Rifampicin is a potent inducer of liver cytochrome enzymes. Other enzyme inducers are:
Carbamazepine
Sodium valproate
Phenytoin
Phenobarbitone

Insulin is secreted from the ? cells of the pancreas. It consists of 51 amino acids arranged in two chains. It interacts with cell surface receptors (not the nuclear receptors and thus mechanism of action is not similar to steroids).
Since insulin can pass from plasma to interstitium and lymphatics, it can be measured in lymph but the concentrations here can be up to 30% less than that of plasma.

It decreases blood glucose by stimulating the entry of glucose in muscle and fat (by increasing the synthesis of Glucose transporters)

A post-tetanic count of 5 denotes a deep neuromuscular blockade.

Post tetanic count (PTC) is a well-established method of evaluating neuromuscular recovery during intense neuromuscular blockade. It cam ne used when there is no response to single twitch, tetanic, or train-of-four (TOF) stimulation to assess the intensity of neuromuscular blockade and to estimate the duration after which the first twitch in the TOF (T1) is likely to reappear.

During a nondepolarizing block, the high frequency of tetanic stimulation will induce a transient increase in the amount of acetylcholine released from the presynaptic nerve ending, such that the intensity of subsequent muscle contractions will be increased (potentiated) briefly (period of post-tetanic potentiation, which may last 2 to 5 min. The neuromuscular response to stimulation during post tetanic potentiation can be used to gauge the depth of block when TOF stimulation otherwise evokes no responses. The number of post tetanic responses is inversely proportional to the depth of block: fewer post tetanic contractions denote a deeper block. When the post tetanic count (PTC) is 6 to 8, recovery to TOF count = 1 is likely imminent from an intermediate-duration blocking agent; when the PTC is 0, the depth of block is profound, and no additional NMBA should be administered.

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.

Phase IIa studies are usually pilot studies designed to demonstrate clinical efficacy or biological activity (‘proof of concept’ studies) whereas phase IIb studies determine the optimal dose at which the drug shows biological activity with minimal side-effects (definite dose-finding studies).

Phase III and Phase IV studies are performed on larger set of participants (usually hundreds to thousands) when safety and efficacy have been established.

Staphylococcus aureus infection is the most likely cause.

Surgical site infections (SSI) occur when there is a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

SSI comprise up to 20% of healthcare associated infections and approximately 5% of patients undergoing surgery will develop an SSI as a result.
The organisms are usually derived from the patient’s own body.

Measures that may increase the risk of SSI include:
-Shaving the wound using a single use electrical razor with a disposable head
-Using a non iodine impregnated surgical drape if one is needed
-Tissue hypoxia
-Delayed prophylactic antibiotics administration in tourniquet surgery, patients with a prosthesis or valve, in clean-contaminated surgery of in contaminated surgery.

Measures that may decrease the risk of SSI include:
1. Intraoperatively
– Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
-Cover surgical site with dressing

In contrast to previous individual RCT’s, a recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection and wound edge protectors do not appear to confer benefit.

2. Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated. Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used.

The left gastric artery is the smallest branch that originates from the coeliac trunk—the coeliac trunk branches of the abdominal aorta at the vertebral level of T12.

The left gastric artery runs along the superior portion of the lesser curvature of the stomach. A peptic ulcer that is serious enough to erode through the stomach mucosa into a branch of the left gastric artery can cause massive blood loss in the stomach, leading to hematemesis. The patient also takes Naproxen, a non-steroidal anti-inflammatory drug that is a common cause for peptic ulcers in otherwise healthy patients.

The left gastric artery is responsible for 85% of upper GI bleeds. In cases refractory to initial treatment, angiography is sometimes needed to embolise the vessel at its origin and stop bleeding. During an angiogram, the radiologist will enter the aorta via the femoral artery, ascend to the level of the 12th vertebrae and then enter the left gastric artery via the coeliac trunk.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

Electrocautery, also known as diathermy, is a technique for coagulation, tissue cutting, and fulguration that uses a high-frequency current to generate heat (cell destruction from dehydration).

The two electrodes in bipolar diathermy are the tips of forceps, and current passes between the tips rather than through the patient. Bipolar diathermy’s power output (40-140 W) is lower than unipolar diathermy’s typical output (400 W). There is no earthing in the bipolar circuit.

A cutting electrode and a indifferent electrode in the form of a metal plate are used in unipolar diathermy. The high-frequency current completes a circuit by passing through the patient from the active electrode to the metal plate. When used correctly, the current density at the indifferent electrode is low, and the patient is unlikely to be burned. Between the patient plate and the earth is placed an isolating capacitor. This has a low impedance to a high frequency current, such as diathermy current, and is used in modern diathermy machines. The capacitor has a high impedance to current at 50 Hz, which protects the patient from electrical shock.

High frequency currents (500 KHz – 1 MHz) are used in both unipolar and bipolar diathermy, which can cause tissue damage and interfere with pacemaker function (less so with bipolar diathermy).

The effect of diathermy is determined by the current density and waveform employed. The current is a pulsed square wave pattern in coagulation mode and a continuous square wave pattern in cutting mode.

The Weibull distribution are used to describe various types of observed failures of the components. it is used in reliability and survival analysis.

Regression Analysis is used to measure the relationship between among two or more variable. It determines the effect of independent variables on the dependent variables.

Student t-test is one of the most commonly used method to test the hypothesis. It determines the significant difference between the means of two different groups.

A time series is a collection of observations of well-defined data obtained at regular interval of time.

Kaplan-Meier estimator is used to estimate the survival function from lifetime data. It can be derived from maximum likelihood estimation of hazard function. It is most likely used to measure the fraction of patient’s life for a certain amount of time after treatment.

In first order kinetics the rate of elimination is proportional to plasma concentration.

Rate of elimination is described by the following equation:

C = C0. e^-kt

Where:
C=drug concentration,
C0= drug concentration at time zero (extrapolated),
k = rate constant and
t = time.

The initial concentration of this drug is 12 mcg/ml therefore:

The plasma concentration will have halved to 6 mcg/ml at 2 hours.
The plasma concentration will have halved to 3 mcg/ml at 4 hours and
The plasma concentration will have halved to 1.5 mcg/ml t 6 hours.