Question 281#

Which one of the following statements regarding growth hormone is incorrect?

A. Doesn't act directly on chondrocytes or osteoblasts

Correct Answer A:

Growth hormone acts both directly on tissues (e.g. stimulates division and multiplication of cartilage chondrocytes) and also indirectly following the secretion of insulin-like growth factor 1.

Growth hormone:
Growth hormone (GH) is an anabolic hormone secreted by the somatotroph cells of the anterior lobe of the pituitary gland. It has actions on multiple organ systems and is important in postnatal growth and development. 

Growth hormone is also responsible for changes in protein, lipid, and carbohydrate metabolism.

Mechanism of action:

• Acts on a transmembrane receptor for growth
• Binding of GH to the receptor leads to receptor dimerization
• Acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver 

Conditions associated with GH disorders:

• Excess GH: acromegaly
• GH deficiency: resulting in short stature

Question 282#

The atrial natriuretic peptide receptor is an example of a:

A. Ligand-gated ion channel

Correct Answer C:

Membrane receptors:
There are four main types of membrane receptor: ligand-gated ion channels, tyrosine kinase receptors, guanylate cyclase receptors and G protein-coupled receptors.

Ligand-gated ion channel:

• Generally mediate fast responses
• e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate receptors

Tyrosine kinase receptors:

• Contain intrinsic enzyme activity
• e.g. insulin, growth factors, interferon

Guanylate cyclase receptors:

• Contain intrinsic enzyme activity
• e.g. atrial natriuretic factor receptors

G protein-coupled receptors:

• Generally mediate slow transmission and affect metabolic processes
• Activated by a wide variety of extracellular signals e.g. Peptide hormones, biogenic amines, lipophilic hormones, light
• Consist of 3 main subunits: alpha, beta and gamma
• Ligand binding causes conformational changes to receptor, this induces exchange of GDP for GTP
• e.g. Muscarinic acetylcholine, adrenergic receptors, GABA-B

Question 283#

Which one of the following cells secretes the majority of tumour necrosis factor in humans?

A. Neutrophils

Correct Answer B:
Tumour necrosis factor:
 Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with multiple roles in the immune system.

TNF is secreted mainly by macrophages and has a number of effects on the immune system, acting mainly in a paracrine fashion:

• Activates macrophages and neutrophils
• Acts as co-stimulator for T cell activation
• Key mediator of bodies response to Gram negative septicaemia
• Similar properties to IL-1
• Anti-tumour effect (e.g. phospholipase activation)

TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce apoptosis. It also cause activation of NFkB.

Endothelial effects include increase expression of selectins and increased production of platelet activating factor, IL-1 and prostaglandins.

TNF promotes the proliferation of fibroblasts and their production of protease and collagenase. It is thought fragments of receptors act as binding points in serum Systemic effects include pyrexia, increased acute phase proteins and disordered metabolism leading to cachexia.

TNF is important in the pathogenesis of rheumatoid arthritis - TNF blockers (e.g. infliximab, etanercept) are now licensed for treatment of severe rheumatoid.

TNF blockers:

• Infliximab: monoclonal antibody, IV administration
• Etanercept: fusion protein that mimics the inhibitory effects of naturally occurring soluble TNF receptors, subcutaneous administration
• Adalimumab: monoclonal antibody, subcutaneous administration
• Adverse effects of TNF blockers include reactivation of latent tuberculosis and demyelination Infliximab is also used in active Crohn's disease unresponsive to steroids

Question 284#

A new anti-epileptic drug is trialed for children with absence seizures. There are 250 children in the control group and 150 children assigned to take the new drug. After 4 months 100 children in the control group had had a seizure compared to 15 children in the group taking the new medication.

What is the relative risk reduction?

A. 4

Correct Answer D:

• Relative risk reduction = (EER - CER) / CER
• Experimental event rate, EER = 15 / 150 = 0.1
• Control event rate, CER = 100 / 250 = 0.4
• Relative risk reduction = (EER - CER) / CER = (0.1 - 0.4) / 0.4 = -0.75 or a 75% reduction

Relative risk:

Relative risk (RR) is the ratio of risk in the experimental group (experimental event rate, EER) to risk in the control group (control event rate, CER). The term relative risk ratio is sometimes used instead of relative risk. 

To recap:

•  EER = rate at which events occur in the experimental group
• CER = rate at which events occur in the control group

For example, if we look at a trial comparing the use of paracetamol for dysmenorrhoea compared to placebo we may get the following results:

• Experimental event rate, EER = 60 / 100 = 0.6
• Control event rate, CER = 20 / 80 = 0.25
• Therefore the relative risk ratio = EER / CER = 0.6 / 0.25 = 2.4

If the risk ratio is > 1 then the rate of an event (in this case experiencing significant pain relief) is increased compared to controls. It is therefore appropriate to calculate the relative risk increase if necessary (see below).

If the risk ratio is < 1 then the rate of an event is decreased compared to controls. The relative risk reduction should therefore be calculated (see below).

Relative risk reduction (RRR) or relative risk increase (RRI) is calculated by dividing the absolute risk change by the control event rate.

Using the above data, RRI = (EER - CER) / CER = (0.6 - 0.25) / 0.25 = 1.4 = 140%

Question 285#

You are a ST1 doctor in General Medicine. During an on-call you are in A&E seeing a patient who has a pneumothorax. On arriving you find the A&E ST2 doctor attempting to perform an aspiration. He appears to about to insert the needle at the wrong landmark.

What is the most appropriate action?

A. Tell your colleagues about what happened in the mess to ensure they are aware of the doctors limitations

Correct Answer E:

If you have concerns regarding the management of a patient it is important to act on them. It may be that you are wrong - the ST2 doctor may actually be performing the aspiration using a recognized, safe technique. This should not however stop you voicing your concerns - failing to do so may put the patient at risk.

If you feel unable to do you should discuss your concerns with someone who is in a position to act. Saying nothing puts the patient at potential harm. Filling in a clinical incident form after the event will not alter this.

Spreading rumours in the mess about a doctors ability is unprofessional and unlikely to lead to a resolution of the problem.