CSGD Quiz 3 2009

1

Which one of the following is the most common form of cognitive impairment in Australia?


  Vascular dementia.

  Mixed vascular dementia and Alzheimer’s Disease.

  Alzheimer’s Disease.

  Frontal lobe dementia.

  Viral encephalitis.


See "Differential Diagnoses of Dementia" graph.

A is incorrect: Vascular dementia counts for only 5% of prevalence. B is incorrect: Mixed vascular and AD accounts for only about 10%. C is correct: standalone AD accounts for 65% of dementia prevalence. D is incorrect: FLD is grouped with "other dementias" which collectively account for 8%. E is incorrect: Viral encephalitis, e.g. herpex simplex encephalitis, is probably too acute to be considered a dementia in mosts cases, and is relatively rare anyway.

2

Which one of the following statements about regulation of gene expression is correct?


  Chromatin remodelling involves acetylation and deacetylation of histone proteins.

  Constitutively expressed genes typically include enhancer sequences.

  Transcriptionally active chromatin usually has promoter sequences that are methylated.

  Steroid hormone receptors are examples of transcription factors with leucine zipper motifs.

  RNA polymerase interacts directly with enhancer sequences of genes.


When chromatin is remodelled such that histones are acetylated this is usually associated with that chromatin becoming transcriptionally active. Steroid hormone receptors have zinc-finger motifs.

A is correct: Acetylation of chromatin causes it to unfold, allowing transcription. This process is considered epigenetic. B is incorrect: Constitutively active genes are expressed constantly and generally require only promoter sequences and basal transcription factors. Enhancer sequences are a feature of REGULATED gene expression. C is incorrect: Transcriptionally active chromatin (euchromatin) is unmethylated. D is incorrect: Leucine zipper motifs are features of protein dimer transcription factors. E is incorrect: RNA polymerase binds to the promoter region; transcription factors mediate the activity of enhancer sequences.

3

Which one of the following statements relating to learning and memory is correct?


  Experimental evidence has shown that long-term memory formation in the brain involves cell death in the cerebellum.

  Experimental evidence has shown that long-term memory formation in the brain involves plasticity at synapses mediated by specific receptors and signaling pathways.

  Experimental evidence has shown that long-term memory formation in the brain involves gliogenesis in the striatum.

  Memory deficits in Huntington’s disease are due to the toxic effects of beta-amyloid protein on specific neuronal populations in the brain.

  Memory deficits in Alzheimer’s disease are due to the toxic effects of polyglutamine-expanded protein on specific neuronal populations in the brain.


Synaptic plasticity is a key neural mechanism for learning and memory.

A is incorrect: The cerebellum is involved in memory, but cell death is not a feature of LTP. B is correct: Synapses may become more sensitive to activation and new synapses may grow in response to e.g. activity AMPA/NMDA receptors and gene transcription. C is incorrect: Gliogenesis is not thought to be a part of LTP. D is incorrect: Huntington's is associated with polyglutamine inclusions. E is incorrect: AD is associated with a build-up of β-amyloid protein.

4

A 25 year-old woman delivers her first child at 38 weeks of gestation. The neonate has hepatosplenomegaly (enlarged liver and spleen), a patent ductus arteriosus, and cataracts. When 8 weeks pregnant the mother developed a maculopapular rash, enlarged cervical lymph nodes, sore throat and generalised joint aches. This resolved within 1 week. The subsequent course of the pregnancy was uncomplicated. Which one of the following assessments during the pregnancy would have been most likely to have identified the cause of the problems in the baby?


  Karyotype assessment on amniotic fluid.

  Cervical herpes simplex viral culture.

  Serial maternal serum rubella titres.

  Urinalysis for cytomegalovirus.

  A detailed medication history.


The woman’s symptoms are suggestive of rubella, and the timing of the illness is during foetal organogenesis. A serological rise in rubella antibodies helps to diagnose acute or recent rubella, differentiating infection from previous immunization.

5

Glenda, age 26, has epilepsy which was poorly controlled despite trying various anticonvulsants. For the last 2 years, however, she has been taking sodium valproate and this has achieved excellent control of her epilepsy. Glenda presents for advice about what she should do if she conceives. She has heard that valproate taken during pregnancy increases the risk of birth defects, e.g. abnormal facial appearance. Which one of the following would be the most appropriate advice to give her?


  She should stop taking the valproate as soon as she confirms she is pregnant.

  She should stop taking the valproate as soon as she confirms she is pregnant, but recommence it again at 14 weeks of gestation.

  She should continue the valproate through the first trimester of pregnancy then cease it.

  She should commence folic acid therapy when she wishes to conceive, and continue it and the valproate throughout the pregnancy.

  She should change her anticonvulsant therapy as soon as she confirms she is pregnant.


The risks for the baby if Glenda continues valproate are substantial. However the risks to mother and baby from poorly controlled epilepsy are often greater. It is believed that folic acid supplementation reduces the risk of neural tube defects (particularly in this situation, and in many other women).

6

Antidepressant drugs which act by inhibiting monoamine oxidase have a recognised side-effect known as the “cheese reaction”. Which one of the following is the most correct explanation for why moclobemide is considered less likely to have this side-effect than earlier MAO inhibitors?


  Moclobemide is selective for monoamine oxidase A.

  Moclobemide is a reversible inhibitor of monamine oxidase.

  Moclobemide competes with dietary amines for uptake across the gastrointestinal tract.

  Moclobemide is selective for monoamine oxidase B.

  Moclobemide also inhibits neuronal uptake of monoamines.


(Statement A is true but is not the best explanation.)

The cheese reaction is caused by the build-up of the amine tyramine which is found in many foods such as cheese. It has sympathomimetic effects which can become pathological when levels are high enough. MAO is responsible for metabolising amines such as tyramine, and so MAOIs may contribute to such a build-up.

A is incorrect: Moclobemide is MAO-A selective (meaning that it preferentially acts on 5-HT) but this is not strongly associated with its effect on tyramine metabolism. B is correct: Reversibility mitigates the build-up of tyramine. C is incorrect: MAOIs do not compete with amines for gut uptake; their effect is on monoamine metabolism. D is incorrect: It is MAO-A selective. E is incorrect: MAOIs reduce monoamine metabolism, not their reuptake.

7

Which one of the following drugs that can be used to alleviate anxiety has as its primary site of action a target outside the central nervous system?


  The 5-HT1A receptor agonist, buspirone.

  The barbiturate, phenobarbital.

  The benzodiazepine, diazepam.

  The non-benzodiazepine, zopiclone.

  The β-adrenoceptor antagonist, propranolol.


The only anxiolytics whose primary action is outside the CNS are the β-adrenoceptor antagonists, which work by treating the physical manifestations of anxiety - they inhibit the SNS activation associated with the anxiety "fear response.

8

Which one of the following statements about ageing is correct?


  Cartilage in the nose and ears continues to grow.

  Diastolic blood pressure continues to rise.

  Parathyroid hormone levels decrease.

  There is an increase in subcutaneous fat in the skin.

  Cardiac stroke volume decreases.


A is correct: Other changes in the face include loss of bone and muscle mass (often leading to sunken cheek appearance) B is incorrect: Diastolic BP typically stops rising before age 60. C is incorrect: PTH levels generally increase with age (associated with increased bone resorption). D is incorrect: Skin shows a LOSS of subcutaneous fat, collagen, moisture and decreased elasticity. E is incorrect: Cardiac SV is usually unchanged but ejection fraction is often reduced.

Note: The 2010 lecture notes state that EF is unchanged, and SV increases as a compensation for changed preload/afterload conditions so that overall CO is maintained.

9

Polypharmacy is most associated with which one of the following?


  Less time in hospital.

  Greater patient satisfaction.

  Improved management of multiple illnesses.

  Increased visits to the pharmacy.

  Reduced compliance.


Factors associated with multiple drug use include: age, female gender, number of diagnoses, recent hospitalisation and depression.

A is incorrect: Polypharmacy is associated with increased hospitalisations. B is incorrect: Depression and increased incidence of ADRs are both associated with polypharmacy. C is incorrect: Rational polypharmacy does this in theory, but is not achieved in practice as often as desired. D is incorrect. E is correct: Polypharmacy contributes to 'pill burden', through which costs, regimen complexity and ADRs may cause reduced compliance.

10

Deterioration in an older person may be due to one or more of dementia, delirium or depression. Which one of the following guidelines is most correct?


  Hallucinations occur in dementia and delirium but not in depression.

  Mini Mental State Examination (MMSE) performance is unchanged by depression.

  Sleep patterns are often disturbed in delirium and depression but not in dementia.

  Impaired and fluctuating conscious state is a distinguishing sign of delirium.

  The onset is typically insidious for dementia, rapid for depression, and gradual for delirium.


A is incorrect: All three "D's" can present with hallucinations. B is incorrect: All three "D’s" can impair MMSE performance. C is incorrect: All three "D's" can alter sleep patterns. D is correct: Delirium characteristically has a relatively rapid onset and fluctuating conscious state. E is incorrect: As for D. Depression has a variable period of onset.