Download Describe in YOUR OWN WORDS, WITHOUT using

BME 301
Exam 2
March 29, 2005
Name:
The exam consists of 7 questions. Show all work to receive credit. Clearly organize your work
and draw a box around your final answers. NEATNESS COUNTS! Good Luck!
Problem 1 (15):
Problem 2 (15):
Problem 3 (15):
Problem 4 (10):
Problem 5 (15):
Problem 6 (10):
Problem 7 (20):
Extra Credit (3):
Total (100):
1. Cancer Screening
a. Name three cancers routinely screened for in the U.S. and the screening technique/test
used.
Female breast cancer-mammography
Cervical cancer-pap smear,
Prostate cancer-serum PSA & digital rectal examination,
Colon and rectal cancer-fecal occult blood & flexible sigmoidoscopy/colonoscopy
b. Do most people in the US adhere to screening recommendations? What factors cause
people not to be screened?
Adherence rates range from 50-80%. Patients with less education and no health insurance are
less likely to be screened.
c. We do not routinely screen women for ovarian cancer. Why not?
Using the available tests, the number of false positives that would result from testing would be
much greater than the number of women whose cancer would be detected early. The follow up
test (diagnostic laparoscopy) has a 1% complication rate. Testing could actually cause more
harm than good.
2. (a) What is an antibody? Describe its structure and its function in the immune system.
An antibody can be thought of as a bridge between a pathogen and the tool to kill it. Antibodies have two
important regions: (1) Fab region: which binds free antigen or binds surface of virus infected cell (2) Fc
region: which binds macrophages and neutrophils and induces phagocytosis or binds natural killer cell
and induces killing
(b) Explain the term “immunologic memory.”
Immunologic memory refers to the adaptive component of the immune system and its ability to
produce a more rapid and stronger immune response to an antigen that it has been exposed to
previously.
(c) Describe the cellular-level processes that enable the adaptive immune system to have
immunologic memory.
The first time the immune system is exposed to a foreign pathogen, a clone of B cells and T cells which
recognize this antigen are built up. After the infection is over, most die off. Some, called memory cells,
remain. The second time the adaptive immune system is activated by that antigen, the response is much
faster and stronger because the memory cells are much easier to activate.
3. Describe in your own words, WITHOUT using equations or other mathematical expressions or
the words “true”, “false”, “positive”, or “negative” the following terms with regard to a screening
test for ovarian cancer:
a. True Positive –
A test result that indicates someone has ovarian cancer when they really do have it
b. False Positive –
A test result that indicates someone has ovarian cancer when they really don’t have it
c. False Negative –
A test result that indicates someone doesn’t have ovarian cancer when they really do have it
d. True Negative –
A test result that indicates someone doesn’t have ovarian cancer when they really don’t have it
e. PPV –
The likelihood that you really have ovarian cancer if your test is positive OR
The percentage of women with a positive test who really have ovarian cancer
f.
NPV –
The likelihood that you really do not have ovarian cancer if your test is negative OR
The percentage of women with a negative test who really do not have ovarian cancer
g. Suppose we have two new screening tests for ovarian cancer – Test A and Test B. When tested in
a large population, we find the following sensitivity and specificity values for the two tests.
Test
Test A
Test B
Se
60%
95%
Sp
95%
60%
Your mother knows that you have taken BME301. She is worried about her risk of ovarian cancer
because both her mother and sister died of ovarian cancer at a young age. She asks your advice about
which screening test to undergo. Which test would you recommend that she take? Why?
Test B. We want a test with a high sensitivity for someone who is at higher risk – we don’t want to risk a
false negative result. While test B will result in more false positives, the risk of following up a false
positive result is of less concern than the risk of missing a cancer.
4. Two scientists want to know if a certain drug is effective against high blood pressure.
The first scientist wants to give the drug to 1,000 people with high blood pressure and see how many
experience lower blood pressure levels.
The second wants to give the drug to 500 people with high blood pressure and not give the drug to
another 500 people with high blood pressure and see how many people in both groups experience lower
blood pressure.
a. What is the better way to test this drug?
The two group method.
b. Why is it better to test the drug this way?
We need to compare results of our drug with those in a control group to determine whether the effects of
the new drug are different than those due to no intervention.
5. (a) Compare and contrast live, attenuated virus vaccines, carrier vaccines and DNA vaccines.
Live attenuated vaccine: A live attenuated vaccine is made when we grow a pathogen in host cells
repeatedly to weaken it so it cannot produce disease in healthy people but it can still produce a strong
immune response that protects against future infection. The disadvantage is that it can produce disease in
an immuno-compromised individual.
Carrier vaccine: A carrier vaccine uses a virus of bacterium that does not cause disease to carry viral
antigens to an antigen presenting cell. The advantage of this approach is that it makes memory B and T
cells but does not pose a danger of real infection.
DNA Vaccine: A DNA vaccine uses a portion of DNA that codes for a few viral genes. DNA injections
can produce memory B cells and memory T killer cells. Reasons are not fully understood. No danger
that it would cause infection. Animal trials have been very successful; human trials have been less
successful thus far.
(b) If you wish to make a vaccine for HIV, describe the advantages and limitations of the three
approaches above. What strategy appears most promising in current clinical trials?
Live attenuated vaccine: While it stimulates cell and antibody mediated immunity, this strategy is too
dangerous for HIV, because the virus constantly mutates.
Carrier vaccine: While it stimulates cell and antibody mediated immunity, immunocompromised
individuals can become ill due to the carrier. Also, booster shots must use a different carrier.
DNA Vaccine: Human trials are underway. This approach, in combination with carrier vaccines, appears
most promising in current human trials.
6. The Belmont Report establishes the three fundamental ethical principles that guide the ethical conduct
of research involving human participants: 1) Respect for Persons; 2) Justice; and 3) Beneficence. These
principles require that all subjects participating in medical research give informed consent.
a. Define informed consent.
Informed consent means that a subject has been fully informed of the risks and benefits of participating in
a study and has voluntarily chosen to participate.
The following story appeared in The Oregonian this month. Read it and answer the question below.
Blood trial could omit consent form
Doctors seek community consensus to test a blood substitute on trauma patients who may not be conscious
ANDY DWORKIN
How would you feel knowing that a doctor could experiment on you, without your permission, while you were
unconscious? What if that experiment could help save your life and test a possible treatment for wounded soldiers or
car crash victims? Doctors want Portland-area residents to ponder those questions as they move toward joining a
study of a blood substitute called PolyHeme. Trauma medics with Legacy Health System, Oregon Health & Science
University and local ambulance companies would take part in a national trial comparing PolyHeme with the salt-water
solution now carried on ambulances.
This is no ordinary research project. In most trials, scientists must tell each potential participant about the possible
risks and rewards before getting their agreement to participate, a process called "informed consent." But PolyHeme
would go to people unconscious from blood loss when treatment starts. A seldom-used and ethically controversial
1996 Food and Drug Administration regulation lets researchers waive informed consent to test potential life-saving
treatments when there is no other way to conduct the research. Instead of individual consent, the FDA says
researchers must teach local residents about the trial and gauge their feelings. So Legacy and OHSU workers are
mailing letters to local officials and holding three public meetings to explain the trial and ask for feedback. "This is not
a sure thing that the study will happen," said Lise Harwin, a Legacy communications coordinator who helped plan the
public education. "What we're trying to do now is get feedback to determine if it will." Portland researchers have spent
more than a year planning the trial, and both hospitals' research-review boards have approved the idea. But those
boards won't give their final approval until they consider public reaction.
Scientists have spent decades searching for a blood substitute, which trauma doctors say is desperately needed.
Donated blood is too delicate and has too short a shelf life to carry on ambulances. Instead, paramedics use durable
saline solution. But saline can't carry oxygen through the body; PolyHeme does. PolyHeme, which is made from
expired blood donations, has a longer shelf life than blood and can be administered to a person of any blood type.
Local research boards "haven't established a particular percent or number" of negative responses from the
community that would cause them to stop the trial, Allee said. One reason is that researchers assume people worried
about the process are more likely to comment than those who support it.
b. Suppose you are a member of the OHSU IRB. Would you have voted to approve this trial? Why or
why not? Support your answer using the principles of the Belmont Report.
7. A patient comes to your office complaining of abdominal fullness and a change in bowel habits.
She reports a family history of breast cancer and ovarian cancer. You suspect she may have
ovarian cancer and order a serum CA125 test. The sensitivity of this test is 35% and the
specificity is 98.5%. The incidence of ovarian cancer in this population is 0.1%. The test comes
back positive.
(a) If you gave this test to 1,000,000 women, how many patients would have a true positive (TP)
result, a false positive (FP) result, a true negative (TN) result and a false negative (FN) result?
Test Positive
Test Negative
Disease Present
350
650
# with Disease = 1,000
Disease Absent
14,985
984,015
#without Disease = 999,000
# Test Pos =
# Test Neg =
Total Tested = 1,000,000
TP =
350
FP =
14,985
TN =
984,015
FN =
650
(b) Given her positive test result, what is the likelihood that your patient really has ovarian
cancer?
PPV = 350/(250+14,985) = .0228
There is a 2.28% chance that the patient has ovarian cancer.
(c) What test would you recommend that your patient undergo next?
Transvaginal sonography
Extra Credit:
In the pictures below, where is Dr. Koop hiding?
He’s on RNA.
He’s in Rwanda.
He’s in the Philip.pines