Raised platelet levels have emerged as a cancer risk marker, according to a large population-based study published in 2017(link is external). According to the study, 12 percent of men and 6% of women with thrombocytosis were diagnosed with cancer within a year. These figures increased to 18% in men and 10% in women if a second platelet count was taken within 6 months of the first and showed an increased or stable elevated platelet count.The researchers discovered that thrombocytosis linked to cancer is most common in colorectal and lung cancers, and it is linked to a worse prognosis. Furthermore, one-third of the cancer patients in the study had no other symptoms that would have prompted an immediate cancer referral.The exact mechanism by which these cancers cause thrombocytosis is unknown, but one theory proposes the existence of pathogenic feedback loops between malignant cells and platelets, with a reciprocal interaction between tumour growth and metastasis, as well as thrombocytosis and platelet activation. Another hypothesis is that thrombocytosis occurs independently of cancer but aids in its spread and progression.The findings show that routinely testing for thrombocytosis could cut the time it takes to diagnose colorectal and lung cancer by at least two months. In the UK, this could result in around 5500 earlier cancer diagnoses per year.Because the positive predictive value of thrombocytosis in middle age for cancer (10%) is higher than the positive predictive value for a woman in her 50s presenting with a new breast lump (8.5%), this is clearly an important research paper that should be used to adjust future clinical practise. The current NICE guidelines predate these new research findings, so we’ll have to wait and see how they affect cancer referral guidelines in the UK.Because there are so many possible cancers associated with thrombocytosis, the treating clinician should take a thorough history and perform a thorough clinical examination if a patient is diagnosed with it. Further investigation and the most appropriate referral route should be aided by this information.It’s worth noting that the patients in the study had their blood tests done for a medical reason rather than as a random screening test.If there are no other symptoms to guide investigation and referral (one-third of the patients in the study had no other symptoms), keep in mind that the two most common cancers encountered were colorectal and lung cancer, so a chest X-ray and a faecal immunochemical test (FIT) for faecal blood may be reasonable initial investigations.

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

Nail clippings for microscopy and culture are a diagnostic test for fungal infection. Because some fungi are restricted to the lower parts of the nail, clippings should be taken from the discoloured or brittle parts and cut back as far as possible from the free edge.

Megaloblastic anaemia occurs when there is inhibition of DNA synthesis as red blood cells are produced. Impairment of DNA synthesis causes the cell cycle to be unable to progress from the growth stage to the mitosis stage. As a result, there is continuous cell growth without division, with an increase in mean corpuscular volume (MCV), which presents as macrocytosis. The most common cause of this defect in red cell DNA synthesis is hypovitaminosis, in particular, vitamin B12 deficiency or folate deficiency.Folate is an essential vitamin that can be found in most foods, and is highest in liver, green vegetables and yeast. 200 – 250 μg is found in the normal daily diet, and about 50% is absorbed. The daily adult requirement is about 100 μg and its absorption is principally from the duodenum and jejunum. Folate stores are normally only adequate for 4 months and so clinical features of folate deficiency usually become evident after this time.

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

The presence of dyspnoea makes alpha-1 antitrypsin deficiency the more likely diagnosis as biliary atresia does not cause respiratory symptoms. Deficiency of the enzyme alpha-1 antitrypsin causes uninhibited elastase activity and a decrease in elastic tissue. This causes liver cirrhosis leading to an elevation of conjugated bilirubin and emphysema in the lungs.Rhesus disease, hereditary spherocytosis and breast milk jaundice cause an elevation of unconjugated bilirubin thus ruling it out in this case. Breast milk jaundice occurs due to an inability of the newborn to metabolize the proteins in breast milk. Rhesus disease occurs when an Rh negative mother gives birth to an Rh positive baby. The jaundice would have been accompanied by anaemia and oedema. Hereditary spherocytosis occurs due to extravascular haemolysis as defective RBCs are removed by the spleen. The patient would present with jaundice, splenomegaly and possibly an aplastic crisis (if Parvovirus B19 infection).

Abductor pollicis longus is a muscle found in the posterior compartment of the forearm. It is one of the five deep extensors in the forearm, along with the supinator, extensor pollicis brevis, extensor pollicis longus and extensor indicis.Abductor pollicis longus is innervated by the posterior interosseous nerve (C7, C8), which is a continuation of the deep branch of the radial nerve. The radial nerve is a branch of the posterior cord of the brachial plexus.Blood supply to the abductor pollicis longus muscle comes from the interosseous branches of the ulnar artery.Acting alone or with abductor pollicis brevis, abductor pollicis longus pulls the thumb away from the palm. More specifically, it produces (mid-) extension and abduction of the thumb at the first metacarpophalangeal joint. This action is seen in activities such as bowling and shovelling.Working together with the long and short extensors of the thumb, the muscle also helps to fully extend the thumb at the metacarpophalangeal joint. This action is important for loosening the hand grip, for example, when letting go of objects previously being held. Abductor pollicis longus also helps to abduct the hand (radial deviation) at the radiocarpal joint.

A lesion at the optic chiasm will result in a bitemporal hemianopia.A lesion of the optic nerve will result in ipsilateral monocular visual loss.A lesion of the optic tract will result in a contralateral homonymous hemianopia.

Forceful expiration is primarily produced by the deeper thoracic muscles (internal and innermost intercostal muscles, subcostals and transversus thoracis) aided by contraction of the abdominal wall muscles which increase intra-abdominal pressure thus further reducing the volume of the thorax.

Neisseria gonorrhoeae is primarily spread by sexual contact or through transmission during childbirth. It causes gonorrhoea which is a purulent infection of the mucous membrane surfaces.

Neostigmine is used specifically for reversal of nondepolarizing (competitive) blockade and is anticholinesterase. It acts within one minute of intravenous injection, and the effects last for 20 to 30 minutes. After this time period, a second dose may then be necessary.

Etomidate causes less hypotension than thiopental sodium and propofol during induction. However, it is associated with a high incidence of extraneous muscle movements, which can be minimised by an opioid analgesic or a short-acting benzodiazepine given prior to induction. Pain on injection is common and there is a high rate of thrombophlebitis in the postoperative period. Postoperative nausea and vomiting commonly occur. Etomidate suppresses adrenocortical function, particularly during continuous administration, and it should not be used for maintenance of anaesthesia. It should be used with caution in patients with underlying adrenal insufficiency, for example, those with sepsis.

Total adult haemoglobin comprises about 96 – 98 % of normal adult haemoglobin (HbA). It consists of two alpha (α) and two beta (β) globin chains.

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.

Extensor carpi ulnaris is a fusiform muscle in the posterior forearm. It spans between the elbow and base of the little finger. This muscle belongs to the superficial forearm extensor group, along with anconaeus, brachioradialis, extensor carpi radialis longus, extensor carpi radialis brevis, extensor digitorum and extensor digiti minimi muscles.Like all the muscles of this compartment, extensor carpi ulnaris works as an extensor of the wrist. Moreover, due to its specific course, this muscle also acts to adduct the hand.Extensor carpi ulnaris is innervated by the posterior interosseous nerve (C7, C8), a branch of the deep division of the radial nerve. The radial nerve stems from the posterior cord of the brachial plexus.Blood supply to the extensor carpi ulnaris muscle is provided by branches of the radial recurrent and posterior interosseous arteries, which stem from the radial and ulnar arteries, respectively.

Myeloma laboratory findings include:- The presence of a paraprotein in serum or urine (the paraprotein is IgG in 60 percent of cases, IgA in 20 percent, and light chain only in almost all the rest),- Increased serum immunoglobulin-free light chain proteins generated by plasma cells but not coupled with heavy chains – Reduced IgG, IgA, and IgM levels in the blood (immune paresis)- Anaemia, whether normochromic, normocytic, or macrocytic.  – On a blood film, a Rouleaux formation has been marked. – In advanced illness, neutropenia and thrombocytopenia are common. – ESR is high. – Plasma cells in the bone marrow are overabundant, typically in aberrant forms. – Hypercalcemia- Creatinine levels are high. – Serum albumin levels are low in advanced illness. 60 percent of patients have osteolytic lesions, osteoporosis, or pathological fractures.

Platelets are the first cells to be attracted to the wound site due to the release of the Von Willebrand factor from the damaged endothelium. Platelets, in turn, release cytokines such as platelet-derived growth factor, which will attract other inflammatory cells to the wound site.

All opioids have the potential to cause:Gastrointestinal effects – Nausea, vomiting, constipation, difficulty with micturition (urinary retention), biliary spasmCentral nervous system effects – Sedation, euphoria, respiratory depression, miosisCardiovascular effects – Peripheral vasodilation, postural hypotensionDependence and tolerance

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

Chemotherapy that is too aggressive weakens your immune system, putting you at risk for a fungal and many other infection. Neutropenia is a condition in which a person’s neutrophil count is abnormally low. Neutrophils are an infection-fighting type of white blood cell. Neutrophils fight infection by killing bacteria and fungi (yeast) that infiltrate the body. Fungal organisms are significant pathogens in the setting of neutropenia.

Absolute risk reduction (ARR) is computed as the difference between the absolute risk in the control group (ARC) and the absolute risk in the treatment group (ART).ARR = ARC-ARTARR = (25/500) – (10/500)ARR = 0.03

IgA is the major Ig in secretions, particularly from the gastrointestinal tract (but also in saliva, tears, sweat and breast milk).IgE is important for mast cell degranulation in allergic and antiparasitic response. In the allergic response, the plasma cell produces IgE-antibodies, which, like antibodies of other immunoglobulin isotypes, are capable of binding a specific allergen via its Fab portion.IgG is the most abundant in plasma (comprising 80% of normal serum immunoglobulin) and the main circulatory Ig for the secondary immune response.

Juxtapulmonary or ‘J’ receptors are located on alveolar and bronchial walls close to the capillaries. Their afferents are small unmyelinated C-fibres or myelinated nerves in the vagus nerve. Activation causes depression of somatic and visceral activity by producing apnoea or rapid shallow breathing, a fall in heart rate and blood pressure, laryngeal constriction and relaxation of skeletal muscles via spinal neurones. J receptors are stimulated by increased alveolar wall fluid, pulmonary congestion and oedema, microembolism and inflammatory mediators. J receptors are thought to be involved in the sensation of dyspnoea in lung disease.

Majority of carbohydrates are broken down into monosaccharides (glucose, fructose galactose) and are absorbed by the small intestine. Enzymes released from the brush border break down carbohydrate. Some carbohydrates, such as cellulose, are not digested at all, despite being made of multiple glucose units. This is because the cellulose is made out of beta-glucose that makes the inter-monosaccharide bindings different from the ones present in starch, which consists of alpha-glucose. Humans lack the enzyme for splitting the beta-glucose-bond.The principal brush border enzymes are dextranase and glucoamylase. Other brush border enzymes are maltase, sucrase, and lactase.Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides. Dextranase and glucoamylase, then further break down oligosaccharides.Trypsin aids in digestion of protein.Chymotrypsin is a proteolytic enzyme that digests proteinCarboxypeptidase hydrolyses the first peptide or amide bond at the carboxyl or C-terminal end of proteins and peptides

FUSEDCARS can be used to remember some of the causes of a normal anion gap acidosis:Fistula (pancreaticoduodenal)Ureteroenteric conduitSaline administrationEndocrine (hyperparathyroidism)DiarrhoeaCarbonic anhydrase inhibitors (e.g. acetazolamide)Ammonium chlorideRenal tubular acidosisSpironolactone

An increase in ejection fraction means that a higher fraction of the end-diastolic volume is ejected in the stroke volume (e.g. because of the administration of a positive inotropic agent). When this situation occurs, the volume remaining in the ventricle after systole, the end-systolic volume, will be reduced. Cardiac output, stroke volume, and mean arterial pressure will be increased.

In restrictive lung disorders there is a reduction in the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1). The decline in the FVC is greater than that of the FEV1, resulting in preservation of the FEV1/FVC ratio (>0.7%).In obstructive lung disease, FEV1is reduced to <80% of normal and FVC is usually reduced but to a lesser extent than FEV1. The FEV1/FVC ratio is reduced to 80% in the presence of symptomsModerate airflow obstruction = FEV1 of 50-79%Severe airflow obstruction = FEV1 of 30-49%Very severe airflow obstruction = FEV1<30%.Spirometry is a poor predictor of durability and quality of life in COPD but can be used as part of the assessment of severity.COPD can only be diagnosed on spirometry if the FEV1 is <80% and FEV1/FVC ratio is < 0.7.

Carpal tunnel syndrome (CTS) is an entrapment neuropathy caused by compression of the median nerve as it travels through the wrist’s carpal tunnel. It is the most common nerve entrapment neuropathy, accounting for 90% of all neuropathies. Early symptoms of carpal tunnel syndrome include pain, numbness, and paraesthesia’s. These symptoms typically present, with some variability, in the thumb, index finger, middle finger, and the radial half (thumb side) of the ring finger. Pain also can radiate up the affected arm. With further progression, hand weakness, decreased fine motor coordination, clumsiness, and thenar atrophy can occur.The muscles innervated by the median nerve can be remembered using the mnemonic ‘LOAF’:L– lateral two lumbricalsO– Opponens pollicisA– Abductor pollicisF– Flexor pollicis brevisIn the early presentation of the disease, symptoms most often present at night when lying down and are relieved during the day. With further progression of the disease, symptoms will also be present during the day, especially with certain repetitive activities, such as when drawing, typing, or playing video games. In more advanced disease, symptoms can be constant.Typical occupations of patients with carpal tunnel syndrome include those who use computers for extended periods of time, those who use equipment that has vibration such as construction workers, and any other occupation requiring frequent, repetitive movement.

An action potential is a self-propagating response, successive depolarisation moving along each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and does not decrease in size. Conduction in myelinated fibres is much faster, up to 50 times that of the fastest unmyelinated nerve. Myelinated fibres are insulated except at areas devoid of myelin called nodes of Ranvier. The depolarisation jumps from one node of Ranvier to another by a process called saltatory conduction. Saltatory conduction not only increases the velocity of impulse transmission but also conserves energy for the axon because depolarisation only occurs at the nodes and not along the whole length of the nerve fibre. Larger diameter myelinated nerve fibres conduct nerve impulses faster than small unmyelinated nerve fibres.

A rapid IV bolus of adenosine is given, followed by a saline flush. The standard adult dose is 6 mg, followed by 12 mg if necessary, and then another 12 mg bolus every 1-2 minutes until an effect is seen.Patients who have had a heart transplant, on the other hand, are extremely sensitive to the effects of adenosine and should start with a lower dose of 3 mg, then 6 mg, and finally 12 mg.