Due to their increased risk of cardiovascular adverse events, coxibs and diclofenac are contraindicated in people with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and mild, moderate, or severe heart failure. Other NSAIDs are only contraindicated in people with severe heart failure. Selective inhibition of COX-2 is associated with less gastrointestinal intolerance. In single doses NSAIDs have analgesic activity comparable to that of paracetamol, therefore given their side effect profile, paracetamol is preferred, particularly in the elderly. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. Mefenamic acid has only very mild anti-inflammatory properties.

Beta-blockers are contraindicated in Raynaud’s syndrome. Beta-blockers may be indicated in:HypertensionPheochromocytoma (only with an alpha-blocker)AnginaSecondary prevention after ACSArrhythmias including atrial fibrillationHeart failureThyrotoxicosisAnxietyProphylaxis of migraineEssential tremorGlaucoma

Entonox is a mixture of 50% Oxygen and 50% nitrous oxide and is given in an inhaled form as a quick form of analgesia. Entonox causes non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors, which are a subtype of the glutamate receptor. It is stored in blue and white cylinders and administered via a pressure regulator and demand valve. The administration of this medicine reduces pain and anxiety in paediatric and dental procedures ands during labour. Effects are apparent after 20 seconds, and peak action occurs after 3 to 5 minutes as it is a drug with a rapid onset and the patient will also recover rapidly from its effects. Entonox is widely used as it does not accumulate in the body and does not cause many side effects. However, a notable side effect is the inhibition of Vitamin B12 synthesis.

ANP acts to: Inhibit Na+ reabsorption in the distal nephron (through inhibition of ENaC in principal cells)Suppress the production of reninSuppress the production of aldosteroneSuppress the production of ADHCause renal vasodilation, increasing the glomerular filtration rate

For anaesthesia, nitrous oxide is commonly used in a concentration of around 50 – 66% in oxygen in association with other inhalation or intravenous agents. Nitrous oxide cannot be used as the sole anaesthetic agent due to lack of potency, but is useful as part of a combination of drugs since it allows reduction in dosage of other agents. 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. Nitrous oxide increases cerebral blood flow and should be avoided in patients with, or at risk of, raised intracranial pressure. Nitrous oxide may be administered by any trained personnel experienced in its use.

An ambulatory blood pressure reading of >150/95 is classified as stage 2 hypertension, according to the NICE care pathway for hypertension, and the patient should be treated with an antihypertensive drug.A calcium-channel blocker, such as amlodipine, would be the most appropriate medication for a 59-year-old Caucasian man.

Pleural aspiration describes a procedure whereby pleural fluid or air may be aspirated via a system inserted temporarily into the pleural space. This may be for diagnostic purposes (usually removing 20–50 ml fluid) or therapeutic to relieve symptoms. In the literature it is varyingly called thoracocentesis, thoracentesis or pleural aspiration.In determining the correct patient position and site of insertion, it is important for the operator to be aware of the normal anatomy of the thorax and the pathology of the patient. Patient position is dependent on the operator preference and the site of the pathology. In the case of a posterior lying locule, this may be specific to the image-guided spot where fluid is most likely to be obtained. In most circumstances, however, the site of insertion of the needle is either in the triangle of safety or the second intercostal space in the midclavicular line. The patient may therefore either sit upright leaning forward with arms elevated but resting on a table or bed, thereby exposing the axilla, or lying on a bed in a position. The needle is inserted in the space just above the chosen rib to avoid damaging the neurovascular bundle. It is common practice to insert the needle more posteriorly for a pleural aspiration, but it should be noted that the neurovascular bundle may not be covered by the lower flange of the rib in this position and a more lateral or anterior site of insertion is considered safer.

Advantages: ideal for studying associations between an exposure and an outcome when the exposure is uncommon, the time sequence of events can be assessed, they can provide information on a wide range of disease outcomes, the absolute and relative risk of disease can be measured directly, they can give a direct estimation of disease incidence ratesDisadvantages: costly and can take long periods of time if the outcome is delayed, subject to subject-selection and loss to follow-up bias, large sample size required for rare outcome of interest so it is not useful for rare diseases, prone to confounding

A blowout fracture is an isolated fracture of the orbital walls without compromise of the orbital rims. The common mechanisms are falls, high-velocity ball-related sports, traffic accidents, and interpersonal violence.The frontal, ethmoidal, sphenoid, zygomatic, and lacrimal bones form the bony structures of the orbit. Medially, the maxillary and the lacrimal bone form the lacrimal fossa. Together with the lamina papyracea of the ethmoid bone, they form the medial wall. The sphenoid bone forms the posterior wall and houses the orbital canal. Lateral to the orbital canal lies the superior orbital fissure housing cranial nerves III, IV, V, and VI. The zygomatic bone forms the lateral wall. Superior and inferior borders are the frontal and maxillary bones. Located around the globe of the eye and attached to it are 6 extraocular muscles; the 4 rectus muscles and the superior and inferior oblique muscles. The fat and connective tissue around the globe help to reduce the pressure exerted by the extraocular muscles.The goal of treatment is to restore aesthetics and physiological function. The problem with orbital blowout fractures is that the volume of the orbit can be increased, resulting in enophthalmos and hypoglobus. In addition, the orbital tissue and inferior rectus muscle can become trapped by the bony fragments leading to diplopia, limitation of gaze, and tethering. Finally, the orbital injury can lead to retinal oedema, hyphema, and significant loss of vision.While some cases may be managed with conservative care, others may require some type of surgical intervention.

Advantages:relatively quickrelatively cheap and easy to performparticularly suitable for studying associations between an exposure and an outcome when the outcome is uncommon or if the outcome occurs decades after exposurea wide range of risk factors can be investigated in each studyDisadvantages:subject to recall biasunlike in a whole population study, absolute risk cannot be quantifiedtemporal relationship between exposure and outcome can be difficult to establishunsuitable for rare risk factorsprone to confounding

Ciprofloxacin increases plasma concentrations of theophylline. There is an increased risk of convulsions when quinolones are given with NSAIDs or theophylline. There is an increased risk of tendon damage when quinolones are given with corticosteroids. Quinolones are known to increase the QT-interval and should not be taken with concomitantly with other drugs that are known to cause QT-interval prolongation. There is an increased risk of myopathy when erythromycin or clarithromycin are taken with simvastatin or atorvastatin.

G-cells are a type of cell found in the stomach’s pyloric antrum, duodenum, and pancreas. The secretion of the peptide hormone gastrin is their major function.The table below summarizes the many cell types found in the stomach, as well as the substances secreted by each cell type and the function of the secretion:Cell type/ Substance secreted/ Function of secretionParietal cells/ Hydrochloric acid/ Kills microbes and activates pepsinogenParietal cells/ Intrinsic factor/Binds to vitamin B12 and facilitates its absorptionChief cells/ Pepsinogen/ Protein digestionChief cells/ Gastric lipase/ Fat digestionG-cells/ Gastrin/ Stimulates gastric acid secretionEnterochromaffin-like cells (ECL cells) /Histamine/ Stimulates gastric acid secretionMucous-neck cells/ Mucous and bicarbonate/ Protects stomach epithelium from acidD-cells/ Somatostatin/ Inhibits gastric acid secretion

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

The management of bleeding in a patient receiving heparin depends upon the location and severity of bleeding, the underlying thromboembolic risk, and the current aPTT (for heparin) or anti-factor Xa activity (for LMW heparin). As an example, a patient with minor skin bleeding in the setting of a mechanical heart valve (high thromboembolic risk) and a therapeutic aPTT may continue heparin therapy, whereas a patient with major intracerebral bleeding in the setting of venous thromboembolism several months prior who is receiving heparin bridging perioperatively may require immediate heparin discontinuation and reversal with protamine sulphate. If haemorrhage occurs it is usually sufficient to withdraw unfractionated or low molecular weight heparin, but if rapid reversal of the effects of the heparin is required, protamine sulphate is a specific antidote (but only partially reverses the effects of low molecular weight heparins). Clinician judgment and early involvement of the appropriate consulting specialists is advised.

Prochlorperazine is a phenothiazine drug as it is categorized as a first-generation antipsychotic. It mainly blocks the D2 (dopamine 2) receptors in the brain. Along with dopamine, it also blocks histaminergic, cholinergic, and noradrenergic receptors.It exerts its antiemetic effect via dopamine (D2) receptor antagonist. It is used to treat nausea and vomiting of various causes, including labyrinthine disorders.

In hypokalaemia, initial potassium replacement therapy should not involve glucose infusions, as glucose may cause a further decrease in the plasma-potassium concentration. Glucose infusions are used for the other indications like diabetic ketoacidosis, hypoglycaemia, routine fluid maintenance in patients who are nil by mouth (very important in children), and in hyperkalaemia.

As the common bile duct descends, it passes posterior to the first part of the duodenum before joining with the pancreatic duct from the pancreas, forming the hepatopancreatic ampulla (ampulla of Vater) at the major duodenal papilla, located in the second part of the duodenum. Surrounding the ampulla is the sphincter of Oddi, a collection of smooth muscle which can open to allow bile and pancreatic fluid to empty into the duodenum.

Acute ITP is most common in children. In approximately 75% of cases, the episode follows vaccination or infection such as chicken pox or glandular fever. Most cases are caused by non-specific immune complex attachment to platelets. Acute ITP usually has a very sudden onset and the symptoms usually disappear in less than 6 months (often within a few weeks). It is usually a self-limiting condition and over 80% of children recover without treatment; in 5 – 10% of cases a chronic form of the disease develops.

Features include:- severe anaemia (becoming apparent at 3 – 6 months when the switch from gamma-chain to beta-chain production takes place)- failure to thrive- hepatosplenomegaly (due to excessive red cell destruction, extramedullary haemopoiesis and later due to transfusion related iron overload)- expansion of bones (due to marrow hyperplasia, resulting in bossing of the skull and cortical thinning with tendency to fracture)- increased susceptibility to infections (due to anaemia, iron overload, transfusion and splenectomy)- osteoporosis- hyperbilirubinaemia and gallstones- hyperuricaemia and gout- other features of haemolytic anaemia- liver damage and other features of iron overload

The following are the mechanisms of breathing during inspiration and expiration, whether normal or forced.Normal inspiration is an active process, with the diaphragm as the main muscle. The diaphragm descends, ribs move upward and outward, and the lungs become wider and taller.In forced inspiration, which commonly occurs during exercise, the external intercostals and accessory muscles, such as the sternocleidomastoid, anterior serrati, scalenes, alae nasi, genioglossus and arytenoid are involved. The ribs move upward and outward, and the abdominal contents move downward.Normal expiration is a passive process, while in forced expiration, the internal intercostals and abdominal muscles, such as the rectus abdominis, internal and external obliques and transversus abdominis are involved. The ribs move downward and inward, and the abdominal contents move upward.

Both the medial and lateral pterygoids are innervated by the mandibular division of the trigeminal nerve.

ALL affects children predominantly.The CNS is commonly involved in ALL.The Philadelphia chromosome is present in 25% of adult ALL and 5% of childhood ALL cases.The cure rate in children is approximately 80% in children and 50% in adults.ALL is classified into 3 groups using the French-American-British (FAB) classification:ALL-L1: small uniform cellsALL-L2: large varied cellsALL-L3: large varied cells with vacuoles.

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue and cause the characteristic clinical feature of lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-Sternberg cells present in HL. Hodgkin lymphoma can present at any age but is rare in children and has a peak incidence in young adults. There is an almost 2 : 1 male predominance. Most patients present with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15% and inguinal nodes in 6-12%. Modest splenomegaly occurs during the course of the disease in 50% of patients; the liver may also be enlarged. Bone marrow failure involvement is unusual in early disease. The prognosis depends on age, stage and histology, but overall approximately 85% of patients are cured. Alcohol‐induced pain and pruritus are two well‐known but rare symptoms in HL.

Amiodarone has a chemical structure that is similar to that of thyroxine and can bind to the nuclear thyroid receptor. It can cause both hypothyroidism and hyperthyroidism, though hypothyroidism is far more common, with 5-10% of patients suffering from it.

If a patient presents with one of the following types of wounds, they are at risk of contracting tetanus and should be vaccinated immediately:1) Contaminated puncture-type wounds from gardening and farming (as they may contain tetanus spores)2) Wounds containing foreign bodies3) Open (compound) fractures4) Wounds or burns with sepsis5) Animal bites and scratches (animal saliva does not contain tetanus spores unless the animal was routing in soil or lives in an agriculture setting)Extremely high-risk tetanus-prone wounds are any of the above wounds with one of the following:1) Any wound contaminated by materials containing tetanus spores, e.g., soil, manure2) Burns or wounds with extensive devitalised tissue3) Wounds or burns with surgical intervention delayed for more than six hours even if the initial injury was not heavily contaminatedThe CDC recommends that adults who have never been vaccinated for tetanus receive a quick shot of the tetanus vaccine along with a booster dose ten years later. A tetanus-prone wound in an unvaccinated individual should also receive a high dose of tetanus immunoglobulin. The injected antibodies will prevent tetanus infection as the patient does not have any pre-existing antibodies against the disease.In this case, the patient has a high risk, contaminated wound. He should receive a high dose of tetanus immunoglobulin along with the tetanus vaccine. (The preventative dose of tetanus immunoglobulin is 250 IU in most cases unless over 24 hours have passed since the injury or the wound is heavily contaminated, then 500 IU should be given.) His physician also needs to be contacted to arrange the remainder of the course as indicated in this case.

Haemoglobin is a 64.4 kd tetramer consisting of two pairs of globin polypeptide chains: one pair of alpha-like chains, and one pair of non-alpha chains. The chains are designated by Greek letters, which are used to describe the particular haemoglobin (e.g., Hb A is alpha2/beta2).Two copies of the alpha-globin gene (HBA2, HBA1) are located on chromosome 16 along with the embryonic zeta genes (HBZ). There is no substitute for alpha globin in the formation of any of the normal haemoglobins (Hb) following birth (e.g., Hb A, Hb A2, and Hb F). Thus, absence any alpha globin, as seen when all 4 alpha-globin genes are inactive or deleted is incompatible with extrauterine life, except when extraordinary measures are taken. A homotetramer of only alpha-globin chains is not thought to occur, but in the absence of alpha chains, beta and gamma homotetramers (HbH and Bart’s haemoglobin, respectively) can be found, although they lack cooperativity and function poorly in oxygen transport. The single beta-globin gene (HBB) resides on chromosome 11, within a gene cluster consisting of an embryonic beta-like gene, the epsilon gene (HBE1), the duplicated and nearly identical fetal, or gamma globin genes (HBG2, HBG1), and the poorly expressed delta-globin gene (HBD). A heme group, consisting of a single molecule of protoporphyrin IX co-ordinately bound to a single ferrous (Fe2+) ion, is linked covalently at a specific site to each globin chain. If the iron is oxidized to the ferric state (Fe3+), the protein is called methaemoglobin.Alpha globin chains contain 141 amino acids (residues) while the beta-like chains contain 146 amino acids. Approximately 75 percent of haemoglobin is in the form of an alpha helix. The non helical stretches permit folding of the polypeptide upon itself. Individual residues can be assigned to one of eight helices (A-H) or to adjacent non helical stretches.Heme iron is linked covalently to a histidine at the eighth residue of the F helix (His F8), at residue 87 of the alpha chain and residue 92 of the beta chain. Residues that have charged side groups, such as lysine, arginine, and glutamic acid, lie on the surface of the molecule in contact with the surrounding water solvent. Exposure of the hydrophilic (charged) amino acids to the aqueous milieu is an important determinant of the solubility of haemoglobin within the red blood cell and of the prevention of precipitation.The haemoglobin tetramer is a globular molecule (5.0 x 5.4 x 6.4 nm) with a single axis of symmetry. The polypeptide chains are folded such that the four heme groups lie in clefts on the surface of the molecule equidistant from one another.

All vaccines are contraindicated in individuals with: A confirmed anaphylactic reaction to a previous dose of the vaccine or a vaccine containing the same antigens.A confirmed anaphylactic reaction to a component in the vaccine e.g. neomycinThere is no evidence that vaccinating pregnant women with inactivated vaccine or toxoids harms the woman or foetus. The current protocol is that a child with history of egg allergy can be safely vaccinated with Fluenz tetra. However, if they had a previous severe anaphylaxis to egg requiring intensive care, then Flenz tetra is contraindicated. BCG, yellow fever or oral typhoid vaccinations are not safe in HIV positive patients.The normal times recommended for immunization of full-term babies should also be applied to premature infants and correction for gestational age should not be implemented.Concurrent antibiotic therapy is not a contraindication to vaccination.

On ingestion, vitamin B12 is bound to R protein found in saliva and gastric secretions, which protects it from digestion in the stomach. Intrinsic factor is secreted by gastric parietal cells. Receptors for the IF-B12 complex are present in the membrane of epithelial cells of the terminal ileum, which bind the complex and allow uptake of vitamin B12 across the apical membrane by endocytosis. Vitamin B12 is then transported across the basal membrane into the portal blood where it is bound to transcobalamin II and processed by the liver. In pernicious anaemia, there are autoantibodies against gastric parietal cells and intrinsic factor, resulting in vitamin B12 deficiency anaemia.

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 infection (CDI) 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. CDI is the most severe consequence of antibiotic treatment and is a major cause of morbidity and mortality. Risk for CDI has been found to be greatest with clindamycin followed by fluoroquinolones Tetracyclines are not associated with risk for CDI.

The pectoralis major is the superior most and largest muscle of the anterior chest wall. It is a thick, fan-shaped muscle that lies underneath the breast tissue and forms the anterior wall of the axilla.Its origin lies anterior surface of the medial half of the clavicle, the anterior surface of the sternum, the first 7 costal cartilages, the sternal end of the sixth rib, and the aponeurosis of the external oblique of the anterior abdominal wall.The insertion of the pectoralis major is at the lateral lip of the intertubercular sulcus of the humerus. There are 2 heads of the pectoralis major, the clavicular and the sternocostal, which reference their area of origin. The function of the pectoralis major is 3-fold and dependent on which heads of muscles are involved:- Flexion, adduction and medial rotation of the arm at the glenohumeral joint- Clavicular head causes flexion of the extended arm- Sternoclavicular head causes extension of the flexed armArterial supply of the pectoralis major, the pectoral artery, arises from the second branch of the axillary artery, the thoracoacromial trunk.The 2 heads of the pectoralis major have different nervous supplies. The clavicular head derives its nerve supply from the lateral pectoral nerve. The medial pectoral nerve innervates the sternocostal head. The lateral pectoral nerve arises directly from the lateral cord of the brachial plexus, and the medial pectoral nerve arises from the medial cord.