In the United Kingdom, antibiotic resistance is becoming a significant factor in the treatment of urinary tract infections and pyelonephritis. E. coli (the main causative organism of both urinary tract infections and acute pyelonephritis) resistance to the following antibiotics in laboratory-processed urine specimens is:30.3 percent trimethoprim (varies by area from 27.1 to 33.4 percent )19.8 percent co-amoxiclav (varies by area from 10.8 to 30.7 percent )Ciprofloxacin (Cipro): 10.6% (varies by area from 7.8 to 13.7 percent )Cefalexin has a concentration of 9.9%. (varies by area from 8.1 to 11.4 percent )

Haemoglobin is composed of four polypeptide globin chains each with its own iron containing haem molecule. Haem synthesis occurs largely in the mitochondria by a series of biochemical reactions commencing with the condensation of glycine and succinyl coenzyme A under the action of the key rate-limiting enzyme delta-aminolevulinic acid (ALA) synthase. The globin chains are synthesised by ribosomes in the cytosol. Haemoglobin synthesis only occurs in immature red blood cells.There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F:- Normal adult haemoglobin (HbA) makes up about 96 – 98 % of total adult haemoglobin, and consists of two alpha (α) and two beta (β) globin chains. – Haemoglobin A2 (HbA2), a normal variant of adult haemoglobin, makes up about 1.5 – 3.5 % of total adult haemoglobin and consists of two α and two delta (δ) globin chains.- Foetal haemoglobin is the main Hb in the later two-thirds of foetal life and in the newborn until approximately 12 weeks of age. Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin. Red cells are destroyed by macrophages in the liver and spleen after , 120 days. The haem group is split from the haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled to plasma via transferrin or stored in macrophages as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in excess bilirubin and jaundice.

Tuberculosis is an infection caused by the microorganism Mycobacterium tuberculosis. TB can affect any organ system in the body, but it most commonly affects the lungs, followed by the lymph nodes. Option Tuberculosis is spread by the faecal-oral route: It is spread by inhalation of droplet nuclei. There are different methods to diagnose a tuberculosis infection. 1) Direct Microscopy: The organisms are visualised using Ziehl-Neelsen or Auramine staining. This is the quickest method to establish a diagnosis and start treatment.2) Culture: M. tuberculosis can be grown on Lowenstein-Jensen or Ogawa mediums, but it can take up to 8 weeks; therefore, ZN staining is also performed to start treatment immediately. Option There are several types of vaccine currently available: The BCG vaccine is the only vaccine approved to prevent TB and is administered at birth. Option Miliary tuberculosis refers to tuberculosis that affects the spine: Miliary tuberculosis refers to a tuberculosis infection disseminated throughout the body’s organ systems via the blood or lymphatics. Pott’s disease is extrapulmonary TB that affects the spine. It usually affects the lower thoracic and upper lumbar regions.Option A Ghon focus typically appears at the apex of a lung: The Ghon focus is a primary sign of TB that forms in the lung of previously unaffected patients. It typically occurs in the mid or lower zones of the lung.

A L’Abbé plot is a scatter plot with the risk in the control group on the x-axis and the risk in the experimental group on the y-axis. It can be used to evaluate heterogeneity in meta-analysis. Furthermore, this plot can aid to choose a summary measure (odds ratio, risk ratio, risk difference) that will result in more consistent results.

At altitude, the oxygen fraction is unaltered but the barometric pressure and thus partial pressure of oxygen is reduced.

Pain scoring systems are processes for assessing pain and the severity of illnesses that have been scientifically designed and tested. An example of ordinal categorical data is a pain scoring system.

Chronic ITP is a relatively common disorder. The highest incidence is in women aged 15 – 50 years. It is the most common cause of thrombocytopaenia without anaemia or neutropaenia. It is usually idiopathic but it may been seen in association with other conditions. Platelet autoantibodies (usually IgG) result in the premature removal of platelets from the circulation by macrophages of the reticuloendothelial system. In many causes the antibody is directed against the glycoprotein IIb/IIIa or Ib complex. The normal platelet lifespan of 10 days is reduced to a few hours. Total megakaryocyte mass and platelet turnover are increased to approximately five times normal. Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged.  In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia.

Damage to the hypoglossal nerve results in weakness of the tongue, with deviation of the tongue towards the weak side on protrusion.

Phenytoin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism.Metronidazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism.NSAIDs, when given with Warfarin, increase anticoagulation.

Dipyridamole inhibits both the reuptake of adenosine and phosphodiesterase, preventing the degradation of cAMP and thus blocking the platelet aggregation response to ADP.

Aldosterone: A rise in [K+] in the extracellular fluid of the adrenal cortex directly stimulates aldosterone release. Aldosterone promotes the synthesis of Na+/K+ATPases and the insertion of more Na+/K+ATPases into the basolateral membrane, and also stimulates apical sodium and potassium channel activity, overall acting to increase sodium reabsorption and potassium secretion.pH changes: Potassium secretion is reduced in acute acidosis and increased in acute alkalosis. A higher pH increases the apical K+channel activity and the basolateral Na+/K+ATPase activity – both changes that promote K+secretion.Flow rates: Increased flow rates in the collecting duct reduce K+concentration in the lumen and therefore enhance K+secretion. Increased flow also activates BK potassium channels, and ENaC channels which promote potassium secretion and sodium reabsorption respectively.Sodium delivery: Decreased Na+delivery to the collecting ducts results in less Na+reabsorption and hence a reduced gradient for K+secretion.Magnesium: Intracellular magnesium can bind and block K+channels inhibiting K+secretion into the tubules. Therefore magnesium deficiency reduces this inhibitory effect and so allows more potassium to be secreted into tubules and can cause hypokalaemia.

A regular broad-complex tachycardia is likely to be ventricular tachycardia or a regular supraventricular rhythm with bundle branch block. A ventricular tachycardia (or broad-complex tachycardia of uncertain origin) should be treated with amiodarone 300 mg IV over 10 – 60 min, followed by an infusion of 900 mg over the next 24 hours. If previously confirmed as SVT with bundle branch block, the patient should be treated as for narrow-complex tachycardia.

Contraindications indications of Captopril include:- Bilateral renal artery stenosis- Hypersensitivity to ACE inhibitors- Anuria- History of ACEI-induced angioedema- Hereditary or idiopathic angioedema- Co-administration of Neprilysin inhibitors (e.g., sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hours of switching to or from sacubitril/valsartan.If ACE inhibitors are used, they should be initiated only under specialist supervision and renal function should be monitored regularly. ACE inhibitors should also be used with particular caution in patients who may have undiagnosed and clinically silent renovascular disease. This includes patients with peripheral vascular disease or those with severe generalised atherosclerosis.

Negative predictive value (NPV) is the proportion of individuals with a negative test result who do not have the disease.NPV = d/(c+d)

The presence of Reed-Sternberg cells is pathognomonic for Hodgkin’s Lymphoma, which is a disease-causing neoplastic transformation of lymphocytes. There is a bimodal age distribution with peaks in the 20s and 60s. Patients typically present with enlarged, rubbery, non-tender lymph nodes. Symptoms such as fever, night sweats and weight loss may be present. Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.The Ann Arbour clinical staging is as follows:Stage I: one involved lymph node groupStage II two involved lymph node groups on one side of the diaphragmStage III: lymph node groups involved on both sides of the diaphragmStage IV: Involvement of extra-nodal tissues, such as the liver or bone marrowDiagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy. Multiple myeloma most commonly presents with bone pain, especially in the back and ribs. In non-Hodgkin’s lymphoma, Reed-Sternberg cells are not present. Acute lymphoblastic leukaemia will present with features of anaemia, thrombocytopenia and leukopenia. The most common symptoms of chronic lymphocytic leukaemia are fatigue, night sweats and low-grade fever.

Glomerular filtration is a passive process. It depends on the net hydrostatic pressure across the glomerular capillaries, the oncotic pressure, and the intrinsic permeability of the glomerulus.The mean values for glomerular filtration rate (GFR) in young adults are 130 ml/min/1.73m2 in males and 120 ml/min/1.73m2in females.The GFR declines with age after the age of 40 at a rate of approximately 1 ml/min/year.The Cockcroft and Gault formula overestimates creatinine in obese patients. This is because their endogenous creatinine production is less than that predicted by overall body weight.Creatinine is used in the estimation of GFR because it is naturally produced by muscle breakdown, not toxic, not produced by the kidney, freely filtered at the glomerulus, not reabsorbed from the nephron, and does not alter GFR.

Adverse effects include:Common: NauseaUncommon: VomitingRare: Abdominal pain, hypertension, hypotension, tachycardia

Myofibrils, which are around 1 m in diameter, make up each myofiber. The cytoplasm separates them and arranges them in a parallel pattern along the cell’s long axis. These myofibrils are made up of actin and myosin filaments that are repeated in sarcomeres, which are the myofiber’s basic functional units.Myofilaments are the filaments that make up myofibrils, and they’re made mostly of proteins. Myofilaments are divided into three categories:Myosin filaments are thick filaments made up mostly of the protein myosin.Actin filaments are thin filaments made up mostly of the protein actin.Elastic filaments are mostly made up of the protein titin.The sarcomere is a Z-line segment that connects two adjacent Z-lines.The I-bands are thin filament zones that run from either side of the Z-lines to the thick filament’s beginning.Between the I-bands is the A-band, which spans the length of a single thick filament.The H-zone is a zone of thick filaments that is not overlaid by thin filaments in the sarcomere’s centre. The H-zone keeps the myosin filaments in place by surrounding them with six actin filaments each.The M-band (or M-line) is a disc of cross-connecting cytoskeleton elements in the centre of the H-zone.The thick filament is primarily made up of myosin. The thin filament is primarily made up of actin. Actin, tropomyosin, and troponin are found in a 7:1:1 ratio in thin filaments.

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.

Pericardiocentesis is a procedure that removes excess fluid from the pericardium. As a result, it’s used in cases of cardiac tamponade, which occurs when there’s too much fluid in the space around the heart. During the procedure, a needle and a small catheter are inserted 1 to 2 cm inferior and to the left of the xiphochondral junction into the pericardial cavity.

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.

Cyclizine is a piperazine derivative that functions as an antihistamine (H1-receptor antagonist). To prevent nausea and vomiting, it is thought to act on the chemoreceptor trigger zone (CTZ) and the labyrinthine apparatus. It has a lower antimuscarinic effect as well.

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:GlycogenolysisGluconeogenesisLipolysis in adipose tissueThe secretion of glucagon is also stimulated by:AdrenalineCholecystokininArginineAlanineAcetylcholineThe secretion of glucagon is inhibited by:InsulinSomatostatinIncreased free fatty acidsIncreased urea productionGlycolysis 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.

Bile is synthesised in the liver. Bile functions to eliminate endogenous and exogenous substances from the liver, to neutralise gastric acid in the small intestine, and to emulsify fats in the small intestine and facilitate their digestion and absorption. Bile is stored and concentrated in the gallbladder. Bile passes out of the gallbladder via the cystic duct. Bile passes into the duodenum through the ampulla of Vater regulated by the sphincter of Oddi.

Amoxicillin is used first line for low to moderate severity community acquired pneumonia, exacerbations of chronic bronchitis, for acute otitis media, for acute sinusitis, for oral infections/dental abscess, for Listeria meningitis (in combination with another antibiotic), for infective endocarditis (in combination with another antibiotic) and for H. Pylori eradication (in combination with metronidazole/clarithromycin and a PPI). Flucloxacillin is used first line for acute cellulitis.

In the absence of any contra-indications, high-dose NSAIDs are the first-line treatment for acute gout. Naproxen 750 mg as a stat dose followed by 250 mg TDS is a commonly used and effective regime.Aspirin should not be used in gout as it reduces the urinary clearance of urate and interferes with the action of uricosuric agents. Naproxen, Diclofenac or Indomethacin are more appropriate choices.Allopurinol is used prophylactically, preventing future attacks by reducing serum uric acid levels. It should not be started in the acute phase as it increases the severity and duration of symptoms.Colchicine acts on the neutrophils, binding to tubulin to prevent neutrophil migration into the joint. It is as effective as NSAIDs in relieving acute attacks. It also has a role in prophylactic treatment if Allopurinol is not tolerated.NSAIDs are contra-indicated in heart failure as they can cause fluid retention and congestive cardiac failure. Colchicine is the preferred treatment in patients with heart failure or those who are intolerant of NSAIDs.

Receiver-operating characteristic (ROC) analysis was originally developed during World War II to analyse classification accuracy in differentiating signal from noise in radar detection. Recently, the methodology has been adapted to several clinical areas heavily dependent on screening and diagnostic tests, in particular, laboratory testing, epidemiology, radiology, and bioinformatics. ROC analysis is a useful tool for evaluating the performance of diagnostic tests and more generally for evaluating the accuracy of a statistical model (e.g., logistic regression, linear discriminant analysis) that classifies subjects into 1 of 2 categories, diseased or non diseased. Its function as a simple graphical tool for displaying the accuracy of a medical diagnostic test is one of the most well-known applications of ROC curve analysis.The closer the ROC curve is to the upper left corner, which has 100% sensitivity and 100% specificity, the higher the overall accuracy of the diagnostic test.

The following approaches have some benefit in adult patients with reflux:Weight loss or weight management for individuals who are overweightHead of bed elevation is important for individuals with nocturnal or laryngeal symptoms, but its value for other situations is unclear.The following lifestyle approaches also are used frequently. There is some evidence that these lifestyle changes improve laboratory measures of reflux (such as lower oesophageal sphincter pressure).Dietary modification – A practical approach is to avoid a core group of reflux-inducing foods, including chocolate, peppermint, and alcohol, which may reduce lower oesophageal sphincter pressure. Acidic beverages, including colas with caffeine and orange juice also may exacerbate symptoms. Avoiding the supine position soon after eating.Promotion of salivation by either chewing gum or using oral lozenges. Salivation neutralizes refluxed acid, thereby increasing the rate of oesophageal acid clearance.Avoidance of tobacco (including passive exposure to tobacco smoke) and alcohol. Nicotine and alcohol reduce lower oesophageal sphincter pressure, and smoking also diminishes salivation.

Bumetanide is a loop diuretic that inhibits sodium, chloride, and potassium reabsorption by acting on the Na.K.2Cl co-transporter in the ascending loop of Henlé. This reduces the osmotic gradient that forces water out of the collecting duct system and prevents the formation of a hypertonic renal medulla. This has a strong diuretic effect on the body.It’s primarily used in patients with heart failure who aren’t responding to high doses of furosemide. Bumetanide and furosemide differ primarily in terms of bioavailability and pharmacodynamic potency.In the intestine, furosemide is only partially absorbed, with a bioavailability of 40-50 percent. Bumetanide, on the other hand, is almost completely absorbed in the intestine and has a bioavailability of about 80%. Bumetanide is 40 times more potent than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide.Bumetanide also lowers the concentration of neuronal chloride, making GABA’s action more depolarizing. In the neonatal period, it is being studied as an antiepileptic.

The medial half of the flexor digitorum profundus is innervated by the ulnar nerve. Paralysis of this muscle results in loss of flexion at the distal interphalangeal joint of the ring and little finger. Flexion at the proximal interphalangeal joint is preserved as this is a function of the flexor digitorum superficialis which is innervated by the median nerve. The ulnar nerve is not correct as ulnar nerve injury at the wrist would not affect the long flexors, and the injury must have been more proximal.