usmle step 1 cs U.S. citizens or permanent residents
By Live Dr - Mon Dec 01, 12:58 am
SPECIAL SITUATIONS 42
tives who are U.S. citizens or permanent residents. It is advisable for SRPs to
apply for H1B visas as soon as possible in the official year (beginning October
1) when the new quota officially opens up.
According to the Web site www.immihelp.com, as of October 17, 2000, the
following beneficiaries of approved H1B petitions are exempt from the H1B
Beneficiaries who are in J1 nonimmigrant status in order to receive graduate
medical education or training, and who have obtained a waiver of the
two-year home residency requirement;
Beneficiaries who are employed at, or who have received an offer of employment
at, an institution of higher education or a related or affiliated
Beneficiaries who are employed by, or who have received an offer of employment
from, a nonprofit research organization;
Beneficiaries who are employed by, or who have received an offer of employment
from, a governmental research organization;
Beneficiaries who are currently maintaining, or who have held within the
last six years, H1B status, and are ineligible for another full six-year stay as
an H1B; and
Beneficiaries who have been counted once toward the numerical limit
and are the beneficiary of multiple petitions.
H1B visas are intended for “professionals” in a “specialty occupation.” This
means that an IMG intending to pursue a residency program in the United
States with an H1B visa needs to clear all three USMLE Steps before becoming
eligible for the H1B. The ECFMG administers Steps 1 and 2, whereas
Step 3 is conducted by the individual states. You will need to contact the
FSMB or the medical board of the state where you intend to take Step 3 for
details (see p. 33, USMLE Step 3 and the IMG).
H1B Application. An application for an H1B visa is filed not by the IMG but
rather by his or her employment sponsor–in your case, by the SRP in the
United States. If an SRP is willing to do so, you will be told about it at the
time of your interview for the residency program.
Before filing an H1B application with the DHS, an SRP must file an application
with the U.S. Department of Labor affirming that the SRP will pay at
least the normal salary for your job that a U.S. professional would earn. After
receiving approval from the Labor Department, your SRP should be ready to
file the H1B application with the DHS. The SRP’s supporting letter is the
most important part of the H1B application package; it must describe the job
duties to make it clear that the physician is needed in a “specialty occupation”
(resident) under the prevalent legal definition of that term.
Most SRPs prefer to issue a SEVIS Form DS-2019 for a J1 visa rather than file
papers for an H1B visa because of the burden of paperwork and the attorney
costs involved in securing approval of an H1B visa application. Even so, a sizable
number of SRPs are willing to go through the trouble, particularly if an
IMG is an excellent candidate or if the SRP concerned finds it difficult to fill
all the available residency slots (although this is becoming rarer with continuing
cuts in residency slots). If an SRP is unwilling to file for an H1B visa because
of attorney costs, you could suggest that you would be willing to bear
the burden of such costs. The entire process of getting an H1B visa can take
anywhere from 10 to 20 weeks.
H1B Premium Processing Service. According to the Web site www.myvisa.com,
the DHS offers the opportunity to obtain processing of an H1B visa application
within 15 calendar days. Within 15 days of receiving Form I-907, the
DHS will mail you a notice of approval, request for evidence, intent to deny,
or notice of investigation for fraud or misrepresentation. If the notice requires
the submission of additional evidence or indicates an intent to deny, a new
15-day period will begin upon delivery to the DHS of a complete response to
the request for evidence or notice of intent to deny. The fee for this service is
$1000. With this service, the total time needed to obtain an H1B visa has become
significantly shorter than that required for the J1.
Although an H1B visa can be stamped by any U.S. consulate abroad, it is advisable
that you have it stamped at the U.S. consulate where you first applied
for a visitor visa to travel to the United States for interviews.
A Final Word
IMGs should also be aware of a new program called the National Security
Entry-Exit Registration System, which aims to tighten up homeland security
by keeping closer tabs on nonimmigrants residing in or entering the United
States on temporary visas.
Male citizens or nationals of specific countries who are already residing in the
United States may be required to report to a designated DHS office for registration,
which includes being fingerprinted, photographed, and interviewed
under oath. The official list of countries includes Bangladesh, Egypt, Indonesia,
Jordan, Kuwait, Pakistan, Saudi Arabia, Afghanistan, Algeria, Bahrain, Eritrea,
Lebanon, Morocco, North Korea, Oman, Qatar, Somalia, Tunisia, the
United Arab Emirates, Yemen, Iran, Iraq, Libya, Sudan, and Syria. Different
registration deadlines and criteria have been assigned to citizens of the abovementioned
countries, so please refer to http://uscis.gov for details.
If you are entering the United States, you may be registered at the port of entry
if you are (1) a citizen or national of Iran, Iraq, Libya, Sudan, or Syria; (2)
a nonimmigrant who has been designated by the State Department; or (3) any
other nonimmigrant identified by immigration officers at airports, seaports,
and land ports of entry in accordance with new regulation 8 CFR 264.1(f)(2).
If you will be staying in the United States for more than 30 days, you will then
SPECIAL SITUATIONS 44
be required to register in person at a DHS district office within 30 days for an
interview and will be required to reregister annually.
Once you are registered, certain special procedures will apply. If you leave the
United States for any reason, you must appear in person before a DHS inspecting
officer at a preapproved airport, seaport, or land port and leave the United
States from that port on the same day. If you change your address, employment,
or school, you must report to the DHS in writing within ten days using
Form AR-11 SR. If any of these regulations are not followed, you may be considered
out of status and subject to arrest, detention, fines, and/or removal
from the United States, and any further application for immigration may be affected.
For the most up-to-date information regarding policies and procedures, please
Despite some significant obstacles, a number of viable methods are available
to IMGs who seek visas to pursue a residency program or eventually practice
medicine in the United States. There is no doubt that the best alternative for
an IMG is to obtain an H1B visa to pursue a medical residency. However, in
cases where an IMG joins a residency program with a J1 visa, there are some
possibilities for obtaining waivers of the two-year foreign residency requirement,
particularly for those who are willing to make a commitment to perform
primary care medicine in medically underserved areas.
Resources for the IMG
3624 Market Street, Fourth Floor
Philadelphia, PA 19104-2685
Fax: (215) 386-9196
The ECFMG telephone number is answered only between 9:00 A.M. and
12:30 P.M. and between 1:30 P.M. and 5:00 P.M. Monday through Friday
EST. The ECFMG often takes a long time to answer the phone, which is
frequently busy at peak times of the year, and then gives you a long voicemail
message–so it is better to write or fax early than to rely on a lastminute
phone call. Do not contact the NBME, as all IMG exam matters
are conducted by the ECFMG. The ECFMG also publishes an information
booklet on ECFMG certification and the USMLE program, which
gives details on the dates and locations of forthcoming USMLE and English
tests for IMGs together with application forms. It is free of charge and
is also available from the public affairs offices of U.S. embassies and consulates
worldwide as well as from Overseas Educational Advisory Centers.
You may order single copies of the handbook by calling (215) 386-5900,
preferably on weekends or between 6 P.M. and 6 A.M. Philadelphia time, or
by faxing to (215) 387-9963. Requests for multiple copies must be made by
fax or mail on organizational letterhead. The full text of the booklet is also
available on the ECFMG’s Web site at www.ecfmg.org.
P.O. Box 619850
Dallas, TX 75261-9850
Fax: (817) 868-4099
The FSMB has a number of publications available, including The Exchange,
Section I, which gives detailed information on examination and licensing
requirements in all U.S. jurisdictions. The cost is $30. (Texas residents
must add 8.25% state sales tax.) To obtain these publications, submit
the online order form. Payment options include Visa or MasterCard. Alternatively,
write to Federation Publications at the above address. All orders
must be prepaid with a personal check drawn on a U.S. bank, a cashier’s
check, or a money order payable to the federation. Foreign orders must be
accompanied by an international money order or the equivalent, payable
in U.S. dollars through a U.S. bank or a U.S. affiliate of a foreign bank. For
Step 3 inquiries, the telephone number is (817) 868-4041. You may e-mail
the FSMB at firstname.lastname@example.org or write to Examination Services at the address
The Internet newsgroups misc.education.medical and bit.listserv.
medforum can be valuable forums through which to exchange information
on licensing exams, residency applications, and the like.
Immigration information for IMGs is available from the sites of Siskind
Susser, a firm of attorneys specializing in immigration law: www.visalaw.
Another source of immigration information can be found on the Web site
of the law offices of Carl Shusterman, a Los Angeles attorney specializing
in medical immigration law: www.shusterman.com.
The AMA has dedicated a portion of its Web site to information on IMG
demographics, residencies, immigration, and the like: www.ama-assn.org/
International Medical Placement Ltd., a U.S. company specializing in recruiting
foreign physicians to work in the United States, has a site at
Two more useful Web sites are www.myvisa.com and www.immihelp.
First Aid for the International Medical Graduate, 2nd ed., by Keshav
Chander (2002; 313 pages; ISBN 0071385320), is an excellent resource
written by a successful IMG. The book includes interviews with successful
IMGs and students gearing up for the USMLE, complete “getting settled”
information for new residents, and tips for dealing with possible social and
cultural transition difficulties. The book provides useful advice on the U.S.
SPECIAL SITUATIONS 46
curriculum, the health care delivery system, and ethical issues–and the
differences IMGs should expect. Dr. Chander points out the weaknesses
often found in IMG hopefuls and suggests ways to improve their performance
on standardized tests as well as on academic and clinical evaluations.
As a bonus, the guide contains information on how to get good fellowships
after residency. The bottom line is that this is a reassuring guide
that can help IMGs boost their confidence and proficiency. A great “first
of its kind” that will empower IMGs with information that they need to
Other books that may be useful and of interest to IMGs are as follows:
International Medical Graduates in U.S. Hospitals: A Guide for Directors
and Applicants, by Faroque A. Khan and Lawrence G. Smith (1995; ISBN
Insider’s Guide for the International Medical Graduate to Obtain a Medical
Residency in the U.S.A., by Ahmad Hakemi (1999; ISBN
FIRST AID FOR THE OSTEOPATHIC MEDICAL STUDENT
What Is the COMLEX Level 1?
In 1995, the National Board of Osteopathic Medical Examiners (NBOME) introduced
a new assessment tool called the Comprehensive Osteopathic Medical
Licensing Examination, or COMLEX-USA. As with the former NBOME
examination series, the COMLEX-USA is administered over three levels. In
1995, only Level 3 was administered, but by 1998 all three levels were implemented.
The COMLEX-USA is now the only exam offered to osteopathic students.
One goal of this changeover is to have all 50 states recognize this examination
as equivalent to the USMLE. Currently, the COMLEX-USA exam
sequence is accepted for licensure in all 50 states.
The COMLEX-USA series assesses osteopathic medical knowledge and clinical
skills using clinical presentations and physician tasks. A description of the
COMLEX-USA Written Examination Blueprints for each level, which outline
the various clinical presentations and physician tasks that examinees will encounter,
is given on the NBOME Web site. Another stated goal of the COMLEX-
USA Level 1 is to create a more primary care-oriented exam that integrates
osteopathic principles into clinical situations. As of July 1, 2004, the NBOME
has initiated the administration of a Performance Evaluation/Clinical Skills component
of the COMLEX-USA designated Level 2-PE, which candidates must
pass in order to be eligible for the COMLEX Level 3.
To be eligible to take the COMLEX-USA Level 1, you must have satisfactorily
completed at least one-half of your sophomore year in an American Osteopathic
Association (AOA)-approved medical school. In addition, you must obtain
verification that you are in good standing at your medical school via approval
of your dean. Applications may be downloaded from the NBOME Web
For all three levels of the COMLEX-USA, raw scores are converted to a percentile
score and a score ranging from 5 to 800. For Levels 1 and 2, a score of
400 is required to pass; for Level 3, a score of 350 is needed. COMLEX-USA
scores are usually mailed eight weeks after the test date. The mean score on
the June 2003 exam was 500 with a standard deviation of 79.
If you pass a COMLEX-USA examination, you are not allowed to retake it to
improve your grade. If you fail, there is no specific limit to the number of
times you can retake it in order to pass. Level 2 and 3 exams must be passed
in sequential order within seven years of passing Level 1.
What Is the Structure of the COMLEX Level 1?
The final paper-and-pencil COMLEX Level 1 examination was administered
on October 11-12, 2005. Starting in May 2006, the NBOME will begin delivering
the COMLEX Level 1 by computer. This conversion to a computerbased
examination will reduce test duration from two days to one day; de-
SPECIAL SITUATIONS 48
crease the total number of questions from about 800 to 400; and diminish the
total testing time from 16 hours to 8 hours.
The computer-based COMLEX Level 1 examination will consist of multiplechoice
questions that will remain in the same format as that of the paper-andpencil
COMLEX Level 1 examination. Most of the questions will be in onebest-
answer format, but a small number will be matching-type questions.
Some one-best-answer questions will be bundled together around a common
question stem that will usually take the form of a clinical scenario. New question
formats may gradually be introduced, but candidates will be notified if
The content covered by the examination will remain similar. Because the
computer-based test is new, it is difficult to predict what kinds of photos will
Questions will be grouped into sections of 50 questions, each in a manner
similar to the USMLE. Reviewing and changing answers may be done only in
the current section. A “review page” will be presented for each block in order
to advise test takers of questions completed, questions marked for further review,
and incomplete questions for which no answer has been given.
Only two optional breaks will be permitted during the test session. These
breaks will be offered after the first two sections of the morning or afternoon
session have been completed. This is an important departure from the
USMLE. More information about the computer-based COMLEX-USA examinations
can be obtained from www.nbome.org.
What Is the Difference Between the USMLE and the COMLEX-USA?
Although the COMLEX-USA and the USMLE are similar in scope, content,
and emphasis, some differences are worth noting. For example, the
COMLEX-USA Level 1 tests osteopathic principles in addition to basic science
materials but does not emphasize lab techniques. In addition, although
both exams often require that you apply and integrate knowledge over several
areas of basic science to answer a given question, many students who took
both tests in 2004 reported that the questions differed somewhat in style. Students
reported, for example, that USMLE questions generally required that
the test taker reason and draw from the information given (often a two-step
process), whereas those on the COMLEX-USA exam tended to be more
straightforward. Furthermore, USMLE questions were on average found to be
considerably longer than those on the COMLEX-USA.
Students also commented that the COMLEX-USA utilized “buzzwords,” although
limited in their use (e.g., “rose spots” in typhoid fever), whereas the
USMLE avoided buzzwords in favor of descriptions of clinical findings or
symptoms (e.g., rose-colored papules on the abdomen rather than rose spots).
Finally, the 2004 USMLE had many more photographs than did the
COMLEX-USA. In general, the overall impression was that the USMLE was
a more “thought-provoking” exam, while the COMLEX-USA was more of a
Who Should Take Both the USMLE and the COMLEX-USA?
Aside from facing the COMLEX-USA Level 1, you must decide if you will
also take the USMLE Step 1. We recommend that you consider taking both
the USMLE and the COMLEX-USA under the following circumstances:
If you are applying to allopathic residencies. Although there is growing
acceptance of COMLEX-USA certification on the part of allopathic residencies,
some allopathic programs prefer or even require passage of the
USMLE Step 1. These include many academic programs, programs in
competitive specialties (e.g., orthopedics, ophthalmology, or dermatology),
and programs in competitive geographic areas (such as California).
Fourth-year doctor of osteopathy (DO) students who have already matched
may be a good source of information about which programs and specialties
look for USMLE scores. It is also a good idea to contact program directors
at the institutions you are interested in to ask about their policy regarding
the COMLEX-USA versus the USMLE.
If you are unsure about your postgraduate training plans. Successful
passage of both the COMLEX-USA Level 1 and the USMLE Step 1 is
certain to provide you with the greatest possible range of options when you
are applying for internship and residency training.
The clinical coursework that some DO students receive during the summer
of their third year (as opposed to their starting clerkships) is considered helpful
in integrating basic science knowledge for the COMLEX-USA or the
How Do I Prepare for the COMLEX-USA Level 1?
Student experience suggests that you should start studying for the COMLEXUSA
four to six months before the test is given, as an early start will allow
you to spend up to a month on each subject. The recommendations made in
Section I regarding study and testing methods, strategies, and resources, as
well as the books suggested in Section IV for the USMLE Step 1, hold true
for the COMLEX-USA as well.
Another important source of information is in the Examination Guidelines
and Sample Exam, a booklet that discusses the breakdown of each subject
while also providing sample questions and corresponding answers. Many students,
however, felt that this breakdown provided only a general guideline
and was not representative of the level of difficulty of the actual COMLEXUSA.
The sample questions did not provide examples of clinical vignettes,
which made up approximately 25% of the exam. You will receive this publication
with registration materials for the COMLEX-USA Level 1 exam, but
you can also receive a copy and additional information by writing:
SPECIAL SITUATIONS 50
8765 W. Higgins Road, Suite 200
Chicago, IL 60631-4174
Fax: (773) 714-0631
or by visiting the NBOME Web page at www.nbome.org.
Level 1 Practice Items is a new feature offered by the NBOME. It contains
about 200 COMLEX-USA Level 1 items and answers. It is important to note
that items in this booklet have been used in previous exams. The booklet costs
$15 and can be purchased via the NBOME Web site.
The 2004 COMLEX-USA exam consisted of 120 multiple-choice questions
and 80 clinical vignette questions per test booklet. There were four test booklets,
two of which had approximately ten matching questions. Each multiplechoice
question accompanied a small case (about one to two sentences long).
In 2003, students reported an emphasis in certain areas. For example:
There was an increased emphasis on lower limb anatomy.
High-yield osteopathic manipulative technique (OMT) topics on the 2004
exam included basic craniosacral theory, sacral testing/diagnosis, lumbar
mechanics, spinal motion and diagnosis, and an emphasis on the sympathetic
and parasympathetic innervation of viscera.
Specific topics were repeatedly tested on the exam. These included cardiovascular
physiology and pathology, acid-base physiology, diabetes, benign
prostatic hyperplasia, sexually transmitted diseases, measles, and rubella.
Thyroid and adrenal function, neurology (head injury), specific drug treatments
for bacterial infection, migraines/cluster headaches, and drug
mechanisms also received heavy emphasis.
Behavioral science questions were based on psychiatry.
Since topics that were repeatedly tested appeared in all four booklets, students
found it useful to review them in between the two test days. It is important
to understand that the topics emphasized on the 2004 exam may
not be stressed on the 2005 exam. However, some topics are heavily tested
each year, so it may be beneficial to have a solid foundation of the abovementioned
FIRST AID FOR THE PODIATRIC MEDICAL STUDENT
The National Board of Podiatric Medical Examiners (NBPME) tests are designed
to assess whether a candidate possesses the knowledge required to practice
as a minimally competent entry-level podiatrist. The NBPME examinations
are used as part of the licensing process governing the practice of
podiatric medicine. The NBPME exam is recognized by 44 states, the U.S.
Army, the U.S. Navy, and the Canadian provinces of Alberta, British Columbia,
and Ontario. Individual states use the examination scores differently;
therefore, doctor of podiatric medicine (DPM) candidates should refer to the
NBPME Bulletin of Information: 2006 Examinations.
The NBPME Part I is generally taken after the completion of the second year
of podiatric medical education. Unlike the USMLE Step 1, there is no behavioral
science section, nor is biomechanics tested on the NBPME Part I. The
exam samples seven basic science disciplines: general anatomy (10%); lower
extremity anatomy (22%); biochemistry (10%); physiology (12%); medical microbiology
and immunology (15%); pathology (15%); and pharmacology
(16%). A detailed outline of topics and subtopics covered on the exam can be
found in the NBPME Bulletin of Information, available on the NBPME Web
Your NBPME Appointment
In early spring, your college registrar will have you fill out an application for
the NBPME Part I. After your application and registration fees are received,
you will be mailed the NBPME Bulletin of Information: 2006 Examinations.
The exam will be offered at an independent location in each city with a podiatric
medical school (New York, Philadelphia, Miami, Cleveland, Chicago,
Des Moines, and Oakland/San Francisco). You may take the exam at any of
these locations regardless of which school you attend. However, you must designate
on your application which testing location you desire. Specific instructions
about dates the exam is offered and registration deadlines can be found
in the NBPME Bulletin.
The NBPME Part I is a written exam of 150 questions. The test consists entirely
of multiple-choice questions, typically with four answer choices. Examinees
have three hours in which to take the exam and are given scratch paper
and a calculator, both of which must be turned in at the end of the exam.
Some questions on the exam will be “trial questions.” These questions are
evaluated as possible future board questions but are not counted in your
Interpreting Your Score
Three to four weeks following the exam date, test takers will receive their
scores by mail. NBPME scores are reported as pass/fail, with a scaled score of
SPECIAL SITUATIONS 52
at least 75 needed to pass. Eighty-five percent of first-time test takers pass the
NBPME Part I. Failing candidates receive a report with one score between 55
and 74 in addition to diagnostic messages intended to help identify strengths
or weaknesses in specific content areas. If you fail the NBPME Part I, you
must retake the entire examination at a later date. There is no limit to the
number of times you can retake the exam.
Preparation for the NBPME Part I
Students suggest that you begin studying for the NBPME Part I at least three
months prior to the test date. The suggestions made in Section I regarding
study and testing methods for the USMLE Step 1 can be applied to the
NBPME as well. This book should, however, be used as a supplement and
not as the sole source of information. Keep in mind that you need only a passing
score. Neither you nor your school or future residency will ever see your
actual numerical score. Competing with colleagues should not be an issue,
and study groups are beneficial to many.
Approximately 22% of the NBPME Part I focuses on lower extremity
anatomy. In this area, students should rely on the notes and material that they
received from their class. Remember, lower extremity anatomy is the podiatric
physician’s specialty–so everything about it is important. Do not forget to
study osteology. Keep your old tests and look through old lower extremity class
exams, since each of the podiatric colleges submits questions from its own exams.
This strategy will give you an understanding of the types of questions that
may be asked. On the NBPME Part I, you will see some of the same classic
lower extremity anatomy questions you were tested on in school.
The NBPME, like the USMLE, requires that you apply and integrate knowledge
over several areas of basic science in order to answer the questions. Students
report that many questions emphasize clinical presentations; however,
the facts in this book are very useful in helping students recall the various diseases
and organisms. DPM candidates should expand on the high-yield pharmacology
section and study antifungal drugs and treatments for Pseudomonas,
methicillin-resistant S. aureus, candidiasis, and erythrasma. The high-yield
section focusing on pathology is very useful; however, additional emphasis on
diabetes mellitus and all its secondary manifestations, particularly peripheral
neuropathy, should not be overlooked. Students should also focus on renal
physiology and drug elimination, the biochemistry of gout, and neurophysiology,
all of which have been noted to be important topics on the NBPME Part
A sample set of questions is found in the NBPME Bulletin of Information:
2006 Examinations. These samples are similar in difficulty to actual board
questions. If you do not receive an NBPME Bulletin or if you have any questions
regarding registration, fees, test centers, authorization forms, or score reports,
please contact your college registrar or:
P.O. Box 510
Bellefonte, PA 16823
Fax: (814) 357-0581
or visit the NBPME Web page at www.nbpme.info.
SPECIAL SITUATIONS 54
FIRST AI D FOR THE STUDENT WITH A DISABI LITY
The USMLE provides accommodations for students with documented disabilities.
The basis for such accommodations is the Americans with Disabilities
Act (ADA) of 1990. The ADA defines a disability as “a significant limitation
in one or more major life activities.” This includes both
“observable/physical” disabilities (e.g., blindness, hearing loss, narcolepsy)
and “hidden/mental disabilities” (e.g., attention-deficit hyperactivity disorder,
chronic fatigue syndrome, learning disabilities).
To provide appropriate support, the administrators of the USMLE must be informed
of both the nature and the severity of an examinee’s disability. Such
documentation is required for an examinee to receive testing accommodations.
Accommodations include extra time on tests, low-stimulation environments,
extra or extended breaks, and zoom text.
Who Can Apply for Accommodations?
Students or graduates of a school in the United States or Canada that is accredited
by the Liaison Committee on Medical Education (LCME) or the
AOA may apply for test accommodations directly from the NBME. Requests
are granted only if they meet the ADA definition of a disability. If you are a
disabled student or a disabled graduate of a foreign medical school, you must
contact the ECFMG (see below).
Who Is Not Eligible for Accommodations?
Individuals who do not meet the ADA definition of disabled are not eligible
for test accommodations. Difficulties not eligible for test accommodations include
test anxiety, slow reading without an identified underlying cognitive
deficit, English as a second language, and learning difficulties that have not
been diagnosed as a medically recognized disability.
Understanding the Need for Documentation
Although most learning-disabled medical students are all too familiar with the
often exhausting process of providing documentation of their disability, you
should realize that applying for USMLE accommodation is different from
these previous experiences. This is because the NBME determines whether
an individual is disabled solely on the basis of the guidelines set by the ADA.
Previous accommodation does not in itself justify provision of an accommodation,
so be sure to review the NBME guidelines carefully.
Getting the Information
The first step in applying for USMLE special accommodations is to contact
the NBME and obtain a guidelines and questionnaire booklet. This can be
obtained by calling or writing to:
Office of Test Accommodations
National Board of Medical Examiners
3750 Market Street
Philadelphia, PA 19104-3102
Internet access to this information is also available at www.nbme.org. This
information is also relevant for IMGs, since the information is the same as
that sent by the ECFMG.
Foreign graduates should contact the ECFMG to obtain information on special
accommodations by calling or writing to:
3624 Market Street, Fourth Floor
Philadelphia, PA 19104-2685
When you get this information, take some time to read it carefully. The
guidelines are clear and explicit about what you need to do to obtain accommodations.
SPECIAL SITUATIONS 56
S E C T I O N I I
“There comes a time when for every addition of knowledge you forget
something that you knew before. It is of the highest importance, therefore, not
to have useless facts elbowing out the useful ones.”
–Arthur Conan Doyle, A Study in Scarlet
“Never regard study as a duty, but as the enviable opportunity to learn.”
“Live as if you were to die tomorrow. Learn as if you were to live forever.”
HOW TO USE THE DATABASE
The 2006 edition of First Aid for the USMLE Step 1 contains a revised and expanded database of basic
science material that student authors and faculty have identified as high yield for board reviews. The information
is presented in a partially organ-based format. Hence, Section II is devoted to the foundational
principles of behavioral science, biochemistry, embryology, microbiology and immunology, and pharmacology.
Section III focuses on organ systems, with subsections covering the embryology, anatomy and histology,
physiology, pathology, and pharmacology relevant to each. Each subsection is then divided into
smaller topic areas containing related facts. Individual facts are generally presented in a three-column
format, with the Title of the fact in the first column, the Description of the fact in the second column,
and the Mnemonic or Special Note in the third column. Some facts do not have a mnemonic and are
presented in a two-column format. Others are presented in list or tabular form in order to emphasize key associations.
The database structure used in Sections II and III is useful for reviewing material already learned. These
sections are not ideal for learning complex or highly conceptual material for the first time. At the beginning
of each subsection, we list supplementary high-yield clinical vignettes and topics that have appeared on recent
exams in order to help focus your review.
The database of high-yield facts is not comprehensive. Use it to complement your core study material
and not as your primary study source. The facts and notes have been condensed and edited to emphasize
the essential material, and as a result each entry is “incomplete.” Work with the material, add your own
notes and mnemonics, and recognize that not all memory techniques work for all students.
We update the database of high-yield facts annually to keep current with new trends in boards content as
well as to expand our database of information. However, we must note that inevitably many other very
high yield entries and topics are not yet included in our database.
We actively encourage medical students and faculty to submit entries and mnemonics so that we may enhance
the database for future students. We also solicit recommendations of alternate tools for study that
may be useful in preparing for the examination, such as diagrams, charts, and computer-based tutorials
(see How to Contribute, p. xvii).
The entries in this section reflect student opinions of what is high yield. Owing to the diverse sources of
material, no attempt has been made to trace or reference the origins of entries individually. We have regarded
mnemonics as essentially in the public domain. All errors and omissions will gladly be corrected
if brought to the attention of the authors, either through the publisher or directly by e-mail.
H I G H -Y I E L D P R I N C I P L E S I N
“It’s psychosomatic. You need a lobotomy. I’ll get a saw.”
–Calvin, “Calvin & Hobbes”
A heterogeneous mix of epidemiology, biostatistics, ethics, psychology,
sociology, and more falls under this heading. Many medical students
do not study this discipline diligently because the material is felt
to be “easy” or “common sense.” In our opinion, this is a missed opportunity.
Each question gained in behavioral science is equal to a
question in any other section in determining the overall score.
Many students feel that some behavioral science questions are less
concrete and require an awareness of the social aspects of medicine.
For example: If a patient does or says something, what should you do
or say in response? These so-called quote questions now constitute
much of the behavioral science section. We have included several examples
in the high-yield clinical vignettes. Medical ethics and medical
law are also appearing with increasing frequency. In addition, the
key aspects of the doctor-patient relationship (e.g., communication
skills, open-ended questions, facilitation, silence) are high yield. Basic
biostatistics and epidemiology are very learnable and high yield. Be
able to apply biostatistical concepts such as specificity and predictive
values in a problem-solving format.
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 60
BEHAVIORAL SCIENCE-HIGH-YIELD CLINICAL VIGNETTES
Woman with anxiety about a What process does this Systematic desensitization.
gynecologic exam is told to relax exemplify?
and to imagine going through
the steps of the exam.
65-year-old man is diagnosed What do you do? Assess whether telling patient will
with incurable metastatic negatively affect his health. If not,
pancreatic adenocarcinoma. His tell him.
family asks you, the doctor, not
to tell the patient.
Man admitted for chest pain is What defense Denial.
medicated for ventricular mechanism is he using?
tachycardia. The next day he
jumps out of bed and does 50
pushups to show the nurses he
has not had a heart attack.
You find yourself attracted to What do you say? Nothing! The tone of the
your 26-year-old patient. interview must be very professional;
it is not acceptable to have any sort
of romantic relationship with
patients. If you feel your actions
may be misinterpreted, invite a
chaperone into the room.
Large group of people is What type of study is Cohort study.
followed over 10 years. Every 2 this?
years, it is determined who
develops heart disease and who
Girl can groom herself, can hop How old is she? Four years old.
on 1 foot, and has an
Man has flashbacks about his What is the diagnosis? Normal bereavement.
girlfriend’s death 2 months
ago following a hit-and-run
accident. He often cries and
wishes for the death of the
36-year-old woman with a strong What do you do? Discuss the risks and benefits of
family history of breast cancer not having a mammogram. Each
refuses a mammogram because patient must give her own
she heard it hurts. informed consent to each procedure;
if the patient refuses, you must abide
by her wishes.
BEHAVIORAL SCIENCE-HIGH-YIELD CLINICAL VIGNETTES (continued)
4-year-old girl complains of a How was she infected? Sexual abuse.
burning feeling in her genitalia;
otherwise she behaves and sleeps
normally. Smear of discharge
shows N. gonorrhoeae.
72-year-old man insists on What do you do? Although you want to encourage
stopping treatment for his the patient to take his medication,
heart condition because it the patient has the final say in his
makes him feel “funny.” own treatment regimen. You
should investigate the “funny”
feeling and determine if there are
drugs available that don’t elicit this
particular side effect.
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 62
Case-control study Observational study. Sample chosen based on Often retrospective.
presence (cases) or absence (controls) of disease.
Information collected about risk factors.
Cohort study Observational study. Sample chosen based on The Framingham heart study
presence or absence of risk factors. Subjects was a large prospective
followed over time for development of disease. cohort study.
Meta-analysis Pooling data from several studies (often via a Cannot overcome limitations
literature search) to achieve greater statistical of individual studies or bias
power. in study selection.
Clinical trial Experimental study. Compares therapeutic benefits Highest-quality study when
of 2 or more treatments, or treatment and placebo. randomized and double-blind.
Bias Occurs when 1 outcome is systematically favored Ways to reduce bias:
over another. 1. Blind studies (single vs.
1. Selection bias–nonrandom assignment to double)
study group 2. Placebo responses
2. Recall bias–knowledge of presence of 3. Crossover studies (each
disorder alters recall by subjects subject acts as own
3. Sampling bias–subjects are not control)
representative; therefore results are not 4. Randomization
4. Late-look bias–information gathered at an
Prevalence vs. Prevalence = total cases in population at a given time
incidence total population
new cases in population over a given
time period Incidence is new incidents.
total population at risk during
Prevalence . incidence × disease duration. When calculating incidence,
Prevalence > incidence for chronic diseases (e.g., don’t forget that people
diabetes). previously positive for a disease
Prevalence = incidence for acute disease (e.g., are no longer considered at risk.
Sensitivity Number of true positives divided by number of all SNOUT = SeNsitivity rules
people with the disease. OUT.
Probability of a positive test given that a person
has the disease.
False negative rate is equal to 1 – sensitivity.
High sensitivity is desirable for a screening test.
Specificity Number of true negatives divided by number of all SPIN = SPecificity rules IN.
people without the disease.
Probability of a negative test given that a person is
free of the disease.
False positive rate is equal to 1 – specificity.
High specificity is desirable for a confirmatory test.
Positive predictive Number of true positives divided by number of people
value (PPV) who tested positive for the disease.
The probability of having a condition given a positive
Negative predictive Number of true negatives divided by number of people
value (NPV) who tested negative for the disease.
The probability of not having the condition given a
Unlike sensitivity and specificity, predictive values are
dependent on the prevalence of the disease.
The higher the prevalence of a disease, the higher the
positive predictive value of the test. The lower the
prevalence, the higher the negative predictive value.
Odds ratio vs. relative risk
Odds ratio (OR) Odds of having disease in exposed group divided
by odds of having disease in unexposed group.
Odds are calculated within a group as number
with disease divided by number without disease.
Approximates relative risk if prevalence of disease
is not too high.
Used for case-control studies.
Relative risk (RR) Disease risk in exposed group divided by disease
risk in unexposed group.
Risk is calculated within a group as number with
disease divided by total number of people in
Used for cohort studies.
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
 a b
 a b
Odds ratio =
a + b
c + d
a/(a + b)
c/(c + d)
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 64
BEHAVIORAL SCIENCE-EPIDEMIOLOGY/BIOSTATISTICS (continued)
Precision vs. Precision is: Random error–reduced
accuracy 1. The consistency and reproducibility of a test precision in a test.
(reliability) Systematic error–reduced
2. The absence of random variation in a test accuracy in a test.
Accuracy is the trueness of test measurements
Statistical Terms that describe statistical distributions:
Normal ˜ Gaussian ˜ bell-shaped (mean = median =
Bimodal is simply 2 humps.
Positive skew is asymmetry with tail on the right
(mean > median > mode).
Negative skew has tail on the left (mean < median
Null (H0) Hypothesis of no difference (e.g., there is no association
between the disease and the risk factor in the
Alternative (H1) Hypothesis that there is some difference (e.g., there is
some association between the disease and the risk
factor in the population).
Type I error (a) Stating that there is an effect or difference when If p < .05, then there is less than
none exists (to mistakenly accept the experimental a 5% chance that the data
hypothesis and reject the null hypothesis). p is will show something that is
judged against a, a preset level of significance not really there. a = you
(usually < .05). “saw” a difference that did
p = probability of making a type I error. not exist–for example,
convicting an innocent man.
(1 – ß)
Type II error (ß) Stating that there is not an effect or difference when ß = you did not “see” a
one exists (to fail to reject the null hypothesis difference that does exist–
when in fact H0 is false). ß is the probability of for example, setting a guilty
making a type II error. man free.
Power (1 – ß) Probability of rejecting null hypothesis when it is in If you . sample size, you .
fact false. It depends on: power. There is power in
1. Total number of end points experienced by numbers.
population Power = 1 – ß.
2. Difference in compliance between
treatment groups (differences in the mean
values between groups)
3. Size of expected effect
Standard deviation n = sample size. Normal (Gaussian) distribution:
vs. error s = standard deviation.
SEM = standard error of the mean.
SEM = s/vn.
Therefore, SEM < s and SEM decreases as n
Confidence interval Range of values in which a specified probability If the 95% CI for a mean
of the means of repeated samples would be difference between 2
expected to fall. variables includes 0, then
CI = confidence interval. there is no significant
CI = range from [mean – Z(SEM)] to difference and H0 is not
[mean + Z(SEM)]. rejected. If the 95% CI for
The 95% CI (corresponding to p = .05) is often odds ratio or relative risk
used. For the 95% CI, Z = 1.96. includes 1, H0 is not rejected.
t -test vs. t-test checks difference between the means of Mr. T is mean.
ANOVA vs. .2 2 groups.
ANOVA checks difference between the means of ANOVA = ANalysis Of
3 or more groups. VAriance of 3 or more
.2 checks difference between 2 or more percentages variables.
or proportions of categorical outcomes (not .2 = compare percentages (%)
mean values). or proportions.
Correlation r is always between -1 and 1. Absolute value indicates strength of correlation between 2
coefficient (r) variables.
Coefficient of determination = r2.
Disease prevention 1°–prevent disease occurrence (e.g., vaccination). PDR:
2°–early detection of disease (e.g., Pap smear). Prevent
3°–reduce disability from disease (e.g., Detect
exogenous insulin for diabetes). Reduce disability
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 66
BEHAVIORAL SCIENCE-EPIDEMIOLOGY/BIOSTATISTICS (continued)
Important prevention measures
Risk factor Services
Diabetes Eye, foot exams; urine tests
Drug use Hepatitis immunizations; HIV, TB tests
Alcoholism Influenza, pneumococcal immunizations; TB test
Overweight Blood sugar tests for diabetes
Homeless, recent TB test
High-risk sexual HIV, hepatitis B, syphilis, gonorrhea, chlamydia tests
Reportable Only some infectious diseases are reportable in all B. A. SSSMMART
diseases states, including AIDS, chickenpox, gonorrhea, Chicken or you’re Gone:
hepatitis A and B, measles, mumps, rubella, Hep B
salmonella, shigella, syphilis, and TB. Hep A
Other diseases (including HIV) vary by state. Salmonella
Leading causes of death in the United States by age
Infants Congenital anomalies, short gestation/low birth weight, sudden infant death syndrome,
maternal complications of pregnancy, respiratory distress syndrome.
Age 1-14 Injuries, cancer, congenital anomalies, homicide, heart disease.
Age 15-24 Injuries, homicide, suicide, cancer, heart disease.
Age 25-64 Cancer, heart disease, injuries, suicide, stroke.
Age 65+ Heart disease, cancer, stroke, COPD, pneumonia, influenza.
Medicare and Medicare and Medicaid are federal programs that MedicarE is for Elderly.
Medicaid originated from amendments to the Social MedicaiD is for Destitute.
Medicare Part A = hospital; Part B = doctor bills.
Medicaid is federal and state assistance for very
low income people.
Autonomy Obligation to respect patients as individuals and to honor their preferences in medical care.
Informed consent Legally requires: Patients must understand
1. Discussion of pertinent information the risks, benefits, and
2. Patient’s agreement to the plan of care alternatives, which include
3. Freedom from coercion no intervention.
Exceptions to 1. Patient lacks decision-making capacity (not legally competent)
informed consent 2. Implied consent in an emergency
3. Therapeutic privilege–withholding information when disclosure would severely harm
the patient or undermine informed decision-making capacity
4. Waiver–patient waives the right of informed consent
Decision-making 1. Patient makes and communicates a choice The patient’s family cannot
capacity 2. Patient is informed require that a doctor
3. Decision remains stable over time withhold information from
4. Decision is consistent with patient’s values and the patient.
5. Decision is not a result of delusions or
Oral advance Incapacitated patient’s prior oral statements commonly used as guide. Problems arise from
directive variance in interpretation. If patient was informed, directive is specific, patient made a
choice, and decision was repeated over time, the oral directive is more valid.
Written advance Living will–patient directs physician to withhold or withdraw life-sustaining
directive treatment if the patient develops a terminal disease or enters a persistent vegetative
Durable power of attorney–patient designates a surrogate to make medical decisions
in the event that the patient loses decision-making capacity. Patient may also specify
decisions in clinical situations. Surrogate retains power unless revoked by patient. More
flexible than a living will; supersedes living will if both exist.
Nonmaleficence “Do no harm.” However, if benefits of an intervention outweigh the risks, a patient may
make an informed decision to proceed.
Beneficence Physicians have a special ethical responsibility to act in the patient’s best interest
(“physician is a fiduciary”). Patient autonomy may conflict with beneficence. If the
patient makes an informed decision, ultimately the patient has the right to decide.
Confidentiality Confidentiality respects patient privacy and autonomy. Disclosing information to family
and friends should be guided by what the patient would want. The patient may also
waive the right to confidentiality (e.g., insurance companies).
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 68
BEHAVIORAL SCIENCE-ETHICS (continued)
Exceptions to 1. Potential harm to others is serious
confidentiality 2. Likelihood of harm to self is great
3. No alternative means exist to warn or to protect those at risk
4. Physicians can take steps to prevent harm
1. Infectious diseases–physicians may have a duty to warn public officials and
identifiable people at risk
2. The Tarasoff decision–law requiring physician to directly inform and protect
potential victim from harm; may involve breach of confidentiality
3. Child and/or elder abuse
4. Impaired automobile drivers
5. Suicidal/homicidal patient–physician may hold patient involuntarily for a
period of time
Malpractice Civil suit under negligence requires: The 3 D’s.
1. Physician breach of duty to patient Unlike a criminal suit, in which
(Dereliction) the burden of proof is “beyond
2. Patient suffers harm (Damage) a reasonable doubt,” the
3. Breach of duty causes harm (Direct) burden of proof in a
The most common factor leading to litigation is malpractice suit is “more
poor communication between physician and likely than not.”
Situation Appropriate response
Patient is noncompliant. Work to improve the physician-patient relationship.
Patient has difficulty taking Provide written instructions; attempt to simplify treatment regimens.
Family members ask for information Avoid discussing issues with relatives without the permission of the
about patient’s prognosis. patient.
A 17-year-old girl is pregnant and Many states require parental notification or consent for minors
requests an abortion. for an abortion. Parental consent is not required for emergency
situations, treatment of STDs, medical care during pregnancy,
prescriptions for contraceptives, and management of drug addiction.
A terminally ill patient requests In the overwhelming majority of states, refuse involvement in any form of
physician assistance in ending physician-assisted suicide. Physician may, however, prescribe medically
his life. appropriate analgesics that coincidentally shorten the patient’s life.
Patient states that he finds you Ask direct, closed-ended questions and use a chaperone if necessary.
attractive. Romantic relationships with patients are never appropriate.
Patient refuses a necessary procedure Attempt to understand why the patient wants/does not want the
or desires an unnecessary one. procedure. Address the underlying concerns. Avoid performing
Patient is angry about the amount Apologize to the patient for any inconvenience. Stay away from efforts
of time he spent in the waiting to explain the delay.
Patient is upset with the way he was Suggest that the patient speak directly to that physician regarding his
treated by another doctor. concerns. If the problem is with a member of the office staff, tell the
patient you will speak to that individual.
A child wishes to know more about Ask what the parents have told the child about his illness. Parents of a
his illness. child decide what information can be relayed about the illness.
Patient continues to smoke, believing Ask how the patient feels about his smoking. Offer advice on cessation
that cigarettes are good for him. if the patient seems willing to make an effort to quit.
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 70
Apgar score Score 0-2 at 1 and 5 minutes in each of 5 categories: APGAR:
(at birth) 1. Color (blue/pale, trunk pink, all pink) Appearance (color)
2. Heart rate (0, < 100, 100+) Pulse
3. Reflex irritability (0, grimace, grimace + cough) Grimace
4. Muscle tone (limp, some, active) Activity
5. Respiratory effort (0, irregular, regular) Respiration
10 is perfect score.
Low birth weight Defined as < 2500 g. Associated with greater incidence of physical and emotional
problems. Caused by prematurity or intrauterine growth retardation. Complications
include infections, respiratory distress syndrome, necrotizing enterocolitis,
intraventricular hemorrhage, and persistent fetal circulation.
Infant deprivation Long-term deprivation of affection results in: The 4 W’s: Weak, Wordless,
effects 1. . muscle tone Wanting (socially), Wary.
2. Poor language skills Deprivation for > 6
3. Poor socialization skills months can lead to
4. Lack of basic trust irreversible changes.
5. Anaclitic depression
6. Weight loss
7. Physical illness
Severe deprivation can result in infant death.
Anaclitic Depression in an infant owing to continued separation from caregiver–can result in failure
depression to thrive. Infant becomes withdrawn and unresponsive.
Regression in Children regress to younger behavior under stress-physical illness, punishment, birth of
children a new sibling, tiredness. An example is bed-wetting in a previously toilet-trained child
Physical abuse Sexual abuse
Evidence Healed fractures on x-ray, cigarette burns, Genital/anal trauma, STDs, UTIs
subdural hematomas, multiple bruises,
retinal hemorrhage or detachment
Abuser Usually female and the 1° caregiver Known to victim, usually male
Epidemiology ~3000 deaths/year in the United States Peak incidence 9-12 years of age
Approximate age Motor milestone Cognitive/social milestone
3 mo Holds head up, Moro reflex disappears Social smile
4-5 mo Rolls front to back, sits when propped Recognizes people
7-9 mo Sits alone, crawls Stranger anxiety, orients to voice
12-14 mo Upgoing Babinski disappears
15 mo Walks Few words, separation anxiety
12-24 mo Climbs stairs, stacks 3 blocks Object permanence
18-24 mo Stacks 6 blocks Rapprochement
24-48 mo Parallel play
24-36 mo Core gender identity
30-36 mo Stacks 9 blocks Toilet training
3 yrs Rides tricycle, copies line or circle drawing Group play
4 yrs Simple drawings (stick figure), hops on 1 foot Cooperative play, imaginary
6-11 yrs Reads; understands death Development of conscience
(superego), same-sex friends,
identification with same-sex
11 yrs (girls) Abstract reasoning (formal
13 yrs (boys) operations), formation of
Changes in the 1. Sexual changes–sexual interest does not . Additional changes with aging:
elderly Men: slower erection/ejaculation, longer 1. . vision, hearing, immune
refractory period response, bladder control
Women: vaginal shortening, thinning, and 2. . renal, pulmonary, GI
2. Sleep patterns– . REM sleep, . slow-wave 3. . muscle mass, . fat
sleep, . sleep latency, . awakenings during Intelligence does not ..
3. Common medical conditions–arthritis,
hypertension, heart disease, osteoporosis
4. Psychiatric problems (e.g., depression) become
5. . suicide rate
Grief Normal bereavement characterized by shock, denial, guilt, and somatic symptoms.
Typically lasts 6 months to 1 year. May experience illusions.
Pathologic grief includes excessively intense or prolonged grief or grief that is delayed,
inhibited, or denied. May experience depressive symptoms, delusions, and
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 72
BEHAVIORAL SCIENCE-DEVELOPMENT (continued)
Kübler-Ross grief Denial, Anger, Bargaining, Grieving, Acceptance. Death Arrives Bringing Grave
stages Stages do not necessarily occur in this order, and Adjustments.
> 1 stage can be present at once.
Stress effects Stress induces production of free fatty acids, 17-OH corticosteroids, lipids, cholesterol,
catecholamines; affects water absorption, muscular tonicity, gastrocolic reflex, and
mucosal circulation. May exacerbate certain physical disorders (including CHF,
diabetes mellitus, rheumatoid arthritis, irritable bowel syndrome, and gastric ulcer
Sexual dysfunction Differential diagnosis includes:
1. Drugs (e.g., antihypertensives, neuroleptics, SSRIs, ethanol)
2. Diseases (e.g., depression, diabetes)
3. Psychological (e.g., performance anxiety)
Body-mass index BMI is a measure of weight adjusted for height. < 18.5 underweight;
(BMI) 18.5-24.9 normal;
weight in kg
(height in meters)2
> 30.0 obese.
Intelligence quotient Stanford-Binet and Wechsler are the most famous tests of intelligence quotient (IQ).
Stanford-Binet calculates IQ as mental age/chronological age × 100.
Wechsler Adult Intelligence Scale uses 11 subtests (6 verbal, 5 performance).
Mean is defined at 100, with standard deviation of 15.
IQ < 70 (or 2 standard deviations below the mean) is one of the criteria for diagnosis
of mental retardation (MR). IQ < 40–severe MR. IQ < 20–profound MR.
IQ scores are correlated with genetic factors and are highly correlated with school
Intelligence tests are objective (not projective) tests.
Classical Learning in which a natural response (salivation) Pavlov’s classical experiments
conditioning is elicited by a conditioned, or learned, stimulus with dogs–ringing the bell
(bell) that previously was presented in conjunction provoked salivation.
with an unconditioned stimulus (food).
Operant Learning in which a particular action is elicited because it produces a reward.
conditioning Positive reinforcement–desired reward produces action (mouse presses button to get food).
Negative reinforcement–removal of aversive stimulus . behavior (mouse presses
button to avoid shock). Do not confuse with punishment.
Reinforcement Pattern of reinforcement determines how quickly a behavior is learned or extinguished.
Continuous Reward received after every response. Rapidly Think vending machine–stop
extinguished. using it if it does not deliver.
Variable ratio Reward received after random number of responses. Think slot machine–continue
Slowly extinguished. to play even if it rarely
Transference and countertransference
Transference Patient projects feelings about formative or other important persons onto physician
(e.g., psychiatrist = parent).
Countertransference Doctor projects feelings about formative or other important persons onto patient.
Structural theory Freud’s 3 structures of the mind.
of the mind
Id Primal urges, sex, and aggression. (I want it.)
Superego Moral values, conscience. (You know you can’t have it.)
Ego Mediator between the unconscious mind and the external world. (Deals with the
Topographic Conscious–what you are aware of.
theory of the Preconscious–what you are able to make conscious with effort (e.g., your phone
Unconscious–what you are not aware of; the central goal of Freudian psychoanalysis is to
make the patient aware of what is hidden in his/her unconscious.
Oedipus complex Repressed sexual feelings of a child for the opposite-sex parent, accompanied by rivalry
with same-sex parent. First described by Freud.
HIGH-YI E LD PRINCIPLES BEHAVIORAL SCIENCE
BEHAVIORAL SCIENCE HIGH-YI E LD PRINCIPLES 74
BEHAVIORAL SCIENCE-PSYCHOLOGY (continued)
Ego defenses All ego defenses are automatic and unconscious reactions to psychological stress.
Altruism Guilty feelings alleviated by unsolicited Mafia boss makes large donation
generosity toward others. to charity.
Humor Appreciating the amusing nature of an Nervous medical student jokes about
anxiety-provoking or adverse situation. the boards.
Sublimation Process whereby one replaces an Aggressive impulses used to succeed
unacceptable wish with a course of in business ventures.
action that is similar to the wish but does
not conflict with one’s value system.
Suppression Voluntary (unlike other defenses) withholding Choosing not to think about the
of an idea or feeling from conscious USMLE until the week of the exam.
Mature women wear a SASH: Sublimation, Altruism, Suppression, Humor.
Acting out Unacceptable feelings and thoughts are Tantrums.
expressed through actions.
Dissociation Temporary, drastic change in personality, Extreme forms can result in multiple
memory, consciousness, or motor behavior personalities (dissociative identity
to avoid emotional stress. disorder).
Denial Avoidance of awareness of some painful A common reaction in newly diagnosed
reality. AIDS and cancer patients.
Displacement Process whereby avoided ideas and feelings Mother yells at child because she is
are transferred to some neutral person or angry at her husband.
Fixation Partially remaining at a more childish level Men fixating on sports games.
Identification Modeling behavior after another person Abused child becomes an abuser.
who is more powerful (though not
Isolation Separation of feelings from ideas and events. Describing murder in graphic detail with
no emotional response.
Projection An unacceptable internal impulse is A man who wants another woman
attributed to an external source. thinks his wife is cheating on him.
Rationalization Proclaiming logical reasons for actions Saying the job was not important
actually performed for other reasons, anyway, after getting fired.
usually to avoid self-blame.
Reaction formation Process whereby a warded-off idea or feeling A patient with libidinous thoughts enters
is replaced by an (unconsciously derived) a monastery.
emphasis on its opposite.
Regression Turning back the maturational clock and Seen in children under stress (e.g.,
going back to earlier modes of dealing bed-wetting) and in patients on
with the world. dialysis (e.g., crying).
Repression Involuntary withholding of an idea or
feeling from conscious awareness.
The basic mechanism underlying all
Splitting Belief that people are either good or bad. A patient says that all the nurses are
cold and insensitive but that the
doctors are warm and friendly.
H I G H -Y I E L D P R I N C I P L E S I N
“Biochemistry is the study of carbon compounds that crawl.”
This high-yield material includes molecular biology, genetics, cell biology,
and principles of metabolism (especially vitamins, cofactors,
minerals, and single-enzyme-deficiency diseases). When studying
metabolic pathways, emphasize important regulatory steps and enzyme
deficiencies that result in disease. For example, understanding
the defect in Lesch-Nyhan syndrome and its clinical consequences is
higher yield than memorizing every intermediate in the purine salvage
pathway. Do not spend time on hard-core organic chemistry,
mechanisms, and physical chemistry. Detailed chemical structures
are infrequently tested. Familiarity with the latest biochemical techniques
that have medical relevance–such as enzyme-linked immunosorbent
assay (ELISA), immunoelectrophoresis, Southern blotting,
and PCR–is useful. Beware if you placed out of your medical
school’s biochemistry class, for the emphasis of the test differs from
that of many undergraduate courses. Review the related biochemistry
when studying pharmacology or genetic diseases as a way to reinforce
and integrate the material.
BIOCHEMISTRY-HIGH-YIELD C LI N ICAL VIGNETTES
Full-term neonate of uneventful What is the diagnosis? PKU.
delivery becomes mentally
retarded and hyperactive and
has a musty odor.
Stressed executive comes What is the mechanism? NADH increase prevents
home from work, consumes 7 gluconeogenesis by shunting
or 8 martinis in rapid succession pyruvate and oxaloacetate to
before dinner, and becomes lactate and malate.
2-year-old girl has an . in What is the diagnosis? Kwashiorkor.
abdominal girth, failure to thrive,
and skin and hair depigmentation.
Alcoholic develops a rash, What is the vitamin Vitamin B3 (pellagra).
diarrhea, and altered mental deficiency?
51-year-old man has black spots What is the diagnosis? Alkaptonuria.
in his sclera and has noted that
his urine turns black upon
25-year-old male complains What is the disease, Familial hypercholesterolemia;
of severe chest pain and has and where is the defect? LDL receptor.
xanthomas of his Achilles
BIOCHEMISTRY HIGH-YI E LD PRINCIPLES
Chromatin Condensed by (-) charged DNA looped twice Think of beads on a string.
structure around (+) charged H2A, H2B, H3, and H4
histone octamers (nucleosome bead). H1 ties
nucleosomes together in a string (30-nm fiber).
In mitosis, DNA condenses to form mitotic
Heterochromatin Condensed, transcriptionally inactive.
Euchromatin Less condensed, transcriptionally active. Eu = true, “truly transcribed.”
Nucleotides Purines (A, G) have 2 rings. Pyrimidines (C, T, U) PURe As Gold: PURines.
have 1 ring. Guanine has a ketone. Thymine has CUT the PY (pie):
a methyl. Deamination of cytosine makes uracil. PYrimidines.
Uracil found in RNA; thymine in DNA. THYmine has a meTHYl.
G-C bond (3 H-bonds) stronger than A-T bond
(2 H-bonds). . G-C content . . melting
Nucleotides are linked by 3′-5′ phosphodiesterase bond.
Transition vs. Transition–substituting purine for purine or TransItion = Identical type.
transversion pyrimidine for pyrimidine.
Transversion–substituting purine for pyrimidine TransVersion = conVersion
or vice versa. between types.
Genetic code Unambiguous–each codon specifies only 1 amino acid.
features Degenerate–more than 1 codon may code for same amino acid.
Commaless, nonoverlapping (except some viruses).
Universal (exceptions include mitochondria, archaeobacteria, Mycoplasma, and some
HIGH-YI E LD PRINCIPLES BIOCHEMISTRY
Purine (A, G) Pyrimidine (C, T, U)
histones H2A, H2B, H3, H4
Mutations in DNA Silent–same aa, often base change in 3rd position Severity of damage: nonsense
of codon (tRNA wobble). > missense > silent.
Missense–changed aa (conservative–new aa is
similar in chemical structure).
Nonsense–change resulting in early stop codon. Stop the nonsense!
Frame shift–change resulting in misreading of all
nucleotides downstream, usually resulting in a
Prokaryotic DNA Single origin of replication–continuous DNA DNA polymerase III has
replication and synthesis on leading strand and discontinuous 5′ . 3′ synthesis and
DNA polymerases (Okazaki fragments) on lagging strand. proofreads with 3′ . 5′
DNA topoisomerases create a nick in the helix to exonuclease.
relieve supercoils. DNA polymerase I excises
Primase makes an RNA primer on which DNA RNA primer with 5′ . 3′
polymerase III can initiate replication. exonuclease.
DNA polymerase III elongates the chain by adding
deoxynucleotides to the 3′ end until it reaches
primer of preceding fragment. 3′ . 5′
exonuclease activity “proofreads” each added
DNA polymerase I degrades RNA primer.
DNA ligase seals.
Eukaryotic DNA Eukaryotic genome has multiple origins of replication. Replication begins at a
polymerases consensus sequence of AT base pairs.
Eukaryotes have separate polymerases (a, ß, ., d, e) for synthesizing RNA primers,
leading-strand DNA, lagging-strand DNA, mitochondrial DNA, and DNA repair.
DNA repair: single Single-strand, excision repair-specific glycosylase recognizes and removes damaged
strand base. Endonuclease makes a break several bases to the 5′ side. Exonuclease removes
short stretch of nucleotides. DNA polymerase fills gap. DNA ligase seals.
78 BIOCHEMISTRY HIGH-YI E LD PRINCIPLES
DNA repair defects Xeroderma pigmentosum (skin sensitivity to UV light), ataxia-telangiectasia (x-rays),
Bloom’s syndrome (radiation), and Fanconi’s anemia (cross-linking agents).
Xeroderma Defective excision repair such as uvr ABC Autosomal recessive.
pigmentosum endonuclease. Results in inability to repair
thymidine dimers, which form in DNA when
exposed to UV light.
Associated with dry skin and with melanoma and
DNA/RNA/protein DNA and RNA are both synthesized 5′ . 3′. Imagine the incoming
synthesis direction Remember that the 5′ of the incoming nucleotide nucleotide bringing a gift
bears the triphosphate (energy source for bond). (triphosphate) to the 3′ host.
The 3′ hydroxyl of the nascent chain is the target. “BYOP (phosphate) from 5
Protein synthesis also proceeds in the 5′ to 3′ to 3.”
direction. Amino acids are linked N
Types of RNA mRNA is the largest type of RNA. Massive, Rampant, Tiny.
rRNA is the most abundant type of RNA.
tRNA is the smallest type of RNA.
Eukaryotes RNA polymerase I makes rRNA. I, II, and III are numbered as
RNA polymerase II makes mRNA. their products are used in
RNA polymerase III makes tRNA. protein synthesis.
No proofreading function, but can initiate chains. a-amanitin is found in death
RNA polymerase II opens DNA at promoter site cap mushrooms.
(A-T-rich upstream sequence–TATA and CAAT).
a-amanitin inhibits RNA polymerase II.
Prokaryotes RNA polymerase makes all 3 kinds of RNA.
Start and stop AUG (or rarely GUG) is the mRNA initiation codon. AUG inAUGurates
codons Eukaryotes–AUG codes for methionine, which protein synthesis.
may be removed before translation is completed.
Prokaryotes–the initial AUG codes for a formylmethionine
Stop codons–UGA, UAA, UAG. UGA = U Go Away.
UAA = U Are Away.
UAG = U Are Gone.
HIGH-YI E LD PRINCIPLES BIOCHEMISTRY
Regulation of gene expression
Promoter Site where RNA polymerase and multiple other Promoter mutation commonly
transcription factors bind to DNA upstream from results in dramatic . in
gene locus. amount of gene transcribed.
Enhancer Stretch of DNA that alters gene expression by binding
transcription factors. May be located close to, far
from, or even within (in an intron) the gene whose
expression it regulates.
Operator Site where negative regulators (repressors) bind.
Introns vs. Exons contain the actual genetic information INtrons stay IN the nucleus,
exons coding for protein. whereas EXons EXit and are
Introns are intervening noncoding segments of DNA. EXpressed.
Splicing of mRNA Introns are precisely spliced out of 1° mRNA transcripts. A lariat-shaped intermediate
is formed. Small nuclear ribonucleoprotein particles (snRNP) facilitate splicing by
binding to 1° mRNA transcripts and forming spliceosomes.
RNA processing Occurs in nucleus. After transcription: Only processed RNA is
(eukaryotes) 1. Capping on 5′ end (7-methyl-G) transported out of the
2. Polyadenylation on 3′ end (˜ 200 A’s) nucleus.
3. Splicing out of introns
Initial transcript is called heterogeneous nuclear
Capped and tailed transcript is called mRNA.
tRNA structure 75-90 nucleotides, cloverleaf form, anticodon end is opposite 3′ aminoacyl end. All
tRNAs, both eukaryotic and prokaryotic, have CCA at 3′ end along with a high
percentage of chemically modified bases. The amino acid is covalently bound to the 3′
end of the tRNA.
80 BIOCHEMISTRY HIGH-YI E LD PRINCIPLES
tRNA charging Aminoacyl-tRNA synthetase (1 per aa, uses ATP) Aminoacyl-tRNA synthetase
scrutinizes aa before and after it binds to tRNA. If and binding of charged
incorrect, bond is hydrolyzed by synthetase. The tRNA to the codon are
aa-tRNA bond has energy for formation of peptide responsible for accuracy of
bond. A mischarged tRNA reads usual codon but amino acid selection.
inserts wrong amino acid.
tRNA wobble Accurate base pairing is required only in the first 2 nucleotide positions of an mRNA
codon, so codons differing in the 3rd “wobble” position may code for the same
Protein synthesis Met sits in the P site–peptidyl. The incoming ATP–tRNA Activation
amino acid binds to the A site–aminoacyl, (charging).
hydrolyzing Met’s bond to its tRNA while GTP–tRNA Gripping and
simultaneously forming a peptidyl bond between Going places (translocation).
the 2 amino acids. The ribosome shifts 1 codon
toward the 3′ end of the mRNA, shifting the
uncharged tRNA into the E position and the
dipeptidyl tRNA into the P site.
HIGH-YI E LD PRINCIPLES BIOCHEMISTRY
ATP AMP + PPi
E P A
The lower the Km, the higher
HINT: Competitive inhibitors
cross each other
Enzyme regulation Enzyme concentration alteration (synthesis and/or destruction), covalent modification
methods (e.g., phosphorylation), proteolytic modification (zymogen), allosteric regulation (e.g.,
feedback inhibition), and transcriptional regulation (e.g., steroid hormones).
Cell cycle phases M (mitosis: prophase-metaphase- G stands for Gap or Growth; S
anaphase-telophase) for Synthesis.
S (synthesis of DNA)
G0 (quiescent G1 phase)
G1 and G0 are of variable duration. Mitosis is
usually shortest phase. Most cells are in G0.
Rapidly dividing cells have a shorter G1.
BIOCHEMISTRY HIGH-YI E LD PRINCIPLES
1 slope =
Km = [S] at Vmax
Resemble substrate Yes No
Overcome by . [S] Yes No
Bind active site Yes No
Effect on Vmax Unchanged .
Effect on Km . Unchanged
(G1, S, G2)