High-dose NSAIDs are the first-line treatment for acute gout. In the absence of any contraindications, Naproxen 750 mg as a stat dose followed by 250 mg TDS is commonly used.Aspirin is contraindicated in gout. It reduces the urinary clearance of urate and also interferes with the action of uricosuric agents. Colchicine is preferred in patients with heart failure or in those who are intolerant of NSAIDs. It is as effective as NSAIDs in relieving acute attacks.Colchicine acts on the neutrophils, binding to tubulin to prevent neutrophil migration into the joint. Where Allopurinol is not tolerated, it has a role in prophylactic treatment of gout.Allopurinol should not be started in the acute phase of gout as it increases the severity and duration of symptoms. It is used as a prophylaxis in preventing future attacks and acts by reducing serum uric acid levels.

A total neutrophil count of greater than 7.5 x 109/L is called neutrophilia. Typhoid fever usually causes leukopenia or neutropenia. Both localised and generalised bacterial infections can cause neutrophilia. Metabolic disorders such as – gout- eclampsia- uraemia can also cause neutrophilia. Acute neutrophilia, in which immature neutrophils can be seen, is referred to as a left shift and can be seen in conditions such as appendicitis.

Barbiturates induce hepatic enzymes. The enzyme gamma aminolevulinic acid synthetase, which produces porphyrins, can be induced and in susceptible patients an attack of acute intermittent porphyria can occur. Thiopental is absolutely contraindicated in these patients.

Flecainide is an antiarrhythmic drug of class Ic that works by blocking the Nav1.5 sodium channel in the heart, prolonging the cardiac action potential and slowing cardiac impulse conduction. It has a significant impact on accessory pathway conduction, particularly retrograde conduction, and significantly reduces ventricular ectopic foci.Many different arrhythmias can be treated with flecainide, including:Pre-excitation syndromes (e.g. Wolff-Parkinson-White)Acute atrial arrhythmiasVentricular arrhythmiasChronic neuropathic painThe use of flecainide is contraindicated in the following situations:Abnormal left ventricular functionAtrial conduction defects (unless pacing rescue available)Bundle branch block (unless pacing rescue available)Distal block (unless pacing rescue available)Haemodynamically significant valvular heart diseaseHeart failureHistory of myocardial infarctionLong-standing atrial fibrillation where conversion to sinus rhythm not attemptedSecond-degree or greater AV block (unless pacing rescue available)Sinus node dysfunction (unless pacing rescue available)Flecainide should only be used in people who don’t have a structural heart problem. The CAST trial found a significant increase in sudden cardiac death and all-cause mortality in patients with an ejection fraction of less than 40% after a myocardial infarction, where it tended to be pro-arrhythmic.Anti-arrhythmic drugs have a limited and ineffective role in the treatment of atrial flutter. It’s important to keep in mind that flecainide shouldn’t be used by itself to treat atrial flutter. When used alone, there is a risk of inducing 1:1 atrioventricular conduction, which results in an increase in ventricular rate that is paradoxical. As a result, it should be used in conjunction with a beta-blocker or a calcium channel blocker with a rate-limiting effect.

Myosin is the major constituent of the thick filament. Actin is the major constituent of the THIN filament. Thin filaments consist of actin, tropomyosin and troponin in the ratio 7:1:1.

Gastric lipase, commonly known as LIPF, is an acidic lipase released by gastric chief cells, which are found deep within the stomach lining’s mucosal layer. It’s an enzymatic protein that’s in charge of fat digestion in the stomach.

Cetirizine is a competitive inhibitor at the H1-receptor (an antihistamine).

Chemoreceptors are activated when the chemical composition of their immediate surroundings changes. Peripheral chemoreceptors, together with central chemoreceptors, regulate respiratory functions. They detect changes in arterial blood oxygen levels. Decreased arterial Po2 (partial pressure of oxygen) reflexly stimulates peripheral chemoreceptors. When peripheral chemoreceptors detect changes in arterial blood oxygen, they will trigger cardiorespiratory changes such as an increase in breathing and blood pressure. These reflexes are important for maintaining homeostasis during hypoxemia.

Avulsion fractures of the fibular head are rare and are so-called the arcuate signal. The “arcuate signal” is used to describe an avulsed bone fragment related to the insertion site of the tendon of the biceps femoris associated with the arcuate complex, which consists of the fabellofibular, popliteofibular, and arcuate ligaments. Such lesions are typically observed in direct trauma to the knee with excessive varus and internal rotation forces or indirect trauma with the same direction of the force.

The spring-ligament complex is a significant medial arch stabilizer. The two important functions of this ligament include promoting the stability of the talonavicular joint by acting as a support for the talus head and by acting as a static support to maintain the medial longitudinal arch.

Cortisol is a steroid hormone produced in the zona fasciculata of the adrenal cortex. It is released in response to stress and low blood glucose concentrations.Cortisol acts to: raise plasma glucose by stimulating glycolysis and gluconeogenesis in the liver and inhibiting peripheral glucose uptake into storage tissues, increase protein breakdown in skeletal muscle, skin and bone to release amino acids, increase lipolysis from adipose tissues to release fatty acidsand at higher levels and mimic the actions of aldosterone on the kidney to retain Na+ and water and lose K+ ionssuppress the action of immune cells

Facial nerve palsy can result in inability to close the eye due to paralysis of the orbicularis oculi muscle. Elevation of the eyelid in eye opening is a function of the levator palpebrae superioris muscle and the superior tarsal muscle, innervated by the oculomotor nerve and the sympathetic chain respectively.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT is frequently considered in the differential diagnosis of thrombocytopenia occurring in patients on heparin therapy. HIT is a challenging diagnosis because of routine heparin use in hospitalized patients, the common occurrence of thrombocytopenia. The process of heparin dependent IgG antibodies binding to heparin/platelet factor 4 complexes activates platelets and produces a hypercoagulable state. This syndrome typically develops 5-10 days (range 4-15 days) after heparin is commenced. It can occur with unfractionated heparin, low molecular weight heparin, or, rarely, fondaparinux. The diagnosis of HIT requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin dependent platelet activating HIT antibodies. Discontinuation of heparin alone or initiation of a vitamin K antagonist alone like warfarin, is not sufficient to stop the development of thrombosis in patients with acute HIT. If there is moderate clinical suspicion for HIT, all sources of heparin must be discontinued and there must be consideration of anticoagulant treatment with a non-heparin drug.

Aspirin inhibits cyclo-oxygenase irreversibly by covalently acetylating the cyclo-oxygenase active site in both COX-1 and COX-2. The production of prostaglandin and thromboxane is reduced as a result. As a result, platelet activation and aggregation are reduced. A single dose of aspirin has a half-life of 7-10 days, which is the time it takes for the bone marrow to produce new platelets.Aspirin only inhibits COX-1, the enzyme that produces thromboxane A2, at low doses (75 mg per day), and thus has a primarily anti-thrombotic effect.Aspirin inhibits both COX-1 and COX-2 at medium to high doses (500-5000 mg per day). COX-2 is involved in the production of prostaglandins, so it has an anti-inflammatory effect at these concentrations.Aspirin, when used as an antipyretic for a viral illness in children, can cause Reye’s syndrome. Reye’s syndrome is a potentially fatal liver disease that causes encephalopathy and liver failure.The inability of aspirin to reduce platelet production of thromboxane A2, and thus platelet activation and aggregation, is known as aspirin resistance. Although the exact frequency and mechanism of aspirin resistance are unknown, it is thought to affect about 1% of users. Women are more likely than men to experience this phenomenon.According to new research, taking aspirin on a regular basis lowers the risk of colorectal cancer. It may also protect against cancers of the breast, bladder, prostate, and lungs.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:Immunological side effectsErrors in administration (episodes of ‘wrong blood’)Viruses and Infections (bacterial, viral, possibly prion)ImmunodilutionA culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.The following is a list of the most common transfusion reactions and complications:1) Reaction to a febrile transfusionThe temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.The most common response (1 in 8 transfusions).Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.Only supportive. The use of paracetamol is beneficial.2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when theFever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.Early on, many people report a sense of ‘impending doom.’The most serious reaction. ABO incompatibility is frequently caused by a clerical error.STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.3) Haemolytic reaction that is delayedIt usually happens 4 to 8 days after a blood transfusion.Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.Positive Coombs test for direct antiglobulin.Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.The majority of delayed haemolytic reactions are harmless and do not require treatment.Anaemia and renal function should be monitored and treated as needed.4) Reaction to allergensForeign plasma proteins are usually to blame, but anti-IgA could also be to blame.Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.Anaphylaxis is a rare occurrence.Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.5) TRALI (Transfusion Related Acute Lung Injury)Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.The most common cause of death from transfusion reactions is this.STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.The use of diuretics should be avoided.6) TACO (Transfusion Associated Circulatory Overload)Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.Blood transfusions should be given slowly, over the course of 3-4 hours.

Blocking ACE also diminishes the breakdown of the potent vasodilator bradykinin which is the cause of the persistent dry cough. Angiotensin-II receptor blockers do not have this effect, therefore they are useful alternative for patients who have to discontinue an ACE inhibitor because of persistent cough.

A commensal is an organism that is part of the normal flora.

ALL is the most common leukaemia in children, with a peak incidence between the ages of 2 and 5.ALL has a wide range of clinical symptoms, but many children present with an acute illness that resembles coryza or a viral infection. ALL also has the following features:Weakness and sluggishness all overMuscle, joint, and bone pain that isn’t specificAnaemiaPetechiae and unexplained bruisingOedemaLymphadenopathyHepatosplenomegalyThe following are typical features of a full blood count in patients with ALL:Anaemia (normocytic or macrocytic)Leukopenia affects about half of the patients (WCC 4 x 109/l).Around 25% of patients have leucocytosis (WCC > 10 x 109/l).Around 25% of patients have hyperleukocytosis (WCC > 50 x 109/l).Thrombocytopaenia

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 daysCough (usually non-productive and occurs in approximately 90%)Pleuritic chest painHaemoptysisHeadacheNausea, vomiting and diarrhoeaAnorexiaLegionella 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.

Absolute risk reduction (ARR) of treatment = risk of death in control group – risk of death in treatment groupARR = (10/1000) – (5/1000) = 5/1000 = 0.005Number needed to treat (NNT) = 1/ARR = 1/0.005 = 200Therefore 200 people would need to be treated to prevent one extra death.

Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia, and is rarer than haemophilia A. Haemophilia B tends to be similar to haemophilia A but less severe. The two disorders can only be distinguished by specific coagulation factor assays.The incidence is one-fifth of that of haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and low factor IX.Haemophilia B inherited in an X-linked recessive fashion, affecting males born to carrier mothers.There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

A cricothyrotomy involves making an opening in the median cricothyroid ligament (the medial part of the cricothyroid membrane), between the cricoid cartilage below and the thyroid cartilage above.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.Cushing’s syndrome has a wide range of clinical manifestations that are dependent on the degree of cortisol overproduction. The appearance might be vague and the diagnosis difficult to detect when cortisol levels are just somewhat elevated. On the other hand, in long-term cases of severely increased cortisol levels, the presentation might be colourful and the diagnosis simple.Cushing’s syndrome has the following clinical features:Obesity and weight growth in the true senseSupraclavicular fat pads are fat pads that are located above the clavicle.Buffalo humpFullness and plethora of the face (‘moon facies’)Muscle atrophy and weakening at the proximal levelDiabetes mellitus, also known as impaired glucose toleranceHypertensionSkin thinning and bruisingDepressionHirsutismAcneOsteoporosisAmenorrhoea or oligomenorrhoeaCortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater during the whole 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed. As a result, random cortisol testing is not an effective screening technique and is not advised.The following are the two most common first-line screening tests:Cortisol levels in the urine are measured every 24 hours.A diagnosis of Cushing’s syndrome can be made if more than two collections measure cortisol excretion more than three times the upper limit of normal.Physical stress (e.g., excessive exercise, trauma), mental stress (e.g., sadness), alcohol or drug misuse, complex diabetes, and pregnancy can all cause false positives.Renal dysfunction, inadequate collection, and cyclical Cushing’s disease can all cause false negatives.The overnight low-dose dexamethasone suppression test (LDDST) involves giving 1 mg of dexamethasone at 11 p.m. and measuring blood cortisol levels at 8 a.m. the next day.Cushing’s syndrome is diagnosed when cortisol is not suppressed to less than 50 nmol/L.It might be difficult to tell the difference between mild Cushing’s disease and normal cortisol production.False positives can occur as a result of depression, severe systemic sickness, renal failure, prolonged alcohol misuse, old age, and the use of hepatic enzyme-inducing medicines, among other things.False negatives are extremely uncommon in Cushing’s disease patients.A characteristic biochemical picture might also be helpful in confirming the diagnosis of Cushing’s syndrome. The following are the primary characteristics:HypokalaemiaAlkalosis metabolique

The FDA categorizes Paracetamol as an NSAID (nonsteroidal anti-inflammatory drug) as it is believed to selectively inhibit cyclo-oxygenase 3 (COX-3) receptors in the brain and spinal cord. COX-3 is a unique variant of the more known COX-1 and COX-2. It is responsible for the production of prostaglandins in central areas, which sensitizes free nerve endings to the chemical mediators of pain. Therefore, by selectively inhibiting COX-3, paracetamol effectively reduces pain sensation by increasing the pain threshold.Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects.The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centres in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat.

PTH is synthesised and released from the chief cells of the four parathyroid glands located behind the thyroid gland.It is a polypeptide containing 84 amino acids and it controls free calcium in the body.The following stimuli causes release of PTH:Increased plasma phosphate concentrationDecreased plasma calcium concentrationPTH release is inhibited by:Normal or 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)

Angiotensin-converting enzyme (ACE) inhibitors are the most common cause of drug-induced angioedema in the United Kingdom and the United States, owing to their widespread use.Angioedema is caused by ACE inhibitors in 0.1 to 0.7 percent of patients, with data indicating a persistent and relatively constant risk year after year. People of African descent have a five-fold higher chance of contracting the disease.Swelling of the lips, tongue, or face is the most common symptom, but another symptom is episodic abdominal pain due to intestinal angioedema. Itching and urticaria are noticeably absent.The mechanism appears to be activated complement or other pro-inflammatory cytokines like prostaglandins and histamine, which cause rapid vasodilation and oedema.Other medications that are less frequently linked to angioedema include:Angiotensin-receptor blockers (ARBs)Nonsteroidal anti-inflammatory drugs (NSAIDs)Bupropion (e.g. Zyban and Wellbutrin)Beta-lactam antibioticsStatinsProton pump inhibitorsThe majority of these reactions are minor and can be treated by stopping the drug and prescribing antihistamines.

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.

Causes of neutropaenia:Drug-induced (e.g. chemotherapy, chloramphenicol, co-trimoxazole, phenytoin, carbamazepine, carbimazole, furosemide, chloroquine, clozapine, some DMARDs)Benign (racial or familial)CyclicalImmune (e.g. SLE, Felty’s syndrome, hypersensitivity and anaphylaxis)LeukaemiaInfections (e.g. HIV, hepatitis, fulminant bacterial infection)General PancytopaeniaHypersplenism, aplastic anaemia, malignant infiltration of bone marrow, megaloblastic anaemia, chemotherapy, myelodysplasia

A funnel plot is a scatter plot of the effect estimates from individual studies against some measure of each study’s size or precision. The standard error of the effect estimate is often chosen as the measure of study size and plotted on the vertical axis with a reversed scale that places the larger, most powerful studies towards the top. The effect estimates from smaller studies should scatter more widely at the bottom, with the spread narrowing among larger studies. In the absence of bias and between study heterogeneity, the scatter will be due to sampling variation alone and the plot will resemble a symmetrical inverted funnel. A triangle centred on a fixed effect summary estimate and extending 1.96 standard errors either side will include about 95% of studies if no bias is present and the fixed effect assumption (that the true treatment effect is the same in each study) is valid.

In infants and young children, lymphocytosis often occurs in response to infections that would normally produce a neutrophil reaction in adults.Lymphocytosis occurs in:1. Viral infections (e.g. infectious mononucleosis, HIV, rubella, mumps, viral hepatitis, cytomegalovirus, herpes simplex or zoster)2. Bacterial infections (e.g. pertussis, tuberculosis, toxoplasmosis, syphilis)3. Chronic lymphoid leukaemias4. Acute lymphoblastic leukaemias5. Non-Hodgkin lymphoma6. Thyrotoxicosis