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Question 1 top Download PDF

A 57-year-old man with hypercholesterolaemia and hypertension treated with simvastatin 80 mg/day and hydrocholorothiazide 25 mg/day develops myalgia and atypical chest pain.  A stress test and coronary angiogram are normal.  Diltiazem (controlled delivery) 180 mg/day is added for persisting hypertension.  Four weeks later he presents with shoulder and pelvic girdle pain and stiffness of seven to ten days duration and more recent ‘bloody discolouration of the urine’.  Examination reveals mild proximal weakness, normal neck flexor and extensor power, no difficulty with swallowing and no rash.
Laboratory tests reveal: 


2.7 mmol/L  [3.4-5.0]  
creatinine 80 μmol/L  [60-110]
bilirubin  24 μmol/L  [0-25]  
alkaline phosphatase (ALP) 48 U/L  [38-126] 
alanine transaminase (ALT) 112 U/L  [14-51]  
aspartate transaminase (AST) 259 U/L  [15-45]
gamma glutamyltranspeptidase (GGT) 38 U/L  [0-30]   
albumin     32 g/L  [33-48] 
total protein  65 g/L  [61-79]
creatine kinase (CK) 30 568 U/L  [<170]


The most likely diagnosis is:
A. hypokalaemic myopathy.
B. hypothyroid myopathy.
C. polymyositis.
D. simvastatin myopathy.
E. diltiazem myopathy.
Answer D (This question is probably more about myalgia than cardiology…..just realized it )

Approach to myopathy


  1. Inflammatory disorders
  2. Endocrinopathy: hypothyroidism or Cushing's syndrome
  3. Electrolyte disorders
  4. Metabolic myopathyies (disorders of carbohydrate, lipid and purine metabolism)
  5. Drugs and toxins
  6. Infections
  7. Various causes of rhabdomyolysis (trauma, seizures, alcohol, exertion)

Hypokalaemic myopathy

  • severe hypokalaemia can also cause muscle weakness, rhabdomylysis, and myoglobinuria
  • usually does not occur at K concentrations above 2.5 if hypokalemia develps slowly. 

Hypothyroid myopathy

  • hypothyroidim should always be excluded in patients with an unexplained increase in serum CK.
  • can range from asymptomatic elevation in serum CK, myalgia (with no enzyme rise) and proximal muscle weakness with CK rise that clinically resembles polymyositis. 

Polymyositis (onset of Sx is the difference)

  • T cell mediated muscle injury, idiopathic 
  • clinical suspicion of PM is raised by Sx of weakness, myalgia and elevation of serum levels of muscle enzymes(CK, LDH, AST, ALT)
  • also have to eliminate use of drugs causing myalgia eg. Colchicine, statin, alcohol, cocaine, hydroxychloroquine
  • onset is insidious with gradual worsening over a  period of several months

 Statin myopathy (uncommon)

  • affects 0.1% of patients
  • range from myalgias to myositis to rhabdomyolysis
  • time course
    • mean duration of onset of Sx from start of therapy: 6.3 months
    • mean time to resolution of Sx after discontinuation : 2.3 months

a) myalgias:

  • people complaining of muscle aches " benign myalgia"2-11% (no diff from placebo)
  • elevation in CK above normal - 30% (statin treated & placebo)
  • pts with new onset myalgias and easy fatiguability resolved with discontinuation of drug

b)  myositis

  • CK X 10 times normal + myalgia à 0.5%  of pts in large clinical trials
  • consider other causes of CK elevations : hypothyroidm, trauma

c) rhabdomyolysis (0.1%)

  • large trials, massive rhabdomyolysis with ARF not seen in pts who did not have other risk factors
  • RF: given concurrently with cyclosporine or gemfibrozil,
  • case reports of concurrent use with niacin, macrolide, digoxin, warfarin,     antifungal meds (drugs that intefere with CYP3A4)
  • muscle biopsy: myonecrosis without vasculitis or significant inflammation

Pravastatin (statin of choice with cyclosporine) & fluvastatin have less intrinsic muscle toxicity.  After CK has returned to baseline, pts may be tried on a statin less linkly to cause muscle toxicity with careful monitoring.
Up to date says that "Routine monitoring of serum CK not recommended but useful to obtain baseline CK level for reference prior to starting statin.  Pts should alerted to report the new onset of myalgias or weakness"

Diltiazem myopathy
Not in the literature.


Rheumatology - myositis

Pharmacology - cardiovascular

Cardiology - Coronary disease

Question 2 top Download PDF

A 65-year-old woman presents with a scalp laceration sustained after her second syncopal episode in seven days. She takes metoprolol, simvastatin and amitryptyline for hypertension, hypercholesterolaemia and depression respectively. Cardiovascular examination and all non-invasive cardiac investigations are unremarkable.
For which of the following ECG findings is electrophysiology testing least useful for management?
A. Polymorphic ventricular extrasystoles.
B. Paroxysmal atrial fibrillation (rate 110/minute).
C. Significant QT prolongation.
D. Second degree heart block during sleep.
E. Sinus bradycardia.

Answer C - significant QT prolongation

I have approached the question in these separate headings

  1. Evaluation of syncope
    • Causes of syncope
    • Types of syncope
    • History
  2. Investigations
  3. Indications of Electrophysiology testing
  4. Arrythymias particularly A and C
  5. Types of QT syndromes
  6. Treatment of QT syndromes

Causes of syncope

  1. cardiac - bradyarrythmia or tachyarrhythmia 23%
  2. Neurally mediated 58%- vasovagal
  3. Neurologic or psychiatric 1%
  4. Unexplained syncope 18%

Types of syncope

  1. Vasovagal syncope
    • precipitating events such as fear, severe pain, emotional distress,
      instrumentation or prolonged standing
  2. Situational syncope
    • occurs during or immediately after urination, defecation, cough or swallowing
  3. Orthostatic syncope
    • documentation of orthostatic hypotension ass with syncope or presyncope
  4. Cardiac ischemia related syncope

Most specific predictors of neurally mediated syncope --abdominal discomfort bf LOC, nausea anad diaphoresis during recovery phase

History is important

  1. Associated symptoms
  2. Prodrome
  3. Posititon
  4. Warninig -without warning? arrhythmic
  5. Preceding events
  6. Duration of symptoms.
  7. Recovery
    • prolonged recovery suggest a vagal event
    • significant neurologic changes or confusion during recovery period maybe due to stroke or seizure
  8. Witness
  9. Exertional syncope
    • ventricular tachycardia & obstruction (AS or HCOM)
  10. Age
    • neurocardiogenic more likely to occur among young
    • although long QT syncrome or HCOM can also occur in the young
  11. Pre existing medical conditions
  12. Injury
  13. Medications
  14. Eating
    • vagal surge upon swallowing can cause bradycardia and hypotension in predisposed patient


1) ECG :

According to European Society of Cardiology ECG abnormalities suggesting an arrhythmic cause of syncope

  1. Bifascicular block- LBBB or RBBB combinded with left anterior or left posterior fascicular block
  2. Inraventricular conduction abnormalities (QRS duration > 0.12s)
  3. Mobitz II second degree atrioventricular block
  4. Asymptomatic sinus bradycardia (<50bpm) or sinoatrial block
  5. Preeexcited QRS complexes (preexcitation syndrome)
  6. Prolonged QT interval
  7. ECG typical of Brugada s undrome (RBBB pattern with ST elevation in lead V1-V3)
  8. ECG suggestive of arrhythmogenic R ventricular dysplasia (- ve T waves in R precordium, opsilon waves and ventricular late potentials)
  9. Q waves suggesting MI
2) Holter monitor
3) Echocardiography
  • dx underlying structural heart disease eg. L ventricular dysfunction, HCOM, AS
4) Neurologic tests
  • eg EEG, CT brain, MRI brain, carotid Doppler U/S
  • testing was rarely useful.
5) Exercise testing
  • role in pts with a hx of exertion-related syncope or exercise induced
  • failure to shorten QT interval with exercise may be a sign of congenital prolonged QT syndrome when abnormality is not apparent on ECG
6) Upright tilt table test
  • indicated in cases of unexplained single syncopal episodes in high risk settings (potential risk of physical injury or occupational implications) or recurrent episodes after cardiac causes of syncope have been excluded.
  • if syncope is reproduced, attributable to neurocardiogenic
7) Brain natriuretic peptide
  • released from myocardial cells in response to volume expansiong and increased cardiac wall stress
  • a plasma BNP ? 40 identified cardiac syncope with a sensitivity and specificity of 82 and 92 %.
8) Electrophysiology
  • to determine presence of extra electrical pathway
  • extra electrical pathyway can be located and destroyed

Indications for cardiac electrophysiologic study

  • Diagnosis and management of bradyarrhythmias
  • To acquire corroborative data in symptomatic patients with episodic
  • Define the level of atrioventricular (AV) conduction abnormality
  • Diagnosis and management of tachyarrhythmias
  • To define the mechanism of narrow-complex tachycardia
  • To define the mechanism of wide-complex tachycardia
  • To reproduce the clinically documented narrow or wide-complex tachycardia for mapping and transcatheter ablation
  • Syncope of unknown etiology
  • To assess the sinus node function, the AV conduction, and to search for inducible sustained ventricular tachyarrhythmias in patients with syncope and organic heart disease

Arrythmias that I don't know much about:

1) Polymorphic ventricular extrasystoles

Extrasystole means premature beats therefore the polymorphic ventricular extrasystoles is also known as ventricular premature beats (VPB)
Caused by various different reentrant circuits
Varying coupling cycles between the sinus beats and the VPB

This question mentions significant long QT interval indicating that we know the diagnosis already and it is a medical emergency and should be treated straight away. Electrophysiology testing will not be required for diagnosis or treatment ie ablation)

2) Long QT syndrome:
  • congenital or acquired
  • ass with polymorphic ventricular tachycardia ie Torsade de pointes
Cause of acquired LQTS
  • medications ? antiarrhythmic drugs, nonsedating antihistamines, macrolide antibiotics, antipsychotics, antidepressants
  • electrolyte disorders ? hypokalaemia, hypomagnesemia, hypocalcemia, renal/liver impairment
  • structural heart disease
  • stroke, brain injury
  • HIV infection
  • eating disorders

Treatment of torsade de pointes due to long QT syndrome

Acquired LQTS

Magnesium sulfate (2g IV blous of 50% Mg sulfate)
Isoproterenol (2mcg/min titrate to achieve HR 100bpm)
Sodium bicarbonate (for quinidine-related arrhythmia)
Amiodarone (?)
Temporary pacing (atrial or ventricular) -- if don't respond to Mg sulfate

Congenital LQTS

Beta blockers
Mexiletine (?)
Permanent dual chamber pacemaker
Left cardiac sympathetic denervation (cardiothoracic sympathectomy)
Implantable cardioverter-defibrillator


Cardiology - Arrhythmias


Question 3 top Download PDF

Which of the following diabetic neurological complications is most likely to improve with time?

A. Diabetic amyotrophy.
B. Orthostatic hypotension.
C. Gustatory sweating.
D. Loss of deep tendon reflexes.
E. Painful peripheral neuropathy

Classification of Diabetic Neuropathies


  1. Distal, primarily sensory polyneuropathy
    • a.  Mainly large fibers affected
    • b. Mixed
    • c. Mainly small fibers
  2. Autonomic neuropathy
  3. Chronically evolving proximal motor neuropathy


  1. Acute or subacute proximal motor neuropathy
  2. Cranial mononeuropathy (Isolated to the 6th or 7th nerve palsies - diplopia)
  3. Truncal neuropathy(painful)
  4. Entrapment neuropathy in the limb

Symmetric polyneuropathy
            Most common

  • Sx:  distal sensory loss, hyperesthesia, paresthesia and dysesthesia
  • Pain typically involves the lower extremities and is usually present at rest and worsens at night
  • Acute ( last < 12 mths) and chronic form
  • Pain eventually subsides and disappears

Diabetic polyradiculopathy

  • Usually self- limited and resolve over 6-12 months
  • Severe disabling pain in the distribution of one or more nerve roots
  • Accompanied by motor weakness
  • Intercostal or truncal radiculopathy causes pain over thorax or abdomen
  • Involvement of lumbar plexus or femoral nerve cause pain in thigh or hip (ass with muscle weakness in hip flexors or extensors (diabetic amyotrophy)


  • Less common than polyneuropathy
  • Presents with pain and motor weakness in the distribution of single nerve
  • Vascular etiology suggested
  • 3rd CN involvement most common – diplopia
  • Others: IV, VI or VII (Bell’s palsy)

Autonomic Neuropathy

  • Involve cholinergic, noradrenergic and peptidergic (peptides such as pancreatic polypepetide, substance P)
  • Multi- systems: cardiovascular, GIT, genitourinary, sudomotor and metabolic systems

The most likely answers are A and E.  The painful peripheral neuropathy is in the acute stage and it will gradually become painless but that would not be considered as “improving”.  Therefore the answer is A : diabetic amyotrophy


Endocrinology: Diabetic Complications - neuropathy


Question 4 top Download PDF

Question 4 – Endocrinology

An 84-year-old 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 breast cancer at age 60 years. There is a past history of deep venous thrombosis (DVT). Dual-energy X-ray absorptiometry (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.

Definition of Osteoporosis
-           bone mineral density [BMD] 2.5 SD below the mean of young women

Risk factors for Osteoporosis

  • Female
  • Lack of estrogen
  • Long term steroid use
  • Hyperthyroidism
  • Hyperparathyroidism
  • Low 1,25-OH Vitamin D
  • Drugs- heparin, cyclosporine, vitamin A
  • Smoking
  • Menopause- related bone loss
  • Age related bone loss


  • Calcium/Vitamin D
  • weight training
  • Cessation of smoking


  1. Raloxifene
    • Selective Estrogen receptor Modulator (SERM)
    • MORE trial
      • 4 yrs of raloxifene treatment (60mg/day), Lumbar spine and femoral neck    BMD increased from 2.0 to 2.7% in raloxifene groups compared with placebo
      • reduced risk of vertebral # (ARR 1.3 per 1000)
      • Benefit of raloxifene on BMD and on nonvertebral # risk still measurable after 7 years of treatment
    • Side effects
      • No increase risk of endometrial Ca
      • Increased risk of incidence of thromboembolic disease (RR 3.1 compared with placebo)
      • No difference in overall stroke risk but ass with increased risk of fatal stroke
      • CHD
      • Hot flushes
      • Influenza- like symptoms
      • Peripheral edema
      • Leg cramps
  2. Bisphosphonate
    • Inhibit osteoclastic bone resoption
    • Poorly absorbed orally (1-5% of oral dose) and absorption is best on empty stomach
    • Plasma half life is approximate 1 hr
    • Persists in bone for lifetime
    • Relative risk of vertebral # 0.52
    • Relative risk of non vertebral # was 0.51
    • Side effects
      • Gastrointestinal symptoms
      • Slightly reduce serum Ca concentration
      • IV adminstration of bisphosphonates
        • transient flu-like febrile illness
        • Associated with transient lymphopenia 
        • bone pain - rapid infusion
      • Osteonecrosis of jaw
  3. Calcitonin
    • Binds to osteoclasts and inhibit bone resorption
    • shown to increase the BMD of vertebral spine by 1.5%
    • reduce risk of vertebral #.
    • Alendronate results in greater increases in spine and hip bone density compared with nasal calcitonin
    • Expensive
    • Used 1st line in patients with substantial pain from acute osteoporotic # because of analgesis actions
  4. Strontium ranealate
    • 2 atoms of stable strontium with an organic moiety (ranelic acid)
    • Oral agent
    • Decreases osteoclast differentiation and activity
    • Promotes bone formation by stimulating the replication of preosteoblasts

2 large clinical phase III trials
1.  Spinal Osteoporosis Therapeutic Invervention (SOTI)
2.  Treatment of Peripheral Osteoporosis  (TROPOS)

41% risk reduction for vertebral # over 3 years (NNT = 9)
16% risk reduction fo all non-vertebral # over 3 years

Tolerability & safety
nausea    (6.6% vs 4.3% placebo)
Diarrhoea (6.5% vs 4.6% placebo) --> resolved after 1st 3 months of therapy
Anti-fracture efficacy of strontium ranelate is in line with any conventional therapy in osteoporosis
Effective & well tolerated
Not commercially  available yet

Answer:  Vit D


Endocrinology: ostoeporosis


Question 5 top Download PDF

Which of the following is the strongest contraindication to the administration of influenza vaccine?
A. Egg anaphylaxis.
B. Previous local reaction to influenza immunization.
C. Recent pneumococcal immunization.
D. Pregnancy.
E. Immunodeficiency.

  • Acute respiratory illness caused by influenza A or B viruses
  • Influenza A undergo periodic changes in the antigenic characteristics of their envelope glycoproteins, the hemagglutinin and neuraminidase
  • 3 major subtypes of hemagglutinins (H1, H2 and H3) and 2 subtypes of neuraminidases (N1 and N2) 

In Australia, use inactivated vaccine Recommended for
1)  >age 65
2)  Aboriginal and Torees Strait Islander aged > 50
3)  Children and adults with chronic conditions - diabetes, cancer, cardiovascular disease, kidney disease , immune deficiency disorders and respiratory illness
4)  Hospital workers
5)  Residents of NH + long-term care facilities
6)  contacts of high risk patients


-  Anaphylaxis  to hens' eggs
-  Individuals who develop Guillain- Barre syndrome within 6 weeks after a previous influenxa immunization


-  influenza is ass with excess complications and death in pregnant woman
-  2006 ACIP report recommended influenza vaccination of pregnant woman regardless of stage of pregnancy and of women who will be pregnant during the influenza season. 
-  no adverse fetal effects demonstrated
-  maternal systemic reactions rare

HIV infection

-  Recommends vaccine for HIV infected patients
-  those with CD4 counts > 400/microL appear to be able to make antibody
-  2nd dose of vaccine does not seem to generate a response in those who do not make An following the 1st immunization
-  RCT in 102 HIV infection pt-  significant reductions in resp symptoms and in lab confirmed symptomatic influenza
-  LAIV appears safe in pts with CD4 counts > 200


-  Inactivated influenza vaccine can be administered safely to patients with immunosuppression
-  do not appear to exacerbate chronic neurologic diseases such as multiple sclerosis

Answer :  A

Up to date: Influenza vaccine


Infectious Diseases: common community-acquired infection :LRTI

Question 6 top

Question 7 top Download PDF

Prior to which of the following procedures is antibiotic prophylaxis most appropriate?
A. Colonoscopy with polypectomy.
B. Colonoscopy in a patient with a knee prosthesis.
C. Percutaneous endoscopic gastrostomy placement.
D. Endoscopic retrograde cholangiopancreatography (ERCP).
E. Band ligation of oesophageal varices.

1st instinct is to pick B.   That's not the answer.  

Principles of Antibiotic prophylaxis

  1. Significant risk of infection?
    • eg. Colonic resection
    • post operative infection even if uncommon would have severe consequence (eg. Iprosthetic implant)
  2. Adequate concentration of antimicrobial at time of contamination
    • vanc need 1-2 hr pre procedure
    • IM Ab given at time of premedication for surgery
    • Rectal metronidazole – 2-4 hrs pre
    • Oral tinidazole 6-12 hrs pre
  3. Single dose is sufficient but if procedure not completed within 3 hrs of initiating prophylaxis, a 2nd dose should be given
  4. Site of surgery
    •   Most contaminating organisms are aerobic Gram –ve (E.coli, Klebsiella) +/- anerobic Gram –ve organism (Bacteroides)
Upper GI procedures

There is no evidence to suggest that patients undergoing routine upper or lower gastrointestinal endoscopy require antibiotic prophylaxis. However , if patients undergoing procedures that have a higher incidence of bacteriaemia (eg. Those involving biliary tract, sclerotherapy, oesophageal dilatation or ERCP) may benefit, althought this is UNPROVEN.

Metronidazole + Cephazolin 1g  OR gent 2mg/kg at time of induction

Gastrostomy tube insertion

There is EVIDENCE that Ab prophylaxis reduces the risk of infectious complications.
Cephazolin or gent. 
Vancomycin if allergic to beta lactams or colonised with MRSA

Prosthetic joint infections (NO EVIDENCE)

Preoperative antimicrobial prophylaxis is standard for all patients undergoing joint replacement

Dental procedures:
  1. Not advised for antibiotic prophylaxis for pt with prosthetic joints to undergo routine dental procedures such as cleaning , scaling of teeth or filing of dental cavity
  2. Ab prophylaxis can be “considered in selected prosthetic joint pts who may be at increased risk for bacteremia in association with dental procedure (evidence is limited). 
    • high risk procedures:  extractions, periodontal procedures, dental implants, root canals
    • increased risk are pts with RA, SLE,immnosuppressive drugs or radiation, diabetes, HIV, malignancy or those within 2 yrs of joint replacement surgery
Urologic procedures (American Urological association + American Acadamy of Orthopedics)
  1. Most pts do not need Ab prophylaxis
  2. Prophylaxis can be considered in some pts especially if immunosuppresed or undergoing a high risk procedure  eg, lithotripsy  or surgery involving bowel segments


Endocarditis prophylaxis

Risk stratification for Endocarditis prophylaxis (ACCEPTED BUT UNPROVEN)

Little or no cost benefit in treateing patient with low risk abnormalities having procedures with low incidence of bacteraemia

  1. Patient characterisits
  2. High, low and intermediate risk cardiac lesion
  3. Specific procedures

Cardiac conditions that have a risk for infective endocarditis

High risk

Medium - risk

prosthetic heart valve

Acquired valvular dysfunction eg Rh heart disease in non-indegenous pts

Complex cyanotic Congenital heart disease

congenital cardiac malformations other than those definied as high-or low risk

Pulmonary shunts/ conduits

hypertrophic cardiomyopathy

Previous infective endocarditis

significant valvular/haemodynamic dysfunction associated with septal defects

mitral valve prolapse with clnically significant regurgitation


Acquired valvular dysfunction eg Rh heart disease in indegenous pts


Need for antibiotic prophylaxis for patients with a cardiac condition undergoing a dental or other procedures

Cardiac condition




High risk

Medium risk

Low risk

High risk




Medium risk




Low risk




 Most appropriate meaning the only one with evidence would be C. 

Reference: Antibiotic Therapeutic guidelins


Infectious Diseases: Principles of antibiotic prophylaxis.

Pharmacology: Infections

Question 8 top Download PDF

A 42-year-old man in the intensive care unit following a motor vehicle accident develops Staphylococcus aureus bacteraemia. He is commenced on vancomycin. Following the first infusion he develops a rash involving the face and upper trunk. His blood pressure falls to 100/70 mmHg.
What is the most appropriate next step?
A. Stop vancomycin, commence linezolid.
B. Stop vancomycin, commence dalfopristin/quinupristin.
C. Commence rapid desensitisation for vancomycin.
D. Continue vancomycin but slow the rate of infusion.
E. Continue vancomycin but premedicate with hydrocortisone.

Vancomycin hypersensitivity
  1. “red man syndrome” does not represent a true allergic response
  2. wide range reactions from localized skin reactions to generalized cardiovascular collapse
  1. IgE-mediated anaphylaxis
  2. “Pseydo-allergic” anaphylactoid reaction
Anaphylaxis (IgE MEDIATED)

Immunologically-mediated reactioni involving IgE antibodies
Rare with vancomycin
Occurs after subsequent administrations after dev of IgE antibodies to the drug

Anaphylactoid reaction (NON-IgE MEDIATED)

Non-immunologically mediated response
Can develop with 1st administration
Direct mast cell-mediated release of mediators such as histamine

  1. affected by opiates
  2. induce a dose or rate-related mast cell degranulation
  3. other agents include radiocontrast dye, muscle relaxants (potentiate mast cell degranulation)
Red Man syndrome

Most common adverse reaction, not life-threatening
Infusion-related histamine-like reaction
Characterized by flushing (upper body more that lower body), pruritus, chest pain, muscle spasms and occasionally hypotension
Frequency of syndrome:  10% - 70-90% (large range)
Prevention: pretreatment with anti-histamines
                   Slower infusion rates

Hypersensitivity Manisfestations
  1. Skin rash
    • Maculopapular/urticarial skin eruptions|
    • Vancomycin-related linear IgA bullous dermatosis (LABD)
    • IgA autoantibodies deposited in linear pattern along epidermal basement membrane
    • Rare but under-recognised
    • Discontinue vancomycin or try prednisolone
  2. Hematologic
    • leykocytosis
    • eosinophilia
    • neutropenia
    • thrombocytopenia
    • agranulocytosis (rare)
  3. Renal
    • 5 pts developed acute interstitial nephritis

RMS is the most common reaction but does not represent true hypersensitivity, better to distinguish RMS from hypersensitivity reactions to avoid falsely labeling a pt as allergic or discontinuing the drug unnecessarily.

  • Histamine vs tryptase levels
  • no replicable test for differentiating true hypersensitivity from anaphylactoid reactions to vancomycin
  • if tryptase levels are high, greated likelihood that reaction is IgE-mediated.


  1. Severe symptoms:  bronchospasm, respiratory distress, hypotension
    • discontinue vancomycin
  2. RMS
    • slow infusion rate
    • treatment with antihistamine
    • if reactions do not disappear with measures, cease vancomycin
    • consider desenzitization procedures

Alternative treatments to vancomycin

  1. Quinupristin-dalfopristin
    • used for tx of vancomycin resistant enterococcal infections and complicated skin infections due to MSSA
    • synergy against MRSA when quinupristin-dalfopristin combined with vancomycin
    • overall response rate is 71%
    • adverse reactions: arthralgia, myalgias, nausea and hyperbilirubinemia
  2. Linezoid
    • bacteriostatic antisteaphylococcal agent
    • used for nosocomial pneymonia and complicated skin infections 
    • excellent tisue distribution and taken orally as well as IV
    • added advantage of inhibiting bacterial toxin production
  3. Daptomycin
    • new class of antibiotics (cyclic lipopeptides)
    • disrupt bacterial membrane function
    • approved for use in complicated skin and soft tissue infections and bacteremia with or without endocarditis due to S.aureus
    • cannot be used for gram +ve pneumonia as does not achieve sufficiently high concentrations in resp tract and it is inactivated by surfactant
  4. Tigecylcin
    • novel glycylcycline antibiotic
    • strong activity against gram +ve, gram –ve, aerobic, anaerobic and atypical bacterial species (VRE, MRSA, penicillin resistant streptococcus pneymoniae)
    • approved for complicated skin infections and complicated intraabdominal infections but not approved for use in bloodstream infections
  5. Teicoplanin
    • same spectrum of activity as vancomycin
    • less side effecets
    • teicoplanin compared to linezolid- no sig difference in clinical success or microbiological success

Back to the Question

This is a tricky question once again, as the patient develops a rash in his upper trunk and also hypotension.  It does sound like red man syndrome although having hypotension would be a more severe form of RMS.

Quote from Up to Date
“The syndrome may be effectively prevented by pretreatment with anti-histamines [13], and slower infusion rates of vancomycin may reduce the frequency and severity of the reactions. One study in 10 normal volunteers analyzing histamine levels, occurrence and severity of RMS, and vancomycin infusion time found a higher incidence of RMS and increased severity when vancomycin was infused over one hour compared to when the same volunteers received the drug over two hours; peak plasma histamine levels and the total release of histamine were greater during the one-hour infusion [15].”

Answer D – Slow infusion rate down.

Up to date: Vancomycin hypersensitivity


Pharmacology: Infections


Question 9 top Download PDF

A previously well 37-year-old man presents with lethargy and easy bruising over several weeks. Physical examination is unremarkable apart from occasional bruises.
His full blood examination shows:
haemoglobin 125 g/L [128-175]
mean cell volume (MCV) 82 fL [80-97]
white cell count 8.8 x 109/L [3.9-12.7]
(normal white cell differential)
platelets 1060 x 109/L [150-396]
His blood film is shown below.

The most likely diagnosis is:
A. essential thrombocythaemia.
B. occult haemorrhage.
C. primary myelofibrosis.
D. occult carcinoma.
E. chronic myeloid leukaemia.


Diffentials for elevated platelet count


Essential thrombocythaemia
Another myeloproliferative disorder –

  • Polycythaemia Rubra vera
  • CML


Iron deficiency anaemia
Severe haemolysis
Infection, inflammation

Essential thrombocythaemia
Definition: persistent elevation of peripheral blood platelet count as a result of increased marrow production in the absence of a systemic cause of thrombocytosis

Clinical features

  1. Thrombosis- both arterial (peripheral vessels with gangrene of toes, coronary and mesenteric arteries) and venous (Budd-Chiari syndrome, DVT)
  2. Asymptomatic (20%)
  3. Excessive haemorrhage (spontaneously or  traumatic)
  4. Splenomegaly (30%) and in other atrophied because of infarction but massive splenomegaly is more characteristic of other myeloproliferative disorders

No clonal marker for this disorder, clinical criteria have been proposed to distinguish it from other chronic myeloproliferative disorders which may also present with thrombocytosis

Laboratory features

    • Platelets are >1000 X 10 9/L
    • Raised red or WCC (30%)
    • Blood film: platelet anisocytosis with circulating megakaryocyte gragments
    • Autoinfarction of spleen causes changes in red cells – target , Howell/Jolly bodies)
    • JAK2 mutation present in 30 – 50%
    • Serum uric acid raised
    • Serum LDH raised
    • Bone marrow: hypercellular with increased number of megakaryocytes 


    1. Chemotherapy
    2. Hydroxyurea to maintain platelet count below 600 X 10 9/L
    3. Alpha interferon and oral anagrelide
      • Effective but more S.E
    4.  Asprin (75mg) daily
      • Except those with haemorrhage


    • Median survival more than 20years
    • Main cause of morbidity and mortality: thrombosis and haemorrhage
    • Transformation to AML may occur


    Chronic myeloid leukaemia

    Lab findings

    • Raised WCC (50 X 10 9/L) – mainly neutrophils and myelocytes
    • Basophils prominent
    • Platelet count may be raised
    • Raised serum uric acid
    • Bone marrow aspirate: hypercellular with raised myeloid/erythroid ratio
    • Cytogenetic analysis of bone marrow cells :
      • Philadelphia chromosome in > 95% of metaphases
      • BCR – ABL fusion gene is detectable by FISH and its RNA product by PCR.


    Lab findings

      • Normocytic anemia
      • Leucocytosis and thrombocytosis with circulating megakaryocyte fragments occur early
      • Leucopenia and thrombocytopenia occur later
      • Blood film: red cell poikilocytosis with teardrop forms and circulating red cell and white cell precursors

  • Serum LDH is raised
  • Bone marrow aspirate is usually unsuccessful (‘dry tap’)
  • Trephine biopsy shows increased cellularity, increased megakaryocytes and fibrosis

Answer: A Essential


Haematology:Platelet disorders




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The major cause of death in patients more than six months following cardiac transplantation is:
A. graft-versus-host reaction.
B. opportunistic infection.
C. rejection.
D. malignancy.
E. coronary artery disease.

In the first 30 days:

  • Graft failure -40%
  • Multiorgan failure - 14 %
  • Non-CMV infection - 13 %
  • Acute rejection - 7 %

Between 31 days and one year:

  • Non-CMV infection - 33 %
  • Graft failure - 18 %
  • Acute rejection - 12 %
  • Allograft vasculopathy - 5 %
  • Lymphoma and other malignancies - 4 %

From one year to three years:

  • Allograft vasculopathy - 14 %
  • Graft failure -17 %
  • Lymphoma and other malignancies- 4 and 10 %, respectively
  • Non-CMV infection- 13 %
  • Acute rejection - 10 %

At more than five years:

  • Allograft vasculopathy - 15 %
  • Graft failure -14 %
  • Lymphoma and other malignancies - 5 and 18 %, respectively
  • Non-CMV infection - 10 %
  • Renal failure - 6 %
  • Acute rejection - 1 %


Cardiology : Cardiac Transplantion

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A 56-year-old female is an unrestrained front seat passenger in a motor vehicle accident. She suffers midshaft femoral fracture with no other significant injuries. Fourteen hours after the injury she suddenly becomes dyspnoeic, cyanosed and obtunded.

With 5cm H2O of continuous positive airway pressure (CPAP) and fractional inspired oxygen concentration of 0.6 applied via a face mask, her arterial blood gases are:

pH 7.18 [7.36-7.44]
PaCO2 60 mmHg [35-45]
PaO2 61 mmHg [80-100]
base excess –6.8 [-2.0-2.0]

Her chest X-ray is shown below. An echocardiogram shows an enlarged right ventricle with calculated peak pulmonary systolic pressures of 45 mmHg. The left ventricle, left atrium and left-sided valves are all normal. The The ECG is normal

Which is the most likely diagnosis?
A. Acute respiratory distress syndrome.
B. Fat embolism.
C. Aspiration pneumonitis.
D. Cardiogenic pulmonary oedema.
E. Pulmonary thromboembolism.

Learning Issues:

What is ARDS? (Definitition, Cxr)
How to diagnose & treat fat embolism?
What are normal Pulmonary artery pressures?

Definition of ARDS

Refers to the severe end of the spectrum of "acute lung injury”
Acute lung injury is a syndrome of acute and pesistent lung inflammation with increased vascular permeability

3 clinical features:

1)  bilateral chest Xray infiltrates
2)  ratio of PaO2/FiO2 ratio of 201-300 regardless of level of positive end expeiratory pressure
3)  no clinical evidence of elevated L atrial pressure, PA pressure < 18mm Hg

ARDS has worser hypoxia PaO2/FiO2 ratio of < 200.  Acute in onset: 4 to 18hrs and presists for days to weeks
Histological features:  diffuse alveolar damage
Inhospital mortality of 39%
Risk factor for ARDS :smoking


ARDS closely resembles severe hemodynamic pulmonary edema due to heart failure

1) Brain Natriuretic peptide
2)  TTE

Normal PA systolic pressures: 15-25
Raised when volume overloaded
L heart failure
Primary lung disease
Pulmonary embolism
Mitral valve disease
Hypoxaemia with pulmonary vasoconstriction
L to R shunts

3)  Pulmonary artery catheterization

Other conditions that are confused with ARDS

-  diffuse alveolar hemorrhage
-  Acute interstitial pneumona
-  Idiopathic acute eosinophilic pneumonia
-  Lymphoma or acute leukemia

Causes of ARDS

1)  Sepsis
2)  Aspiration (pH <2.5 – cause severe lung injury)
3)  Severe trauma and surface burns
            - bilateral lung contusion
            -  fat embolism (long bone #), occurs 12 – 48 hrs after injury 
            -  sepsis from burns/trauma ( 12 – 48 hrs)
            - massive traumatic tissue injury
4)  Massive blood transfusion
            - > 15 units blood
5)  Transfusion-relatied lung injury (TRALI)
6)  Lung & bone marrow transplantation
-  2-3 d post surgery, lung transplant recipients prone to primary graft failure (due to imperfect preservation of transplanted lung)
7)  Drugs and alcohol
            -  asprin, cocaine, opiods, phenothiazines, TCA
            -  radiologic constrast
            -  alcohol has shown to increase risk but not cause ARDS

Fat Embolism Syndrome
Ass with long bone and pelvic closed #
Occurs 24- 72 hrs after insult, rarely as early as 12 hrs or later than 2 weeks
Classic triad :  hypoxemia, neurological abnormalitis and a petechial rash
            -  rash occurs on the head, neck anterior thorax, subconjunctiva and axillae
            -  occlusion of dermal capillaries by fat globules leading to extravasation of erythrocytes 


  1. presence of triad
  2. Cxr:  normal in majority, minority have diffuse or patchy air space consolidation
  3. V/Q scans : mottled pattern of subsegmental perfusion defects with normal ventilation
  4. CT chest: focal areas of ground glass opaxification with interlobar septal thickening
  5. Bronchoscopy:  growing evidence to detect fat droplets in alveolar macrophages
  6. Currently no sensitive, specific test for diagnosis


  1. early immobilization
  2. risk further reduced by operative correction
  3. supportive care
  4. mortality 5- 15%
  5. corticosteroid prophylaxis
  6. double blind study of 64 of lower extremity long bone # to receive either placebo or methyprednisolone 7.5mg/kg QID for 3 days.  FES dx in 9 out of 41 placebo pts and 0 of 21 steroid treated pt. No complications from steroid treatment


Back to the Question
Is it ARDS?

According to the definition of ARDS, the pt’s 3 features are:
Cxr: bilateral infiltrates which is seen on the Cxr provided
PaO2/FiO2 ratio:  61/ 0.6 = 100 (does not fulfil criteria)
PA pressure > 18mmHg

Does not meet the definition of ARDS.  Therefore not A

Is it fat embolism?

Pt had a long bone # and therefore could have a fat emobolism.  Pt’s Sx did occur 14 hrs after accident so it is in the right time frame.  Pt is hypoxaemic and is obtunded so fits the picture so far but we don’t know about whether she has a rash. 

Is it aspiration pneumonitis?

Pt’s risk for aspiration pneumonia is that she is obtunded.   But it is most likely that the hypoxaemia has attributed to her being obtunded.   The question gives a lot of information about the # which makes it less likely aspiration. 

Is it cardiogenic pulmonary edema?

The Cxr, raised PA pressure points towards pulmonary edema.  Although she has normal L ventricle, age of 56 makes it less likely she has cardiac failure.

Is it pulmonary thromboembolism?

Its too early for a pulmonary thromboembolism to form.

Most likely answer B Fat embolism.


Respiratory : Respiratory emergency


Question 16 top Download PDF

A doctor makes a diagnosis of hypertrophic cardiomyopathy in a 34-year-old woman. She responds well to medication and returns for regular follow-up appointments.
Which one of the following is the most appropriate action to extend care to the woman’s family?

A. Advise the woman of the genetic basis of hypertrophic cardiomyopathy.
B. Advise the woman that her immediate relatives should seek medical advice
regarding their risk of hypertrophic cardiomyopathy.
C. Contact the relatives regarding the risk of them having hypertrophic cardiomyopathy.
D. Contact the relatives’ doctors and recommend that the relatives be assessed regarding the possibility of hypertrophic cardiomyopathy.
E. Confirm the familial basis of the diagnosis of hypertrophic cardiomyopathy by DNA testing.

The genetics of the disease has to be understood before answering the question. Although I have to say I struggled between the decision of Option A or B.

Answer B. Advise the woman that her immediate relatives should seek medical advice
regarding their risk of hypertrophic cardiomyopathy.

Genetics of disease

  • autosomal dominant disease
  • 10 causative genes identified (missense type)
  • function of genes:

encoding proteins of cardiac sarcomere? components of the thick or thin filaments with contractile, structural or regulatory functions

Varied phenotype

Wide variation in pattern of L ventricular hypertrophy within a single family pedigree

  • environmental influences and modifier genes
  • Hypertrophy could represent an adaptive response to malfunctioning contractile ability of cardiac myocytes
  • 4 main types:
    1. Hypertrophic
    2. Restrictive
    3. Arrhythmogenic Right Ventricular
    4. Intracellular pathophysiological mechanisms of different mutations poor understood

Routine genotyping

is currently not recommended

  • large no. of possible mutations
  • expensive and complex lab techniques

Family screening

  • advised that all 1st degree relatives are screened for the condition
  • this is recommended as HCOM may be present without any Sx
  • evaluation involves physical examination, ECG and ECHO


  • if tests show no abnormality ? HCOM excluded
  • ? although small no. of pts the abnormal gene may still be present. Therefore they may still pass on the gene to next generation


  • regular clinical evalulation every 3 yrs till puberty
  • yearly till full growth spurt (20yrs)

Common practice hasa been to discontinue examination in relatives who have completely normal TTE and ECGs after age 25years on assumption that late onset disease is rare.
However growing awareness that late-onset disease in patiens with sarcomeric protein disease is in fact common has led to new recommendations that adult relatives are clinically screened every 5 years.


Cardiology - Cardiomyopathy



Hypertrophic cardiomyopathy: state-of-the-art review, with focus on the management of outflow obstruction
J. C. Kovacic and D. W. M. Muller
Internal Medicine Journal 2003: Volume 33 Issue 11 Page 521 - November 2003



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A 68-year-old woman is prescribed haloperidol 2 mg nocte for treatment of delirium while hospitalised for treatment of advanced metastatic breast cancer. Two weeks after admission she becomes increasingly agitated and is noted to be constantly pacing around her bed. She complains of difficulty relaxing and feels she cannot keep herself still.
What is the most likely explanation of these symptoms?
A. Dystonic reaction.
B. Akathisia.
C. Anxiety/panic disorder.
D. Major depression.
E. Restless legs syndrome


Repetitive, patterned, tiwisting and sustained movements that may be either slow or rapid
Adverse extrapyrimidal effects that occur shortly after initiation of neuroleptic drug therapy


  • Drug-induced alteration of dopaminergic-cholinergic balance in nigrostriatum
  • Most drugs produce dystonic reactions by nigrostriatal dopamine D2 receptor blockade- leads to an excess of striatal cholinergic output. 

Clinical manisfestations

  • Occur shortly after initiation of drug treatment
  • 50% occur within 48 hrs
  • 90% occur within 5 days of initiation of treatment
  • risk factors: Fhx of dystonia, recent hx of alcohol/cocaine use, treatment with potent dopamine D2 receptor antangonist (eg. Haloperidol)


  • Oculogyric crisis (deviation of eyes in all directions)
  • Buccolingual crisis
  • Protrusion of tongue
  • Trismus (tonic contraction of muscles of mastication)
  • Forced jaw opening
  • Difficulty in speaking
  • Torticollis
  • Altered mental state


  • Extremely unpleasant subjective sensation of “inner” restlessness that manifests itself with an inability to sit still or remain motionless
  • Common cause: neuroleptic antipsychotics – phenothiazines, haloperidol, rarely antidepressants

Restless leg syndrome
Symptoms of spontaneous,continuous leg movements associated with unpleasant paresthesias
Occur at rest and relieved by movement
Sleep disturbances

Primary idiopathic disorder
Associated with variety of underlying medical disorders

FHx: consistent with dominant inheritance (40% of pts with idiopathic RLS)
RLS arises from dysfunction of hypothalamic dopaminergic cells that are the source of spinal cord dopamine
Evidence that support hypothesis:
Increased incidence of RLC in Parkinson’s disease
Data from Spect,and PET are conflicting


  • Iron deficiency – studies not conclusive, but warrant measurement of serum ferritin levels and a trial of oral iron therapy when ferritin levels are low
  • Uremia – incidence of 6 – 60% in dialysis pt
  • Diabetes Mellitus
  • Parkinson’ disease
  • Rheumatic disease – relationship bet RLS and Rheumatic disease is unclear.  One study showered RLS present in 25% of pts with RA compared with 4% controls with OA or seronegative arthorpathy
  • Venous insufficiency -

Minimal criteria:

  • Desire to move extremities – often associated with paresthesias or dysensthesias
  • Motor restlessness
  • Worsening of Sx at rest with at least partial and temporary relief during activity
  • Worsening of Sx in the evening or at night

Important to exclude:

  • Fe deficiency
  • Renal failure
  • Peripheral neuropathy, lumbosacral radiculopathy and ordinary leg cramps should be considered

RLS should be differentiated from akathisia

  • Akathisia is a more constant, generalized feeling of motor restlessness unassociated with subjective discomfort localizing to the legs
  • RLS has a circadian rhythm (worse at night when pt is sitting or in bed)

Treatment – devised by Restless legs syndrome foundation

Intermittent RLS

Dopamine agonists
Low potency opiods

Daily RLS

Daily RLS
Dopamine agonists
Low potency opioids

Refractory RLS
(Daily RLS treated with dopamine agonist but with poor response)

Change to gabapentin
Change to different dopamine agonist
Add second agent – gabapentin, benzodiazepine or opioid
Change to high potency opioid or tramadol


Evidence for treatment

  • Levodopa
    • Small randomised trials showed good response compared to placebo
    • Problems
      • Worsening of RLS symptoms earlier in day after evening dose of medication- 70%
      • Recurrence of RLS early in the morning
      • Recurrence of symptoms in 2nd half of the night
  •  Dopamine agonist (pramipexole & ropinerole)
  • Directly stimulate dopamine areceptors and have longer half life (4-6hrs) than levodopa
  • Superior to levodopa for treatment of daily RLS
  • Adverse effects:  nausea, lightheadedness and fatigue


  •  Benzodiazepines
  • Useful in mild cases of RLS
  • No controlled trials
  • Short activing – triazolam, zolpedem, zaleplon (for sleep onset insomnia)
  • Intermediate acting – temazepam (for RLS that awakens the pt later at night)
  • Longer duration – clonazepam

4.  Opiods

  • Shown to reduce no. of sleep arousal,s PLMS frequency and increase sleep efficiency
  • Tramadol, oxycodone, methadone, codeine

5.  Gabapentin

  • Effective in open label study
  • Safe among’ dialysis patients
  • Start from 100-300mg – tendency for drug to cause somnolence and gait unsteadiness

Anxiety/panic disorder

Anxiety is diagnosed by a GAD7 questionnaire and ‘being so restless that it is hard to sit still’ is  indeed one of the symptoms but there are many other symptoms that need to be fulfilled before a diagnosis of anxiety/panic disorder.

Unlikely answer.


Again, this diagnosis is made by a constellation of symptoms that are present for everyday for a minimum of 2 weeks.  At least 5 out of the 9 symptoms:

  • Depressed mood
    • Loss of interests/pleasure
    • Change in sleep
    • Change in appetite or weight
    • Change in psychomotor activity
    • Loss of energy
    • Trouble concentrating
    • Thoughts of worthlessness or guilt
    • Thoughts about death or suicide

The most likely answer is B Akathisia


Neurology: Involuntary movements

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A 65-year-old man presents to the emergency department with ischaemic chest pain. No abnormalities are noted on examination apart from mild hypotension.
His full blood examination shows:

haemoglobin                                                                             125 g/L [128-175]
white cell count                                                                        10.2 x 109/L [3.9-12.7]
(normal white cell differential)
platelets                                                                                   180 x 109/L [150-396]

Coagulation investigations show:
activated partial thromboplastin time (APTT)                    100 seconds [26-38]
APTT 1:1 mix (patient: normal plasma)                             52 seconds
prothrombin time-international normalised ratio (PT-INR) 1.2 [1.0-1.3]
thrombin clotting time (TCT)                                                       200 seconds [<24]
fibrinogen                                                                                 4.5 g/L [2.0-4.0]
reptilase time                                                                            18 seconds [<24]

The most likely cause of the coagulation test abnormalities is:
A. disseminated intravascular coagulation.
B. administration of low-molecular weight heparin.
C. administration of thrombolytic agent.
D. lupus inhibitor.
E. administration of unfractionated heparin.

Coagulation pathways


Intrinsic and common pathway

Prothrombin time

Extrinsic and common pathway

Thrombin time

Final step fibrinogen to fibrin

Last step of fibrin crosslinked through action of factor XIII not tested



Prothrombin time

  • Extrinsic and common pathyway
  • Factor VII, II, X, V and fibrinogen
  • Expressed as ratio INR

Causes of prolonged PT

  1. Warfarin
  2. Vit K deficiency
  3. Factor II, VII, V and fibrinogen deficiency
  4. Liver disease

Mediated by inhibition of Vit K dependent factors – II, VII, IX & X


  • Monitor intrinsic coagulation pathyway and final common pathway
  • Monitor heparin therapy

Causes of prolonged APTT

  1. Hepain
  2. von  Willebrand disease
  3. Lupus anticoagulant
  4. Defiiency of factors VIII, IX or XI, XII, prekallikrein or HMW kininogen


  • Activates antithrombin (AT), which irreversibly inactivates prothrombin, factor Xa, factors XIIa, XIa and IXa


  • Inactivate factor Xa
  • No need for monitoring because the anticoagulant response to a fixed dose of LMWH is highly correlated with patient’s body weight
  • Monitoring via anti-factor Xa activity

Thrombin time

  • Final step of clotting pathyway (fibrinogen to fibrin)

Causes of prolonged TT

  1. Hepain or hepain like compounds (danaparoid)
  2. Presence of fibrin/fibrinogen degradation products
  3. Disorders of fibrin
  4. High concentration of serum proteins (myeloma. Amyloidosis)

Reptilase time

  • Reptilase is an enzyme similar to thrombin that is found in venom of Bothrops snakes
  • Differs from thrombin by generating fibrinopeptide A but not fibrinopeptide B from fibrinogen and by resisting inhibition by heparin via antithrombin
  • Similar to thrombin time in measuring conversion of fibrinogen to fibrin

Causes of prolonged time

  • All the causes which prolong TT except heparin
  • Useful for determing if heparin is cause of prolonged TT

Activated whole blood clotting time (ACT)

  • Addition of activating agent (eg. Celite, kaolin) to sample of freshly drawn whole blood and measure time (in seconds) for formation of clot
  • When heparin concentrations exceed 1.0U/ml (used in CABGs and PTCA), APTT becomes infinitely prolonged
  • ACT shows a graded response to heparin concentration in the range of 1 to 5 U/mL

Lupus anticoagulants

Presence of antiphospholipid antibody (aPL) produces the LUPUS ANTICOAGULANT PHENOMENON


  • Ab against plasma proteins bound to anionic phospholipids
  • Cause APTT prolongation
  • APTT does not correct after 1:1 dilution with normal pooled plasma in a non bleeding patient
  • Adding phospholipid that corrects clotting time confirms presence of lupus anticoagulant phenomenon
  • Increased risk of venous and arterial thrombosis



Common Causes



Intrinsic pathway affected

  • Von Willebrand’s disease
  • Isolated deficiencies of factors VIII, IX & XI
  • Heparin therapy
  • Lupus anticoagulant phenomenon



Extrinsic pathway

  • Warfarin therapy
  • Chronic liver disease
  • Vitamin K deficiency
  • Factor VII deficiency (rare)



Final pathway affected
Assess thrombin time – if normal common pathway affected

  • Factor II, V or X abnormalities
  • Liver disease
  • DIC
  • Overanticoagulation with warfarin




Pt with apparent bleeding diathesis

  • Thrombocytopenia
  • Mild deficiency of VWF
  • Platelet dysfunction
  • Factor XIII deficiency


Back to the question

  1. APTT, thrombin time increased
  2. Normal INR
  3. Normal Reptilase time

Intrinsic pathway and the step from fibrinogen to fibrin (final step) affected
Since reptilase time is normal, the answer is D – Unfractionated heparin


Haematology: Coagulation

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Question 26 top Download PDF

A 56-year-old forestry worker develops a widespread rash involving the trunk and lower limbs two weeks following a tick bite. He is generally unwell with myalgias, fevers, headache and anorexia. The rash is papular, non-blanching and not itchy, and is shown above. What is the most appropriate management?

A. Treat expectantly.

B. Doxycycline.

C. Ciprofloxacin.

D. Ceftriaxone.

E. Phenoxymethylpenicillin (penicillin V).


Tick bites: think of Rickettsial infections

Rickettsial infections

  • small obligate intracellular bacteria
  • transmitted by arthropods

Incubation period: 1-2 weeks

Clinical manisfestations: 
  • abrupt flu-like with prominent fever, chills, headache, myalgia and anorexia
  • About 4-10 days after onset of Sx, a maculopapular rash appears on trunk and periphery
Confirmation of dx:
  • Serology
  • PCR detection of rickettsial DNA

Doxycycline – ANSWER B


Fever and Rash

  • Categorising the rash:
    • Pupuric
    • Diffuse erythematous (look like sunburn)
    • Maculopapular
    • Vesicular


Sequential approach to the patient with a fever and a rash

Life threatening conditions
  • Meningococcal disease
  • Toxin-mediated staphylococcal or streptococcal infections
  • Rickettsial infections in those with an appropriate travel history
  • Secondary syphilis or drug eruptions
Well defined conditions
  • Measles
  • Rubella
  • Infectious mononucleosis
  • Kawasaki disease
  • Ross River virus infection
  • Exanthem subitum
  • Erythema infectiosum
  • Acute HIV infection
  • Dengue fever
Classical non infectious dermatological syndromes
  • erythema multiforme
  • erythema nodosum
  • Stevens-Johnson syndrome

Causes of pupuric rash

Infectious (bacterial)

Infectious (viral)

Non infectious




Staphylococcal septicaemia


Henoch Schonlein pupura


Hepatitis B





Causes of diffuse erythematous rash

Infectious (bacterial)

Infectious (Viral)


Streptoccal scarlet fever


Kawasaki disease

Streptococcal TSS

Enteroviral infection


Staphylococcal scarlet fever



Staphylococcal TSS



Staphylococcal scalded skin syndrome



Causes of maculopapular rash

Infectious (bacterial)

Infectious (Viral)




Drug reaction

Rickettsial infections



Secondary syphillis

Enteroviral infections


Enteric fever (typhoid and paratyphoid)

Parvovirus infection

Juvenile rheumatoid arthritis



Erythema multiforme


HIV, Acute HepB, Dengue,
Ross River virusS

Pityriasis rosea

Causes of vesicular rash         



Non infectious


Varicella Zoster



Herpes Simplex Virus

Erythema multiforme

Rickettsial infections eg Rickettsial pox

Enteroviral infection eg hand & foot



Parvovirus B19 infection



Small pox


reference: Infectious Diseases, A clinical approach 2nd edition Chapter 13 Fever and rash pg 148


Infectious diseases

Question 27 top

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Question 30 top Download PDF

A 73-year-old man presents with a 12-month history of left leg pain radiating from the buttock to the heel. There is no associated back pain. Neurological examination reveals straight leg raising of 60 degrees on the left with a positive dorsiflexion test. Power is normal with a reduced left ankle jerk. The remainder of the neurological examination is normal. His lumbar magnetic resonance imaging (MRI) scan at the L5/S1 region is shown above.

The most likely diagnosis is:
A. L5/S1 disc protrusion.
B. left L5/S1 facetal pain.
C. schwannoma involving the left S1 nerve root.
D. malignant inflitration of the left S1 nerve root.
E. piriformis syndrome.

Disc prolapse

  • Herniation occurs laterally and compresses adjacent nerve roots
  • May occasionally occur centrally, compressing the cauda equina
  • Associated hypertrophy of degenerated facet joints often a further source of back and leg pain and is an important cause of root compression. 

  • Lateral disc herniation usually compress the nerve root exiting through the foramen below the affected level
  • Eg. An L3/4 lesion will compress L4 nerve root
  • Lumbar disc lesions occur at any level but L4/5 and L5/S1 are the commonest sites (95%)

Clinicla features
Lateral disc protrusion:

  • Leg pain from root irritation/ compression produces pain the distribution of affected root
  • Numbness or tingling in distribution of nerve rot

Mechanical signs

  • Straight leg raising L5 and S1 root compression causes limitation to less than 60 degrees and produces pain down the back of the leg
  • Dorsiflexion of foot while leg I elevated aggravates the pain
  • Elevation of “good” leg may produce pain in the other leg.

Central disc protrusion

  • Symptoms and signs are usually bilateral, although one side is often worse than the other
  • Leg pain extends bilaterally down the back of thighs
  • Pain disappear with the onset of paralysis
  • Paraesthesis occurs in the sacral area
  • Loss of bladder and urethral sensation with intermittent or complete retention of urine occurs in most patients
  • Anal sensation is usually impaired and accompanies constipation.
  • Motor loss: presents as foot drop with complete loss of power in dorsiflexors and plantarflexors of both feet
  • Ankle jerks are usually absent


  • Lateral disc protrusion
    •  Conservative (most bouts of leg pain settle spontaneously by taking simple measures)
      • Analgesia
      • Avoiding heavy lifting and bending
      • Using an orthopaedic mattress
      • A plaster jacket
      • Bed rest
    • Surgery indications
  • Severe unremitting leg pain despite conservative measures
  • Recurrent attacks of leg pain especially when causing repeated time loss from work
  • Development of neurological deficit
  • 80% obtain good results, root damage in <1%
  • Central disc protrusion
  • Compression of cauda equina from a central disc constitutes a neurosurgical emergency


Facet joint

  • Most common cause of all recurrent, disabling low back and neck problems
  • Rarely involve spinal nerves
  • Symptoms
  • Acute episodes of lumbar and cervical facet joint pain, intermittent, generally unpredictable
  • Persisting joint tenderness overlying inflamed facet joint
  • Diagnosis
  • CT scan gives most information
  • MRI scan is not quite as useful but good at investigating possible disc problems
  • Most definitive diagnosis: facet joint injection with small vol of a combination of Xray constrast material, local anesthetic and cortison  à if relieved, diagnostic


Malignant infiltration
Extradural (78%) – metastasis, myeloma, neurofibroma, lymphoma
Intradural (18%)- meningioma, schwannoma
Intramedullary (4%)- astrocytoma


  • Occurs in about 5% of all cancer patients
  • Primary site: breast, lung, prostate and kidney
  • Clincial features: bone pain and tenderness preceeding limb and autonomic dysfunction
  • Management
    • Radiotherapy
    • Surgical decompression results are poor. 



  • Slowly growing benign tumours
  • Occur at any level arising from posterior nerve roots
  • Lie entirely within the spinal canal or go through the intervertebral foramen
  • Occur in the 30-60 age group
  • Present with root pain
  • MRI or CT myelogram identifies intradural/extramedullary lesion
  • Obligue Xrays may show foraminal enlargement
  • Neurofibromas are identical apart from their microscopic appearance and their association with multiple neurofibromatosis  (Von Recklinhausen’s disease- café aulait spots)

Piriformis syndrome

  • Piriformis muscle either irritate or compress the proximal sciatic nerve due to spasm and/or contracture
  • Diagnosis of exclusion
  • Ddx:
    1. lumbosacral radiculopathy
    2. Buttock pain
    3. Ischial tuberosity bursitis
    4. Sciatica
  • Sx: deep pain in buttocks aggravated by sitting, climbing stairs or performing squats


Difficult diagnosis to make and not much concensus on treatment,
Treatment: Ultrasound and other heat modalities prior to physical therapy – physio referral
Home stretching program

Back to the question:

The MRI does show a lateral protrusion of the lumbar disc.  This would be most likely diagnosis.
Facet joint problems will be hard to see on MRI and does not present with neurological symptoms. 
It is definitely not the piriformis syndrome as there is obvious pathology seen in the MRI.  As for Schwanoma and the malignant infiltrate, it is less likely.

Answer A.


Neurology: Radiculopathy

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One week after a 47-year-old male has transphenoidal pituitary surgery for a histologically confirmed non-functioning pituitary tumour, the following endocrine results are obtained:

thyroid-stimulating hormone (TSH) <0.05 mIU/L [0.30-5.00]
free thyroxine (FT4) 16 pmol/L [10-23]

Synacthen Test:
0800 plasma cortisol 90 nmol/L [100-700]
0900 plasma cortisol 680 nmol/L [>550]

luteinising hormone (LH) <1 IU/L [2-8]
follicle-stimulating hormone (FSH) <1 IU/L [2-8]
testosterone 8 nmol/L [10-30]
growth hormone (GH) <0.03 ng/ml [ <10]

What is the next most appropriate management step at this point in time?

A. Observe and repeat testing in six months.
B. Commence thyroxine.
C. Commence hydrocortisone.
D. Commence testosterone.
E. Commence growth hormone.

This patient has overall reduced pituitary function.  But the most important hormone that may be life threatening in cases of infection is cortisol. 

Short Synacthen test
High dose ACTH
Indications:  Used in pts acutely unwell or pt who present with signs and symptoms suggestive of primary adrenal insufficiency

Procedure:  an IV line is placed 30 mins before the test for rapid phlebotomy and to eliminate temporary rise in cortisol ass with a needle stick.  IV line kept open with NaCl (50ml/hr).  Blood is drawn for ACTH and cortisol.  Synacthen 250mcg is injected over 2 mins as IV bolus.  Blood is taken at 30 and 60 mins post injection.

If pt is receiving hydrocortisone, medication should be withheld for at least 12 hrs before testing.  If pt is receiving dexamethasone, there is some cross-reativity in some assays and cortisol levels may not be accurate.

A criteria for minimal normal cortisol response of 500-550nmol/L are required
A serum cortisol value of 550nmol/L or more at any time during the test (even bf test) is indicative of normal adrenal function. (even if 1st criteria not fulfilled)
Secondary adrenal insufficiency
Normal adrenal gland will respond to maximally stimulating concentrations of exogenous ACTH.

Primary adrenal insufficiency
The endogenous ACTH secretion will be already elevated and there should be little or no adrenal response to exogenous ACTH

Low dose ACTH
Indications:  Pts with subtle signs of adrenal insufficiency or patients who have been treated with glucocorticoids and determination of adrenal reserve is necessary.  Pts ho have autoimmune disease and may have early adrenocortical insufficiency may be best assessed with this test. 

Procedure: same as above but 1mcg of Synacthen is used

Pituitary surgery

Respond normally to high-dose ACTH test
Fail to respond to insulin-induced hypoglycemia (cannot increase ACTH secretion).


  1. important to determine if patient has hypothyroidism which increases the risk of respiratory arrest following postoperative administration of opiates of barbiturates.  Hypothyroidism should be corrected preoperatively
  2. Identify a marker such as FSH or free alpha subunit to monitor response to surgery

Immediate post op

  1. diabetes insipidus, SIADH or both
    1. associated with manipulation of pituitary and its stalk during surgery
    2. major cause is inappropriate ADH release from injured posterior pituitary gland
    3. UO and serum sodium conc should be measure often
    4. Cortisol deficiency may contribute to hyponatremia
    5. Pts with polyuria due to DI should be treated with aqeuous vasopressin
    6. Desmopressin (longer acting) should be avoided at this time because it might cause hyponatremia if DI suddenly remits.  Used if DI lasts for more thant 4-5 days
    7. Maintenance hydrocortisone should be prescribed at discharge.

Short term post op (4-5 wks)

  1. evaluation for amount of residual adenoma, visual function and hormonal function
    1. MRI (edema from surgery could obscure image)
    2. Monitoring serum conc of ganadotroph adenoma product ex FSH or alph subunit
  1. Hormonal function
    1. serum thyroxine
    2. early AM cortisol 48 hrs after discontinuation of hydrocortisone.  (< 83nmol/L à hypoadrenal, > 497nmol/L à normal adrenal function)

* Up to date says that Synacthen test should not be used as it may give a falsely normal result an recommended metyrapone test


    1. serum testosterone (males)
    2. serume estradiol (females)
    3. 24hr urine volume if pt has significant nocturia

water deprivation test performed if UO is > 3L/day, if >6L/day (definitely DI

Long term post op    (Every 6 – 2 months)

  1. Detect growth of residual adenoma tissue
    1. vision testing
    2. MRI
    3. Monitor serum marker

       If no regrowth after a year or 2, the interval between scans can be lengthened
      If residual tissue grows progressively, it should be treated by radiation therapy

  1. Adequeacy of hormonal replacement    

Answer:  hydrocortisone C. 
I found this question extremely hard as there was no definite firm answer in all my readings.  But Up to date says that hydrocortisone should be prescribed at discharge and has no mention of all the other hormones until 4-5 weeks post op when hormonal function is tested.


Endocrinology: Hypopituitarism


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A 30-year-old man has previously undergone splenectomy (six months prior) for chronic idiopathic thrombocytopenic purpura (ITP). Apart from occasional bruising, there are no haemorrhagic symptoms.
His full blood examination shows:
haemoglobin                             135 g/L [128-175]
mean cell volume (MCV)            96 fL [80-97]
white cell count                                     11.7 x 109/L [3.9-12.7]
(normal white cell differential, post-splenectomy)
platelets                                    44 x 109/L [150-396]

Repeated autoimmune and viral serology remain negative.
The most appropriate management of his thrombocytopenia is:
A. danazol.
B. immunoglobulin.
C. prednis(ol)one.
D. azathioprine.
E. observation.

Chronic Idiopathic thrombocytic purpura


  • Women age 20 – 40 commonly ratio 3: 1
  • Autoimmune disorder: Antibodies directed against target antigens on glycoprotein IIb/IIIa or less frequently Gp Ib/IX
  • Low plt count may be the initial manisfestation of SLE


  • Normal Hb and WCC
  • Plt < 20 X 10 9/L
  • Bone marrow examination:  normal or increased numbers of megakaryocytes
  • PT and APTT are normal, fibrinogen is normal

ITP occurs in association with some malignancies (eg. CLL, non HL, myelodysplasia), infections (EBV, HIV and malaria), connective tissue disorder (SLE). 
Patients should be tested for ANF and anticardiolipin antibodies


  • Prednisolone
  • IV immunoglobulin
  • obtaining a temporary rise in plt count
  • meningismus and headache, hepatitis C virus
  • Splenectomy
  • For non responders with continuing symptoms and/or very low platelet counts
  • 2nd line after prednisolone
  • Additional immunosuppressive therapy
    • Azothioprine,
    • Cyclophosphamide
    • Cyclosporin A, Rhesus anti-D – cause hemolysis
    • Rituximab (anti CD 20)  * most commonly used*
  • preferable to long term steroids
  • eliminates normal B cells including those producing antiplatelet antibody
  • B cell depletion is transient
  • Few S.E or toxicities
    • Danazol
    • Attenuated androgen
    • Limited use, efficacy unknown

Persistant thrombocytopenia after splenectomy

Immunosuppressive drugs as above – should only be used to raise plt count temporarily and to support patients before surgery, labor and delivery
Not substitutes for splenectomy

If patient not bleeding and maintains plt count > 20,000/microL, withhold therapy

Answer D Observation
Plt count is acceptable at 44 X 10 9/L.  Severe spontaneous bleeding were seen below platelet levels 10,000/microL = 10 X 10 9/L




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A 24-year-old man with a previous diagnosis of schizophrenia has been receiving depot haloperidol monthly for four years. He presents with the gradual onset of choreoathetoid movements of his upper limbs.
The most likely explanation for this presentation is:

A. dystonia.
B. drug-induced Parkinson’s disease.
C. tardive dyskinesia.
D. amphetamine abuse.
E. akathisia.


Sustained abnormal posture produced by contraction of large trunk and limb muscles eg sustained head retraction or sustained inversion of foot
Adverse extrapyrimidal effects that occur shortly after initiation of neuroleptic drug therapy


  • Drug-induced alteration of dopaminergic-cholinergic balance in nigrostriatum
  • Most drugs produce dystonic reactions by nigrostriatal dopamine D2 receptor blockade- leads to an excess of striatal cholinergic output. 
  • Drugs: metoclopramide, haloperidol

Clinical manisfestations

  • Occur shortly after initiation of drug treatment
  • 50% occur within 48 hrs
  • 90% occur within 5 days of initiation of treatment
  • risk factors: Fhx of dystonia, recent hx of alcohol/cocaine use, treatment with potent dopamine D2 receptor antangonist (eg. Haloperidol)


  • Oculogyric crisis (deviation of eyes in all directions)
  • Buccolingual crisis
  • Protrusion of tongue
  • Trismus (tonic contraction of muscles of mastication)
  • Forced jaw opening
  • Difficulty in speaking
  • Torticollis
  • Altered mental state


  • Anticholinergics eg benztropine for 24-48 hrs helps symptoms settle

Drug-induced Parkinson’s disease

  • Rigidity, akinesia, gait disturbance
  • Drugs: Dopamine receptor blocking drugs (antipsychotic, antiemetic drugs), reserpine, tetrabenazine, alpha-methyl-dopa, lithium, flunarizine, cinnarizine
  • Sx occur one month of started neuroleptics in 50% of cases and 3 months in 90%.
  • More likely to be to be symmetric
  • Twice as common in females than males
  • Metaclopramide tends to induce parkinsonism frequently affecting females over age 60 particularly with renal failure
  • Risk factors: concomitant fluoxetine therapy



Tardive dyskinesia

  • Late-onset of choreoathetotic movements of tongue face, neck, trunk or limbs
  • Associated with prolonged exposure to antipsychotic medications
  • Results from development of drug induced supersensitive dopamine receptors
  • Major risk factors
    • Use of conventional antipsychotic medications
    • Older age
    • Longer duration of treatment
  • Risk is significantly lower with atypicals

Pts on long term maintenance treatment should be monitored periodically for development of symptoms

  • Dose reduction
  • Consider aypical
  • If severe Sx, consider treatment with clozapine – good efficacy in reduced TD Sx. 


Amphetamine abuse

  • High dose stimulants over long periods of time causes structural deficits  - cingulated, limbic and paralimbic cortices and significant reductions in hippocampal vol
  • Symptoms:
        • depression, fatigue, poor concentration
        • mild parkinsonian features (myoclonus – inappropriate, spontaneous muscle contractions), tremor, bradykinesia
        • paranoid psychosis (reversible after prolonged drug free state)


  • Extremely unpleasant subjective sensation of “inner” restlessness that manifests itself with an inability to sit still or remain motionless
  • Common cause: neuroleptic antipsychotics – phenothiazines, haloperidol, rarely antidepressants

Answer: Tardive dyskinesia
Best describes choreoathetoid movements


Neurology: Movement Disorder

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Which one of the following medications is most likely to result in an increase in circulating insulin concentrations?
A. Metformin.
B. Acarbose.
C. Rosiglitazone.
D. Repaglinide.
E. Orlistat (Xenical).

Answer:D Repaglinide

From Chapter 61 Insulin, OHA and the pharmacology of the Endocrine Pancreas Stephen N Davis and Faryl K. Granner

Drug (class)




Half life

Adverse reactions

HbA1c lowering

cholesterol effect


Stimulate insulin realease from pancreatic B cells by binding to and blocking the ATP sensitive K channel

GIT , bound to albumin


3-5hrs, hypoglygemic effects

hypoglycemia, nausea + vomitting



Repalinide (meglitinide) - used for multiple prandial use

Stimulate insulin realease from pancreatic B cells by binding to and blocking the ATP sensitive K channel


liver, 10% in kidney (use cautiously in renal failure)

peaks after 1hr, half life 1 hr





1)  Reduces glucose levels by decreasing hepatic glucose producing
2)  Increasing insulin action in muscle and fat
3)  reuduce plaama TG by 15-20%

small intestines

Excreted unchanged in urine


(20%) diarrhea, abdominal discomfort, nausea, metallic taste, anorexia, reduce intestinal absorption of Vit B12 and folate, lactic acidosis



Thiazolidinediones (pioglitazone, rosiglitazone)

1) selective agonists for nuclear peroxisome proliferator-activated receptor  gamma (PPAR)  2)activates insulin-responsive genes that reglate carboydrate and lipid metabolism  3)  activate genes that regulate free fatty-acid metabolism


liver P450 cytochrome

maximam clinican effect after 6-12 wks

weight gain, edema (avoided in pt with NYHA class 3 & 4)


lower TG 110-20%, increase HDL 19%, LDL 12%

Alpha- Glucosidase Inhibitor (acarbose, miglitol)

1) inhibit action of intestinal brush border alpha-glucosidase resulting in slowing absorption of carbohydrates                2)  blunting post-prandial rise in plasma glucose

poorly absorbed



malabsorption, flatulence, diarrhea, abdominal bloaing

profound effect on HbA1c in severely hyperglycemic T2Dm pt, in mild-mod hyperglycemia <1%



Pharmacology: Endocrinology

repeated question 2003 paper two question 63


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A 73-year-old man presents with a two-day history of increasing headache and mild left-sided weakness. On examination, he is alert, with normal language and higher mental functions. He has a mild left facial weakness with a mild left hemiparesis. Sensory examination is normal. There is mild left sided hyperreflexia with an upgoing left plantar response. His blood pressure is 170/80 mmHg. His non contrast cranial computed tomography (CT) scan is shown here.

The most appropriate management is:
A. craniotomy and removal of lesion.
B. dexamethasone.
C. glyceryl trinitrate infusion.
D. mannitol infusion.
E. observation.

Intracerebral haemorrhage


  1. Hypertension
  2. Amyloid angiopathy
  3. Ruptured saccular aneurysm
  4. Vascular malformation
  5. Hemorrhagic infarction (venous sinus thrombosis)
  6. Septic emobolism (bacterial endocarditis)
  7. Brain tumour
  8. Bleeding disorders, anticoagulants, thrombolytic therapy

Common sites:
Territory of penetrator arteries that branch off major intracerebral arteries , often at 90 deg angles with parent vessel
Vessels supply
pons and midbrain (penetrators of basilar arterery),
thalamus (thalamostriata penetrators off P1 and P@ segments of posterior cerebral afteries)  putamen and caudate (lenticulostriate penetrators off the M1 segment of middle cerebral artery)

Mechanism of brain injury

  1. Primary direct mechanical injury to brain parenchyma by expanding clot
  2. Increased intracranial pressure
  3. Herniation secondary to mass effect

Secondary brain injury

Decreased bflocal neuronal ischemiafurther cytotoxic edematoxic release of inflammatory mediators

Blood brain barrier breakdown and dysregulation of hemostasis via inflammatory cascade activation and MMP overexpression

Haemorrhage enlargement

  • Haemorrhage enlarges in the 1st 6 hrs after presentation
  • Frequency of significant hemorrhage enlargment (>33% vol increase) over 24 hr is 38% of patients
  • Enlargement of hematoma associated with neurologic deterioration

Aiims of treatment:
Minimising secondary brain ischemia
Preventing hematoma enlargement


  • Framingham study: 8% of all strokes , 25% of strokes in Japan
  • Incidence of ICH increases with age, doubling every 10 years after age 35
  • Rate of occurrence is highest in Asian, intermediate in blacks and lowest in whites

Risk factors

  • Hypertension
    • Doubled risk of ICH
  • Smoking
  • Hypocholesterolemia
    • Treatment with statins does not appear to increase risk of primary ICH
  •  Cerebral amyloid angiopathy

Clinical presentation

Neurologic symptoms do not begin abruptly and are not maximal at onset (compared to brain embolism and sunarachnoid hemorrhage)


  • headache, vomiting and altered level of consciousness
  • seizures occur in 7 – 9 % of ICH, more common in lobar hemorrhages (affecting cortical tissue)
  • complain of stiff neck and meningismus if there is intraventribular blood
  • stupor or coma is ominous unless pt had thalamic hemorrhage (involvement of reticular activating system), recover after blood is reabsorbed
  • ECG changes: prolonged QT interval, depressed ST segment, flat or inverted T waves, U waves and tall peaked T waves


Site of hemorrhage

Neurological signs


  • Hemiplegia, hemisensory loss, homonymous hemianopsia, gaze palsy, stupor and coma




  • Usually originate in the dentate nucles, extend into the hemisphere and 4th ventricle and possibly into the pontine.
  • Inability to walk due to imbalance, vomiting, headache, neck stiffness, gaze palsy and facial weaknss
  • No hemiparesis
  • Crucial diagnosis to make since patients frequently deteriorate and require surgery



  • Extend in a transverse direction to the posterior limb of the internal capsule, downward to put pressure on the tectum of midbrain or may rupture into 3rd ventricle
  • Hemiparesis, hemisensory loss, transient homonymous hemianopsia
  • Upward gaze with miotic pupils that are unreactive, peering at the tip of the nose, skewed, or “wrong way eyes” toward the weak side
  • Aphasia may occur if bleed affects the dominant hemisphere or neglect in non dominant hemisphere



  • Most often affect parietal and occipital lobes
  • Higher incidence of seizures
  • Occipital hemorrhages frequently present with very dense contralateral homonymous hemianopsia
  • Haemorrhage in frontal region will produce contralateral pleqia or paresis of leg with relative sparing of arm



  • Medial hematoma that extends into the bass of pons
  • Deep coma over first few mins following hemorrhage
  • Total paralysis
  • Pupils pinpoint



  • 30 day mortality from ICH 35 – 52 %
  • Half of these deaths occur within the 1st few days
  • Only small no. of patients function independently after event
  1. Initial ICH vol and level of consciousness
    • ICH vol of 60cm or > on initial CT and a GCS of 8 or < predicted a 30 day mortality of 91%
    • ICH vol. of < 30cm and GCS of 9 or > predicted a 30 d mortlity of 19%.
  2. Hematoma growth
    • Independent predictor of mortality and poor outcome
    • Each 10% increasein haematoma vol, pt were 5% more likely to die and 16% more likely to increase one point on the mRS (modified Rankin scale)
  3. Early neurologic deterioration
  4. Preciding anticoagulant or antiplatelet use
  5. ICH score (predict mortality after ICH)
    • Components:
      • GCS
      • ICH vol
      • Intraventricular extension of hemorrhage
      • Infratentorial origin
      • Age  


Recommendations for Initial medical Therapy
Class I

  • Monitoring and Mx of patients with ICH should take place in an ICU setting
  • Appropriate antiepileptic therapy should always be used for treatment of clinical seizures in pts with ICH
  • Sources of fever should be treated and antipyretic med should be administered to lower temp in febrile patients with stroke

Class II

  • Treatment of elevated ICP should include a balanced and graded approach that begins with simple measures such as elevation of head of bed and analgesia and sedation.  More aggressive therapies to decrease elevated ICP, such as osmotic diuretics (mannitol and hypertonic saline solution), drainage of CSF via ventricular catheter, neuromuscular blockage, and hyperventilation, generally require ICP monitoring, bp to maintain CPP > 70mmHg
  • Hyperglycemia should be treated
  • Target bp in various situations and potential meds are : labetolo, nicardipine,, esmolol, enalapril, hydralazine, nipride, nitroglycerin.
  • Brief period of prophylactic antiepileptic therapy soon after ICH onset may reduce risk of early seizures in patient with lobar hemorrhage


Intracranial pressure control

    • ICP monitoring
    • Cerebral perfusion pressure
    • Maintained abover 60mmHg
    • CPP = MAP – ICP
    • Medical therapies : Mannitol, hyperventilation, barbiturate coma, temperature management


  • To achieve plasma hyperosmolality (300 -310 mosmol/kg)
  • Hypotonic fluids are contrainidicated
  • Mild hypernatremia should be tolerated


  • PaCO2 of 25 – 30 mmHg
  • Effect only lasts for mins to a  few hours

Steroids should not be used to lower ICP.  Dexamethasone did not improve outcome and did increase complication rates, primarily infection

Barbiturate Coma

  • Depresses cerebral metabolic activity
  • Effective in lowering refractory hypertension but ineffective or potentially harmful as 1st line or prophylactic treatment in pts with brain injuries
  • Common complication : hypotension

Temperature management

  • Cooling to 32 -34C can be effective in lowering refractory intracranial hypertension
  • Longer term )24 – 4hrs) is ass with relatively high rate of complications

Hemostatic therapy

  • Activated recombinant factor VIIa
  • Promotes hemostasis at sites of vascular injury
  • Evidence suggests that treatment within first 3 -4 hr after onset to slow profession of bleeding has shown promise in one moderate sized phase II trial
  • Efficacy and safety of this treatment must be confirmed in phase III trials before its use

Recommendations for Prevention of Deep Vein Thrombosis and PE
Class I
Patients with acute primary ICH and hemiparesis/hemiplegia should have intermittent pneumatic compression for prevention of CTE

Class II

  1. After documentation of cessation of bleeding, low dose S/C LMWH or enoxaparin may be considered in pts with hemiplegia after 3 -4 days from onset
  1. Pts with an ICH who develop an acute proximal VTE or subclinical PE should be considered for acute placement of vena cava filter
  1. Decision to add lont-term antithrombotic therapy severak weeks or more after placement of vena cava filter must take into consideration the likely cause of hemorrhage (amyloid has higher risk of recurrent ICH vs HT), ass with conditions with increased arterial thrombotic risk (eg AF) and the overall health and mobility of the patient


Recommendations for Surgical Approaches
Class I

  1. Patients with cerebellar hemorrhage >3cm who are deteriorating neurologically or who have brain stem compression and/or hydrocephalus from ventricular obstruction should have surgical removal of hemorrhage asap.


Class II

  1. Although stereotactic infusion of urokinase into the clot cavity within 72 hrs of ictus apparently reduces the clot burden and risk of death, rebleeding is more common and functional outcome is not improved; therefore, its usefulness is unknown


  1. For patients presenting with lobar clots within 1cm of the surface, evacuation of supratentorial ICH by standard craniotomy might be considered.

Class III

  1. The routine evacuation of supratentorial ICH by standard craniotomy within 96 hrs of ictus is not recommended


Recommendations for Timing of Surgery
Class II
No evidence at present indicates that ultra-early craniotomy improves functional outcomes or mortality rate.  Operative removal within 12 hrs, particularly when performed by less invasive methods , has most supportive evidence, number of subjectes treated within this windown is very small.
Very early craniotomy may be associated with an increased risk of recurrent bleeding.

Class III 

1..        Delayed evacuation by craniotomy appears to offer little if any benefit with a fairly high degree of certainty.  In those patients presenting in coma with deep hemorrhages, removal of ICH by craniotomy may actually worsen outcome and is not recommented


Recommendations for Decompressive Craniectomy
Class II
Too few data currently exist to coment on the potential of  decompressive craniectomy to improve outcome in ICH


Resumption of antiplatelet therapy

Not much data
Asprin reduces ischemic stroke by 25%.
AHA/ASA guidelines state that antiplatelets should be discontinued for at least 1 – 2 weeks

Back to the question:

Key information given:
Pt’s symptoms started 2 days ago with insidious onset of symptoms.  He is alert with mild facial weakness and hemiparesis.  His SBP is quite high at 170.  CT brain shows quite a large bleed probably more than 30mm.

Options given:

  • Surgery

No clear indication that this patient needs surgery at this point in time as the patient is not neurologicall bleeding and it would be a delayed evatuation with has llittle or no benefit

  • dexamethasone

No benefit in fact increases complication rates eg infection

  • GTN infusion

Bp is at 170 Cut off from the guidelines is > 180mmHg.  Therefore no need to lower bp.

Suggested Recommended Guidelines for Treating
Elevated Blood Pressure in Spontaneous ICH
1. If SBP is _200 mm Hg or MAP is _150 mm Hg, then consider
aggressive reduction of blood pressure with continuous intravenous
infusion, with frequent blood pressure monitoring every 5 minutes.
2. If SBP is _180 mm Hg or MAP is _130 mm Hg and there is
evidence of or suspicion of elevated ICP, then consider monitoring
ICP and reducing blood pressure using intermittent or continuous
intravenous medications to keep cerebral perfusion pressure _60
to 80 mm Hg.
3. If SBP is _180 mm Hg or MAP is _130 mm Hg and there is not
evidence of or suspicion of elevated ICP, then consider a modest
reduction of blood pressure (eg, MAP of 110 mm Hg or target blood
pressure of 160/90 mm Hg) using intermittent or continuous
intravenous medications to control blood pressure, and clinically
reexamine the patient every 15 minutes.

  • Mannitol infusion

No indication that he has a high ICP so you would not give mannitol unless we know what his ICP is.

Therefore the answer is (believe it or not)
e) Observation.

Guidelines for management of Spontaneous ICH in adults June 2007 www.sroke.ahajournals.org


Neurology subarachnoid haemorrhage

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A 35-year-old man who is receiving erythropoietin (EPO) therapy for anaemia associated with end stage renal disease presents with lethargy. There is no obvious source of bleeding.
Blood investigations show:
haemoglobin 65 g/L [110-160]
mean corpuscular volume (MCV) 100 fL [83-97]
reticulocyte count 15 x 109/L [50-100]
The most likely cause of his anaemia is:
A. red cell aplasia.
B. reduced iron stores.
C. non-neutralising anti-EPO antibodies.
D. aluminium toxicity.
E. myelodysplasia.


Main features

  1. Mild macrocytic anemia
  2. Low reticulocyte count – hypoproduction of rbc


This is a horrible question due to the rareness of the condition (165 cases worldwide)

*Pure red cell aplasia* (Answer)

3 characterisitcs

  1. Anaemia
  2. Reticulocytopenia
  3. Absent or rare erythroid precusor cell on bone marrow


  1. Idiopathic
  2. Thymoma
  3. Myelodysplastic syndromes
  4. Viral infection (parvo virus B 19(
  5. Drugs – phenytoin, chloramphenicol

Anti-EPO Ab

  • Mediated by IgG autoantibodies
  • Eprex more indicated in PRCA,
  • ? uncoated rubber stoppers in syringes
  • Subcut administration has been ass with greater immunogenicity than IV

Clinical manisfestation

  • Hb level declines by > 2g/dL/month
  • Reticulocyte count < 20000/microL
  • Drop in platelet count
  • Normal WCC
  • Elevated serum transferring saturation and serum ferritin, reflecting decreased utilization of iron secondary to diminished erythropoisis


  • Bone marrow aspirate – severe erythroid hpoplasia
  • Anti EPO Ab




While on EPO therapy and Hb falls, signifies Fe deficiency or infection
Other factors that interfere with EPO are Aluminium toxicity and hyperparathyroidism

Reduced Fe stores

  • Microcytic picture
  • A higher reticulocyte count



  • Will show more macrocytosis – large rbc
  • Anaemia present in majority of cases + bi or pancytopenia,
  • Circulating myeloblasts



Haematology: Anaemia


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A 28-year-old woman becomes unwell the day after returning from a month-long holiday in Thailand. She complains of a fever with severe headache, myalgia and sore eyes. On the fourth day her temperature settles but two days later recurs and she then develops a generalised rash.
On examination she is pyrexial with a temperature of 37.9oC. Pulse is 80/minute, and blood pressure 120/80 mmHg. There is a diffuse macular rash over the chest and abdomen. The rest of the examination is normal.
Blood tests show a normal haemoglobin, normal leukocyte count, and normal platelets. Blood film examinations for malaria parasites are negative on three occasions.

Which one of the following is the most likely diagnosis?

A. Scrub typhus.
B. Typhoid.
C. Acute schistosomiasis.
D. Dengue.
E. Leptospirosis.

Scrub typhus

Organism: mite borne infectious disease - Orientia tsutsugamushi (described by Chinese in 3rd century)
Gram -ve coccobacillus
Antigenically distinct from the typhus group rickettsiae

Vectors:  larval trombiculid mites of genus Leptotrombidium
                Larval mites (also known as chiggers)

Incubation period:  up to 2 weeks

Disease occurs 7 - 10 days after the bite of an infected chigger


Asia Pacific rim (Korea, China, Taiwan, Japan, India, Thailand, Malaysia, Queensland, Australia)
Study described presence f scrub typhus in remote rain forest region of NT of Australia

Clinical manisfestations

High fever
Intense generalized headache
Diffuse myalgias

Rash, eschar and other signs and symptoms are also present


No laboratory test diagnostically reliable in early phases of scrub typhus

Blood abnormalities

  1. Severe illness - develop thrombocytopenia
  2. Elevations in heaptic enzymes, bilirubin and Cr
  3. Leukopenia or leukocytosis can occus but most have normal WBC
Confirmation of O.tsutsugamushi infection
  1. Serology
    • indirect fluorescent antibodu (IFA) test
  2. Biopsy of an eschar or generalized rash
    • pathological hallmark of scrub typhus is a lumphohistiocytic vasculitis
  3. Culture
    • only available in a few centres'
  4. PCR
    • even in early course of infection
    • sensitive and specific assay


Refer to Q 87 for the explanation of the other diseases
Back to the Question:

Important features:
Waxing and waning fevers- characteristic of Dengue fever.
Incubation period is less than 2 weeks
Develops a macular rash

Again, they ask for the most likely diagnosis.  Therefore the answer is D.  Dengue Fever


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


Question 59 top Download PDF

A 67-year-old man, with a history of smoking 20 cigarettes per day, presents with acute onset of painless loss of vision in the right eye, as if a curtain has suddenly descended over the right eye. After five minutes, vision returned quite rapidly. There are no associated neurological symptoms. Cranial magnetic resonance imaging (MRI) is normal. His carotid angiogram is shown below:


Which one of the following interventions will give the greatest reduction in his risk of stroke or death in the next year?
A. Aspirin.
B. Aspirin/dipyridamole.
C. Clopidogrel.
D. Early revascularisation (< 6 weeks).
E. Late revascularisation (> 6 weeks).

Medical therapy

1)  Asprin

  1. 18% reduction in end points (cardiovasscular and non-cardiovascular events and mortality)
  2. optimal dose of asprin is uncertain, there is no compelling evidence that any specific dose is more effective than another
  3. suggested a dose of 50-81mg/day

Asprin plus dipyridamole

  1. Significantly more effective than asprin alone for stroke prevention
  2. Now considered first line initial therapy for preventing recurrent non cardioembolic ischemic strokes

Asprin plus clopidogrel

  1. Does not offer greater benefit for stroke prevention than either agent alone but does substantially increase the risk of bleeding complications (MATCH trial)
  2. But does show a benefit over asprin alone in patients with acute coronoary syndromes

2)  Clopidgogrel

  1. An alternative to asprin if not tolerated

3)  Ticlopidine

  1. Rarely used due to side effects
  2. Should be reserved for patients intoleratnt of asprin and clopidogrel
  3. Similar to clopidogrel in action (adenosine phosphate inhibitor)
  4. Severe neutropenia 1% of pt

4)  Oral anticoagulation

  1. Recommended for atrial fibrillation with a recentl stroke of TIA
  2. Recomment asprin for pt with AF and cardioembolic stroke who have contraindications to anticoagulation

Symptomatic 70-99%

CEA recommended with recently symptomatic carotid stenosis of 70 – 99 % who have a life expectancy of at least 5 years

  1. Provided the perioperative risk of stroke of death for the surgeon or center is < 6%
  2. NNT to prevent one stroke over 5 years is 6.3

Symptomatic 50-69%
Beneficial for men with 50-69% symptomatic stenosis

  1. NNT over 5 years in this group is 22. 

However women with 50-69% symptomatic carotid stenosis have not shown clear benefit

  1. Medical management rather than CEA for women with recently symptomatic carotid stenosis of 50-69%.


Symptomatic <50%

Medical management for symptomatic carotid stenosis < 50%
CEA not beneficial for symptomatic carotid stenosis of 30-49%
CEA is harmful for symptomatic patients with less than 30% stenosis

Timing of surgery (Grade 1B)

Greatest benefit if performed within 2 weeks of last symptomatic event with >70% carotid stenosis
CEA may not be beneficial if performed 2 weeks or longer after the last event if pt has 50-69% stenosis
Recommend CEA to be performed without delay,preferably within 2 weeks of last symptomatic event

Other factors:
CEA is not associated with significant benefit for patients with near occlusion of the symptomatic ipsilateral internal carotid artery
Patients with hemispheric TIA appear to have greater benefit than pts with transient retinal ischemia
Coexisting severe contralateral carotid stenosis or occlusion may increase perioperative risk but does not cancel out benefit. 

Back to the question:

Patient with symptomatic carotid artery stenosis (70%), the greatest benefit would be early revascularisation. Answer D.


Neurology: Stroke


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A 57-year-old 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 magnetic resonance imaging (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.



T1 weighted image

  • Water molecules in a sample are excited with the imposition of a strong magnetic field
  • Causes millions of water molecules to precess simultaneously and it is this precession of protons which produces signals in MRI

T2 weighted images

  • Constrast is produced by measuring the loss of coherence or synchrony between the water protons.
  • When water is in an environment where it can freely tumble, relaxation tends to take longer. 

General rules

  • Prolonged T1 relaxation time gives hypointensity i.e more black
  • Prolonged T2 relaxation time gives hyperintensity ie. More white

T1 relaxation time

T2 relaxation time

Tissue / lesion

++ increase Intensity

increase Intensity

CSF, cyst, hygroma, cerebromalacia

decreased Intensity

increased Intensity

Ischemia, oedema, demyelination, most malignant tumours

increased Intensity

Slight increased Intensity

Subacute/chronic haemorrhage


increased Intensity



decreased Intensity

Acute haemorrhage



Meningioma (usually identified from structural change or surrounding oedema


Diffusion weighted imaging

  • Fast MRI to detect a signal related to the movement of water molecules between 2 closely spaced radiofrequency pulses (diffusion)
  • Can detect abnormalities dues to ischemia within 3 to 30 mins of onset
  • Acute strokeà swelling of ischemic brain parenchymal cells follws failure of energy dependent Na/K ATPase pumps and is believed to increase the ratio of intracellular to extracellular volume fractions
  • DWI contains additional component of T2 effect
  • Increased T2 signal due to vasogenic edema can “shine through” on DWI images—making it difficult to distinguish vasogenic from cytotoxic edema on these images


  • Induce strong local magnetic fields – particularly shortening the T1 component
  • After IV administration, leakage of gadolimium through regions of damaged blood brain barrier produces marked enhancement of MRI signal eg. Ischaemia, infection, tumours, and demyelination
  • help differentiate tumour tissue from surrounding edema.

Contralateral hemiplegia
Contralateral hemianaesthesis and hemianopia
Aphasia (dominant)
Neglect of contralateral limbs / Dressing difficulty|non dominant

This is not the answer as the patient would have many more symptoms. 


In hypertensive patients, up to 70% occur in the basal ganglia/ thalamic region
Arteries in the brain damaged by exposure to chronic hypertension are the perforator arteries which serve the basal ganlia, thalamus and pons

The MRI T2 weighted one shows an increased intensity which occurs in ischemia and not haemorrhage.  Therefore this is not a haemorrhage.


  • Usually asymptomatic
  • Most common cause of lobar hemorhage in elderly
  • Deposition of congophillic material in small to medium sized blood vessels à cause breakdown of blood vessel wall with haemorrhage
  • Cause single and recurrent lobar hemorrhages


Biggest independent risk fact : AGE

Clinical features

  • Intracerebral hemorrhage
  • Spontaneous lobar hemorrhage
  • CAA-related hemorrhages have predilection to cluster in posterior brain regions and display an additional tendency to cluster in the same lobe within indivicual patients. 



  • Suspected clinically in pts over age of 60 who have multiple lobar hemorrhages in the absence of any obvious cuase
  • GOLD STANDARD: post mortem


  • Same as any other acute intracerebral hemorrhage
  • Attention to ICP and bp control
  • High recurrence rate, avoid anticoagulant and anti platelet agents

This is not the answer as it is not visbile on imaging.  It is a diagnosis of clinical suspicion.


Difficult to distinguish edema of acute plaque from gliosis and demyelination of a chronic plaque with conventional MRI technology
It is unlikely to be this answer as the question mentions it is a 57 year old man who has hypertension and is a smoker.  Having slurred speech is an unlikely presenting symptom of demyelination. 

Answer is D.


Neurology: Stroke


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A 67-year-old man with a history of heavy smoking presents with new onset angina. On examination he is found to be plethoric and hypertensive with no other abnormalities noted.
His full blood examination shows:
haemoglobin                             205 g/L [128-175]
haematocrit                               57% [36-50]
mean cell volume (MCV)            78 fL [80-97]
white cell count                                     11.6 x 109/L [3.9-12.7]
neutrophils                                9.50 x 109/L [1.50-6.00]
lymphocytes                             0.60 x 109/L [0.70-3.15]
monocytes                                0.30 x 109/L [0.15-0.60]
eosinophils                               0.80 x 109/L [0.00-0.40]
basophils                                  0.40 x 109/L [0.00-0.15]
platelets                                    499 x 109/L [150-396]
red cell mass                            39 mL/kg [28-35]
plasma volume (derived)            49 mL/kg [40-50]
serum erythropoietin                  4.9 IU/L [4.8-21.9]

The most likely explanation for these findings is:
A. carcinoma of the lung.
B. high affinity haemoglobin.
C. dehydration.
D. chronic obstructive pulmonary disease.
E. polycythaemia vera.





Polycythaemia rubra vera


EPO appropriately increased

  1. High altitude
  2. Cyanotic congenital heart disease
  3. Chronic lung disease
  4. Hb variant with increased oxygen ability

EPO inappropriately increased

  1. Renal disease: hypernephroma, renal cyst, hydronephrosis
  2. Uterine myoma
  3. Other tumours eg. Hepatocellular carcinoma, bronchial carcinoma


Plasma volume depletion
Stress (‘pseudp-polycythaemia’)
Diuretic therapy

True polycythaemia exists when the total red cell mass (RCM), measure by dilution of isotopically labelled red cell, is increased above normal.

Relative polycythaemia exists when an elevated haemoglobin concentration is caused by reduction in plasma volume

Clinical features

  1. Raised RCM – ruddy complexion
  2. Hyperviscosity – headaches and visual disturbances, thrombosis
  3. Haemorrhage
  4. Pruritus, gout
  5. Enlarged spleen (75%) (distinguishes between  PCV and others

Lab findings

  1. Raised haematocrit, red cell count and RCM
  2. Raised WCC (75%)
  3. Bone marrow: hypercellular with prominent megakaryocytes
  4. Iron stores are depleted
  5. Abdo U/S – exclude renal disease, assess spleen size

Differential dx
1.  Relative polycythaemia arise when plasma volume is reduced

  1. Dehydration
  2. Vomiting
  3. Diuretic therapy

2.  Young male adults (especially smokers)

  1. Ass with stress, increased vasomotor tone and HT
  2. WCC, plt count, RCM and bone marrow normal

Other test:

  1. Cxr – exclude lung disease
  2. Haemoglobin oxygen dissociation curve – to identify a variant Hb with increased O2 affinity
  3. Serum EPO assay



  1. Asprin
  2. Regular venesection
  3. Chemotherapy (oral hydroxyurea)

Median survival is 16 years – thrombosis main cause of morbidity and mortality
30% develop myelofibrosis
5% develop AML


Haematology:Polycythaemias-primary and secondary


Question 71 top Download PDF

A 49-year-old man sees you six weeks after inferior Q-wave myocardial infarction treated at a country hospital. Current drug treatment is aspirin 100mg, ramipril 5mg, and atorvastatin 20mg daily. He is obese (body mass index 31 kg/m2 [18-25]). Glycosylated haemoglobin is 6.0%.
Fasting lipid profile reveals:
total cholesterol 4.8 mmol/L [2.5-5.2]
high-density lipoprotein (HDL) cholesterol 0.5 mmol/L [0.9-1.8]
triglycerides 9.80 mmol/L [0.10-1.85]
Which one of the following is the most effective drug treatment to lower the triglyceride level?
A. Add a bile acid binding resin.
B. Increase the dose of atorvastatin.
C. Add metformin.
D. Change atorvastatin to an alternative statin.
E. Add a fibrate

This patient has extremely high TG and the most effective agent to reduce TG is the fibrate.

Therefore answer is E.


Cardiology - Coronary Disease: Risk factors and management (primary and secondary prevention)


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A 75-year-old woman with known chronic obstructive pulmonary disease (COPD) is admitted to hospital with a two-day history of worsening breathlessness, cough and sputum production. On admission her arterial blood gases breathing air show:

pH 7.31 [7.35-7.45]
PaCO2 62 mmHg [35-45]
PaO2 42 mmHg [>75]

Which of the following interventions is most likely to reduce her risk of intubation and ventilation?

A. Antibiotics.
B. Non-invasive continuous positive airway pressure.
C. Oral corticosteroids.
D. Non-invasive positive pressure ventilation.
E. Nebulised bronchodilators.


Treatment of acute exacerbation of COAD
Hypercapnic respiratory failure


  1. Infection (50-60%)
    • Bacterial
    • Viral
  2. Environment
    • Pollution (10%)
    • Temperature
  3. Unknown (30%)

Treatment for acute exacerbations of COAD

  1. Beta-adrenegic agonist
  2. Anticholinergic agents
  3. Corticosteroid
      1. reduced 30 and 90 day treatment failure rate
      2. reduced hospital stay
      3. improve lung function
  4. Limited spectrum Ab
      1. reduced mortality
      2. reduced treatment failure rate
      3. accelerate improvement of peak exp flow rates
  5. Mechanical ventilation
    • NIPPV (Non invasive positive pressure ventilation)
    • Consist of CPAP and BIPAP

Indications for NIPPV

-  acute exacerbations of COPD
-  acute cardiogenic pulmonary edema
-  hypoxemic respiratory failure


- use of NPPV associated with fewer intubations, decreased mortality and shortened ICU admissions
-  comparing medical care to NPPV + medical care à risk of death lower in NPPV group
-  reduction in nosocomial infection (line sepsis, reduced stay in ICU)
-  failure of NPPV to prevent intubation was ass with higher mortality iin patients with respiratory failure

Treatments that don’t work

  1. Methylxantines ex aminophylline or theophylline
      1. not recommended
      2. failed to show efficacy compared to bronchodilators
  2. Mucokinetic regimens
      1. little evidence
      2. worsen bronchospasms
      3. use of mechanical techniques such as chest physio, directed coughing provokes bronchoconstriction


Answer:  D.  Only NIPV reduces the risk of intubation and ventilation.  Did not specify whether it is CPAP or BIPAP.


Respiratory: COPD Smoking-related chronic lung disease


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A 72-year-old man with a history of coronary artery bypass grafting is admitted with biventricular failure. His full blood examination is normal on admission. In addition to therapy for cardiac failure, he receives thromboprophylaxis with subcutaneous unfractionated heparin, 5000 units twice daily. On day 8 of admission, he complains of left leg pain and an ultrasound shows extensive thrombosis extending from the popliteal to the external iliac veins. His full blood examination now reveals thrombocytopenia (platelets 35 x 109/L [150-396]) and a test for heparin-induced thrombocytopenia by enzyme-linked immunosorbent assay (ELISA) is positive. There is no current evidence of bleeding.

In addition to stopping the heparin, which of the following is the most appropriate immediate treatment option?

A. Observation.
B. Dalteparin.
C. Platelet transfusion.
D. Intravenous immunoglobulin.
E. Danaparoid.

Suspected HIT:

  1. Thrombocytopenia,
  2. thrombosis with thrombocytopenia,
  3. a plt count which has fallen by > 50% or
  4. necrotic skin lesions at injection sites in a pt started on heparin within the preceding 5 to 10 days.

Clinical manifestation: 


4 to 10days after initiation of heparin, 2 weeks is unusual Early onset may be seen if receive heparin in prev 3 to 4 mths
Delayed onset:  occurs after heparin has been withdrawn (average 9 days post withdrawal)

  1. spontaneous bleeding is unusual as thrombocytopenia  rarely drops below 30-60,000/mL
  2. Thrombosis
    • venous & arterial thrombosis
    • mechanism of hypercoagulable state unknown
    • major manisfestations of venou s thrombosis is DVT and PE, venous limb gangrene, cerebral sinus thrombosis
    • arterial thrombosis- less common - stroke, MI, limb ischemia from peripheral arterial ooclusion or organ infarction. 
    • Thrombosis tend to be platelet rich and therefore these clots are "white" due to platelet aggregates à "white clot syndrome"
  3. Skin necrosis
    • affected areas usually fat -rich :  abdomen
    • lesions similar to warfarin-induced skin necrosis, deficiencies of natural anticoargulants are not present 


Antibody response:  IgG and Ig M antibodies provoked by heparin, complex of heparin bound to platelet factor 4 (PF4)
IgG antibody directed against the heparin-PF4 complex binds platelets through the Fc receptor, leading to platelet activation and micro-particle formation.  Platelet rich thrombi form at sites of preexisting pathology or sites of endothelial cell injury

Diagnostic testing

Clinical diagnosis:

  • Unexplained thrombocytopenia
  • Thrombosis ass with thrombocytopenia
  • A plt count fallen 50% or more from prior value
  • Necrotic skin lesions at heparin injection sites

Diagnostic test:  serotonin release assays (gold standard sensitivity 100%, specificity 97%), heparin-induced platelet aggregation assays and solid phase immunoassays


  1. Cessation of all exposure to heparin
  2. LMW heparin should be avoided due to cross reactivity with heparin induced antibodies
  3. Patients remain at risk of thrombosis and therefore require ongoing anticoagulation
    1. lepirudin (recombinant hirudin)
    2. bivalirudin
    3. argatroban
    4. danaparoid
      • 10% cross reactivity between danaparoid and the antibody responsible for HIT
      • persistence of, or recurrence of thrombocytopenia without thrombosis in 6.5% of pts switched from heparin to danaparoid. 
      • Long half life and therefore need to measure anti-Xa levels to monitor its anticoagulant effect and the absence of reversing agent

   To continue until platelet count recovers

Back to the question:
Its not the answer A, Observation because they remain at risk of further thrombosis and therefore need ongoing anticoagulation.

Option B daltaparin (low molecular weight heparin)
Cross reactivity with antibodies and therefore should not be used

Option C  Platelet transfusion 
Spontaneous bleeding begins at platelet count below 40,000/mcL while severe spontaneous bleeding seen at plt counts below 10,000.  With HIT, there is low bleeding and giving platelets may increase the risk of new thromboembolic lesions

Option D
IV immunoglobulins have not much evidence that it works. 

Note:  Warfarin should not be given to patients who already have HIT until the thrombocytopenia resolves. Warfarin in the absence of other anticoagulants should be avoided in patients with HIT until the platelet count rises above 100 ×109/L.14 Because of its early effects on protein C, warfarin can precipitate venous limb gangrene and limb loss
in the extreme prothrombotic milieu of type 2 HIT.

Answer E  Danaparoid.


Haematology: Thrombocytopenia

Question 79 top Download PDF

In an 80-year-old woman with low back pain, which of the following is most suggestive of a diagnosis of spinal canal stenosis?
A. Increased pain with prolonged weight bearing.
B. Lower-extremity numbness with prolonged weight bearing.
C. Loss of lumbar lordosis.
D. Advanced degenerative changes seen on plain radiograph.
E. Loss of vibratory sense in the feet.

According to Up to date


  1. Neurogenic claudication is a hallmark of LCS. 
  2. Usually pain, to be exacerbated with walking, standing, and/or maintaining certain postures, and relieved with sitting or lying
  3. Relieved with lying, sitting or flexion at the waist
  1. Other symptoms: discomfort, sensory loss and weakness in the legs


  1. Most common symtom:
    1. PAIN 93%
    2. Numbness and tingling 63%
    3. Weakness 43%
    4. Symptoms bilateral 68%


  1. Plain radiographs
  1. Can lend support for the diagnosis of LCS and may suggest underlying pathology
  2. Should be limited to pts with clinical findings suggestive of systemic disease or trauma
  3. Guidelines recommend plain radiography for pts with fever, unexplained weight loss, history of cancer, neurologic deficits, alcohol or injection drug abuse, an age of more than 50yrs or trauma
  4. Failure of pain to improve after 4-6 weeks should prompt xray

In an 80 yr old, it is possible to find advanced degenerative changes but would not confirm the diagnosis of spinal canal stenosis

  1.  MRI
  1. Modality of choice
  2. Defines bony anatomy and visualizes soft tissues and neural structures


  1. CT
  1. May be preferable to MRI for bony anatomy
  2. More sensitive than plain radiography for detection of early spinal infections and cancers
  3. When combined with myelography- proveds imaging of neural elements
  4. CT myelography is invasive and therefore MRI preferred but good alternative if MRI contraindicated


According to Merritt’s Neurology (Books @ Ovid)

Signs and Symptoms

  1. Pain aggravated by Valsalva manoeuvres
  2. Lumbar pain may increase after heavy lifting or twisting of spine
  3. Relieved by lying down
  4. If pain not relieved on lying down or worsened, suggesting of disc disease from intraspinal tumour



  1. Loss of lumbar lordosis or flattening of lumbar spine
  2. Splinting and asymmetric prominence of long erector muscles
  3. Range of motion of LS is reduced by the protective splinting of paraspinal muscles
  4. Passive straight leg raising is reduced and increases back and leg pain
  5. Muscle atrophy and weakness
  6. Parasthesia in the region of the involved root

Back to the question:

This question asked for “ most suggestive “.

  1. Increased pain with prolonged weight bearing
  1. This is right as pain can be aggravated by Valsalva manoeuvres
  2. Pain is the most common symptom


  1. Lower extremity numbness with prolonged weight bearing
  1. With parasthesia, it is more likely to have nerve root involvement compared to pain.  
  2. 2nd most common symptom after pain – perhaps for specific to spinal root involvement
  1. Loss of lumbar lordosis
  1. Can be present with LCS
  2. Can occur with lots of other diseases such as osteoporosis


  1. Advanced degenerative changes on plain radiograph
  1. In an 80 year old man, this could be a cause of the lower back pain but does not confirm LCS
  1. Loss of vibratory sense


Answer B.


Neurology: Radiculopathy


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A 67-year-old woman with congestive cardiac failure remains
despite treatment with 40 mg frusemide and 20 mg enalapril daily. On examination she has a pulse rate of 80/minute, blood pressure of 125/70 mmHg and a jugular venous pressure (JVP) of +1 cm. 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.

Cause of Heart failure

  1. Coronary heart disease - ischemic cardiomyopathy
    • systolic dysfuntion
  2. Cigarette smoking
  3. Hypertension
    • Framingham Heart Study:   lifetime risk of developing HF X2 in subjects with bp  160/100 compared to < 140/90
  4. Overweight
  5. Diabetes
  6. Valvular heart disease - calcific aortic stenosis

small print causes or Other causes to impress examiner

  1. alcohol/cocaine abuse
  2. OSA
  3. nutritional deficiencies
  4. myocarditis
  5. hemochromatosis
  6. sarcoidosis
  7. thyroid disease
  8. SLE

Types of cardiac failure

  1. systolic
  2. diastolic
    • ass with aging, hypertension, DM, L ventricular hypertrophy, coronary disease and infiltrative cardiomyopathies
    • tend to be older and overweight
    • women > men
    • have renal dysfunction,
  1. 12 lead ECG
    • if normal, then heart failure due to L  ventricular systolic dysfunction is unlikely
  2. Chest Xray
  3. FBE, UEC, LFT, TFT, fasting lipids
  4. Urinalysis to detect proteinuria or glycosuria
  5. TTE
  6. Plasma concentration of B type natriuretic peptide/ N-terminal pro- B type natriuretic peptide


  1. Treatment of underlying cardiac disease
    • reduce preload (to diminish congestive Sx) & afterload(to improve cardiac function)
  2. Lifestyle management
    • low salt diet (
    • regular aerobic exercise to improve peripheral muscle function
    • annual influenza vaccination
    • smoking cessation
  3. Drugs
    1. Diuretics
      • for rapid symptomatic relief
      • on its own exacerbates neurohormonal activation, therefore demands the use ACE-I and beta blocker
    2. ACEi
      • introduced at low dose and titrated upwards over several weeks
      • monitor symptoms, bp and Cr
    3. AR2B
      • Valsartan HF trial:  patients did not live longer when added to ACEi but did show a reduction in risk of admission to hospital for worsening HF
    4. B- blocker
      • carvedilol, bisoprolol, metoprolol
      • start at low dose and titrate gradually over several weeks
      • improve survival
      • provide anginal relief
      • minimize risk of cardiac decompensation
    5. Spironolactone (25-50mg/d)
      • reduces mortality in pts with moderate or severe Sx due to systolic HF
    6. Digoxin
      • symptomatic treatment of pts with HF & AF
      • no evidence that dig improves survival in pts in sinus rhythm
    7. Drugs that interact with anti-failure drugs or increase fluid retention:
      • NSAIDS
      • Ca antogonist
      • Lithium
      • parenteral corticosteroids
      • tricyclic antidepressants increase risk of arrhythmias
  4. Cardiac surgery
    • coronary bypass surgery if it is the primary cause of HF à muscle is still alive  but not contracting has the potential to recover after revascularisation
    • vavular heart surgeryà lead to improvement in cardiac function and resolution of Sx
  5. Implantable cardioverter-defibrillators
    • primary prevention to reduce total mortality in pts who
      1. 40d post MI
      2. LVEF < 30%
      3. NYHA Class II or III Sx while on chronic medical therapy
      4. reasonable expectation of survival with good functional status for > 1yr
    • secondary prevention in pt with
      1. current or prior Sx of HF
      2. reduced LVEF
      3. Hx of previous cardiac arrest or episodes of sustained ventricular tachycardia
  6. Cardiac resynchronization therapy
    • LVEF < 35%
    • sinus rhythm
    • NYHA class III or IV despite optimal medical therapy
    • cardiac dyssynchrony (QRS duration > 0.12)
  7. HARP team
    • these teams have shown to reduce rate of admission to hospital
    • pt education to identify their early signs of deterioration
      • daily weigh
      • educated to adjust the diuretic dose at early stage of decompensation


Cardiology: Heart Failure

Question 82 top Download PDF

A 25-year-old woman with no significant past medical history presents with weight gain, depression, easy bruising and proximal muscle weakness. On examination she has a plethoric complexion, central obesity with striae and a proximal myopathy. Investigations reveal low plasma concentrations of cortisol and adrenocorticotrophic hormone (ACTH). Which of the following is the most likely diagnosis?
A. Cushing’s disease.
B. Pseudo-Cushing’s syndrome.
C. Factitious Cushing’s syndrome.
D. Ectopic ACTH syndrome.
E. Cortisol-producing adrenal adenoma

Cushing syndrome

  1. result directly from chronic exposure to excess glucocorticoid
  2. this patient has Cushing’s syndrome with her clinical presentation

ACTH Dependent Cushing’s Syndrome

Cushing’s disease

  • Pituitary adenoma
  • Usually microadenomas, 5% macroadenomas
  • Macroadenomas are more likely to have high plasma ACTH concentrations compared to those of macroadenomas.
  • Increased cortisol secretion:
  1. increased urinary excretion of cortisol and 17-OHCS
  2. inhibits hypothalamic CRH secretion
  3. inhibits ACTH secretion by normal nonadenomatous pituitary corticotrophs- atrophy
  4. concentration of CRH in cerebrospinal fluid are reduced

Ectopic ACTH syndrome

  • Nonpituitary tumour secretion of ACTH – usually carcinomas (lung, pancreas, thymus)
  1. Small-cell carcinoma of lung – arise from neuroendocrine cells in the distal bronchioles
  2. ACTH secreting pancreatic and thymic tumours are carcinoid tumors arising from neuroendocrine cells
  • Tumor ACTH secretion is not inhibited by cortisol or other glucocorticoids                                      

Ectopic CRH syndrome
CRH secretion by tumor causes hyperplasia and hypersecretion of pituitary corticotrophs
ACTH hypersecretion, cortisol hypersecretion & bilateral adrenal hyperlasia
Many of these tumours also serete ACTH- in inhibited by dexamethasone
ACTH-Independent Cushing’s Syndrome

Primary adrenocortical hyperfunction

  • Increased cortisol secretion suppresses both CRH and ACTH secretion
  • Normal pituitary corticotrophs, normal zonae fasciculata and reticularis of adrenal glands atrophy
  • Serum dehydroepiandrosterone (DHEA-S) concentrations and urinary excretion of DHEA-S and 17 KS are low relative to urinary 17-OHCS or cortisol excretion

Bilateral micronodular hyperplasia

  • Sporadic and familial forms
  • Carney’s complex: familial form
  • Autosomal dominant
  • 2 major types of findings:
  1. pigmented lentigines
  2. blue nevi on face, neck, and trunk, including the lips, conjunctivae, sclerae
  3. multiple neoplasms – endocrine (testicular Sertoli cells and occasionally adrenal, pituitary or thyroid) and non endocrine (cutaneous, mammary, atrial myxomas)

Bilateral ACTH-independent macronodular hyperplasia

  • Associated with adrenal glands that weigh from 24- 500g
  • Contain multiple nonpigmented nodules greater than 5 mm in diameter
  • Nodules appear to be typical benign adrenal nodules
  • Pathology
  1. Overexpression of eutopic receptors
  2. Inappropriate expression of ectopic receptors
  3. Coupling of eutopic receptors to steroidogenic signalling pathways

Factitious Cushing’s syndrome

  • Rare, < 1% of pts 
  • Refers to surreptitious intake of glucocorticoid
  • Difficult to detect from history and difficult to exclude with laboratory tests
  • Dx:      
  1. low or erratic values for urinary cortisol- suggestion of of ingestion of a synthetic glucocorticoid or intermitten ingestion of cortisol or cortisone
  2. Excessive urinary cortisol relative to serum cortisol concentrations – suggestion of addition of hydrocortisone to urine specimens
  3. Detection of synthetic glucocorticoids in urine

Pseudo-Cushing’s syndrome

  • Physically stressed
  • Severe obesity – visceral obesity, polycystic ovary syndrome
  • Psychological stress- severe major depressive disorder or melancholic syndrome (refer to Tricia’s question 2003 P1 Q 16) 
  • Chronic alcoholism


Back to the question:

Patient does have symptoms of Cushing’s syndrome.  The question is whether the blood test show a ACTH dependent or independent syndrome.  Her cortisol level and ACTH are low

  Cortisol ACTH
Cushings disease increased summpressed
Pseudo-Cushing’s syndrome  increased increased
Factitious Cushing’s syndrome. suppressed suppressed
Ectopic ACTH syndrome. increased increased
Cortisol-producing adrenal adenoma increased suppressed

Diagnostic test

24hr urinary cortisol excretion
basal urinary cortisol excretion is more that 3X the upper limit of normal – diagnostic of Cushing’s sundrome

up to 40% of patients with secere depression or polycystic ovary syndrome may have slightly high 24hr urinary cortisol excretion
people who drink very large volumes of liquid also excrete more cortisol while excretion of Cr and 17 hydroxycorticosteroids remain unaltered. 
If more thant 3L of urine volumes- urinary cortisol excretion should be interpreted with caution

Low dose dexamethasone suppression test
Exogenous dexamethasone substitutes for endogenous cortisol in suppressing ACTH release

Low dose dexamethasone:
To differentiate patients with Cushing;s sundrome of any cause from patients who do not have Cushing’s syndrome.
Dexamethasone dose (1mg)

High dose dexamethasone:
To differentiate patients with Cushing’s disease from patients with ectopic ACTH syndrome


Endocrinology Adrenal Disorders

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A 22-year-old man presents with ten days of fever that started three weeks after returning from visiting family in Bangladesh. He complains of headache, abdominal pains, anorexia, a dry cough and generalised muscular aches and pains.

On examination he looks ill. Temperature is 40.5oC, pulse 92/minute and blood pressure 120/65 mm Hg. On auscultation he has a clear chest. There is generalised abdominal tenderness without rigidity or guarding.

Blood tests show:
haemoglobin 140 g/L [130-180]
white cell count 3.5 x 109/L [4.0-11.0]
Blood films are repeatedly negative for malaria. Renal function, electrolytes, liver enzymes and chest X-ray are normal.

What is the most likely diagnosis?

A. Acute schistosomiasis.

B. Amoebiasis.

C. Leptospirosis.

D. Typhoid.

E. Dengue fever.

Evaluation of fever in returning traveler

In the GeoSentinel study, among patients with systemic febrile illness, the most common specific diagnoses were the following:

  • Malaria
  • Dengue fever
  • Mononucleosis (due to EBV or CMV)
  • Rickettsial infection
  • Typhoid or paratyphoid fever
  1. What processes might cause febrile illness if individual had not traveled
    • routine infections
    • noninfectious disease that cuase fever à thrombophlebitis, PE, drug fever
  2. Dates of travel, duration of stay, activities and exposures, vaccinations/prophylactic Ab
  3. Sexual history
    • STD tha cause fever:  syphilis, disseminated gonococcal infection, HIV, Hep B,CMV, Hep A, Hep C (rare)
  4. Vaccines
    • yellow fever and Hep A vaccines are highly efficacious, making infection   unlikely
    • some travelers lack immunity to measles, rubella and diphtheria because of gaps of immunization
    • malaria chemoprophylaxis is not 100% effective and may experience resistance.
Timing of exposure

If more than a month has lapsed since tropical travel, many infections can be excluded

Physcial examination

1)  Special care for skin lesions
2)  lymphadenopathy
3)  retinal or conjunctival changes
4)  enlargement of liver or spleen
5) genital lesions,
6)  neurologic finding


1)  FBE, LFT, blood cultures,
2)  blood smears for malaria (done urgently that day)
3)  Cxr
4)  Urinalysis

General Principles

  1. 4 major syndromes;
    1. Systemic febrile illness
    2. Acute diarrhea
    3. Dermatologic disorders
    4. Chronic diarrhea
  2. Malaria was the most frequent cause of systemic febrile illness
    Dengue was more frequent in all regions except sub-Sahran Africa and Central America
  3. Rickettsial infections appeared most exclusively among travelers returning from sub Saharan  Africa
    Typhoid fever was the leading systemic febrile illness in those returning from South central  Asia
  4. Parasite-induced diarrhea was more common among travelers than was bacterial diarrhea in all regions except SEA
    In SEA, campylobacter was the predominant pathogen
  5. Insect bites were the most common cause of dermatologic complaints
    Cutaneous larval migrans was the most common skin disorder from Caribbean

Acute Schistosomiasis

Majority are completely asymptomatic although acute Sx more common in nonimmune individuals eg. Travelers, because of a more intense immune response to exposure

  1. Swimmers itch
    • localized dermatitis that result in a pruritic popular rash at the site of larval entry (lower legs/feet)
    • seen within one day of exposure tingling and itching at site of entry follwed by intensely pruritic popular eruption 12-24 hrs later
      seen in people with repeated contact
  2. Katayama fever
    • Sx:  fever, chills, myalgias, arthralgias, dry cough, diarrhea and headache
    • signs:  lymphadenopathy, heapatosplenomegaly
    • Ix:  eggs not frequently excreted in detectable amts but peripheral eosinophilia will be present
    • develop between 4 to 8wks after exposure
    • due to hypersensitivity to schistosome antigens and circulating immune complexes
    • Sx more likely to occur in travelers and other non immune hosts. 

Caused by protozoan Entamoeba histolytica
2 other strains E dispar and E moshkovskii (asymptomatic)
Parasite exists in 2 forms :  1)  cyst stage (infective)  2)  trophozoite stage  (invasive disease)
Infection occus following
a)  ingestion of amebic cysts via contaminated food or water
b)  venereal trarnsmission through fecal-oral contact

Areas with high rates of amebic infection:
India, Africa, mexico, parts of Central and South America


Cysts pass through stomach to small intestine when they excyst to form trophozoites. 
Trophozoites invade and penetrate the mucous barrier of the colon causing tissue destruction and increased intestinal secretion
Cause bloody diarrhea

Clinical manisfestations

Subacute onset: 1 - 3 weeks


  • mild diarrhea to severe dysentery producing abdo pain, diarrhea and bloody stools.
  • Weight loss (<50%)
  • Fevers (8 - 38%)
  • Fulminant colitis with bowel necrosis leadinig to perforation and peritonitis (0.5%)
  • Ass with mortality rate of > 40%


Present as chronic, nondysenteric syndrome of diarrhea, weight loss and abdo pain over years


  1. Microscopy of stools
    • to show cysts or trophozoites. 
    • Cannot differentiate between 3 strains
  2. Antigen testing * BEST*
    • ELISA test specific for E histolytica
  3. Serology
    • Antibodies detectable within 5-7 days of acute infection
    • Indirect hemagglytination is the most sensitive assay and is +ve to app 90% of pts with symptomatic intestinal infection

E.dispar and E.moshkovskii infection does not require treatment
Asymptomatic E. histolytica show be treatmed because of potential risk of developing invasive disease and risk of spread to family members

  1. Metronidazole (500-750mg tds for 7-10 days)
    • 90% success rate
  2. Tinidazole
    • 2g oral daily for 3 days
    • 90-93% cure rate
  3. PLUS If patients have invasive colitis, they should be treated with agents for eliminating luminal cysts
    1. Paromomycin
    2. Diiodohydroxyquin

Follow up stool examinations are required after completion of therapy


(Synonyms: Weil's disease, Swineherd's disease, rice-field fever, cane-cutter fever, swamp fever, mud fever, hemorrhagic jaundice, Stuttgard disease and Canicola fever)

Zoonosis with protean manifestations cause by spirochete, Leptospira interrogans
Spiral shaped
Aerobic spirochetes with 18 or more coils per cell


Majority of clinical cases occur in tropics
Man is incidentally infected after exposure to environment contaminated by animal urine, contaminated urine or via aerosola

Clinical manisfestation

Non specific clinical illness
Disease may manfest as a subclinical illness followed by seroconversion, a self limited systemic infection or a severe, potentially fatal illness accompanied by multiorgan failure

Incubation period: 2-26days (average 10d)
Abrupt onset of fever, rigors, myalgias and headache (75-100%)
Non productive cough (25-50%)
Nausea, vomiting and diarrhoea (50%)
Less common Sx:  arthralgias, bone pain, sore throat, abdo pain


Most cases are mild to moderate
Course may be complicated by:  Renal failure, uveitis, haemorrhage, acute respiratory distress syndrome, myocarditis, rhabdomyolysis


blood and CSF specimens are +ve during the 1st 10d of illness
Isolation of organisms from blood is successful in about 50% of cases
Urine becomes +ve during the 2nd week of illness and remain so for up toe 30d after resolultion of symptoms

Microscopy: Stains with dark field microscopy, silver stain or fluorescent microscopy
Culture:  in 1-2 weeks or may take up to 3 months

Used for confirmation
GOLD STANDARD:  Microscopic agglutination test (MAT)
                                  More specific when a 4 fold or greater rise in titer is detected between acute and convalescent serum specimens
A single titer of > 1: 800 is a strong evidence of current or recent infection

Other Ix:
WCC < 10,000
Urinalysis: freq shows proteinuria, pyuria, granular casts and occasionally microscopic hematuria
Elevated CK - 50%
Elevated hepatic transaminases (40%)
Hyponatremia in severe leptospirosis
Cxr:  (MAY SHOW) small nodular densities which can progress to confluent consolidation or ground glass appearance

  1. self - limiting
  2. doxycycline
    • for outpatients because it is also effective for rickettsial disease (often confused with    leptospirtosis
    • dose:  100mg bd
    • children < 8yo & pregnant women - amoxicillin
  3. Hospitalized / severe disease
    • IV penicillin
    • oral doxycycline
    • ceftriaxone

No vaccine available
Recommend doxycycline prophylaxis for individuals exposed to leptospires in high endemic environment (Vets, military deployed in jungle)

Typhoid fever

Organism:  Salmonella typhi or Salmonella paratyphi A, B, or C
                  Gram -ve bacilli

S.parathypi A: more likel to be nalidixic acid and fluoroquinolone resistant compared to S.typhi
Spread via ingestion of contaminated food or water
High risk areas:  India subcontinent

  • 1st week: rising "stepwise" fever and bacteremia
  • 2nd week:  abdo pain and rash (rose spots, which are faint salmon colored macules on trunk and       abdomen)
  • 3rd week:  hepatosplenomegaly, intestinal bleeding and perforation related to ileocecal lymphatic hyperplasia of the Peyer's patch - occur with secondary  bacteremia and peritonitis

Blood cultures:  +ve in 40-80% of patients
Stool culture: +ve in up to 30-40% , often -ve
Bone marrow- often diagnostic
Blood test:
Leukopenia/ leukocytosis
Abnormal LFT (suggestive of acute viral hepatitis)


Typhoid vaccination-  does not provide protection against paratyphoid fever and neither is completely effective against S.typhi
Caution in what is ingested


Complicated by development and rapid dissemination of typhoidal organisms resistant to ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol

  1. Ciprofloxacin (500mg bd) for 7 - 10days
  2. Ceftriaxone (2-3g daily) for 7-10days

1)  Azithromycin
2)  Chloramphenicol 

Dengue fever

Transmitted by Aedes aegyptii mosquito
Virology: DEN-1, DEN-2, DEN-3, DEN-4 of genus Flavivirus

Incubation period of 4- 7 days  But can be excluded if more than 14days after returning

Clinical presentation:
  1. Asymptomatic infection
    • younger the age, the less symptomatic (Sx less frequent in < 19yo)
  2. Self limited dengue fever
    • Dengue hemorrhagic fever with shock syndrome
    • risk of severe disease higher in sequenctial infection
  3. Classic dengue
    • fever, headache, retroorbital pain, marked muscle a nd joint pains
    • fever last 5 - 7 days
    • develop biphasic (saddleback) fever curve
    • febrile period followed by period of marked fatigue that can last for days to weeks
    • rash occurred between 2 and 5 days after onset of fever
    • Other Sx: 
      • Fever 90%
      • Headache, eye pain, body pain & jt oain (63-78 %)
      • Rash (>50%)
      • GIT Sx - N + V (> 50%)
      • Diarrhea (30%)
      • Resp Sx - cough sore throat, nasal congestion (33%)
  4. Dengue haemorrhagic fever
    • 4 cardinal features by WHO
      1. Increased vascular permeability (plasma leakage syndrome) - haemoconcentration, pleural effusion, asicites
      2. Marked t hrombocypenia ( < 100,000)
      3. Fever lasting 2 - 7days
      4. Haemorrhagic tendency or spontaneous bleeding
  5. Dengue  shock syndrome
Physical examination: 

Macular or maculopapular rash in 50%


A CLINICAL ONE in endemic countries

Serology test:

  • IgM immunoassay (MAC-ELISA) - yield a false negative result if obtained within the 1st 6 days of illness
  • To confirm +ve IgM assay result, a convalescent phasae serum sample should be obtained  10-14 days after the acute phase serum
    Acute and convalescent specimens analysed together by a hemagglutination inhibition (HI) to provide definitive serologic testing

Supportive treatment
1)  IV replacement due to plasma leakage
2)  Blood transfusion if significant bleeding

Sx in patients with dengue resolve in 5-7 days

Back to Question:

The 2 most likely diagnosis is Dengue and typhoid from the general priniciples for someone with fever returning from Asia.  The incubation period is the differentiating factor here as he presents 3 weeks after returning.  Dengue fever can be excluded if presents after 2 weeks.  Abdo pain is also a less common symptom of Dengue fever but hey who knows with these infectious disease, they kinda could get anything really. 

Leptospirosis could be very likely as well as it fits all the description.  Incubation period is around 3 weeks, presents with fever, abdo pain and can have leucopenia.  Why it isn't the answer, I don't know.  But the question does say MOST FREAKING LIKELY.

Therefore the answer is D Typhoid.


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


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An 81-year-old man presents to the emergency department after collapsing while running for a bus. He has a history of hypertension treated with felodipine but no other major illnesses. He has noted mild breathlessness on exertion, worsening over the past few years. Examination reveals blood pressure is 125/90 mmHg. He has a soft systolic murmur but no signs of heart failure. His ECG is shown below. Serum creatine kinase (CK) is 205 U/L [<180]. Troponin level is pending.

Which one of the following is the most appropriate initial management step?

A. Observation.
B. Intravenous heparin.
C. Intravenous amiodarone.
D. Thrombolysis.
E. Primary angioplasty.

ECG shows L ventricular hypertrophy

Diagnosed with:
1) Voltage criteria or
2) Non-voltage criteria

Voltage criteria:

Limb leads:
R wave in lead 1 plus S wave in lead III > 25mm
R wave in lead aVL > 11mm
R wave in lead aVF > 20mm
S wave in lead aVR > 14mm
Precordial leads
R wave in leads V4,5,or 6 > 26mm
R wave in leads V5 or 6 plus S wave in lead V1 > 35mm
Largest R wave plus largest wave in precordial leads > 45mm

Non voltage criteria

Delayed ventricular activation time > 0.05s in leads V5or 6 > 0.05s
ST segment depression and T wave inversion in the left precordial leads

Common causes of left ventricular hypertrophy

1) Hypertension
2) Aortic stenosis
3) Coartation of aorta

This patient has a soft systolic murmur with a history of hypertension. There is no immediate indication to currently treat as a NSTEMI although the mistake of diagnosing it as a STEMI is often made.

Answer: A Observe.


BMJ 2002;324:1264-1267 ( 25 May )Clinical review
ABC of clinical electrocardiography
Conditions affecting the left side of the heart
June Edhouse, R K Thakur, Jihad M Khalil.


Cardiology - Cardiac investigations

Cardiology - Cardiomyopathy


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A 39-year-old woman presents with signs and symptoms of pyelonephritis. Despite being treated for five days with oral cephalexin (500 mg four times/day), a midstream urine culture is positive for enterococci.
The most likely explanation for the lack of response to the prescribed antibiotic is:

A. lack of tissue penetration.
B. poor compliance.
C. antibiotic resistance.
D. oral rather than intravenous therapy.
E. inadequate duration of therapy.

Enterococcal species (formerly known as Group D stretococci) responsible for serious infections

  1. Bacteremia
  2. Infective endocarditis
  3. Meningitis
  4. UTI
  5. Nocosomial infections

Treatment complicated by Antimicrobial resistance

  1. E.faecalis and E. faecium are 2 most important enterococcal species
  2. E faecalis more susceptible to antibiotics (more susceptible to ampicillin but resistant to quinupristin-dalfopristin)
  3. E.faecium hospital acquired ones more resistant to ampicillin or vancomycin but susceptible to quinupristin-dalfopristin

Bacteremia without Endocarditis

  1. common sources of community-acquired bacteremia are genitourinary and GIT tracts
  2. have to suspect the possibility of endocarditis in community-acquired enteroccal bacteremia


  • Ampicillin (2g 4/24ly) for susceptible strains
    Vancomycin (1g bd) if pt allergic to penicillin or resistance
  • If suspect valvular abnormalities,
    Add gentamicin 1mg/kg every 8hrs – but discontinued if organism has high level reistance
  • Length of treatment
    If uncomplicated enterococcal bacteremia 7-10 days
    Complicated 4 -6 weeks
    1. osteomylelitis
    2. high grade bacteremia (2 or more positive blood cultures)
    3. Source not identified
    4. Bacteremia is high grade, pt has valvular heart disease, intravascular catheter

Urinary tract infections

  • Enterococci are responsible for fewer than 5% of UTIs in young women who do not have risk factors such as urinary catheters prior instrumentation or an anatomical abnormality
  • Nosocomial UTIs ass with enterococci are more common


  • removal of urinary catheter “1st line”
  • single agent (amipicillin, amoxicillin, penicillin or vancomycin) is adequate and other beta lactam agents should be reserved for polymicrobial infections
  • Nitrfurantoin can be used including for VRE
  • Fluroquinolones widely used but limited data


  • Enterococci is an uncommon cause and more frequent in neonates
  • more difficult to treat


  • Ampicillin or vancomycin + gentamicin
  • Rifampicin has been used in combination with cell wall active agent for anteroccal meningitis ex vancomycin


Back to the question: Answer C

Since they mention the causative organism is enterocci, the most likely reason why it is not responding to cephalexin is Antibiotic resistance.  There are 3 mechanisms of resistance:

  • transfer of plasmids
  • transfer of plasmids among a broad range of species and genera
  • transfer of specialized transposons at low frequency but to a broad range of different kinds of bacteria


Infectious Diseases: UTI
Pharmacology: Antibiotics

Question 94top Download PDF

A 67-year-old man has a witnessed collapse. His initial rhythm is ventricular fibrillation. The ambulance crew documents return of spontaneous circulation at 17 minutes after the initial collapse. In the emergency department he is ventilated via an endotracheal tube. His blood pressure is 120/70 mmHg. He has a Glasgow coma score of 3 out of a possible 15 points (no response to pain, no eye opening, no vocalization). His ECG is shown below. Co-morbidities are limited to essential hypertension and hypercholesterolemia for some years. His temperature is now 34°C.


Which of the following is the first priority of care for this patient?
A. Brain stem death testing.
B. Coronary angiography.
C. Intravenous thrombolytics.
D. Cool to 33°C.
E. Cerebral computed tomography (CT) scan.

Cause of this pt's VF arrest is most likely AMI considering the ST elevation in V4-6 with incomplete RBBB.  He also has known cardiovascular risk factors.  We do not know if this patient received CPR at all as that would be a contraindication to IV thrombolytics. 

Evaluation of survivor of SCD

  • identification & treatment of acute reversible causes
  • evaluation of structural heart disease
  • neurologic & psychologic assessment
  • if heritable syndrome is suspected or confirmed, evaluation of famly members


  1. coronary heart disease (65-70%) - stable CHD or prior infarctions
    if less than age 40, CHD is significantly less common, structural heart disease and primary electrical disease are more common SCD accounts for 30-50% of deaths in pts with HF therefore all SCD survivors with HF receive an ICD
  2. other types of structural heart disease (10%)
    • myocarditis
    • hypertrophic cardiomyopathy
    • arrhythmogenic R ventricular dysplasia
  3. structurally normal hearts (5-10%)
  4. non cardiac cause (15-35%)
    • trauma
    • bleeding
    • drug intoxification
    • intracranial hemorrhage
    • PE
    • central airway obstruction



Diagnostic angiography
  • unclear whether or not immediate coronary angiography to exclude an ACS should be performed in all SCD surviors
  • evaluated in a consecutive series of 84 such survivors of out of hospital cardiac arrest, all of whom underwent urgent catheterization and angiography.  36 had ST elevation, 18 had LBBB, 8 had ST depression
    Results:  total occlusion of a coronary artery was found in 40 pts and evidence of an unstable lesion in 18
    9 pts without ST elevation or CP had at least one totally occluded coronary arter
    Long term outcomes were better in the 28 pts who had successful urgent PCI

Conclusion: The results apply more directly to the pts with evidence of active ischemia.  It is not known whether it should be a routine urgent angiography;

Neurologic Assessment

A poor clinical outcome following cardiac arrest with 97% specificity if

  • absence of papillary light response after 24hrs
  • absence of corneal reflex after  24hrs
  • absent motor responses to pain after 24hrs
  • absent motor responses after 72hrs

Evoked potentials from brainstem, auditory, visuals have not been adequately evaluated.  Somatosensory evoked potentials (SSEPs) are the best validated and most reliable of the ancillary test currently available à test N20 component of SSEP with median nerve stimulation

  • SSEPs averaged electrical responses in the CNS to somatosensory stimulation. 
  • an absent N20 was 100% predictive dismal outcome

CT and MRI contribute little to assessment of the pt unless stroke, bleeding or trauma is suspected. 


  1. Induced hypothermia
    • target temp 32- 34 degrees for 24 hrs
    • improved neurologic outcome
    • reduced mortality
      • Seen in pt with  VF arrest in whom spontaneous circulation restored, even when pt remains comatose after resuscitation
  2. Family counseling
  1. Asystole: 0-2% survive till hospital discharge
    • factors ass with successful resus:  witnessed arrest, lower pt age, shorter time to arrival of EMS and no tx with atropine for bradyarrhythmia after resus
  2. EMD:  11% survive until hospital d/c
  3. Ventricular tachyarrhythmia: 
    1. VF    25-40% survive till hospital d/c,
      • Witnessed VF had significantly greater likelihood of survival
      • Underlying cause: AMI
    2. Haemodynamically unstable VT à 65-70% survival
      • prognosis is better in pts with monomorphic VT, potential for systemic perfusion during this more organized arrhythmia
      • lower incidence of remote infarction and higher ejection fraction

Factors related to Outcome of resuscitation

  1. VF duration 
  2. Shortening time to resuscitation
  3. Automatic external defibrillators
  4. Adequacy of CPR
  5. Timing of defibrillation
  6. Induced hypothermia

Of all the possible options, the 1st priority of the care of this patient is induced hypothermia as it is the only option that has shown to improve neurological outcome and reduce mortality.  Coronary angiography is still important in this patient's management considering his ECG and the cause of his VF arrest is most likely due to CHD but it would not be the 1st priority.  As for the IV thrombolytics, if the pt received CPR, it would then be contraindicated.  CTbrain and brain stem  death testing are part of the neurological & prognostic evaluation. 


Cardiology Cardiac arrhythmias | myocardial infarction

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A 67-year-old man with chronic obstructive pulmonary disease (COPD) has severe exertional dyspnoea and is receiving maximal inhaled bronchodilator therapy. He no longer smokes.

Lung function tests are as follows:
forced expiratory volume in one second (FEV1) 0.54 L (18% predicted)
forced vital capacity (FVC) 2.87 L (75% predicted)
FEV1/FVC 19%
total lung capacity (TLC) 7.96 L (121% predicted)
residual volume (RV) 5.09 L (245% predicted)
diffusing capacity for carbon monoxide (DLCO) 6.1 mL/min/mmHg (19% predicted)

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

Answer B

Testing us:

  1. severity of COPD - LFT, ABG
  2. treatment of exertional dyspnoea

Other learining issues for ourselves:

  1. What is maximal inhaled brochodilator therapy
  2. How to read LFT

Classification of severity of COPD

Stage Characteristics
0: At risk

Normal Spirometry

Chronic symptoms (cough, sputum production)

I: Mild COPD

FEV1/FVC < 70%

FEV1 ³ 80% predicted

With or without chronic symptoms


FEV1/FVC < 70%

FEV1 50 - 80% predicted

With or without chronic symptoms

III: Severe COPD

FEV1/FVC < 70%

FEV1 30- 50% predicted

With or without chronic symptoms

IV: Very severe COPD  

FEV1/FVC < 70%

FEV1 < 30% predicted or FEV1< 70% predicted + respiratory failure (PaO2 < 60mmHg ± PaCO2 > 50mmHg)


Pulmonary function tests

  • evaluate dyspnea
  • Smokers over age 45 to detect COPD, HF
  • Check recovery from exacerbation of asthma, COPD, HF
Spirometry + bronchodilator
  • Chronic cough or  chest tightness
  • Suspect asthma or COPD
  • Determine response to specific bronchodilatory therapy
  • Differential diagnosis of abnormal spirometry
  • Obstruction: asthma vs COPD
  • Restriction: interstitial (normal)   vs COPD (low)
  • Infiltrates on Cxr
  • Suspect pulmonary vascular disease
  • Evaluate dyspnoea

Flow volume loop  

  • Inspiratory stridor

Lung volumes

  • Low FVC on spirometry: differentiate restriction vs hyperinflation or mixed

6 min walk test 

  • index of physical function in pts with chronic lung disease
  • fall of SpO2 of > 4% ending below 93% - significant desaturation

Methacholine challenge 

  • Suspect asthma but normal spirometry
Approach to patient with dyspnea

Therapy at each stage of COPD

Stage   Recommended treatment

Avoidance of risk factors

influenza vaccination

Mild short acting bronchodilator

regular treatment with 1 or more bronchodilators



regular treatment with 1 or more bronchodilators

inhaled glucocorrticosteroids if significant symptoms


Very severe


inhaled glucocorticosteroids


long term O2 if respiratory failure

consider surgical treatments



  1. Beta-agonist
    1. short acting Beta 2 agonist
      • used when required
      • S.E: tremor, reflex tachycardia, hypokalaemia
    2. long acting
      • use of long acting Beta agonist plus anticholinergic showed to have greater improvement in lung function a nd QOL compared to single agent use 
  2. Anticholinergics
    • reduced frequency of severe exacerbations and respiratory deaths
    • tiotropium (long acting) achieved longer bronchodilation and lessen frequency of acute exacerbations
  3. Corticosteroid
    • Improve symptoms, FEV1 and PaO2 in moderate to severe exacerbations
      • reduce treatment failure, relapse and length of stay
      • mortality  inaltered
  4. Theophylline
    • controversial
    • Reduced dyspnoea, improved ABG, FEV1 compared to placebo
    • problems with toxicity
  5. O2 therapy
    • improve QOL and survival
    • Criteria:  PaO2 < 55, SaO2 < 88%, PaO2 < 59 if eveidence of corpulmonale and RHF
  6. Rehabilitation
    • improve exercise capacity, reduced hospitalization, and enhance QOL
  7. Surgery
    • lung volume reduction surgery or lung transplantation
    • Criteria: 
      • FEV1 < 25% predicted
      • PaO2 > 55
      • Cor pulmonale present
      • < 65 yo
    • Benefits :  functional capacity improved but no survival benefit
  8. Nurtrition
    • high caloric dietary supplements
    • magastrol acetate:  stimulate appetite & wt gain but not shown to improve lung function
  9. Patient education
    • Quit smoking
  10. Prevention
    • pneumococcal vaccine (every 5 years)
    • influenza vaccine (annually)


Respiratory: COPD Smoking-related chronic lung disease

Question 98top

Question 99top

Question 100 top