Clopidogrel, a thienopyridine derivative, prevents platelet aggregation and cross-linking by the protein fibrin by inhibiting the ADP receptor on platelet cell membranes (inhibits binding of ADP to its platelet receptor (P2Y12 ADP-receptor).

The incubation period for Chickenpox is 7-23 days (usually around 2 weeks).

Incubation period of botulism is 18-36 hours

Incubation period of Meningococcaemia is 1-7 days.

Incubation period of Gonorrhoea is 3-5 days.

Incubation period of Hepatitis A is 3-5 weeks.
Other infectious with an incubation period of between 1 and 3 weeks are:
Whooping cough (7-10 days)
Brucellosis (7-21 days)
Leptospirosis (7-12 days)
Malaria (7-40 days depending on strain)
Typhoid (8-21 days)
Measles (10-18 days)
Mumps (14-18 days)
Rubella (14-21 days)

Monocytes account for around 5 to 10% of peripheral white cells. Monocytes in peripheral blood are generally bigger than other leukocytes and feature a large central oval or indented nucleus with clumped chromatin. The abundant cytoplasm staining blue and containing numerous fine vacuoles gives the appearance of ground glass. Cytoplasmic granules are another type of granule.

Monocytes evolve from the granulocyte-macrophage progenitor to become monoblasts, promonocytes, monocytes, and tissue macrophages (in increasing order of maturity). Monocytes only stay in the bone marrow for a short time before exiting to circulate in the bloodstream for 20-40 hours before becoming macrophages.

Like all muscles in the deep posterior compartment of the leg, flexor digitorum longus muscle is innervated by branches of the tibial nerve (root value L5, S1 and S2) which is a branch of sciatic nerve.

N. meningitidis is a Gram-negative cocci and can be found as a commensal as well as an invasive pathogen. It is an important etiologic agent of endemic and epidemic meningitis and meningococcaemia and rarely pneumonia, purulent arthritis, or endophthalmitis. N. meningitidis has also been recovered from urogenital and rectal sites as a result of oral-genital contact. Meningococcal carriage, usually involving nonencapsulated strains, may cause an increase in protective antibody against the pathogenic strains. Of the 12 meningococcal encapsulated serogroups, A, B, C, Y, and W-135 account for most cases of disease in the world. N. meningitidis possesses a polysaccharide capsule that is antiphagocytic and serves as an important virulence factor.

It can be found on the mucosal surfaces of the nasopharynx and oropharynx in 30% of the human population. The organism is transmitted by close contact with respiratory droplet secretions from a carrier to a new host. Only a few newly colonized hosts develop meningococcal disease, with the highest incidence being found in infants and adolescents.

The quadrivalent vaccine Menactra is a polysaccharide-protein conjugated vaccine with antigens to serogroups A, C, Y, and W-135. This conjugate vaccine is licensed for people 2 to 55 years old. This vaccine does not protect against meningitis caused by serogroup B because group B polysaccharide is a very poor immunogen in humans.

ADH, or antidiuretic hormone, is a hormone that regulates water and electrolyte balance. It is released in response to a variety of events, the most important of which are higher plasma osmolality or lower blood pressure. ADH increases plasma volume and blood pressure via acting on the kidneys and peripheral vasculature.

It causes vasoconstriction by binding to peripheral V1 Receptors on vascular smooth muscle via the IP3 signal transduction and Rho-kinase pathways. The systemic vascular resistance and arterial pressure rise as a result. High levels of ADH appear to be required for this to have a major impact on arterial pressure, such as in hypovolaemic shock.

Amoxicillin and Ampicillin are more hydrophilic (broad-spectrum) penicillins than benzylpenicillin and phenoxymethylpenicillin. Because they may penetrate through gaps in the outer phospholipid membrane, they are effective against Gram-negative bacteria. Amoxicillin and Ampicillin are resistant to penicillinase-producing microbes.

Community-acquired pneumonia, otitis media, sinusitis, oral infections, and urinary tract infections are among the most prevalent conditions for which they are prescribed. The normal adult oral dose of Amoxicillin is 500 mg three times/day, which can be increased to 1 g three times/day if necessary. Ampicillin is given to adults in doses of 0.5-1 g every 6 hours.

Osmolality and osmolarity are measurements of the solute concentration of a solution. Although the two terms are often used interchangeably, there are differences in the definitions, how they are calculated and the units of measurement used.

Osmolarity, expressed as mmol/L, is an estimation of the osmolar concentration of plasma. It is proportional to the number of particles per litre of solution.
Measured Na+, K+, urea and glucose concentrations are used to calculate the value indirectly.
It is unreliable in pseudohyponatremia and hyperproteinaemia.

The equations used to calculate osmolarity are:
Osmolarity = 2 (Na+) + 2 (K+) + Glucose + Urea (all in mmol/L)
OR
Osmolarity = 2 (Na+) + Glucose + Urea (all in mmol/L)

Doubling of sodium accounts for the negative ions associated with sodium, and the exclusion of potassium approximately allows for the incomplete dissociation of sodium chloride.

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.

There are three types of muscle:
Skeletal muscle
Cardiac muscle
Smooth muscle

Individual muscle is enveloped in a layer of dense irregular connective tissue called the epimysium. The epimysium protects the muscles from friction against bones and other muscles.

Skeletal muscle is composed of muscle fibres, referred to as myofibers which is ensheathed by a wispy layer of areolar connective tissue called the endomysium. The endomysium is the smallest and deepest component of muscle connective tissue.

Myofibers grouped together in bundles form fascicles, or fasciculi. These are surrounded by a type of connective tissue called the perimysium.

Beneath the endomysium lies the sarcolemma, an elastic sheath with infoldings that invaginate the interior of the myofibers, particularly at the motor endplate of the neuromuscular junction.

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 effects
Errors in administration (episodes of ‘wrong blood’)
Viruses and Infections (bacterial, viral, possibly prion)
Immunodilution

A 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 transfusion
The 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 the
Fever, 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 delayed
It 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 allergens
Foreign 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.

Common side effects of thiazide diuretics include:
Excessive diuresis, postural hypotension, dehydration, renal impairment
Acid-base and electrolyte imbalance
Hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia, hypochloraemic alkalosis
Metabolic imbalance
Hyperuricaemia and gout
Impaired glucose tolerance and hyperglycaemia
Altered plasma-lipid concentrations
Mild gastrointestinal disturbances

CN VI palsies result in a convergent squint at rest (eye turned inwards) with inability to abduct the eye because of unopposed action of the rectus medialis. The patient complains of horizontal diplopia when looking towards the affected side. With complete paralysis, the eye cannot abduct past the midline.

Serum concentrations of the p24 antigen are usually high in the first few weeks after human immunodeficiency virus (HIV) infection and testing for p24 antigen is therefore a useful way of diagnosing very early infection. P24 is the viral protein that makes up most of the core of the HIV.

ELISA and other antibody tests, though a very sensitive way of detecting the presence of HIV, cannot be used in the early stages of the disease. This is because of the window period of 6-12 weeks before antibodies are produced. These tests will be negative during a seroconversion illness.

The ‘rapid HIV test’ is an HIV antibody test. It will also be negative during the ‘window period’ since it takes time for antibodies to be produced. It is called the ‘rapid test’ as it can detect antibodies in blood or saliva much quicker than the other antibody tests and results are often back within 20 minutes.

CD4 and CD8 counts are usually normal in the early stages of the HIV infection and cannot be used in this case.

There usually isn’t any additional bronchodilation with intravenous (IV) aminophylline compared to standard care with inhaled bronchodilators and steroids. IV aminophylline may cause side effects such as arrhythmias and vomiting. However, some additional benefit may be gained in patients with near-fatal asthma or life-threatening asthma with a poor response to initial therapy (5 mg/kg loading dose over 20 minutes unless on maintenance oral therapy, then continuous infusion of 0.5 – 0.7 mg/kg/hr).

Plasma oncotic pressure (πp) is typically 25-30 mmHg.

70% of π p is generated by albumin so Hypoalbuminemia will decrease π p

The osmotic power of albumin is enhanced by the Gibbs-Donnan effect.

The influence of π p on fluid movement is negligible if the capillary reflection coefficient is 0.1. Another way of saying a vessel is highly permeable is saying the reflection coefficient is close to 0.

Glucagon, secreted from the pancreatic islet alpha cells, is considered to be the main catabolic hormone of the body. It raises the concentration of glucose and fat in the bloodstream

There are five different pancreatic islet cells:
Alpha cells (20%) – produce glucagon
Beta cells (70%) – produce insulin and amylin
Delta cells (<10%) – produce somatostatin
Gamma cells (<5%) – produce pancreatic polypeptide
Epsilon cells (<1%) – produce ghrelin

C. Tetanospasmin, an exotoxin produced by tetani, is responsible for the neurotoxic consequences of tetanus.

The tetanus vaccination contains inactivated tetanus toxoid, which induces the body to produce protective antibodies that neutralize the tetanus toxin.

It induces active immunization against Clostridium tetani exotoxin via toxoid-induced Ab generation.

Adverse actions include anticholinergic effects such as drowsiness, dry mouth, and blurred vision, extrapyramidal effects, and postural hypotension. Phenothiazines can all induce acute dystonic reactions such as facial and skeletal muscle spasms and oculogyric crises; children (especially girls, young women, and those under 10 kg) are particularly susceptible.

Meckel’s lies on the antimesenteric surface of the middle-to-distal ileum, approximately 2 feet proximal to the ileocaecal junction. It appears as a blind-ended tubular outpouching of bowel, about 2 inches long, occurring in about 2% of the population, and may contain two types of ectopic tissue (gastric and pancreatic). The rich blood supply to the diverticulum is provided by the superior mesenteric artery.Proximal to the major duodenal papilla the duodenum is supplied by the gastroduodenal artery (branch of the coeliac trunk) and distal to the major duodenal papilla it is supplied by the inferior pancreaticoduodenal artery (branch of superior mesenteric artery). The arterial supply to the jejunoileum is from the superior mesenteric artery.

Corticotropin-releasing hormone (CRH) is a neurotransmitter and peptide hormone. It is generated by cells in the hypothalamic paraventricular nucleus (PVN) and released into the hypothalamo-hypophyseal portal system at the median eminence through neurosecretory terminals of these neurons. Stress causes the release of CRH.

The CRH is carried to the anterior pituitary through the hypothalamo-hypophyseal portal system, where it activates corticotrophs to release adrenocorticotropic hormone (ACTH). Cortisol, glucocorticoids, mineralocorticoids, and DHEA are all produced in response to ACTH.

Excessive CRH production causes the size and quantity of corticotrophs in the anterior pituitary to expand, which can lead to the creation of a corticotrope tumour that generates too much ACTH.

Pericardiocentesis is a procedure done to remove fluid build-up in the sac around the heart known as the pericardium. The pericardium can be tapped from almost any reasonable location on the chest wall. However, for the usual blind pericardiocentesis, the subxiphoid approach is preferred. Ideally, 2-D echocardiography is used to guide needle insertion and the subsequent path of the needle/catheter.

In the subxiphoid approach, the needle is inserted 1 cm inferior to the left xiphocostal angle with an angle of 30 degrees from the patient’s chest with a direction towards the left mid-clavicle.

The fingers may sense a distinct give when the needle penetrates the parietal pericardium. Successful removal of fluid confirms the needle’s position.

Angiotensin-converting enzyme (ACE) inhibitors prevent angiotensin I from being converted to angiotensin II. Angiotensin II has a variety of effects:
Sympathetic activity has increased.
Vasoconstriction in the arteries
Secretion of Vasopressin
Secretion of aldosterone

The increase in systemic blood pressure is caused by arteriolar vasoconstriction. Vasopressin stimulates water reabsorption in the kidneys as well as the thirst sensation. In the distal convoluted tubules and collecting ducts, aldosterone causes the reabsorption of sodium and water from the urine in exchange for potassium secretion. As a result, ACE inhibitors lower systemic blood pressure while also causing hyperkalaemia.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) are used in a variety of clinical settings, including heart failure. According to a meta-analysis, ACE inhibitors reduce death, MI, and overall admission in patients with heart failure by 28%.
ACE inhibitors are also used in the following clinical settings:
Hypertension
Chronic kidney disease
Diabetic nephropathy 
Following a myocardial infarction

In the presence of renal artery stenosis, ACE inhibitors are contraindicated because they can cause or exacerbate renal failure.
The most common side effect of ACE inhibitors is a dry cough caused by increased bradykinin production. There is, however, no known link to fibrosis of the lungs.

Beta-blockers, including those considered to be cardioselective, should usually be avoided in patients with a history of asthma, bronchospasm or a history of obstructive airways disease. However, when there is no alternative, a cardioselective beta-blocker can be given to these patients with caution and under specialist supervision. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken.

Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific nephritogenic strains of group A beta-haemolytic streptococcus. The clinical presentation of PSGN varies from asymptomatic, microscopic haematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), oedema, hypertension, and acute kidney injury.

In the cancer patient, hyponatremia is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH). This develops more frequently with small cell lung cancer (SCLC) than with other malignancies. The pathogenesis of this is as a result of the process whereby ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, resulting in elevation of cAMP levels. Increased cAMP levels cause fusion of intracellular vesicles with the apical membrane. There are water channels called aquaporins in their membranes of these vesicles, and these increase the water permeability, thus facilitating increased water reabsorption and urine concentration. Thus, by increasing water retention, ADH causes blood to be diluted, which then decreases the concentration of solutes like sodium.

A box and whisker plot is defined as a graphical method of displaying variation in a set of data. In most cases, a histogram analysis provides a sufficient display, but a box and whisker plot can provide additional detail while allowing multiple sets of data to be displayed in the same graph.

The procedure to develop a box and whisker plot comes from the five statistics below:

(1) Minimum value: The smallest value in the data set

(2) Second quartile: The value below which the lower 25% of the data are contained

(3) Median value: The middle number in a range of numbers

(4) Third quartile: The value above which the upper 25% of the data are contained

(5) Maximum value: The largest value in the data set

Advanced paediatric life support (APLS) recommends phenytoin as the first choice for second-line anticonvulsant in a patient that continues to seize ten minutes after the second dose of the first-line anticonvulsant (benzodiazepine). (step 3 of the APLS algorithm)

The recommended dose of phenytoin infusion is up at 20 mg/kg over 20 minutes. If the patient has already taken phenytoin as maintenance therapy or is allergic to phenytoin, then a phenobarbitone infusion should be set up at 20 mg/kg over 30-60 minutes.

A type II error occurs when the null hypothesis is wrongly accepted when it is actually false and we conclude that there is no evidence of a difference in effect when one really exists (a false negative result).

Cellular respiration is the process by which cells obtain energy in the form of adenosine triphosphate (ATP). ATP transfers chemical energy from the energy rich substances in the cell to the cell’s energy requiring reactions e.g. active transport, DNA replication and muscle contraction.Cellular respiration is essentially a three step process: 1) Glycolysis, 2)The Krebs cycle, 3)The electron transfer system.The main respiratory substrate used by cells is 6-carbon glucose. Fats and proteins can also be used as respiratory substrates. When fats are being used as the primary energy source, in the absence of glucose, an excess amount of acetyl-CoA is produced, and is converted into acetone and ketone bodies. This can occur in starvation, fasting or in diabetic ketoacidosis. Proteins are used as an energy source only if protein intake is very high, or if glucose and fat sources are depleted.