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2004 FRACP paper two

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Question 1 top

Question 2 top Download PDF

A 42yo man with acromegaly undergoes transphenoidal pituitary surgery for a growth hormone-secreting macroadenoma. Six months post-op he has an elevated insulin-like growth factor type I (IGF-I) concentration. A repeat MRI scan reveals a residual and inoperable tumour confined to the right cavernous sinus only.

Which of the following is the most appropriate mamangement?

A. Expectant management
B. B. Radiotherapy
C. Bromocriptine
D. Octreotide
E. Cabergoline

Answer D. Octreotide


GROWTH HORMONE


Reference: http://www.colorado.edu/kines/Class/IPHY3430-200/17endo1.html

Growth hormone:

  • mobilises fatty acids from adipose tissue
  • opposes action of insulin on glucose metabolism
  • increases muscle growth

IGF-I:

  • produced in liver
  • promote DNA synthesis and cell multiplication

 

ACROMEGALY

  • Almost always caused by somatotroph adenoma
  • Associated with increased morbidity and mortality
  • Almost all patients should be treated

Features:

  • Overgrowth of cartilage and collagen-containing tissues
    • Frontal bossing
    • Deeply furrowed creases on face
    • Growth of lower jaw and laryngeal cartilage
    • Broad, thick hands
    • Thickened heel pads
    • Skin tags
    • Shiny, sweaty skin
  • Symptoms
    • Headache
    • Sweating
    • Poor bite
    • Arthritis
    • Carpal tunnel
    • Symptoms of hypopituitarism
  • Can develop
    • Cardiovascular disease, cardiomyopathy, hypertension
    • Respiratory disease, sleep apnoea
    • Arthropathy
    • Neuropathy
    • Malignancy, colonic polyps
    • Glucose intolerance or diabetes

Autonomous secretion of GH is demonstrated by lack of suppression by glucose

Treatment:

  • Aim is to lower serum IGF-1 concentration to within the reference range for pt’s age and gender and to lower serum GH concentration to < 1ng/mL (1mcg/L) as measure after glucose load
  • If IGF-1 level normalised then life expectancy is close to normal
  • Also aim to rid pt of symptoms without causing hypopituitarism
  • GH cannot often be returned to completely normal
  • Metabolic symptoms (s/a diabetes mellitus) often improve
  • Bone and joint symptoms usually persist

Trassphenoidal Surgery

  • Treatment of choice in pts with somatotrophs that are
    • Small
    • Large but still resectable
    • Large and causing visual impairment
  • GH falls to normal in about 80 – 90% of pts with microadenomas
  • Lower in pts with macroadenomas (ie. 50%) and/or higher pre-op GH concentrations
  • GH concentrations usually fall to normal in 1-2 hrs
  • IGF-1 levels can be normal in 7-10 days but can remain high for months
  • Headaches and vision impairment should improve in days
  • Soft tissue swelling and hyperglycaemia diminish in few days

Recurrence is 3-10%, can be several yrs later. Higher risk if nadir GH concentration after oral glucose load is even slightly high.

Peri-op mortality <1% in pts w large invasive adenomas, negligible in pts w microadenomas. Hormone deficiencies in 0-2% of pts.

Other major complications in ~8% of pts: central diabetes insipidus (2%), CSF rhinorrhoea (2%), meningitis (2%). Less likely with experienced surgeons.

Medical Therapy

Used when surgery alone has not reduced GH and IGF-1 to normal.

  1. Somatostatin analogs - 1st line
    • Octreotide, lanreotide
    • Analogs of growth-hormone-inhibitory hormone (somatostatin)
    • Inhibit GH secretion
    • Octreotide binds to specific receptors for somatostatin and its analogs
    • Octreotide has long acting forms (monthly IM injection) and short acting forms (tds s/c injection)
    • Both can be increased if initial response inadequate
    • Should lead to normalisation of IGF-1 and GH and reduced adenoma size and reduced soft tissue swelling and improved insulin sensitivity, LV function improves, sleep apnoea improves
    • Normalisation of bloods occurs in 40 to 75% of pts
    • Can consider combination with cabergoline if not effective alone
    • Side effects: nausea, abdo discomfort, bliating, diarrhoea, fat malabsorption – tends to resolve in few weeks
    • Octreotide reduces postprandial GB contractility and delays GB emptying so 25% of pts get asymptomatic cholesterol gallstones or sludge in 1st 18/12 of Rx
  2. Dopamide angonists
    • Cabergoline (better than bromocriptine)
    • Inhibit GH secretion
    • Not as good as somatostatin analogues
    • Oral form
    • Reduced GH and IGF-1 to near normal in ~40% of pts
    • Not very effective at reducing adenoma size
  3. GH receptor antagonist
    • Pegvisomant
    • Used if no response to other treatments
    • Blocks native GH from binding
    • Cannot use serum GH to monitor effectiveness of Rx
    • Normalises IGF-1 in 97% of pts
    • Potentially increases adenoma size due to increase GH concentration
    • Side effects: elevated liver enzymes, avoid in pts w abnormal LFTs
    • Combination w somatostatin analogue is good
  4. XRT
    • Used for pts who have failed surgical and medical Mx
    • Stops adenoma growth
    • Slow decline in GH secretion, slow clinical improvement
    • Hormone deficiencies relatively common
    • Other complications: cranial nerve palsies, loss of vision, memory deficits (all rare), increased incidence of other intracranial tumours

Long-term Monitoring

  1. 3-4/12 GH and IGF-1 after glucose
  2. Other pituitary hormones yearly
  3. Adenoma size on MRI – yearly at first
  4. Visual field assessments if close to chiasm
  5. Colonoscopy every 3-4 yrs in pts > 50 (increased risk of polyps)
  6. Regular cardiovascular check-up

Topic

Endrocrinology - acromegaly

 

Question 3 top Download PDF

A 65 yo man presents to outpatients complaining of breathlessness on exercise, which has been progressive over the last four years. He has a 40 pack-year smoking history and has had daily cough with clear sputum production over the past 10 years.

Lung function testing shows:

FEV1 0.70L (30% predicted)
FVC 3.77L (90% predicted)
PaO2 61mmHg [75-90]

Which of the following interventions is most likely to improve his survival?

A. Inhaled anticholinergics
B. Long-term oxygen therapy
C. Inhaled corticosteroids
D. Smoking cessation
E. Lung volume reduction surgery


Severity of COPD

FEV1/FVC less than 0.7 = airflow limitation

Factor
Mild
Moderate
Severe
Spirometry findings – postbronchodilator FEV1% 60 – 80% predicted 40 - 59% predicted Less than 40% predicted
Functional assessment (Activities of daily living) Few symptoms
No effect on daily activities
Breathless on moderate exertion Increasing dyspnoea

Breathless on the flat
Increasing limitation of daily activities Dyspnoea on minimal exertion
Daily activities severely curtailed

Complications No Exclude complications; consider sleep apnoea if there is pulmonary hypertension Severe hyponxaemia (PaO2 ,60mmHg)
Hypercapnia (PaCO2 >45mmHg)
Pulmonary HT
Heart failure
Polycythaemia

TREATMENT OF COPD

Optimise Function
Summary
Evidence Level
Inhaled bronchodilators provide symptom relief and may increase exercise capacity A

Long-acting bronchodilators provide sustained relief of symptoms in moderate to severe COPD
A
Long term use of systemic glucocorticoids is not recommended A
Inhaled glucocorticoids should be condiered in pts with documented response or those who have severe COPD with frequent exacerbations B

Identify and treat hypoxaemia and pulmonary HT
A
Pulmonary rehab reduces dyspnoea, anxiety and depression, improves exercise capacity and quality of life and may reduce hospitalisation A
In selected patients, a surgical approach may be considered for symptom relief C
Prevent or treat osteoporosis A
Inhaled bronchodilators
  • Provide symptom relief and may increase exercise capacity
  • Changes in FEV1, FVC not closely correlated with symptomatic improvement
  • Nebulisers not recommended for routine use in stable pts
  • All bronchodilators (beta -2 agonists and anticholinergics) have similar effects on quality of life
  • Combination of the two may be more effective and better tolerated than higher doses of one alone
Severity
FEV1
Suggested treatment
Mild COPD 60 - 80% Intermittent bronchodilator - salbutamol 200mcg or ipratropium bromide 40mcg as needed before exercise
Moderate COPD 40 - 59% Intermittent or regular bronchodilator - salbutamol 200 - 400mcg QID or ipratropium 40mcg daily. Combination may be considered
Severe COPD less than 40% Regular combination bronchodilator - salbutamol 200 - 400mcg QID and ipratropium 40 - 80mcg daily

Long-acting Bronchodilators

  • Long-acting beta-agonists are not currently subsidised by PBS for COPD
  • Improve exercise endurance, quality of life and reduce exacerbation rate and number of hospitalisations
  • More effective and convenient than short-acting bronchodilators but more expensive
  • Salmeterol 50mcg bd
  • Higher dose does not significantly improve response
  • Tiotropium 18mcg daily is approved by PBS for COPD
  • Reduces dyspnoea and improved health status compared to placebo or ipratropium
  • Reduces exacerbations and hospitalisations
  • Improves exercise endurance by reducing hyperinflation
Theophyllines
  • Modest effect on FEV1 and FVC
  • Slightly improves ABGs in moderate to severe COPD
  • Narrow therapeutic range and potential side effects so rarely used
Oral Glucocorticoids
  • Long-term use not recommended (limited efficacy and potential toxicity)
  • Short-course (2 weeks) can be tried
  • Some patients with stable COPD show a significant response (on spirometry and functional assessment)
Inhaled Glucocorticoids
  • Does not influence rate of decline in FEV1
  • Patients with clinically significant acute bronchodilator reversibility may benefit from long-term inhaled glucocorticoid therapy
  • Also indicated in pts who have frequent exacerbations
  • RCT showed pts with severe non-reversible COPD had reduced exacerbations and a slower decline in quality of life with fluticasone 1000mcg daily
  • No effect on overall decline in lung function
Combination Inhaled Glucocorticoid and Long-acting Bronchodilator
  • Improves quality of life, symptoms and exacerbations
  • But some conflicting results so more studies are necessary
Surgery
  • No survival advantage
  • Bullectomy
  • Lung volume reduction surgery (experimental/palliative)
  • Lung transplantation
Identify and Treat Aggravating Factors
  • Sleep apnoea, hypoventilation and hypoxaemia (overlap syndrome = COPD plus OSA)
  • GORD
  • Aspiration
  • Alcohol and sedatives
  • Hypoxaemia and pulmonary HT
Other Treatment
  • Supplemental oxygen
    • long-term O2 therapy (> 15hrs/day) prolongs life in hypoxaemic patients (PaO2 < 55mmHg)
  • Ventilatory support (CPAP or NIPPV for pts with OSA or hypoventilation)
  • Diuretics – may reduce RV filling pressure and oedema
  • Pulmonary rehabilitation
  • Exercise training
  • Patient education
  • Psychosocial support
  • Chest physio
  • Weight reduction/nutrition
  • STOP SMOKING
    • Reduces the rate of decline in lung function
    • Smoking cessation remains the only effective means to affect the decline in lung function
  • Vaccinations (influenza, pneumococcal)


A. Inhaled anticholinergics may improve quality of life but do not influence survival.

B. Long-term oxygen therapy prolongs life in hypoxaemic patients only (PaO2 < 55mmHg) – this patient does not meet this criteria.

C. Inhaled corticosteroids may reduce exacerbations and reduce decline in quality of life but no effect on survival.

D. Smoking cessation is the only effective means to reduce decline in lung function and thus prolong survival.

E. Lung volume reduction surgery may be appropriate in certain patients, results vary among patient groups. This patient is 65 which is considered to be the upper limit when considering surgery for COPD. He has not been trialed on other therapies and we don’t know anything about his health otherwise so we can’t make a judgement on surgery. There is not clear evidence to say it would improve survival in any case.

Topic

Respiratory - Smoking-related chronic lung disease

 

Question 4 top Download PDF

A 35yo married indigenous woman presents with a 4 day history of fever, mild headache and severe polyarthritis involving the wrists, elbows and knees. Joint pain has been only slightly relieved by naproxen 250mg twice daily and paracetamol 1-2g daily. Prior to the onset of arthritis, she had a sore throat for several days but denies rash, vaginal discharge or history of sexually transmitted diseases.
On examination, she appears unwell with a temperature of 39 degrees, an erythematous throat with tonsillar enlargement and a few small tender cervical lymph nodes. There is tenderness and soft tissue swelling of the wrists and knees. Cardiovascular examination is normal.
Which of the following investigations is most likely to identify the diagnosis?

  1. Blood cultures for Staphylococcus aureus
  2. A high vaginal swab for Neisseria gonorrhoea
  3. A throat swab for Stretococcus species
  4. A stool culture for Yersinia enterocolitica
  5. A synovial fluid culture for Neisseria meningitidis

 

The symptoms described clinically fit with acute rheumatic fever:

        1. Sore throat in past 1-5 weeks
        2. Arthritis typically involving the large joints such as elbows, wrists and knees, classically migratory

    SYMPTOMS OF ACUTE RHEUMATIC FEVER

        1. Sore throat (2/3 patients recall sore throat in past 1-5 weeks)
        2. Polyarthritis (75%, more common in adults)
          • Typically migratory involving mainly the large joints such as the knees, ankles, elbows and wrists
          • Usually subsides within 4 weeks
        3. Carditis (40-50%, more common in younger children)
          • Can cause clinical picture of CCF
        4. Sydenham chorea (15%)
        5. Erythema marginatum (10%)
          • Non-pruritic, non-painful erythematous eruption on trunk
          • Can persist intermittently for weeks to months
        6. Other symptoms that can occur
          • Fever
          • Abdominal pain
          • Epistaxis
          • Arthralgia

     

    SIGNS

        • Polyarthritis
          1. Typical symptoms of inflammatory arthritis can occur
          2. Small joints of hands and spine rarely involved
          3. Classically migratory
        • Carditis
          1. Usually pancarditis
          2. New murmur (MS common, isolated aortic disease rare)
          3. Features of CCF
          4. Pericarditis with rub or effusion
        • Subcutaneous nodules
          1. Associated with severe carditis
          2. Usually appear several weeks after onset
          3. Over bony prominences and tendons
          4. Commonly at elbows, knees, wrists, ankles and over Achilles tendon, occiput or spinous processes of vertebrae
          5. Usually persist for 1-2 weeks
        • Erythema marginatum
          1. Evanescent
          2. Tendency to advance at the margins while clearing in the centre
          3. Can disappear in minutes to hours
          4. On trunk and proximal extremities
        • Sydenham chorea

          • Rapid and uncoordinated involuntary purposeless movements
          • Emotional lability
          • Muscle weakness
          • Disappear during sleep
          • Can involve face, hands and feet

          Untreated attacks last approximately 3 months.
          Chronic rheumatic fever (> 6 months) occurs in < 5%.

           

          CAUSES

        1. Group A beta-haemolytic strep (but not all serotypes)
        2. Thought to be due to an abnormal immune response to streptococcal components
        3. Resulting antibodies cross react with host antigens cause immunologic damage leading to the clinical manifestations
        4. Genetic differences in susceptibility

     

    INVESTIGATIONS

        1. No single specific laboratory test can confirm the diagnosis
        2. Throat culture is the standard test to confirm the presence of group A streptococcus
        3. Rapid antigen detection tests have high specificity but low sensitivity so high number of false negatives
        4. Throat swab more sensitive
        5. ASOT, anitstreptococcal DNAse B titre, antihyaluronidase titre
        6. Need to demonstrate a rise in the titre between acute and convalescent sera (3-6 weeks for ASOT, 6-8 weeks for DNAse B)
        7. Blood cultures to rule out IE, bacteraemia, gonococcal infection

     

    DIAGNOSTIC CRITERIA

    Major Criteria

    1. Carditis
    2. Polyarthritis
    3. Chorea
    4. Erythema marginatum
    5. Subcutaneous nodules

     

    Minor Criteria

    1. Arthralgia
    2. Fever
    3. Elevated acute phase reactants
    4. Prolonged PR interval

     

    Evidence of preceding streptococcal infection

    1. Positive throat culture for group A beta-haemolytic streptococci or positive rapid streptococcal antigen test
    2. Elevated or rising streptococcal antibody titre

     

    Criteria met if:

        1. Evidence of preceding group A streptococcal infection plus 2 major criteria or one major and two minor criteria

     

    COMPLICATIONS

        1. Rheumatic heart disease occurs usually 10 to 20 years after original attack
        2. Mitral valve most commonly involved (classically mitral stenosis)

     

    TREATMENT

    Aim is to:

        1. Symptomatic relief
        2. Eradication of group A beta-haemolytic strep
        3. Prophylaxis against future infection to prevent recurrent cardiac disease

     

     

    Symptomatic Relief:

        1. For arthritis use anti-inflammatories (aspirin 4-8g/day in 4 divided doses or naproxen (5-7.5mg/kg bd)
        2. Paracetamol +/- codeine
        3. For carditis, treat the same as for cardiac failure of any cause

    If treatment for chorea is required can use carbamazepine or valproate

    Eradication:

        1. Phenoxymethylpenicillin (500mg orally bd) for at least 10 days

    OR

        1. Benzathine penicillin G as single dose (900mg IM)

    For patients with penicillin allergy:

        1. Erythromycin 800mg (500mg) orally bd for 10 days

     

    Antibiotic Prophylaxis:

        1. Recurrence rates decline with increasing age
        2. Monthly benzathine penicillin (900mg IM)
        3. If IM route not possible, use phenoxymethylpenicillin 250mg orally bd
        4. For patients with penicillin allergy, erythromycin 400mg (250mg) orally bd
        5. Treatment recommended for minimum 10 years after last episode of acute rheumatic fever or until age 21 (whichever is longer)
        6. If residual heart disease of more than mild severity exists then continue until age 35
        7. If severe valve disease or surgery involved continue until age 40 at least
        8. Guidelines recently published by AHA regarding antibiotic prophylaxis for dental procedures etc (see below)
        9. Do not recommend any prophylaxis for RHD which is different to the previous guidelines (as published in therapeutic guidelines)

     

    References: UTD, e-medicine, Circulation April 19 2007 (circ.ahajournals.org)

     

    GONOCOCCAL ARTHRITIS

        1. Most common cause in young adults (while staph aureus most common overall)
        2. Caused by gram-negative diplococcus Neisseria gonorrhoeae
        3. Due to disseminated gonococcal infection which can manifest as arthritis-dermatitis syndrome (60%) or localised septic arthritis (40%)

     

    Arthritis-Dermatitis Syndrome:

        1. Symptoms usually for 3-5 days before diagnosis
        2. Classic triad of migratory polyarthritis, tenosynovitis and dermatitis
        3. Migratory arthralgias most common presenting symptom
        4. Typically asymmetrical, polyarticular and involve upper extremities more than lower extremities
        5. Wrists, elbows, ankles and knees most commonly affected
        6. Tenosynovitis can occur, usually over dorsum of wrist and hand
        7. Painless, non-pruritic rash, typically on extremities – small papules, pustules or vesicles
        8. Non-specific constitutional symptoms (fever, myalgia, malaise)

     

    Septic Arthritis Form:

        1. Usually 3-6 days after onset of illness
        2. Pain, redness and swelling in one or sometimes multiple joints

     

    Diagnosis:

        1. Blood cultures
        2. Joint aspirate (although often negative)
        3. Culture from primary mucosal infection (positive in 90% of cervical samples, 50-75% of male urethral samples, 20% of pharyngeal samples and 15% of rectal samples)
        4. Urine culture
        5. Proven disseminated gonogoccal infection = positive blood cultures, synovial fluid cultures or other site sources
        6. Probable DGI = positive swab from primary mucosal surface
        7. Possible DGI = clinical syndrome and treatment responsive

     

    Treatment:

        1. Same for both forms
        2. Joint washout rarely required
        3. Ceftriaxone 1g IV daily OR cefotaxime 1g IV tds

     

    Clinical picture does not fit with staph aureus (polyarthritis not a common feature), yersinia (not history of GIT symptoms) or meningococcal infections (headache not prominent, arthritis not a common feature).

    While both B and C could be correct, there are more features that suggest acute rheumatic fever rather than disseminated gonococcal infection:

        1. Symmetrical polyarthritis
        2. No rash
        3. No vaginal discharge or history of STDs
        4. Sore throat and cervical lymphadenopathy

     

    In addition, the criteria for acute rheumatic fever will be met if there is evidence of preceding strep infection (pt has polyarthritis, arthralgia, fever).

    So the answer is C – throat swab for streptococcus

     

    just to be aware of….

    TABLE 3. Cardiac Conditions Associated With the Highest Risk of Adverse Outcome From Endocarditis for Which Prophylaxis With Dental Procedures Is Recommended

        1. Prosthetic cardiac valve
        2. Previous IE
        3. Congenital heart disease (CHD)*
          1. Unrepaired cyanotic CHD, including palliative shunts and conduits
          2. Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure†
          3. Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)
        4. Cardiac transplantation recipients who develop cardiac valvulopathy

     

    *Except for the conditions listed above, antibiotic prophylaxis is no longer
    recommended for any other form of CHD.
    †Prophylaxis is recommended because endothelialization of prosthetic
    material occurs within 6 months after the procedure.

    TABLE 4. Dental Procedures for Which Endocarditis Prophylaxis Is Recommended for Patients in Table 3

        1. All dental procedures that involve manipulation of gingival tissue or the

    periapical region of teeth or perforation of the oral mucosa*

    *The following procedures and events do not need prophylaxis: routine anesthetic
    injections through noninfected tissue, taking dental radiographs, placement of removable
    prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement
    of orthodontic brackets, shedding of deciduous teeth, and bleeding from trauma to the lips.

    TABLE 5. Regimens for a Dental Procedure

    Amoxicillin/Ampicillin 2g orally/IM/IV 30 to 60 mins prior to procedure

    If allergic to penicillin

    Cephalexin 2g orally or clindamycin 600mg orally 30 to 60 mins prior to procedure

    *Or other first- or second-generation oral cephalosporin in equivalent adult or pediatric dosage.
    †Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or
    ampicillin.

    TABLE 6. Summary of Major Changes in Updated Document

    We concluded that bacteremia resulting from daily activities is much more likely to cause IE than bacteremia associated with a dental procedure.
    We concluded that only an extremely small number of cases of IE might be prevented by antibiotic prophylaxis even if prophylaxis is 100% effective.
    Antibiotic prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of IE.
    Limit recommendations for IE prophylaxis only to those conditions listed in Table 3.
    Antibiotic prophylaxis is no longer recommended for any other form of CHD, except for the conditions listed in Table 3.
    Antibiotic prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissues or periapical region of teeth or perforation of oral mucosa only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE (Table 3).
    Antibiotic prophylaxis is recommended for procedures on respiratory tract or infected skin, skin structures, or musculoskeletal tissue only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE (Table 3).
    Antibiotic prophylaxis solely to prevent IE is not recommended for GU or GI tract procedures.
    The writing group reaffirms the procedures noted in the 1997 prophylaxis guidelines for which endocarditis prophylaxis is not recommended and extends this to other common procedures, including ear and body piercing, tattooing, and vaginal delivery and hysterectomy.
    Previous guidelines (from antibiotic guidelines) suggest prophylaxis for medium to high risk groups.
    Prevention of endocarditis: cardiac conditions that have a risk for infective endocarditis with dental and other procedures (Table 2.11)


High-risk conditions

Medium-risk conditions

Low-risk conditions

prosthetic cardiac valves
bioprosthetic
homograft
previous infective endocarditis
complex cyanotic congenital heart disease (transposition, tetralogy of Fallot)
surgically constructed systemic-pulmonary shunts, or conduits
mitral valve prolapse with clinically significant regurgitation
acquired valvular dysfunction (eg rheumatic heart disease) in Indigenous patients

acquired valvular dysfunction (eg rheumatic heart disease) in non-Indigenous patients
congenital cardiac malformations other than those defined as high- or low-risk
hypertrophic cardiomyopathy
significant valvular/haemodynamic dysfunction associated with septal defects

isolated secundum atrial septal defects
surgical repair of septal defects
previous coronary artery bypass grafts or stents
mitral valve prolapse without regurgitation
physiological, functional or innocent murmur
previous Kawasaki disease without valvular dysfunction
cardiac pacemakers
pulmonary stenosis
heart-lung transplants

High-risk procedures

Medium-risk procedures

Low-risk procedures

extraction
periodontal procedures including surgery and root planing
replanting avulsed teeth
other surgical procedures (eg implant placement, apicoectomy)

periodontal probing
intraligamentary and intraosseous local anaesthetic injection
supragingival calculus removal/cleaning
rubber dam placement with clamps (where risk of damaging gingiva)
restorative matrix band/strip placement
endodontics beyond the apical foramen
placement of orthodontic bands
placement of interdental wedges
subgingival placement of retraction cords, antibiotic fibres or antibiotic strips

oral examination
infiltration and block local anaesthetic injection
restorative dentistry
supragingival rubber dam clamping and placement of rubber dam
intracanal endodontic procedures
removal of sutures
impressions and construction of dentures
orthodontic bracket placement and adjustment of fixed appliances
application of gels
intraoral radiographs
supragingival plaque removal

Topic

Infectious Diseases Recognition and management of common community-acquired infection

Question 5 top

Question 6 top

Question 7 top Download PDF

A 57yo man with a long history of poorly controlled hypertension and smoking presents with sudden onset of right-sided sensory change and mild change of speech. On examination his speech is slurred but content and comprehension are normal. He has a mild right hemisensory change to pin-prick, with normal power and symmetrical reflexes.

His MRI scans are shown below (T2 weighted axial image (A) and diffusion weighted image (B)).

The most likely cause of the stroke syndrome is:

A. Left middle cerebral artery thrombosis

B. Left basal ganglia haemorrhage

C. Amyloid angiopathy

D. Left middle cerebral penetrating artery occlusion

E. Acute demyelination

 

This question is very similar to one of I-Lynn’s (2005 paper one question 66)– answer is D.

MRI

  1. T1: Fat and subacute haemorrhage have high signal intensity, water has low signal intensity
  2. T2: Water has high signal intensity
  3. CSF and oedema therefore appear white-ish on T2 and dark on T1
  4. Grey matter has more water than white matter so it also has higher intensity on T2 and lower on T1
  5. T2 images better for oedema, demyelination, infarction and chronic haemorrhage
  6. T1 images better for subacute haemorrhage and fat-containing structures
  7. FLAIR is a T2 image but with the normally high signal of the CSF suppressed – allows better visualisation of lesions adjacent to CSF
  8. Diffusion weighted images are the best to detect acute infarct (<7 days) which show up as high signal lesions; also good for encephalitis and abscesses
  9. Gadolinium is the form of IV contrast used for MRIs – seen as high signal on T1 and low signal on T2
  10. Gadolinium does not cross an intact BBB but with enhance lesions lacking a BBB – good for seeing tumours
  11. MRI less sensitive than CT for acute bleeds

 

MCA STROKES

  1. Contralateral hemiplegia
  2. Hemianaesthesia
  3. Homonymous hemianopia
  4. 1-2 days of gaze preference to ipsilateral side
  5. Dysarthria common due to facial weakness
  6. If dominant hemisphere involved:
    1. Global aphasia
  7. If non-dominant hemisphere involved:
    1. Anosognosia
    2. Construction apraxia
    3. Neglect

 

Partial Syndromes:

  1. Various combinations of face +/- hand +/- arm +/- leg weakness +/- expressive or receptive aphasia +/- sensory loss +/- neglect or quadrantanopia
  2. Due to emboli occluding branches of MCA

 

MCA Lacunar Infarcts:

  1. Lenticulostriate vessel occlusion - pure motor or pure sensory stroke contralateral to lesion
  2. Ischaemia of internal capsule causes primarily facial weakness followed by arm and then leg weakness
  3. Lacunar infarcts of globus pallidus and putamen often have few clinical signs

 

ACA STROKES

  1. Divided into 2 segments:
    1. Precommunal (A1) circle of Willis which connects internal carotid to anterior communicating artery
    2. Postcommunal (A2) segment distal to the anterior communicating artery
  2. Occlusion of proximal ACA usually well tolerated due to collateral flow through anterior communicating artery, MCA and PCA
  3. Occlusion of A2 leads to:
    1. Contralateral paralysis of foot and leg
    2. Lesser degree of paresis of contralateral arm
    3. Sensory loss over toes, foot and leg
    4. Urinary incontinence
    5. Gait apraxia
    6. Slowness

 

ANTERIOR CHOROIDAL ARTERY STROKES

  1. This artery arises from the internal carotid artery and supplies the posterior limb of the internal capsule
  2. Compete syndrome:
    1. Contralateral hemiplegia
    2. Hemianaesthesia
    3. Homonymous hemianopia
  3. However, this area is supplied by other vessels also so minimal deficits may occur

 

PCA STROKES

  1. Supplies the cerebellum, medulla, pons, midbrain, thalamus, hippocampus, medial temporal and occipital lobes
  2. 2 clinical syndromes:
    1. P1 – midbrain, subthalamic and thalamic signs due to proximal disease
      1. 3rd nerve palsy WITH
      2. Contralateral ataxia (Claude’s syndrome) OR
      3. Contralateral hemiplegia (Weber’s syndrome)
    2. P2 – cortical temporal and occipital lobes due to distal disease
      1. Contralateral homonymous hemianopia with macula sparing
      2. Memory disturbance
  3. Bilateral infarcts of distal PCA can cause cortical blindness – pt often unaware

 

VERTEBRAL AND CEREBELLAR ARTERIES

  1. PICA is a branch of the 4th segment of the vertebral artery
  2. Posterior inferior cerebellar artery supplies the lateral medulla and the inferior cerebellum
  3. Lateral medullary syndrome:
    1. Vertigo
    2. Numbness of ipsilateral face
    3. Numbness of contralateral body
    4. Diplopia
    5. Hoarseness
    6. Dysarthria
    7. Dysphagia
    8. Ipsilateral Horner’s syndrome
    9. Caused by occlusion of vertebral or PICA
  4. Rarely medial medullary syndrome can occur with contralateral hemiparesis of arm and leg but sparing the face; can involve hypoglossal nerve and medial lemniscus (causing contralateral loss of joint position sense)
  5. Atherothrombotic lesions of single vertebral artery usually compensated by collaterals from the other vertebral artery
  6. If both arteries involved, collateral flow may be insufficient leading to low-flow TIAs – syncope, vertigo and alternating hemiplegia

 

BASILAR ARTERY

  1. Branches supply the pons and superior cerebellum
  2. Complete occlusion:
    1. Bilateral sensory and motor deficits
    2. Cranial nerve signs
    3. Cerebellar dysfunction
    4. “Locked-in” state
  3. TIAs may cause dizziness, diplopia, dysarthria, facial or circumoral numbness and hemisensory symptoms (pending basilar occlusion – important to recognise) – usually last 5 to 30 mins and occur multiple times in a day
  4. Occlusion of a branch of the basilar artery usually causes unilateral sensory, motor and CN signs

 

Acute stroke syndromes


Artery involved

Syndrome

Pathophysiology

Anterior cerebral artery

Motor and/or sensory deficit (foot >> face, arm)
Grasp, sucking reflexes
Abulia, paratonic rigidity, gait apraxia

Embolic > atherothrombotic

Middle cerebral artery

Dominant hemisphere: aphasia, motor and sensory deficit (face, arm >leg >foot), may be complete hemiplegia if internal capsule involved, homonymous hemianopia.
Non-dominant hemisphere: neglect, anosognosia, motor and sensory deficit (face, arm > leg>foot), homonymous hemianopia.

Embolic > atherothrombotic

Posterior cerebral artery

Homonymous hemianopia; alexia without agraphia (dominant hemisphere); visual hallucinations, visual perseverations (calcarine cortex); sensory loss, choreoathetosis, spontaneous pain (thalamus); III nerve palsy, paresis of vertical eye movement, motor deficit (cerebral peduncle, midbrain).

Embolic > atherothrombotic

Penetrating vessels

Pure motor hemiparesis (classic lacunar syndromes)
Pure sensory deficit
Pure sensory-motor deficit
Hemiparesis, homolateral ataxia
Dysarthria/clumsy hand

Small artery (lacunar) infarct

Vertebrobasilar

Cranial nerve palsies
Crossed sensory deficits
Diplopia, dizziness, nausea, vomiting, dysarthria, dysphagia, hiccup
Limp and gait ataxia
Motory deficit
Coma
Bilateral signs suggest basilar artery disease.

Embolic = atherothrombotic

Internal carotid artery

Progressive or stuttering onset of MCA syndrome, occasionally ACA syndrome as well if insufficient collateral flow.

Atherothrombotic > embolic

 


Eligibility criteria for the treatment of acute ischemic stroke with recombinant tissue plasminogen activator (rt-PA)


Inclusion criteria

Clinical diagnosis of ischemic stroke, with the onset of symptoms within three hours of the initiation of treatment (if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal), and with a measurable neurologic deficit

Exclusion criteria

Historical

Stroke or head trauma within the prior 3 months

Any prior history of intracranial hemorrhage

Major surgery within 14 days

Gastrointestinal or gentitourinary bleeding within the previous 21 days

Myocardial infarction in the prior 3 months

Arterial puncture at a noncompressible site within 7 days

Lumbar puncture within 7 days

Clinical

Rapidly improving stroke symptoms

Only minor and isolated neurologic signs

Seizure at the onset of stroke with postictal residual neurologic impairments

Symptoms suggestive of subarachnoid hemorrhage, even if the CT is normal

Clinical presentation consistent with acute MI or post-MI pericarditis

Persistent systolic BP>185, diastolic BP>110 mmHg, or requiring aggressive therapy to control BP

Pregnancy or lactation

Active bleeding or acute trauma (fracture)

Laboratory

Platelets <100,000/mm3

Serum glucose <50 mg/dL (2.8 mmol/L) or >400 mg/dL (22.2 mmol/L)

INR >1.7 if on warfarin

Elevated partial thromboplastin time if on heparin

Head CT scan

Evidence of hemorrhage

Evidence major early infarct signs, such as diffuse swelling of the affected hemisphere, parenchymal hypodensity, and/or effacement of >33 percent of the middle cerebral artery territory

Adapted from Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1996; 47:835 and Adams, HP, Adams, RJ, Brott, T, et al. Stroke 2003; 34:1056.

Topic

Neurology: Stroke

Question 8 top Download PDF

QUESTION 8

Which of the following is the most appropriate medication to maintain remission in ileo-colonic Crohn’s disease?

A. Nicotine

B. Azathioprine

C. Mesalazine

D. Budesonide

E. Cyclosporin

 

CROHN’S DISEASE

  1. Inflammatory condition
  2. Unknown cause (genetic and environmental factors important)
  3. Can affect any part of GIT
  4. Transmural, focal inflammation
  5. Relapsing and remitting course
  6. Aim of treatment is to induce remission and prevent relapse

 

MILD TO MODERATE ACTIVE DISEASE

  1. Oral or parenteral corticosteroids are most effective
  2. Response rates 60-70% at 12-16 weeks
  3. Prednisone 25 to 60mg orally weaning to zero over 8 to 12 weeks after a clinical response
  4. In ileocaecal disease, budesonide controlled-ileal release formulation is also an option, especially in pts with adverse reactions to corticosteroids in past, but expensive and not on PBS
  5. Budesonide 9mg orally daily reducing to zero over 8-12 weeks after clinical response
  6. Benefit of aminosalicylates are limited and of doubtful clinical significance
  7. Metronidazole has a limited effect as a single agent – 20mg/kg orally in divided doses daily
  8. No evidence for adding antibiotics to steroids

 

SEVERE ACTIVE DISEASE

  1. Initially parenteral therapy
  2. Methylprednisolone 60-80mg IV daily in divided doses or hydrocortisone 100mg IV QID
  3. Broad spectrum antibiotics often also used though no actual evidence for this
  4. Change to oral corticosteroids when disease activity has subsided

 

REFRACTORY ACTIVE DISEASE

  1. Infliximab has 60-70% response rates
  2. Response to single infusion lasts 6-8 weeks
  3. If response, maintenance therapy every 8 weeks is used
  4. Serious adverse effects can occur and it is expensive
  5. If still refractory, surgery may be necessary

 

CHRONIC ACTIVE DISEASE

  1. Consider AZA or 6-MP or MTX (plus folic acid) in pts who do not respond to corticosteroids or those who require prolong steroid therapy
  2. Onset of action may be delay – should be continue for at least 3-6 months (or 2-3 months for MTX)
  3. Infliximab also effective
  4. Consider surgery

 

MAINTENANCE THERAPY

  1. AZA, 6-MP have good evidence
  2. Azathioprine 2 to 2.5mg/kg daily
  3. Mercaptopurine 1 to 1.5mg/kg daily
  4. If not tolerated or ineffective, consider MTX 25mg IM weekly (plus folica acid)
  5. Requires monthly monitoring of FBE and LFTs
  6. Infliximab also shown to be effective
  7. Should not use corticosteroids long-term

 

ILEAL MALABSORPTION

  1. Extensive ileal disease or resection can lead to bile salt malabsorption à bile salt diarrhoea or steatorrhoea
  2. Can occur in absence of active inflammation
  3. Treatment = cholestyramine 4-8g daily to tds
  4. Can also use loperamide

 

BACTERIAL OVERGROWTH

  1. Causes diarrhoea and malabsorption
  2. Augmentin DF or metronidazole or norfloxacin for 1-2 weeks

 

PERIANAL DISEASE

  1. Fissures, fistulas and abscesses are common
  2. Surgery often required
  3. Metronidazole usually used 400mg tds – may be needed for weeks to months +/- ciprofloxacin
  4. Refractory perianal disease may respond to AZA
  5. Infliximab is effective in pts with fistulas unresponsive to other treatment

 

OTHER TREATMENTS

  1. Quit smoking à fewer relapses
  2. Diet important to maintain nutrition, TPN may be required
  3. Risk of Fe, zinc, B12, calcium, mg, folic acid and vitamin D deficiency – replace as required

 

Answer: B

 

ULCERATIVE COLITIS

  1. Mucosal disease
  2. Confined to colon
  3. Continuous inflammatory changes extending from rectum

 

ACTIVE PROCTITIS OR DISTAL COLITIS

  1. Rectal and oral 5-ASA therapy more effective than either alone
  2. Rectal corticosteroids are added if 5-ASA ineffective
  3. Continue rectal therapy until symptoms resolve then wean over several weeks
  4. Consider rectally administered maintenance in pts with repeated relapses
  5. If no response, add oral prednisolone

 

EXTENSIVE UC – MILD TO MODERATE

  1. Rectal therapy alone is ineffective for pts with colitis proximal to splenic flexure
  2. Use 5-ASA +/- prednisolone

 

EXTENSIVE UC – SEVERE

  1. > 8 bloody stools/day plus at least one of:
    1. T>37
    2. HR>100
    3. Hb<100
    4. Albumin<35
  2. Hospital admission, early surgical consultation
  3. Methylprednisolone or hydrocortisone for 5-7 days then oral weaning dose
  4. Deterioration or failure to respond over 3-7 days requires consideration of colectomy
  5. Can use IV cyclosporine or infliximab in specialist centres
  6. Avoid loperamide or other antidiarrhoeal and anticholinergic agents and opioids in severe disease as they can precipitate toxic megacolon

 

CHRONICALLY ACTIVE DISEASE

  1. AZA, 6-MP or infliximab
  2. Consider surgery

 

MAINTENANCE THERAPY

  1. 5-ASA is first line
  2. AZA or 6-MP second line
  3. Can consider infliximab if poor response or surgery

 

5-ASA

  1. Exact mechanism of action not known but exerts anti-inflammatory action in bowel wall
  2. Side effects more common at higher doses – nausea, rash, headache, diarrhoea common
  3. Interstitial nephritis infrequent
  4. Blood dyscrasias, pancreatitis and hepatitis rare
  5. Mesalazine, balsalazide, olsalazine and sulfasalazine
  6. Higher risk of adverse effects with sulfasalazine

 

 

 

 

Crohn’s Disease

 

Ulcerative Colitis

 

Mild-Moderate Active Disease

 

Prednisolone
Consider budesonide for ileal disease only

 

1st line: 5-ASA
2nd line: 5-ASA plus prednisolone
Use rectal for distal disease

 

Severe Active Disease

 

1st line: IV steroids
2nd line: infliximab

 

1st line: IV steroids
2nd line: surgery or cyclosporin or infliximab

 

Chronic Active Disease

 

1st line: AZA, 6-MP, MTX
2nd line: infliximab

 

1st line: AZA, 6-MP
2nd line: infliximab or surgery

 

Maintenance Therapy

 

1st line: AZA or 6-MP
2nd line: infliximab

 

1st line: 5-ASA
2nd line: AZA, 6-MP

Topic

Gastroenterology: Chron's Disease

Clinical Pharmacology

Question 9 top

Question 10 top Download PDF

An 80yo woman with long-standing AF and HT is referred for a 2nd opinion on further management. She has been on metoprolol and started warfarin a month ago. She is asymptomatic.

On examination, she has an apex rate of 60/minute and BP of 136/84. She has no signs of cardiac failure. An ECG confirms AF. A CXR shows cardiomegaly with a cardiothoracic ration of 14.5/28 but clear lung fields. Echocardiography demonstrates left ventricular hypertrophy and diastolic dysfunction. Systolic function is preserved with fractional shortening of 28%. Atrial dimensions are normal.

Which of the following long-term management strategies is most appropriate?

  Attempt DC cardioversion Thromboprophylaxis Anti-arrhythmic therapy
a yes continue wafarin Beta blocker
b yes change to aspirin Beta blocker
c yes change to aspirin Amiodarone
d no continue wafarin Beta blocker
e no continue wafarin Amiodarone

Answer D


Rate control vs Rhythm control in AF

  • Two big trials (RACE and AFFIRM) both show that there is not difference in thromboembolic events between rate control methods and rhythm control methods.
  • It is recommended that all patients with AF be on warfarin unless there is a contraindication
  • This includes patients who have been successfully reverted with either DCR or medications
  • Most likely these patients will still have episodes of AF and can be completely asymptomatic
  • So, the 1st thing is to continue warfarin
  • Rate control or rhythm control are both acceptable approaches
  • In most patients rate control is employed:
    • There is a trend toward reduced mortality with rate control
    • Multiple potential side effects to anti-arrhythmic drugs
    • Recurrent AF is common after reversion (DCR or medication)
  • Rhythm control should be considered for patients who:
    • have persistent symptoms despite rate control
    • cannot be adequately rate controlled
    • have a preference for reversion
  • In addition there is a tendency to attempt rhythm control in young patients with a first presentation of AF (with DCR)
  • So, in this 80yo woman rate control is going to be the best option, especially if it has been working so far
  • Having said this there is a theoretical advantage to rhythm control in patients with heart failure as the failure would be easier to control and in diastolic failure the heart relies on the atrial contraction to push that last bit of blood through to the ventricle
  • There have been to trials on this though, and this patient is not symptomatic with her failure so don’t really need to worry about this
  • Therefore answer is d: continue warfarin, continue Bblocker, not for DCR

Just for some additional info, risk factors for thromboembolic event in AF:

  • age > 65
  • female
  • Hx of TIA/stroke
  • HT
  • DM
  • CCF

Topic

Cardiology - Arrhythmias

Question 11 top Download PDF

Which of the following is the most likely organism causing the presentation shown in the photographs above?

  1. Neisseria meningitides
  2. Staphylococcus aureus
  3. Mycoplasma pneumoniae
  4. Listeria monocytogenes
  5. Coxsackievirus

The pictures show a classic strawberry tongue with erythema of the palms.

MYCOPLASMA PNEUMONIA

· Associated with a mild erythematous maculopapular or vesicular rash
· Not associated with tongue changes
· Can also cause Steven-Johnson syndrome

NEISSERIA MENINGITIDIS

· Associated with a maculopapular rash early in course of illness (typically trunk and lower extremities)
· Can develop to petechiae/purpura
· Haemorrhage may be evident on mucous membranes
· No tongue changes

LISTERIA

· Not associated with a rash

COXSACKIE

· Hand, foot and mouth syndrome:

  • fever
  • oral vesicles which then ulcerate on the buccal mucosa and tongue
  •  peripherally distributed small, tender vesicles on the hands and feet

· Occasionally coxsackie can cause petichial or purpuric rash

By exclusion, staphylococcus aureus must be the correct answer. None of the other conditions are associated with the appearances shown.

TOXIC SHOCK SYNDROME

· Caused by toxin-producing strains of staph aureus (TSS)
· Similar disease associated with group A strep (strep pyogenes) – streptococcal toxic shock syndrome (STSS)
· Toxins released are superantigens – activate a large number of T cells
· The results is massive cytokine release (TNF-a, IL-1, IL-2, IFN-g)
· Superantigens do not require processing by APCs but interact directly with MHC II and the V part of the T cell receptor
· Result is fever, rash, hypotension, tissue injury and shock
· Absence of an antibody to toxic shock syndrome toxin-1 is a major risk factor
· Mortality of TSS is 5-15% (STSS mortality is 30-50%)
· Both are rare

Skin and Mucous Membranes:

· Diffuse macular erythrodermal rash (can look like sunburn)
· Scarlatiniform eruption is often present
· erythema and oedema of palms and soles
· Hyperaemia of conjunctiva and mucous membranes
· Strawberry tongue
· Delayed desquamation of palms and soles (usually 2-3 weeks later)

Multisystem Involvement:

· Fever >38.9
· Cardiovascular: hypotension, cardiomyopathy
· Gastrointestinal: nausea, vomiting, diarrhoea
· Muscular: rhabdomyolysis, severe myalgia, muscle tenderness, muscle weakness
· Renal: uraemia, acute renal failure
· Neuro: encephalopathy (probably related to cerebral oedema)
· Pulmonary: ARDS
· Hepatic: elevated enzymes and bilirubin, centrilobular hepatic necrosis
· Haematological: Thrombocytopaenia, leukocytosis, DIC
· Metabolic: Electrolyte imbalances, metabolic acidosis, hypophosphataemia, hypocalcaemia

Associations:

· Influenza
· Sinusitis
· Tracheitis
· IV drug use
· HIV
· Burn wounds
· Allergic contact dermatitis
· Gynaecological infection
· Postpartum period

 

Diagnosis:

To meet the diagnostic criteria, must have all of:
· Fever >38.9
· Hypotension
· Diffuse erythroderma
· Desquamation (later)
· Involvement of at least 3 organ systems

Treatment:

· IV antis
· Supportive
· Treat cause

References: e-medicine, UTD and google

Topic

Infectious Diseases: Bacterial Infections

 

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Question 19 top Download PDF

A 65yo man presents with sudden onset of severe headache. He appears generally unwell and has a blood pressure of 90/60mmHg. There are no focal neurological signs and visual field testing is normal. An urgent non-contrast T1 weighted magnetic resonance imaging (MRI) scan is shown below (coronal view).

Which of the following is the most appropriate first step in management?

A. Glucocorticoid administration

B. Emergency transphenoidal surgery

C. Pituitary radiotherapy

D. Dopamine agonist therapy

E. Somatostatin analogue therapy

This patient has pituitary apoplexy.
Apoplexy is defined as a sudden neurological impairment usually due to a vascular process (ie. haemorrhage or infarct).

Pituitary apoplexy is characterised but thunderclap headache (95%), vomiting (69%), decreased conscious state, visual changes (50-60%), ocular paresis (78%) and hormonal dysfunction.

There is usually an existing pituitary adenoma.

CT often normal. MRI is most sensitive test. In the first 3-5 dyas haemorrhage within the sella is isointense or hypointense on T1-weighted images and  hypointense on T2-weighted images. Usually heterogeneous appearance of pituitary.
Treatment:

  1. Medically stabilise the patient
  2. High-dose corticosteroids
  3. Immediate evaluation of EUC, glucose and pituitary hormones and treat as necessary
  4. Once medically stable, transphenoidal resection

 

Correct answer is A – corticosteroid administration.

While B (surgery) is part of the management, it comes later in the treatment.

C (radiotherapy) does not have an immediate role in the treatment of apoplexy. It may be used as one of the later option for treatment of pituitary adenomas if surgery fails.

D and E are forms of medical management for specific types of pituitary adenomas – dopamine for prolactinomas and somatostatin for GH adenomas.

Topic

Endocrinology: Assessment and management of functioning and non functioning anterior pituitary tumours

 

Question 20 top Download PDF

 

In adult Philadelphia-chromosome-positive chronic myeloid leukaemia (in chronic phase), treatment with which of the following agents is associated with the greatest likelihood of achieving a complete cytogenetic response?

A. Hydroxyurea

B. Radioactive phosphorus

C. Interferon

D. Cytosine arabinoside

E. Imatinib

 

MYELOPROLIFERATIVE DISORDERS

  1. Heterogeneous group of disorders characterised by cellular proliferation of one or more haematological cell lines in the peripheral blood, distinct from acute leukaemia
  2. Consists of 4 diseases:
    1. CML
    2. Polycythaemia rubra vera
    3. Essential thrombocytosis
    4. Myelofibrosis
  3. Clonal origin
  4. Common attribute is acquired activating mutation of gene coding for tyrosine kinases
  5. In CML, tyrosine kinase activity of bcr-abl hybrid gene is increased
  6. In PRV, ET and MF mutations occur in JAK2 gene

 

CML

  1. Increased proliferation of granulocytic cell line without loss of capacity to differentiate
  2. Peripheral blood shows increased number of granulocytes and their immature precursors including occasional blast cells

 

Pathophysiology

  1. Characterised by cytogenetic aberration à reciprocal translocation between long arms of chm 22 and 9 t(9,22)
  2. Results in shortening of chm 22 = Philadelphia chromosome
  3. This translocation relocates an oncogene (abl) from long arm of chm 9 to long arm of chm 22 in BCR region
  4. Resulting bcr-abl fusion gene encodes protein with strong tyrosine kinase activity
  5. Autophosphorylation and constitutive activation of tyrosine kinase

 

Epidemiology

  1. Typically affects middle aged (40s to 50s)
  2. M>F

 

Phases of Disease

  1. Chronic Phase (3-5yrs)
    1. Splenomegaly
    2. Leukocytosis
    3. Few symptoms
    4. Easily controlled with medications
  2. Accelerated Phase
    1. Occurs few months before blast crisis
    2. Survival 1 to 1.5 yrs
    3. Counts more difficult to control with medications
    4. Diagnosis with one or more of:
      1. Blast cells (10 to 19% of peripheral WBCs or nucleated BM cells)
      2. Peripheral basophils (>20%)
      3. persistent thrombocytopaenia (<100) or thrombocytocis (>1000)
      4. Increasing splenomegaly or leukocytosis unresponsive to Rx
      5. Cytogenetic evidence of clonal evolution
  3. Blast Crisis
    1. Similar to acute leukaemia
    2. Survival 3-6 months
    3. Marked increase in BM or peripheral blast count (>20%)
    4. Large foci or clusters of blasts in BMBx
    5. Maybe soft tissue/skin leukaemic infiltrates, extramedullary blast proliferation
    6. Symptoms due to anaemia, thrombocytopaenia, basophilia, rapidly enlarging spleen
    7. Failure of medications to control leukocytosis and splenomegaly
    8. 2/3 – myeloid blasts, 1/3 – lymphoid blasts
    9. Usually further chromosomal abnormalities found at this time

 

Clinical Manifestations

  1. Insidious
  2. Often asymptomatic at diagnosis
  3. Enlarged spleen +/- liver
  4. Fatigue, weight loss, low grade fever, night sweats à hypermetabolic symptoms
  5. Hyperviscosity à visual disturbances
  6. Gout

 

Pathology

  1. WCC 20-60, predominantly neutrophils
  2. Neutrophils have decreased apoptosis à long-lived cells à reduced enzymes/granules à low score on leukocyte alkaline phosphatase staining
  3. Mild basophilia and eosinophilia is common
  4. Early myeloid cells (eg: myeloblasts, myelocytes, metamyelocytes) and nucleated RBCs in peripheral blood and in BM – this differentiates CML from AML in which there is a “leukaemic gap”
  5. Mild to moderate anaemia usually normochromic, normocytic
  6. Platelets can be low, normal or sometimes increased
  7. Increased urate

 

Bone Marrow

  1. Hypercellular
  2. Expansion of myeloid line (neutrophils, eosinophils, basophils)
  3. Megakaryocytes prominent
  4. Mild fibrosis in reticulin stain
  5. Philadelphia chromosome (also often seen in peripheral blood)
  6. Additional chromosomal abnormalities may be found as patients enter blast crisis phase

 

Treatment

  1. Aims of treatment:
    1. Haematological remission (normalisation of peripheral blood counts, no immature cells, no clinical signs of disease)
    2. Cytogenetic remission (complete = no Ph+ cells; partial = 1-35% Ph+ cells; minor = 35-95% Ph+ cells)
    3. Molecular remission (no brc-abl TK)
  2. Imatinib (Gleevec) competitively binds to ATP receptor of BCR-ABL TK à inhibits TK activity in cells with brc-abl à inhibits proliferation and induces apoptosis
  3. Side effects = oedema, muscle cramps, nausea, diarrhoea, abnormal LFTs, rash (porphyria)
  4. Degree of suppression of BCR-ABL TK predicts freedom from progression
  5. Other TK inhibitors are dasatinib and nilotinib
  6. Imatinib resistance can occur by 3 mechanisms:
    1. Amplification and over expression of BCR-ABL
    2. Mutations of BCR-ABL kinase domain
    3. Drug influx-efflux-OCT-1 expression
  7. If resistance occurs can increase dose (variable response) or change to other TK inhibitor
  8. Other treatment options include hydroxyurea (haematological remission but cytogenetic/molecular remission rare), IFN and BM transplant

 

Prognosis

  1. Much better since imatinib became available ?estimated life expectancy
  2. Poorer prognosis associated with advanced age, more blasts, more basophils, larger spleen, more eosinophils and low platelets

 

Answer: E

Topic

Heamatology:Leukaemias

 

Question 21 top Download PDF

A 42yo man presents with a 2 year history of increasing right facial numbness. He has a history of intermittent unsteadiness, mild hearing loss and vertigo but has otherwise been well. Cranial MRI (T1 weighted following gadolinium contrast) is shown below.

The most likely diagnosis is:

A. Multiple sclerosis

B. Neurofibromatosis type 2

C. Cerebellar haemangioblastoma

D. Meningioma

E. Pontine glioma

 

Mutliple Sclerosis:

    • Multiple hyperintense lesions on T2 weighted images
    • Clearly not the answer – the MRI above shows 2 large-ish lesions on T1 – not the appearance of MS
    • Also clinical history really doesn’t fit

    Meningioma

      • Usually benign
      • Attached to dura
      • May invade the skull but infrequently invade the brain
      • Most common across the sagittal sinus, over cerebral convexities, in the cerebellar-pontine angle and along the dorsum of the spinal cord
      • Peaks in middle age
      • Often found incidentally
      • Can present with:
      1. Focal or generalised seizures
      2. Raised ICP
      3. Gradually worsening neurology
      • CT: well-defined extra-axial mass; smooth contour, adjacent to dural structures; isointense but uniformly bright enhancement
      • MRI: isointense or hypointense on T1 and isointense to hyperintense on T2; Strong homogeneous enhancement with gadolinium; most show “dural tail” of contrast

      1. Location of lesions in this question do not suggest a meningioma
      2. 2 discrete lesions also makes it unlikely and there is no dural tail

      Glioma

        • Account for 50 to 60% of brain tumours
        • Include astrocytomas, oligodendrogliomas and mixed gliomas
        • Astrocytomas are most common primary intracranial neoplasm
        • Low-grade astrocytomas are more common in children
        • High-grade astrocytomas are more common in adults and are usually supratentorial
        • Common presentations include headache, seizures, focal neurological signs
        • Usually hypointense on T1 and show heterogeneous enhancement with gadolinium
        • On T2 images the oedema is hyperintense and cannot be distinguished from tumour

        1. Oligodendrogliomas are more benign than astrocytomas
        2. Typically supratentorial
        3. The MRI in the question shows very homogeneous lesions – not at all typical of gliomas

        HAEMANGIOBLASTOMA

        1. Uncommon
        2. Occur mainly in cerebellum and spinal cord
        3. Associated with Von Hippel-Lindau disease – an AD disorder in which patients develop haemangioblastomas, pancreatic cysts and carcinomas, renal masses and phaeochromocytomas
        4. Can also occur sporadically
        5. Usually seen in children and young adults
        6. Multiple tumours suggest VHL disease
        7. Present due to direct compression or tumour-associated haemorrhage
        8. Paraneoplastic erythrocytosis can occur due to elevated EPO produced by tumour
        9. MRI: enhancing nodule associated with a cyst located in the cerebellum or a homogeneously enhancing lesion on the surface of the spinal cord

         

        1. Treatment = surgery +/- XRT
        2. Although possible as the answer, the MRI in the question does not show the cyst within the lesion
        3. I think VHL is also less common than NF2 (but don’t quote me on that)

        NEUROFIBROMATOSIS

          • Neurofibromatosis type 1 = cutaneous neurofibromas, cafe au lait spots, freckling of non-exposed areas, hamartomas of the iris and pseudoarthrosis of the tibia
          • Neurofibromas are benign peripheral nerve tumours composed of Schwann cells and fibroblasts, generally asymptomatic
          • NF1 associated with increased risk of nervous system tumours
          • NF2 = bilateral vestibular schwannomas in >90% and a characteristic type of cataract
          • Cafe au lait spots and peripheral neurofibromas are rare
          • Schwannomas usually present with progressive unilateral deafness in 3rd decade

           

          1. Treatment = surgery in attempt to maintain hearing for as long as possible
          2. Further schwannomas likely to occur with NF2

          Answer: b

          Topic

          Neurology: neoplastic disease

          Repeat question 2003 paper two question 44

           

           

           

          Question 22 top

          Question 23 top Download PDF

          A 32-year-old man has a splenectomy following a motorcycle accident. Which of the following organisms is most likely to cause overwhelming post-splenectomy infection in this man?
          A. Streptococcus pneumoniae.
          B. Neisseria meningitidis.
          C. Staphylococcus aureus.
          D. Escherichia coli.
          E. Haemophilus influenzae.

          ROLE OF THE SPLEEN
          • Neutrophils in spleen ingest circulating bacteria, especially unopsonised organisms
          • Spleen contains nearly half the body’s total immunoglobulin-producing B cells
          • So, spleen clears bacteria from circulation and also stimulates the production of opsonising antibody
          • This is particularly important in the clearance of encapsulated organisms
          POST-SPLENECTOMY SEPSIS
          • This is a fulminant and rapidly fatal illness
          • Incidence estimated to be 1/175 patient years in children and 1/400-500 patient years in adults
          • More common if co-existing immunocompromised
          BACTERIAL PATHOGENS
          • Encapsulated organisms
          • Most common is Streptococcus pneumonia (>50% of infections, >50% of deaths)
          • Other organisms include Neisseria meningitides and Haemophilus influenza
          • Some other uncommon organisms that may be associated with asplenia are Capnocytophaga canimorsus (from dog bites) and Bordetella holmesii (mainly in immunocompromised)
          SYMPTOMS
          • Need to be cautious in asplenic pts with fever
          • PSS can follow minor URTI or LRTI
          • Can also develop without antecedents
          • Intractable rigors
          • High fever
          • Rapid manifestation of complications of baceraemia (such as petechiae, purpure, hypotension)
          EXAMINATION
          • Acutely unwell
          • Tachycardia, hypotension
          • May find source of sepsis (eg: otitis media, pharyngitis, sinusistis, pneumonia)
          • DIC
          MANAGEMENT
          • ICU
          • Fluid resuscitation, often need inotropes
          • Empirical antibiotics:
            • Vancomycin 1g bd
            • Ceftriaxone 2g daily
          PREVENTION
          • Pneumcoccal (every 5 yrs), meningococcal and H. influenzae vaccinations
          • Early oral antibiotics for fever vs. daily prophylaxis
          • Daily prophylaxis is debatable in adults

          Answer is A – S. pneumonia most common pathogen in post-splenectomy sepsis

          Topic

          Infectious Diseases - Infections in special hosts - surgical

          Question 24 top Download PDF

          QUESTION 24

          A 45-year old man presents with a one-week history of anorexia, vomiting and abdominal pain. He denies any fever, but has noted his sclera to be icteric in the last three days. There is a history of intravenous drug use to the age of 25 years. There are no recent prescribed or over-the-counter medications. He drinks the equivalent of 100g of alcohol per day, with frequent heavy intake on weekends.

          Examination confirms icterus, but there are no peripheral stigmata of chronic liver disease. There is moderate to severe tenderness in the right upper quadrant. The liver is percussed at 18cm in the mid-clavicular line. There is no splenomegaly. Cardiovascular,respiratory and peripheral nervous system examinations are normal.

          Routine blood tests show:

          white cell count                                                   12.5 x 109/L                          [3.5-10.5]
          haemoglobin                                                         145 g/L                                  [125-165]
          platelet count                                                       345 x 109/L                           [150-450]
          sodium                                                                   132 mmol/L                          [135-150]
          potassium                                                              4.1 mmol/L                            [3.5-5.0]
          urea                                                                        8.2 mmol/L                            [3.5-8.0]
          creatinine                                                              0.10 mmol/L                         [0.06-0.10]
          bilirubin                                                                                 125 μmol/L                           [7-21]
          alkaline phosphatase (ALP)                                235 U/L                                  [40-110]
          gamma glutamyltranspeptidase(GGT)               976 U/L                                 [10-40]
          aspartate transaminase (AST)                            780 U/L                                  [15-40]
          alanine transaminase (ALT)                                560 U/L                                  [15-40]
          albumin 34 g/L [35-45]

          The most likely explanation for this clinical scenario is:

          A. Advanced cirrhosis

          B. Alcoholic hepatitis

          C. Acute cholecystitis

          D. Acute viral hepatitis

          E. Hepatoma

           

          Just for reference, 1 beer contains 12g of alcohol.

          This patient does not have any evidence of chronic liver disease so can eliminate advanced cirrhosis. Hepatomas are associated with chronic liver disease and are generally asymptomatic.

          ACUTE VIRAL HEPATITIS

          Acute viral hepatitis is possible but less likely in this patient as he has not recent risk factors.

          Acute hepatitis A in adults can vary from flu-like illness to fulminant hepatic failure. Clinical features include jaundice and hepatomegaly. Notable laboratory findings are marked elevations of ALT and AST usually >1000, bilirubin and ALP. ALT often >ALT. Also get elevated acute phase reactants.

          Acute hepatitis B is asymptomatic in 70% of patients. In symptomatic patients, features include anorexia, nausea, jaundice, RUQ discomfort. AST and ALT often 1000 to 2000 – ALT > AST.

          Acute hepatitis C is usually asymptomatic (in 75%). If symptomatic – malaise, nausea, RUQ discomfort, jaundice.

          ACUTE CHOLECYSTITIS

          1. Abdominal pain main feature
          2. Nausea, vomiting, anorexia can occur
          3. Increased WCC, neutrophils
          4. In uncomplicated cholecystitis, may not see elevated bilirubin or ALP
          5. Can get a mild elevation in ALT and AST with jaundice and obstructive picture
          6. Elevations in ALT and AST are too severe in this case and picture is more hepatocellular than obstructive

           

          ALCOHOLIC HEPATITIS

          This patient has a history of alcohol abuse and acute hepatitis – this fits with alcoholic hepatitis.

          Clinical Features

          1. Fever
          2. Hepatomegaly – hepatic swelling due to cell injury and protein retention plus underlying fatty liver
          3. Jaundice
          4. Anorexia
          5. Ascites (30%) – due to transient hepatic swelling and portal obstruction rather than fixed fibrosis
          6. Tender hepatomegaly common, abdominal pain is not

           

          Pathogenesis

          1. Severe alcoholic liver disease in men usually develops after >60-80g per day of alcohol for 10 years
          2. Lower amounts of alcohol needed in women
          3. Other risk factors include hepatitis C, genetic factors and malnutrition
          4. Most alcoholics don’t get alcoholic liver disease (only 15%)

           

          Laboratory Features

          1. Modest elevation in AST, ALT (2 to 7x)
          2. AST/ALT usually >1
          3. GGT elevated but non-specific
          4. Bilirubin may be markedly elevated without corresponding elevations in ALP

           

          Prognosis

          1. Critically ill patients with alcoholic hepatitis have short-term mortality rates near 70%
          2. Severe alcoholic hepatitis present when INR elevated, anaemic, bilirubin >137, renal failure, ascites

           

          Treatment

          1. Abstinence
          2. Nutritional support

           

          Answer: B

          Topic

          Gastroenterology: Acute and chronic liver disease

           

          Question 25 top

          Question 26 top Download PDF

          QUESTION 26

          Which of the following antibiotics most commonly leads to oesophageal ulceration?

          A. Amoxycillin

          B. Ciprofloxacin

          C. Clindamycin

          D. Doxycycline

          E. Erythromycin

           

          Answer:

           Doxycycline

          Topic

          Gastroenterology:oesophageal dysmotility, infections and reflux

          Clinical Pharmacology

           

          Question 27 top

          Question 28 top Download PDF

          A 45 yo man presents with increasing breathlessness on exertion and poor sleep quality. Physical examination shows paradoxical breathing.
          Which of the following is the most appropriate investigation to confirm a diagnosis of bilateral diaphragm paralysis?

          A. Erect and supine vital capacity
          B. Arterial blood gas analysis
          C. Sleep study
          D. Diaphragm fluoroscopy (sniff test)
          E. Maximum inspiratory pressure

          answer:A. Erect and supine vital capacity


          DIAPHRAGMATIC PARALYSIS

          Normal Diaphragm Function
          • 2 components
            • Non-contractile central tendon
            • Contractile muscle fibres which radiate circumferentially and insert into lower 6 ribs and costal cartilages and L1 to L3
          • Innervated by C3 to C5 via ipsilateral phrenic nerve
          • Contraction has the effect of:
            • Decreasing intrapleural pressure
            • Raising the rib cage using the abdomen as a fulcrum
            • Expanding the rib cage by generating positive intraabdominal pressure
          • Diaphragm performs most of the work of normal ventilation
          • Assisted by some of the accessory muscle of respiration
          Paralysis
          • Accessory muscles assume some or all of the work of breathing
          • Weakening of accessory muscles can lead to ventilatory failure (due to fatigue)
          Bilateral Paralysis
          Aetiology:
          • Usually seen with severe generalised muscle weakness
          • Sometimes can be the first or only muscle involved
          • Motor neuron disease (eg: post-polio syndrome, GBS)
          • Myopathy (eg: muscular dystrophy, hyperthyroidism, hypothyroidism)
          • Idiopathic less common
          Clinical Manifestations:
          • Dyspnoea that worsens in supine position
          • Occurs within minutes of lying down
          • Associated tachypnoea and rapid shallow breathing
          • Daytime fatigue
          • Paradoxical abdominal wall retraction during inspiration
          • Hypoxaemia, hypercapnia, atelectasis
          • If severe: ventilatory failure, pulmonary HT, erythrocytosis
          Diagnosis:

          1) CXR

          • Elevated hemidiaphragms, small lung volumes, atelectasis

          2) Vital Capacity

          • Vital capacity in upright and supine positions (50% decrease in VC when supine compared to 10% in normal pts)

          3) EMG

          • EMG - can help differential neuropathy from myopathy but requires expertise to perform and interpret

          4) Maximal Inspiratory Pressure

          • Detects diaphragm dysfunction and paralysis, but can sometimes be normal due to preserved strength of accessory muscles

          5) Transdiaphragmatic Pressure

          • Gold standard
          • Transnasal placement of balloon at lower third of oesophagus to detect changing pleural pressures, and another balloon in stomach to detect changes in abdominal pressure
          • Expertise required

          6) Fluoroscopy

          • Can be misleading as movement of ribs and accessory muscles can give false appearance of diaphragmatic displacement
          • This limitation is not an issue in unilateral paralysis where sniff fluoroscopy is positive in over 90% of cases


          Unilateral Paralysis

          Aetiology:
          • Phrenic nerve injury
          • Herpes zoster, cervical spondylosis, polio, compressive tumours, pneumonia
          • Idiopathic
          Clinical Manifestations:
          • Often asymptomatic at rest
          • Dyspnoea with exercise
          • Orthopnoea, but less intense than with bilateral paralysis
          Diagnosis:
          • Radiological tests usually enough to diagnose (ie. Fluoroscopy).

          1) CXR

          2) Fluoroscopic sniff test – paradoxical elevation of the paralysed hemidiaphragm with inspiration is positive in over 90% of pts


          3) Reduced vital capacity (less so than with bilateral paralysis), VC reduced by 15 to 25% in supine position

          4) EMG has limited role in unilateral paralysis


          Blood gas analysis and sleep study have no role in the investigation of diaphragmatic paralysis.

          Fluoroscopy is useful (and often sufficient for diagnosis) in unilateral paralysis but not bilateral paralysis where it can be misleading.

          Maximum inspiratory pressures can be affected by accessory muscle use so will not assist in the diagnosis when the diaphragm is the only muscle affected.

          Erect and supine vital capacities are easy and will show a significant reduction in the supine position in bilateral paralysis of the diaphragm so this is the most useful investigation to confirm the diagnosis.

          Topic

          Respiratory- Assessment of respiratory symptoms and signs including

           

          Question 29 top

          Question 30 top

          Question 31 top Download PDF

          A young woman with advanced ovarian cancer presents with nausea, vomiting and abdominal pain. Her abdominal X-rays are shown below.

          Which of the following treatments is most likely to improve her symptoms?

          A. Ondansetron

          B. Domperidone

          C. Octreotide

          D. Hyoscine

          E. Prochlorperazine

           

          This woman has a bowel obstruction – multiple air-fluid levels of erect AXR and dilated bowel on supine AXR.

          Given this, pro-kinetic agents are contraindicated. These include the dopamine agonists (domperidone and prochlorperazine as well as metoclopramide).

          Ondansetron is a 5HT3 antagonist. Not sure if this is a pro-kinetic agent but suspect that it is.

          Hyoscine and octreotide are both used to help control nausea and vomiting in malignant bowel obstructions.

          Hyoscine is an anticholinergic. It is helpful in controlling symptoms of colic also. It acts by reducing gastric and intestinal secretions that contribute to abdominal pain, nausea and vomiting.

          Octreotide selectively inhibits secretion of fluids and electrolytes into the gut lumen and is usually used when other measures fail in palliative cases.

          Palliative Care Guidelines Recommend:

          1. Hyoscine to reduce colic
          2. Haloperidol 0.5-2.5mg orally or subcutaneously bd for nausea    and/or
          3. Cyclizine               or
          4. Levomepromazine
          5. If symptoms persist then octreotide is the next option

           

          Cyclizine and levomepromazine are available under the special access scheme in Australia but are otherwise unregistered.

          The correct answer is C.

           

          Topic

          Gastroenterology: persistent vomiting

          Pharmacology

          Question 32 top Download PDF

          An 18 yr old woman with type 1 diabetes mellitus is at most risk of developing which of the following conditions?

          A. Addison’s disease
          B. Pernicious anaemia
          C. Hashimoto’s thyroiditis
          D. Primary ovarian failure
          E. Systemic lupus erythematosus

          PATHOGENESIS OF T1DM

          • T1DM results from autoimmune destruction of the insulin-producing beta-cells in the islets of Langerhans.
          • Occurs in genetically susceptible individuals and is probably triggered by environmental agents.
          • Long latent period where pt is asymptomatic and euglycaemic.
          • Type 1B diabetes mellitus refers to non-autoimmune islet destruction.
          • Six genes are known to influence the risk of T1DM.
          • One of these genes codes for MHC class II molecules to which antigens involved in the pathogenesis of T1DM bind.
          • Allows antigen to be presented to T cells which are the main effector cell in the process.
          • Islet cell autoantibodies (ICAs) are present in 70-80% of pts w T1DM.
          • Autoantigens include glutamic acid decarboxylase which is present in the islets. Autoantibodies to GAD are found in 70% of pts w T1DM.
          • Also insulin and proinsulin autoantigens/autoantibodies, insulinoma-associated protein 2 autoantigens/autoantibodies.
          • B cells may play a role in the development of T1DM but are not essential to the process.
          • T1DM associated with other autoimmune disorders:
            • Thyroid autoimmunity (1 in 4)
            • Antiadrenal antibodies and adrenal insufficiency (about 1-2%)
            • Polyglandular autoimmune disease (adrenal insufficiency, autoimmune thyroid disease and gonadal insufficiency are major components)
            • Transglutaminase autoantibodies in ~ 10%, coeliac disease on Bx in about half of these (most asymptomatic)
            • IPEX is a rare syndrome of overwhelming autoimmunity in neonates. Usually die of severe enteritis. Mutation of foxp3 (gene for regulatory T cells)
            • Autoimmune polyendocrine syndrome type 1 is caused by a mutation of AIRE gene (autoimmune regulator), which normally provides protection from autoimmunity

          Environmental factors

          • Perinatal factors (eg: age greater than 25, pre-eclampsia, neonatal resp disease, jaundice)
          • ?Viruses may play a role (eg: Coxsackievirus, enterovirus)
          • ?Dietary (eg: cow’s milk, timing of exposure to cereals)

          Topic

          Endocrinology - The pathophysiological basis of insulin-dependent and non insulin-dependent diabetes and implications of this for treatment



          Question 33 top Download PDF

          A 72yo man with a history of chronic obstructive pulmonary disease (COPD) presents with an intercurrent lower respiratory tract infection. Apart from plethora and pulmonary signs associated with his respiratory disease, no other abnormalities are found.

          Full blood examination shows:

                          Haemoglobin                                        199 g/L                                  [128-175]
                          Haematocrit                                          0.59                                        [0.36-0.50]
                          Mean cell volume                                82 fL                                       [80-97]
                          White cell count                  13.5 x 109/L                         [3.9-12.7]
                                          Differential:
                                                          Neutrophils           10.1 x 109/L         [1.9-8.0]
                                                          Lymphocytes        0.9 x 109/L            [0.9-3.3]
                                                          Monocytes            1.9 x 109/L            [0.3-1.1]
                                                          Eosinophils            0.5 x 109/L            [0-0.5]
                                                          Basophils               0.1 x 109/L            [0-0.1]
                          Platelet count                                       405 x 109/L                          [150-396]
                          Red cell mass                                        41 mL/kg                               [28-35]
                          Plasma volume                                     44 mL/kg                               [40-50]
                          Serum erythropoietin                         34.0 IU/L                                [4.4-26.4]

          The most likely cause of the elevated haematocrit is:

          A. Dehydration

          B. Chronic hypoxaemia

          C. Polycythaemia vera

          D. Spurious polycythaemia

          E. Low affinity haemoglobin

           

          Haematocrit measures the proportion of blood volume that is occupied by red blood cells. Determined by multiplying the red cell count by the mean cell volume.

          Dehydration can cause an increased haematocrit but would be associated with a reduced plasma volume. Can therefore exclude A.

          Spurious polycythaemia is when the patient has a chronically reduced plasma volume leading to elevated Hb and HCT. Again plasma volume would be reduced.

          Polycythaemia vera is associated with a raised Hb and HCT but the serum EPO level is normal to low.

          The most common cause of polycythaemia is hypoxia due to pulmonary disease. In this case the EPO would be raised.

          Low affinity haemoglobin mutants are genetic defects causing cyanosis from birth (if alpha globin chain defective) or in the 1st year of life (if beta-globin chain defective). Causes cyanosis and anaemia.

          High affinity haemoglobin mutants have erythrocytosis and increased red cell mass. I think EPO would be normal however. In any case this is rare and is not one of the possible answers anyway.

           

           

Major causes of erythrocytosis

  1. Autonomous (inappropriate) increase of Epo - inappropriately high serum Epo

Erythropoietin-producing neoplasms

Renal cell carcinoma

Hepatocellular carcinoma

Hemangioblastoma

Uterine fibroids

Erythropoietin-producing renal lesions

Following renal transplantation (some cases are independent of erythropoietin)

  1. Appropriate increases in erythropoietin - appropriately high serum erythropoietin

Hypoxemia secondary to:

Chronic pulmonary disease

Right-to-left cardiac shunts

Sleep apnea

Massive obesity (Pickwickian syndrome)

High altitude

Red cell defects

Some cases of congenital methemoglobinemia

Chronic carbon monoxide poisoning (including heavy smoking)

Cobalt

  1. Germline and somatic mutational causes of polycythemia

Polycythemia vera

Activating mutations of the erythropoietin receptor

Chuvash polycythemia

Methemoglobinemia

Idiopathic familial polycythemia

High oxygen affinity hemoglobins

Absence of or decrease in 2,3 BPG mutase

From UTD

Topic

Haematology : Polycythaemias-primary and secondary

 

Question 34 top

Question 35 top Download PDF

A 22yo woman with primary generalised epilepsy presents for advice regarding a planned pregnancy. At age 16 years, she presented with a seizure following sleep deprivation and alcohol excess. She was commenced on phenytoin, but after two further seizures in similar circumstances she was changed to sodium valproate and has been seizure-free for three years. She seeks pre-conception advice regarding ongoing anticonvulsant therapy.

To have the best probability of a successful pregnancy, the patient should be advised to minimise provoking factors, take folate and:

  1. Continue sodium valproate therapy
  2. Stop anticonvulsant therapy
  3. Change to carbamazepine therapy
  4. Change to topiramate therapy
  5. Change to clonazepam therapy

From therapeutic guidelines…

TREATMENT OF EPILEPSY
  1. Exclude non-epileptic causes such as breath-holding attacks, arrhythmias, pseudoseizures
  2. Classify type of epilepsy based on history, neurological exam, EEG and imaging
  3. Identify and avoid precipitants if possible (eg: drugs, sleep deprivation, alcohol withdrawal)
Single Seizure
  1. After a single seizure, only 30-50% of patients will have a recurrence
  2. Consider:
    • Symptoms (?previous unrecognised seizures)
    • Signs (EEG or neuro abnormalities increase the risk of recurrence)
    • Seizure type (certain syndromes are more likely to be recurrent – eg: juvenile myoclonic epilepsy, partial seizures)
    • Age (elderly have higher risk of recurrence)
    • Patient wishes
  3. Lowest recurrence rates associated with normal EEG and examination, no identifiable cause for SZ or clear avoidable precipitant
Second Seizure
  1. Treatment usually indicated after 2 or more SZ in 6-12 month period
  2. About 80% of these pts will have recurrence
  3. Exception is if there is a clear avoidable precipitant
Drug Choice
First Line Second Line
Partial  
Carbamazepine > valproate Gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbitone, phenytoin, pregabalin, tiagabine, topiramate
Generalised tonic-clonic  
Valproate, lamotrigine Carbamazepine, oxcarbazepine, phenobarbitone, phenytoin, topiramate
Absence  
Valproate, ethosuximide Clobazam, clonazepam, lamotrigine
Myoclonic  
Valproate Clobazam, clonazepam, phenobarbitone
Infantile spasms  
Tetracosactrin (ACTH analogue), prednisolone Clonazepam, nitrazepam, vigabatrin, valproate
Lennox-Gastaut syndrome  
Valproate Lamotrigine, topiramate, clonazepam

Infantile spasm (West syndrome) – usual onset 4 to 12 months. Brief sudden contractions of the head, neck and trunk. Characteristically spasms occur in runs and last several minutes. Hypsarrhythmia is typically seen on EEG but not essential for diagnosis.

Lennox-Gastaut syndrome – usually onset is 18 months to 3 years. Difficult to control. Characterised by multiple seizure types including tonic (especially nocturnal), myocloninc, atypical absence and tonic-clonic seizures.

Absence – Usual onset 4 to 9 years (childhood) or 10 to 15 years (juvenile). If infrequent, may not require treatment. 50% of patients will also have GTCS. Ethosuximide and valproate are equally effective for absence SZ but ethosuximide does not protect against GTCS. Continue treatment until EEG ceases to show 3 per second spike wave activity and no seizures have occurred for 2 years.

Myoclonic – avoid carbamazepine as it can worsen myoclonic and absence seizures. Also avoid gabapentin, pregabalin, oxcarbazepine and tiagabine.

Treatment Withdrawal

  1. May be considered after 2-3 years without SZ
  2. Slowly wean dose (over weeks to months)
  3. Good prognosis to remain SZ-free if history of few seizures, absence seizures only, younger age when SZ control achieved, normal neuro exam, no brain lesion

Contraception

  1. Several antiepileptics induce hepatic enzymes and increase metabolism of OCP
  2. High risk of contraceptive failure
  3. Carbamazepine, phenytoin, oxcarbazepine, barbiturates and topiramate

Pregnancy

  1. Consider withdrawal of treatment if SZ-free for >2 years
  2. Risk of congenital malformation, even if antiepileptics stopped once pregnancy confirmed
  3. All antiepileptics are potentially teratogenic, no one is safe
  4. If antiepileptics need to be continued, generally the choice is the agent that best controls the epilepsy at the lowest possible dose
  5. Should be offered counselling and pre-natal screening (AFP and U/S)
  6. Folic acid may have role in preventing neural tube defects (5mg daily for 3/12 before and after conception)
  7. Valproate = ADEC D
  8. Carbamazepine = ADEC D
  9. Topiramate = ADEC B3
  10. Clonazepam = ADEC C

 

This patient has not had a seizure for more than 3 years. Previous seizures were provoked. Treatment withdrawal prior to pregnancy is the best option for her.

Answer is B – stop anticonvulsant therapy

Topic

Neurology:

 

 

 

Question 36 top Download PDF

A 35-year-old man with a history of severe penicillin allergy presents with a fever and a widespread rash part of which is shown in the photograph below.

Which of the following is the most appropriate immediate treatment?

A. Penicillin
B. Cetriaxone
C. Erythromycin
D. Ciprofloxacin
E.Vancomycin

The initial step is to appreciate the diagnosis of meningitis caused by neisseria meningitidis

Neisseria meningitidis is the 2nd most common cause of community-acquired adult bacterial meningitis (Strep pneumoniae is the most common).
Usually affects children and young adults.

Can get meningitis without meningococcaemia, meningococcaemia without meningitis or can get both together.

CLINICAL MANIFESTATIONS

  • Fever
  • Nausea and vomiting
  • Headache
  • Decreased concentration
  • Myalgias, leg pain
  • Rapid disease progression

PHYSICAL SIGNS

  • Hypotension/postural hypotension
  • Diaphoresis
  • Petechiae (occurs in 50% of pts on presentation)
  • Meningism }
  • Purpuric rash } Late signs
  • Impaired conscious state }

Focal neurological signs and seizures uncommon (compared to H. influenzae or S. pneumoniae)

Rash

  • Petechial rash usually on trunk and lower body
  • Mucous membranes may show haemorrhage
  • Petechiae can coalesce into purpuric lesions
  • Petechiae correlate with the degree of thrombocytopaenia
  • Sometimes can have maculopapular rash similar to viral exanthems

COMPLICATIONS

  • DIC
  • Purpura fulminans – acute cutaneous haemorrhage and necrosis due to vascular thrombosis and DIC
  • Myocarditis
  • Immune complex manifestations (eg: arthritis, pleurisy, vasculitis, pericarditis)
  • Conus medullaris syndrome
  • Cranial nerve dysfunction (especially 6th, 7th and 8th)

From Emedicine Meningitis

Table 5. CSF Picture of Meningitis According to Etiologic Agent

Agent Opening Pressure WBC count per mL Glucose (mg/dL) Protein (mg/dL) Microbiology
Bacterial meningitis 200-300 100-5000; >80% PMNs* <40 >100 Specific pathogen demonstrated in 60% of Gram stains and 80% of cultures
Viral meningitis 90-200 10-300; lymphocytes Normal, reduced in LCM and mumps Normal but may be slightly elevated Viral isolation, PCR assays
Tuberculous meningitis 180-300 100-500; lymphocytes Reduced, <40 Elevated, >100 Acid-fast bacillus stain, culture, PCR
Cryptococcal meningitis 180-300 10-200; lymphocytes Reduced 50-200 India ink, cryptococcal antigen, culture
Aseptic meningitis 90-200 10-300; lymphocytes Normal Normal but may be slightly elevated Negative findings on workup
Normal values 80-200 0-5; lymphocytes 50-75 15-40 Negative findings on workup

CT is not usually helpful in the diagnosis.

RISK FACTORS

Risk factors for meningococcal infection include:

  1. deficiencies in terminal complement components (eg, membrane attack complex, C5-C9), which increases attack rates but is associated with surprisingly lower mortality rates;
  2. properdin defects that increase the risk of invasive disease;
  3. antecedent viral infection, household crowding, chronic medical illness, corticosteroid use, and active or passive smoking;
  4. overcrowding, as is observed in college dormitories (college freshmen living in dormitories are at highest risk) and military facilities, which has been reported for a clustering of cases.

Download the Therapeutic guidelines flow chart for diagnosis of Meningitis

EMPERICAL THERAPY OF MENINGITIS

Ceftriaxone 4g IV daily (or 2g IV bd)
OR
Cefotaxime 2g IV 6/24

If patient is immunosuppressed or Listeria infection is suspected add

Benzylpenicillin 2.4g IV 4/24
OR
Ampicillin 2g IV 4/24

(Listeria is resistant to cephalosporins)

If gram positive diplococci are seen or a pneumococcal antigen assay in CSF is positive or if the patient has been heavily pretreated with a beta lactam add

Vancomycin 12.5mg/kg up to 500mg IV 6/24

This is to ensure that strep pneumoniae isolates that display intermediate or high resistance to penicillin and/or cephalosporins are adequately covered.

In patients with immediate hypersensitivity to penicillin and/or cephalosporins use

Vancomycin 12.5mg/kg up to 500mg IV 6/24
PLUS
Ciprofloxacin 400mg IV 12/24
OR
Moxifloxacin 400mg IV daily


TREATMENT OF N. MENINGITIDIS

Benzylpenicillin 1.8g IV 4/24

For patients hypersensitive to penicillin (excluding immediate-hypersensitivity reatction) use

Ceftriaxone 4g IV daily or 2g IV bd
OR
Cefotaxime 2g IV 6/24

For patients with immediate penicillin or cephalosporin hypersensitivity use

Ciprofloxacin 400mg IV 2/24


So the answer really depends on whether this patient has immediate hypersensitivity to penicillin or not. It is not entirely clear from the question but I guess you have to assume that he does not. Therefore the answer is B – ceftriaxone is empirical therapy for meningitis.

Topic

Infectious Diseases - Meningitis

 

 

Question 37 top

Question 38 top Download PDF

An 84yo female nursing home resident is ambulant but rarely goes outside. She is thin, eats little and has reflux oesophagitis. Medical history includes mastectomy and radiation therapy for breat cancer at age 60 years. There is a past history of DVT. DEXA scan reveals a t score of -2.2 at the spine and -3.0 at the femoral neck. Serum calcium is normal.

In addition to calcium supplementation, which of the following is the most appropriate initial therapy for her osteoporosis?

    A. Alendronate

    B. Calcitonin

    C. Vitamin D

    D. Oestrogen

    E. Raloxifene

    TREATMENT OF OSTEOPOROSIS

    Calcium Supplementation

    • Evidence that calcium supplementation can reduce the rate of bone loss
    • Limited evidence that it can reduce fracture rates
    • Shown to be safe and effective so is an essential part of treatment

    Specific osteoporosis Pharmacotherapy

    • Prior fracture is required for access to these therapies on PBS

    1) Bisphosphonates

    • Slow bone loss and may improve BMD by 4 to 9% over 2-3yrs
    • Reduce bone resorption
    • 40-50% reduction in fracture rate (but trials were done with daily dosing)
    • First line therapy in post-menopausal osteoporosis
    • Should treat for at least 3-4yrs and then rpt BMD
    • Alendronate or risendronate are usually first choice of treatment
    • In this patient there would be concern about PUD

    2) Raloxifene

    • Selective oestrogen receptor modulator (SERM)
    • Prevents post-menopausal bone loss
    • Reduces risk of vertebral fractures by 36% over 4yrs
    • Contraindicated if history of VTE

    3) Calcitriol

    • Some evidence for reduction in vertebral fractures in post-menopausal osteoporosis
    • Use as monotherapy is controversial and not supported by current evidence
    • Only for patients intolerant of other therapies
    • Avoid in pts with history of hypercalciuria/calcium-containing kidney stones

    4) Oestrogen/Progestin Therapy

    • In the past was 1st line therapy
    • Reduces bone turnover, prevents bone loss and improves BMD by 4-7%
    • Evidence to suggest reduction in spine and hip fractures
    • Need to weigh up risks (breast Ca, stroke, IHD, DVT) and benefits
    • Limit to 5yrs of treatment
    • Usually started at menopause but has limited role in treating older women
    • Would be of concern in this patient mainly given past history of DVT

    5) Teriparatide
    - Human parathyroid hormone
    - Increases bone formation
    - Given as daily subcutaneous injection
    - Reduces vertebral fractures in post-menopausal women by 65%
    - Restricted use due to study showing rats developed bone sarcomas with its use (ie. Must be over 25yrs, no history of Paget’s or certain metabolic disorders, no prior XRT to bone)
    - Consent required
    - Limit use to 18mths

    Vitamin D

    • Efficacy of agents used to treat osteoporosis probably depends on adequate calcium and vitamin D nutrition
    • Where nutritional status is in doubt, supplements should be prescribed
    • Ergocalciferol is clearly indicated in proven vitamin D deficiency, in institutionalised or housebound people and women shrouded for cultural reasons
    • Evidence suggests that serum 25-hydroxy vitamin D levels should be maintained > 50nmol/L
    • Calcitriol is not appropriate for the prevention or treatment of vitamin D deficiency


    This patient is almost certainly vitamin D deficient. This is the first choice in treating osteoporosis. Other therapies listed require a prior fracture for PBS approval. There are also some adverse effects which would be of concern in this patient.

    Topic

    Endocrinology: Osteoporosis


     

    Question 39 top Download PDF

    In patients with familial Creutzfeldt-Jakob disease, which of the following types of mutation is most likely to be identified in the prion protein gene?

    A. Promoter methylation

    B. Deletion with frameshift

    C. Splice-junction mutation

    D. Missense mutation

    E. Nonsense mutation

     

    Prion Disease

    • Neurodegenerative
    • Long incubation periods
    • Progress inexorably once clinical symptoms appear
    • 5 human prion diseases:
      • Kuru
      • Creutzfeld-Jakob disease (sporadic is most common prion disease)
      • Variant CJD
      • Gerstmann-Staussler-Scheiker syndrome (GSS)
      • Fatal familial insomnia (FFI)
    • Prion diseases are disorders of protein conformation
    • Prions reproduce by binding to the normal cellular isoform of the prion protein (PrPc) and stimulate conversion into the disease causing isoform (PrPSc)
    • Role of PrPc unknown
    • Normally exists primarily in alpha helical conformation
    • PrPSc is beta helical
    • PrPSc is transported to the nervous system via axons
    • Leads to apoptosis and cell death
    • Prions are only known infectious pathogens that are devoid of nucleic acid
    • Can be infectious, genetic or sporadic
    • fCJD results from mutation of PRNP gene which codes for PrPc
    • GSS, FFI and fCJD are all caused by dominantly inherited PRNP gene mutations
    • Kuru has occurred in the Fore people of New Guinea after ritualistic canabalism – now almost disappeared
    • vCJD results from exposure to tainted beef from cattle with BSE
    • Scrapie in sheep is another form of animal prion disease
    • sCJD ?results from sporadic mutation or spontaneous conversion of PrPc to PrPSc

    CJD

    • Sporadic (85-95%)
    • Familial (5-15%)
    • Iatrogenic (<1%)
    • Variant

    Neuropathology

      • Often some atrophy of brain but frequently normal on gross examination
      • Spongiform changes (neuronal vacuoles – see picture below)
      • Astrocyte gliosis (constant but non-specific finding)
      • Neuronal loss without inflammation
      • Accumulation of the abnormal prion protein
      • In vCJD there is the characteristic feature of “florid plaques” – amyloid plaques surrounded by vacuoles give appearance of a flower

      Clinical Features
      sCJD

      • Rapidly progressive mental deterioration and myoclonus are cardinal features of sCJD
      • Mean age of onset is ~60yrs
      • Mood changes, sleep disturbance are also common
      • Death usually within 1 year
      • Extrapyramidal signs (such as hypokinesia, nystagmus, ataxia) occur in ~2/3 patients
      • Corticospinal tract signs occur in 40 to 80% - hyperreflexia, extensor plantar responses, spacicity
      • fCJD has slightly earlier onset than sCJD but similar features (?)

       

      iCJD

      • Accidental transmission has occurred with corneal transplantation, contaminated EEG electrode implantation and surgical procedures including dural grafts
      • Also may be associated with human growth hormone and pituitary gonadotropin therapy
      • Largely cerebellar signs early in disease
      • Earlier onset than sCJD

       

      vCJD

      • >140 cases have occurred, >90% in Britain
      • Thought to be from beef tainted with BSE
      • Younger age of onset than sCJD (mean 29yrs)
      • Less rapid progression than sCJD
      • Psychiatric symptoms predominate early
      • Ataxia commonly first neurological sign (average onset 4-6 months)
      • Cognitive decline common with advancement of disease
      • Sensory symptoms also common

       

      Diagnosis

        • Brain biopsy is gold standard
        • MRI
        • EEG: can support diagnosis but no definitive – characteristic pattern of periodic synchronous bi- or triphasic sharp wave complexes (very specific for sCJD, occasionally seen in fCJD, not in vCJD)
        • Protein 1433 common in sCJD
        • Genetic testing for PRNP in fCJD and sCJD

        WHO Diagnostic Criteria (probable sCJD)

        • Progressive dementia
        • At least 2 out of the following 4 clinical features: myoclonus, visual or cerebellar disturbance, pyramidal/extrapyramidal dysfunction, akinetic mutism
        • Typical EEG and/or positive 1433 CSF assay with clinical duration to death less than 2 years
        • Routine investigations should not suggest an alternative diagnosis
        • Definitive diagnosis requires brain tissue with typical features or gene mutation for fCJD/sCJD

         

        Treatment and Prognosis

        • No treatment
        • Always fatal

         

        Genetics

        • Gene encoding PrP (PRNP) is located on short arm of chromosome 20
        • In familial CJD a missense mutation involving the substitution of lysine for glutamine in codon 200 is the most common PRNP gene mutation
        • Over 50 mutations of the PRNP gene have been identified

         

        A Bit on Genetics Generally

          • Missense mutations are types of point mutations where a single nucleotide is changed to cause substitution of a different amino acid
          • Eg: in sickle cell disease, the 17th nucleotide of the gene for the beta chain of Hb is changed from codon CAG (for glutamic acid) CTG (for valine)
          • A nonsense mutation is also a point mutation that results in a premature stop codon
          • A promoter is a regulatory region of DNA located upstream of the gene, providing a control point for regulated gene transcription – I suppose methylation could potentially cause the failure of protein production by this gene
          • Splicing is a modification of genetic information after transcription – introns are removed and exons are joined
          • Mutations of a splice site result in loss of function of that site à premature stop codon, loss of an exon or inclusion of an intron

          From Wikipedia (the absolute basics):
          Deoxyribonucleic acid, or DNA is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all living organisms. The main role of DNA is the long-term storage of information and it is often compared to a set of blueprints, since DNA contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.
          Chemically, DNA is a long polymer of simple units called nucleotides, with a backbone made of sugars and phosphate atoms joined by ester bonds. Attached to each sugar is one of four types of molecules called bases. It is the sequence of these four bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA, in a process called transcription. Most of these RNA molecules are used to synthesize proteins, but others are used directly in structures such as ribosomes and spliceosomes.
          Within cells, DNA is organized into structures called chromosomes and the set of chromosomes within a cell make up a genome. These chromosomes are duplicated before cells divide, in a process called DNA replication. Eukaryotic organisms such as animals, plants, and fungi store their DNA inside the cell nucleus, while in prokaryotes such as bacteria it is found in the cell's cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA, which helps control its interactions with other proteins and thereby control which genes are transcribed.

          Topic

          Neurology: Dementia

           

          Question 40 top Download PDF

          A 55yo woman with a long history of constipation-predominant irritable bowel syndrome presents for review. She complains of worsening constipation and increased bloating. She had a normal colonoscopy at the age of 40 years.

          She presented to the emergency department six days ago with abdominal bloating which sibsided following an enema. An abdominal X-ray is shown below.

           

          The most appropriate next step is to:

          A. Increase fibre intake

          B. Add a laxative to her regimen

          C. Perform a colonoscopy

          D. Perform an abdominal CT scan

          E. Perform an upper abdominal ultrasound

           

          I’m not entirely sure what this XR is mean to be showing us. But if you ignore that and look at the history only, we have a 55yo woman with an altered bowel habit. Her last colonoscopy was 15 years ago.

          Really we have to exclude a colorectal cancer. The best way to do this is with a colonoscopy. So that is the answer – C.

           

          Topic

          Gastroenterology: Colon Cancer

          Question 41 top

          Question 42 top Download PDF

          A 60yo man presents with a 6 month history of increasing bilateral leg pain, exacerbated by walking more than 100-150m and often forcing him to stop and sit to relieve the pain. He has a long history of hypertension and hyperlipidaemia and he suffered a myocardial infarction 6 months previously.

          Examination reveals bruits over both carotids and the femoral arteries but all pedal pulses are readily palpable. Ankle reflexes are absent. Proprioception is absent at the toes but sensation is otherwise intact.

          Which one of the following investigations is most likely to establish the cause of this main’s leg pain?

          A. Arterial Doppler studies of the lower limb

          B. Nerve conduction studies of the lower limb

          C. Lower limb arteriography

          D. A bone scan with SPECT (single photon emission computed tomography) of the lumbosarcral spine

          E. A CT scan of the lumbar spine

           

          Initially the history sounds like vascular claudication but the clinical findings don’t fit – the pedal pulses are all present plus there is loss of the ankle reflexes and proprioception in the toes. This points towards neurogenic claudication. Given the picture of spinal canal stenosis, the most appropriate investigation would be a CT of the lumbar spine.
          Arterial Doppler and arteriography would be looking for vascular disease but pulses are normal. Nerve conduction studies would be for peripheral neuropathy but this patient has bilateral symmetrical lower limb pain without weakness and minimal sensory changes.
          A SPECT scan I suppose would be looking for malignancy – would not be a major concern without back pain, leg weakness or sphincter dysfunction.

          SPINAL CANAL STENOSIS

            • Narrowing of the lumbar spinal canal
            • Can cause neurogenic claudication when severe
            • Usually bilateral
            • Often provoked by standing without walking, relieved by walking
            • Focal weakness, sensory loss or reflex changes may occur when spinal stenosis is associated with radiculopathy
            • Can be congenital or acquired or combination of the two
            • Factors that may contribute include degenerative disease (spondylosis, scoliosis), trauma, spine surgery, endocrine disorders (acromegaly, osteoporosis, hypoparathyroidism) and Paget’s disease
            • Conservative treatment = NSAIDs, physio, analgesia
            • Surgery considered when medical therapy fails – 65-80% get relief of pain, 25% get recurrent stenosis

            Topic

            Neurology: peripheral neuropathy

            Question 43 top Download PDF

            For which of the following conditions is non-invasive positive pressure ventilation (NPPV) least likely to be of benefit?

            A. COPD with acute hypercapnic hypoxic respiratory failure
            B. Obesity-hypoventilation syndrome with chronic hypercapnic respiratory failure
            C. Pneumonia in a stem cell allograft patient with acute hypoxic respiratory failure
            D. Community-acquired pneumonia with acute hypercapnic hypoxic respiratory failure
            E. Duchenne muscular dystrophy (DMD) with chronic hypercapnic respiratory failure

            NPPV

            • Decrease work of breathing
            • Improves alveolar ventilation
            • Improves gas exchange
            Indications:
            • PaCO2 greater than 45mmHg
            • pH less than 7.35 but greater than 7.10
            Diagnosis:
            • COPD exacerbations
            • APO
            • Pneumonia
            • Chronic hypoventilation
            Contraindications:
            • Respiratory arrest
            • Trauma/surgery to face
            • Excessive secretions
            • Aspiration risk
            • Impaired metal status/uncooperative
            • Haemodynamic instability
            • Life-threatening refractory hypoxaemia
            Exacerbations of COPD
            • Reduces mortality
            • Reduces intubation
            • Reduces complications
            Hypoxaemic Respiratory Failure
            • Hypoxaemic respiratory failure is defined as PaO2:FiO2 ratio < 200 in the absence of CO2 retention
            • May increase lung volumes, recruit collapsed alveoli and reduce work of breathing
            • Conflicting results
            • Less efficacious than in hypercapnic exacerbations of COPD
            • Not for routine use
            APO
            • CPAP effective
            • Improves oxygenation and hypercapnia
            • Decreases work of breathing
            • Reduces intubation
            • Reduces mortality
            • BiPAP can be used if CPAP fails
            Acute Asthma
            • No randomised control trials
            • Uncontrolled trial suggest benefit in severe asthma but not routinely recommended
            Immunosuppressed
            • Reduces intubation and thus complications of intubation including nosocomial infections
            Neuromuscular Disorders
            • No randomised control trials due to ethical considerations
            • Several uncontrolled trials demonstrate benefit in symptoms
            Obesity-Hypoventilation Syndrome
            • Definition = obesity and alveolar hypoventilation during wakefulness which cannot be attributed to pulmonary or pleural pathology
            • NPPV is mainstay of treatment
            • CPAP and BiPAP used
            • Should receive PPV at night to reduce daytime somnolence and improve alveolar ventilation

            Guidelines for selecting patients with chronic respiratory failure for non-invasive ventilation

            Chronic hypoventilation:
            • Daytime PaCO2 45 mmHg OR
            • Nocturnal hypoventilation with sustained O2 desaturation AND symptoms (such as morning headache, hypersomnolence, etc)
            • Appropriate diagnosis
              • Neuromuscular diseases
              • Thoracic deformity
              • Obesity hypoventilation syndrome
              • OSA unresponsive to CPAP
            In Summary:

            A. BiPAP of the most benefit in the setting of acute hypercapnic exacerbation of COPD
            B. and E. NPPV is the mainstay of treatment in these conditions and provides significant symptomatic relief
            C. NPPV is of proven benefit in immunocompromised patients as it reduces intubation and nosocomial infections

            Answer D. NPPV may be of benefit in the setting of pneumonia but the main problem is the VQ mismatch which cannot be corrected with NPPV

            Topic

            Respiratory - Sleep disorders | Coad | Pneumonia | Asthma


            Question 44 top Download PDF

            A 47yo woman with advanced cancer is admitted at 3am with a four-day history of weakness, nausea, vomiting and constipation. Her serum calcium is 3.8mmol/L [2.2-2.6] and albumin is 32g/L [31-44].

            The most appropriate initial step in her management is:

            A. Intravenous rehydration

            B. Diuretics

            C. Steroids

            D. Bisphosphonates

            E. Calcitonin

            CAUSES OF HYPERCALCAEMIA

            Increased Bone Resorption
            1. Primary and secondary hyperparathyroidism
            2. Malignancy
            3. Hyperthyroidism
            4. Other – Paget’s disease, oestrogens or anti-oestrogens in metastatic breast cancer, hypervitaminosis A, retinoic acid
            Increased Intestinal Calcium Absorption
            1. Increased calcium intake
              • Renal failure (often with vitamin D supplementation)
              • Milk-alkali syndrome
            2. Hypervitaminosis D
              • Enhanced intake of vitamin D or metabolites
              • Chronic granulomatous disease
              • Malignant lymphoma
              • Acromegaly
            Miscellaneous
            1. Chronic lithium intake
            2. Thiazide diuretics
            3. Pheochromocytoma
            4. Adrenal insufficiency
            5. Rhabdomyolysis and acute renal failure
            6. Theophylline toxicity
            7. Familial hypocalciuric hypercalcaemia
            8. Immobilisation
            9. TPN

             

            Malignancy and hyperparathyroidism are most common causes.

            In sarcoid and other granulomatous disease hypercalcaemia is due to enhanced intestinal absorption due to increased endogenous calcitriol production.

            Calcium elevation in hyperparathyroidism is usually mild so treatment is aimed at correcting the hyperparathyroidism.

            Hypercalcaemia in patients with familial hypocalciuric hypercalcaemia is also mild and produces few symptoms.

            CLINICAL MANIFESTATIONS

            1. Central nervous system dysfunction
            2. Muscle weakness
            3. Constipation
            4. Increased gastrin secretion
            5. Pancreatitis
            6. Acute and chronic renal insufficiency
            7. Nephrogenic diabetes insipidus
            8. Distal renal tubular acidosis
            9. Nephrolithiasis
            10. Shortening of QT interval
            11. Corneal calcium deposition (band keratopathy)

             

            TREATMENT
            There are 5 approaches:

            1. Increase urinary calcium excretion
              • Isotonic saline with or without a loop diuretic
            2. Diminished bone resorption
              • Calcitonin
              • Bisphosphonates
              • Gallium nitrate
              • Plicamycin (rarely used)
            3. Decreased intestinal calcium absorption
              • Corticosteroids in hypervitaminosis D due to chronic granulomatous disease or increased intake and in haematological malignancies
              • Oral phosphate in chronic hypercalcaemia
            4. Chelation of ionised calcium
              • EDTA or intravenous phosphate (rarely used)
              • Oral phosphate in chronic hypercalcaemia
            5. Dialysis

            Treatment of hypercalcaemia usually begins with normal saline administration to produce volume expansion and increase urinary calcium excretion. It rarely normalises the calcium however (unless hypercalcaemia mild).
            Concurrent treatment with bisphosphonates +/- calcitonin is usually needed to treat underlying cause (most commonly malignancy).

            Increase Urinary Calcium Excretion
            • Filtered calcium is passively reabsorbed in the proximal tubule and loop of Henle
            • Actively reabsorbed in the distal tubule under the influence of PTH
            • Can inhibit passive reabsorption and increase excretion by increasing fluid volume with IV normal saline
            • Many patients are dehydrated at presentation due to hypercalcaemic-induced salt wasting
            • Aim to maintain UO 100-150mL/hr after rehydration
            • Loop diuretic can be used if fluid overload develops – this also increases calcium excretion by inhibiting calcium reabsorption in the loop of Henle
            Inhibit Bone Resorption
            • Should be concurrent with volume repletion
            • Options are calcitonin, bisphosphonates and gallium nitrate
            • Bisphosphonates are usually used
            • They interfere with the metabolic activity of osteoclasts and thus inhibit calcium release from bone
            • More potent that calcitonin
            • Examples are pamidronate and zoledronic acid
            • Maximum effect in 2-4 days
            • Gallium nitrate carries risk of nephrotoxicity
            Decreased Intestinal Absorption
            • Increased absorption is usually associated with excess administration of vitamin D or with overproduction of calcitriol (eg: sarcoid)
            • Glucocorticoids decrease endogenous calcitriol production
            • Oral phosphate complexes with calcium in the gut and reduces intestinal absorption
            Chelation of Ionised Calcium
            • EDTA or IV phosphate but now rarely used due to toxicity
            Dialysis
            • Last resort
            • May be indicated in severe hypercalcaemia of malignancy and renal impairment or heart failure where fluids cannot be safely administered
            Mild Chronic Hypercalcaemia
            • Risk of nephrocalcinosis and nephrolithiasis
            • Oral hydration
            • High salt diet
            • Glucocorticoids can be considered for lymphoma, granulomatous disease
            • Oral phosphate
            • No pharmacological treatment is common
            More Severe or Symptomatic Hypercalcaemia
            • ie. serum calcium > 3.0
            • Normal saline
            • Bisphosphonate or calcitonin
            Severe Hypercalcaemia
            • Consider haemodialysis if serum calcium >4.5

             

            This patient has severe hypercalcaemia. She will be dehydrated. The first step in the management is to rehydrate with normal saline and then continue fluids to maintain a urine output of 100-150mL/hr.
            Bisphosphonates (or calcitonin) will be needed to treat this level of hypercalcaemia but is not the initial step.
            Diuretics are only used if the patient becomes overloaded – use a loop diuretic as thiazides can contribute to hypercalcaemia.
            Steroids are sometimes used in certain causes of hypercalcaemia, usually due to elevated calcitonin production (granulomatous disease, lymphoma).

            Answer is A.

            Topic

            Endocrinology: Hypercalcaemia

             

            Question 45 top

            Question 46 top Download PDF

            Which of the following is most likely to prevent recurrent febrile non-haemolytic transfusion reactions in a patient requiring regular transfusion?

            1. Warm blood to 370C
            2. Leucodepletion
            3. Gamma-irradiation
            4. CMV-negative donors
            5. Slow transfusion time

             

            TRANSFUSION REACTIONS

            1. Occur in 1-6% of transfusions
            2. More common in haem/onc pts
            3. Can be immunological, infectious, chemical and physical
            4. Acute or delayed
            5. Major immunological reactions:
              1. Febrile non-haemolytic transfusion reactions
              2. Acute haemolytic transfusion reactions
              3. Delayed haemolytic transfusion reactions
              4. Urticarial transfusion reactions
              5. Transfusion-related acute lung injury
              6. Post-transfusion purpure
              7. Graft vs host disease (rare, primarily in immunocompromised)

             

            FEBRILE NON-HAEMOLYTIC REACTIONS

            1. Most common transfusion reaction
            2. Fever, chills, sometimes mild dyspnoea within 1-6hrs of PRBCs or plt
            3. Benign, no lasting sequelae
            4. About 15% of pts who have FNHTR will have second reaction with further transfusions
            5. Caused by cytokines which accumulate during storage of blood components
            6. Thought that interaction between donor leukocytes and recipient antibodies leads to cytokine release from donor leukocytes

             

            Management

            1. Stop transfusion
            2. Send bloods for haemolysis screen
            3. Antipyretics

             

            Prevention

            1. Leukodeplete blood (though few RCTs)

             

            Answer: B

            ACUTE HAEMOLYTIC REACTIONS

            1. Medical emergency
            2. Rapid destruction of donor RBCs by preformed recipient Abs
            3. Usually due to ABO incompatibility
            4. Occasionally due to acquired alloantibodies (eg: anti-Rh, anti-Jka)
            5. IgM Abs fix complement and cause rapid intravascular haemolysis
            6. Can lead to DIC, shock, ARF due to ATN

             

            Clinical Presentation

            1. Classic triad of fever, flank pain and red/brown urine (rarely seen)
            2. Fever, chills
            3. DIC à bleeding

             

            Initially…

            1. Stop transfusion
            2. ABC
            3. N/Saline infusion
            4. DAT, repeat XM, FBE

             

            Treatment

            1. Generous IVT for UO >100-200mL/hr
            2. If DIC, consider heparinisation
            3. Rx of hyperkalaemia (may need dialysis and cardiac monitoring)
            4. Monitor EUC, coags
            5. Consider vasopressor (eg: dopamine)

             

            DELAYED HAEMOLYTIC REACTIONS

            1. Due to Ab response occurring after re-exposure to foreign red cell Ag previously encountered by transfusion, transplantation or pregnancy
            2. Ab usually against Kidd or Rh
            3. Reactions seen 2 to 10 days after transfusion
            4. Usually extravascular haemolysis, gradual
            5. May see mild fever, falling HCT, mild increase in unconjugated bilirubin and spherocytosis
            6. Diagnosis often made by blood bank when pt has new positive antibody screen on next XM
            7. No treatment required usually

             

            ANAPHYLACTIC REACTIONS

            1. Within a few minutes of transfusion beginning
            2. 1 in 20,000 to 50,000
            3. Usually due to anti-IgA antibodies in an IgA deficient patient
            4. Treatment = stop infusion, adrenaline, airway management etc
            5. Use IgA deficient blood next time

             

            URTICARIAL REACTIONS

            1. Occurs when soluble allergenic substances in the plasma of donated blood react with pre-existing IgE antibodies à mast cells and basophils release histamine
            2. Can continue transfusion if not severe
            3. Anti-histamine

             

            TRANSFUSION-RELATED ACUTE LUNG INJURY

            1. 1 in 2000
            2. Acute respiratory distress, hypoxaemia, hypotension, fever, pulmonary oedema initially without signs of LVF
            3. Usually begins within 2-4 hours of transfusion commencing
            4. Wide clinical spectrum
            5. Death in ~ 10%

             

            Pathogenesis

            1. Pulmonary agglutinin reaction
            2. Though to require 2 insults:
              1. Stimulus (eg: surgery, transfusion, infection) primes neutrophils and activates endothelial cells à increased adhesion molecules à neutrophil adherence to pulmonary endothelium
              2. 2nd stimulus activates neutrophils à toxic mediators released, endothelial damage, increased capillary permeability. This 2nd process may be initiated by a lipid-soluble species formed during storage of blood
            3. Treatment = supportive

             

            POST-TRANSFUSION PURPURA

              • Uncommon
              • Occurs primarily in women
              • Severe thrombocytopaenia develops 5-10 days after transfusion of platelet-containing products (including PRBCs)
              • Low plts last days to weeks
              • Immune-mediated
              • Treatment = IVIG

              Topic

              Haematology: Transfusion

              Question 47 top

              Question 48 top Download PDF

              A 68-year-old man is sent for a second opinion regarding recurrent iron deficiency anaemia requiring blood transfusion.
              Over the last three years, he has required an average of 4 units of packed cells every three months despite oral iron supplements. There is no history of melaena. Bone marrow examination is normal except for absent iron stores.
              Gastroscopy and colonoscopy have been negative on three separate occasions, the last being two months ago. Small bowel biopsy is normal. The patient had a barium meal and follow-through six months ago which was normal.
              General health is good and he is on no regular medications.

              Which of the following investigations is most likely to find the cause of his iron deficiency?

              A. Small bowel enema.
              B. Repeat gastroscopy and colonoscopy.
              C. Enteroscopy.
              D. Abdominal angiography.
              E. Labelled red cell scan.

              I think that this one can be logically worked out by excluding most of the answers.
              A small bowel enema is unlikely to provide any further information that the small bowel follow through. I’m not even sure if it’s possible to do a small bowel enema.
              There seems to be little point in repeating the scopes – he’s had 3 of each and the last was only 2 months ago.
              Abdominal angiography is generally used for patients with an acute bleed that cannot be located or controlled by endoscopic methods. Angiography will only be useful for an arterial bleed. Requires blood loss of 1 to 1.5 mL/minute. The options are to inject vasopressin which causes generalised vasoconstriction, or embolisation.
              A labelled red cell scan requires bleeding at a rate of 0.1-0.5 mL/minute. More sensitive than angiography but less specific. Can only localise the bleeding to an area of the abdomen, not the exact site.

              So the correct answer in this man with chronic blood loss is to look harder at his small bowel – enteroscopy (or more likely a pill cam these days): C

              Topic

              Gastroenterology:Nutrition

              Haematology: anaemia


              Question 49 top Download PDF

              An unconscious 50yo man is brought to the emergency department four hours after an intentional overdose of approximately fifty 50mg amitriptyline tablets. He has had a brief convulsion in the ambulance on the way to hospital. An ECG shows a sinus tachycardia with widened QRS complexes of 0.13 seconds. Monitoring shows runs (lasting up to 5 seconds) of a broad complex tachycardia.

              He is intubated and transferred to ICU.

              The most important initial management is:

              A. amiodarone therapy
              B. phenytoin therapy
              C. bicarbonate therapy
              D. lignocaine therapy
              E. haemodialysis

              Answer C


              TCAs:

              • Inhibit reuptake of noradrenaline and serotonin into presynaptic terminals
              • Also block cholinergic, histaminergic, alpha1-adrenergic and serotonergic receptors (but not related to therapeutic effects)
              • Indicated for major depression, some anxiety disorders, nocturnal enuresis, urge incontinence, pain management, OCD, ADHD and migraine prophylaxis
              • Infrequently can cause cardiac arrhythmias at therapeutic doses
              • Relative contraindications include prolonged QT syndrome


              Amitriptyline Overdose

              • Confusion, poor concentration, seizures
              • Visual hallucinations
              • Drowsiness
              • Hypothermia
              • Tachycardia, BBB, impaired conduction, CCF
              • Dilated pupils
              • Convulsions
              • Severe hypotension
              • Stupor, coma
              • Polyradiculopathy
              • Agitation, hyperactive reflexes, muscle rigidity, vomiting, hyperpyrexia
              • Urinary retention

               


              Sodium bicarbonate is indicated when the QRS interval is >0.10 seconds or the QTc is >0.42 seconds.

              Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.).

              Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion.

              Physostigmine (1-2 mg slow I.V. for adults or 0.5 mg slow I.V. for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade, or for anticholinergic effects, but should only be used as a last measure in life-threatening situations.

              Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

              Therefore answer is C.

              Topic

              Cardiology - Arrhythmias

              Pharmacology - Clinical Toxicology


              Question 50 top Download PDF

              A 43yo woman presents with a 2 day history of mid-thoracic back pain and leg weakness. On examination, cranial nerve and upper extremities are normal. Lower extremity examination reveals normal tone, with brisk reflexes (left greater than right) and an upgoing left plantar response. Power is reduced with grade 4/5 power in hip flexion and ankle dorsiflexion. Sensory examination reveals reduced sensation to pin-prick and temperature involving the right leg to the level of the umblilicus. Her MRI scans are shown below.

              The most likely diagnosis is:

              A. Transverse myelitis

              B. Spinal cord compression

              C. Anterior spinal artery thrombosis

              D.Spinal cord arteriovenous malformation

              E. Syringomyelia

               

              SPINAL CORD DISEASES

              There are a number of causes of spinal cord pathology; these are best divided into acute and chronic causes.
              Acute:

              1. Compressive myelopathies
                1. Neoplastic
                2. Epidural abscess
                3. Epidural haematoma
                4. Haematomyelia
              2. Acute transverse myelopathies (non-compressive)
                1. Spinal cord infarction
                2. Immune-mediated (eg: SLE, sarcoidosis)
                3. Infectious and parainfectious
                4. Demyelinating diseases
                5. Idiopathic transverse myelitis

              Chronic:

              1. Sponylitic myelopathy
              2. Vascular malformations
              3. Retrovirus-associated myelopathy
              4. Syringomyelia
              5. MS
              6. Subacute combined degeneration (B12 deficiency)
              7. Tabes Dorsalis (syphilis)
              8. Familial spastic paraplegia
              9. Adrenomyeloneuropathy
              10. Toxins
              11. Paraneoplastic
              12. Radiation damage
              13. Primary lateral sclerosis

              This patient has an acute myelopathy so this immediately rules out syringomyelia and AV malformation. The clinical information suggests a predominantly left sided lesion with spastic weakness of the left leg >right leg and loss of pain and temperature of the right leg. The sensory level suggests a lesion around T10.
              I would expect spinal artery thrombosis to cause symmetrical symptoms.
              The options that remain are transverse myelitis and cord compression. I don’t think you can really differentiate the 2 based on the history provided so need to look at the MRI. It looks to me like there is something pushing on the spinal cord in the thoracic region. My immediate thought was of vertebral mets but not sure if this is actually the case or not. Usually mets look hypointense on T1. This image is T2. The horizontal plane scan looks like there may be destruction of the vertebral body which would fit with mets.
              Anyway the correct answer is B spinal cord compression.

              Important to differentiate between compressive and non-compressive myelopathies as compression needs immediate intervention. Ultimately need MRI to decide between the 2 but pain prior to development of neurological signs is more suggestive of compression.

              COMPRESSIVE MYELOPATHIES

              Neoplastic

              1. Almost any malignancy can metastasise to the spinal column
              2. Most common ones are breast, prostate, lung, kidney and lymphoma
              3. Thoracic cord most commonly involved (but lumbosacral region more common with prostate and ovarian Ca)
              4. Pain is first symptom – usually precedes compressive symptoms by weeks to months
              5. Urgent MRI is required when signs of compression present
              6. Radicular symptoms only means imaging can be delayed for 24-48hrs if necessary
              7. Pain alone means the scan can wait a few days
              8. Treatment for mets = high dose steroids, XRT
              9. Intradural tumours are usually benign and slow growing (meningiomas, neurofibromas most common)
              10. Symptoms usually start with radicular pain followed by asymmetric progressive spinal cord syndrome
              11. Treatment = surgery
              12. Intramedullary tumours are uncommon – present with cord or hemicord syndromes
              13. Mostly ependymomas, haemangioblastomas or low-grade astrocytomas

               

              Spinal Epidural Abscess

              1. Clinical triad of pain, fever and rapidly progressive weakness
              2. Inflammatory markers raised
              3. Risk factors include impaired immune function, IVDU, infection of skin or other tissues
              4. 2/3 result from haematogenous spread of skin, soft tissue or deep visceral infection
              5. 1/3 result from direct extension of local infection (eg: vertebral OM, decubitus pressure ulcers, complications of LP/epidural/spinal surgery)
              6. Most cases due to staph aureus, others include strep, GNB, anaerobes and fungi
              7. TB important in developing world
              8. Treatment = decompressive laminectomy with debridement and long-term Abx

               

              Epidural Haematoma

              1. Haemorrhage into epidural or subdural space
              2. Rare complication of LP/epidural
              3. Acute onset of pain and variable signs of cord compression
              4. Treatment = surgery, reversal of clotting defects if present

               

              Haematomyelia

              1. Haemorrhage into spinal cord itself
              2. Due to trauma, vasculitis, vascular malformation, bleeding disorders or spinal cord neoplasm
              3.  Therapy is supportive

               

              ACUTE TRANSVERSE MYELOPATHIES

              1. Acute transverse myelopathies are rapidly progressive spinal cord syndromes
              2. Associated with leg weakness, incontinence and bilateral sensory loss not due to cord compression
              3. Time from onset to maximum symptoms is often hours to days but can occur more slowly
              4. 5 general causes of acute transverse myelopathies:
                1. Spinal cord infarction
                2. Systemic disorders including SLE and sarcoidosis
                3. Infectious
                4. Demyelinating diseases
                5. Idiopathic transverse myelitis

               

              Spinal Cord Infarction

              1. There is a single anterior spinal artery and paired posterior spinal arteries which are the main blood supply to the spinal cord
              2. Anterior spinal artery supplies the anterior 2/3 of the spinal cord
              3. Spinal cord ischaemia can occur at any level but is most common in the upper-thoracic segments (watershed area)
              4. Infarction results in spastic paralysis, dissociated sensory loss affecting pain and temperature but sparing vibration and position sense, and loss of sphincter control
              5. Onset can be sudden but is more often progressive over a few minutes to hours
              6. Back pain at the level of infarction is common
              7. Areflexia due to spinal shock is often present early but spasticity appears with time
              8. Infarction in the territory of the posterior spinal arteries can also occur leading to loss of vibration and position sense
              9. Spinal cord infarction is associated with aortic atherosclerosis, aortic dissection and hypotension
              10. Other possible causes include cardiogenic emboli, vasculitis and surgical interruption of the aorta
              11. In many cases no cause is found
              12. MRI may show infarction
              13. Treatment aimed at predisposing condition

               

              Immune-Mediated

              1. Acute transverse myelopathies occur in ~1% of pts with SLE and can be presenting symptom
              2. CSF normal or mildly elevated lymphocytes, antiphospholipid antibodies present in 2/3 of cases
              3. May respond to steroids or cyclophosphamide
              4. Other immune-mediated causes include Sjrogren’s syndrome, mixed connective tissue disease, Behcet’s syndrome and vasculitis with pANCA antibodies
              5. Sarcoid myelopathy can mimic a tumour with large oedematous swelling
              6. CSF can show elevated lymphocytes and oligoclonal bands
              7. Look for other evidence of sarcoid – CXR/CT, slit lamp examination for uveitis, serum ACE
              8. Treat with steroids +/- immunosuppressants

               

              Infectious

              1. Many viruses associated with acute myelitis caused by direct infection of the spinal cord
              2. Herpes zoster most common, others include HSV 1 + 2, EBV, CMV, rabies
              3. Treat with antivirals
              4. Bacterial causes less common but almost any species can be responsible including mycoplasma
              5. Schistosomiasis is important parasitic cause in endemic areas
              6. Consider toxoplasmosis particularly in patients with AIDS
              7. Postinfectious myelitis or postvaccinial myelitis can occur with many agents

               

              Demyelination

              1. MS can present as acute transverse myelopathy but rare in Caucasians
              2. Neuromyelitis optica is a syndrome of ATM plus optic neuritis that is associated with MS as well as other immune-mediated diseases such as SLE
              3. MRI for diagnosis, including MRI brain to assess for other lesions (and thus likelihood of progressing to MS)
              4. Treat with steroids

               

              Idiopathic Transverse Myelitis

              1. No cause found in about ¼ of cases of ATM
              2. In cases associated with inflammation (eg: contrast enhancement on MRI or CSF leukocytosis) but no evidence of infection, glucocorticoids are 1st treatment choice, followed by plasma exchange

               

              CHRONIC MYELOPATHIES

              Spondylitic Myelopathy

              1. Common in elderly
              2. Bony impingement and overgrowth of soft tissue causes compression of nerve roots
              3. Neck and shoulder pain are early symptoms, followed by radicular arm pain, most often C5-C6 distribution with muscle wasting in hands
              4. Compression of cervical cord produces a slowly progressive spastic paraparesis, parasthesia especially vibration sense
              5. Urgency or incontinence in advanced cases
              6. Diagnosis with MRI
              7. Treatment = surgery, cervical collar can help in milder cases

               

              Vascular Malformations

              1. AVMs most often located posteriorly at or below a mid-thoracic level
              2. Typically present in middle age with progressive myelopathy
              3. Acute deterioration can occur with haemorrhage
              4. At presentation most patients have sensory, motor and bladder disturbances
              5. Can be mixture of UMN and LMN signs
              6. Diagnosis by MRI (but may miss small AVMs) and spinal angiography
              7. Treatment = embolisation

               

              Retrovirus-Associated

              1. Slowly progressive spastic paraparesis with variable sensory and bladder disturbance is common presentation associated with HTLV-I
              2. Usually thoracic level
              3. Insidious onset, may be asymmetric signs, hyperreflexia only sign in arms
              4. No treatment except symptomatic
              5. Progressive myelopathy can also occur with AIDS – posterior and lateral tracts affected resembling subacute combined degeneration

               

              Syringomyelia

              1. Developmental, slowly enlarging cavity in cervical cord
              2. Insidious onset in teens or early 20s
              3. Irregular progression, may be spontaneous arrest for several years
              4. Pathophysiology controversial
              5. Central cord syndrome with dissociated sensory loss and areflexic weakness of ULs
              6. Cape like distribution of pain/temperature loss
              7. As lesion enlarges, spastic weakness of LLs and Horner’s syndrome may occur
              8. Associated with Chiari type 1 malformation (protrusion of cerebellar tonsils through foramen magnum)
              9. Treatment = ?surgery – generally unsatisfactory

               

              MS

              1. Chronic progressive myelopathy is common
              2. Typically asymmetrical

               

              Subacute Combined Degeneration

              1. Due to B12 deficiency
              2. Predominant involvement of posterior and lateral tracts
              3. Presents with paraesthesia in hands and feet, early loss of vibration and position sense, progressive spastic and ataxic weakness
              4. Reflexes may be absent due to superimposed peripheral neuropathy

               

              Tabes Dorsalis

              1. Rare
              2. Characteristic fleeting but repetitive lancinating pains in legs>arms,face,back
              3. Primarily affects dorsal columns
              4. Loss of position sense à sensory ataxia in 50%
              5. Cardinal signs = loss of reflexes in legs, impaired position and vibratory sense, Romberg’s sign and bilateral Argyll Robertson pupils
              6. Can get paraesthesia and bladder disturbances also

              Familial Spastic Paraplegia

              1. AD, AR and X-linked forms
              2. Present with progressive spasticity and weakness in legs (corticospinal tracts predominantly affected)
              3. Usually symmetrical
              4. Sensory signs generally absent
              5. Variable age of onset

               

              Adrenomyeloneuropathy

              1. X-linked, variant of adrenoleukodystrophy
              2. Presents as progressive spastic paraparesis in early adulthood
              3. Adrenal insufficiency

               

              Primary Lateral Sclerosis

              1. Degenerative disorder resembling ALS but without LMN involvement
              2. Spasticity and weakness +/- dysphonia and dysarthria

               

               

               

               

               

              Lesion of the Cervical Cord

              1. Upper cervical cord lesions produce spastic quadriplegia and diaphragm weakness – breathing by accessory muscle only
              2. Lesions at C5 result in LMN weakness of biceps, deltoid, brachioradialis and rhomboids with loss of BJ and inversion of brachioradialis jerk (UMN signs in rest of UL and LLs)
              3. Lesions at C8 produce wasting of intrinsic muscles of hand (UMN signs in LL)

               

              Lesions of Thoracic Cord

              1. Sensory level on trunk (nipples T4, umbilicus T10)
              2. UMN weakness of LLs
              3. T7-8 causes loss of upper abdominal reflex
              4. T10-11 causes loss of lower abdominal reflex and upwards displacement of umbilicus

               

              Lesions of Lumbar Cord

              1. L1 – loss of cremasteric reflex
              2. L4 – LMN weakness and wasting of quadriceps, loss of KJ
              3. L5-S1 – LMN weakness of knee flexion and hip extension (S1) and abduction (L5) plus ankle and foot movements, KJ present, AJ lost, no plantar response, anal reflex present

               

              Lesions of Sacral Cord/Conus Medullaris

              1. Saddle anaesthesia (S3-S5)
              2. Prominent bladder and bowel dysfunction, impotence
              3. Loss of anal reflex
              4. Muscle strength largely preserved

               

              Cauda Equina

                • Low back or radicular pain
                • Asymmetric leg weakness
                • Asymmetric sensory loss
                • Variable areflexia
                • Relative sparing of bladder and bowel function

                Topic

                Neurology:spinal cord compresson

                 

                Question 51 top Download PDF

                A 67-year old woman with congestive cardiac failure remains breathless on moderate exertion despite treatment with 40mg frusemide and 20mg enalapril daily. On examination she has a pulse rate of 80/minute, blood pressure of 125/70mmHg and a JVP of 1cm. She has a soft systolic murmur with no added sounds, her chest is clear and she has no oedema. An ECG shows sinus rhythm. A chest X-ray shows cardiomegaly with a cardiothoracic ratio of 15.5/28 but no pulmonary congestion. Echocardiography demonstrates systolic dysfunction with fractional shortening of 18% and mild mitral regurgitation. Her serum creatinine level is normal.

                Which of the following is the most appropriate next step in treatment?

                a) Increase the frusemide dose
                b) Add digoxin
                c) Add an aldosterone antagonist
                d) Add an angiotensin II receptor antagonist
                e) Add a beta blocker

                Answer e) Add a beta blocker, prolong survival and order of therapy diuretic ACEI and betablocker

                Heart Failure Therapy

                General principles:

                Aim is to relieve symptoms, slow progression and prolong survival.

                Involves modification of lifestyle factors, reviewing medication which may be contributing to heart failure and commencing medications to treat heart failure.

                Need to correct systemic conditions that may be contributing (eg: thyroid disorders)

                Need to treat underlying conditions:

                1. HT
                2. IHD
                3. Valvular heart disease
                4. AF (loss of atrial enhancement of ventricular filling can compromise CO and rapid ventricular rate may diminish LV filling in diastole)

                Medications to treat HF:

                Improve symptoms with
                1. Digoxin
                2. Diuretics
                3. BB
                4. ACE-I
                5. ARB
                Prolong survival with:
                1. ACE-I
                2. BB
                3. ARB
                4. Hydralazine/nitrates (in selected patients)
                5. Spironolactone (in selected patients)
                Order of therapy:
                1. Loop diuretics should be started first to control fluid and improve symptoms.
                2. ACE-I (or ARBs if ACE-I not tolerated) are introduced once diuretics optimised. Start at low dose and titrate up at 1-2 week intervals.
                3. Beta blockers are started once pt stable on frusemide and ACE-I. Titrate up.
                4. Digoxin is started if pt has ongoing symptoms despite being on above regimen.
                5. ARB, spironolactone or hydralazine + nitrate can be added if pt still symptomatic.
                ACE-I
                • Improve survival in all severities of HF
                • Maximum dose is recommended if tolerated (trials showing improved survival used maximum doses only)
                ARBs
                • Appear to be as or possibly slightly less effective than ACE-I
                • Recommended in patients who cannot tolerate an ACE-I
                • Seems to be benefit when ACE-I and ARB combined
                Beta Blockers
                • Carvedilol, metoprolol and bisoprolol improve survival in patients with NYHA class II to III HF and probably class IV
                • Reduced hospitalisations
                • Relative contraindications
                  • HR < 60bpm
                  • Hypotension
                  • Signs of peripheral hypoperfusion
                  • PR > 0.24 sec
                  • 2nd or 3rd degree heart block
                  • Severe COAD
                  • Asthma
                • Should have minimal or no evidence of fluid retention prior to starting BB
                • Metoprolol has high specificity for beta-1 adrenergic receptors
                • Carvedilol blocks beta-1, beta-2 and alpha-1 adrenergic receptors
                • Unknown which is better, but pts with low BP may tolerate metoprolol better than carvedilol
                • Expect improvement in 4 to 10 weeks
                • Start at lowest dose and titrate to maximum if tolerated
                Hydralazine plus nitrates
                • Produce modest benefit
                • Less effective than ACE-I
                • Reduced mortality, fewer hospitalisations
                Digoxin
                • For symptom control
                • Reduced hospitalisations but probably little effect on survival
                • Recommended for patients who have class II, III or IV symptoms despite treatment with ACE-I, BB and frusemide
                Diuretics
                • For symptom control
                • Fluid retention can also diminish the response to ACE-I and ARBs and risk decompensation if BB commenced
                • If pt overloaded, aim weight reduction of 1kg per day
                • IV more potent than oral
                • Can consider adding a thiazide for a synergistic effect
                Spironolactone
                • Prolongs survival
                • May prevent adverse effects of hyperaldosteronism on the heart
                • Evidence suggests that it should be used in selected patients with moderate to severe HF
                • Need to monitor closely especially U+Es
                CCBs
                • No direct role in treatment of HF
                • Peripheral CCBs seem to be safe to use for treatment of other conditions in patients with HF
                Statins
                • Recommended for secondary prevention of cardiac disease, independent of HF
                Be caution with:
                • NSAIDS: Increase afterload due to vasoconstriction
                • Thiazolidinediones: Cause fluid retention
                • Metformin: Increase risk of lactic acidosis in patients who are have other medical problems
                • Antiarrhythmics: Most have some negative inotropic effect; amiodarone is generally considered safe
                Ventricular arrhythmias and ICD
                • Almost all patients with HF have ventricular premature beats and 50-70% have non-sustained VT
                • Associated with increased risk of sudden cardiac death
                • Sudden cardiac death estimated to cause 1/3 of mortality in HF patients.
                • Sudden cardiac death reduced with BB
                • No proven benefit from antiarrhythmics
                • ICD in patients with class II to III HF and LVEF < 35% give significant survival benefit
                Pacemakers
                • In patients in SR with LVEF < 35%, prolonged QRS and moderate to severe HF despite medical treatment there is clear survival benefit from cardiac resynchronization (biventricular pacemaker)
                EPO
                • Two small trials have shown benefit in patients with mild anaemia and HF
                • Awaiting further trials

                Lifestyle modifications
                • Smoking
                • Alcohol
                • Salt
                • Daily weight
                • Weight loss if obese
                • Cardiac rehab

                Refractory HF

                • IV inotropes and/or IV vasodilators
                • Mechanical circulatory support
                • Usually in patients waiting for transplant

                Transplant

                • Survival after transplant is 79% at one year and 50% at 8.8 years
                • If pt survives 1st year then annual mortality is about 4% per year
                Classification of severity (NYHA)
                • Class I - symptoms of HF only at levels that would limit normal individuals
                • Class II - symptoms of HF with ordinary exertion
                • Class III - symptoms of HF on less than ordinary exertion
                • Class IV - symptoms of HF at rest
                Stages of HF

                There are several stages in the evolution of HF, as outlined by an ACC/AHA task force:

                • Stage A - High risk for HF, without structural heart disease or symptoms
                • Stage B - Heart disease with asymptomatic left ventricular dysfunction
                • Stage C - Prior or current symptoms of HF
                • Stage D - Advanced heart disease and severely symptomatic or refractory HF

                References:

                ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult

                Guidelines for the prevention, detection and management of people with chronic heart failure in Australia 2006 Henry Krum, Michael V Jelinek, Simon Stewart, Andrew Sindone, John J Atherton and Anna L Hawkes, on behalf of the CHF Guidelines Core Writers. MJA MJA 2006; 185 (10): 549-556

                Guidelines for the prevention, detection and management of people with chronic heart failure in Australia 2006 , by the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand.

                 

                Topic

                Cardiology - Heart Failure

                 

                Question 52 top Download PDF

                A 35yo man presents with bilateral gynaecomastia. He has a past history of viral orchitis. He has hypertension treated with spironolactone and admits to binge drinking of alcohol. Examination reveals normal body hair distribution and 20mL testicles bilaterally. He has moderate bilateral gynaecomastia.

                Investigations show:

                Serum:
                Testosterone normal
                LH <1 [1-9]
                Oestradiol 250 [40-110]
                Prolactin 350 [<400]
                DHEAS 10 [2-12]

                Which of the following is the most important next step in management of his gynaecomastia?

                A. Cease alcohol intake
                B. MRI scan of pituitary
                C. Testicular ultrasound
                D. Karyotype analysis
                E. Cease treatment with spironolactone

                Answer C. Testicular ultrasound

                GYNAECOMASTIA

                • Definition: histologically benign proliferation of the glandular tissue of the male breast and clinically by the presence of a rubbery or firm mass extending concentrically from the nipples
                • DDx: carcinoma (usually eccentrically located and unilateral), neurofibromas, lymphangiomas, haematomas, lipomas, dermoid cysts, pseudogynaecomosta = fat)

                Pathogenesis

                • Decreased androgen production, increased oestrogen production or increased availability of oestrogen precursors for peripheral conversion to oestrogen.
                • Other mechanism is androgen receptor blockade and increased binding of androgen to sex-hormone biding globulin (SHBG)
                • There is an imbalance between inhibitory effects of androgen and stimulatory effects of oestrogen

                Sites of sex hormone production in males

                from uptodate

                Sites of production and metabolism of sex steroid hormones in males.
                E2: estradiol; T: testosterone; E1: estrone; SHBG: sex hormone binding globulin; A: androstenedione; ER: estrogen receptor; AR: androgen receptor; DHT: dihydrotestosterone.
                Adapted from Braunstein, GD. Pubertal gynecomastia. In: Pediatric Endocrinology, Lifshitz, F (Ed), Marcel Dekker, New York, 1996, p. 197.

                • In adult men, 95% of testosterone, 15% of oestradiol and <5% of oestrone secreted by the testes
                • Androstenedione secreted by adrenal glands
                • Most of oestradiol and oestrone converted from androstenedione in tissues
                • Most androgens and oestrogens are bound to SHBG, androgens bind more strongly
                • Any substance that displaces sex hormones from SHBG will tend to displace oestrogens more

                Specific conditions

                • Persistent pubertal gynaecomastia (25%)
                • Drugs (10- 25%)
                • No detectable abnormality (25%)
                • Cirrhosis or malnutrition (8%)
                • Primary hypogonadism (8%)
                • Testicular tumours (3%)
                • Secondary hypogonadism (2%)
                • Hyperthyroidism (1.5%)
                • Chronic renal insufficiency (1%)

                Drugs associated with gynecomastia

                Antiandrogens/inhibitors of androgen synthesis
                • Cyproterone acetate
                • Flutamide
                • Finasteride
                Antibiotics
                • Ethionamide
                • Isoniazid
                • Ketoconazole
                • Metronidazole
                Antiulcer drugs
                • Cimetidine
                • Ranitidine
                • Omprazole
                Cancer chemotherapeutic drugs
                • Alkylating agents
                • Methotrexate
                • Vinca alkaloids
                • Combination chemotherapy
                • Imatinib
                Cardiovascular drugs
                • Amiodarone
                • Captopril
                • Digitoxin
                • Diltiazem
                • Enalapril
                • Methyldopa
                • Nifedipine
                • Reserpine
                • Spironolactone
                • Verapamil
                Drugs of abuse
                • Alcohol
                • Amphetamines
                • Heroin
                • Marijuana
                • Methadone
                Hormones
                • Androgens
                • Anabolic steroids
                • Chorionic gonadotropin
                • Estrogens
                • Growth hormone
                Psychoactive drugs
                • Diazepam
                • Haloperidol
                • Phenothiazines
                • Tricyclic antidepressants
                Other
                • Auranofin
                • Diethylproprion
                • Domperidone
                • Etretinate
                • Metoclopramide
                • Phenytoin
                • Penicillamine
                • Sulindac
                • Theophylline

                • - Spironolactone can increase the aromatisation of testosterone to oestradiol, enhance the conversion of testosterone to androstenedione, decrease the testosterone production rate by the testes and displace testosterone from SHBG, thereby increasing its metabolic clearance rate. Can also act as an antiandrogen by binding to androgen receptors and displacing testosterone/dihydrotestosterone from the receptors.
                • Spironolactone vs placebo: endocrine side effects 10% vs 3%
                • Endocrine side effects were same as in placebo group for epleronone (more selective aldosterone antagonist)

                Cirrhosis:

                • Increased production rate of androstenedione from the adrenals
                • Enhanced aromatisation of androstenedione to oestrone
                • Increased conversion of oestrone to oestradiol
                • Elevated serum SHBG ? reduced free testosterone

                Malnutrition

                • Gonadotropin and testosterone levels probably lower during starvation
                • Oestrogen levels normal (due to production from adrenal precursors)

                Male hypogonadism

                Primary increased LH decreased testosterone
        • Congenital (eg: Klinefelter’s or enzymatic defect in testosterone production)
        • Trauma
        • Infection
        • Infiltrative disorders
        • Vascular insufficiency
        • Ageing
      • Leads to decreased serum testosterone concentration and a compensatory rise in LH release
      • Excess LH results in enhanced Leydig cell stimulation with inhibition of enzymes and increased aromatisation of testosterone to oestradiol ? increased oestradiol secretion

     

    Secondary decreased or normal LH, decreased testosterone
    • Due to hypothalamic or pituitary abnormalities
    • Production of LH is deficient ? low testosterone production
    • Adrenal cortex continues to produce oestrogen precursors


    Testicular Neoplasms increased oestradiol, decreased or normal LH or increased hcG

    • Germ cell tumours 95% of testicular neoplasms
    • 2.5-6% have gynaecomastia at presentation – poor prognostic sign
    • Due to increased hCG
    • Leydig cell tumours 2% of testicular neoplasms
    • ~10% malignant
    • 6-10yo precocious puberty
    • 26-35yo testicular mass, gynaecomastia, impotence, loss of libido
    • Secrete oestradiol, which also inhibits gonadotropin secretion leading to reduced testosterone production and secondary hypogonadism
    • Sertoli cell tumours ? excessive aromatase activity

    Hyperthyroidism increased LH, increased testosterone

    • 10-40% of men with Grave's disease get gynaecomastia
    • Increased concentration of SHBG ? increased binding of testosterone relative to oestradiol
    • Enhanced aromatisation

    Chronic renal failure and dialysis

    • 50% of haemodialysis pts
    • Leydig cell dysfunction ? low serum testosterone, appropriately elevated gonadotropins

    Feminising adrenocortical tumours increased oestradiol, decreased or normal LH

    • Rare
    • Malignant in 75% of cases
    • Median survival 1.5yrs
    • Serum dehydroepianodrosterone sulfate, 17-hydroxyprogesterone and oestradiol increased
    • Testosterone low

    Ectopic production of hCG increased hCG

    • hCG-secreting hepatoblastomas ? precocious puberty
    • Large cell carcinoma of lung, gastric carcinoma, renal cell carcinoma, occasionally hepatoma

    Androgen insensitivity syndromes increased LH, increased testosterone

    • Defect or absence of intracellular androgen receptor
    • Variable clinical spectrum

    Evaluation of gynecomastia

From uptodate

Algorithm for interpretation of serum hormone levels and suggestions for further evaluation of patients with gynecomastia.
Nl: normal; hCG: human chorionic gonadotropin; LH: luteinizing hormone; T: testosterone; E2: estradiol; CT: computed tomography; T4: thyroxine; TSH: thyroid-stimulating hormone; MRI: magnetic resonance imaging.
Adapted from Braunstein, GD. N Engl J Med 1993; 328:490.

Topic

Endocrinology - Assessment and principles of management of adult hypogonadism


Question 53 top Download PDF

Angiostrongylus cantonensis, the rat lung worm, is acquired by eating the intermediate snail or slug host or contaminated vegetables.

Which of the following clinical syndromes is most characteristic of this parasite?

  1. Haematuria
  2. Rectal bleeding
  3. Ascending cholangitis
  4. Eosinohpilic meningitis
  5. Visceral larva migrans

Protozoa are single-celled animals.

Two common methods of transmission are:

  1. Being bitten by blood-sucking insects
  2. Accidentally ingesting the infective stages

Protozoa infect body tissue and organs as:

  1. Intracellular parasites in a wide variety of cells
  2. Extracellular parasites in the blood, intestine or urogenital systems

Helminths are parasitic worms. There are three main groups:

  1. Tapeworms (Cestoda)
  2. Flukes (Trematoda)
  3. Roundworms (Nematoda)

Angiostrongylus is a nematode and is one of the zoonoses. It is acquired by eating the larvae in snails, crustaceans or vegetables. The larvae are found in the CNS in humans.

Eosinophilic meningitis is associated with some parasitic infections, in particular, 3 helminths:

  1. Angiostrongylus cantonensis
  2. Baylisascariasis
  3. Gnathostomiasis

With each of these, eosinophilic meningitis is caused by migration of larvae within the nervous system. Angiostrongylus cantonensis is the most common parasite to cause eosinophilic meningitis.

Occurs primarily in Asia, the Pacific basin, New Guinea and several smaller Pacific islands.

Clinical manifestations:

  1. Excruciating headache most common presentation
  2. Fever, neck stiffness, nausea and vomiting are frequent but can be absent
  3. Ocular symptoms (eg: unilateral blurred vision) can occur if larvae migrate to ocular tissue
  4. Focal neurological signs can occur

Outcome:

  1. Usually self-limiting course
  2. Fatalities uncommon
  3. Treatment = supportive measure and antihelminthic agent

Answer is D – eosinophilic meningitis.
HUMAN TAPEWORM INFECTIONS


SPECIES

ACQUIRED FROM

SITES IN HUMANS

Adult worms

 

 

Taenia saginata

Larvae in beef

Intestine

Taenia solium

Larvae in pork

Intestine

Diphyllobothrium latum

Larvae in fish

Intestine

Hymenolepis nana

Eggs or larvae in beetles

Intestine

Larval worms

 

 

Taenia solium (cysticercosis)

Eggs in food or water contaminated with human faeces

Brain, eyes

Echinococcus granulosus (hydatid disease)

Eggs passed by dogs

Liver, lung, brain

HUMAN FLUKE INFECTIONS


SPECIES

ACQUIRED FROM

SITES IN HUMANS

Schistosoma haematobium

Schistosoma japonicum

Schistosoma mansoni

 

Penetration of skin by larval stages released by snails

Blood vessels of bladder

Blood vessels of intestine

Blood vessels of intestine

Clonorchis sinensis

Ingesting fish infected with larval stages

Liver

Fasciola hepatica

Ingesting vegetation with larval stages

Liver

Paragonimus westermani

Ingesting crabs infected with larval stages

Lungs

HUMAN NEMATODE INFECTIONS


SPECIES

ACQUIRED BY

SITES IN HUMANS

Ascaris lumbricoides

Ingestion of eggs

Small intestine

Enterobius vermicularis

Ingestion of eggs

Large intestine

Hookworms

- Ancylostoma dudenale

- Necator americanus

- Strongyloides stercoralis

- Trichuris trichiura

 

Skin penetration by infected larvae

Skin penetration by infective larvae

Ingestion of eggs

 

Small intestine

Small intestine

Small instestion (adults), general tissues (larvae)
Large intestine

Brugia malayi

Mosquito bite

Lymphatics (adult)
Blood (larvae)

Onchocerca volvulus

Bite of simulium fly

Skin
Eyes (larvae only)

Wuchereria bancrofti

Mosquito bite

Lymphatics (adults)
Blood (larvae)

Loa loa

Bite of deer fly

Tissues

Angiostrongylus cantonensis

Ingestion of snails, crustacea

CNS (larvae)

Anisakis simplex

Ingestion of larvae in fish

Stomach, small intestine

Capillaria phillipinensis

Ingestion of larvae in fish

Small intestine

Topic

Infectious Diseases: Helminthic Infections

Question 54 top Download PDF

QUESTION 54

A 45-year-old woman presents with a three-year history of recurrent rash, characterised as palpable purpura over both legs. Some of these lesions have ulcerated.
Laboratory results include:
serum:
creatinine                                      0.10 mmol/L         [0.06-0.11]
alanine transaminase (ALT)        51 U/L                    [15-50]
aspartate transaminase (AST)    64 U/L                    [15-45]
hepatitis C antibody                     positive
cryoglobulins                                positive with 8% cryoprecipitate
urinalysis normal

Which of the following is the most appropriate management?
A. Plasmapheresis and corticosteroids.
B. Corticosteroids and interferon α.
C. Interferon α and ribavirin.
D. Cyclophosphamide and corticosteroids.
E. Cyclophosphamide and ribavirin.

HAEMATOLOGICAL MANIFESTATIONS OF HEPATITIS C

  1. Essential mixed cryoglobulinaemia
  2. Monoclonal gammopathies (can be associated with myeloma)
  3. Lymphomas

 

ESSENTIAL MIXED CRYOGLOBULINAEMIA (TYPE II CRYOGLOBULINAEMIA)

  1. Lymphoproliferative disorder
  2. Cryoglobulins are immunoglobulins that precipitate in the cold and dissolve on rewarming
  3. Leads to deposition of circulating immune complexes in small to medium-sized blood vessels
  4. Cryoglobulins associated with myeloma/Waldenstrom’s macroglobulinaemia (type I), Hep C (type II), chronic inflammatory conditions and autoimmune disease (type III)
  5. 95% of pts with essential mixed cryoglobulinaemia have hepatitis C or IgG to hep C
  6. May be due to hep C virus binding to B lymphocytes via CD81 and lowering their threshold for activation
  7. Patients with hep C and cryoglobulinaemia also have high levels of rheumatoid factor – secreted by HCV-infected lymphocytes

 

Clinical Manifestations

  1. Classic triad of:
    1. Palpable purpure
    2. Arthralgias
    3. Weakness
  2. Other features include lymphadenopathy, hepatosplenomegaly, peripheral neuropathy, renal disease
  3. Renal disease occurs in 35-60% of pts with type II cryoglobulinaemia
  4. Generally chronic, smoldering course

 

Diagnosis

  1. Low complement (especially C4)
  2. Raised RF
  3. Hepatitis C serology
  4. Circulating cryoglobulins
  5. Can biopsy the purpuric skin lesions
  6. Consider renal biopsy if diagnosis still in doubt
  7. Can get spurious leukocytosis and thrombocytosis

 

Treatment

  1. Main indication for treatment is progressive systemic disease
  2. First confirm hepatitis C infection
  3. Interferon alpha plus ribavirin is treatment of choice
  4. In patients with normal or near normal renal function, use pegylated interferon but if Cr clearance <50 use non-pegylated interferon
  5. In patients with severe/fulminant disease, plasmapheresis and immunosuppressive therapy is appropriate (methylprednisolone or cyclophosphamide)
  6. Risk of worsening hep C infection if immunosuppression used

 

Prognosis

  1. Untreated patients tend to die of hepatic or cardiovascular disease, not due to complications of cryoglobulinaemia
  2. No long term studies in treated patients
  3. Variable prognosis in renal disease – some patients undergo complete remission, some develop ESRF

 

Answer: C

Topic

Gastroenterology: Viral Hepatitis

 

Question 55 top

Question 56 top

Question 57 top Download PDF

A 47-year-old man on long-term haemodialysis presents with a fever (39.5°C) and chills. He has had multiple thrombosed fistulas and a thrombosed right axillary vein. He had a left subclavian catheter inserted under ultrasound guidance three days ago.
On examination he looks well, with a blood pressure of 170/80 mmHg and an exit site of the vascular access catheter with the appearance shown below.

Which of the following management strategies would be most appropriate in his case?
A. Intravenous vancomycin and observation.
B. Immediate haemodialysis.
C. Intravenous cephalexin and observation.
D. Intravenous vancomycin and catheter removal.
E. Replace vascular catheter with a re-wire technique.

Recommended treatment for CVC infections where MRSA is suspected is vancomycin plus gentamicin.

Removal of the line is recommended but if access is an issue then leaving the line in is sometimes considered (assuming the patient is stable).

Indications for line removal:

  • Infection due to gram-negative bacilli (especially Pseudomonas aeruginosa), multiple bacteria, or fungi
  • Insertion site infection
  • Granulocytopenia
  • Valvular heart disease
  • Septic thrombophlebitis
  • Endocarditis
  • Metastatic abscesses

This patient has insertion site infection which is an indication for removal of the catheter.

So the correct answer is D – catheter removal and vancomycin.

Most catheter-related infections are caused by coagulase-negative staphylococcus, staph aureus or enterococcus.

Less common pathogens include candida species and gram negative organisms such as E. Coli, Klebsiella and Pseudomonas.

MRSA is becoming more and more common – 25 to 60% of isolates in hospital and 70% in ICU (numbers for MKSAP). About 1/3 patients with previous MRSA colonisation or prior infection will develop a subsequent MRSA infection.

Duration of treatment should be at least 2-3/52 (ID seems to suggest 4-6/52 usually).

Risk factors for MRSA infection include duration of antibiotic administration presence of severe underlying illness, exposure to health care system / ICU.

Mortality from line sepsis varies from 12 to 25%.

Positive blood cultures require exclusion of endocarditis with TOE.

Coagulase-negative staph is low-virulence and can usually be treated with 1-2/52 of flucloxacillin.

Topic

Infectious Diseases - Hospital acquired infection

 

 

Question 58 top Download PDF

A 35yo woman from the UK is referred for investigation of an abnormal chest XR taken for immigration screening. She is asymptomatic.

Which one of the following is the most likely diagnosis?

A. Sarcoidosis
B. Tuberculosis
C. Hodgkin’s lymphoma
D. Non-Hodgkin’s lymphoma
E. Small cell lung cancer

XR shows bilateral hilar lymphadenopathy. In an asymptomatic 35yo this is most likely to be sarcoidosis.

SARCOIDOSIS

Definition: Multi-system granulomatous disorder of unknown aetiology. Characterised by non-caseating granulomas.
Typically affects young adults
Presentation
Bilateral hilar adenopathy
Pulmonary reticular opacities
Skin, joint and/or eye lesions

Clinical Manifestations

Usually present between ages of 10 and 40yrs
50% incidental finding on CXR
Lung symptoms most common: cough, SOB, chest pain
Common extrapulmonary symptoms: eye, skin lesions
Systemic features: malaise, fever, weight loss


CXR

Classic finding is bilateral adenopathy
Can be absent or can be present with other abnormalities
Stages based on CXR:
Stage I = bilateral hilar adenopathy
Stage II = bilateral hilar adenopathy and reticular opacities
Stage III = reticular opacities with shrinking hilar nodes
Stage IV = Reticular opacities with evidence of volume loss, mainly upper lobes, may also see bronchiectasis/calcification/cavitation

Can get nodular sarcoid which can look like metastatic disease

Topic

Respiratory - Investigations | Sarcoidosis


Question 59 top Download PDF

Therapeutic blockade of alpha 4 integrins is currently under clinical trial for several diseases. On the basis of known pathogenesis, patients with which one of the following conditions are most likely to receive benefit from this treatment?

  1. Migraine
  2. Stroke
  3. Multiple sclerosis
  4. Alzheimer’s disease
  5. Epilepsy

Answer is C – note this is the only condition that has an immunological basis. Alpha 4 integrins are adhesion molecules which help T cells pass through capillary walls.

DEMYELINATING DISORDERS
  • Characterised by inflammation and selective destruction of CNS myelin
  • Peripheral NS is spared
MULTIPLE SCLEROSIS
  1. Characterised by a triad of:
    • Inflammation
    • Demyelination
    • Gliosis (scarring)
  2. Can be relapsing-remitting or progressive
  3. Manifestations can vary greatly from mild to rapidly evolving and incapacitating
PATHOGENESIS
  • Acute lesions are characterised by perivenular cuffing with inflammatory cells (mainly T cells and macrophages) which also infiltrate the surrounding white matter
  • BBB is disrupted but vessel wall is preserved
  • In >50% of cases, myelin-specific autoantibodies promote demyelination and stimulate macrophages and microglial cells
  • As lesions evolve, astrocytes proliferate (gliosis)
  • Surviving oligodendrocytes may partially remyelinate the surviving naked axons – shadow plaques
PHYSIOLOGY
  • Normal nerve conduction in myelinated axons occurs in saltatory manner – action potential jumps from one node of Ranvier to the next
  • This allows much faster conduction
  • Following demyelination, conduction block can occur due to hyperpolarisation of the exposed segment (due to exposure of voltage-dependent K channels)
  • This block is temporary – sodium channels which are normally localised at the nodes redistribute along the demyelinated segment and allow conduction
EPIDEMIOLOGY
  • Female > Male (approximately 2:1)
  • Age of onset typically 20-40yrs
  • Rarely can begin as early as 2yrs or as late as 70s
  • There is a genetic susceptibility to MS
    • Increased risk if relative has MS
  • MHC class II is one area associated with MS susceptibility
IMMUNOLOGY
  • Autoimmune cause for MS has support but not proven
  • Autoreactive T cells directed against components of myelin
  • Evidence to support this theory includes:
    • Inflammation with disruption of BBB seen in early stages of demyelinating lesions
    • T cells, B cells and macrophages seen on histology
    • Increased oligoclonal IgM and IgG in CSF
    • Myelin reactive T cells found in MS plaques, in CSF and in peripheral circulation
    • Th 1-type immune activation is a feature (as marked by IL12, IL18)
    • Risk of developing MS linked with class II MHC
    • Immunomodulatory drugs that reduce Th1 response can reduce disease activity
    • Myelin basic protein (MBP) is an important T cell antigen in exoerimental allergic encephalomyelitis and probably also in humans
    • Activated MBP-reactive T cells are often found in CSF of MS patients
    • Autoantibodies directed against myelin (such as myelin oligodendrocyte glycoprotein) probably act with T cells to cause demyelination
  • Viral infections could possibly stimulate the immune system to cause MS (EBV has been considered)
  • Also genetic and environmental factors
CLINICAL MANIFESTATIONS

Features Suggestive of MS
  • Relapses and Remissions
  • Onset between 15 and 50 years
  • Optic neuritis
  • Lhermitte’s sign
  • Internuclear ophthalmoplegia
  • Fatigue
  • Uhthoff’s phenomenon
Features not Suggestive of MS
  • Steady progression
  • Onset before age 10 or after age 50
  • Corical deficits such as aphasia, apraxia, alexia, neglect
  • Rigidity, sustained dystonia
  • Convulsions
  • Early dementia
  • Deficit developing within minutes
Optic Neuritis
  • Most common type of involvement of visual pathways
  • Usually presents with acute or subacute unilateral eye pain that is accentuated by ocular movements
  • Followed by variable degree of visual loss affecting mainly central vision
  • Bilateral simultaneous ON rare in MS, suggests alternative diagnosis
  • Afferent pupillary defect may be found
  • May see disc oedema if head of optic nerve involved, or can be normal fundus examination in acute setting
  • Later optic disc becomes pale due to axonal loss and gliosis
  • 90% of patient regain normal vision over 2-6 months
  • Progression to MS ranges from 15 to 75%
Internuclear Ophthalmoplegia
  • This refers to abnormal horizontal ocular movements with lost or delayed adduction and horizontal nystagmus of the abducting eye
  • Caused by a lesion of the medial longitudinal fasciculus on the side of diminished adduction
  • If bilateral, usually get vertical nystagmus on upward gaze
  • Bilateral INO is most suggestive of MS but can also be seen with intra-axial brain stem lesions (including Wernicke’s encephalopathy)
  • Other common gaze disturbances in MS include
    • Horizontal gaze palsy
    • “One and a half” syndrome – horizontal gaze palsy plus INO
    • Acquired pendular nystagmus
Motor Symptoms
  • Paraparesis or paraplegia due to lesions in descending motor tracts
  • Usually have UMN signs
  • Asymmetrical
  • Occasionally reflexes are reduced due to lesions of the reflex arc at a segmental level
Sensory Symptoms
  • Paraesthesias (pins and needles, burning, prickling etc) and hypesthesias (reduced sensation)
  • Pain is a common symptom
  • Reflect spinothalamic, posterior column or dorsal root lesions
  • Lhermitte’s symptom is the electic shock-like sensation that radiates down the back into the legs; evoked by neck flexion (can also occur with disorders of C spine)
Heat Sensitivity
  • Neurological symptoms produced by an elevation of the body’s core temperature
  • Eg: transient blurred/loss of vision which occurs during a hot shower or with physical exercise (Uhthoff’s symptom)
  • Also fever can cause similar effects (pseudo-relapse)
Coordination
  • Ataxia usually manifests as cerebellar tremors
  • Slurred speech
  • Failure of fixation suppression suggest cerebellar or cerebello-vestibular connection dysfunction
Bladder/Bowel Dysfunction
  • Urgency is most common
  • Urinary incontinence becomes more common as disease progresses
  • Constipation more common that faecal incontinence
  • Sexual dysfunction also common
Cognitive Dysfunction
  • Memory loss, impaired attention, difficulties with problem solving, slower information processing, problems shifting between tasks
  • Impairment sufficient to impede daily activities is rare

Vertigo

  • Can appear suddenly
  • Commonly associated with cranial nerve abnormalities such as facial numbness, diplopia, hypoacusis
Nystagmus
  • Pendular nystagmus can occur
  • Usually develops later in course
Epilepsy
  • More common in patients with MS than in the general population
  • Can be tonic-clonic or partial
Paroxysmal Symptoms
  • Brief duration (30 sec to 2 min) and high frequency (5 to 40/day)
  • No change in consciousness
  • Self limiting course (weeks to months)
  • Include Lhermitte’s symptom, tonic contraction of a limb, face or trunk, paroxysmal dysarthria/ataxia, paroxysmal sensory disturbances
DISEASE COURSE

Relapsing/Remitting MS
  • 85% of cases
  • Discrete attacks generally evolve over days to weeks
  • Often there is complete recovery over ensuing weeks to months
Secondary Progressive MS
  • Always begins as RRMS
  • At some point, clinical course changes so that there is steady deterioration unassociated with acute attacks (which may continue or cease during this phase)
  • 50% of pts with RRMS will develop SPMS after 15 years
Primary Progressive MS
  • 15% of cases
  • No attacks but steady decline
  • Onset usually later in life
  • Disability develops faster
Progressive/Relapsing MS
  • 5% of cases
  • Steady deterioration from disease onset
  • Occasional superimposed attacks
DIAGNOSIS

Basically you need evidence of involvement of 2 or more areas of CNS (either acute attacks or progressive), mainly involving the white matter and not attributable to another disease. “Multiple in time and multiple in space”.

Definite MS if all 5 criteria fulfilled
Probable MS if all 5 criteria fulfilled except a) only one objective abnormality despite two symptomatic episodes or b) only one symptomatic episode despite two or more objective abnormalities
At risk for MS if criteria 1,2,3 and 5 fulfilled; patient has only one symptomatic episode and one objective abnormality

MRI
  • Characteristic abnormalities found in >95% of patients with MS
  • Multifocal hyperintense lesions on T2 weighted images involving brain, brain stem and spinal cord
  • Burden of disease has weak correlation with clinical disability
  • May see dark holes on T1 images corresponding to some of the hyperintense lesions on T2

Evoked Potentials
  • Measure CNS electric potentials evoked by repetitive stimulation of selected peripheral nerves or of the brain
  • Best to test a pathway that is not clinically involved
  • Abnormalities of one or more EP modalities occur in 80 to 90% of patients with MS
  • Seem to test visual EPs most often at Austin but can also do auditory, somatosensory and motor
CSF
  • Protein usually slightly elevated
  • Oligoclonal bands (2 or more found in 75 to 90% of patients with MS)
  • Mild mononuclear pleocytosis common
PROGNOSIS
  • Most patients have progressive neurological disability
  • At 15 years from diagnosis only 20% have no functional limitation
  • After 25 years 80% will require assistance to ambulate
  • Difficult to determine prognosis for an individual
  • Good prognostic factors include
    • ON or sensory symptoms at onset
    • Those who recover completely from an acute attack
    • <40yrs at onset (but not childhood)
    • Women
    • RRMS
    • <2 relapses in first year
    • Minimal impairment at 5 years
  • Poor prognostic features include
    • Truncal ataxia
    • Action tremor
    • Pyramidal symptoms
    • Progressive course without relapses
  • <20% of patient have a benign course and never develop neurological disability
  • Pregnancy seems to lessen attacks, but more frequent attacks in post-partum period

TREATMENT

Acute Relapses
  • Establish whether really an acute relapse or due to infection/fever or depression (pseudo relapse)
  • Mild relapses do not require treatment (other than symptomatic treatment)
  • Moderate relapses (some disability and symptoms have become unpleasant or are worsening) – prednisolone 75mg daily for 4 days then 25mg daily for 4 days
  • Severe relapses (including ON with severe visual loss, paraplegia or brainstem symptoms) – admit and give methylprednisolone 1g IV daily for 3 days (or 0.5g daily for 5 days)
  • In patients who continue to deteriorate despite treatment, plasmapheresis should be considered
  • May reduce severity and duration of acute attacks but not effect on long-term disability
Treatment of Underlying Disease
  • Immunomodulators generally first line and immunosuppressants second line
  • May reduce attack frequency and slow progression but do not reverse symptoms or arrest disease
Immunomodulators
  • Requirements for PBS subscription are
    • Relapsing-remitting MS
    • Ambulatory patient
    • 2 or more attacks in 2 years
    • Confirmation of the diagnosis by MRI
  • Currently available immunomodulators
    • Interferon beta-1b (s/c 2nd daily)
    • Interferon beta-1a (IM weekly)
    • Glatiramer acetate (s/c daily)
    • Natalizumab (IV monthly)
  • Interferon beta reduces the frequency and severity of attacks and the number and size of lesions on MRI
  • Unknown if there is any effect on long term disability
  • Minority of patients develop neutralising antibodies – if persistent may need to change drug or add immunosuppressant
  • Glatiramer acetate has similar effects to interferon beta
  • Natalizumab (monoclonal antibodies against alpha4-integrins) selectively inhibits adhesion molecules (alpha4-integrins), slowing the entry of T cells through cerebral capillaries
  • Reduces relapses, new lesions and disability
  • Used in patients intolerant or not responding to other immunomodulators
  • ?risk of PML (quoted as 1 in 1000 but not convincing evidence of a link)
Immunosuppressants
  • Used for some pts with primary progressive or secondary progressive MS or those who have not responded to immunomodulators
  • Dangerous if pt has recurrent UTIs, need to weigh up risks and benefits
  • Methotrexate may reduce progression (limited trials); monitor FBE, LFTs
  • Azathioprine seems to have similar benefits to immunomodulators; monitor FBE, LFTs
  • Mitozantrone is a chemotherapy agent which helps stabilise the disease in severe and progressive cases
  • More likely to help in pts still having some relapses or who have inflammation on MRI
  • Risk of cardiotoxicity as well as all the usual chemotherapy risks

 

ADEM

  • Acute demyelinating encephalomyelitis
  • Monophasic course
  • Frequently associated with antecedent viral infection (especially measles) or vaccination (especially smallpox or rabies)
  • Hallmark is widely scattered small foci of perivenular inflammation and demyelination
  • Immune response to MBP can be detected in most patients
  • If severe, onset is abrupt and progression is rapid (hours to days)
  • Fever, headache, meningism, lethargy, coma, seizures, may be signs of disseminated neurological disease
  • Elevated CSF protein and lymphocytes generally ~200 cells occurs in 80%
  • Initial treatment = high dose steroids
  • Consider plasma exchange or IV Ig if refractory
  • Prognosis variable, 5 to 20% mortality with measles encephalomyelitis
Topic

Neurology: MS

 

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Question 65 top Download PDF

A 68yo man presents with an altered conscious state. Three days prior to presentation he had an episode of ataxia and vertigo with residual imbalance. On the day prior to presentation he developed an acute horizontal diplopia, which persists. He is brought to hospital after a sudden deterioration in his level of consciousness.

The most likely diagnosis is:

A. Pontine haemorrhage

B. Paraneoplastic syndrome

C. Acute disseminated encephalomyelitis (ADEM)

D. Multiple cardioembolic strokes

E. Basilar artery thrombosis

 

This patient presents with a stepwise decline in neurological function suggestive of crescendo TIAs. A pontine haemorrhage may cause the signs listed in the question but the onset would be sudden rather than over a few days.

ADEM is usually associated with constitutional symptoms and some degree of encephalopathy though neurological signs can vary.

Paraneoplastic syndromes tend to be subacute, developing over weeks to months, or even chronic, over months to years.

Multiple cardioembolic strokes is possible but less likely than a single lesion, especially as there is no known history of AF.

The clinical features described are consistent with a posterior circulation stroke – ataxia and vertigo suggest cerebellar or spinocerebellar tract problems. Horizontal diplopia indicates a problem with the horizontal gaze centre

BASILAR ARTERY THROMBOSIS

  1. Basilar artery formed at pontomedullary junction by the 2 vertebral arteries
  2. Gives off a number of branches to the cerebellum and pons
  3. Terminal branch is the PCA which supplies the midbrain and thalamus and parts of the temporal and occipital lobes
  4. Atheroma occurs more often at the origin and termination of the basilar artery
  5. Clinical picture varies depending on the site of the occlusion and the presence of retrograde flow
  6. May be features involving the corticospinal, corticobulbar, ascending sensory tracts and cranial nerve nuclei
  7. In complete basilar artery occlusion there will be bilateral sensory and motor signs as well as cranial nerve and cerebellar dysfunction
  8. Generally the proximal and distal parts of the basilar artery are occluded by emboli while the mid-section is usually atherothrombotic

Clinical

    • A stuttering and progressive course of symptoms is seen in patients with atherosclerotic occlusion
    • A lot of patients will have TIAs for several days to weeks prior to the occlusion
    • Most common heralding symptoms include:
    1. Hemiparesis, facial paresis or quadraparesis
    2. Dysarthria
    3. Vertigo, nausea and vomiting
    4. Headache
    5. Visual disturbances
    6. Altered consciousness
    • If occlusion due to emboli then the presentation is of sudden onset of severe motor and bulbar symptoms with reduced consciousness
    • Eye signs reflect involvement of vertical gaze centre of midbrain, abducens nucleus, horizontal gaze centre and/or medial longitudinal fasciculus resulting in:
    1. Ipsilateral abducens palsy
    2. Ipsilateral conjugate gaze palsy
    3. Internuclear ophthalmoplegia
    4. One-and-a-half syndrome (ipsilateral conjugate gaze palsy and internuclear ophthalmoplegia)
    5. Skewed deviation
    6. Ocular bobbing (due to lesion in pons)
    • Other pontine signs are:
    1. Ataxia
    2. Facial weakness
    3. Dysarthria
    4. Dysphagia
    5. Hearing loss
    • Locked-in syndrome is due to occlusion of the proximal and middle segments of the basilar artery à ischaemia of basis pontis but tegmentum of pons spared à quadriplegia, consciousness preserved
    • Top-of-the-basilar syndrome is due to ischaemia of the upper brainstem and diencephalon (usually due to embolus) à reduced consciousness, visual symptoms (such as hallucinations or blindness), 3rd nerve palsy, papillary abnormalities
    • Important to recognise heralding signs of occlusion as complete occlusion carries poor prognosis

    Topic

    Neurology: Stroke

     

    Question 66 top Download PDF

    QUESTION 66

    A 28yo man presents with a fractured ankle requiring surgical fixation.

    Full blood examination shows:

                Haemoglobin                           115g/L                         [128-175]
                Red cell count                         5.6x1012/L                  [4.0-5.7]
                Mean cell volume                    62fL                            [80-97]
                White cell count                      12.5x109/L                  [3.9-12.7]
                                                                (mild neutrophilia)
                Platelet count                          390x109/L                   [150-396]
                Serum ferritin                          95ug/L                         [15-325]

    Haemoglobin (Hb) studies show:

                HbA2                                      5.2%                            [1.8-3.5]
                HbF                                         1.2%                            [0-2.0]
                HbH preparation                     no HbH bodies seen
                Hb electrophoresis                  no abnormal Hb bands seen
    The most likely explanation for his anaemia is:

    1. B-thalassaemia trait
    2. Chronic blood loss
    3. Anaemia of chronic disease
    4. Congenital sideroblastosis
    5. Sickle cell trait

     

    THALASSAEMIA

    1. Hereditary disorder, autosomal recessive
    2. Reduced or absent production of one or more globin chains
    3. Most pts with alpha or beta thalassaemia minor (trait) are asymptomatic
    4. More common in Mediterranean populations

     

    Beta Thalassaemia

    1. Impaired production of beta globin chains à relative excess of alpha chains
    2. Excess alpha globin chains are unstable, incapable of forming soluble tetramers and precipitate within the cell à shortened RBC lifespan
    3. Degree of alpha globin chain excess determines the severity of clinical manifestations

    Major:

    1. Two defective B-globin genes
    2. Severe, transfusion dependent anaemia
    3. Symptoms emerge late in 1st year of life when HbF levels decline
    4. Signs/Symptoms:
      1. Chronic anaemia – pallor, irritability, growth retardation
      2. Stigmata of haemolysis
      3. Ineffective erythropoiesis – bony abnormalities, hepatosplenomegaly
      4. Fe overload – effects endocrine organs, heart
    5. Profound microcytic anaemia, bizarre red cell morphology
    6. Patients with higher levels of HbF have less severe disease
    7. Patients with co-inheritance of alpha thalassaemia also have milder disease due to less imbalance between alpha and beta chains
    8. Rx = transfusion for Hb 90-100, Fe chelation, ?allogenic haematopoietic transplantation

    Minor:

    1. One normal beta globin allele and one beta thalassaemic allele
    2. Rarely symptomatic
    3. Hypochromic, microcytic RBCs
    4. Microcytosis usually much more profound and the anaemia milder than seen in Fe deficiency
    5. HCT >30%, MCV <75fL
    6. In Fe deficiency MCV rarely low without low HCT also
    7. RDW usually normal (increased in Fe deficiency)
    8. Splenomegaly in 15-20%
    9. Target cells on film
    10. Reticulocytes normal or slightly increased
    11. >90% haemoglobin will be HbA
    12. Elevated HbA2 diagnostic of thalassaemia (but normal HbA2 does not exclude thalassaemia trait)
    13. HbA2 = alpha-delta tetramers, usually ~4-6% in thalassaemia trait

    B-Thalassaemia Minor

    Fe Deficiency

    Microcytic MCV significantly reduced

    Microcytic MCV mildly reduced

    HCT > 30%

    HCT < 30%

    RDW normal

    RDW increased

    Ferritin normal

    Ferritin reduced

    Target cells

    Microcytic, hypochromic only

    Elevated HbA2

    Normal HbA2

    Sideroblastic Anaemia

    1. Hereditary or acquired
    2. Mitochondria inheritance (X-linked)
    3. Acquired due to toxins, drugs, nutritional deficiencies
    4. Ringed sideroblasts seen in bone marrow
    5. Ferritin increased, decreased TIBC, increased transferring saturation
    6. MCV normal or increased but can occasionally be low

     

    HbH is for alpha thalassaemia when 3 of 4 alpha alleles are defective.
    Hb electrophoresis is used for diseases such as sickle cell.

    Answer: A

    Topic

    Haematology: Anaemia

     

    Question 67 top Download PDF

    A 26yo man presents with a 2 day history of fevers, rigors, headache, malaise, nausea and vomiting, dry cough, mild arthralgia and backache. He reports no shortness of breath, diarrhoea, neck stiffness or photophobia. He reports that he returned from a diving trip to the Solomon Islands seven days ago. He has taken doxycycline regularly as malarial prophylaxis.

    On day 3 after the onset of the illness he develops a rash over his trunk (shown below) and face. A petechial rash was noted on his lower limbs.

    Which of the following is the most likely diagnosis?

    A. Malaria

    B. Dengue fever

    C. Typhoid fever

    D. Q fever

    E. Measles

    Answer b

    This picture is not really very helpful in making the diagnosis. He has a maculopapular rash which could occur with just about anything. It is important to note that he also has a petechial rash on his legs which was surreptitiously slipped in at the end of the question. This is only associated with dengue fever.

    DENGUE FEVER

    1. Incubation period is 3 to 7 days (maximum 14 days)
    2. Should be suspected in travelers who have returned to Australia in the last week
    3. Can also occur in far North Queensland and NT
    4. Transmitted by mosquitos
    5. There are 4 viral serotypes, all flaviviruses with single stranded enveloped RNA (DEN-1 to DEN-4)
    6. Infection with one serotype confers life-long immunity to that serotype but not the others
    7. Infection with a second serotype at any time can lead to dengue haemorrhagic fever
    HISTORY
    1. Fever (typically begins on day 3, occasionally falls after 2-4 days and then returns 24 hours later = saddleback fever)
    2. Can exclude dengue in a traveler returned > 14 days ago
    3. Headache, retroorbital pain
    4. Myalgia, arthralgia
    5. Rash
    6. Nausea, vomiting, abdominal pain
    7. Malaise
    8. Cough, sore throat
    9. Haemorrhagic manifestations (more common in DHF but also occur in DF) eg: purpura, epistaxis
    EXAMINATION
    1. Fever
    2. Rash (maculopapular)
    3. Conjunctival injection
    4. Pharyngeal erythema
    5. Lymphadenopathy
    6. Hepatomegaly
    INVESTIGATIONS
    1. Leukopaenia
    2. Thrombocytopaenia
    3. Elevated AST

    DENGUE HAEMORRHAGIC FEVER

    1. Four cardinal features:
      1. Increased vascular permeability evidenced by haemoconcentration (20% or greater rise in haematocrit above baseline), pleural effusion or ascites
      2. Marked thrombocytopaenia (< 100)
      3. Fever lasting 2 to 7 days
      4. Haemorrhagic tendency (as demonstrated by a positive tourniquet test) or spontaneous bleeding (can also occur with DF)
    2. Dengue shock syndrome is when shock is present along with these four criteria
    DIAGNOSIS
    1. Mainly clinical
    2. IgM (can get false negatives in first 6 days of illness), should test convalescent sample also to confirm diagnosis
    TREATMENT
    1. No specific treatment for DF
    2. Avoid NSAIDS or aspirin due to thrombocytopaenia
    3. In DHF, need aggressive fluid resuscitation, blood transfusion

    MALARIA

    1. 600 to 800 cases a year in Australia
    2. Mostly in returned travelers (but not excusively)
    PARASITES
    1. Four species of malaria:
      1. Plasmodium falciparum (potentially lethal)
      2. Plasmodium malariae (can persist in circulation of > 20yrs)
      3. Plasmodium vivax (commonest, relapses from dormant liver stages months to years after infection)
      4. Plasmodium ovale (least common, can also relapse)
    2. All species cause influenza-like symptoms with fever and anaemia
    3. Serious complications occur only with falciparum (eg: cerebral malaria, ARF, shock)
    4. Begins with mosquito bite when sporozoites are injected
    5. Sporozoites are rapidly passed to the liver where they multiple before bursting the infected cells and releasing thousands of merozoites into the circulation
    6. Merozoites invade RBCs
    7. Mature and undergo asexual division (schizogony) into schizonts
    8. Schizonts burst the infected cell and release daughter merozoites that can invade other RBCs
    9. Hepatic infection (5 days to several weeks) is asymptomatic
    10. Typical symptoms of malaria occur at the time of schizont rupture when parasite toxins act on host cells to release cytokines
    11. P. falciparum alters the surface of infected RBCs causing them to adhere to endothelial cells in various capillary beds as they mature
    12. When sequestration occurs in the brain, lung, gut, placenta or kidney can cause serious problems
    13. Also can make diagnosis difficult as parasite may be undetectable in peripheral blood at this time
    14. At some time during replication, sexual forms are produced that can be taken up by a feeding mosquito and fertilized in the mosquito midgut à sporozoites in salivary glands à transmission to other humans

    CLINICAL MANIFESTATIONS

    1. Fever in a returned traveler to endemic area = malaria until proven otherwise
    2. Rigors
    3. Malaise
    4. Headache
    5. Vomiting and diarrhoea may occur
    6. Cough
    7. Rash not a feature
    8. Fever occurring less than 1 week after reaching endemic area is very unlikely to be malaria
    9. Falciparum usually occurs within 4 weeks of leaving endemic area (but can be later)
    10. Vivax and ovale can relapse years later

    SEVERE MALARIA (FALCIPARUM)

    1. Can progress rapidly to ARF, ARDS, severe metabolic acidosis, DIC, shock or cerebral malaria
    2. Neurological symptoms in cerebral malaria – seizures, hypertonicity, gaze palsies, delirium, psychosis or come
    3. Severe malaria =
      1. Any degree of altered consciousness, jaundice, oliguria, severe anaemia or hypoglycaemia
      2. A parasite count about 100,000/mm3 (>2% RBC parasitized)
      3. Patient is vomiting or clinically acidotic

    DIAGNOSIS

    1. Thick and thin smear of peripheral blood is gold standard
    2. Thick smear is to concentrate the parasites, species diagnosis best made on thin film
    3. Single negative smear does not exclude malaria, repeat if clinical suspicious high (every 8 – 12 hours)
    4. Thrombocytopaenia common
    5. CSF is normal in cerebral malaria
    6. Patients from malarious areas who are semi-immune may have parasites in their blood but this may not be the cause for their fever
    TREATMENT
    1. All patients with falciparum need admission and close monitoring for complications
    2. Pts with other species can be treated as outpatients if not unwell
    Vivax, Ovale and Malariae:
    1. P. vivax, P. ovale and P. malariae are treated with chloroquine
    2. Chloroquine resistance reported in PNG, Indonesia, SE Asia
    3. Chloroquine resistance: artemether + lumefantrine or mefloquine or quinine are alternatives
    4. Primaquine is used for P. vivax and P. ovale to reduce the possibility of replase (but does not eliminate risk)
    5. All patients who are to receive primaquine must be tested for G6PD deficiency as this drug can cause lysis of RBCs
    6. Patients who have relapses despite primaquine may need repeated course or higher doses
    Uncomplicated Falciparum:
    1. P. falciparum is treated with artemether  + lumefantrine
    2. Alternatives are quinine plus doxycycline or clindamycin
    3. OR atovaquone + proguanil
    4. OR mefloquine
    5. Atovaquone + proguanil and mefloquine should not be used for treatment of malaria in patients who took these drugs as prophylaxis
    Severe Malaria:
    1. Assume infective species to chloroquine-resistant falciparum
    2. Artesunate IV is first choice
    3. Alternative is quinine IV (if artesunate not immediately available) beginning with a loading dose
    4. Do not give loading dose if patient has received 3 or more doses of quinine or quinidine in the previous 48 hours or if mefloquine prophylaxis has been used in the previous 24 hours or a mefloquine treatment dose within the last 3 days
    5. Need to monitor BSL with quinine as it stimulates insulin secretion
    6. Cardiac monitoring is also advised if there is pre-existing heart disease (quinine can cause arrhythmias)
    MONITORING
    1. Parasite count every 12-24 hours (may rise initially) until all parasites are cleared
    2. IV should be changed to oral antimalarial as soon as possible
    3. Treat with oral quinine plus doxycycline or clindamycin for total of 7 days of quinine
    PREVENTION
    1. For areas with chloroquine-sensitive malaria – chloroquine
    2. For areas with chloroquine-resistant malaria – mefloquinine or doxycycline
    3. For areas with mefloquine-resistant malaria - doxycycline

    TYPHOID

    1. Can clinically mimic malaria
    2. Caused by salmonella typhi (or salmonella paratyphi à paratyphoid)
    CLINICAL FEATURES
    1. Incubation period 5 to 21 days
    2. Fever, chills (classical rising fever and bacteraemia in first week)
    3. Abdominal pain (classically in 2nd week)
    4. Headache
    5. Rash – faint rose spots on trunk (week 2)
    6. Hepatosplenomegaly, GI bleeding/perforation (3rd week)
    7. Diarrhoea not common
    8. Sepsis, altered conscious state
    9. Relative bradycardia (ie. High temperature but low normal HR)
    DIAGNOSIS
    1. Blood cultures (positive in 40 to 80%)
    2. Stool culture (30 to 40%)
    3. BM aspirate has much higher sensitivity, even after antibiotic treatment
    4. Anaemia
    5. Leukopaenia > leukocytosis
    TREATMENT
    1. Ciprofloxacin 500mg orally bd for 7 to 10 days
    2. If cipro resistant use Ceftriaxone or azithromycin

    MEASLES

    1. Characterised by 3 to 4 days of fever, cough, coryza and conjunctivitis
    2. Followed by rash which starts on face and neck and spreads downwards
    3. Koplik spots (small white spots inside the cheek) appear 1-2 days before the rash and are pathognomonic
    4. Supportive treatment
    5. Rare but potentially serious complications include bacterial superinfection, measles pneumonia, post-infectious encephalomyelitis and subacute sclerosing panencephalitis

    Q FEVER

    • Q fever not associated with a rash
    • Classically presents as fever in an abattoir worker
    • Can be acute or chronic relapsing
    • Treatment is oral doxycycline

    Topic

    Infectious Diseases: Evaluation of acutely ill, febrile travellers and patients from overseas.

     

    Question 68 top Download PDF

    A 76yo woman with a 45 pack year smoking history presents with a six-month history of worsening dry cough. HRCT scans of the thorax are shown below.

    Based on these scans, which of the following is the most likely cause of her cough?
    A. Chronic bronchitis
    B. Emphysema
    C. Interstitial pulmonary fibrosis
    D. Bronchiolitis obliterans
    E. Bronchiectasis

    CT shows honey-combing in the peripheral areas of the lower lobes. This is consistent with IPF.

    The following Emedicine articles provide HRCT images for

    Chronic Bronchitis

    Emphysema

    Interstitial pulmonary fibrosis

    Bronchiolitis obliterans

    Bronchiectasis

    Topic

    Respiratory: Interstitial lung disease | Respiratory investigations

    Question 69 top Download PDF

    A 54yo Indian woman complains of a constant pain in her hips which is worse on standing and walking. She has mild weakness of hip flexion and walks with difficulty. She is a vegetarian and avoids dairy products. She immigrated to New Zealand three years ago. A pelvic X-ray is normal. The following blood tests are obtained:

    Alkaline phosphatase (ALP)   457U/L          [30-115]
    Corrected calcium                 2.13mmol/L     [2.15-2.57]
    Phosphate                          0.79mmol/L    [0.90-1.55]
    PTH     16.0pmol/L       [1.3-7.6]

    The most appropriate next investigation is:

    1. Dual-energy X-ray absorptiometry (DEXA) scan
    2. Bone biopsy
    3. Isotope bone scan
    4. Vitamin D levels
    5. 24-hour urinary calcium

    This woman has secondary hyperparathyroidism due to hypocalcaemia.
    Also note that her phosphate level is low.
    This picture could be seen in pseudohypoparathyroidism or in vitamin D abnormalities.
    Elevated ALP and the musculoskeletal pain fits with osteomalacia due to vitamin D deficiency.
    This is also more likely given the dietary history (vitamin D largely from dairy and fish) and the move from a warm environment to a cool environment (UTD specifically mentioned Indian immigrants in this situation – don’t get enough sunlight).

    The correct answer is D.

    DEXA seems to be used for the diagnosis of osteoporosis but not much for osteomalacia.

    A bone biopsy is the gold standard for osteomalacia but it is rarely used any more. Usually the diagnosis can be made on clinical features and bloods.

    A bone scan may be useful if there is concern of osteoblastic bone mets. This wound not be an initial investigation though.

    24 hour urinary calcium is not going to be helpful as renal losses of calcium alone do not cause hypocalcaemia (see below).

    HYPOCALCAEMIA

    Causes:

    1. Hypoparathyroidism
      • Surgical resection
      • Idiopathic
      • Infiltration
      • HIV infection
      • Pseudohypoparathyroidism
    2. Vitamin D deficiency
      • Including chronic renal failure
    3. Extracellular deposition/intravascular binding of calcium
      • Hyperphosphataemia
      • Acute pancreatitis
      • Osteoblastic bone mets
      • Intravascular complexing with citrate, lactate, forscarnet or EDTA
      • Acute respiratory alkalosis
    4. Disorder of magnesium metabolism
    5. Others
      • Sepsis
      • AD hypocalcaemia
      • Fluoride intoxication
      • Drugs

    HYPOPARATHYROIDISM

      1. Hereditary / Idiopathic
      2. Acquired
        • Surgical removal
        • Post-surgical fibrosis
        • Infiltrative diseases
        • HIV
      3. Calcimimetics
        • Cinacalcet – bind to calcium-sensing receptor on PT gland and lower the threshold for its activation by extracellular calcium --> decreased PTH release

    Low parathyroid hormone levels mean that calcium reabsorption from the kidneys, intestinal calcium absorption and calcium release from bone are not increased in response to low serum calcium levels.

    Pseudohypoparathyroidism

    • Characterised by end-organ resistance to the effects of PTH
    • Normally PTH binds to the PTH receptor, which activates cAMP through guanine nucleotide regulator proteins (Gs). These proteins consist of alpha, beta and gamma subunits
    • Pseudohypoparathyroidism is classified into type I and II, type I further subdivided into Ia, Ib and Ic
    • Ia: Decreased Gs-alpha protein
      • Hypocalcaemia, hyperphosphataemia, normal or high PTH, low calcitriol, vitamin D may be low due to suppression by hyperphosphataemia and decreased PTH stimulation
      • Can also affect other endocrine systems – resistance to TSH, gonadotropins, glucagon
      • Albright’s hereditary osteodystrophy (features include round face, short stature, short 4th MC)
    • Ib: Resistance to PTH with abnormal cAMP response to PTH (likely due to receptor abnormality)
    • Ic: Resistance to multiple hormonal receptors but normal Gs-alpha protein expression
    • II: PTH raises cAMP normally but fails to increase levels of serum calcium or urinary phosphate excretion
      • Hypocalcaemia, hypophosphaturia, elevated PTH
      • First need to rule out vitamin D deficiency

    VITAMIN D DEFICIENCY

      • Vitamin D deficiency leads to impaired calcium absorption from the gut
      • Hypocalcaemia results in secondary hyperparathyroidism which causes calcium release from bone and reabsorption of calcium in the kidneys
      • PTH can maintain normal serum calcium levels for a time but vitamin D deficiency leads to resistance to PTH in bone and renal tubules --> hypocalcaemia
      • PTH then causes only mild increase in serum calcium
      • PTH also has the effect of promoting phosphaturia à hypophosphataemia which exacerbates demineralisation of bone
      • Combined effect of lower Ca2+ and low PO4 leads to loss of bone mineralisation and if prolonged, osteomalacia
      • Non-specific musculoskeletal pain is common
      • ALP often elevated due to PTH-mediated bone turnover
      • Because PTH stimulates 1-alpha hydroxylase, there is increased synthesis of 1,25(OH)2 vitamin D despite a deficiency of 25(OH)D so make sure the correct form of vitamin D is measured
    Causes:
    1. Deficient Intake/Absorption
      • Dietary deficiency
      • Inadequate sunlight exposure
      • Malabsorption (Gastrectomy, Small bowel disease)
      • Pancreatic insufficiency
    2. Defective 25-hydroxylation
      • Biliary cirrhosis
      • Alcoholic cirrhosis
      • Anticonvulsants
    3. Defective 1-alpha 25-hydroxylation
      • Hypoparathyroidism
      • Renal failure (CRF also leads to impaired PO4 excretion)
      • Vitamin D-dependent rickets type 1 – mutation in 1-alpha hydroxylase à osteomalacia, hypocalcaemia, secondary hyperparathyroidism, markedly decreased 1,25 (OH)2 vitamin D, no alopecia
    4. Defective Target Organ Response to Calcitriol
      • Vitamin D-dependent rickets type 2 – osteomalacia, hypocalcaemia, secondary hyperparathyroidism, normal 25 vitamin D, markedly increased 1,25(OH)2 vitamin D, alopecia

    MAGNESIUM ABNORMALITIES

    1. Hypomagnesemia causes
      • PTH resistance
      • Decreased PTH secretion
    2. Severe hypermagnesemia (Mg >5)
      • Rare
      • Suppresses PTH

    EXTRACELLULAR DEPOSITION

    • Acute hyperphosphataemia causes calcium deposition in bone and extraskeletal tissue
    • Chronic hyperphosphataemia (usually due to CRF) inhibits calcium efflux from bone and reduces calcium absorption due to reduced renal synthesis of vitamin D
    • Acute pancreatitis causes precipitation of calcium soaps in the abdomen
    • Osteoblastic metastases can sometimes cause hypocalcaemia, presumably due to deposition of calcium within the mets
    • Hungry bone syndrome occurs in patients with primary hyperparathyroidism who undergo parathyroidectomy – leads to deposition of calcium in bone

    INTRAVASCULAR BINDING

    • Citrate, lactate and foscarnet chelate calcium in serum
    • Acute respiratory alkalosis increases calcium binding to albumin and also reduces ionised calcium concentration

    HYPERCALCIURIA

    • Can lead to a negative calcium balance but not hypocalcaemia due to the compensatory mechanisms of PTH

    DRUGS

    1. Agents that inhibit bone resorption
      • Calcitonin
      • Bisphosphonates
      • Oestrogens
    2. Chemotherapy agents
      • Cisplatin
      • Cytosine arabinoside
      • Doxorubicin
    3. Antimicrobials
      • Ketoconazole
      • Foscarnet
      • Pentamidine
    4. Diuretics
      • Frusemide
    5. Cinacalcet

    INVESTIGATION OF HYPOCALCAEMIA

    • Serum albumin
      • To exclude factitious hypocalcaemia
    • Serum ionised calcium
    • Magnesium
    • Serum phosphate
      • High PO4 in healthy kidneys is due to hypoparathyroidism or pseudohypoparathyroidism
      • High PO4 and PTH occurs in renal failure – impaired PO4 excretion
      • Low PO4 indicates either excess PTH secretion (secondary hyperparathyroidism) or low dietary phosphate intake
    • PTH
      • Low in hypoparathyroidism
      • PTH elevated in pseudohypoparathyroidism and abnormalities of vitamin D metabolism
      • PTH can be high or low in hypomagnesemia
    • Vitamin D
    • ALP
      • In PTH deficiencies, ALP normal or slightly low
      • Elevated in osteomalacia and rickets
    • Skeletal XRs
      • Look for osteomalacia, rickets and osteoblastic metastases
    • Bone biopsy
      • Can confirm the diagnosis of osteomalacia

     

    Topic

    Endocrinology: Hypocalcaemia

     

    Question 70 top Dowload PDF

    A 45-year old asymptomatic man returns for follow-up. He was diagnosed 10 years ago with aortic regurgitation due to a congenital bicuspid aortic valve. He has never had endocarditis.

    Which one of the following echocardiographic profiles most strongly indicates the need for aortic valve replacement?

      LVEDD (mm)
    [35-55]
    FS
    [0.30-0.40]
    LA size (mm)
    [<40]
    A 70 0.30 60
    B 75 0.40 40
    C 70 0.25 45
    D 65 0.45 50
    E 75 0.35 55

    LVEDD Left ventricular end-diastolic diameter
    LVESD Left ventricular end-systolic diameter
    FS Fractional shortening = (LVEDD – LVESD)/LVEDD
    LA Left atrial

    AORTIC REGURGITATION

    • AR is never normal (as opposed to mild MR/TR which can be normal).

    Severity of AR

    Considered severe if one or more of the following:

    • Regurgitant fraction = 50%
    • Vena contracta width > 6mm
    • Regurgitant volume = 60mL
    • Central jet width = 65% of LV outflow tract
    • An effective regurgitant orifice area = 0.30 cm2

    Current guidelines re: AR and AVR:

    • Recommend replacement when end-systolic dimension is > 55mm (in asymptomatic patients).


    FS = (LVEDD – LVESD)/LVEDD

    a) LVESD = 49
    b) LVESD = 45
    c) LVESD = 52.5
    d) LVESD = 35.75
    e) LVESD = 45

    Therefore correct answer is C, where pt is approaching LVESD where AVR is recommended.


    Causes of AR:

    1. Chronic leaflet degeneration is most common cause (ie. Aortic sclerosis). Usually associated with hypertension and increasing age.
    2. Rheumatic disease
    3. Bicuspid aortic valve
    4. Endocarditis causing acute, severe AR. 10% will also have MV disease.
    5. Subaortic stenosis: high velocity of blood strikes stenotic aortic valve causing damage to valve and change in architecture.
    6. Myxomatous disease: caused by aortic root disease and associated with MV prolapse.
    7. Marfan’s syndrome: Associated with MV prolapse but AR not due to aortic root disease as in 6.
    8. Aortic root disease (eg: proximal dissection, hypertensive dilation, sinus of valsalva aneurysm).
    9. Aortic dissection causing severe, acute AR.
    10. Sinus of valsalva aneurysm (this is a form of aortic root aneurysm) characterised by asymmetric dilatation of one of the sinuses.
    11. Rheumatoid nodules (rare)
    12. Leaflet fenestrations (commonly found post mortem)
    13. VSD

    References:

    ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease - Full Text

    Topic

    Cardiology - Atrial Regurgitation

     

    Question 71 top Download PDF

    An 86yo woman with moderate Alzheimer’s disease, including difficulty with language, is increasingly agitated and believes there are people living in her ceiling, despite ongoing reassurance to the contrary. The patient lives with her son who seeks your advice regarding management of these delusions.
    Which of the following would be most beneficial?

    1. Commence a benzodiazepine
    2. Find alternative accommodation
    3. Isolate and rest the patient in her room
    4. Address factors in the home that exacerbate the delusion
    5. Commence respite in a day care centre

    Answer = D
    Dementia = an acquired deterioration in cognitive abilities that impairs the successful performance of ADLs. Impairment in memory plus language, visuospatial ability, calculation, judgement or problem solving.

    ALZHEIMER’S DEMENTIA

    Clinical Manifestations
    1. Characterised with insidious onset memory loss progressing over time to include dyspraxia, dysphasia and personality change
    2. 20% of patients do not present with memory complaints but with other problems such as word-finding, organisational or navigational difficulties
    3. In end-stage AD, patients may become rigid, mute, incontinent and bedridden
    4. Typical duration 8 to 10 years (ranges from 1to 25 years)
    Diagnosis
    1. Imaging may be normal early in disease
    2. Late in disease, diffuse cortical atrophy and hippocampal atrophy on MRI
    3. Laboratory tests should be essentially normal
    Epidemiology
    1. Major risk factors are age and family history
    2. 20-40% of population over 85yrs affected
    Pathology
    1. Most severe in hippocampus, temporal cortex and nucleus basalis of Meynert
    2. Neuritic (senile) plaques and NFTs accumulate in small numbers in normal aging but in excess in AD
    3. Neuritic plaques contain a central core that includes amyloid, proteoglycans, apo E4, alpha-1, antichymotrypsin and other proteins
    4. Plaque core surrounded by debris of degenerating neurons, microglia and macrophages
    5. Amyloid angiopathy = accumulation of amyloid in cerebral arterioles – can lead to cerebral lobar haemorrhages
    6. NFTs are twisted neurofilaments that represent abnormally phosphorylated tau protein
    Genetics
    1. Some cases of AD are related to certain genes (eg: point mutations in APP gene on chm 21 causes early-onset AD)
    2. Adults with trisomy 21 who survive beyond age 40 consistently develop progressive dementia typical of AD
    3. A couple of other genes have been identified which are associated with early onset AD
    4. ApoE (especially ApoE4) on chm 19 associated with late-onset familial and sporadic forms of AD – may be involved in the clearance of amyloid
    Treatment
    1. Avoid cholinesterase inhibitors where possible
    2. Non-pharmacological treatment is most important
    3. Cholinesterase inhibitors offer modest benefits in mild to moderate AD – slow decline
    4. Donepezil is usually first choice as once daily and fewer side effects
    5. No clear evidence to suggest that switching agents will produce a better response
    6. Side effects include GI upset, insomnia, vivid dreams, asthma, bradyarrhythmias, cramps and dizziness
    7. Memantine is an antagonist of NMDA and is for moderate to severe AD – may slow deterioration
    Treating Behavioural Disturbances
    1. Avoid typical antipsychotics in patients with suspected DLB or Parkinson’s disease
    2. To control hallucinations, delusions or seriously disturbed behaviour use risperidone, olanzapine or haloperidol
    3. To relieve symptoms of anxiety or agitation give oxazepam 15mg once to 4 times a day (for short time only)
    VASCULAR DEMENTIA
    1. Can be divided into multi-infarct dementia and diffuse white matter disease
    2. Often step-wise decline but can be gradual with diffuse white matter disease (due to multiple lacunar infarcts)
    3. Tau may play a role in familial forms
    4. CADASIL is a form of dominantly inherited diffuse white matter disease = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
    5. Progressive dementia in the 5th to 7th decades in multiple family members who may also have a history of migraine and recurrent stroke without HT
    6. Due to mutations in notch 3 gene which can be tested for
    7. No treatment
    FRONTOTEMPORAL DEMENTIA
    1. Begins between 50 and 70 yrs
    2. Behaviour symptoms, predominate early, memory typically spared
    3. Planning, judgement and language commonly affected
    4. Can sometimes have motor abnormalities early
    5. Poor insight
    6. Late in disease, apathy and withdrawal
    7. Marked atrophy of temporal and/or frontal lobes, can be asymmetrical
    8. Tau plays a role
    9. Large overlap with PSP, CBD and MND
    10. Pick’s disease usually refers to a subset of FTD patients with certain pathological findings
    11. Symptomatic treatment only
    PROGRESSIVE SUPRANUCLEAR PALSY
    1. Begins with falls and a vertical supranuclear gaze paresis
    2. Progresses to symmetric rigidity and dementia
    3. Stiff posture, hyperextension of the neck, slow gait, frequent falls
    4. Limited voluntary eye movements but oculocephalic reflexes (doll’s head manoeuvre) retained therefore supranuclear
    5. Dementia similar to FTD
    CORTICAL BASAL DEGENERATION 
    1. Slowly progressive dementia
    2. Typically presents with unilateral onset with rigidity, dystonia and apraxia of one arm and hand (“alien hand”)
    3. Eventually becomes bilateral and includes dysarthria, slow gait, action tremor and dementia
    DEMENTIA WITH LEWY BODIES
    • Visual hallucinations, parkinsonism, fluctuating alertness and falls
    • Dementia may precede or follow parkinsonism
    • Fluctuating pattern
    • Usually better memory but worse visuospatial deficits than AD
    • Lewy bodies are intraneuronal cytoplasmic inclusions, found in cortex, amygdala, cingulated cortex and substantia nigra
    • Anticholinergics may help
    • Dx on MRI or SPECT

    Topic

    Neurology: Dementia

    Question 72 top

    Question 73 top Download PDF

    A 45yo woman has a history of terminal ileal Crohn’s disease for which she has a terminal ileal resection eight years ago. Surgery was complicated by small bowel leak post operatively, requiring laparotomy and prolonged drainage with bowel rest (total parenteral nutrition). Following recovery she remained well until 2 weeks ago, when she presented with two episodes of abdominal pain, bloating and vomiting which lasted two to three hours each and then resolved. There has been no change in bowel habit and no fever. She is on no medication.

    Examination reveals mild tenderness in the lower abdomen. Bowel sounds are normal.

    A CT scan is performed and representative slices are shown below.

    Which of the following is the most likely cause for her current symptoms?

    A. Adhesions

    B. Recurrence of Crohn’s disease

    C. Psoas abscess

    D. Colonic carcinoma

    E. Irritable bowel syndrome

     

    There seems to be a lot of clinical information provided when all that you really need to do is look at the CT scan.

    The scan shows a thin line of oral contrast in the transverse colon (I think) which is obviously different from the contrast in the rest of the bowel. It suggests a stricture in the bowel which would be consistent with a skip lesion of Crohn’s disease. Therefore the answer is recurrence of Crohn’s disease – B. This would also fit with the clinical history provided.

    From the history adhesions could be causing a bowel obstruction but I would think that would be unlikely to spontaneously resolve.

    A psoas abscess does not normally present with bloating and vomiting.  Generally symptoms will include abdominal or back pain or referred pain to the hip with fever. A psoas abscess can develop from fistulae to the retroperitoneum so is a possible complication of Crohn’s disease.

    This woman would be young to have a colon cancer, although she is at increased risk with her history of Crohn’s disease. Again it would be unlikely that an obstruction due to a malignancy would resolve.

    By making the diagnosis of Crohn’s we have excluded IBS from the differentials. IBS is a diagnosis of exclusion.

    A BIT ABOUT CROHN’S DISEASE

    1. Transmural inflammation
    2. Can affect any part of the GIT
    3. Commonly patients will have involvement of the terminal ileum +/- colon
    4. Relapsing/remitting course

     

    Clinical Manifestations

    1. Diarrhoea +/- bleeding
    2. Abdominal pain
    3. Repeated episodes of small bowel (or less commonly large bowel) obstruction due to fibrotic stricture
    4. Fatigue
    5. Weight loss
    6. Fever
    7. Fistulae
    8. Abdominal abscess
    9. Perianal disease (abscesses, fistulae, pain)

     

    Diagnosis

    1. Colonoscopy with intubation of terminal ileum
      1. Cobblestone appearance
      2. Focal inflammation/ulceration next to normal mucosa
      3. Skip lesions
    2. Small bowel follow through if not accessible by colonoscopy
      1. Strictures
    3. Pill-cam may be useful but should not be used in patients with suspected strictures
    4. Antibodies
      1. ANCA
      2. ASCA (anti-Saccharmyces cerevisiae antibodies) – seems more specific for Crohn’s over ulcerative colitis
    5. CRP – generally higher in Crohn’s than UC

     

    Complications

    1. Obstruction
    2. Haemorrhage
    3. Perforation
    4. Fistulae
    5. Abscesses
    6. Toxic megacolon
    7. Malabsorption
      1. Bile salts absorbed in distal ileum à steatorrhoea, malnutrition, clotting abnormalities, osteomalacia, hypocalcaemia, gallstones
    8. Malignancy
      1. Increased risk compared to general population
      2. Number of patients with Crohn’s who get colorectal Ca is still small

     

    Systemic Complications

    1. Eye involvement – uveitis, iritis and episcleritis
    2. Skin disorders – erythema nodosum and pyoderma gangrenosum
    3. Arthritis
    4. Primary sclerosing cholangitis
    5. Secondary amyloidosis à Renal failure

     

    Treatment

      • Acute exacerbations = steroids
      • Maintenance therapy = immunosuppressants (ie. azathioprine or 6-MP)
      • Surgical management

      Topic

      Gastroenterology: Chron's Disease

       

      Question 74 top

      Question 75 top Download PDF

      Which one of the following features is most suggestive of autosomal dominant familial hypercholesterolaemia rather than other causes of hypercholesterolaemia?

      A. Tendon xanthomas.
      B. Corneal opacities.
      C. Lipaemia retinalis.
      D. Eruptive xanthomas.
      E. Recurrent pancreatitis.

      Answer: A        
      XANTHOMAS

      • Xanthelasma palpebrarum
        • Most common
        • Asymptomatic
        • Usually bilateral and symmetrical
        • Soft, velvety, yellow, flat, polygonal papules around the eyelids
        • Common in the upper eyelid near the inner canthus
        • May be associated with hyperlipidemia of any type
      • Tuberous xanthomas
        • are firm, painless, red-yellow nodules
        • The lesions can coalesce to form multilobated tumors
        • Usually develop in pressure areas, such as the extensor surfaces of the knees, the elbows, and the buttocks
        • Particularly associated with hypercholesterolemia and increased levels of LDL
        • Can be associated with familial dysbetalipoproteinemia and familial hypercholesterolemia
        • May be present in some of the secondary hyperlipidemias (eg, nephrotic syndrome, hypothyroidism).

      • Tendinous xanthomas
        • appear as slowly enlarging subcutaneous nodules related to the tendons or the ligaments
        • Most common locations are the extensor tendons of the hands, the feet, and the Achilles tendons
        • Associated with severe hypercholesterolemia and elevated LDL levels
        • Can also be associated with some of the secondary hyperlipidemias, such as cholestasis
      • Eruptive xanthomas
        •  most commonly arise over the buttocks, the shoulders, and the extensor surfaces of the extremities
        • Rarely, the oral mucosa or the face may be affected
        • Lesions typically erupt as crops of small, red-yellow papules on an erythematous base
        • May spontaneously resolve over weeks
        • Pruritus is common
        • May be tender
        • Associated with hypertriglyceridemia, particularly that associated with types I, IV, and V (high concentrations of VLDL and chylomicrons)
        • May also appear in secondary hyperlipidemias, particularly in diabetes
      • Plane xanthomas
        • Mostly macular and rarely form elevated lesions
        • Can occur in any site
        • Involvement of the palmar creases is characteristic of type III dysbetalipoproteinemia
        • Can also be associated with secondary hyperlipidemias, especially in cholestasis
        • Generalized plane xanthomas can cover large areas of the face, the neck, and the thorax, and the flexures can also be involved
        • May be associated with monoclonal gammopathy and hyperlipidemia, particularly hypertriglyceridemia
      • Xanthoma disseminatum and verruciform xanthoma are particular forms of xanthomas that occur in normolipemic patients
      • Xanthoma disseminatum develops in adults as red-yellow papules and nodules with a predilection for the flexures. Characteristically, the mucosa of the upper part of the aerodigestive tract is involved. It has a benign clinical course and usually resolves spontaneously.
      • Verruciform xanthoma predominantly occurs in the oral cavity of adults as a single papillomatous yellow lesion. Verruciform xanthoma is considered to be a reactive condition with benign behavior, and it is treated with local excision.
      • Lipoprotein patterns can be determined as follows:
        • I - Elevated triglyceride levels with increased chylomicron levels
        • IIa - Elevated cholesterol level because of increased LDL level
        • IIb - Elevated cholesterol and triglyceride levels because of increased LDL and VLDL levels
        • III - Elevated cholesterol and triglyceride levels, with the presence of beta-VLDL
        • IV - Elevated triglyceride levels because of increased VLDL level
        • V - Elevated triglyceride levels because of increased VLDL level and the presence of chylomicrons

       
      A:  Tendonous xanthoma are associated with severe hypercholesterolaemia and elevated LDL levels, including FH.

      B: Corneal opacities (corneal arcus) are a feature of hypercholesterolaemia and is associated with familial forms but many subjects with normal cholesterol levels also have corneal arcus.

      C: Lipaemia retinalis is associated with extremely elevated triglyceride levels – blood becomes a creamy white colour so in this picture arteries and veins can only be distinguished by the vessel size

      D: Eruptive xanthoma – Associated with hypertriglyceridaemia

      E: Recurrent pancreatitis: Acute pancreatitis in childhood is a common presentation for familial lipoprotein lipase deficiency which causes a type I pattern of hyperlipidaemia ie. Elevated triglycerides and chylomicrons but normal cholesterol.

      FAMILIAL HYPERCHOLESTEROLAEMIA
      1. Autosomal dominant
      2. Severe elevations of total cholesterol and LDL
      3. Heterozygous form in 1/500
      PATHOPHYSIOLOGY
      1. Absent or grossly malfunctioning LDL receptors
      2. Gene for receptor is located on short arm of chromosome 19
      3. Receptor is the primary determinant of LDL uptake
      4. LDL binds to receptor, apolipoprotein B-100 (apoB) is critical in this process
      5. Receptor also can bind apoE which is found on most lipoproteins other than LDL
      5 classes of mutations:
        1. Null alleles that result in complete absence of LDL receptor
        2. Defective transport alleles , which disrupt normal folding and lead to failure of transport of the receptor to the cell surface or transport of a truncated, mutated receptor
          • 2a: completely block the transport of the receptor from the endoplasmic reticulum to the Golgi apparatus
          • 2b: partial blockade of transport of the receptor from the ER to the Golgi apparatus
        3. Defective binding alleles that affect the binding of LDL and in some cases VLDL also
        4. Defective internalisation alleles that affect the concentration of receptors in the clathrin-coated pits for internalisation by hepatocytes
        5. Defective recycling alleles that prevent dissociation of the receptor and the ligand and thus interrupting recycling of the receptors

        Topic

        Endocrinology: Investigation and management of hyperlipidemia

         

        Question 76 top Download PDF

        In human immunodeficiency virus (HIV)-infected patients receiving combination antiretroviral therapy, including nucleoside reverse transcriptase inhibitors, which of the following drug side-effects is least likely to be due to mitochondrial toxicity?
        A. Lactic acidosis.
        B. Pancreatitis.
        C. Stevens-Johnson syndrome.
        D. Myopathy.
        E. Peripheral neuropathy.

        Mitochondrial toxicity is a recognised side effect of nucleoside reverse transcriptase inhibitors which can cause:

        • Myopathy
        • Peripheral neuropathy
        • Hepatic steatosis with lactic acidosis
        • Lipoatrophy
        • Pancreatitis likely to be related (but not definitely established)

        ROLE OF MITOCHONDRIA

        • Main function is oxidative phosphorylation (fatty acids and pyruvate --> ATP)
        • Oxidative phosphorylation is also responsible for neutralisation of free radicals and beta-oxidation of free fatty acids
        • Mitochondria general reactive oxygen species (ROS) during oxidative phosphorylation
        • Oxidative stress can occur if there is an imbalance between the production of ROS and cellular antioxidant defences
        • Mitochondrial DNA polymerase is a target of oxidative damage

        PATHOGENESIS

        • Nucleoside analogues have a high affinity for viral reverse transcriptase
        • They can also bind human DNA-polymerases, however, including mitochondrial DNA polymerase gamma (which is exclusively responsible for replication of mtDNA)
        • By inhibiting mtDNA polymerase gamma, can lead to depletion of mtDNA --> organelle dysfunction --> impaired oxidative phosphorylation --> decreased ATP --> increased electron leakage from electon-transport chain --> increased ROS --> damage to proteins, lipids and mtDNA --> further oxidative damage and lipid peroxidation
        • Metabolism of pyruvate shifted to lactate --> lactate accumulation

        CLINICAL MANIFESTATIONS

        Myopathy:
        • Proximal muscle weakness
        • Tenderness
        • Myalgia
        • Increased CK
        • “Ragged-red” fibres on histology
        • Particularly associated with ZDV

        Lipoatrophy:

        • Particularly associated with d4T
        Hepatic Steatosis:
        • Rare
        • Hepatic steatosis and hepatic failure
        • Lactic acidosis
        • NRTIs should be stopped promptly
        • Supportive treatment
        • Associated with ZDV, ddI and d4T
        Lactic Acidosis:
        • Rare
        • Symptomatic -fatigue, weakness, dyspnoea, tachypnoea, nausea and vomiting, abdominal pain, weight loss
        • Asymptomatic more common - usually not constant, poor predictive value in these cases
        Pancreatitis:
        • Has not been clearly established that pancreatitis is related to mitochondrial toxicity but this is likely
        • ddI greater than d4T
        Bone Marrow Suppression:
        • May be related to mitochondrial toxicity
        • Associated with ZDV
        Neuropathy:
        • Didanosine and stavudine
        • Peripheral neuropathy
        RISK FACTORS
        • Female
        • Concominant use of ribavirin with ddI for treatment of hepatitis C

        DIAGNOSIS

        • Gold standard: muscle or liver biopsy

        So the only option that is not associated with mitochondrial toxicity is C – Stevens-Johnson syndrome

        Topic

        Infectious Diseases - HIV

        Clinical Pharmacology - Infections

        Question 77 top

        Question 78 top

        Question 79 top Download PDF

        A 21 yo overseas student from India presents with malaise, mild shortness of breath and low-grade fevers over four weeks. Her chest XR is shown below.

        Which one of the following investigations is most likely to provide the diagnosis?

        A. Pleural fluid aspiration
        B. Mantoux testing
        C. Sputum culture
        D. Bronchoscopy
        E. Pleural biopsy


        TIME COURSE

        • Parapneumonic: 1-2 weeks
        • TB pleurisy: six weeks to 4 months

        CXR

        • At least 75mL of pleural fluid is required to obliterate the posterior costophrenic sulcus on lateral XR
        • Al least 175mL are needed to obscure the lateral costophrenic sulcus on an erect PA XR
        • 500mL will obscure the diaphragmatic contour
        • 1000mL will reach the level of the fourth rib anteriorly
        • Absent air bronchograms
        • Pulmonary vessels are visible through the opacity


        TRANSUDATIVE EFFUSIONS

        • Most common cause is LVF
        • 90% bilateral in LVF
        • Other common causes include pericarditis, cirrhosis and renal failure
        • Most often due to imbalances in hydrostatic and oncotic pressures in the chest
        • Can also result from movement of fluid from peritoneal or retroperitoneal spaces or iatrogenic causes (eg: migrated CVC)
        • Can occasionally loculate and mimic tumours (if sitting in fissure)
        • Rarely can have bilateral pleural effusions of different origins (eg: Transudate 2’ LVF on R and exudate 2’ pneumonia/empyema on L); this is Contarini’s condition
        • Most transudates have protein < 3.0g/dL
        • Transudates normally have pH in range of 7.40 to 7.55

        Causes of transudative pleural effusions:

        1) CCF
        2) Cirrhosis (rare without ascites)
        3) Nephrotic syndrome
        4) Peritoneal dialysis
        5) Hypoalbuminaemia
        6) Atelectasis
        7) Constrictive pericarditis
        8) SVC obstruction
        9) Urinothorax (ipsilateral obstructive uropathy)
        10) PE
        11) Hypothyroidism


        EXUDATES

        - Pneumonia then malignancy most common

        Causes (many and varied):

        1. Infective
          1. Pneumonia
          2. Subphrenic/hepatic/splenic
        2. Increased negative intapleural pressure (eg: atelectasis)
        3. Malignancy
        4. Connective tissue disease
        5. Endocrine (eg: hypothyroidism)
        6. Iatrogenic
          1. Drug-induced
          2. Oesophageal perforation
          3. CVC migration/misplacement
          4. Post-CABG
          5. Radiation injury
        7. Lymphatic abnormalities (eg: chylothorax, yellow nail syndrome)
        8. PE
        9. Sarcoidosis
        10. Pericardial disease
        11. Trapped lung
        12. Haemothorax
        13. Movement of fluid from abdomen to pleural space
          1. Pancreatitis
          2. Pseudocyst
          3. Meigs’ syndrome
          4. Abscess

        - Large unilateral exudate in a young person is suspicious for TB
        - In older people malignancy is more common
        - If one of the following criteria is present the fluid is virtually always an exudate:

        • i. Pleural fluid protein/serum protein > 0.5
        • ii. Pleural fluid LDH/serum LDH > 0.6
        • iii. Pleural fluid LDH > 2/3 upper limit of normal serum LDH


        OTHER LABORATORY MEASUREMENTS

        Protein:

        • TB exudates will almost always have protein concentrations > 4.0g/dL
        • When protein is in the range of 7-8g/dL should consider Waldenstrom’s macroglobulinaemia and multiple myeloma

        LDH:

        • LDH > 1000 IU/L characteristically found in empyema, rheumatoid pleurisy and pleural paragonimiasis
        • Pneumocystis jiroveci pneumonia characteristically has pleural/serum LDH >1.0 and pleural/serum protein <0.5

        Glucose:

        • A glucose concentration < 3.33mmol/L or a pleural/serum ration < 0.5 narrows the DDx of exudates to
          1. Rheumatoid pleurisy
          2. Empyema
          3. Malignancy
          4. TB
          5. Lupus
          6. Oesophageal rupture
        • Other causes of exudates have glucose levels similar to serum concentrations

        pH:

        • Above conditions also associated with low pleural pH (<7.30)
        • Exudates normally have pH in range of 7.30 to 7.45

        Cell Counts:

        • Lymphocytosis associated w TB, lymphoma, sarcoidosis, rheumatoid, yellow nail syndrome and chylothorax
        • Eosinophilia associated with pneumothorax, haemothorax, pulmonary infarction, benign asbestos pleural effusion, parasitic disease, fungal infection, drugs and malignancy


        EMPYEMA

        • Vast majority due to pulmonary infections
          • Anaerobic or mixed aerobic-anaerobic most common
        • Other possible causes are trauma and surgical procedures
        • Three stages in the evolution of empysemas:
          1. Exudative pleural effusion w greater than 15,000 leukocytes/microliter
          2. Fibrinopurulent stage w adhesions
          3. Organising stage w development of a thick pleural peel
        • Can be easily drained in stage 1
        • Decortication may be required in stages 2 and 3
        • Diagnosis by CT
        • In the 2nd and 3rd stages, CT shows enhancement of the visceral and parietal pleurae (split pleura sign)
        • Empyemas tend to compress surrounding lung rather than destroy it (as opposed to lung abscesses)

        MALIGNANCY

        • 2nd most common cause of exudate
        • 80% of them are 2’ to breast, lung, ovary or lymphoma
        • Due to
          1. Increased pleural membrane permeability
          2. Decreased clearance due to lymphatic obstruction
          3. Bronchial obstruction --> atelectasis and decreased intrapleural pressure --> pleural liquid accumulation


        HAEMOTHORAX

        • Definition: Bloody pleural effusion with a haematocrit > half the value in peripheral blood
        • Trauma, PE, metastatic disease, anticoagulation, leaking aortic aneurysm
        • High attenuation on CT
        • MRI can determine age of blood


        CHYLOTHORAX

        • Usually due to mediastinal tumours (especially lymphoma or bronchogenic carcinoma)
        • Trauma and surgery
        • A few other rare causes
        • Large effusion
        • Low attenuation on CT
        • Due to disruption of the thoracic duct leading to formation of a chylous duct cyst which can perforate to cause the effusion
        • Trauma to lower third of thoracic duct causes R sided effusions, trauma to upper 2/3 causes L sided effusions


        So, getting back to the question, this woman most likely has TB pleurisy.

        A. AFBs on pleural fluid. This is the primary diagnostic test in tuberculous pleuritis. Positive in 42% of patients with pleural TB.

        B. A positive Mantoux test (or quantiferon gold) indicates infection with M. tuberculosis but does not diagnose active disease. Therefore it may support but not establish the diagnosis.

        C. High quality, spontaneously expectorated sputum is better for detection of AFB. Diagnostic yield is related to number of samples, quality and quantity. Positive in 20 to 50% of cases, more commonly in patients with parenchymal disease.

        D. Bronchoscopy is used to obtain respiratory secretions in a person who cannot produce enough sputum or who have negative sputums. Similar yield for induced sputum samples.

        Answer E. Pleural Biopsy Positive in 64% of patients with pleural TB. Histological examination will show granulomas which is virtually diagnostic of TB. Yield is greater when more samples (ie 4-6) are taken.

        Topic

        Respiratory: Investigations | TB

        Question 80 top

        Question 81 top Download PDF

        A 28yo woman presents to the emergency department with a 4 day history of headache and blurring of vision. She has previously been well. She is on no medication.

        On examination she is very confused and disorientated. Her blood pressure is 230/140 mmHg. Her JVP in not elevated, heart sounds are normal and lung bases clear. Her reflexes are generally brisk. Fundoscopy shows bilateral haemorrhages, exudates and papilloedema.

        Which of the following is the most appropriate treatment?

        1. Intravenous sodium nitroprusside
        2. Intravenous frusemide
        3. Oral nifedipine
        4. Intramuscular hydralazine
        5. Oral enalapril

        MALIGNANT HYPERTENSION

        • Malignant HT is marked HT with retinal haemorrhages, exudates or papilloedema
        • Hypertensive encephalopathy is the presence of signs of cerebral oedema caused by breakthrough hyperperfusion from severe and sudden rises in BP

        Mechanism:

        • With mild to moderate elevations in BP above normal the initial response is arterial vasoconstriction --> tissue perfusion maintained at constant level
        • With more severe elevations in BP, autoregulation fails --> vasodilation -->rise in pressure in arterioles and capillaries --> damage to vascular wall --> narrowing or obliteration of vascular lumen
        • In the brain breakthrough vasodilation leads to the development of cerebral oedema and hypertensive encephalopathy
        • BP at which vascular damage occurs depends on baseline BP
        • If normally hypertensive, pt will have arteriolar hypertrophy that minimises transmission of pressure to the capillaries so malignant HT will occur at higher levels (eg: DBP >120)
        • If usually normotensive, malignant HT can occur with DBP >100
        • Patients with impaired autoregulation may also develop malignant HT at relatively low BPs

        Clinical Manifestations:

        • Retinal haemorrhages and exudates (representing ischaemic damage and leakage of blood/plasma from affected vessels) and papilloedema
        • Malignant nephrosclerosis --> ARF, haematuria and proteinuria
        • Neurological symptoms due to bleeding, lacunar infarcts or hypertensive encephalopathy
        • Hypertensive encephalopathy = insidious onset of headache, nausea, vomiting followed by non-localising neurological symptoms such as restlessness and confusion --> SZ, coma if not treated
        • MRI (T2): oedema of white matter of the parieto-occipital regions = RPLS
        • When MRI reveals primarily pontine abnormalities the condition is called hypertensive brainstem encephalopathy

        Treatment:

        • Nitroprusside infusion (first choice): arteriolar and venous dilator
          • Acts within seconds
          • Duration of action 2-5 mins
          • Potential for cyanide toxicity limits prolonged use, esp in renal impairment
            OR
        • Diazoxide IV                 OR
        • Hydralazine IV               OR
        • Clonidine IV or IM
        • Oral agents can be used if less urgent – nifedipine, captopril, amlodipine, felodipine, methyldopa, prazosin
        • Risk of ischaemia if BP lowered too much

        Aim of Treatment:

        • Initial goal is to reduce BP by no more than 25% in first 2 hours
        • Then aim about 160/100 within 2 to 6 hours
        • More aggressive hypotensive therapy is unnecessary and may cause ischaemia
        • Once BP controlled, change to oral therapy
        • Aim DBP 85 – 90 mmHg over 2-3 months
        • Often associated with a transient decline in renal function

        Prognosis:

        • Most patients have moderate to severe acute and chronic vascular damage so at risk of vascular disease
        • 90% survival

        Answer: A

        REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME

        • Not always reversible
        • Not always confined to the white matter
        • Clinical syndrome of:
          • Insidious onset of headache (usually constant, non-localised)
          • Confusion
          • Decreased consciousness
          • Visual changes (hemianopia, neglect, auras, hallucinations etc)
          • Seizures
          • Associated characteristic MRI findings of cerebral white matter oedema
        • Need to distinguish from ischaemic stroke as treatment very different (can do DWI on MRI – infarct hyperintense)

        Pathogenesis:

        • May be due to autoregulatory failure with malignant HT or cerebral ischaemia due to reactive focal vasoconstriction (autoregulatory failure more likely)
        • May also be associated with endothelial dysfunction
        • Combination of acute hypertension and endothelial damage results in hydrostatic oedema w leakage of serum through capillary walls, protein extravasation and fibrinoid necrosis
        • More likely in white matter as grey matter more tightly packed
        • Not sure why the posterior brain is involved more

        Causes:

        • Hypertensive encephalopathy
        • Acute or chronic renal diseases
        • Vasculitis – SLE, PAN
        • Endocrine disorders – phaeochromoctoma, primary aldosteronism
        • Porphyria
        • Thermal injury
        • Cocaine/amphetamines/other stimulants
        • Eclampsia
        • TTP
        • HUS
        • Hypercalcaemia
        • Immunosuppressants
        • Other medications such as HAART, EPO, GCSF, IVIg
        • Blood transfusions
        • Contrast exposure

        Topic

        Neurology: headache | raised intracranial pressure

         

         

        Question 82 top

        Question 83 top Download PDF

        Which of the following antibiotics would be the most appropriate choice for the treatment of a vancomycin-resistant Enterococcus faecalis bloodstream infection?
        A. Cefoxitin.
        B. Linezolid.
        C. Amikacin.
        D. Tobramycin.
        E.Rifampicin.

        Tobramycin and amikacin are both aminoglycosides and have very similar spectrum to gentamicin (ie. mainly gram negatives).

        Cefoxitin is a moderate spectrum cephalosporin. It is not effective against enterococcus (even vancomycin-sensitive strains). MSSA has intermediate sensitivity to it and MRSA is resistant to it.

        None of the cephalosporins cover enterococcus at all.

        Rifampicin is good for MRSA but does not cover enterococcus at all.

        To cover enterococcus faecalis need to use ampicillin or piperacillin.
        To cover enterococcus faecum need to use piperacillin.

        To cover VRE need to use linezolid which covers basically all the gram positive organisms but not one gram negative and few anaerobes. Answer: B

        Reference: AMH

        Topic

        Pharmacology: infections

        ID: hospital-acquired infection

         

        Question 84 top Download PDF

        A previously well 46yo woman presents acutely unwell with right iliac fossa pain and fever. A laparotomy is planned.

        The following pre-operative results are obtained:

                        Haemoglobin                                    124 g/L                                  [113-159]
                        WCC                                                 15.3 x 109/L                        [3.9-12.7]
                        Platelet count                                   150 x 109/L                          [150-396]

                        APTT                                                  56 seconds                          [26-38]
                        APTT mixing study
                             (1:1 mix, patient plasma with normal plasma)               48 seconds

                  Prothrombin time-INR                         1.2                                          [1.0-1.3]
                        Fibrinogen                                     4.5 g/L                                   [2.0-4.0]
                        D-dimer                                           0.2                                          [<0.2]
                        Thrombin clotting time                    18 seconds                          [<24]

        Which of the following is the most likely cause of the prolonged APTT?

          A. Disseminated intravascular coagulation

          B. Heparin contamination

          C. Lupus inhibitor

          D. Factor XI deficiency

          E. Haemophilia carrier

          APTT used to asses intrinsic pathway (prekallikreinm HMWK, factors XII, XI, IX and VIII) and final common pathway (factors II, V, X and fibrinogen)

          Prolonged in deficiency of (or inhibitor to) any clotting factors except VII

          Also certain lupus anticoagulants cause APTT prolongation in vitro (but associated with risk of thrombosis)

          Lupus anticoagulant activity can be identified when a prolonged APTT is not reversed by diluting the patient’s plasma with normal plasma 1:1 à this procedure will reverse the clotting abnormality associated with factor deficiencies

          Prothrombin time measures the extrinsic pathway (tissue factor and factor VII) and the common pathway

          Prolonged in vitamin K deficiency, liver disease, deficiencies of factors VII, X, II, V or fibrinogen, antiphospholipid antibodies

          Thrombin time measures final part of clotting cascade – conversion of fibrinogen to fibrin

          Prolonged with heparin, direct thrombin inhibitors (such as hirudin or argatroban) or heparin-like compounds (danaparoid), fibrin/fibrinogen degradation products, hypofibrinogenaemia, dysfibrinogenaemia or hyperfibrinogenaemia, bovine thrombin antibodies, high concentration of serum proteins as in multiple myeloma and amyloidosis

            • DIC manifests as bleeding, organ dysfunction and thromboembolism
            • Fibrinogen decreased, D-dimer elevated, increased INR, increased APTT

            Topic

            Haematology: Coagulation

             

            Question 85 top

            Question 86 top

            Question 87 top

            Question 88 top

            Question 89 top Download PDF

            A 30yo man presents with a dry cough and shortness of breath. His CXR is shown below.

            The most likely diagnosis is:
            A. Pneumonia
            B. Pericardial effusion
            C. Thymoma
            D. Non-small cell lung cancer
            E. Lymphoma

            MEDIASTINAL MASSES

            Anterior mediastinum:

            • Thymomas
            • Lymphomas
            • Teratomatous neoplasms
            • Thyroid masses
            Middle mediastinum:
            • Vascular masses
            • Lymph node enlargement from mets of granulomatous disease
            • Pleuropericardial and bronchogenic cysts
            Posterior mediastinum:
            • Neurogenic tumours
            • Meningocoeles
            • Meningomyelocoeles
            • Gastroenteric cysts
            • Oesophageal diverticular

            AGE DISTRIBUTION

            • In children neurogenic tumours and enterogenous cysts are most common
            • In adults neurogenic tumours, thymomas and thymic cysts are common
            • Lymphomas and germ cell tumours are most common between ages 20 and 40

            Answer E. Lymphoma
            Topic

            Respiratory - Mediastinal malignancy and benign mediastinal masses.

            Question 90 top

            Question 91top

            Question 92top

            Question 93top Download PDF

            A 16yo adolescent male presents with lethargy and lower respiratory tract infection. Physical examination shows him to be febrile, icteric and pale in addition to respiratory findings.

            Full blood examination shows:

                            Haemoglobin                                        67g/L                      [128-175]
                            Mean cell volume                                86fL                        [80-97]
                            White cell count                                  13.0 x 109/L          [3.9-12.7]
                                            Differential:
                                                            Neutrophils           10.2 x 109/L          [1.9-8.0]
                                                            Lymphocytes        0.8 x 109/L             [0.9-3.3]
                                                            Monocytes            1.6 x 109/L             [0.3-1.1]
                                                            Eosinophils            0.3 x 109/L             [0-0.5]
                                                            Basophils               0.1 x 109/L             [0-0.1]
                            Platelet count                                       390 x 109/L           [150-396]
                            Reticulocyte count                              213 x 109/L           [9-116]

            The blood film is shown below.

             

            The most likely cause of the anaemia is:

            1. Paroxysmal cold haemoglobinuria
            2. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
            3. Red cell aplasia
            4. Cold agglutinin haemolysis
            5. Sickle cell anaemia

             

            The raised reticulocyte count and jaundice suggest haemolytic anaemia – can immediately remove red cell aplasia from the list. Sickle cell anaemia is diagnosed in early childhood (and there are no sickle cells on film anyway).

             

             

            Table 93–2. Red Blood Cell Morphology in the Diagnosis of Hemolytic Anemia (Harrision’s)

            Morphology

            Cause

            Syndromes

            Spherocytes

            Loss of membrane

            Hereditary spherocytosis, immunohemolytic anemia

            Target cells

            Increased ratio of RBC surface area to volume

            Hemoglobin disorders: thalassemias, hemoglobin S, C, etc.; liver disease

            Schistocytes

            Traumatic disruption of membrane

            Microangiopathy, intravascular prostheses

            Sickled cells

            Polymerization of hemoglobin S

            Sickle cell syndromes

            Acanthocytes

            ?Abnormal membrane lipids

            Severe liver disease (spur cell anemia)

            Agglutinated cells

            Presence of IgM antibody

            Cold agglutinin disease

            Heinz bodies

            Precipitated hemoglobin

            Unstable hemoglobin, oxidant stress

            HAEMOLYSIS

            1. 3 categories:
              1. Molecular defect inside RBC (enzymopathies or haemoglobinopathies)
              2. Abnormal membrane structure and function
              3. Environmental factor (trauma, autoantibody)
            2. Hereditary or acquired

             

            1. Hereditary haemolytic anaemias due to membrane abnormalities:
              1. Hereditary spherocytosis
              2. Hereditary elliptocytosis
              3. Hereditary stomatocytosis
            2. Hereditary haemolytic anaemias due to RBC enzyme defects:
              1. Defects in Embden-Meyerhof pathway
              2. Defects in hexose-monophosphate shunt including G6PD deficiency
            3. Hereditary Haemoglobinopathies:
              1. Structural (HbS, altered O2 affinity, unstable Hbs)
              2. Thalassaemia
              3. Thalassaemia haemoglobin variants
              4. Hereditary persistence of fetal haemoglobin
              5. Acquired haemoglobinopathies (eg: toxic exposure, carboxyhaemoglobin)
            4. Acquired Haemolytic Anaemias:
              1. Entrapment (hypersplenism)
              2. Immune
                1. Warm-reactive (IgG) antibody
                2. Cold-reactive IgM antibody (cold agglutinin disease)
                3. Cold-reactive IgG antibody (paroxysmal cold haemoglobinurua)
                4. Drug-dependent antibody
              3. Traumatic
                1. Impact haemolysis
                2. Macrovascular – prostheses
                3. Microvascular – TTP/HUS, others
              4. Toxic effects on membrane
                1. Spur cell anaemia
                2. External toxins (eg: spider bites, metals)
                3. Paroxysmal nocturnal haemoglobinuria


             

            G6PD DEFICIENCY

            Epidemiology

            1. X-linked inherited disorder
            2. Primarily men affected but homozygous women found in some populations
            3. Carrier women can also have haemolytic attacks

             

            Pathophysiology

            1. G6PD enzyme catalyses the oxidation of glucose-6-phosphate to 6-phosphogluconate while concomitantly reducing NADP+ to NADPH
            2. NADPH is a required cofactor in many reactions and maintains glutathione in its reduced form
            3. Red cells rely on G6PD as it is the only source of NADPH
            4. Reduced glutathione acts as a scavenger for oxidative metabolites within the cells and converts hydrogen peroxide to water
            5. In G6PD deficiency the red cells are at risk of oxidative stress and rapid haemolysis can occur (eg: when exposed to oxidative drugs)

             

            Clinical Manifestations

            1. Variable
            2. Most often asymptomatic
            3. Can present with neonatal jaundice or acute haemolytic anaemia
            4. Haemolytic anaemia can be triggered by oxidative drugs, infection or ingestion of fava beans
            5. Gallstones common
            6. Splenomegaly may be present

            Diagnosis

            1. G6PD enzyme activity
            2. Usual signs of haemolysis during an acute attack
            3. Associated with Heinz bodies which are denatured haemoglobin

             

            Treatment

            1. Avoid precipitants including antimalarials, nitrofurantoin, ciprofloxacin, norfloxacin, vitamin K, sulfamethoxazole, mothballs

             

            SICKLE CELL ANAEMIA

            1. Mutant haemoglobin
            2. Most common form in Western world is Hb S
            3. Aries from mutation substituting thymine for adenine à valine instead of glutamine in Hb beta chain
            4. Resulting Hb forms polymers under deoxy conditions and has changes in solubility and molecular stability
            5. Under deoxy conditions, Hb S has decreased solubility, increased viscosity and forms polymers
            6. After recurrent episodes of sickling the membranes are damaged and cannot reoxygenate (irreversibly sicked cells)
            7. Cardinal signs:
              1. Haemolytic anaemia
              2. Painful vasoocclusive crises
              3. Multiple organ damage with microinfarcts
            8. Sickle cells cause vasoconstriction and microthrombi for a number of reasons:
              1. Express very late antigen (VLA)-4 which adheres to vascular cell adhesion molecules (VCAM)-1
              2. VCAM-1 upregulated by hypoxia and inhibited by NO (which is also a vasodilator)
              3. Hypoxia inhibits NO and free Hb scavenges NO
              4. Deformed sickle cells express CD18 which adheres to the endothelium
              5. Sickle cells also adhere to macrophages
              6. Sickle cells have increased IgG which plays a role in vasoocclusive crises by activating clotting factors (triggered by infection)

             

            Clinical Features

            1. Common in black population
            2. Presents in childhood with chronic haemolytic anaemia and painful vasooclussive crises
            3. Infants largely protected in first 6 months of life by HbF
            4. Crises can be triggered by infection, change in temperature or there may be no precipitant
            5. Severe deep pain in extremities
            6. Severe abdominal pain (resembling acute abdomen)
            7. May be accompanied by fever, malaise and leukocytosis
            8. Can last hours to days
            9. Anaemia is universal
            10. Aplastic crisis can occur with parvovirus B19 infection – infects RBC progenitor cells in BM à cessation of erythropoiesis
            11. Splenomegaly à infarcts àfibrosis à autosplenectomy à risk of infection with encapsulated organisms
            12. Hand-foot syndrome = dactylitis = swelling of dorsum of hands and feet, cortical thinning and destruction of metacarpal and metatarsal bones
            13. Acute chest syndrome = chest pain, tachypnoea, leukocytosis, pulmonary infiltrates (medical emergency)
            14. CNS involvement – stroke
            15. Haemosiderin deposits in myocardium, dilated ventricles, microinfarcts
            16. Gallstones
            17. Bone and joint infarctions à stunted growth, aseptic necrosis, chronic pain
            18. Microinfarcts of lungs, pulmonary HT (?2’ low NO)
            19. Loss of concentrating ability of kidneys
            20. Retinal vascular changes, proliferative retinitis
            21. Leg ulcers
            22. Priapism
            23. High rates of fetal loss

             

            Diagnosis

            1. Sickle cells on peripheral blood smear
            2. Hb electrophoresis

             

            Treatment

            1. Manage anaemia (balanced diet, Fe tablets if deficient, transfusions only in certain situations eg: acute chest syndrome, stroke)
            2. Manage pain (opioids)
            3. Avoid infections (vaccinations especially pneumococcal)
            4. Prevent and treat complications (eg: stroke)
            5. Acute vasooclusive crisis managed with IVT and analgesia, supportive care
            6. ?hydroxyurea
            7. ?BM transplant

             

            PAROXYSMAL COLD HAEMAGLOBINURIA

            1. Due to cold-reacting IgG antibody
            2. Does not cause much agglutination
            3. Readily fixes complement
            4. Antigen is P antigen on red cells which is present on RBCs of almost all people
            5. Occurs primarily in 2 situations:
              1. In children 7-10 days following a viral infection or following other infections including Mycoplasma pneumonia and Klebsiella pneumonia
              2. In adults PCH can occasionally occur in association with other autoimmune abnormalities and rarely in lymphomas or CLL – usually chronic, lasting several years
            6. As blood circulates to the peripheries and cools the antibody and complement are fixed to the RBC surface
            7. Complement cascade is completed when the RBCs are subsequently warmed to 37 degrees
            8. Results in lysis by complement, intravascular haemolysis, haemoglobinuria and haemosiderinuria

             

            Clinical Manifestations

            1. Cardinal features are haemolysis with dark urine (haemoglobinuria) beginning a few minutes to several hours after exposure to cold
            2. Constitutional symptoms, back pain, leg pain, abdominal cramps, chills and fever can occur
            3. Raynaud phenomenon  and urticaria can also occur
            4. Haemolysis does not persist once cold exposure ended
            5. Spherocytes, erythrophagocytosis by neutrophils can be seen on film
            6. Degree of anaemia variable, can be severe in childhood, usually moderate in adults
            7. Coombs’ test positive during haemolytic episode but may be negative between crises

             

            Diagnosis

            1. IgG antibody that reacts with red cells at reduced temperature but not at 37 degrees
            2. Radiolabeled monoclonal anti-IgG is more sensitive

             

            Treatment

            1. Treatment of acute attack in children is supportive
            2. Warm environment
            3. For chronic condition – prednisolone, or if this fails, cyclophosphamide or azathioprine
            4. Avoid cold environments

             

            COLD AGGLUTININ HAEMOLYSIS

            Pathogenesis

            1. IgM antibodies generally react with polysaccharide antigens on the RBC surface at lower temperatures
            2. IgG antibodies generally react at body temperature (and are therefore associated with warm agglutination)
            3. A single IgM can bind 2 RBCs together which can result in agglutination
            4. When blood circulates to colder parts of the body interaction occurs between the cell and antibody leading to complement activation and haemolysis
            5. Amount of haemolysis varies depending on the amount of antibody in the plasma, the thermal amplitude, the degree of inhibition of antibody binding by C3d (present on red cell surfaces) and the degree of complement fixation
            6. Antigens are polysaccharides present on all red cells
            7. Antibodies are produced in response to either infection or paraneoplastic or neoplastic growth of a single immunocyte clone
            8. Occur commonly with mycoplasma pneumonia and infectious mononucleosis, less commonly with viral infections
            9. Peak titre usually occurs 2-3 weeks after onset of infection with haemolysis more likely to occur at this time
            10. Antibodies due to paraneoplastic causes, however, remain in circulation over long periods à chronic cold agglutinin disease

            Clinical Features

            1. Anaemia
            2. Blue peripheries
            3. Haemolysis
            4. Splenomegaly
            5. Look for underlying lymphoma

             

            Laboratory Findings

            1. Anaemia
            2. Haemolysis
            3. Coomb’s positive
            4. Cold agglutinins

             

            Treatment

            1. Avoid cold
            2. Cyclophosphamide, steroids
            3. Rituximab (?)
            4. Plasmapheresis

             

             

            The answer is B – G6PD deficiency but I don’t know why it couldn’t be cold agglutinin or paroxysmal cold haemoglobinuria associated with mycoplasma infection. Perhaps because the haemolysis tends to occur a week or two after the infection with cold haemolysis disorders?

             

            Topic

            Haematolgy: Anaemia

            Question 94top

            Question 95top Download PDF

            A 45yo man with a long history of asthma presents to hospital with acute shortness of breath, requiring intubation and ventilation for respiratory support. A chest X-ray reveals right upper lobe consolidation. He is treated with intravenous methylprednisolone, metronidazole and ceftriaxone with his clinical course complicated by renal and cardiac failure requiring inotropic support and a short period of dialysis. Attempts to wean ventilation support are unsuccessful. Nerve conduction studies reveal the following:

            Nerve

            Distal latency

            Conduction velocity

            Amplitude

            Right peroneal motor

            5.3ms [<6.1]

            40m/s [>40]

            0.5mV [>2]

            Right tibial motor

            5.0ms [<6.6]

            42m/s [>41]

            1.0mV [>4]

            Right sural sensory

            4.1ms [<4.5]

            -

            9µV [>6]

            Needle examination reveals fibrillation potentials with small motor unit potentials in all muscles examined.

            The most likely diagnosis is:

            A. Critical illness myopathy

            B. Critical illness neuropathy

            C. Acute polymyositis

            D. Acute inflammatory demyelinating polyneuropathy

            E. Steroid myopathy

            • Conduction velocity is normal so demyelination is unlikely
            • Amplitude is reduced in motor but not sensory axons – axonal degenerative neuropathy is unlikely to be purely motor
            • Also, reduced amplitude is only seen when axonal degenerative neuropathy is advanced
            • Earlier in axonal neuropathies collaterals develop to the muscle fibres so the amplitude is normal
            • Small motor unit potentials suggest myopathy
            • Fibrillations are common in neuropathies but can also occur in myopathy
            • This is therefore most likely to be a myopathy
            • Critical illness myopathy is the most common cause in ICU

            DIFFERENTIAL DIAGNOSIS

            • Critical illness myopathy and critical illness neuropathy are major causes (or combination of the 2)
            • Other acute and subacute myopathies can occur including rhabdomyolysis, cachectic myopathy and rarely GBS

            CRITICAL ILLNESS MYOPATHY

            • Typically associated with IV glucocorticoids (rare if not exposed to IV steroids)
            • Begins several days after treatment initiated
            • Flaccid quadriparesis, failure to wean from ventilation
            • Sensation normal
            • Facial muscle weakness can also occur but EOM weakness is rare
            • NCS show reduced amplitude of motor pathways, sensory pathways normal
            • EMG - fibrillation common, short duration, low amplitude and sometime polyphasic MUPs
            • Can be distinguished from critical illness neuropathy by preservation of sensory function
            • Treatment is supportive
            • Recovery over weeks to months
            • More common when non-depolarising neuromuscular blocking agents also used
            • Muscle biopsy shows loss of thick filaments and atrophic fibres

            Major Diagnostic Features:

            • Sensory nerve amplitudes > 80% lower limit of normal in two or more nerves
            • Needle EMG with short-duration, low-amplitude MUPs with early or normal full recruitment with or without fibrillation potentials
            • Absence of a decremental response on repetitive nerve stimulation
            • Muscle histopathologic findings of myopathy with myosin loss

            Supportive Features:

            • Motor amplitudes <80% lower limit of normal in 2 or more nerves without conduction block
            • Elevated CK
            • Demonstration of muscle inexcitability

            Answer: A

            CRITICAL ILLNESS NEUROPATHY

            • Typically associated with prolonged illness, usually sepsis and MOF
            • May be suspected when unable to wean from ventilator
            • Exact mechanism unclear
            • Diffuse weakness, decreased reflexes, distal sensory loss
            • Cranial nerves intact
            • NCS – diffuse symmetric, distal axonal sensorimotor neuropathy
            • EMG/NCS - low amplitude motor and sensory action potentials
            • Fibrillations develop over time
            • CK normal
            • Muscle biopsy shows neurogenic atrophy
            • Treatment is supportive
            • Spontaneous recovery usually occurs over weeks to months.

            Diagnostic Criteria:

            • Setting of critical illness, particularly if complicated by sepsis, MOF and SIRS
            • Difficulty weaning from ventilator that is not related to cardiopulmonary causes
            • Possible limb weakness
            • Electrophysiological evidence of axonal motor and sensory polyneuropathy

            Electrophysiological Studies:

            • Sensory and motor nerve amplitudes <80% lower limit of normal in 2 or more nerves on NCS
            • Absence of conduction block of F-waves
            • Needle EMG with reduced recruitment of normal motor unit potentials (early) followed by fibrillation potentials and reduced recruitment of long-duration, high-amplitude MUPs (after weeks)
            • Absence of decremental response on repetitive nerve stimulation

             

            Supportive features

            • Normal CSF protein and normal serum CK

             

            C – Polymyositis is one of the inflammatory myopathies – others are dermatomyositis and inclusion body myositis. Usually present with progressive muscle weakness. Rare for respiratory muscles to be involved in acute cases. Likely autoimmune process. CK always elevated in PM. Diagnosis of exclusion. EMG shows short duration, low amplitude polyphasic potentials on voluntary action and fibrillations, complex repetitive discharges and positive sharp waves at rest.

            D – GBS manifests as a rapidly ascending areflexic motor paralysis with or without sensory disturbance. Autoimmune basis. Rare in this setting.

            E – Glucocorticoid-related myopathies can occur with chronic treatment or as “acute quadriplegic” myopathy secondary to high dose IV steroids (seems to be the same as A). In chronic setting, proximal muscle weakness develops, accompanied by cushingoid manifestations. EMG normal, muscle biopsy shows preferential type 2 muscle fibre atrophy.

             

            SENSORY NERVE CONDUCTION STUDIES

            • Sensory stimulus leads to generation of action potential = sensory nerve action potential (SNAP)
            • Number of functioning neurons is estimated by the amplitude of SNAP
            • State of myelin of axons is estimated by conduction velocity of SNAP
            • In degenerative neuropathies, primary feature is reduced amplitude of SNAP (eg: diabetic neuropathy)
            • In demyelinating disorders or nerve entrapment velocity is reduced (eg: GBS or carpal tunnel syndrome)
            • In radiculopathies, both amplitude and conduction velocity are normal as the lesion in proximal to the cell bodies of the axons (in the dorsal root ganglion)

             

            MOTOR NERVE CONDUCTION STUDIES

            • The motor axon is stimulated and the action potential produced is measured in the muscle
            • The amplitude of the muscle action potential indicates the number of activated muscle fibres
            • Distal latency is the time taken for the action potential to result in muscle contraction – ie. AP travels down axon, acetylcholine released into neuromuscular junction and muscle action potential is generated
            • Therefore slowing of the distal latency could be due to a problem in the axon or in the neuromuscular junction
            • In axonal degenerative neuropathies, motor nerve conduction studies are not significantly abnormal until the process is moderately advanced
            • There may be slight slowing of conduction and prolongation of distal latency due to loss of the largest axons
            • Early in the disease collateral axons form to supply denervated muscle fibres – thus the action potential produced in the muscle remains normal
            • Only when the disease is advanced and denervation is occurring faster than collaterals can develop does the amplitude decrease
            • Important to test for sensory conduction in cases of possible degenerative neuropathy, otherwise many will be missed
            • In demyelination, slow conduction and prolongation of distal latency is seen
            • In radiculopathy the motor NCS is usually normal but if there is sufficient axonal loss there might be slight slowing of velocity
            • Focal neurapraxic lesions (ie. compression of nerve such as in carpal tunnel) causes slower conduction and decreased amplitude, but nerves distal to the lesion will be normal
            • Nerves proximal to the lesion will show normal velocity but reduced amplitude
            • Note that myopathy can cause decreased muscle action potentials in motor NCS

             

            EMG

            • Best test to distinguish between neuropathic and myopathic processes

             

            Myopathic:

            • Small, short duration polyphasic muscle APs
            • Motor units recruited in excessive numbers

             

            Neuropathic:

            • Muscle denervation – reduced number of motor units activated but increased rate of firing of remaining motor units
            • Collateral supply leads to large polyphasic muscle APs
            • Other features suggestive of denervation are fasciculations, positive sharp waves, complex repetitive discharges and fibrillations (but this can also occur in myopathy)

             

            DEMYELINATION

            • Slow nerve conduction velocity
            • Marked prolongation of distal latencies
            • Conduction block = major decrease in muscle AP on proximal stimulation compared to distal stimulation
            • Dispersion of evoked muscle APs

            AXONAL NEUROPATHY

            • Decreased amplitude in sensory nerves and in motor nerves late in disease
            • Relative preservation of velocity

            NERVE COMPRESSION

            • Decreased amplitude and velocity at site of lesion

            RADICULOPATHY

            • Normal

            So my suggestion for this type of question is to:

            • Look at the EMG and decide whether it is neuropathic or myopathic
            • If myopathic – don’t need to worry about the NCS
            • If neuropathic – look at the velocity in particular

            • Slow velocity suggests demyelination or nerve compression
              • Amplitude reduced in compression
              • Amplitude normal in demyelination
            • Normal velocity suggests axonal degenerative neuropathy
              • Near normal amplitude may indicate mild to moderate diseae
              • Reduced amplitude may suggest severe disease
              • Sensory amplitude should be low

            Topic

            Neurology: Myopthies

            Question 96top Download PDF

            A 32yo woman if found to have high blood pressure (180/105mmHg) at an insurance medical examination. She is asymptomatic. Clinical examination is normal. Similar blood pressure readings are recorded on 2 follow-up examinations.

            Serum biochemistry shows:

                        Sodium                         146mmol/L                    [134-146]
                        Potassium                    2.5mmol/L                     [3.4-5.0]
                        Creatinine                      0.08nmol/L                    [0.06-0.12]

            Which of the following investigations is the most appropriate next step?

            A. 24 hour urinary electrolytes

            B. Upright plasma aldosterone to renin ratio

            C. Captopril renogram

            D. Adrenal CT scanning

            E. 24 hour urinary aldosterone

            PRIMARY HYPERALDOSTERONISM

            • Causes
              • Adrenal adenoma
              • Bilateral idiopathic adrenal hyperplasia
              • Familial forms of primary hyperaldosteronism
              • Adrenal carcinoma
            • Conn’s syndrome refers specifically to an adrenal adenoma producing excess aldosterone
            • More common in women, usually occurs between 30 and 50yrs
            Presentation
            • Spontaneous hypokalaemia, especially if associated with hypertension
            • Severe and/or persistent hypokalaemia when taking low to moderate doses of K-wasting diuretics
            • Refractory HT
            Symptoms
            • HT and associated complications
            • Muscle weakness
            • Abdominal distension
            • Ileus from hypokalaemia
            • Oedema is NOT a feature and if present suggests an alternative diagnosis
            Investigations

            - Plasma rennin activity (PRA) is very low in patients with primary mineralocorticoid excess
            - Raised PRA (in associating with HT and hypokalaemia) is seen with diuretic therapy, renovascular or malignant hypertension and rarely rennin-secreting tumours
            - When PRA is suppressed and plasma aldosterone concentration (PAC) is raised, this suggests primary hyperaldosteronism
            - Secondary hyperaldosteronism (eg: renovascular disease) should be considered when both PRA and PAC are increased
            - An alternate source of mineralocorticoid receptor stimulation (eg: hypercortisolism, licorice ingestion) should be considered when PRA and PAC are both suppressed
            - Test should be performed at 0800
            - Most anti-hypertensives can be continued and postural stimulation is not required
            - Cannot interpret test if patient on spironolactone or eplerenone
            - ACE-Is may falsely elevate PRA so a low PAC/PRA ration does not exclude primary hyperaldosteronism but if PRA is very low/undetectable this makes PH very likely

            • 24 hour urine no longer used to diagnose PH
            • Used if above blood tests do not show the expected results or if there is suspicion of surreptitious vomiting or laxative abuse
            • Inappropriate K wasting is defined as urinary K >30meq/day in a pt with hypokalaemia
            • An appropriately low rate of K excretion in the urine suggests extrarenal losses (eg: vomiting, diarrhoea) or diuretic treatment with the urine being collected after the diuretic effect has worn off
            • Aldosterone excretion can be measured with high values being consistent with primary hyperaldosteronism if the PRA is low
              • Elevate PAC/PRA ratio indicates either
                • PH (high PAC, low PRA)
                • Non-aldosterone mineralocorticoud excess (low PAC, low PRA)
              • To confirm the diagnosis, need to do aldosterone suppression testing
                • Sodium loading (orally or IV) to suppress aldosterone
                • Then collect 24 hour urine for aldosterone, sodium and Cr

              • Once diagnosis of PH is confirmed, need to differentiate adrenal adenoma (or rarely carcinoma) from bilateral idiopathic hyperplasia as treatment is different
              • Adenomas (30-60%) should be surgically removed if possible
              • Adrenal hyperplasia is generally milder and should be treated with an aldosterone receptor antagonist
              • CT or MRI are ok for initial investigation
              • >4cm unilateral mass suggests carcinoma
              • Can be difficult to differentiate adenomas and hyperplasia on imaging
              • Adrenal vein sampling – measuring aldosterone in samples of adrenal venous blood is gold standard to distinguish between adenomas and hyperplasia

              Correct answer is B – aldosterone:renin ratio.
              A – 24 hour urine no longer used to diagnose hyperaldosteronism. May be useful if blood tests inconsistent with diagnosis ?other cause.
              C – Captopril renogram is used in the diagnosis of renal artery stenosis
              D – CT scan may be useful once diagnosis of primary hyperaldosteronism is made on bloods/urine. Will help to determine cause – adrenal adenoma/carcinoma/hyperplasia
              E –Aldosterone suppression test, using 24 hour urinary aldosterone levels, is used to confirm the diagnosis of PH but is not the initial test

              SECONDARY HYPERTENSION

              • Consider secondary HT when pts develop HT under age 35 or over age 55
              • Causes are primarily:
                • Renal
                • Endocrine
              • Coarctation of the aorta is a further cause
              • Renal
                • Renovascular – stenosis of renal vessels leads to reduced flow and activation of rennin-angiotensin system à angiotensin II elevates blood pressure by vasoconstriction and by stimulation aldosterone which results in sodium retention
                • Renal parenchymal  - likely multiple mechanisms including rennin-angiotensin system and sodium retention
                • Renin secretion by juxtaglomerular cell tumours or nephroblastomas (rare)
              • Endocrine
                • Adrenal hypertension
                  • Primary hyperaldosteronism – sodium retention (in exchange for potassium loss in the renal tubule)
                  • Cushing’s syndrome - ?due to corticosteroids causing sodium retention
                  • Phaeochromocytoma – increased secretion of adrenaline and noradrenaline by tumour à excessive stimulation of adrenergic receptors à vasoconstriction
                • Acromegaly
                • Hypercalcaemia
                  • May be associated with HT due to direct vasoconstrictive effect
                  • Hyperparathyroidism can also lead to renal parenchymal disease with nephrolithiasis and nephrocalcinosis
              LABORATORY TESTS FOR EVALUATION OF HYPERTENSION
              • Urine for protein, blood and glucose and M/C/S
              • Haematocrit
              • Serum potassium
              • Serum Cr and urea
              • Fasting glucose
              • Cholesterol
              • TFT
              • Calcium and phosphate
              • ECG
              • CXR

              ADRENAL CORTEX

              • Produces 3 major classes of steroids:
                • Glucocorticoids
                • Mineralocorticoids
                • Adrenal androgens
              Aldosterone
              • Main effect is to regulate extracellular fluid volume and potassium balance
              • Aldosterone stimulates
                • Na-K ATPase pump which reabsorbs Na and excretes K into the urine
                • Na channels which passively reabsorb Na
              • Aldosterone secretion is controlled by
                  • Renin-angiotensin system
                  • ACTH
                  • Potassium
              • Via feedback from the macula densa, juxtaglomerular cells release renin in response to low ECF volume stimulates angiotensin stimulates aldosterone stimulates Na and water retention
              • Potassium directly stimulates aldosterone secretion
              • Physiological amounts of ACTH stimulate aldosterone acutely but this is not maintained unless ACTH is administered in a pulsatile fashion

              Topic

              Endocrinology:Endocrine causes of hypertension

               

              Question 97top Download PDF

              A 67 yo man with COPD has severe exertional dyspnoea and is receiving maximal inhaled bronchodilator therapy. He no longer smokes. Lung function tests are as follows:

              FEV1 0.54L (18% predicted)
              FEV1/FVC 19%
              TLC 7.96L (121% predicted)
              Residual Volume 5.09L (245% predicted)
              DLCO 6.1mL/min/mmHg (19% predicted)’

              Arterial blood gases on room air are as follows:
              PaO2 65mmHg
              PaCO2 52mmHg
              pH 7.36

              Which of the following is the most appropriate management to reduce this man’s exertional dyspnoea?

              A. Inhaled corticosteroids
              B. Pulmonary rehabilitation program
              C. Lung volume reduction surgery
              D. Supplemental oxygen
              E. Lung transplantation


              Pulmonary Rehabilitation:

              • Pulmonary rehabilitation is one of the most effective interventions in COPD and has been shown to reduce symptoms, disability and handicap and to improve function
              • This is achieved by:
                • Improving CV fitness, muscle function and exercise endurance
                • Enhance confidence and coping strategies, improve compliance and use of treatment devices
                • Improve mood by controlling anxiety and panic, decreasing depression and reducing social impediments

              Supplemental Oxygen:

              • Long-term continuous oxygen therapy is appropriate for patients who have PaO2 consistently < 55mmHg
              • Continuous oxygen can be used for patients with polycythaemia (Hb >170), pulmonary HT, right heart failure if stable PaO2 55- 59mmHg
              • Intermittent oxygen therapy has not been proven to be of benefit but can be considered for:
                • Pts who desaturate on exertion – may improve exercise capacity
                • Isolated pts prone to sudden life-threatening episodes while awaiting medical attention
                • Pts travelling by air
              • Nocturnal oxygen therapy can be used in pts who are hypoxaemic during sleep
              • That is if sats fall to < 88%
              • Need to exclude sleep apnoea
              Inhaled Corticosteroids:
              • May reduce exacerbations in certain patients and may reduce the rate of decline in quality of life
              • Has not been shown to improve symptoms as such

              So answer is B pulmonary rehabilitation.

              Topic

              Respiratory - Smoking-related chronic lung disease


              Question 98top

              Question 99top Download PDF

              A 30-year-old medical officer sustains a needle-stick injury while treating a trauma patient in the emergency department. She had undergone a three-dose course of hepatitis B vaccine 10 years earlier and one year following this course was documented to be hepatitis B surface antibody (HbsAb)-positive. However, on repeat testing (done as a result of this incident), the medical officer is now found to be HbsAb-negative. The source patient in the needle-stick injury is known to be an intravenous drug user, and is shown to be hepatitis B surface antigen (HbsAg)-positive on baseline serology. Human immunodeficiency virus (HIV) and hepatitis C serology are negative.

              In addition to counselling, which of the following is the most appropriate immediate action following this needle-stick injury?

              A. Booster hepatitis B vaccination.
              B. Hepatitis B immunoglobulin.
              C. Hepatitis B vaccine and hepatitis B immunoglobulin.
              D. No action required.
              E. Post exposure prophylaxis for HIV.

              The following body fluids pose a risk for blood borne virus transmission:

              1. Blood, serum, plasma and all biological fluids visibly contaminated with blood
              2. Pleural, amniotic, pericardial, peritoneal, synovial and cerebrospinal fluids
              3. Uterine/vaginal secretions
              4. Semen
              5. Laboratory specimens that contain concentrated virus

              HIV

              • Risk of transmission ~0.3% from blood exposure and ~0.09% after mucous membrane exposure
              • Risk increased if:
                • Injury with a device visibly contaminated with blood
                • Injury with a hollow bore needle that has been placed directly in an artery or vein of the source patient
                • Deep injury to the exposed person
                • Source patient with advanced HIV disease or high viral load

              Hepatitis B

              • Transmission rates 6-30% from patients who are HBsAg positive
              • Higher risk if source patient is HBVe antigen positive

              Hepatitis C

              • Risk of transmission 3-10% when source patient HCV antibody positive

              TESTING OF SOURCE PATIENT

              • Test for HIV antibody, HBsAg and HCV antibody
              • If HCV antibody positive,  test for HCV PCR for hepatitis C RNA (transmission much less likely to occur from a source who is PCR negative)

              MANAGEMENT OF EXPOSED PERSON
              Immediate Management:

              1. Remove contaminated clothing
              2. Wash area with soap and water and apply antiseptic
              3. Flush exposed mucous membranes with large amounts of water

              Evaluation of Exposure:

              • Examine for nature of exposure and counselling about the possibility of transmission

              Testing of Exposed Person:

              1. Assess risk of tetanus, consider tetanus immunoglobulin/Td vaccine
              2. Test for HIV antibody, HCV antibody and antibody to HBsAg
              3. If source patient found to be HIV, HBV and HCV negative, no further action generally required unless there is reason to suspect the person is seroconverting or at high risk of bloodborne viral infection at the time of the exposure
              4. If source is positive for one of these viruses, pregnancy testing should be offered to exposed women of childbearing age

              POST-EXPOSURE PROPHYLAXIS
              HIV

              1. HIV PEP recommended – for percutaneous exposure to potentially infectious blood or body fluids (increased risk of HIV transmission)
              2. HIV PEP offered (but not actively recommended) – for ocular mucous membrane or non-intact skin exposure to potentially infectious blood or body fluids (less increased risk of HIV transmission)
              3. HIV PEP not offered – for any exposure to non-bloodstained urine, saliva or faeces (not potentially infectious for HIV)
              4. Limited data on the efficacy of PEP for HIV and potential toxicity need to be considered (especially if pregnant – limited data on toxicity)
              5. Usually use ZDV and 3TC
              6. Need to consider the antiretroviral drug history of the source patient also
              7. Can consider addition of 3rd antiretroviral drug (usually a protease inhibitor) for exposures that are particularly high risk
              8. Didanosine and ddC currently have no role in PEP
              9. Commence therapy ASAP after exposure (but can be considered at any point after exposure)
              10. Continue therapy for four weeks

              HEPATITIS B

              1. If exposed person known to be immune to HBV (antiHBsAg ≥ 10mIU/mL) or if testing within 48hrs of exposure shows the exposed person to be immune à no further action required
              2. Testing for HBeAg and/or HBV DNA in persons who are HBsAg positive can assist in determining the risk of transmission
              3. If exposed person not immune to HBV or immune status in unknown, HBV immunoglobulin should be given within 48-72hrs
              4. In addition, HBV vaccine should be started from HCWs who have not received the vaccine

              HEPATITIS C

              1. There is no PEP for hepatitis C
              2. The option of interferon-ribavirin prophylaxis is under review
              3. Source should be tested for HCV RNA to determine risk of transmission

               

              COUNSELLING

              • Must not donate blood, semen, organs or tissue for 6 months
              • Should not share implements that could be contaminated with blood (eg: razors, toothbrushes)
              • Should be informed of risk of sexual and IV transmission of HIV and HBV for 6 months and should be counselled about safe sex and safe injecting
              • Should be advised about the remote risk of seroconversion of HIV up to 12 months after exposure

              Topic

              Infectious Diseases: Infection control in hospital and notification of infectious diseases

              Question 100 top Download PDF

              Which of the following anticonvulsant drugs is most likely to cause a clinically important interaction with lamotrigine?

              1. Clonazepam
              2. Gabapentin
              3. Vigabatrin
              4. Carbamazepine
              5. Sodium valproate

              Lamotrigine:

              • Stabilises presynaptic neuronal membranes by blocking voltage-dependent and use-dependent sodium channels
              • Used for partial and generalised seizures
              • Severe skin reactions (eg: Stevens-Johnson syndrome) can occur in 1 in 50-300 children and 1 in 1000 adults
              • More likely if also taking valproate or with rapid dose escalation of lamotrigine
              • Stop treatment immediately if rash occurs
              • Other common side effects include diplopia, dizziness, ataxia, headache, somnolence, hyperkinesia, nausea, vomiting
              • Rare side effects: multi-organ hypersensitivity syndrome, neutropaenia, thrombocytopaenia

               

              Carbamazepine decreases lamotrigine concentration, reducing its efficacy. Lamotrigine may increase the concentration of carabazepine epoxide, increasing adverse CNS effects of carbamazepine. May need to adjust doses

              Valproate increases lamotrigine’s concentration and toxicity, including rashes. Stop immediately if rash occurs.

              No interaction with clonazepam, gabapentin or vigabatrin.

              Correct answer is E – valproate.

              While carbamazepine can interact and cause changes in concentrations, the increased risk of severe skin reactions with valproate is much more clinically important.

              Topic:

              Neurology: Epilepsy

              Pharmacology: Neurology