Cholera is caused by Vibrio cholerae, a motile, Gram-negative, curved bacillus. It is transmitted through water and food (especially seafood) and is primarily a disease seen in developing countries where there is poor sanitation and lack of safe water supplies.The cholera toxin leads to stimulation of adenyl cyclase, ADP-ribosylation of the G regulatory protein, inactivation of GTPase leading to active outpouring of NaCl. The cholera toxin consists of an A (the toxin) and B subunit. The B subunit attaches to the gut mucosa and presents the A subunit to the cell. The toxin stimulates adenyl cyclase by irreversible ADP-ribosylation of the GTP binding domain of adenyl cyclase leading to the opening of chloride channels resulting in an outpouring of NaCl and water into the lumen of the gut and causing secretory diarrhoea.Incubation period is between 2 and 5 days, but can be as short as just a few hours.

The most important medicine for treating anaphylactic responses is adrenaline. It decreases oedema and reverses peripheral vasodilation as an alpha-adrenergic receptor agonist. Its beta-adrenergic effects widen the bronchial airways, enhance the force of cardiac contraction, and inhibit the release of histamine and leukotriene. The first medicine to be given is adrenaline, and the IM route is optimal for most people.In anaphylaxis, age-related dosages of IM adrenaline are given:150 mcg (0.15 mL of 1:1000) for children under the age of six  300 mcg (0.3 mL of 1:1000) for a child aged 6 to 12 years 500 mcg  (0.5 mL of 1:1000) for children aged 12 and above500 mcg (0.5 mL of 1:1000) for adults 

Malaria results from infection with single-celled parasites belonging to the Plasmodium genus. Five species of Plasmodium are known to cause disease in humans: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Chloroquine remains the mainstay of treatment for uncomplicated vivax malaria.The female Anopheles mosquito serves as the biologic vector and definitive host. A complication of infection with P. falciparum is blackwater fever, a condition characterized by haemoglobinuria. Plasmodium ovale has the longest incubation period, which can be up to 40 days. Plasmodium falciparum has a shorter incubation period of 7-14 days.

The DVLA sends a detailed information sheet about their licence and driving to all drivers with diabetes mellitus. The primary danger of driving while diabetic is hypoglycaemia.The DVLA must be notified of the following diabetic patients:All of the drivers are on insulin. (Licenses are being reviewed more frequently.)Those who are at high risk of hypoglycaemia and have had more than one episode of severe hypoglycaemia in the previous year. (Severe hypoglycaemia is defined as requiring the assistance of another person to manage.)Those who are unaware of their hypoglycaemiaAnyone who has ever been in a car accident due to hypoglycaemiaAnyone with diabetic retinopathy who needs laser treatment (to both eyes or to a second eye if sight only in one eye)Patients with diabetes complications that impair their ability to drive.To drive, drivers with insulin-treated diabetes must meet the following requirements:They need to be aware of hypoglycaemia.They must not have had more than one episode of hypoglycaemia in the previous 12 months that necessitated the assistance of another person.They must check their blood glucose levels no later than 2 hours before the first journey.While driving, they must check their blood glucose levels every two hours.The visual acuity and visual field standards must be met.Any significant changes in their condition must be reported to the DVLA. Furthermore, on days when they are not driving, group 2 licence holders must test their blood glucose twice daily using a metre that can store three months’ worth of readings.In addition to this advice, the DVLA also offers the following advice to diabetic patients:When taking tablets that have the potential to cause hypoglycaemia (such as sulfonylureas and glinides), monitoring may be necessary if there has been more than one episode of severe hypoglycaemia.Drivers must show good control and be able to recognise hypoglycaemia.Verify that your vision meets the required standard.If a patient feels hypoglycaemic or has a blood glucose level of less than 4.0 mmol/L, they should not drive. Driving should not be resumed until blood glucose levels have returned to normal, which should take 45 minutes.If there are any warning signs, patients should carry rapidly absorbed sugar in their vehicle and stop, turn off the ignition, and eat it.If resuscitation is required, a card stating which medications they are taking should be carried.If hypoglycaemia causes an accident, a diabetic driver may be charged with driving under the influence of drugs.

Varicella-zoster immunoglobulin (VZIG) is indicated for post exposure prevention and treatment of varicella. It is recommended as prophylaxis for high-risk patients with no known immunity (i.e. no known previous chickenpox) who have had a significant exposure to varicella-zoster (considered >4 hours close contact).The high-risk groups are:1. Neonates2. Pregnant women3. The immunocompromised (e.g. cancer, immunosuppressive therapies)4. Those on high dose steroids (children on more than 2 mg/kg/day for more than 14 days, or adults on 40 mg/day for more than a week)This patient is at high risk of developing adrenal insufficiency and may need a temporary increase in her steroid dose during infection or stress. It would be inappropriate to stop or wean down her dose of prednisolone and can cause side effects.Since he is on steroids without immunity for chickenpox, he is at risk of developing severe varicella infection, with possible complications including pneumonia, hepatitis and DIC. If he develops a varicella infection, he will need to be admitted and require a specialist review and intravenous Acyclovir.

The rate of baroreceptor firing slows down when blood pressure falls too low. This causes an increase in sympathetic stimulation of the heart, resulting in an increase in cardiac output. It also causes vasoconstriction by activating alpha 1 receptors in smooth muscle, which causes sympathetic stimulation of peripheral vessels. Alpha2 receptors can be found in both the brain and the peripheral nervous system. They control sympathetic outflow in the brain stem. Beta1 receptors, which are found on the cell membrane of cardiac muscle cells, stimulate heart rate and myocardial contractility. The smooth muscle cell membrane contains beta2 receptors, which promote smooth muscle relaxation in the lungs causing bronchodilation, GI tract, and peripheral blood vessels.

Muscles of the posterior compartment of the leg, innervated by the tibial nerve, perform plantar flexion of the foot at the ankle joint. The fibularis longus (innervated by the superficial fibular nerve) assists in plantar flexion but is not the most important.

In adults, there are 32 teeth, 16 in the upper jaw and 16 in the lower jaw. On each side in both upper and lower arches, there are two incisors, one canine, two premolars and three molar teeth.

Aspirin contraindications include: hypersensitivity to NSAIDs; asthma, rhinitis, and nasal polyps; and usage in children or teens.There is little evidence of allergic cross-reactivity for salicylates. However, due to similarities in chemical structure and/or pharmacologic activities, the possibility of cross-sensitivity cannot be completely ruled out.

Aspirin (at analgesic doses) is contraindicated in:People with a history of true hypersensitivity to aspirin or salicylates (symptoms of hypersensitivity to aspirin or salicylates include bronchospasm, urticaria, angioedema, and vasomotor rhinitis)People with active or previous peptic ulcerationPeople with haemophilia or another bleeding disorderChildren younger than 16 years of age (risk of Reye’s syndrome)People with severe cardiac failurePeople with severe hepatic impairmentPeople with severe renal impairmentN.B. Owing to an association with Reye’s syndrome, aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated, e.g. for Kawasaki disease.

The results of meta-analysis are often displayed graphically in a forest plot. A properly constructed forest plot is the most effective way to graphically display the relative strength of multiple studies attempting to answer the same question. A typical meta-analysis consists of three main objectives that include estimation of effect sizes from individual studies and a pooled summary estimate with their confidence intervals (CIs), heterogeneity among the studies, and any publication bias. The forest plot illustrates the first two of these objectives. Forest plots visualize the effect measure and CI of individual studies, which provide the raw data for the meta-analysis, as well the pooled-effect measure and CI. The individual studies also can be grouped in the forest plot by some of their characteristics for ease of interpretation such as by study size or year of publication. When comparing the outcomes between an intervention and a control group, dichotomous outcome variables are expressed as ratios (i.e. odds ratios, ORs or risk ratios, RRs), while for continuous outcomes, a weighted mean difference is reported.

In restrictive lung disease, the FEV1/FVC ratio is usually >0.7%.In obstructive lung disease, FEV1 is reduced to <80% of normal and FVC is usually reduced. The FEV1/FVC ratio is reduced to 80% in the presence of symptomsModerate airflow obstruction = FEV 1 of 50-79%Severe airflow obstruction = FEV 1 of 30-49%Very severe airflow obstruction = FEV1<30%.Spirometry is a poor predictor of quality of life in COPD. However, it can be used as part of the assessment of severity of COPD.

Proinsulin is synthesised as a single-chain peptide. A connecting peptide (C peptide) within storage granules is removed by proteases to yield insulin. Insulin:1. is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds. 2. is produced by beta cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas. 3. release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin. However, most output is driven by the rise in plasma glucose concentration that occurs after a meal. 4. effects are mediated by the receptor tyrosine kinase.

Fibrinoid necrosis occurs in malignant hypertension where increased arterial pressure results in necrosis of smooth muscle wall. Eosinophilic and fibrinous deposits are seen.

Absolute risk and relative risk are used to assess the strength of a relationship between a disease and a factor that may affect it.Absolute risk (AR) is the risk of developing a disease over a time period:AR = the number of events that occur in a group / number of people in that groupThe absolute risk reduction (ARR) is the difference between the absolute risk in the control group (ARC) and the absolute risk in the treated group (ART). ARR = ARC – ARTThe control group is the warfarin group, therefore the ARC is 20/500 (0.04). Treatment group is the ticagrelor group and ART = 30/300 (0.1). ARR = 0.04 – 0.1 = -0.06. This shows that treatment with ticagrelor increases risk of developing stroke. This is also termed a relative risk increase.Relative risk, or risk ratio, (RR) is used to compare the risk in the two different groups. It is the ratio of the absolute risks of the disease in the treatment group (ART) to the absolute risk of the disease in the control group (ARC):RR=ART /ARCTherefore RR = 0.1 / 0.04 = 2.5RR < 1 means the intervention reduces the risk of the outcome being studiedRR = 1 means the treatment has no effect on the outcome being studiedRR > 1 means the intervention increased the risk of the outcome being studiedSince RR is 2.5, ticagrelor increases the risk of stroke.SUMMARYAbsolute risk reduction is -0.06Absolute risk in warfarin group = 0.04Relative risk = 2.5Ticagrelor has no effect on stroke is incorrect because RR is not =1

Endocarditis is infective or non infective inflammation (marantic endocarditis) of the inner layer of the heart and it often involves the heart valves.Risk factors include:Prosthetic heart valvesCongenital heart defectsPrior history of endocarditisRheumatic feverIllicit intravenous drug useIn the presentation of endocarditis, the following triad is often quoted:Persistent feverEmbolic phenomenaNew or changing murmurFlucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis.

According to the CDC definition, a patient co-infected with HIV can be diagnosed with AIDS if he or she has:A CD4 T-cell count of less than 200 cells/mm3 or;A CD4 T-cell percentage of total lymphocytes of less than 15% or;An AIDS defining infectionA Streptococcal throat infection is not an AIDS defining infection.A normal CD4 count ranges from 500-1000 cells/mm3. A CD4 (not CD8) count of less than 200 cells/mm3 is AIDS defining.The CD4 count can vary from day to day and depending upon the time that the blood test is taken. It can also be affected by the presence of other infections or illnesses. Treatment with anti-retroviral therapy should be considered at CD4 count of less than 350 cells/mm3.Serum concentrations of the p24 antigen (the viral protein that makes up most of the core of the HIV) are usually high in the first few weeks after human immunodeficiency virus (HIV) infection and testing for p24 antigen is therefore a useful way of diagnosing very early infection.

Molecular weight is the main factor in determining whether a substance is filtered or not – molecules < 7 kDa in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma. The epithelial lining of the Bowman's capsule consists of a single layer of cells called podocytes. The glomerular capillary endothelium is perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 70 kDa to pass freely.

98% of cases of myeloma occur over the age of 40 years with a peak incidence between 65 and 70 years. The disease is twice as common in black individuals compared to those of white or Asian origin. Laboratory findings include presence of a paraprotein in serum/urine (the paraprotein is IgG in 60% of cases, IgA in 20% and light chain only in almost all the rest) and marked Rouleaux formation on blood film. There is no cure for myeloma. The overall median survival is now 7-10 years and in younger (less than 50 years) patients it can be over 10 years.

Bile is secreted by hepatocytes. It is isotonic and resembles plasma ionically. This fraction of bile is called the bile acid-dependent fraction. As it passes along the bile duct, the bile is modified by epithelial cells lining the duct by the addition of water and bicarbonate ions; this fraction is called the bile acid-independent fraction. Overall, the liver can produce 500 – 1000 mL of bile per day. The bile is either discharged directly into the duodenum or stored in the gallbladder. The bile acid-independent fraction is made at the time it is required i.e. during digestion of chyme. The bile acid-dependent fraction is made when the bile salts are returned from the GI tract to the liver, and is then stored in the gallbladder until needed. The gallbladder not only stores bile but concentrates it by removing non-essential solutes and water, leaving bile acids and pigments, mainly by active transport of Na+into the intercellular spaces of the lining cells which, in turn, draws in water, HCO3-and Cl-from the bile and into the extracellular fluid. Within a few minutes of a meal, particularly when fatty foods have been consumed, the gallbladder contracts and releases bile into the bile duct. The sphincter of Oddi is relaxed, allowing the bile to pass into the duodenum through the ampulla of Vater.

Colonic mass movement describes the intense contraction that begins halfway along the transverse colon and pushes the intestinal contents in the proximal colon towards the rectum. It occurs shortly after a meal due to distension of the stomach and duodenum as part of the gastrocolic reflex and if faeces is present in the rectum, stimulates the urge to defecate. Distention of the rectum causes firing of afferent cholinergic parasympathetic fibres. The internal sphincter is made up of circular smooth muscle innervated by the autonomic fibres, and the more distal external sphincter is composed of striated muscle innervated by motor fibres from the pudendal nerve. During defaecation, relaxation of pelvic muscles straightens the rectum.

Exposure to nitrous oxide for prolonged periods, either by continuous or by intermittent administration, may result in megaloblastic anaemia as a result of interference with the action of vitamin B12; neurological toxic effects can occur without preceding overt haematological changes. Depression of white cell formation may also occur.

Resistant to the effects of adrenaline in anaphylaxis is seen in patients taking beta-blockers.Glucagon can be used to overcome the effects of the beta-blockade if initial doses of adrenaline are unsuccessful in patients taking beta-blockers.

A refractory period follows each action potential. The absolute refractory time and the relative refractory period are two divisions of refractory periods. Because the sodium channels seal after an AP, they enter an inactive state during which they cannot be reopened regardless of membrane potential, this time occurs.The sodium channels slowly come out of inactivation during the relative refractory period that follows. During this time, a stronger stimulus than that required to initiate an action potential can excite the cell. The strength of the stimulus required early in the relative refractory period is relatively high, and it steadily decreases as more sodium channels recover from the inactivation of the refractory period.Nodes of Ranvier are periodic holes in a myelinate axon when there is no myelin and the axonal membrane is exposed. There are no gated ion channels in the portion of the axon covered by the myelin sheath, but there is a high density of ion channels in the Nodes of Ranvier. Action potentials can only occur at the nodes as a result of this.

IgA is the predominant antibody class in secretions and tremendous quantities are secreted into various body spaces and onto mucosal surfaces (the gut lumen, the pharynx and sinuses, the larger airways, although not the alveoli). Because of its size, the majority of IgM is found in the circulation.Along with IgM, IgD is predominant among the surface receptors of mature B cells, where it plays a key role in B cells activation.IgE has the lowest concentration in normal human serum. It plays a prominent role in immune responses to helminth parasites, and in allergic reactions.IgG is the most abundant immunoglobulin and constitutes 75 percent of serum immunoglobulin in an adult human

Diagnosis is made from microscopy and culture of skin scrapings, hair samples or nail clippings depending on the site of infection. The lesions of ringworm typically have a dark outer ring with a pale centre. Tinea capitis is ringworm affecting the head and scalp. Spread is via direct skin contact. Treatment is usually topical, oral antifungals are reserved for refractory infection.

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.In the presence of UVB light, 7-dehydrocholesterol is converted to cholecalciferol in the epidermal layer of the skin, resulting in 1,25-dihydroxycholecalciferol.Cholecalciferol is then converted to 25-hydroxycholecalciferol in the endoplasmic reticulum of liver hepatocytes by 25-hydroxylase (calcifediol).Finally, 1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney. The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is induced by parathyroid hormone or hypophosphatemia.The following are the primary effects of 1,25-dihydroxycholecalciferol:Calcium and phosphate absorption in the small intestine is increased.Calcium reabsorption in the kidneys is increased.Increases phosphate reabsorption in the kidneys.Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)

Meckel’s diverticulum has certain classic characteristics.1. It lies on the antimesenteric border of the middle-to-distal ileum2. It is approximately 2 feet proximal to the ileocaecal junction3. It appears as a blind-ended tubular outpouching of bowel4. It is about 2 inches long, 5. It occurs in about 2% of the population, 6. It may contain two types of ectopic tissue (gastric and pancreatic). 7. The diverticulum is supplied by the superior mesenteric artery.8. Proximal to the major duodenal papilla the duodenum is supplied by the gastroduodenal artery (branch of the coeliac trunk)9. Distal to the major duodenal papilla it is supplied by the inferior pancreaticoduodenal artery (branch of superior mesenteric artery).10. The arterial supply to the jejunoileum is from the superior mesenteric artery.

Ciprofloxacin and other quinolone antibiotics work by blocking DNA gyrase, an enzyme that compresses bacterial DNA into supercoils, as well as a type II topoisomerase, which is required for bacterial DNA separation. As a result, they prevent nucleic acid synthesis.The following is a summary of the many modes of action of various types of antimicrobial agents:Action Mechanisms- Examples:Cell wall production is inhibitedVancomycinVancomycinCephalosporinsThe function of the cell membrane is disrupted NystatinPolymyxinsAmphotericin B Inhibition of protein synthesisChloramphenicolMacrolidesAminoglycosidesTetracyclinesNucleic acid synthesis inhibitionQuinolonesTrimethoprimRifampicin5-nitroimidazolesSulphonamidesAnti-metabolic activityIsoniazid

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.PTH is synthesised by and released from the chief cells of the four parathyroid glands that are located immediately behind the thyroid gland.PTH is released in response to the following stimuli:Decreased plasma calcium concentrationIncreased plasma phosphate concentration (indirectly by binding to plasma calcium and reducing the calcium concentration)PTH release is inhibited by the following factors:Normal/increased plasma calcium concentrationHypomagnesaemiaThe main actions of PTH are:Increases plasma calcium concentrationDecreases plasma phosphate concentrationIncreases osteoclastic activity (increasing calcium and phosphate resorption from bone)Increases renal tubular reabsorption of calciumDecreases renal phosphate reabsorptionIncreases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)