Clinical sciences Flashcards
1
Q
What are funnel plots used for?
A
Used to demonstrate publication bias in meta analysases
2
Q
How do you interpret funnel plots?
A
Symmetrical, inverted funnel shape - pub bias unlikely
asymmetrical funnel - relationship present between treatment effect and study size –> publication bias or systematic difference between smaller and larger studies (small study effects)
3
Q
thin acending loop of henle - what can and cant get through?
A
Impermeable to water
Highly permeable to Na and Cl
4
Q
early-onset breast cancer, sarcoma and leukaemia
Condition? gene?
A
Li-Fraumeni syndrome - p53 mutation
5
Q
What is p53 gene for?
A
Crucial role in cell cycle - prevents entery into S phase until DNA has been checked and repaired
May also regulate apoptosis
6
Q
Which pneumocytes secrete surfactant?
A
Pneumocyte type 2 - can differentiate into type 1 during lung damage
7
Q
Difference between cranial and nephrogenic DI
A
Cranial - deficiency of ADH
Nephrogenic - insensitivity to ADH
8
Q
Where does ADH act and what does it do?
A
ADH promotes water reabsorption via insertion of aquaporin 2 channels in collect ducts
9
Q
What triggers release of ADH?
A
extracellular fluid osmolality increase
volume decrease
pressure decrease
angiotensin II
10
Q
What reduces secretion of ADH?
A
extracellular fluid osmolality decrease
volume increase
temperature decrease
11
Q
C1 inhibitor (C1-INH) protein deficiency - consequence?
A
causes hereditary angioedema
C1-INH is a multifunctional serine protease inhibitor
probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues
12
Q
C1q, C1rs, C2, C4 deficiency (classical pathway components) - consequence?
A
predisposes to immune complex disease
e.g. SLE, Henoch-Schonlein Purpura
13
Q
C3 deficiency - consequence?
A
causes recurrent bacterial infections
14
Q
C5 deficiency - consequence?
A
predisposes to Leiner disease
recurrent diarrhoea, wasting and seborrhoeic dermatitis
15
Q
C5-9 deficiency - consequence?
A
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infection
16
Q
What diseases is endothelin involved in?
A
primary pulmonary hypertension (endothelin antagonists are now used),
cardiac failure,
hepatorenal syndrome
and Raynaud’s.
17
Q
Calculation of absolute risk reduction?
A
Absolute risk reduction = (Control event rate) - (Experimental event rate)
18
Q
Where in nephron does majority of glucose reabsorption occur?
A
Proximal convoluted tubule
19
Q
What is the genetic phenomenon of anticipation? Which disorders are more likley to experience this?
A
earlier onset in successive generations
Particularly present in trinucleotide repeat disorders
20
Q
Most common cause of Down Syndrome (genetically)
A
Nondisjunction
21
Q
prenatal tests showing low circulating levels of pregnancy-associated plasma protein-A (PAPP-A) and an abnormal nuchal translucency screening test
Diagnosis?
A
Downs syndrome
22
Q
Examples of mitochondrially inherited disease?
A
Leber’s optic atrophy
symptoms typically develop at around the age of 30 years
central scotoma → loss of colour vision → rapid onset of significant visual impairment
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
23
Q
Children of fathers with mitochondrialy inherited disease?
A
For a man with mitochondrial disease, none of his children will inherit the condition
24
Q
What is Gaucher’s disease? How does it present?
A
Gaucher’s disease is an autosomal recessive disease and it is the most common lipid storage disorder
Leads to accumulation of glucocerebrosidase in brain, liver and spleen
Present with hepatosplenomegaly and aseptic necrosis of femur
25
Which metabolic disorder causes:
Developmental delay
Cherry red spot on macula
+- hepatosplenomegaly
If no hepatosplenomegaly - Tay-Sachs disease
If hepatospenomegaly - Niemann-Pick disease
26
Most common cardiac and renal abnormalities in Turner's?
Cardiac - Biscuspid aortic valve (15%), coarctation of aorta (5-10%)
Increased risk of aortic dilatation and dissection
Renal - horseshoe kidney
27
What does specificity and sensitivity mean?
Specificity - Proportion of patients without the condition who have a negative test result
TN / (TN + FP)
Sensitivity - Proportion of patients with the condition who have a positive test result
Sensitivity = TP / (TP + FN )
28
What is lead time bias?
Occurs when two tests for a disease are compared, the new test diagnoses the disease earlier, but there is no effect on the outcome of the disease
29
HLA DR3 is associated with which conditions?
dermatitis herpetiformis
Sjogren's syndrome
primary biliary cirrhosis
T1DM (More strongly associated with DR4)
30
How to calculate NTT?
NNT = 1 / Absolute Risk Reduction
31
Short stature + primary amenorrhoea
Diagnosis?
Turners syndrome
32
What are the parametric tests and non-parametric tests? When to use which?
Parametric - normally distributed data
Parametric tests:
- Students t test (paired v unpaired - single group of patients if paired)
- Pearsons product moment coefficient - correlated
Non-parametric tests
- Mann Whitney U test
- Wilcoxon signed rank test
- Chi-squared test
- Spearman, Kendall rank - correlation
33
Which statistical test to use when:
comparing ordinal, interval, or ratio scales of unpaired data
Mann-Whitney U
Nominal = categorical = qualitative
No sense of order
E.g ; sex , color
Frequency/proportion ; percentages
Ordinal
Rank , satisfaction , fanciness
Frequency/proportion ; percentages
Interval / ratio = scale = quantitative = parametric
Number of costumers
Weight
Age
Size
34
Which statistical test to use when:
comparing two sets of observations on a single sample, e.g. a 'before' and 'after' test on the same population following an intervention
Wilcoxon signed rank
35
Which statistical test to use when:
Comparing proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
Chi-squared
36
Karyotype in Turners?
45 XO
37
Which dermatological condition is associated with Coeliac - how does this look? Which HLA is this associated with?
Dermatitis herpetiformis - intensely itchy, papulovesicular, blistering rash, similar to that seen in herpes infection
Associated with HLA DR3
38
How can you work out variance if you know SD?
SD^2 = variance
39
Which studies are most affected by recall bias?
Case control studies
40
Multiple sarcomas at young age - what genetic condition and what gene + its role?
Li-Fraumeni syndrome
Mutation in p53 (tumour suppressor gene 17p) - holds cell cycle at G1/S phase checkpoint allowing for detection + repair of DNA damage
41
When is the mean, mode and median the same?
in a normal distribution of data-
42
Which chromosome encodes for HLA antigens?
Chromosome 6
43
Why can sepsis lead to Hypotension?
Sepsis -> release of IL1 which causes vasodilation and hence hypotension
44
What do the different subunits of troponin bind to?
troponin C: binds to calcium ions
troponin T: binds to tropomyosin, forming a troponin-tropomyosin complex
troponin I: binds to actin to hold the troponin-tropomyosin complex in place
45
What is the purpose of secondary messenger system? what can trigger the cGMP system?
Secondary messengers - allow for amplification of external stimulus
ANP and NO act as ligand hormones for cGMP system
46
What describes the power of a study? how can you calculate it?
the probability that a statistically significant difference will be detected / probability of (correctly) rejecting the null hypothesis when it is false / which also means the probability of confirming the alternative hypothesis when the alternative hypothesis is true
Power = 1 - probability of type 2 error (beta)
47
Inheritance of G6PD?
X linked recessive so no male to male transmission
Hence titos son's can't have G6PD
48
Where is phosphate reabsorbed in the nephron?
PCT is responsible for phosphate reabsorption
49
What are the main parts of antibodies and what binds to each part?
Fab region: antigen-binding fragment - the region that binds to antigens
Fc region: fragment crystallizable region - the tail region of an antibody that interacts with cell surface receptors
50
Reactive arthritis HLA?
HLA B27
51
What is Fabry disease? How is it inherited?
X linked recessive - lysosomal storage condition
leads to kidney failure, HF, body pain and skin issues
52
What is a type 2 error in stats?
Type II error - the null hypothesis is accepted when it is false
53
What is the usual outcome measure in cohort studies?
Relative risk
54
What cytokine is involved in development of granulomas?
Inf-gamma = used in macrophage activation which leads to the formation of granuloma
may be useful in chronic granulomatous disease and osteopetrosis
55
What happens during reverse transcriptase PCR? what is this used for?
RNA is converted to DNA
It is used to detect gene expression
56
the probability of obtaining a result by chance at least as extreme as the one that was actually observed, assuming that the null hypothesis is true
What does this describe?
P value
57
how can you calculate standard error of mean?
Standard deviation / square root (No. of patients)
58
Difference between type 1 and 2 errors?
Type I: the null hypothesis is rejected when it is true (false +ve)
Type II: the null hypothesis is accepted when it is false (false -ve)
59
What are some examples of X linked dominant conditions?D
Alports
Retts
Vit D resistant rickets
60
What is the main action of PCR reactions?
DNA amplification
61
What is incidence?
The incidence is the number of new cases per population in a given time period.
62
What is prevalence? point v period?
The prevalence is the total number of cases per population at a particular point in time
point prevalence = number of cases in a defined population / number of people in a defined population at the same time
period prevalence = number of identified cases during a specified period of time / total number of people in that population
63
What is the relationship between incidence and prevalence?
prevalence = incidence * duration of condition
in chronic diseases the prevalence is much greater than the incidence
in acute diseases the prevalence and incidence are similar. For conditions such as the common cold the incidence may be greater than the prevalence
64
Early strokes / MIs + proteinuria + typical rash (angiokeratomas)? How does the rash look and what is the condition / inheritances?
rash in a bathing-suit distribution - angiokeratomas
X linked recessive deficiency of alpha-galactosidase A -> FABRY DISEASE
65
When to use Wilcoxon signed rank test?
Non-parametric
compares two sets of observations on a single sample, e.g. a 'before' and 'after' test on the same population following an intervention
66
Effect of metanalyses on power and p value v individual studies?
Increase power
decreaase p value
67
Which virus is a RF for oropharnyngeal ca? what else is this a RF for?
HPV 16/18
Also for cervical, vulval, anal, penile
68
Which Ca is increased risk with EBV?
Burkitt's lymphoma
Hodgkin's lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
69
Risk of which ca with Hep B+C?
HCC
70
Human T-lymphotropic virus 1 increased risk of which conditions?
Adult T cell leukaemia
Tropical spastic paraparesis
71
How to calculate NNT? and everything in the calculation?
1/(Absolute risk reduction)
Absolute risk reduction = CER-EER or EER-CER
EER = (Number who had particular outcome with the intervention) / (Total number who had the intervention)
CER = (Number who had a particular outcome with the control/ (Total number who had the control)
72
Homocystinuria - what is the tx?
B6 (Pyridoxine) supplementation
73
What are the features of diabetic nephropathy under biopsy?
Kimmelstiel-Wilson lesions (odulular hyaline areas develop in the glomuli), nodular glomerulosclerosis
74
What are diseases inherited in a mitochondrial pattern? (5)
Leber's optic atrophy
symptoms typically develop at around the age of 30 years
central scotoma → loss of colour vision → rapid onset of significant visual impairment
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
75
ABL is the oncogene for?
Chronic myeloid leukaemia
76
c-MYC and n-MYC is the oncogene for?
cMYC = Burkitt's lymphoma
nMYC = Neuroblastoma
77
BCL2 is the oncogene for?
Follicular lymphoma
78
RET is the oncogene for?
Multiple endocrine neoplasia (types II and III)
79
RAS is the oncogene for?
Many cancers especially pancreatic
80
erb-B2 is the oncogene for?
erb-B2 (HER2/neu) = Breast + ovarian Ca
81
Which cytokine is responsible for activating macrophages?
Interferon-γ
82
Which conditional are generally Autsomally recessive - exceptions?
Autosomal recessive conditions are 'metabolic'
exceptions: inherited ataxias
83
Which conditions are generally autosomally dominant? exceptions?
Autosomal dominant conditions are 'structural'
exceptions: Gilbert's, hyperlipidaemia type II
84
MoA of homocystinuria?
deficiency of cystathionine beta synthase
85
Causes of lens dislocation - upward v downward?
Lens dislocation
'Moon is up and home is down'
Moon = marfanoid and home= homocystinurea
86
Urinalysis and microscopy reveals muddy brown granular casts.
Pathology?
Acute tubular necrosis
87
Features of DiGeorge syndrome? What is underlying pathology?
CATCH22:
C - Cardiac abnormalities
A - Abnormal facies
T - Thymic aplasia
C - Cleft palate
H - Hypocalcaemia/ hypoparathyroidism
22 - Caused by chromosome 22 deletion
1o immunodeficiency disorder caused by T-cell deficiency and dysfunction - increased risk of viral and fungal infections
88
mitochondrial inheritance
onset < 20-years-old
external ophthalmoplegia
retinitis pigmentosa
What is the disorder?
Kearns-Sayre syndrome
'Cant see yar'
89
Turners features?
ABC Clowns
A - primary Amenorrhea
B - absent Barr body
C - Cystic fibrosis
C - Cardiac anomalies (most common - coarctation of aorta)
L - Lymphoedema, low thyroid
O - Ovaries under developed (streak ovaries)
W - Webbed neck
N - Nipples widely placed
S - Short stature, Sensoneural hearing loss, Short 4th metacarpal
90
Cell cycle - what is the resting phase?
G0
91
Cell cycle - what phase determines length of cell cycle, what controls this?
G1 (Gap1) = under influence of p53
92
What is the shortest phase of the cell cycle?
Mitosis (M)
93
Which disease is associated with:
developmental delay and cherry red spot on the macula, without hepatomegaly or splenomegaly
What if hepato / splenomegaly present?
Tay-Sachs disease
If megaly present - Niewman-pick disease
94
What is gauchers disease how does it present?
lysosomal storage disease which presents with massive splenomegaly.
At Gaucho they serve up massive spleens
95
McArdles disease presentation?
Glycogen storage disease -> myalgia and myoglobinuria with exercise
Think of that TV show
96
Where does ADH act?
Collecting ducts - collects the water!!!
97
Psoriatic arthritis - HLA?
HLA B27
98
a shortened neck and a protruding tongue. There are a number of white spots visible in her iris.
Suggestive of which disorder and genetic abnormality?
Downs - Nondisjunction
99
Role of p53 gene?
Regulates cell cycle - preventing entry into the S phase until DNA has been checked and repaired
100
HLA DR3 is associated with which disorder?
Dermatitis herpetiformis
101
burning pain/paraesthesia in childhood
angiokeratomas
These are features of which disorder?
What else may be seen? What causes this?
Fabry disease - caused by deficiency of alpha-galactosidase A (X-linked recessive)
Proteinuria + early cardiovascular disease
102
Which abx should be avoided in breastfeeding?
Ciprofloxacin,
tetracycline,
chloramphenicol,
sulphonamides
103
Which psych drugs are CI in breast feeding?
lithium, benzodiazepines, clozapine
104
Which drugs non-psych / abx should be avoided in breastfeeding?
aspirin
carbimazole
methotrexate
sulfonylureas
cytotoxic drugs
amiodarone
105
What is Tay-Sachs disease?
An AR inherited lysosomal storage disorder due to mutated HEXA gene
more common in ashkenazi jews
106
Haemophilia A inheritance?
X linked recessive
107
What are TH1 v TH2 cells
Th1 = IFN gamma, 2,3,4 + type 4 hypersensitivity
Th2 = IgE, 4,5,6,10,13 (all the higher numbers of IL) - involved in humoral immunity (ab)
108
What is a silent mutation?
A mutation that does not change the amino acid, often base change in 3rd position of codon
109
What is a nonsense mutation?
A mutation that results in a stop codon
110
What is a Missense mutation?
A point mutation that changes the amino acid sequence, which in turn may make the protein non-functional
111
What is a frameshift mutation?
Caused by insertion or deletion of a number of nucleotides which results in the subsequent reading of the DNA 'downstream' being completely wrong
112
Blue sclera
What investigation distinguishes between the different ddx?
osteogenesis imperfecta - normal homogentisic acid
Alkaptonuria - raised homogentisic acid
113
MoA of NO?
vasodilation + inhibits platelet aggregation
114
Wilson and Junger criteria for screening tests?
1. The condition should be an important public health problem
2. There should be an acceptable treatment for patients with recognised disease
3. Facilities for diagnosis and treatment should be available
4. There should be a recognised latent or early symptomatic stage
5. The natural history of the condition, including its development from latent to declared disease should be adequately understood
6. There should be a suitable test or examination
7. The test or examination should be acceptable to the population
8. There should be agreed policy on whom to treat
9. The cost of case-finding (including diagnosis and subsequent treatment of patients) should be economically balanced in relation to the possible expenditure as a whole
10. Case-finding should be a continuous process and not a 'once and for all' project
115
HLA DR2 conditions associated?
Dr - has 2 good features - He is Nice and Good :)
DR2 - Narcolepsy and Goodpasture
116
Which statistical test to use for correlation between two things?
parametric (normally distributed): Pearson's coefficient
non-parametric: Spearman's coefficient
Some weird correlation between pearson and spearman however pearson is a normal name and spearing a man is not a normal thing to do
117
Which condition are girls with X linked recessive disorders likely to have and why?
Turners as there is only one X chromosome
118
What are the different phases of clinical trials?
0 Exploratory studies - small n number asess pharmacokinetics + dynamics
I Safety assessment - done on healthy volunteers
II Assess efficacy - IIa optimal dosing, IIb assessing efficacy (small numbers with disease)
III Assess effectiveness - 100-1000s usualy RCT v established mx
IV Postmarketing surveillance - Monitors for long-term effectiveness and side-effects
119
What is the most common cardiac issue in downs?
Endocardial cushion defects - aka atrioventricular septal defect (AVSD) or atrioventricular canal defect
120
is the probability of obtaining a result by chance at least as extreme as the one that was actually observed, assuming that the null hypothesis is true
Means what?
This is the p value
121
What can linear regression be used for?
When analysing data on a scatter plot, linear regression may be used to predict how much one variable changes when a second variable is changed
122
Interferon-alpha where is this produced and what action does this have?
Produced by leucocytes and has antiviral action
123
Interferon-beta where is this produced and what action does this have?
Produced by fibroblasts and has anti-viral action
Reduces the frequency of exacerbations in patients with relapsing-remitting MS
124
Interferon-gamma where is this produced and what action does this have?
Mainly made by NK cells and also TH1 cells
Weaker antiviral action - more of a role in immunomodulation, particularly macrophage activation
125
What is associated with HLA DR4
Type 1 diabetes mellitus*
Rheumatoid arthritis - in particular the DRB1 gene (DRB1*04:01 and DRB1*04:04 hence the association with DR4)
126
Proportion of different immunoglobulins in the blood?
IgG 75%
IgA 15%
IgM 10%
IgD 1%
IgE 0.1%
GAMDE
127
Which type of studies are commonly affected by recall bias?
Case-control studies
128
Penetrance v expressivity? examples of diseases?
Penetrance = describes 'how likely' it is that a condition will develop
eg. incomplete penetrance = retinoblastoma, huntingtons v achondroplasia = complete (100%) penetrance
Expressivity = describes the 'severity' of the phenotype
eg high expressivity = NFib
129
What can influence penetrance and expressivity?
Modifier genes
Environmental factors
Allelic variation
130
Which one of the following types of immunoglobulins are responsible for haemolytic blood transfusion reactions?
IgM
131
Most commonly produced immunoglobulin in the body?
IgA
132
IL-8 source and role?
Produced by macrophages important for neutrophil chemotaxis
133
Where is IL 12 produced and what does this do?
Dendritic cells, macrophages, B cells all produce IL-12 and this activates NK cells and stimulates differentiation of naive T cells into Th1 cells
134
Where is TNFa produced and what does it do?
Macrophages prodcue TNFa which induces fever and induces neutrophil chemotaxis
135
IL-10 where is this produced and what is its role?
IL-10 is produced by TH2 cells and it:
- inhibits Th1 cytokine production
- AKA human cytokine synthesis inhibitory factor and is an 'anti-inflammatory' cytokine
136
Which immunoglobulin is involved in activation of B cells?
IgD
137
What provides immunity against parasites and how?
IgE synthesised by plasma cells activates eosinophils leading to attack parasitic infections
138
hyperacute organ rejection is caused by which cell?
B cells
139
What cells act as APCs?
B cells
140
Which cells recognise MHC I and MHC II molecules?
MHC I = Cytotoxic T cells
MHC II = Helper T cells
141
What antigens are expressed by Hepler T cells and cytotoxic T cells?
Helper T cells - CD4, CD3, TCR + CD28
Cytotoxic T cells - CD8, CD3, TCR
142
Which cells mediates acute and chronic organ rejection?
Helper T cells + Cytotoxic T cells
143
Which cell of the adaptive immune response is a major source of IL2
Helper T cells
144
Intention to treat analysis - what to do if people drop out of trial?
include patients who dropped out of trial
145
Relative risk reduction calculation?
(EER - CER) / CER
146
WT1 gene mutation is associated with?
Wilms tumour - this is the tumour supressor gene associated with this
147
Tumour suppressor genes examples
p53
APC - Colorectal ca
BRAC1 + 2
NF1
Rb - retinoblastoma
WT1 - Wilms tumour
Multiple tumor suppressor 1 (MTS-1, p16) - Melanoma
148
What is a cohort study used for?
Observational and prospective. Two (or more) are selected according to their exposure to a particular agent (e.g. medicine, toxin) and followed up to see how many develop a disease or other outcome.
The usual outcome measure is the relative risk.
149
What is a case control study used for what is the outcome mesaure?
Observational and retrospective.
Patients with a particular condition (cases) are identified and matched with controls. Data is then collected on past exposure to a possible causal agent for the condition.
The usual outcome measure is the odds ratio.
Inexpensive, produce quick results
Useful for studying rare conditions
Prone to confounding
150
What does a cross sectional study do and what does it tell us?
Provide a 'snapshot', sometimes called prevalence studies
Provide weak evidence of cause and effect
151
Fundoscopy demonstrates peripapillary telangiectasia
Which condition may this be seen in? inheritance?
Lebers hereditary optic neuropathy
Mitochondrial inheritance
152
achondroplasia - mutation in what gene and inheritancce?
Gain of function mutation in the FGFR3 (fibroblast growth factor receptor) gene
AD inheritance
153
How to calculate Likelihood ratio for a netgative / positive test result? what does this mean?
Likelihood ratio for a positive test result = sensitivity / (1 - specificity) - How much the odds of the disease increase when a test is positive
Likelihood ratio for a negative test result = (1 - sensitivity) / specificity - How much the odds of the disease decrease when a test is negative
154
CA 15-3 - use and which ca?
Marker used for breast cancer therapy monitoring
155
How to calculate relative risk?
Relative risk = EER / CER
156
What is the major genetic susceptibility locus for RA?
The HLA-DRB1 gene
157
Acute anterior uveitis - HLA?
HLA-B27
158
HLA-DQ2/DQ8 - disease?
Coeliac
159
HLA-A3 - is associated with?
Haemochromatosis
160
HLAs which are class I and class II
HLA A, B and C are class I antigens
HLA DP, DQ, DR are class II antigens
161
Describe which is more / less in +ve and -ve skewed distribution?
alphabetical order: mean - median - mode
'>' for positive, '<' for negative
162
What is used to analyse survival over time?
Hazard ratio
163
How to calculate down syndrome risk at a given age?
Age 20 = 1/5000
Down's syndrome risk - 1/1000 at 30 years then divide by 3 for every 5 years
164
Levels of evidence?
Ia - evidence from meta-analysis of randomised controlled trials
Ib - evidence from at least one randomised controlled trial
IIa - evidence from at least one well-designed controlled trial which is not randomised
IIb - evidence from at least one well-designed experimental trial
III - evidence from case, correlation and comparative studies
IV - evidence from a panel of experts
165
What are the features of Vit D resistant rickets and how is it diagnosed? mx?
failure to thrive
normal serum calcium, low phosphate, elevated alkaline phosphotase
x-ray changes: cupped metaphyses with widening of the epiphyses
Diagnosis - increased urinary PO4
Mx - High dose vit D + oral phosphate
166
elfin-like facies
characteristic like affect - very friendly and social
learning difficulties
short stature
transient neonatal hypercalcaemia
supravalvular aortic stenosis
Suggestive of what disorder?
Williams
167
Fitness to fly with haem disorders?
patients with a haemoglobin of greater than 8 g/dl may travel without problems (assuming there is no coexisting condition such as cardiovascular or respiratory disease)
168
Fitness to travel following surgery?
travel should be avoided for 10 days following abdominal surgery
laparoscopic surgery: after 24 hours
colonoscopy: after 24 hours
following the application of a plaster cast, the majority of airlines restrict flying for 24 hours on flights of less than 2 hours or 48 hours for longer flights
169
Flying during pregnancy?
most airlines do not allow travel after 36 weeks for a single pregnancy and after 32 weeks for a multiple pregnancy
most airlines require a certificate after 28 weeks confirming that the pregnancy is progressing normally
170
Fitness to fly with Respiratory disease?
pneumonia: should be 'clinically improved with no residual infection'
pneumothorax: absolute contraindication, the CAA suggest patients may travel 2 weeks after successful drainage if there is no residual air. The British Thoracic Society used to recommend not travelling by air for a period of 6 weeks but this has now been changed to 1 week post check x-ray
171
Fitness to fly with Cardiovascular disease?
unstable angina, uncontrolled hypertension, uncontrolled cardiac arrhythmia, decompensated heart failure, severe symptomatic valvular disease: should not fly
uncomplicated myocardial infarction: may fly after 7-10 days
complicated myocardial infarction: after 4-6 weeks
coronary artery bypass graft: after 10-14 days
percutaneous coronary intervention: after 3 days
stroke: patients are advised to wait 10 days following an event, although if stable may be carried within 3 days of the event
172
nephrotic syndrome and sensory neuropathy bilaterally in the arms
Corneal findings + skin findings are suggestive of what dx?
Fabrys disease
173
X linked recessive conditions?
A - androgen insensitivity syndrome
B - Becker/Duchenne dystrophy
C - colour blindness
D - Diabetes insipidus (nephrogenic)
E - eyes (retinitis pigmentosa)
F - Fabry
G - G6PD deficiency
H - haemophilia A/B, Hunter's
174
genotype:phenotype correlation in mitochondiral disease?
mitochondrial diseases often exhibit poor genotype-phenotype correlation, meaning that the same genetic defect can result in a wide range of clinical manifestations
175
Generally what types of diseases are mitochondrial?
Rare neurological ones
176
Man with mitochondrial disease - inheritance to children?
None of his children can get it
177
What test is used to assess for mutated oncogenes?
Polymerase chain reactions
RT PCR - used for gene expression within tissue sample and cant detect mutations in genome
178
What do leukotrienes do?
Mediators of inflammation and allergic reactions
cause bronchoconstriction, mucous production
increase vascular permeability, attract leukocytes
leukotriene D4 has been identified as the SRS-A (slow reacting substance of anaphylaxis)
179
Tell me about leukotriene production?
Secreted by leukocytes formed from arachidonic acid by action of lipoxygenase
NSAID induced bronchospasm in asth
180
What disorders are caused by deletion of chromosome 15?
Prader-Willi - paternal - microdeletion of paternal 15q11-13 (70% of cases), also maternal uniparental disomy of chromosome 15
AngelMan syndrome - maternal
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When to use ANOVA test?
One-way analysis of variance analysis (ANOVA) - used for parametric/approximately normally distributed data, when the mean needs to be compared for more than 2 groups
182
Turners has increased risk of what GI disorder?
Crohns
183
Different phases of cell division?
Prophase Chromatin in the nucleus condenses
Prometaphase Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes
Metaphase Chromosomes aligned at middle of cell
Anaphase The paired chromosomes separate at the kinetochores and move to opposite sides of the cell
Telophase Chromatids arrive at opposite poles of cell
Cytokinesis Actin-myosin complex in the centre of the cell contacts resulting in it being 'pinched' into two daughter cells
184
What is involved in control of respiration? what triggers these?
Central regulatory centres
- medullary respiratory centre
- apneustic centre (lower pons)
- pneumotaxic centre (upper pons)
Central + peripheral chemoreceptors
- central: raised [H+] in ECF stimulates respiration
- peripheral: carotid + aortic bodies, respond to raised pCO2 & [H+], lesser extent low pO2
Pulmonary receptors
- stretch receptors, lung distension causes slowing of respiratory rate (Hering-Bruer reflex)
- irritant receptor, leading to bronchoconstriction
- juxtacapillary receptors, stimulated by stretching of the microvasculature
185
Main features of homocystinuria?
Musc: Marfinoid appearance, osteoporosis, kyphosis
Neuro - LD + seiures
Ocular - myopia + downward dislocation of lens
Arterial + VTE
Malar flush + livedo reticularis
NB no risk of renal stones - this is seen in cystinuria
186
cyanide-nitroprusside test - when is this +ve?
Homocystinuria + cystinuria (latter = risk of renal stones)
187
Which part of cell cycle does Vincristine act on?
Metaphase - when chromosomes align at the middle at of the cell and then begin to separate
Vincristine binds to the tubulin protein, preventing the formation of microtubules and preventing the initiation of chromosome separation -> apoptosis
188
What condition presents similarly to Turners but in men? What is the karyotype?
Noonans - similar but also PV stenosis, triangular face, low set ears, factor 11 deficiency
Normal karyotype caused by AD defect in chromosome 12
189
Examples of trinucleotide repeat disorders?
Trineucleotide Repeat Disorders Mnemonic:
'My fragile Friend Hunts for Spine and Teeth'
Myotonic dystrophy (CTG)
Fragile X (CGG)
Friedreich's ataxia* (GAA)
Huntington's (CAG)
Spinocerebellar ataxia
Spinobulbar muscular atrophy
Dentatorubral pallidoluysian atrophy
190
Which conditions are Inf-a useful in?
Hepatitis B & C,
Kaposi's sarcoma,
metastatic renal cell cancer,
hairy cell leukaemia
191
Plasma viscosity in GCA?
Raised just like ESR and CRP
192
Describe types of hypersenitivity reactions?
Type I - Anaphylactic
Type II - Cell bound
Type III - Immune complex
Type IV - Delayed hypersensitivity
Type V - Antibodies recognise and bind to cell surfaces eg MG and Graves
193
Juvenile gout, is characterized by hyperuricemia + orange coloured sand secondary to hyperuricemia
Dx and inheritanced?
Lesch-Nyhan syndrome, X linked recessive
194
How to calculate pre-test and post-test probability?
Pre-test probability = Prevalence of condition
Post-test probability = post test odds / 1 + post test odds
195
How to calculate pre-test and post-test odds?
Pre-test odds = pre-test probability / (1 - pre-test probability)
The odds that the patient has the target disorder before the test is carried out
Post-test odds = pre-test odds x likelihood ratio of +ve test
The odds that the patient has the target disorder after the test is carried out
where the likelihood ratio for a positive test result = sensitivity / (1 - specificity)
196
Which receptors do INF-a. INF-b and INF-y bind to?
IFN-alpha and IFN-beta bind to type 1 receptors
IFN-gamma binds only to type 2 receptors.
197
Adverse effects of INF-a mx?
flu-like symptoms and depression
198
Fluorescence in situ hybridisation (FISH) - usec case?
Fluorescence in situ hybridisation uses a labelled probe to detect a genomic sequence on a chromosome and is less sensitive than PCR
170
120 - new -> 18
50 old -> 10
199
Intelligence in Turners?
Normal
200
Features of congenital toxo?
Cerebral calcification
Chorioretinitis
Hydrocephalus
