capacity for oxygen (DLO2) cannot be measured directly but the rate of diffusion in the lungs can be estimated by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO), not by measuring total lung capacity. The rate of transfer of a gas may be diffusion or perfusion limited; carbon monoxide transfer is diffusion-limited, oxygen transfer is usually perfusion-limited.

The biceps brachii muscle is one of the chief muscles of the arm. The origin at the scapula and the insertion into the radius of the biceps brachii means it can act on both the shoulder joint and the elbow joint, which is why this muscle participates in a few movements of the arm. It derives its name from its two heads which merge in one unique distal body, defining the unusual structure of the muscle.

The biceps brachii muscle is supplied by the musculocutaneous nerve (C5-C6), a branch of the brachial plexus.

Arterial supply to the biceps brachii muscle varies considerably, coming from up to eight vessels originating from the brachial artery in the middle third of the arm.

In the shoulder joint both muscle heads partially enforce opposite movements. The long head pulls the arm away from the trunk (abduction) and turns it inwards (inward rotation) whereas the short head pulls the arm back towards the trunk (adduction). When both heads contract simultaneously it leads to an arm bend (flexion). In the elbow joint the muscle bends the forearm (flexion) and rotates it outwards (supination). The supination is most powerful in a flexed elbow. In addition to the movement functions, the biceps has the important task to support the humeral head within the shoulder joint. Its antagonist is the triceps brachii in the posterior compartment of the arm.

Aciclovir is active against herpesviruses but does not eradicate latent virus.

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Helicobacter pylori is a curved or helix-shaped, non-spore forming, Gram-negative, microaerophilic bacteria. It is motile, having multiple flagella at one pole. It has a lipopolysaccharide component in its outer membrane.

Major Actions of Insulin:
↑ Glucose uptake into cells
↑ Glycogenesis
↓ Glycogenolysis
↓ Gluconeogenesis
↑ Protein synthesis
↓ Protein degradation
↑ Fat deposition
↓ Lipolysis
↓ Ketoacid production
↑ K+ uptake into cells

Major Actions of Glucagon:
↓ Glycogenesis
↑ Glycogenolysis
↑ Gluconeogenesis
↓ Fatty acid synthesis
↑ Lipolysis
↑ Ketoacid production

Features of osteomalacia include:
Bone pain (particularly bone, pelvis, ribs)
Neuromuscular dysfunction (particularly in the gluteal muscles, leading to waddling gait
Pseudofractures on x-ray (looser zones)
Elevated alkaline phosphatase, hypocalcaemia and low phosphate due to secondary hyperparathyroidism

A history of stroke and poor nutritional status points towards a nutritional deficiency as the most likely cause of her symptoms. The examination would differentiate between Vitamin B12 and Folic acid deficiency as in the former. The patient has a beefy red tongue and symptoms indicating peripheral nervous system involvement or subacute combined spinal cord degeneration. The patient may also have a lemon-yellow skin colour, loss of proprioception and vibratory sense and oral ulceration.

Investigations in B12 deficiency can reveal the following:
1. Macrocytic anaemia
2. Neutropoenia
3. Thrombocytopaenia
4. Blood film: anisocytosis, poikilocytosis
5. Low serum B12
6. Raised serum bilirubin (haemolysis)
7. Intrinsic factor antibodies
8. Positive Schilling test

Legionella pneumophilais a Gram negative bacterium that is found in natural water supplies and in the soil, transmitted predominantly via inhalation of aerosols generated from contaminated water (direct person-to-person spread of infected patients does not occur). It is the cause of Legionnaires’ disease. Outbreaks of Legionnaires’ disease have been linked to poorly maintained air conditioning systems, whirlpool spas and hot tubs.

The clinical features of the pneumonic form of Legionnaires’ disease include:
Mild flu-like prodrome for 1-3 days
Cough (usually non-productive and occurs in approximately 90%)
Pleuritic chest pain
Haemoptysis
Headache
Nausea, vomiting and diarrhoea
Anorexia

Legionella pneumophilainfections can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur with Legionnaires’ disease and will result in hyponatraemia as is seen in this case.
Legionella pneumophilainfections are resistant to amoxicillin but can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used. The majority of cases of Legionnaires’ disease are caused by Legionella pneumophila, however many other species of Legionella have been identified.
Legionella longbeachae is another less commonly encountered species that has also been implicated in outbreaks. It is predominantly found in soil and potting compost, and has caused outbreaks of Pontiac fever, the non-respiratory and less severe variant of Legionnaires’ disease.

Neutropenia is defined as a total neutrophil count of < 2.0 x 109/l.
It can be caused by:
Viral infections
Collagen disease e.g. SLE and RA
Chemotherapy and radiotherapy
Hypersplenism
Marrow infiltration
Vitamin and folate deficiency
Drug reactions
Drugs that cause neutropenia include flecainide, phenytoin, carbimazole, indomethacin and co-trimoxazole.

Acute mastoiditis is a complication (rare) of acute otitis media (AOM) and the commonest causative organism is Streptococcus pneumoniae.

Generally, acute mastoiditis presents with:
Pyrexia
Recent history of AOM
Mastoid swelling and erythema
Otalgia
Otorrhoea and perforation of tympanic membrane
Post-auricular pain
Protrusion of the ears

The female Anopheles mosquito is the vector for Plasmodium falciparum transmission. Treponema pallidum is transmitted through sexual transmission or direct skin contact. Clostridium perfringens is spread by direct skin contact or through oral-faecal route. The oral-faecal pathway is how Vibrio cholerae spreads. Mycoplasma tuberculosis is spread via the airborne route.

Fat-soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut. Deficiency may present in the newborn (haemorrhagic disease of the newborn) or in later life. Deficiency may be caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin. The activity of factors II, VII, IX and X are vitamin K dependent as well as that of protein C and protein S. Both PT and APTT are prolonged.

Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific nephritogenic strains of group A beta-haemolytic streptococcus. The clinical presentation of PSGN varies from asymptomatic, microscopic haematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), oedema, hypertension, and acute kidney injury.

Only a very small fraction of the thyroid hormones circulating in the blood are free. The majority is bound to transport proteins. Only the free thyroid hormones are biologically active, and measurement of total thyroid hormone levels can be misleading.

The relative percentages of bound and unbound thyroid hormones are:
Bound to thyroid-binding globulin -70%
Bound to albumin -15-20%
Bound to transthyretin -10-15%
Free T3 -0.3%
Free T4 -0.03%

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium-channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

The following summarises the toxicity of calcium-channel blockers:
Cardiac effects
Vascular smooth muscle tone affects
Metabolic effects
Excessive negative inotropy: myocardial depression
Negative chronotropy: sinus bradycardia
Negative dromotropy: atrioventricular node blockade
Decreased afterload
Systemic hypotension
Coronary vasodilation
Hypoinsulinaemia
Calcium channel blocker-induced insulin resistance

Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. Outcomes from a meta-analysis may include a more precise estimate of the effect of treatment or risk factor for disease, or other outcomes, than any individual study contributing to the pooled analysis. The examination of variability or heterogeneity in study results is also a critical outcome.
The benefits of meta-analysis include a consolidated and quantitative review of a large, and often complex, sometimes apparently conflicting, body of literature. The specification of the outcome and hypotheses that are tested is critical to the conduct of meta-analyses, as is a sensitive literature search.

Important medical questions are typically studied more than once, often by different research teams in different locations. In many instances, the results of these multiple small studies of an issue are diverse and conflicting, which makes the clinical decision-making difficult. The need to arrive at decisions affecting clinical practise fostered the momentum toward evidence-based medicine. Evidence-based medicine may be defined as the systematic, quantitative, preferentially experimental approach to obtaining and using medical information. Therefore, meta-analysis, a statistical procedure that integrates the results of several independent studies, plays a central role in evidence-based medicine.

Lithium levels are raised by NSAIDs because renal clearance is reduced. Lithium is a small ion (74 Daltons) with no protein or tissue binding and is therefore amenable to haemodialysis. Lithium is freely distributed throughout total body water with a volume of distribution between 0.6 to 0.9 L/kg, although the volume may be smaller in the elderly, who have less lean body mass and less total body water. Steady-state serum levels are typically reached within five days at the usual oral dose of 1200 to 1800 mg/day. The half-life for lithium is approximately 18 hours in adults and 36 hours in the elderly.
Lithium is excreted almost entirely by the kidneys and is handled in a manner similar to sodium. Lithium is freely filtered but over 60 percent is then reabsorbed by the proximal tubules.