high roads and low roads

decoding

2006-01-15T21:33:00.000-05:00

It's a new year, which means this blog is up and running once again. For those of you coming across this page for the first time, the same caveat as before holds true: this page is strange. Blogspot is meant to be a study aid, and the stuff that's on this page is Finnegan's Wake-esque as a result--random thoughts from sports, top 40 music, cheap DVDs, news headlines, and the like, jumbled together with the stuff I'm learning in school and on my own in preparation for the USMLE Step 1 examination coming up in June (i.e. the first of many official tests I need to pass to become a doctor). As well, please forgive any spelling/grammar/syntax mistakes. You know I'm normally anal about such things, but unlike my premeditated Xanga, this is all pure brainfart. So, without further ado...

NYTimes.com today posted a headline about a newly identified gene that confers risk unto individuals for developing type 2 diabetes (i.e. insulin-resistant diabetes). The finding is significant for several reasons, the foremost being that this gene appears to be found in more than a third of all people. Diabetes is a complex trait, meaning that a broad variety of genes and environmental influences work in concert to generate the diabetes illness in an individual. But the identification of a gene with a particularly strong association with diabetes is significant because type 2 diabetes can be well controlled with diet, exercise, and other lifestyle modifications. Moreover, discovery of this gene can not only spur the development of a useful diagnostic test for diabetes, but also a gene-directed therapy for diabetes. And, personally, the best part about this study is that the authors are one of the chief collaborative groups with my current embattled mentor. Why he wasn't a co-author of the study I don't know, however.

the reader's muscle

2005-09-23T21:44:00.000-04:00

from ben marcus' feature article in the october 2005 issue of harper's:

In the left temporal lobe of the brain, below the central sulcus of Ronaldo, but above and tucked behind both Broca's area and Heschl's gyri, sits Wernicke's area, a tufted bundle of flesh responsible for language comprehension... Think of Wernicke's area as the reader's muscle, without which all written language is an impossible tangle of codes, a scribbled bit of abstract art that can't be deciphered. Here is where what we read is turned into meaning, intangible strings of language animated into legitimate shapes. If we do not read, or do so only rarely, the reader's muscle is slack and out of practice, and the stranger, harder texts, the lyrically unique ones that work outside the realm of familiarity, just scatter into random words. The words may be familiar, but they fail to work together as architectural elements of a larger world.

queen amygdala

2005-09-22T15:15:00.000-04:00

on tuesday night's season premiere of House M.D., a young girl showed extraordinary courage in facing her impossibly dire situation. naturally, dr. house dismissed her bravery as unremarkable, going so far as to posit that the girl was not showing genuine, organic courage but rather that her courage was merely a "fake" emotion conjured by her damaged brain.

it was my first time watching a full episode of house. at first i was skeptical, but by the end i was hooked. and what made it all the more riveting was my freshly garnered understanding of brain anatomy. the amygdala is the so-called "fear center" of the brain. a clot in that region of the girl's brain, so the logic went, could have canceled her fear response, thereby explaining her intrepidness. but omar epps spotted the clot in her hippocampus, and so house was wrong, which he in the end grudgingly admitted.

however, according to the notes for a class i had today, projections from the hippocampus to the amygdala provide sensory information about the context of fearful stimuli, a sort of background picture as the brain tries to size up a scary situation. a lesion in this pathway should somehow erase certain components of fear, although which i do not know yet.

you can't spell sclerotic without erotic

2005-09-21T14:21:00.000-04:00

ever wondered what the sclerosis in multiple sclerosis and amyotrophic lateral sclerosis--aka lou gehrig's disease--stands for? well, i always have, and i've also always wondered why it's not multiple scleroses. after all, it's not called the march of dimis, right? har

anyway, here is my newfound understanding of sclerosis. the term is not derived from any neuroanatomy per se but rather from the word sclera, also known as the white of your eye. if you've ever poked at your eye with your finger as i do every morning to put in my contacts, you know that your eyeball is firm and springy, as if it were covered in taut rubber. in sclerotic diseases, the body responds with a process called reactive astrocytosis. this is, in essence, scar formation in the nervous system, analogous to the shiny, tough scars that form on your skin after a cut heals. like superficial scars, these nervous glial scars were found on autopsy to be much firmer than average nervous tissue, and thus the name sclerosis was born. in multiple sclerosis, for example, the immune system goes haywire and starts attacking the body's own nerve cells, resulting in sclerotic lesions that eventually clog up the nervous system. the image i always think of is wolverine plunging the syringe full of liquid adamantium into lady deathstrike, thereby filling her circulatory system with metal. beautiful, i know.

negligent

2005-09-16T12:29:00.000-04:00

i haven't been posting because i don't have internet access at home.

exam is on monday, pray for me please.

yumch

2005-09-08T17:19:00.000-04:00

the four muscles actively involved in chewing are (drumroll please):

the masseter, the lateral pterygoids, the medial pterygoids, and the temporalis. the buccinator (ever wonder what the bucc. on music scores stood for?) helps keep food centered in the mouth; if they push too hard, cheeks are bitten.

one of the boys

2005-09-07T17:08:00.000-04:00

today was a good day, despite having fallen further behind in neuro. i went to ccf rather anxious about work--i had to meet with my lab project advisor and my writing partner (both cards fellows), and i thought i would be facing a double busting of the chops. but, as it turned out, overworked genius doctors in training still have the capacity for sympathy. vivek even asked me to teach his kid mandarin, so i'm going over to his place sunday to babble meaninglessly in chinese with his son for 3 hours, to the tune of $30 too. then brian, instead of reaming me for my 32109482093rd crappy draft of the review we're working on, calmly suggested that we pass my latest effort to the boss for another go round. on top of all this, my very first pcr was a success; i would post a picture of the radiograph here but that would be too loserly even for me.

still, the point of this blog is to study, and that's not happening right now. i've thought about making this more public too, since ideally there would be some element of accountability by virtue of people reading. but the reason i didn't just start blogging about school stuff on xanga was because i didn't want to clog people's subscriptions with my irrelevant bullshit (read: blatant swipe at certain xangas), although it could be argued that i was doing that before i made the switch. in any case, neuro stuff is pending. personal guarantee.

sigh

2005-09-06T13:49:00.000-04:00

i've never been this busy before, never ever. the bird flu i contracted from dr. wang last week didn't help the cause either. now i'm mired in two reviews, a world of pain otherwise known as neuro, and already dragging my feet with lab work. like today, i'm copping out of lab so i can finish a second draft of a paper, but of course i can't email it out until tomorrow because my house still doesn't have internet.

all this on top of the fact that i still wish i owned a jetski, so that i could have driven down to louisiana over the long weekend and shuttled people out of their personal public health hell. everything--my insignificant but significant problems, everyone else's significant but insignificant problems--is making me so mad, but i don't even have time to fume.

it's good to be a guy

2005-09-01T18:59:00.000-04:00

so, today i had one of those moments where something completely obvious but heretofore unnoticed suddenly becomes apparent to you. like, for example, the morning i realized that the word "deodorant" was, in effect, "de-odorant," i.e. something that removes odor. previous to that epiphanous moment, someone could have divided the word as deodo-rant and i would not have noticed anything out of the ordinary.

anyway, this morning i was frantically trying to catch up on neuroanatomy when i came across the term "epidural." epidurals are perhaps most famous as those fearsome shots administered to expectant mothers delivering their babies in order to numb their pain. well, it turns out that the dura mater is a membrane that covers the central nervous system--not just the brain, as i had previously though. the epidural space is that thin sliver of space immediately outside of the dura, containing mostly fatty tissue, lymphatics, and tangles of veins (in the spinal region). an injection of local anesthetic into this epidural space produces a so-called "saddle" nerve block, aka a paravertebral nerve block. and this is why women receive epidurals, although my mom was a soldier and decided to go without one for both me and my sister. which is why i'm a soldier too.

you're it

2005-08-30T16:38:00.000-04:00

busy day today, so i'm just gonna post a link:

http://www.nytimes.com/2005/08/30/health/policy/30nih.html

it's an article on dr. elias zerhouni, director of the NIH and former mentor to my former mentor at hopkins. he's a radiologist by training, and one of his innovations was a technology known as MRI tagging. MRI images can be taken and compiled much like frames in a video or movie. as a result, MRI videos show high-resolution movement of, say, a beating heart. tagging MRI means to impose a magnetic "grid" on the images, which acts as if it were embedded in the tissue itself. the grid then moves along with the heart, bending and warping accordingly. a computer precisely measures the movement of the grid. this allows for quantification of heart movement, which is useful in determining what parts of a heart have died or lost function after a heart attack, for example.

feeling nervous

2005-08-29T16:01:00.000-04:00

whereas the hematology/oncology unit was well-organized and logical in its execution, the vaunted neurology unit makes no such promises. in fact, judging by today's introductory lectures, the neuro unit will be filled with the sort of senseless (hAR) jargon that i utterly despise. i imagine therefore that this blog will see some heavy use in the coming 1.5 months. to begin, let's start with something basic: a list of the cranial nerves.

I Olfactory
II Optic
III Oculomotor
IV Trochlear
V Trigeminal
VI Abducens
VII Facial
VIII Vestibulocochlear
IX Glosspharyngeal
X Vagus
XI Accessory
XII Hypoglossal

tonight's task: memorize these twelve buggers, preferably while grilling brats and dr. luo's special recipe pork chops with davey and huge euge.

hamburgers

2005-08-26T17:22:00.000-04:00

did well on my exam today. i attribute my success to the full breakfast i ate this morning--two eggo waffles, a sausage patty, two strips of bacon, a pork sung sandwich, and a glass of low sodium v8. not the hamburger breakfast that got brett killed in pulp fiction, but still delicious. oh, and my lucky johns hopkins hospital scrubs probably helped too. atul gawande says that doctors--surgeons in particular--aren't very superstitious. i find that hard to believe though. surgeons, after all, are traditionally the jocks of medicine. and athletes are famously superstitious--wade boggs' chicken and reggie miller's pregame buzzer beaters, for example. i'll look into this...

QUITTER!

2005-08-24T13:15:00.000-04:00

the happy family

lance armstrong is being accused of having used the performance-enhancing drug EPO in 1999, when he won his first of seven consecutive tour de france titles. EPO stands for erythropoietin, a hormone produced by the kidneys to stimulate the production of erythrocytes, aka red blood cells. for this reason, individuals who suffer from kidney disease may develop a serious anemia because they cannot produce homeostatic amounts of EPO. EPO also shortens the time for red blood cell maturation. therefore, an athlete who "doped" his blood with EPO would produce more red blood cells, increase his oxygen-carrying capacity, and experience a prolonged boost in stamina.

supposedly, back in 1999 EPO was undetectable but both its benefits and risks were well known. a marked increase in EPO results in more red blood cells, ultimately thickening the blood and heightening one's risk for stroke or other vessel-obstructing events (although, ironically, EPO has been found to help stroke patients recover neurologic function). also, in settings of extended exercise--like, i don't know, maybe riding a bicycle for thousands of miles--the body demands extraordinary amounts of water, some of which is eventually shifted out of the bloodstream and into the tissues for use. this thickens the blood even more.

in mr armstrong's case, he allegedly had taken EPO to help his recovery from cancer, although that was prior to his first tour victory. still, i can't say believe his unequivocal denials of doping, and i think he chose the right time to retire. but, regardless of truth behind the drug accusations leveled against him, as the daily show pointed out after lance's most recent tour de france win, he is a quitter.

and the above photo is my adoring family. notice how remarkably the genes from my parents segregated to produce me and my sister.

billy rubin

2005-08-23T09:10:00.000-04:00

in the book the silence of the lambs, there is a scene where hannibal lecter walks senator martin (the father of the girl stuck in the pit) through the riddle of "billy rubin." buffalo bill's name is a pun on "bilirubin," the organic substance perhaps best known as the yellow tint in jaundiced individuals. i read the book after my sophomore year in high school, before i had seen the movie. jonathan demme cut out this scene from the movie, which i thought was a shame, but otherwise i found the film version to be almost as scary as the book. almost.

an elevated bilirubin level is a symptom of any number of physiologic abnormalities. in the context of hematology, elevated bilirubin levels indicate the breakdown of hemoglobin in the body, as can happen in settings of extravascular and intravascular hemolysis, i.e. the destruction of red blood cells either outside or inside the circulation. one component of hemoglobin in particular--protoporphyrin--is further broken down, resulting in unconjugated bilirubin. the liver typically conjugates bilirubin in order to produce bile, but excess unconjugated bilirubin cannot be processed fast enough by the liver nor excreted in the urine. as a result, it builds up in tissues, thereby yielding the yellowish tinge that characterizes jaundice and scleral icteri (yellowing of the eye).

the potential causes of this red blood cell destruction, as we were taught in class, are most likely either an autoimmune hemolytic anemia, where the body inappropriately produces antibodies against its own red blood cells, or hereditary spherocytosis, where a genetic defect results in the faulty construction of red blood cell membranes, causing RBCs to be abnormally small, inflexible (they look like tiny spheres under a microscope), and thus more susceptible to lysis. the test to differentiate between the two potential etiologies is the direct coombs test, which basically looks for antibodies against RBCs.

tomorrow: photos from the weekend

getting old

2005-08-20T11:36:00.000-04:00

i have loved bill simmons ever since discovering him the summer before college, back when he was still the boston sports guy and not the hollywood half-sports-half-entertainment wannabe hack that he is now. what used to make him so fresh and sublime was his status as sportswriter for the fans. most great sports columnists are great because 1) of decades of experience or 2) of their unparalleled access to superstar athletes. back in 2000, simmons had neither--he was a 30-yr old boston native who lived and died by his boston teams. and what made him funny was that you could relate to him, his angst, his highs and lows. he'd witnessed bird and the celtics at their peak and the red sox at their choking worst. that gave him a different kind of credibility, and top of that he was outrageously funny in his observations of the absurdities of gen X culture, a la letterman and jon stewart. my favorite series he wrote was his story about meeting charles barkley at tnt. he sounded completely awestruck, just like any fan would be, and that was completely unlike any other sportswriter.

but now simmons is past his prime. gone are creative gems like the ewing theory and the vengeance scale. what started as hilarious riffs on the karate kid are now full-scale reviews of movies, and it's painfully apparent that he's overstretching his expertise as he tries to make himself into some kind of pop culture guru. plus he's married now with a kid--can he still write about tecmo football with any sort of legitimacy? it's time for him to retire, or at the very least stop trying so hard. he still puts out good stuff every so often, like his recent column on the wide receiver prima donna phenomenon. but he's finally getting old.

and speaking of old people, my negligent senior thesis advisor, professor charles rosenberg, always referred to the history of pernicious anemia as a classic story in the history of medicine. i never really knew what he was talking about. but now that we've learned about pernicious anemia in class, i still don't really know what he's talking about. i do know, however, that pernicious anemia is the most common cause of vitamin b12 deficiency in adults in temperate climates.

"boob"

2005-08-19T11:11:00.000-04:00

happy friday. here is an article from the latest new england journal, by docstar atul gawande, about the delicate nature of the physical exam.

Naked
Atul Gawande, M.D., M.P.H.

There is an exquisite and fascinating scene in Kandahar, a movie set in Afghanistan under the Taliban regime, in which a male physician is asked to examine a female patient. They are separated by an opaque screen. Behind it, the woman is covered from head to toe by her burka. The two do not talk directly to each other. The patient's young son serves as the go-between. She has a stomachache, he says.

"Does she throw up her food?" the doctor asks.

"Do you throw up your food?" the boy asks.

"No," the woman says, perfectly audibly, but the doctor waits as if he has not heard.

"No," the boy tells him.

For the exam, the doctor has cut a two-inch circle in the screen. "Tell her to come closer," he says. The boy does. She brings her mouth to the opening, and through it he looks inside. "Have her bring her eye to the hole," he says. And so the exam goes. Such, apparently, can be the demands of decency.

When I started my surgical practice two years ago, I was not at all clear about what my own etiquette of examination should be. Expectations are murky; we have no clear standards in the United States; and the topic can be fraught with hazards. Physical examination is deeply intimate, and the way a doctor deals with the naked body — particularly when the doctor is male and the patient female — inevitably raises questions of propriety and trust.

No one anywhere seems to have discovered the ideal approach. A surgical colleague who practices in Iraq told me about the customs of physical examination there. He said he feels no hesitation about examining female patients completely when necessary, but because a doctor and a patient of opposite sex cannot be alone together without eyebrows being raised, a family member will always accompany them for the exam. Women do not remove their clothes or change into a gown for the exam, and only a small portion of the body is uncovered at any one time. A nurse, he said, is rarely asked to chaperone: if the doctor is female, it is not necessary, and if male, the family is there to ensure that nothing unseemly occurs.

In Caracas, according to a Venezuelan doctor I met, female patients virtually always have a chaperone for a breast or pelvic exam, whether the physician is male or female. "That way there are no mixed messages," the doctor said. The chaperone, however, must be a medical professional. So the family is sent out of the examination room, and a nurse brought in. If a chaperone is unavailable or has refused to participate, the exam is not done.

A Ukrainian internist told me that she has not heard of doctors in Kiev using a chaperone. If a family member is present, he or she will be asked to leave. Both patient and doctor wear their uniforms — the patient a white examining gown, the doctor a white coat. Last names are always used. There is no effort at informality to muddy the occasion. This practice, she believes, is enough to solidify trust and preclude misinterpretation of the conduct of care.

A doctor, it appears, has a range of options.

In 2003, I set up my clinic hours, and soon people arrived to see me. I was, I realized, for the first time genuinely alone with patients. No attending physician in the room or getting ready to come in; no bustle of emergency room personnel on the other side of a curtain. Just a patient and me. We'd sit down. We'd talk. I'd ask about whatever had occasioned the visit, about past medical problems, medications, the family and social history. Then the time would come to have a look.

There were, I will admit, some awkward moments. I had an instinctive aversion to examination gowns. At our clinic they are made of either thin, ill-fitting cloth or thin, ill-fitting paper. They seem designed to leave patients exposed and cold. I decided to examine my patients while they were in their street clothes. If a patient with gallstones wore a shirt she could untuck for the abdominal exam, this worked fine. But then I'd encounter a patient in stockings and a dress, and the next thing I knew, I had her dress bunched up around her head, her tights around her knees, and both of us wondering what the hell was going on. An exam for a breast lump one could manage, in theory: the woman could unhook her brassiere and lift or unbutton her shirt. But in practice, it just seemed weird. Even checking pulses could be a problem. Pant legs could not be pushed up high enough. Try pulling them down over shoes, however, and . . . forget it. I finally began to have patients change into the damn gowns. (I haven't, however, asked men to do so nearly as often as women.)

As for having a chaperone present with female patients, I hadn't settled on a firm policy. I found that I always asked a medical assistant to come in for pelvic exams and generally didn't for breast exams. I was completely inconsistent about rectal exams.

I surveyed my colleagues about what they do and received a variety of answers. Many said they bring in a chaperone for all pelvic and rectal exams — "anything below the waist" — but only rarely for breast exams. Others have a chaperone for breast and pelvic exams but not for rectal exams. Some did not have a chaperone at all. Indeed, an obstetrician–gynecologist estimated that about half the male physicians in his department do not routinely use a chaperone. He himself detests the word "chaperone" because it implies that mistrust is warranted, but he offers to bring in an "assistant" for pelvic and breast exams. Few of his patients, however, find the presence of the assistant necessary after the first exam, he said. If the patient prefers to have her sister, boyfriend, or mother stay for the exam, he does not object — but he is under no illusion that a family chaperone offers protection against an accusation of misconduct. Instead, he relies on his reading of a patient to determine whether bringing in a nurse–witness would be wise.

One of our residents, who was trained partly in London, said he found the selectivity here strange. "In Britain, I would never examine a woman's abdomen without a nurse present. But in the emergency room here, when I asked to have a nurse come in when I needed to do a rectal exam or check groin nodes on a woman, they thought I was crazy. `Just go in there and do it!' they said." In England, he said, "if you need to do a breast or rectal exam or even check femoral pulses, especially on a young woman, you would be either foolish or stupid to do it without a chaperone. It doesn't take much — just one patient complaining, `I came in with a foot pain and the doctor started diving around my groin,' and you could be suspended for a sexual-harassment investigation."

Britain's standards are stringent: the General Medical Council, the Royal College of Physicians, and the Royal College of Obstetricians and Gynaecologists specify that a chaperone must be offered to all patients who undergo an "intimate exam" (i.e., involving the breasts, genitalia, or rectum), irrespective of the sex of the patient or of the doctor.1,2 A chaperone must be present when a male physician performs an intimate exam of a female patient. The chaperone should be a female member of the medical team, and her name should be recorded in the notes. If the patient refuses a chaperone and the examination is not urgent, it should be deferred until it can be performed by a female physician.

In the United States, we have no such guidelines. As a result, our patients have little idea of what to expect from us. To be sure, some minimal standards have been established. The Federation of State Medical Boards has spelled out that touching a patient's breasts or genitals for a purpose other than medical care is a disciplinable offense. So are oral contact with a patient, encouraging a patient to masturbate in one's presence, and providing services in exchange for sexual favors. Sexual impropriety — which involves no touching but is no less proscribed — includes asking a patient for a date, criticizing a patient's sexual orientation, making sexual comments about the patient's body or clothing, and initiating discussion of one's own sexual experiences or fantasies.3 I can't say anyone taught me these boundaries in medical school, but I would like to think that no one needed to.

The difficulty for those of us who do not behave badly is that medical exams remain inherently ambiguous. Any patient can be led to wonder: Did the doctor really need to touch me there? Even when doctors simply inquire about patients' sexual history, can anyone be certain of the intent? The fact that all medical professionals have blushed or found their thoughts straying during a patient visit reveals the potential for impropriety in any encounter.

The tone of an office visit can turn on a single word, a joke, a comment about a tattoo in an unexpected place. One surgeon told me of a young patient who expressed concern about a lump in her "boob." But when he used the same word in response, she became extremely uncomfortable and later made a complaint. Another woman I know left her gynecologist after he made an offhand, probably inadvertent, but admiring comment about her tan lines during a pelvic exam.

The examination itself — the how and where of the touching — is, of course, the most potentially dicey territory. If a patient even begins to doubt the propriety of what a doctor is doing, something is not right. So what then should our customs be?

There are many reasons to consider setting tighter, more uniform professional standards. One is to protect patients from harm. About 4 percent of the disciplinary orders that state medical boards issue against physicians are for sex-related offenses. One of every 200 physicians is disciplined for sexual misconduct with patients sometime during his or her career.4 Some of these cases involve such outrageous acts as having intercourse with patients during pelvic exams. The vast majority of cases involved male physicians and female patients, and virtually all occurred without a chaperone present.5 About one third of cases studied in one state involved actual sexual intercourse with patients; two thirds involved sexual impropriety or inappropriate touching short of sexual contact. Another goal might be to reduce false accusations arising from misinterpretation.

Nonetheless, eliminating misconduct and accusations would be the wrong aim to guide medical care. The trouble is not that such acts are rare (though the statistics suggest they are), nor that total prevention — zero tolerance — is impossible. It is that, at some point, the measures required to achieve total prevention will approach the Talibanesque and harm care of patients.

Embracing more explicit standards for medical encounters, however, might actually improve relationships with patients — and that does stand as a worthy goal. The new informality of medicine — with white coats disappearing, and patient and doctor sometimes on a first-name basis — has blurred boundaries that once guided us. If physicians are unsure about what is appropriate behavior for themselves, is it any surprise that patients are, too? Or that misinterpretation can occur? We have jettisoned our old customs but have not bothered to replace them.

My father, a urologist, has thought carefully about how to avert such uncertainties. From the start, he felt the fragility of his standing as an outsider, an Indian immigrant practicing in a rural Ohio town. In the absence of guidelines to reassure patients that what he does as a urologist is routine, he has made painstaking efforts to avoid question.

The process begins before the exam. He always arrives in a tie and white coat. He is courtly. Although he often knows patients socially and doesn't hesitate to speak with them about personal matters (the subjects can range from impotence to sexual affairs), he keeps his language strictly medical. If a female patient must put on a gown, he steps out while she undresses. He makes a point of explaining what he is going to do during the examination and why. If the patient lies down and needs further unzipping or unbuttoning, he is careful not to help. He wears gloves even for abdominal examinations. If the patient is female or under 18 years of age, then he brings in a nurse as a chaperone, whether the exam is "intimate" or not.

His approach has succeeded. I grew up knowing many of his patients, and they trust him completely. I find, however, that some of his practices do not seem quite right for me. My patients are as likely to have problems above the waist as below, and having a chaperone present for a routine abdominal exam or a check of groin pulses feels to me absurd. I don't don gloves for nongenital exams. Nonetheless, I have tried to emulate the spirit of my father's visits — the decorum in language and attire, the respect for modesty, the precision of examination. As I think further about his example, it has also led me to make some changes: I now uniformly use an assistant not just for pelvic exams but also for rectal exams of female patients and as patients desire, for breast exams as well. For the comfort and reassurance of patients, these seem to be reasonable customs, even expectations, for more of us to accept.

A professor once told my medical school class that patients can tell when you've seen a thousand naked patients and when you haven't. I now know that's true. But I have also come to recognize that no patient has seen a thousand doctors. They therefore have little idea, coming to a doctor's office, of what is "normal" and what is not. This we can change.

Source Information

Dr. Gawande is a general and endocrine surgeon at Brigham and Women's Hospital and an assistant professor at Harvard Medical School and at the Harvard School of Public Health, Boston.

References

1. Intimate examinations. London: General Medical Council Standards Committee, December 2001.
2. Gynaecological examinations: guidelines for specialist practice. London: Royal College of Obstetricians and Gynaecologists, July 2002.
3. Ad Hoc Committee on Physician Impairment. Report on sexual boundary issues. Dallas: Federation of State Medical Boards of the United States, April 1996.
4. Dehlendorf CE, Wolfe SM. Physicians disciplined for sex-related offenses. JAMA 1998;279:1883-1888. [Abstract/Full Text]
5. Enbom JA, Thomas CD. Evaluation of sexual misconduct complaints: the Oregon Board of Medical Examiners, 1991 to 1995. Am J Obstet Gynecol 1997;176:1340-1348. [ISI][Medline]

the IRA

2005-08-18T18:48:00.000-04:00

the first research job i enjoyed was as a clinical research assistant in cardiology at johns hopkins. i was in way over my head, reading all kinds of articles that i couldn't understand at all, but i enjoyed the hospital setting and just hanging out with doctors. my project involved compiling a database of patient info--in retrospect it was a shit job, but i thought i was doing something important and challenging at the time. specifically, i was concerned with a particular type of drug that patients were perhaps given during their balloon angioplasties. these drugs were of the GPIIb/IIIa inhibitor class, and there are three such drugs currently on the market--integrilin, reopro, and aggrastat. their scientific names are eptifibatide, abciximab, and tirofiban, respectively.

now i know what they do, and so i thought i would amend my previous post by pointing out that glycoprotein IIb/IIIa receptors are not the mediators per se of platelet aggregation. instead, they are the binding sites for fibrinogen, the precursor to fibrin, i.e. the glue that keeps clots together. incidentally, although drugs blocking these receptors are indicated for the prevention of unwanted clots, the congenital deficiency of these receptors is called Glanzmann's thrombasthenia, a rare but serious bleeding disorder.

sadly though, the love of my life is nowhere to be seen today. maybe tomorrow.

the girl next door

2005-08-17T15:24:00.000-04:00

right now i am sitting at borders across from a beautiful, demure korean girl who is sifting through a massive pile of novels. i have decided that i love her. and so this entry, my first official post of the year, is dedicated to the lovely agashi across the way.

the coagulation cascade is a remarkable piece of biological machinery that keeps our blood flowing when it should and clots it when it shouldn't. in fact, it is so remarkable that it is a commonly cited example, like the eye, of how evolution may fail to explain all the complexities of the human body. the coagulation cascade, in other words, is a kind of "all or nothing" system, i.e. take away any one of its many parts and the whole things breaks. evolution is about incremental change, yet it is difficult to imagine the simpler precursor mechanism to coagulation that should have come before the present clotting system.

anyway, last year we learned about the basics of coagulation--the names of all the different factors, the intrinsic vs. extrinsic pathways, and a couple disorders resulting from disruptions to the cascade. this year we're learning all about what goes wrong in the body, and our first unit is hematology/oncology. a friend of mine from college used to wear a silver bracelet that indicated his having von Willebrand's disease. von Willebrand's factor (VWF) is one of the many coagulation cascade factors that mediate blood clotting. VWF in particular mediates platelet adhesion to the inner lining of blood vessels... ok hold on, the girl just talked to me! and she smiled at me! anyway, so VWF helps platelets adhere to blood vessel endothelium, so-called "primary hemostasis." in order to activate platelets so that they become sticky, VWF binds to the platelet receptor GP1b. this binding then activates a second binding site, GPIIb/IIIa, which allows for tight adhesion of platelets to one another. incidentally, GPIIb/IIIa inhibitors are now crucial drugs in the treatment of heart disease, and their use was made popular by my awesome boss, dr. topol.

so yeah, von Willebrand's disease is the result of some abnormality of VWF, either quantitative or qualitative. quantitative disorders are the most common, such as the partial deficiency of VWF known as type 1 VWD, and this is what i suspect my friend had, although now we'll never know because he lost his bracelet. there are other qualitative variations of the disease where the VWF binds too well to GP1b, or it binds poorly, or it is completely absent (this is quantitative but whatever).

ok i'm much too distracted to continue. go evolution, boo intelligent design.

a storm is coming

2005-07-11T11:18:00.000-04:00

i will start posting soon, really. just need to work the kinks out to start the year. you know, like figuring out how to juggle class, research, studying for boards, hanging out with friends, not going crazy, etc. can't say i know what i'm doing quite yet, but i'm slowly getting there.

is anyone reading this? if so, please say hi, thank you.

"become who you were born to be." - elrond

closer to home

2005-06-12T13:30:00.000-04:00

writing my last few posts, i've discovered that it's awfully hard to explain broad physiologic principles in just a couple paragraphs. not only that, it's a bit of a waste for me to regurgitate concepts that i'm already familiar with, just for the sake of continuity. so i'm gonna scratch that plan and go back to what worked before my comp--sporadic, on-demand posts. at first i was worried that i wouldn't have enough material to untangle, but now, in retrospect, that was a rather hubristic concern. there are more than enough relevant--albeit random--questions that pop up in the course of my day, so i'll address those instead in this space.

so, where better to begin than my current laboratory project. here's the idea (as always, i will try to make this palatable):

as i mentioned before, there's been a shift in thought regarding coronary artery disease (CAD), from a paradigm of progressively clogged vessels to the current understanding of arterial inflammation. arteries, it turns out, become inflamed as the result of what i like to call "molecular irritants," e.g. cholesterol, fats, etc, the same way a mosquito bite becomes red and swollen after you scratch it. there is still clogging and narrowing of arteries, but these deposits alone do not cause, say, a heart attack. rather, inflammation of arteries renders these deposits unstable, causing them eventually to break free and float downstream until they clog a narrow vessel like a coronary artery.

as a result of this new understanding, inflammation has become an attractive target of research. my project concerns the effect of the nervous system on inflammation. (a quick fyi on the autonomic nervous system: there are two pathways that govern your body's reflexive response to stimuli--sympathetic and parasympathetic. sympathetic activation is the famous "fight-or-flight" reflex. parasympathetic activation is the opposite.) it's been shown that parasympathetic stimulation results in decreased activation of an important inflammatory cell--the macrophage. specifically, a receptor for the parasympathetic neurotransmitter acetylcholine resides on the surface of macrophages, and it's also been shown that mutations in the alpha-subunit of this receptor results in a loss of the anti-inflammatory effect imparted by parasympathetic activity. furthermore, these mutations have been characterized at the DNA level, so that the specific genetic sequence underlying each of these mutations is known.

my hypothesis, then, is that these genetic variations, because they result in a loss of anti-inflammatory "protection," may be found in those patients who suffer from premature CAD. for the past ten years, the cleveland clinic has been assembling a database of CAD patients' genetic profiles. using that database, i'll be sequencing the macrophage receptor alpha-subunit gene (the promoter for the gene, to be precise) and looking for a statistically-significant prevalence of gene mutations compared to a population of normal control individuals. nothing too complicated--just an old fashioned case-control association study.

if i'm violating some kind of unwritten rule, where one can't divulge your research interests until publication, i apologize in advance... to no one.

what's most importantly

2005-06-10T19:54:00.000-04:00

the neuromuscular junction is just that: the junction between a nerve ending and a muscle fiber. let's say this particular nerve originates in the brain, and the target muscle fiber is an abdominal muscle. now, let's also say you're sitting in your room, listening to kanye west's new workout plan, and you decide hey, i should do some crunches. you lie down, and a split-second before you crunch, the following happens (very roughly speaking):

first, your brain sends an electrical signal--an action potential--down the length of the nerve towards the neuromuscular junction. the action potential doesn't move uninterrupted along the nerve like an ocean wave, however. instead, it's more like a relay race runner, moving a short distance before initiating a consequent, identical action potential, which then does the same. another way to think of the action potential is as the baton in a relay race. either way, this relay race of action potentials eventually hits the nerve ending, aka the nerve terminal, where the key electrochemical process begins.

one of the more remarkable aspects of cell physiology is the conversion of electrical to chemical energy, and vice versa. in the case of the neuromuscular junction, the action potential causes voltage-gated (i.e. voltage-sensitive) calcium channels to open up. calcium then rushes into the nerve terminal, dramatically changing the ionic milieu of the cytoplasm (each calcium ion carries a 2+ charge). this results in the fusion of tiny vesicles to the plasma membrane, each one containing a certain quantal amount of acetylcholine (ACh), a neurotransmitter. a graphic but effective way of visualizing this release of ACh is to imagine each vesicle as a free-floating uterus containing a baby named ACh. upon depolarization by the action potential, these vesicles move to the nerve terminal and "give birth," releasing the ACh baby to the extracellular world. ok bad metaphor, but it's friday night and i'm about to head out.

anyway, the ACh then moves across the space between the nerve terminal and the muscle fiber--the synaptic cleft--until it reaches the receptors for ACh, called nicotinic receptors (named for their specific reponse to death. i mean cigarettes. i mean nicotine). these receptors are special for all kinds of reasons that i won't get into here. suffice it to say, what's most importantly is that ACh is the indispensable errand boy of all voluntary muscular contractions. botox, for example, blocks the release of ACh, preventing muscle stimulus and thereby also preventing all the muscle activity that leads to wrinkles and such. but, with the appropriate transduction ACh, you can happily do your crunches and eventually score an nba player like kanye says.

cavalier

2005-06-09T22:03:00.000-04:00

right now i'm watching game one of the nba finals. detroit has to be one of the most underrated teams in professional sports history. who's given them any respect in the past two years? detroit's only up 27-24 right now, but even if san antonio goes on to win the series, detroit, in my mind, has earned its wings as one of the great nba teams of the past 25 years.

although they're primarily known for their stingy defense, one of the pistons' hallmarks is its "flex" offense. many teams employ a flex offense, including my beloved university of maryland terrapins, particularly when they feature quick, accurate-shooting guards like juan dixon or, detroit's star guard, richard hamilton. you'll often hear the word "curl" and "rotation" associated with flex offenses. the guard moves in a circle about 15 feet from the basket, running through screens to get open for a mid-range jumpshot. drawn up with x's and o's, a flex offense is a bunch of curved arrows.

in cell physiology, the transport of molecules and ions across cell membranes is often facilitated by so-called transport proteins--integral membrane proteins that allow specific substances to pass in and out of cells. some of these transport proteins need a direct burst of energy to move an ion, for example, across the membrane. the most ubiquitous of these primary active transport proteins is the sodium-potassium pump, aka Na+,K+ ATPase. this ATPase is present in all cell membranes, and it pumps three Na+ ions out of the cell and two K+ ions into the cell. the way my simple brain remembers this is, "Na+" is 3 characters, so 3 sodium ions are pumped out, and "K+" is 2 characters, so 2 potassium ions are pumped in.

another important concept in characterizing transport and receptor proteins is the subunit building block. the Na+,K+ ATPase consists of an alpha and a beta subunit. the alpha subunit is the busy subunit, responsible for the ATPase enzymatic activity (-ase = enzyme) and the binding of both sodium and potassium. likewise, my current research involves examining the gene that codes for an alpha subunit of a nerve receptor. as you can probably deduce from its functions, the Na+,K+ ATPase alpha subunit isn't static--it moves in order to shuttle ions across the plasma membrane, changing shape depending on what's bound to it. specifically, when Na+ binds to the ATPase from the inside of the cell, the enzyme then undergoes a conformational change and rotates to the extracellular (outside) surface of the membrane, where it then releases the sodium and binds a potassium in exchange.

hence the flex offense and the curl. at least for me, thinking of transport proteins as dynamic, shape-shifting entities helps me understand both their functions and their roles better, rather than simply thinking "ok, Na+,K+ ATPase is 3 sodium out, 2 potassium in." like rip hamilton, the ATPase starts from one end of the membrane "court," rotates across to the other end, and releases the shot. it's not the best metaphor--whereas the ATPase alpha subunit carries the Na+ ion, hamilton moves without the ball. but whatever.

oh, and i almost forgot: cavalier! back in high school, my lacrosse team ran a cool play called cavalier, named after the university of virginia mascot. when coach called cavalier, the midfielder with the ball (me) stood up top--think the top of the key in basketball--while the three attackmen ran in a circle in front of the goal, waiting for a pass for a quick score (kinda like a flex offense). unfortunately, the play never worked in a game, but at least it always looked cool.

bada bing!

2005-06-07T18:06:00.000-04:00

made again famous by the sopranos, sonny corleone uttered these famous words after his little brother delivered the monologue that i consider to be the turning point of michael corleone in the godfather. some people point to michael's tender moment at his father's bedside in the hospital; others say it's when he pulled the trigger on sollozzo and mccluskey in louis' restaurant; a strong case can also be made for apollonia's death by car bomb, which presumably sealed michael's fate to a life of violence.

but no, my favorite scene is when michael is sitting in a chair, one leg crossed over the other, simultaneously thinking through and explaining his plan to prevent sollozzo and mccluskey from ever harming his father again. that, i think, was when he irreversibly committed himself to the family, and his monologue--with the slow zoom in on his busted jaw and his droopy eyes--marks the first of his many calculated, cruel masterstrokes of vengeance. it is the beginning of his end.

that's how i like to think of heart disease. the beginning of the end. research shows that coronary arteries start narrowing not at 30 or 40 but at childhood. everyone, it appears, has some baseline degree of heart "disease." but what is it that causes heart disease--specifically, disease of the coronary arteries (CAD), the arteries that supply the heart with blood? is it the infamous things--high blood pressure, high cholesterol, obesity, smoking? how about family history, or IV drug use? or is it something else? my summer research has to do with how heart attacks are inherited, strange as it may sound. after AP bio and bs50 and bs52 and bs57 and the first-year genetics committee, i have a decent handle on how genetics works and the molecular machinery that results in a heart attack gene moving from one generation to the next. what i don't really understand, though, is how CAD works, i.e. its pathogenesis.

it turns out no one else really knows how it works either. as recently as the early 1990s, many physicians and researchers still believed that, if they could eliminate high blood pressure and high cholesterol, the elimination of CAD would follow. unfortunately, CAD isn't so simple, and its pathogenesis is now largely understood to be a complicated inflammatory process. allow me to be a shameless dork here and say that i think inflammation is fascinating. inflammation can be good, can be bad, can be seen and felt, can be invisible and silent, can be acute, can be chronic... it can do pretty much anything, anywhere (think of all the -itis diseases you've heard of. arthritis, gastritis, conjunctivitis, etc. even elephantitis, although not glorified like eminem would have you believe). now it seems it can even result in CAD and heart attacks.

all this brings me back to two of my least favorite subjects--basic cell physiology and immunology. these are the two biology fields that absolutely and obscenely adore using senseless numbers and letters to name things. unsurprisingly, these were the two subjects with which i struggled most last year. and, also unsurprisingly, cell phys and immunology are the cornerstones to the heart disease inflammatory process.

therefore, tomorrow i'll begin with a review of cell phys, using my beloved costanzo review book as my guide. i'll then move through the different organ systems, although slightly out of order so that i can do heart and vasculature first and thereby provide at least some semblance of narrative continuity throughout this summer's posts.

"it's not personal, sonny. it's strictly business."

the emancipation of albert

2005-06-06T21:51:00.000-04:00

a washed-up, old, completely insane mariah carey still has more talent in one alveolus than 99% of recording artists out there today.

busy day. will post for real starting tomorrow.

in the summer, in the city

2005-06-04T22:44:00.000-04:00

after a much-needed week at home in merryland, tomorrow it's back to cleveland for a summer of work. lots of people have asked me why, for this, my last free summer ever, with the chance to go anywhere i want, i decided to stay in cleveland. sometimes, i wonder the same thing. but right now i'm excited to go back. i have a sweet sweet job waiting for me--an exciting project on the genetics of heart attack. and now, unlike earlier this year when i started the project but was utterly lost, i have a handle on the basic physiological processes--hemodynamics, cardiac function, inflammation--that underlie my research.

in other words, like the detroit pistons, i say, "bring on the heat." it'll be nice to experience the working life for a change. 9-to-5 weekdays, carefree weekends, no studying constantly hanging over my head. but, masochist that i am, i'll be updating this blog daily again, mostly with reviewed material from the past year. also, now that i'm no longer haphazardly studying for my comp exam, i'll be reading up in a more organized fashion, so my posts should make more sense from one day to the next. or at least the actual medical content will. my metaphors and mnemonics, on the other hand, will likely become bizarrer and bizarrer. after all, this blog is still all about me and me trying to learn my stuff. ya'll will just have to deal.

yay? yay.

the man who fell out of bed

2005-06-03T10:57:00.000-04:00

i met oliver sacks in high school, at the now infamous "arizona thing." towards the end of senior year, i was invited--along with 400 or so other high school students--to an all expenses-paid 4-day vacation at the phoenician resort. there, we students had the opportunity to cavort with america's rich and famous. lauryn hill, gen. wesley clark, arthur golden, ben carson, 23 nobel prize winners... it was surreal, to say the least. below is a photo of me and composer john williams. nice guy, although not as tall as i'd thought.

me with the man

anyway, oliver sacks was there too, and at the time i had no clue who he was. i didn't know yet that i wanted to be a physician, and dr. sacks struck me as more odd than inspiring. he mumbled and stuttered throughout his speech, his eyes fixed on his feet, and he wrote books with strange titles like the man who mistook his wife for a hat. what a freak.

but, five years later, almost to the day, i've picked up his book and found it to be absolutely mesmerizing. i still only have a rudimentary grasp of the biology with which he's concerned--i know the left and right brain stereotypes like anyone else, and i know how strokes and brain tumors come about. but it's enough for me to appreciate some of the stories he tells. his patients are extraordinary--a man who, yes, mistakes his wife for a hat, a woman who has no sense of "left" (think derek zoolander's ambi-turning deficiency, but without the humor), and a man with memento-style amnesia. human consciousness is one of those black boxes that never really piqued my interest--i'm perfectly happy not knowing how it works, so instead my professional interests, i assumed, would concern diseases with less metaphysical weight. still, dr. sacks' book makes me wonder...

here is an excerpt:

Thus, in one patient under my care, a sudden thrombosis (clot) in the posterior circulation of the brain caused the immediate death of the visual parts of the brain. Forthwith this patient became completely blind--but did not know it. He looked blind--but he made no complaints. Questioning and testing showed, beyond doubt, that not only was he centrally or 'cortically' blind, but he had lost all visual images and memories, lost them totally--yet had no sense of any loss. Indeed, he had lost the very idea of seeing--and was not only unable to describe anything visually, but bewildered when I used words such as 'seeing' and 'light.'... His entire lifetime of seeing, of visuality, had, in effect, been stolen.

f--- medicine

2005-05-26T18:25:00.000-04:00

from today's exam, a surprise question on SIADH--syndrome of inappropriate anti-diuretic hormone. at first glance i did not recognize SIADH, so i turned to my rational, sensible powers of deduction to analyze the syndrome's name. clearly, i thought, SIADH has something to do with abnormal levels of ADH. whether SIADH causes inappropriately high ADH secretion or inappropriately low ADH secretion, however-- well, that's anyone's guess, seeing as "inappropriate" is a SUPREMELY USELESS DESCRIPTION.

as it turns out, SIADH results in excess ADH and hyperconcentrated urine, which in retrospect is mildly suggested by the adjective "inappropriate." but why the medical bigwigs can't just rename it the syndrome of excess anti-diuretic hormone, i haven't a clue. instead, i had to agonize for 5 precious minutes over an ultimately random guess, using approximately zero brain cells in the process. so much for assessing my medical knowledge, my critical thinking skills, my academic aptitude, whatever...

*sigh*

mr. october

2005-05-26T00:07:00.000-04:00

"the straw that stirs the drink." reggie jackson, the former yankee slugger, is known for his postseason heroics, in particular his 3-homers-on-3-pitches world series game (i forget which year). he was the prototypical playoff catalyst, and it is in his honor that i write this last-minute entry on key biochemical enzymes.

in glycolysis, there are four irreversible regulated steps:

D-glucose --> glucose-6-phosphate
- glucokinase in liver, hexokinase everywhere else

fructose-6-phosphate --> fructose-1,6-bisphosphate
- phosphofructokinase (rate-limiting step)
- inhibited by ATP, citrate
- stimulated by AMP, fructose-2,6-bisphosphate

phosphoenolpyruvate --> pyruvate
- pyruvate kinase
- inhibited by ATP, alanine
- stimulated by fructose-1,6-bisphosphate

pyruvate --> acetyl-CoA
- pyruvate dehydrogenase complex
- inhibited by ATP, NADH, acetyl-CoA

the common theme regarding glycolytic enzyme regulation is that high energy molecules or molecules produced by high energy processes inhibit glycolysis, i.e. telling the glycolytic pathway that it no longer needs to metabolize glucose to make energy.

in the citric acid cycle, here are the key regulated enzymes:

citrate synthase
- inhibited by ATP

isocitrate dehydrogenase
- rate-limiting step
- inhibited by ATP, NADH
- promoted by ADP

alpha-ketoglutarate dehydrogenase
- inhibited by succinyl-CoA, ATP, NADH

like glycolysis, the TCA cycle is slowed by those molecules signalling adequate energetic fuel.

bah. i'm pretty sure a lot of what i just wrote is incorrect. sleepy time.

final countdown (1:48)

2005-05-25T15:51:00.000-04:00

pretend you're barry bonds. in addition to the lingering destructive effects of all the 'roids you may or may not have been taking, when you press your hands against a wall to do a basic calf stretch, you notice that your left shoulder blade is sticking out unusually far. you notice it because it's stretching out the under armour heatgear workout shirt you're wearing, and you also feel moderate pain in your left shoulder. as a result, you have to do extra rehab for your injured shoulder, and in doing so you erase any chance of albert's fantasy baseball team making a late summer comeback.

this is injury is known as a winged scapula. it's typically the result of damage to the long thoracic nerve, which ennervates the serratus anterior muscle, which attaches to the scapula (shoulder blade). the resulting paralysis limits the motion of the scapula, causing it to bulge out the back.

tomorrow, it's go time.

the bane, part two

2005-05-24T18:16:00.000-04:00

i know i promised to write something more metaphor-friendly this time around, but i lied. immunology continues to run circles around me, and i need to fight back. what i will do, though, is (try to) place this otherwise intrinsically meaningless discussion of lymphocytes in the context of HIV/AIDS. even if the letters and numbers are still greek to me, at least they'll seem at least collectively more significant in the setting of a truly frightening disease. on that cheery note, here's my basic understanding of lymphocytes, aka T cells and B cells:

in high school health class, you probably learned something about how HIV and AIDS work. the virus kills "helper" T cells, which are part of the body's natural defense system, and the debilitated victim eventually dies from an infection. along with B cells (bone marrow-derived), T cells (thymus-derived) are lymphocytes, specialized cells that are responsible for adaptive immunity--the body's specific response to (presumably) foreign invaders. although functionally distinct, B cells and T cells communicate extensively, signalling one another with dozens of molecules in countless scenarios.

"helper" T cells are called helpers because they don't do any killing--they just signal. appropriately, cytotoxic "killer" T cells do a fair share of the killing. in other words, helper T cells are pussies, albeit clever, essential ones. moreover, helper T cells are further classified into two groups: Th1 and Th2. respectively, two signaling molecules induce the development of a baby (naive) helper T cell into these two distinct types: interleukin-12 (IL-12) and IL-4. the best way for me to remember that IL-12 induces Th1 development is that both IL-12 and Th1 have the number "1" in their names. incidentally, this is one of the prime examples of why immunology makes me want to light myself on fire.

but i digress. Th1 is a key player in cell-mediated immunity, the principle mechanism through which the body defends against viruses and certain bacteria. IL-12 essentially gives helper T cells a heads up that a virus or bacterium is wreaking havoc somewhere, and in turn the activated Th1 cell releases two signaling molecules--IFN-gamma and IL-2--to activate and direct killer cells. IFN-gamma activates macrophages, and IL-2 activates killer T cells. as far as i can tell, the "cell" in "cell-mediated" refers to these killer cells. maybe i'm wrong. boo freaking hoo if i am.

on the other hand, Th2 cells, via IL-4 activation, anchor the antibody-mediated immune process. you can't spell antibody without the letter "b," and so it follows that B cells produce antibodies and are the targets of Th2 signals. again, this is why i hate immunology. most of my classmates, if they see "antibody," they automatically think "B cell." for me, when i see "antibody," i think, "shouldn't it be written 'anti-body'? and why didn't they call it "contra-body" instead? that way, a molecule called ABAB would carry some intrinsic value." it's all i can do not to write "anti-body" in my notes. but again i digress. Th2 cells produce and send out IL-4 and IL-5 molecules to help B cells make antibodies, which then control particular extracellular pathogens.

this brings us back to HIV. HIV does in fact destroy helper T cells, but which ones: Th1 or Th2? i had to google this question for an answer, and even then i couldn't find anything definitive. it appears HIV preferentially invades Th1 cells, but Th1 cells are better at controlling the internalized virus, whereas Th2 cells are less often infected but are weaker upon infection. a third possibility is that HIV infects naive T cells (Th0), but i recently read an abstract arguing against this idea. still, between the two of them, Th1 and Th2 cover the body's chief defense mechanisms against infection, which is why HIV's destruction of both helper T cell-types is so devastating.

deez nutz

2005-05-23T17:25:00.000-04:00

one of my glaring weaknesses as a medical student (and as a person, really) is my pride. there are certain student-ish things i have historically refused to do--reread my notes, use a highlighter, write flash cards, etc. in the course of the past year, however, i've humbly had to break every one of these personal rules in order to manage the sheer bulk of material we have to learn. every rule, that is, except one: the no flash cards rule.

i should qualify this statement first and admit that i have cut 200 blank cards and have even written up two cards--one for choleragen and one for hereditary angioneurotic edema. to this day, those two cards remain unflipped, and therefore i don't count them as flash cards, i.e. they haven't been flashed.

still, as a result, i have abstained from flash card usage all year, often to my detriment. and in no instance was this detriment more obvious than when i was studying immunology. immunology became the bane of my existence because of its insistence on using nonsensical letters and numbers to describe everything that happens within it. the classic, most glaring example of this is the collection of cell surface molecules called CD molecules. even the deceptively simple "CD" name already presents a baffling challenge. call up a med student friend and ask her or him what "CD" stands for, and i bet you my tuition that your friend won't know (answer: clusters of differentiation, which, of course, is no more helpful than CD).

moreover, there are well over 200 of these CD molecules, approximately 1/6 of which we're expected to know, and none of which have useful, descriptive names, unless you naturally think "CD16" screams "phagocytosis." any normal student faced with the task of memorizing 40 CD molecules and their respective functions would head straight to a pile of blank flash cards or think of yet another corny mnemonic to sort everything out. unfortunately, i have neither the discipline nor the cleverness to do either, and so i'm simply going to list the relevant CD molecules below. next entry i promise to use more metaphors.

T-cell markers (CD2-8):

CD2
CD3 - part of the signal transducing complex that associates with the alpha/beta T-cell receptor (TCR, which cannot signal on its own)
CD4 - the receptor for class II major histocompatibility complexes (MHC). CD4 possesses no signal transducing function.
CD5
CD7
CD8 - the receptor for class I MHC. CD8 also does not possess any signal transducing function.

CD28 - provides a critical second signal for activation of T-cells. if the antigen presenting cells do not express the appropriate counter-ligand (CD80 or CD86), T-cells may be anergized (rendered "blind").

myeloid lineage markers (CD11-18):

CD11b
CD13 ]
CD15 ]--- elevated levels of these indicate myeloid leukemia
CD33 ]

B-cell markers (CD19-low 20's):

CD19 - deficiency in CD19 indicates agammaglobulinemia (e.g. low IgG)
CD20
CD21 - also found on follicular dendritic cells
CD22
CD23

CD10 - aka CALLA (common acute lymphoblastic leukemia antigen), CD10 is found on pre B-cells and hence indicates acute B-cell leukemia when detected in high levels. functionally, CD10 is a protease that helps immature B-cells navigate through the extracellular matrix.
CD40 - provides a critical second signal for activation of B-cells, in particular for immunoglobulin class-switching (IgM --> IgE) and for affinity maturation.

natural killer-cell markers:

CD2
CD7
CD8 - expressed at much lower levels than in cytotoxic T-cells
CD16
CD56

monocyte markers:

CD4
CD13
CD14

miscellaneous CDs:

CD32 - neutrophils, monocytes/macrophages, B-cells
CD34 - blasts
CD45 - all white blood cells
(CD45RO - memOry cells)
(CD45RA - nAive cells)
CD64 - monocytes/macrophages

breathe, stretch, shake

2005-05-22T18:36:00.000-04:00

the reason we inhale is to acquire oxygen to fuel our cells, and the reason we exhale is to expel the carbon dioxide that our cells have byproduced. in particular, carbon dioxide (CO2) is a curious gas--found in trace amounts in the air, it's often maligned as a greenhouse gas but is otherwise fairly harmless. dissolved in water, however, CO2 becomes an acid, which is why plain seltzer water tastes mildly sour. this is partially why CO2 must constantly be pumped out of our cells and our blood, so that our bodies' systemic pH does not get so low as to become harmful to normal cellular function.

let's say that, for some unfortunate reason, your lung function has suddenly diminished, and you can't breathe as quickly or as strongly as you normally should. this is hypoventilation. as a result, carbon dioxide is backing up in your blood, and this is lowering your blood's pH (i.e. making it more acidic). how does your body compensate for low blood pH? it has two options: 1) eliminate the CO2 via the lungs, which it currently can't, or 2) neutralize the acid. option two is where your kidneys come in (and where a few of my comp exam questions are sure to attack).

in the event of respiratory acidosis--like the case just described--the kidneys provide a buffer to ameliorate the downward swing in pH: bicarbonate. bicarb is the same compound found in baking soda and antacids, and its action in all uses is similar--to neutralize acid. the kidneys know to produce bicarb because they can sense both the increase in dissolved arterial CO2 and the lowered pH of arterial blood (the kidneys also pump out and excrete acidic hydrogen ions). dissolved bicarbonate equilibrates with the hydrogen ions in solution freed by CO2, and normal pH is restored.

now, let's say that your lungs are working fine again, but for an unrelated yet still unfortunate reason, you decide to shoot vinegar into one of your veins. as this example shows, not all acidoses are caused by pulmonary insufficiency. lung function--and corresponding amount of dissolved CO2--may be perfectly normal when another type of acidosis sets in. this is termed metabolic acidosis, and the body's compensatory response in this situation is slightly different.

in metabolic acidosis, the kidneys still secrete extra bicarbonate to neutralize acidic blood. however, the amount of arterial CO2 in metabolic acidotic patients is below normal. this seems counterintuitive because raised--not lowered--arterial CO2 levels stimuate the kidney cells to excrete hydrogen ions, as described in the respiratory acidosis case. however, because the lungs are functional in this case, they attempt to correct the acidosis by hyperventilating (i know the causation here is muddled but just bear with me), resulting in the decreased dissolved CO2. this, in turn, means that less bicarb is ultimately needed to neutralize blood acid.

all this serves to answer the following prototypical "renal regulation of hydrogen ion balance" test question:

if a patient presents with an extracellular pH of 7.32, an arterial CO2 pressure of 60 mmHg, and an arterial bicarbonate concentration of 30 mEq/L, what type of acid-base disorder does he have?

answer: respiratory acidosis

likewise, if a patient presents with an extracellular pH of 7.21, a pCO2 of 25 mmHg, and a bicarb of 10 mEq/L, what type of acid-base disorder does he have?

answer: metabolic acidosis

(normal values approximately are: pH=7.4, pCO2=40, [HCO3-]=24)

c is for cookie

2005-05-21T23:06:00.000-04:00

in 9th grade, my math teacher wrote on the blackboard one of those cute classroom proverbs that makes teachers seem so wise. this one was a list--maybe 10 items long, i don't remember--of increasingly effective ways of learning. the least effective was reading from a book. the most effective was teaching another person. i grew to despise that math teacher, whom to this day i believe had it out for me and deliberately issued me a poor grade on my final exam, refusing to allow me--or my parents--to see the test. it was my first and last B in high school. needless to say, i'm over it.

but as for her top ten list of best learning methods, i think she was right. it's five days before my end-of-year comprehensive exam, i.e. five days before my first year of medical school is over. i don't necessarily have to pass in order to move on to next year, but i'd like to finish the year on a respectable note. for the past couple days i've sifted through my review books, highlighter in hand, carefully reading every previously-marked page. at this point though, the diminishing marginal utility of every page i read is depressing, and so in these increasingly desperate times i'm looking for a quick, high-yield method of retaining what i'm reading.

enter this shiny new blog. seeing as my primary blog continues to hum along nicely, and as it remains one of the best ways to keep in touch with many of my best friends, i've had trouble justifying this blog's existence. but i think i have a solution (albeit a dry, selfish, nerdy one). every day, starting today, i will post something i have learned in school. it might be a factoid presented to us in class, a summary of a journal article i skimmed in the afternoon, or a difficult concept i can't seem to untangle. whatever it is, i'm fairly sure i'll understand it better just by trying to write it clearly and palatably. and for you, well, maybe you'll find these daily doses of my medical education interesting. if not, i can hardly blame you.

so here's my contribution for the day:

do you remember the sesame street skits with cookie monster and the x-ray machine? cookie monster would step behind the x-ray screen, eat his cookie (100% of which would spray out of his mouth, but that's beside the point), and everyone would watch his cookie bolus make its way down his digestive tract. it was my introduction to gastrointestinal physiology, and i loved it.

so let's say you eat a cookie. after you've chewed it thoroughly and swallowed, the erstwhile cookie slithers down your esophagus, passes through the digestive pearly gates--the lower esophageal sphincter--and settles onto the hot, acid inner surface of your stomach. incidentally, your stomach knew the cookie was coming and made the appropriate preparations to receive it. it's in a relaxed state, thanks to the vasovagal reflex, and therefore ready to be filled. vagal nerve fibers released vasoactive intestinal peptide (VIP) onto myenteric motoneurons to reduce the resting tone of the stomach smooth muscle. also, before you even bit into the cookie, the G cells of your lower stomach (the antrum) released the digestive hormone gastrin into your bloodstream, thereby stimulating the secretion of hydrochloric acid by parietal cells and priming your stomach milieu for the now-famous cookie.

i mentioned the antrum portion of the stomach. the stomach is divided into roughly three sections--the fundus (top), the corpus (middle), and the antrum (bottom). gastric contractions, signaled by gastrin, start in the mid-corpus and increase in force towards the antrum. this asymmetric distribution of motor force results in the characteristic churning motion of the stomach, termed retropulsion. retropulsion pushes antral contents back towards the fundus, where the soupy stomach mixture hits the upper stomach wall and slides down towards the antrum, only to get pushed up again in the next contractile wave. these waves are slow, at roughly 3 per minute, which is why you don't feel your stomach pulsing after you eat. this continues until your cookie resembles putrid orange juice, and this is also where our story ends for today.

p.s. if you spot any mistakes--and there will be plenty i'm sure--please let me know, thanks.

hello

2005-05-16T22:27:00.000-04:00

google changed my life, and so i feel i owe it to them to jump ship from xanga one of these days. this blog will be my life preserver.