usmle step 1 cs U.S. citizens or permanent residents

By Live Dr - Mon Dec 01, 12:58 am


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

annual cap:

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

nonprofit entity;

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


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

consult http://uscis.gov.


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

(215) 386-5900

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

(817) 868-4000

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 usmle@fsmb.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.


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





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-


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

this occurs.

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

be presented.

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

“knowledge-based” exam.

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:



8765 W. Higgins Road, Suite 200

Chicago, IL 60631-4174

(773) 714-0622

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





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.

Exam Format

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


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

I exam.

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

(814) 357-0487

Fax: (814) 357-0581

E-mail: NBPMEOfc@aol.com

or visit the NBPME Web page at www.nbpme.info.



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:



Testing Coordinator

Office of Test Accommodations

National Board of Medical Examiners

3750 Market Street

Philadelphia, PA 19104-3102

(215) 590-9700

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

(215) 386-5900

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.



Behavioral Science




and Immunology




General Principles


“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.”

–Albert Einstein

“Live as if you were to die tomorrow. Learn as if you were to live forever.”




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.

High-Yield Clinical







H I G H -Y I E L D P R I N C I P L E S I N

Behavioral Science


“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.



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

does not.

Girl can groom herself, can hop How old is she? Four years old.

on 1 foot, and has an

imaginary friend.

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.



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.




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

inappropriate time

Prevalence vs. Prevalence = total cases in population at a given time

incidence total population

Incidence =

new cases in population over a given

time period Incidence is new incidents.

total population at risk during

that time

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.

common cold).

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.

Predictive value

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

negative test.

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.





[1] a b

c d


Sensitivity =



Specificity =





a b



c d







[1] a b

c d


Odds ratio =




a + b


c + d

a/(a + b)

c/(c + d)

Relative risk

Attributable risk








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

< mode).

Statistical hypotheses

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.



H1 H0


Power a

(1 – ß)

H0 ß

Study results

No accuracy,

no precision






Accuracy and


x x













x x

x x





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





-1s +1s

-2s +2s

-3s +3s



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

immigrant, inmate

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.

Security Act.

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).




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

Examples include:

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.”



Ethical situations

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

unnecessary procedures.

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.




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

when hospitalized.

Child abuse

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


Developmental milestones

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


School age

6-11 yrs Reads; understands death Development of conscience

(superego), same-sex friends,

identification with same-sex


Adolescence (puberty)

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

dryness function

2. Sleep patterns– . REM sleep, . slow-wave 3. . muscle mass, . fat

sleep, . sleep latency, . awakenings during Intelligence does not ..

the night

3. Common medical conditions–arthritis,

hypertension, heart disease, osteoporosis

4. Psychiatric problems (e.g., depression) become

more prevalent

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





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

25.0-29.9 overweight;

(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

mind number).

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.




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.

of development.

Identification Modeling behavior after another person Abused child becomes an abuser.

who is more powerful (though not

necessarily admired).

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.

High-Yield Clinical





Laboratory Techniques



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.”

–Mike Adams

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.



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




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





Purine (A, G) Pyrimidine (C, T, U)
























Nucleosome core

histones H2A, H2B, H3, H4


Histone H1


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

truncated protein.

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.








Leading strand



fragment DNA





DNA primer

polymerase III


binding protein


polymerase III


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

other cancers.

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

to C.

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.

RNA polymerases

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.










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

RNA (hnRNA).

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.







and splicing




















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

tRNA/amino acid.

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.







Aminoacyl tRNA


5′ 3′







Enzyme kinetics

The lower the Km, the higher

the affinity.

HINT: Competitive inhibitors

cross each other

competitively, while

noncompetitive inhibitors

do not.

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.

G1 (growth)

S (synthesis of DNA)

G2 (growth)

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.



Vmax Km


Noncompetitive inhibitor


Competitive inhibitor

1 slope =














Velocity (V)



Km = [S] at Vmax



Competitive Noncompetitive

inhibitors inhibitors

Resemble substrate Yes No

Overcome by . [S] Yes No

Bind active site Yes No

Effect on Vmax Unchanged .

Effect on Km . Unchanged



G1 S



(G1, S, G2)


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