2011 A Remembered Flashcards
Which of the following immunomodulators is most commonly associated with gum hypertrophy and hypertrichosis?
A. Azathioprine
B. Cyclosporin
C. Methotrexate
D. Mycophenolate
E. Tacrolimus
Azathioprine – GI, myelosupression, alopecia
Cyclosporin - gingival hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, hypercholesterolemia, dyspnea, numbness and tingling particularly of the lips, pruritus, high blood pressure, potassium retention possibly leading to hyperkalemia, kidney and liver dysfunction (nephrotoxicity[23] and hepatotoxicity), hirsutism, burning sensations at finger tips and an increased vulnerability to opportunistic fungal and viral infections.
Methotrexate – GI, mouth sores, myelosuppression, alopecia
Mycophenolate – GI, myelosuppression
Tacrolimus – HTN, renal toxicity, electrolyte imbalance, hyperglycaemia/diabetes, encelopathy, seizures
QUESTION 2
Situs inversus is most commonly associated with which of the following?
A. Absent thymus
B. Asplenia
C. Bilobed right lung
D. Complete heart block
E. Polysplenia
Answer C. Bilobed right lung
Normal positioning of heart and organs is termed situs solitus.
Situs inversus totalis - complete mirror image of internal organs, with spleen intact. Right lung bilobed due to dextrocardia.
Different types of situs inversus….totalis = heart and organs, thoracalis = thorax only (heart and lungs), abdominalis = abdominal organs only (heart intact).
There is also left and right isomerism, where named side of the chest is duplicated in mirror image on alternate side. So, left isomerism is associated with polysplenia due to positioning of spleen on left and right sided isomerism is associated with asplenia for the same reason.
A woman comes to see you who is a regular patient of yours. She is pregnant and has asked for advice concerning SIDS, because her sister’s child died at the age of 3 months of SIDS.
Regarding SIDS, which of the following has not been shown to reduce the risk of SIDS?
A. Breastfeeding.
B. Sleeping in the supine position.
C. Sleeping in an individual cot / bassinet.
D. No smoking in household.
E. Apnoea monitor for first 12 months of life.
E. Apnoea monitor for first 12 months of life.
The Autism diagnostic observation schedule (ADOS) is a tool used in the assessment and diagnosis of autism. The following results were obtained in a study of ADOS as a diagnostic tool:
According to this table, what is the positive likelihood ratio?
A. 1
B. 2
C. 8
D. 36
E. 4
Answer C. 8
Positive Likelihood ratio = sensitivity/1-specificity
Sensitivity = true positive [80]/(true positive+false negative) [80+20] =0.8
Specificity = true negative [810]/(true negative + false positives) [810+90] = 0.9
sensitivity/1-specificity = 0.8/1-0.9 = 8
Which is the principle component of the immune system responsible for the initial response to virally infected cells?
A. HLA class I
B. HLA class II
C. Complement
D. B-cells
E. Immunoglobulin
F. NK cells
Answer F. NK Cells
From Immunology text….Basic Immunology: Functions and Disorders of the Immune System
Virus defense is special type of host defense that involves interferons, NK cells. Interferons (INF 1) are secreted by virus infected cells and trigger surrounding cells to inhibit viral replication. IFN 1 also enhance ability of NK cells.
Innate immunity - First line response to microbe exposure. Immune responses present from birth and not adapted in response to microorganism exposure. Includes physical barriers, enzymes in epithelial and phagocytic cells, cells that release cytokines (macrophages, mast cells, NK cells), complement, CRP, MBL.
NK Cells (Innate immunity) are a class of lymphocytes that recognises infected cells and kills them by secreting a macrophage-activating cytokine. Activated within 12 hours of infection.
Adaptive immunity - B and T cell response, regulated by T cells.
T cells - naive T cells recognise antigens presented by MHC which stimulate proliferation and differentiation into effector and memory T cells. CD4 T cell recognises class II MHC which present antigens ingested from extracellular microbes. CD8 T cell recognises class I MHC which present peptides from cytosolic or nuclear antigens.
B cells - naive B cells express two membrane bound immunoglobulins - IgM and IgD that are antigen receptors. When activated, these B cells undergo clonal expansion (proliferation into antigen-specific cells) and differentiate into plasma cells which actively secrete antibodies.
Complement (Innate and adaptive immunity)- may be activated by the alternative pathway by proteins on the microbe (innate immunity), or by the classical pathway (adaptive) by antibodies binding to microbes. May also be triggered by mannose-binding lectin (lectin pathway) binding to microbe and triggering the proteins of the classical pathway but because no antibodies are activated it is still considered innate immunity.
(similar to Q in 2010 remembered paper (Erickson Stages) but not completely the same. I couldn’t remember all the answers and copied the ones from 2010 but A and E definitely were the same. One answer included something vs sexuality and another one included abstract thinking vs something else.)
An adolescent with type 1 Diabetes Mellitus is being transferred to an adult model of care. Which is the most important psychological challenge that must be dealt with to ensure a successful transition?
A. Identity vs confusion
B. Initiative vs Guilt
C. Autonomy vs shame and doubt
D. Industry vs inferiority
E. Intimacy vs isolation
A. Identity vs confusion
Infancy (0-18m) = Trust Vs mistrust
Toddler (18m -3) = Autonomy Vs shame
Preschool (3-5) = Initiative Vs guilt
School age (5-13) = industry vs inferiority
Adolescence (13-18) = Identity vs role confusion
Young adults = Intimacy Vs isolation
Helicobacter pylori resistance to antibiotic is an increasing problem worldwide. Which of the following antibiotics, which has been used in combination treatment, has the highest incidence of resistance in treatment naïve patients with H. pylori?
A. Amoxicillin
B. Clarithromycin
C. Metronidazole
D. Tetracycline
E. Ciprofloxacin
Answer C. Metronidazole
From eTG…..metronidazole resistance in Australia is 50%, clarithromycin resistance is 5-7%.
First line eradication therapy is PPI + amoxycillin + clarithromycin
In neonatal allo-immune thrombocytopenia, what is the most common human platelet antigen (HPA) sensitisation in the Caucasian population?
A. 1a
B. 2
C. 3a
D. 4
E. 5b
Answer A. 1a
Anti-HPA 1a =75%
Anti-HPA 5b = 16%
Anti-HPA 15b = 4%
Neonatal alloimmune thrombocytopenia occurs when fetal platelets contain an antigen inherited from the father that the mother lacks. The mother forms IgG antiplatelet antibodies that cross the placenta and destroy fetal platelets resulting in fetal and neonatal thrombocytopenia. Maternal antibodies cross the placenta in early midtrimester. Risk of intracranial haemorrhage (10-20% of affected newborns). Can occur in 1st pregnancy and subsequent pregnancies more severe.
In B cell non-Hodgkin lymphoma what is the most likely site of primary organ involvement?
All remembered options included below…
NB: One candidate remembered as non-Hodgkin NON-B cell type.
A. Bone
B. Skin
C. Mediastinum
D. Intestine
E. Thymus
F. Tonsils
Answer D. Intestine
B cell-B for BELLY
T cell - T for Thorax
Non-Hodgkin lymphoma is fifth most commonly diagnosed childhood cancer. Median age of diagnosis is 10 years and risk increases with age. Most common subtypes are from B cell progenitors, but can also be T cell progenitors, mature T or B cells. In childhood NHL usually high grade and aggressive.
B-cell lymphoma most commonly refers to Burkitt’s Lymphoma, a type of small non-cleaved non-hodgkin’s lymphoma. Endemic-type in Africa presents with head and neck disease, but in Australia – “The nonendemic (sporadic) form usually has an abdominal presentation, most often with massive disease and ascites, involving the distal ileum, stomach, cecum and/or mesentery, kidney, testis, ovary, breast, bone marrow, or central nervous system. Presenting symptoms can include those related to bowel obstruction or gastrointestinal bleeding, often mimicking acute appendicitis or intussusception” – UTD
It may refer to diffuse large B-cell lymphoma, but as per UTD (Patients with DLBCL typically present with a rapidly enlarging symptomatic mass, most usually nodal enlargement in the neck or abdomen) the answer is probably the same.
If non-B type (ie. T-cell) - mediastinum.
The following graph shows a variety of drugs effect at different concentrations:

Which of the following statements is true?
A. Drug A is more potent then Drug D
B. Drug A and Drug B have equal potency
C. Drug B is a partial agonist
D. Drug C is a complete agonist
E. Drug C and Drug D have equal efficacy
Answer E. Drug C and D have equal efficacy
Drugs A and B are equally effective and complete agonists (100%). Drugs C and D are also equally effective (50%) and partial agonists. Drug D is the most potent (less concentration required for effect) and drug C least potent.
Children with haemolytic disorders are at risk of iron overload as they require multiple transfusions. The recommended daily intake of iron for children is 1mg/kg/day. What is the amount of elemental iron in a single unit of packed red bloods cells?
A. 5mg
B. 50mg
C. 200mg
D. 500mg
E. 1000mg
C. 200mg
One unit is approximately 220mL. When donated, it is tested for: HIV/AIDS, hepatitis B, hepatitis C, Human T-cell Lymphotropic Virus- HTLV and syphilis.
Which part of the brain is most vulnerable to the effects of hypoglycaemia in the newborn period?
A. Frontal lobe.
B. Hippocampus.
C. Parietal lobe.
D. Occipital lobe.
E. Temporal lobe.
Answer D. Occipital lobe
Transient, isolated hypoglycaemia of short duration does not appear to result in any significant sequelae, but don’t forget that GLU not only supplies fuel to the brain, but also membrane lipids for things like myelin, thus in prolonged hypoGLU, these are used at the expense of brain growth.
The neonatal liver has a reduced ability to produce ketones, especially in the setting of hyperINS (as in the setting of hypoGLU from maternal GDM), thereby denying the brain an alternative fuel.
Permanent neurological sequelae occur in 25-50% with severe, recurrent hypoGLU (under 6m age). These are characterised by;
- Atrophic gyri
- Reduced myelination in cerebral white matter
- Atrophy in cerebral cortex
- MOST COMMONLY PARIETAL AND OCCIPITAL LOBES
(predominantly a posterior pattern)
No infarcts if HIE did not also occur. The cerebellum is always spared if only insult was hypoGLU.
A two-year-old boy presents with a six week history of diarrhoea and lethargy. On clinical examination
he has peripheral and periorbital oedema. Investigations are as follows:
Liver function tests normal except for Albumin 22g/L.
Coagulation studies normal.
Urinalysis normal.
Which faecal test is most likely to reveal the cause of his presentation?
A. Alpha-1 antitrypsin (non digested protein)
B. Proalbumin
C. Chymotrypsin
D. Elastase
E. Tryptase
A. Alpha-1 antitrypsin (non digested protein)
Normal urinalysis in setting of peripheral oedema suggests protein losing enteropathy, especially given the history of diarrhoea, not a nephritic history.
Best test for PLE is faecal alpha-1-anti-trypsin. A1AT has a similar size to albumin (67kDa molecular mass) and is resistant to digestion in the GIT.
Causes of PLE include; celiac, inflammatory bowel disease, SGSyndrome, intestinal lymphangiectasia, amyloid and infection, typically Giardia.
- C – chymotrypsin (a gut proteolytic) is released as inactive chymotrypsinogen, cleaved by trypsin
- D – faecal elastate reflects exocrine pancreatic insufficiency (chronic pancreatitis, CF) but falsely raised in acute diarrhoea
- E – elevated tryptase implies a colitis. Not to be confused with serum trypsinogen (increased in CF pancreatic exocrine insufficiency)
QUESTION 14
A Newborn Screening result is reported as TSH 20mU/L. This would correspond to a plasma TSH of:
A. 10mU/L
B. 20mU/L
C. 40mU/L
D. 60mU/L
E. 80mU/L
Answer C. 40mU/L
Per lab at RCH
- To convert from gurthrie card TSH to serum/plasma TSH multiply by 2.2
- So TSH 20 on Guthrie would correspond to plasma TSH of 44 at that time
The Southern Hemisphere seasonal Influenza vaccine (including H1N1) is best described as which of the following:
A. live attenuated
B. polysaccharide conjugate
C. protein subunit
D. killed whole
E. toxoid
Answer C. protein subunit
IM is an inactivated (trivalent) split and purified, inactive vaccine containing the HAEMAGGLUTININ and NEURAMINIDASE protein subunits of each type.
A 4 week old baby presents with an erythematous rash to the face and arms. A diagnosis of neonatal lupus is made. Which of the following antibodies is the most likely to be positive:
A. Anticardiolipin antibody
B. Anti dsDNA
C. Anti skin basement membrane antibody
D. Anti scl70
E. Anti-SSA/Ro
Answer E. Anti-SSA/Ro
Heart block can manifest later (2-3 months) because it is a scarring process of the AV node that might take time to develop. Complete heart block = ventricular escape rhythym. AV dissociation
Neonatal lupus:
- Anti-Ro = Sjogren’s & heart block, -La = rash
- This is neonate who gets disease manifestations because of mum’s antibodies – the manifestations can be transient or permanent:
- Note that mum may not have had manifestations herself, or she may have Sjogren’s rather than SLE
- The transfer of Anti-SSA/SSB (Ro/La) occurs between 12-16w gestation.
- Cutaneous lesions occur around 6w (4w in this question) after exposure to UV light. 25% of rashes scar!
- If congenital heart block occurs, it is permanent and may require pacing.
- Disease activity: C3
- Specific: Anti-SM (Smith)
- Sensitive: ANA
- Neonatal lupus: Anti-SSA/Ro
Transient manifestations(
- Discoid lesions +/- other manifestations of SLE (rash appears over few days – with exposure to light)
- DCT +ve AIHA, thrombocytopenia, leucopenia
- Myasthenia gravis
- Neonatal hepatitis
- Positive ANA serology, reduced complement
Permanent manifestations
- CHB without other signs of SLE
- Endomyocardial fibroelastoisis
- PDA, septal defects
NOTE
- Vast majority of children born to SLE mothers are normal (90%)
- And if they have neonatal SLE most will require no therapy
- May predate maternal manifestations.
- Placental transfer of anti-Ro/anti-La antibodies from ~18/40
- Anti Ro will be +ve 80% of the time.
- Ro Ab has been demonstrated in fetal myocardium.
- If mother has high levels of antibodies
- 10% chance of neonatal lupus
- 50% skin (malar rash, erythema annulare)
- 50% cardiac manifestations (CHB+/-Hyrdops-AV node fibrosis, permanent)
- thrombocytopenia
- elevated bilirubin
- not all subsequent pregnancies will be affected (~25% - higher risk)
- Anticardiolipin is a RF for recurrent miscarriage
Investigations
- ANA (FANA test)
- Often present.(Sensitive,nonspecific)
- If repeatedly neg, SLE unlikely as 97% +ve at some stage.
- Also raised in Drug Induced LE, Dermatomyositis, Juv Arthritis, Vasculitis, Scleroderma, EBV, CAHep, Hyperextensisbility, IgA def, and 20% of normal(up to 1/640).
- ?The likelihood of rheumatic or autoimmune disease is high in children with +ve ANA.
- DS DNA
- more specific, levels reflect disease activity.
- Anti DS DNA and Low C3 is 100% SLE specific
- CH50,C3,C4
- decreased in active disease.
- Anti Smith
- Only found in SLE. Does not measure activity.
- Hypergammglobulinaemia
- frequenly assoc.
- Anti RNP
- seen in mixed CT picture.
- If pos but neg DS DNA, low risk of nephritis.
- Anti Ro (SS-A)
- Associated with Sjögren’s syndrome, subacute cutaneous lupus, inherited C′ deficiencies, ANA-negative lupus, lupus in the elderly, neonatal lupus,
- congenital heart block.
- Can cause nephritis
- Anti La (SS-B)
- Always assoc with anti-Ro Sjogrens. Low nephritis risk.
- Anti Histone Ab
- More commonly seen with Drug Induced than spont Lupus.
- Anti-erythrocyte/platelet/lymphocyte and neuronal Abs have the obvious associated manifestations.
A girl was born at term weighing 2.5kg. Her chromosome analysis is XX. She is noted to have retrograde micrognathia and a U shaped cleft.
Her picture is shown below.
Which description best summarises these features:
A. Sequence
B. Association
C. Syndrome
D. Deformation
E. Disruption
Answer A. Sequence
Pierre-Robin Sequence
The pattern of multiple anomalies that occurs when a single primary defect in early morphogenesis produces multiple abnormalities through a cascading process of secondary and tertiary errors in morphogenesis is called a sequence.
The Robin malformation sequence is a pattern of multiple anomalies produced by mandibular hypoplasia. Because the tongue is relatively large for the oral cavity, it drops back (glossoptosis), blocks closure of the posterior palatal shelves, and causes a U-shaped cleft palate. There are numerous causes of mandibular hypoplasia, all of which result in characteristic features of Robin sequence.
What is the major objective of a phase I clinical trial?
A. Adverse events in humans.
B. Efficacy of a drug for a given indication.
C. Safety of a drug prior to use in humans.
D. Likely risk ratio.
E. Pharmacological and metabolic effects in humans.
Answer E. Pharmacologic and metabolic effects in humans
Clinical trials: ThEG
Phase0 – can you use this on a dog?!
Phase1 – Toxicity (healthy humans)
Phase2 – Efficacy (diseased humans)
Phase3 – efficacy compared to Gold standard
Phase4 – post-marketting surveillance
A 2-year old with a malignancy has samples sent for analysis by fluorescence in situ hybridization (FISH).
This is an example of which cytogenetic finding?
A. Amplification
B. High level aneusomy
C. Hyperdiploidy
D. Hypodiploidy
E. Tetrasomy
Answer A. Amplification
FISH “lights up” a target sequence which would usually result in two “lights” - one on each chromosome. More lights would indicate amplification of that sequence.
Aneusomy is in a tumour when cells have a different number of chromosomes. There would need to be more than one cell pictured for this to be the answer.
Hyperdipoid is to have more than the diploid number of chromosomes, and hypodiploid has less than the diploid number of chromosomes.
Tetrasomy is four copies instead of two of a particular chromosome.
Patients with Cystic Fibrosis who have pancreatic insufficiency require supplementation of exogenous pancreatic enzymes. Supplementation works best when the dose is adjusted depending on the content of meals.
Which of the following would require the highest dose of pancreatic enzyme supplement?
A. A banana
B. A bowl of canned vegetable soup
C. A fillet of grilled fish
D. A can of cola
E. A 100g packet of roasted peanuts
Answer E. A 100g packet of roasted peanuts.
Pancreatic enzymes are required to avoid fat malabsorption due to pancreatic insufficiency. The higher the fat content of the meal, the higher the dose of pancreatic enzyme. Multiple porcine preparations exist with varying concentrations of lipase, protease and amylase.
Peanuts has the highest fat content of all the answers and will therefore require the highest dose of pancreatic enzyme.
Excessive doses can cause fibrosing colonopathy. Prolonged contact of beads on the oral mucosa can cause ulceration.
PTH is required for calcium metabolism by acting on intestines, bone and kidneys. What decreases in response to PTH?
A. Bone resorption
B. Intestinal absorption
C. Renal PO4 reabsorption
D. Renal Ca reabsorption
E. Vitamin D activation
Answer C. Renal PO4 reabsorption
PTH = calcium in, phosphate out
PTH increases serum calcium in three ways. 1. Increased intestinal absorption; 2. increased bone resorption; and 3. enhanced distal tubular reabsorption
Decreased serum calcium levels stimulate increased PTH secretion. PTH enhances renal production 1,25(OH)2D3 which induces synthesis of calcium binding protein in the intestinal mucosa for increased calcium absorption.
PTH also directly causes bone resorption (and requires 1,25(OH)2D3 for this process).
PTH stimulates calcium reabsorption in the distal tubules and PO4 excretion. Phosphate homeostasis regulated by the kidneys. Almost 100% absorption so serum level is dependent on renal excretion.
If a pregnant woman acquires primary varicella it can affect her baby with limb hypoplasia, skin scarring, and eye abnormalities. At what gestation is a fetus at greatest risk of this syndrome if exposed to varicella infection?
A. < 7 weeks
B. 8-13 weeks
C. 14-20 weeks
D. 21-28 weeks
E. 1 week prior to delivery
Answer C. 14-20 weeks
Congenital Varicella Syndrome
- When pregnant women contract varicella early in pregnancy as many as 25% of the foetuses may become infected.
- Clinically apparent disease in the infant is, however, uncommon
- The congenital varicella syndrome occurs in approximately 0.4% of infants born to women who have varicella during pregnancy before 13wk of gestation and approximately 2% of infants born to women with varicella between 13 and 20wk of gestation.
- Congenital varicella syndrome is characterized by cicatricial skin scarring in a zoster-like distribution, limb hypoplasia, and neurologic (e.g., microcephaly, cortical atrophy, seizures, and mental retardation), eye (e.g., chorioretinitis, microphthalmia, and cataracts), renal (e.g., hydroureter and hydronephrosis) and autonomic nervous system abnormalities (neurogenic bladder, swallowing dysfunction, and aspiration pneumonia).
- The characteristic cutaneous lesion has been called a cicatrix, a zigzag scarring, in a dermatomal distribution, often associated with atrophy of the affected limb
- Virus cannot be cultured from the affected newborn, but viral DNA may be detected in tissue samples by polymerase chain reaction
- Varicella immune globulin has often been administered to the susceptible mother exposed to varicella; not known if this actually helps
- Acyclovir is a class B drug for pregnancy and should be considered only when the benefit to the mother outweighs the potential risk to the foetus
Neonatal Varicella
- Risk for the baby is greatest if the mother contracts VZV close to delivery (especially 5 days prior to two days post)
- The foetus contracts it through the placenta due to maternal viraemia (this may be before mum even has a rash)
- Baby usually develops the rash toward the end of the first week → start of the second week of life
- This is dangerous because the baby receives a large ‘dose’ of virus without corresponding antibodies, as mum is yet to develop them by delivery
- This is why if it’s more than 5 days between transmission and delivery, the risk is ↓ (mum will have had the chance to pass on antibodies)
- Guidelines for VariZIG (human varicella zoster immune globulin)
- Newborns whose mothers demonstrate varicella 5 days before to 2 days after delivery should receive 1 vial of VariZIG as soon as possible.
- All premature infants born 1wk) should receive VariZIG
- If VariZIG not available- give IVIG (not as effective but better than nothing)
- Treat with acyclovir IV when lesions develop
- Neonatal varicella can also follow a postpartum exposure of an infant delivered to a mother who was susceptible to VZV, although the frequency of complications declines rapidly in the weeks after birth
- Infants with community-acquired varicella who experience severe varicella should also get IV acyclovir
Capsule endoscopy is becoming more frequently used. Which of the following is the best indication for the use of capsule endoscopy?
A. Familial polyposis coli
B. Obscure GI bleeding
C. Recurrent intestinal obstruction
D. Swallowing problems
E. Ulcerative Colitis
Answer B. Obscure GI bleeding
Indications for capsule endoscopy include diagnosis of site of obscure GI bleeding, suspected crohns and small bowel tumours.
A 2 year old boy with autism does not respond to his name despite you repeatedly calling it in your clinic room. This is most likely due to a deficit in:
A Auditory processing
B Receptive language
C Hearing
D Social relatedness
E Cognition
Answer D. Social relatedness
- Symptoms of autism spectrum disorder (ASD) most commonly are recognized in the second year of life, but may be present earlier or manifest later when social demands exceed limited capacities.
- Impaired social communication and interaction may manifest as lack of social and emotional reciprocity; lack of seeking to share enjoyment, interests, or achievement; impaired use of nonverbal behaviors to regulate social interaction (eg, eye gaze, facial expression, gestures); and failure to develop age-appropriate peer relationships.
- Restricted and repetitive behaviors, activities, and interests may include stereotyped and repetitive motor mannerisms, inflexible adherence to nonfunctional routines or rituals, preoccupation with stereotyped or restricted patterns of interest, and hyper- or hyposensitivity to sensory input.
- ASD may or may not be associated with intellectual and/or language impairment, and other genetic, medical, or environmental factors.
In meiosis, pairing of homologous chromosomes happens during which of the following phases?
A. Anaphase 1
B. Interphase
C. Metaphase 2
D. Prophase 1
E. Telophase 1
Answer A. Prophase I
Prophase = pairing
Metaphase = middle
Anaphase = apart
Torn in two - telophase
Meiosis begins in the female oocyte during fetal life and is completed years to decades later. In males, it begins in a particular spermatogonial cell sometime between adolescence and adult life and is completed in a few days. Meiosis is preceded by DNA replication so that at the outset each of the 46 chromosomes consists of 2 chromatids. In meiosis, a diploid cell (2n = 46 chromosomes) divides to form haploid cells (n = 23 chromosomes). Meiosis consists of 2 major rounds of cell division. In meiosis I, each of the homologous chromosomes pair precisely so that genetic recombination, involving exchange between 2 DNA strands (crossing over), can occur. This results in a reshuffling of the genetic information on the recombined chromosomes and allows further genetic diversity. Each daughter cell then receives 1 of each of the 23 homologous chromosomes. In oogenesis, 1 of the daughter cells receives most of the cytoplasm and becomes the egg, whereas the other smaller cell becomes the 1st polar body. Meiosis II is similar to a mitotic division but without a preceding round of DNA duplication (replication). Each of the 23 chromosomes divides longitudinally, and the homologous chromatids migrate to opposite poles of the cell. This produces 4 spermatogonia in males, or an egg cell and a 2nd polar body in females, each with a haploid (n = 23) set of chromosomes. Consequently, meiosis fulfills 2 crucial roles: It reduces the chromosome number from diploid (46) to haploid (23) so that upon fertilization a diploid number is restored, and it allows genetic recombination.
A 2yr-old girl with developmental delay presents to the emergency department following a fall off a trampoline. She undergoes a CT brain which is shown below.
This imaging is most consistent with which of the following?
A. Subdural haemorrhage
B. Extradural haemorrhage
C. Subarachnoid haemorrhage
D. Intracerebral haemorrhage
E. Intraventricular haemorrhage
Answer A. Subdural haemorrhage
Subdural collections appear as crescent shaped, often extending widely across the convexity of a cerebral hemisphere.
Extradural haemorrhage is a convex lenticular lesion.
Subarachnoid haemorrhage is a more generalised bleeding pattern which will often follow the contours of the brain.
What inheritance pattern is represented below?
A. Autosomal recessive or autosomal dominant
B. Mitochondrial or X-linked recessive
C. X-linked recessive or autosomal recessive
D. X-linked dominant or X-linked recessive
E. Y-dominant or X-linked recessive
ANSWER C. X-linked recessive or autosomal recessive
- AR: Yes. Unaffected parents, affected children. (Though statistically you would expect ¼ offspring to be affected – bad luck in this case).
- AD: Maybe – only if you qualify it as AD with incomplete penetrance (hence parents not affected) OR anticipation (OR parental germline mosaic)
- Mitoch: Maybe – all offspring of affected mother usually affected but can be spared via heteroplasmy. Would usually expect mother to be affected though. Would be bad luck for her not to have it, and 3 of her 4 kids to be affected.
- XLR: Yes. Unaffected mother and daughter, all sons affected.
- XLD: No. Mother would be affected.
- YD: No. Father would be affected.
Mitochondrial Inheritance
- When the defective gene is encoded in the mitochondrial genome
- Mitochondria = organelles where aerobic metabolism occurs
- Mitochondria contain their own circular 16,000 basepair genome, DNA and RNA polymerases, and protein translation apparatus (ribosomes, tRNA)
- Many mitochondrial proteins are encoded by mitochondrial DNA (BUT some mitochondrial proteins are encoded by the nuclear genome and inherited in a mendelian fashion)
- They are inherited exclusively from the cytoplasm of the oocyte during the formation of the zygote and are therefore exclusively maternal in origin (the sperm contributes only its nucleus)
- Most children of an affected female are usually affected, but to varying degrees
- Children of an affected male are NEVER affected
- Examples include MERRF (myoclonic epilepsy with ragged red fibres), MELAS (mitochondrial myopathy/encephalopathy/lactic acidosis/stroke-like episodes) – both are mutations in the mitochondrial tRNA molecule
- In mitochondrial inheritance, the disease can only be inherited from the mother, and usually ALL of an affected mother’s children are affected
- However, sometimes children can escape inheriting a mitochondrial disorder or can be affected to varying degrees, depending on how the mutation is distributed within the population of mitochondria inherited from the mother – this is known as heteroplasmy
- Heteroplasmy is used to describe the situation where a cell or tissue contains a mixture of mitochondria - both mutant and wild-type. The term homoplasmy describes the situation whereby all the mitochondria have the same genome, either wild-type or mutant
- Symptoms of severe heteroplasmic mitochondrial disorders frequently do not appear until adulthood because many cell divisions and a lot of time is required for a cell to receive enough mitochondria containing the mutant alleles to cause symptoms. An example of this phenomenon is Leber optic atrophy. Individuals with this condition often do not experience vision difficulties until they have reached adulthood. In MELAS, heteroplasmy explains the variation in severity of the disease among siblings.
- Pedigrees will show both male and female affected but only the females pass the disorder on. The pedigree can look superficially like an XR pedigree but there is no male transmission through carrier daughters
- Mitochondria are randomly distributed into daughter cells, thus by chance alone some cells may receive more or less of the mutant mitochondria. Those tissues that receive a larger amount of defective mitochondria will have a lower ATP production. If the tissue is one which requires a large amount of energy such as cell of the nervous system, muscles, kidneys, etc., the person with the mutant mitochondria will be affected.
At age 18 months failure to develop which of the following skills is indicative of developmental delay?
A. Pretend play (cup of tea )
B. Following simple instructions
C. Separation anxiety from mother
D. Failure to use simple gestures (pointing, waving bye-bye)
E.
Paediatric Secrets – Play Activity and Child Development
- 3m – midline hands
- 6m – transfers
- 7-9m – banging, mouthing
- 12m – casting – including use of pointing from 10-12mths; follows simple 1 step commands from 10-12m
- 18m – stacking, lids, switches – exploring; knows multiple 1 step commands
- 24m – imitative play (eg play with doll)
- 36m – imaginative play (eg pretend pillow is doll)
- 48m – simple rule-based games
- Signs of speech-language problems absolutely needing further evaluation (ie RED FLAGS)
What is the anatomical position of a cephalohaematoma?
A. Between the dura and arachnoid mater.
B. Between the dura and skull
C. Between the skull and periosteum.
D. Between the periosteum and aponeurosis.
E. Within the soft tissue.
Answer C. Between the skull and the periosteum
SPADE: Skull < Periosteum < Aponeurosis (galea aponeurotica, hence ‘subgaleal’) < Dermis < Epidermis
Cephalhaematoma = Capped by the sutures
Subgaleal = spreads everywhere
Majority (90%) result from vacuum applied to the head at delivery (Ventouse assisted delivery). The vacuum assist ruptures the emissary veins (connections between dural sinus and scalp veins) leading to accumulation of blood under the aponeurosis of the scalp muscle and superficial to the periosteum[1]. Subgaleal hematoma has a high frequency of occurrence of associated head trauma (40%), such as intracranial hemorrhage or skull fracture. The occurrence of these features does not correlate significantly with the severity of subgaleal hemorrhage.
The arrow in the picture shows:
A. Basophil
B. Eosinphil
C. Lymphocyte
D. Neutrophil
E. Monocyte
Answer B. Eosinophil
Bilobed nucleus with brick red stained granules (after staining with red dye called “eosin”).
A renal biopsy, performed 2 weeks post renal transplant, shows acute cellular rejection (pictured).
Which cell type mediates this immune process:
A. B Cell
B. Macrophage
C. NK Cell
D. Neutrophil
E. T Cell
Answer E. T Cell
Answer E. T Cell
Hyperacute rejection occurs immediately when the kidney is transplanted and is due to preformed antibodies against the donor HLA, ABO, or other antigens. Hyperacute rejection is rare. The only treatment is removal of the graft.
Acute cellular rejection needs to be identified and treated early. Diagnosis of acute rejection in the very young transplant recipient is often not straightforward. Because most small children receive adult-sized kidneys, an elevation in serum creatinine may be a late sign of rejection as a result of the large renal reserve compared with the body mass. Thus, significant allograft dysfunction may be present with little or no increase in the serum creatinine level. One of the earliest and most sensitive signs of rejection is the development of hypertension along with low-grade fever. In children, any increase in serum creatinine, especially if it is accompanied by hypertension, should be considered a symptom of acute rejection until proved otherwise. Late diagnosis and treatment of rejection are associated with higher incidence of resistant rejections and graft loss.
At the present time, renal allograft biopsy with conventional histologic examination remains the gold standard for diagnosing acute rejection among transplant patients with a deterioration in kidney function. The two principal histologic forms of acute rejection are:
Acute cellular renal allograft rejection, which is characterized by infiltration of the allograft by lymphocytes and other inflammatory cells.
Acute antibody mediated rejection, which requires morphologic evidence of acute tissue injury, circulating donor-specific allo-antibodies, and immunological evidence of antibody-mediated process (C4d+). It may not be associated with cellular infiltrates.
Chronic rejection is the leading cause of graft loss and primarily results from immune and nonimmune injuries such as hypertension, diabetes, and hyperlipidemia.
Children often have a gradual decline in their renal function and often have fixed proteinuria and hypertension. Despite initial excitement about the potential of MMF and sirolimus mitigating chronic graft injury, this has not translated readily into observable clinical benefits.
A Forrest Plot represents the results of 2 randomised control trials and 1 meta analysis comparing placebo and treatment with iron supplements in the reduction or resolution of breath holding episodes.
The best interpretation is:
A. A large clinical effect, that is not statistically significant
B. A large clinical effect, that is statistically significant
C. A small clinical effect, that is not statistically significant
D. A small clinical effect, that is statistically significant
E. No clinical effect.
Answer B. A large clinical effect, that is statistically significant
Forest Plots
- A graphical display designed to illustrate the relative strength of treatment effects in multiple quantitative scientific studies addressing the same question (i.e. it looks at a few different studies that have been done to draw some conclusion)
- It is a means of graphically representing a meta-analysis of the results of randomised controlled trials
- Commonly presented with 2 columns. The left-hand column lists the names of the studies. The right-hand column is a plot of the measure of effect (odds ratio) for each of these studies (often represented by a square) incorporating confidence intervals represented by horizontal lines.
- The area of each square is proportional to the study’s weight in the meta-analysis
- The overall meta-analysed measure of effect is often represented on the plot as a vertical line. This meta analysed measure of effect is commonly plotted as a diamond, the lateral points of which indicate confidence intervals for this estimate
- A vertical line representing no effect is also plotted. If the confidence intervals for individual studies overlap with this line, it demonstrates that at the given level of confidence their effect sizes do not differ from no effect for the individual study
- The same applies for the meta-analysed measure of effect: if the points of the diamond overlap the line of no effect the overall meta-analysed result cannot be said to differ from no effect at the given level of confidence
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