Clinical Science Flashcards
1
Q
Features of congenital rubella
A
Classical
- > Sensorineural deafness
- > Congenital cataracts
- > Congenital heart disease (e.g. PDA)
- > Glaucoma
Other
- > Growth retardation
- > Hepatosplenomegaly
- > Purpuric skin lesions
- > ‘Salt and pepper’ chorioretinitis
- > Microphthalmia
- > Cerebral palsy
2
Q
Features of congenital toxoplasmosis
A
Classical
- > Cerebral calcification
- > Chorioretinitis
- > Hydrocephalus
Other
- > Anaemia
- > Hepatosplenomegaly
- > Cerebral palsy
3
Q
Features of congenital cytomegalovirus
A
Most common congenital infection in UK. Mother asymptomatic.
Classical
- > Growth retardation
- > Purpuric skin lesions
Other
- > Sensorineural deafness
- > Encephalitis/seizures
- > Pneumonitis
- > Hepatosplenomegaly
- > Anaemia
- > Jaundice
- > Cerebral palsy
4
Q
Definition of confidence interval
A
A range of values within which the true effect of intervention is likely to lie.
Eg. a confidence interval at the 95% confidence level means that the confidence interval should contain the true effect of intervention 95% of the time
5
Q
How to calculate 95% confidence interval
A
Lower limit = Mean - (1.96 x SD)
Upper limit = Mean + (1.96 x SD)
- For 90% use 1.645 *
- If n<100, check Student T test critical value table instead on 1.96)
6
Q
Definition of standard error of the mean (SEM)
A
Measure of the spread expected for the mean of the observations
Ie. how ‘accurate’ the calculated sample mean is from the true population mean
7
Q
How to calculate SEM
A
SEM = Standard deviation/ Square root (sample size)
=> SEM gets smaller as sample size gets bigger
8
Q
When to use Students T- test
A
Parametric data.
Paired -> Data observed from a single group eg. measurements before and after an intervention
Unpaired -> Data observed from 2 separate groups eg. comparing an intervention in 2 different groups.
9
Q
When to use Pearson’s product-moment coefficient
A
Parametric correlated data
10
Q
When to use Mann-Whitney U test
A
Non-parametric unpaired data.
11
Q
When to use Wilcoxon signed rank test
A
Non parametric data. Compares 2 sets of observations on a single sample
12
Q
When to use chi-squared test
A
Non parametric data. Used to compare percentages and proportions
13
Q
When to use spearman, Kendal rank
A
Non-parametric correlated data
14
Q
What is pre-test probability?
A
The proportion of people with the target disorder in the population at risk at a specific time (point prevalence) or time interval (period prevalence)
15
Q
What is post-test probability?
A
The proportion of patients with that particular test result who have the target disorder
Post-test probability = post test odds / (1 + post-test odds)
16
Q
What is the pre-test odds?
A
The odds that the patient has the target disorder before the test is carried out
Pre-test odds = pre-test probability / (1 - pre-test probability)
17
Q
What is the post-test odds?
A
The odds that the patient has the target disorder after the test is carried out
Post-test odds = pre-test odds x likelihood ratio
where the likelihood ratio for a positive test result = sensitivity / (1 - specificity)
18
Q
Flying recommendations: unstable angina, uncontrolled hypertension, severe valvular disease, uncontrolled arrhythmia, decompensated heart failure
A
Should not fly
19
Q
Flying recommendations: uncomplicated MI
A
After 7-10 days
20
Q
Flying recommendations: complicated MI
A
After 4-6 wks
21
Q
Flying recommendations: coronary artery bypass
A
After 10-14 days
22
Q
Flying recommendations: PCI
A
After 5 days
23
Q
Flying recommendations: pneumonia
A
Should be clinically improving with no residual infection
24
Q
Flying recommendations: pneumothorax
A
Absolute contraindication.
CAA -> 2 weeks for drainage with no residual air
BTS -> 6 wk post pneumothorax/1wk post check XR
25
Flying recommendations: pregnancy
Allowed up to 36 wk for single pregnancy
Allowed up to 32 wk for multiple pregnancy
Often need certificate after 28 wk to say pregnancy progressing normally
26
Flying recommendations: abdominal surgery
After 10 days
27
Flying recommendations: laproscopic surgery
After 24hr
28
Flying recommendations: colonoscopy
After 24 hr
29
Flying recommendations: following application of plaster cast
After 24hr if <2hr flight
| After 48hr if >2hr flight
30
Flying recommendations: haematological conditions
Hb > 80
31
Inheritance of haemophilla A
X-linked recessive
32
S&S Cushings reflex
Hypertension (s) then bradycardia (ps)
Physiological reflex to raised ICP
33
What produces IFN-alpha
Leukocytes
34
What produces IFN-beta
Fibroblasts
35
What produces IFN-gamma?
T cells & NK cells
36
Action of IFN-alpha
Antiviral. Acts on type 1 receptors
37
Action of IFN-beta
Antiviral. Acts on type 1 receptors
38
Action of IFN-gamma
Weaker antiviral. More of a role in immunomodulation and in particular macrophage activation. Acts on type 2 receptors
39
Uses of IFN-alpha
Useful in hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer, hairy cell leukaemia
40
Uses of IFN-beta
Reduces frequency of exacerbations of relapsing-remitting MS
41
Uses of IFN-gamma
May be useful in chronic granulomatous disease and osteopetrosis
42
Side effects of IFN-alpha
Flu-like symptoms & depression
43
Autosomal recessive conditions
Metabolic conditions except INCLUDES inherited ataxias & EXCLUDES Hunters & G6DP deficiency (X-linked) and hyperlipidaemia type II & hypokalaemia periodic paralysis (AD)
```
The following conditions are autosomal recessive:
Albinism
Ataxic telangiectasia
Congenital adrenal hyperplasia
Cystic fibrosis
Cystinuria
Familial Mediterranean Fever
Fanconi anaemia
Friedreich's ataxia
?? Gilbert's syndrome ??
Glycogen storage disease
Haemochromatosis
Homocystinuria
Lipid storage disease: Tay-Sach's, Gaucher, Niemann-Pick
Mucopolysaccharidoses: Hurler's
PKU
Sickle cell anaemia
Thalassaemias
Wilson's disease
```
44
Cause of Turners syndrome
Caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes.
Denoted as 45,XO or 45,X
45
Features Turners syndrome
Short stature
Shield chest, widely spaced nipples
Webbed neck
Bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
Primary amenorrhoea
Cystic hygroma (often diagnosed prenatally)
High-arched palate
Short fourth metacarpal
Multiple pigmented naevi
Lymphoedema in neonates (especially feet)
Gonadotrophin levels will be elevated
There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn's disease
46
What is Fabry (Anderson-Fabry) disease?
X-linked recessive condition
Deficiency of alpha-galactosidase A
Characterised by abnormal deposits of a particular fatty substance called globotriaosylceramide in blood vessel walls throughout the body.
47
Features of Fabry disease
```
Limb pain
Sensory neuropathy
Raynaud's disease
Cardiac arrhythmias, cardiomyopathy
Nephrotic syndrome
Dermatological manifestation; angiokeratomas, Anhidrosis, cornea verticillate
Burning pain/paraesthesia in childhood
Angiokeratomas
Lens opacities
Proteinuria
Early cardiovascular disease
```
48
What is sensitivity?
Proportion of patients with the condition who have a positive test result
TP/(TP+FN)
49
What is specificity?
Proportion of patients without the condition who have a negative test result
TN/(TN+FP)
50
What is positive predictive value?
The chance that the patient has the condition if the diagnostic test is positive
TP/(TP+FP)
51
What is negative predictive value?
The chance that the patient does not have the condition if the diagnostic test is negative
TN/(TN+FN)
52
What is likelihood ratio for a positive test result?
How much the odds of the disease increase when a test is positive
sensitivity / (1 - specificity)
53
What is likelihood ratio for a negative test result?
How much the odds of the disease decrease when a test is negative
(1 - sensitivity) / specificity
54
Properties of normal population
Symmetrical i.e. Mean = mode = median
68. 3% of values lie within 1 SD of the mean
95. 4% of values lie within 2 SD of the mean
99. 7% of values lie within 3 SD of the mean
55
What is homocystinuria
Rare AR disease caused by deficiency of cystathionine beta synthase. This results in an accumulation of homocysteine which is then oxidized to homocystine
56
Features of homocystinuria
Often patients have fine, fair hair
Musculoskeletal: may be similar to Marfan's - arachnodactyly etc
Neurological patients may have learning difficulties, seizures
Ocular: downwards (inferonasal) dislocation of lens
Increased risk of arterial and venous thromboembolism
Also malar flush, livedo reticularis
57
How to diagnose homocystinuria
Cyanide-nitroprusside test (which is also positive in cystinuria)
58
Treatment of homocystinuria
Vitamin B6 (pyridoxine) supplements
59
Source, stimulus & action of Gastrin
Source -> G cells in antrum of stomach
Stimulus -> Distension of stomach, vagus nerve, intraluminal peptides/amino acids
Inhibited by -> Low antral pH, somatostatin
Action -> Increase HCL, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation
60
Source, stimulus & action of CCK
Source -> I cells in upper small intestine
Stimulus -> Partially digested protein and triglycerides
Action -> Increases secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on pancreatic acinar cells, induces satiety
61
Source, stimulus & action of Secretin
Source -> S cells in upper small intestine
Stimulus -> Acidic chime, fatty acids
Action -> Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells
62
Source, stimulus & action of VIP
Source - > Pancreas, small intestine
Stimulus -> Neural
Action -> Stimulates secretion by pancreas and intestines, inhibits acid secretion
63
Source, stimulus & action of Somatostatin
Source -> D cells in the stomach & pancreas
Stimulus -> Fat, bile salts and glucose in the intestinal lumen
Action -> Decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates gastric mucous production
64
Kearns-Sayre syndrome
Mitochondrial inheritance
Onset < 20-years-old
Presentation -> External ophthalmoplegia, Retinitis pigmentosa Ptosis may be seen
65
Rules of mitochondrial inheritance
Inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
All children of affected males will not inherit the disease
All children of affected females will inherit it
Generally encode rare neurological diseases
Poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy)
66
Examples of mitochondrial inheritance
Examples include:
-> Leber's optic atrophy
-> MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
-> MERRF syndrome: myoclonus epilepsy with ragged-red fibres
-> Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa.
Ptosis may be seen
-> Sensorineural hearing loss
67
cAMP system
Neurotransmitter ligands (receptors)
- > Epinephrine (α2, β1, β2)
- > Acetylcholine (M2)
Hormonal ligands
-> ACTH, ADH, calcitonin, FSH, glucagon, hCG,LH, MSH, PTH, TSH, GHRH*
Primary effector
-> Adenylyl cyclase
Secondary messenger
-> cAMP (cyclic adenosine monophosphate)
68
Phosphoinositol system
Neurotransmitter ligands (receptors)
- > Epinephrine (α1)
- > Acetylcholine (M1, M3)
Hormonal ligands
-> angiotensin II, GnRH, GHRH*, Oxytocin, TRH
Primary effector
-> Phospholipase C
Secondary messenger
-> IP3 (inositol 1,4,5 trisphosphate) and DAG (Diacylglycerol)
69
cGMP system
Hormonal ligands
-> ANP, Nitric oxide
Primary effector
-> Guanylate cyclase
Secondary messenger
-> cGMP
70
Tyrosine kinase system
Hormonal ligands
-> Insulin, growth hormone, IGF, PDGF
Primary effector
-> Receptor tyrosine kinase
Secondary messenger
-> Protein phosphatase
71
X-linked dominant conditions
The following conditions are inherited in a X-linked dominant fashion*:
- > Alport's syndrome (in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing)
- > Rett syndrome
- > Vitamin D resistant rickets
72
What chromosome is p53 on?
Chromosome 17
73
Cause of Li-Fraumeni syndrome
p53 mutation
74
What does p53 mutation cause?
Li-Fraumeni syndrome
Most commonly mutated gene in breast, colon and lung cancer
75
What is p53?
Tumour suppressor gene on chromosome 17
Thought to play a crucial role in the cell cycle, preventing entry into the S phase until DNA has been checked and repaired. It may also be a key regulator of apoptosis
76
Role of RER
Translation and folding of new proteins
Manufacture of lysosomal enzymes
Site of N-linked glycosylation
77
Role of SER
Steroid and lipid synthesis
78
Role of Golgi apparatus
Modifies, sorts and packages molecules destined for cell secretion
79
Role of mitochondria
Aerobic respiration
80
Role of nucleus
DNA maintanence
| RNA transcription
81
Role of lysosome
Breakdown of large molecules such as proteins and polysaccharides
82
Role of nucleolus
Ribosome production
83
Role of ribosome
Translation of RNA to proteins
84
Role of peroxisome
Catabolism of very long chain fatty acids and amino acids. Results in formation of hydrogen peroxide
85
Role of proteosome
Involved in degradation of proteins tagged with ubiquitin
86
p53 association
Many cancers esp. breat, lung, colon
| Li-Fraumeni syndrome
87
APC association
Colon cancer
88
BRCA 1+2 association
Breast and ovarian cancer
89
NF1 association
Neurofibromatosis
90
Rb association
Retinoblastoma
91
WT1 association
Wilms tumour
92
MTS-1 association
Melonaoma
93
HLA-A3 association
Haemochromatosis
94
HLA-B5 association
Bechets disease
95
HLA-B27 association
Ank spond
Reiters syndrome
Acute anterior uveitis
96
HLA-DQ2/8 association
Coeliac
97
HLA-DR2 association
Nacroplepsy
| Goodpastures
98
HLA-DR3 association
Dermatitis herpetiformis
Sjogrens syndrome
PBC
99
HLA-DR4 association
T1DM
| RA
100
Events during G0
"Resting" phase. Hepatocytes & neurons here.
101
Events during G1
Cells increase in size. Determines length of cell cycle.
102
Events during S
Synthesis of DNA, RNA & histone. Centrosome duplication
103
Events during G2
Cells continue to increase in size
104
Events during M
Mitosis
105
What is mitosis
Process by which somatic cells divide and replicate. Results in 2 diploid daughter cells.
106
What is meiosis
Process by which gametes are formed.
| Results in 4 haploid cells
107
Stages of mitosis
Prometaphase -> Metaphase -> Anaphase -> Telophase -> Cytokinesis
108
Examples of trinucleoside repeat conditions
```
Fragile X (CGG)
Huntingtons (CAG)
Myotonic dystrophy (CTG)
Freidrichs ataxia (GAA)
Spinocerebellar ataxis
Spinobulbar muscular atrophy
```
109
Trinucleotide repeat responsible for Fragile X
CGG
110
Trinucleotide repeat responsible for Huntington's
CAG
111
Trinucleotide repeat responsible for myotonic dystrophy
CTG
112
Trinucleotide repeat responsible for Freidrich's ataxia
GAA
113
Aim of phase I clinical trial
Determines pharmacokinetics, pharmacodynamics and side effects prior to larger studies.
Conducted on healthy volunteers
114
Aim of phase IIA clinical trial
Assesses optimal dosage
115
Aim of phase IIB clinical trial
Assesses efficacy
116
Aim of phase III clinical trial
Assesses effectiveness
117
Aim of phase IV clinical trial
Post-marketing monitoring of long-term efficacy and side effects.
118
Outcome of cohort study
Relative risk
119
Outcome of case-control study
Odds ratio
120
What is cohort study
Observational and prospective
121
What is a case-control study
Observational and retrospective
122
Characteristics of normal distribution
Mean = median = mode
123
Characteristics of positively skewed distribution
Mean > median > mode
124
Characteristics of negatively skewed distribution
Mean < median < mode
125
What is a funnel plot
Used to demonstrate the existence of publication bias in meta-analyses.
Funnel plots are usually drawn with treatment effects on the horizontal axis and study size on the vertical axis.
126
What does a symmetrical funnel plot mean
Publication bias unlikely
127
What does an asymmetrical funnel plot mean
There is a relationship between treatment effect and sample size
128
Acute phase proteins include
```
CRP
Procalcitonin
Ferritin
Fibrinogen
Alpha-1-antitrypsin
Ceruloplasmin
Serum amyloid A
Serum amyloid P
Haptoglobin
Complement
```
129
Proteins which reduce in the acute phase response are
```
Albumin
Transthyretin
Transferrin
Retinol binding protein
Cortisol binding protein
```
130
Definition of incidence
The number of new cases per population in a given time period
131
Definition of prevalence
The total number of cases per population at a particular point in time
132
C1 - Inhibitor deficiency
Causes hereditary angioedema
133
C1q, C1rs, C2, C4 deficiency
Predisposes to immune complex disease such as SLE, Henoch-Schonlein purpura
134
C3 deficiency
Causes recurrent bacterial infection
135
C5 deficiency
Predispose to Leiner disease which causes recurrent diarrhoea, wasting and seborrheic dermatitis
136
C5 - 9 deficiency
Prone to Neisseria meningitis
137
Which complement deficiency causes hereditary angioedema?
C1 - inhibitor deficiency
138
Which complement deficiency predisposes to immune complex disease?
C1q, C1rs, C2, C4
139
Which complement deficiency predisposes to recurrent bacterial infection?
C3
140
Which complement deficiency predisposes to Leiner disease?
C5
141
S+S Leiner disease
C5 deficiency. Causes recurrent diarrhoea, wasting and seborrheic dermatitis
142
What complement deficiency predisposes to Neisseria meningitis?
C5-9
