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April 2006 E-Newsletter

• Focus on Internal Medicine Careers: Infectious Diseases
• Internal Medicine Interest Group of the Month: State University of New York, Upstate Medical University at Syracuse
• Congratulations to the Winners of the Medical School Awards Program!
• MKSAP Questions (1,2)
• MKSAP Answers (1,2)

Focus on Internal Medicine Careers: Infectious Diseases

Jerrold Ellner, MD, FACP, Professor and Chair of Medicine at University of Medicine and Dentistry of New Jersey—New Jersey Medical School (UMDNJ—NJMS), whose amazing Infectious Disease career has taken him from tuberculosis research in Cleveland to AIDS vaccine trials in Uganda, talked with us about medical school, career options, internal medicine, and life. The interview was conducted by Tony R. Tarchichi, a third year student at UMDNJ—NJMS and the Central Atlantic Region Representative to the ACP Council of Student Members.

IMpact: Would you please give our readers a brief introduction to your career, fellowship training, and some of the things you have done?

Dr. Ellner: I was trained in basic immunology at the National Institutes of Health and was interested in how a human, or host, recognizes infectious agents, and focused on the interaction of antigen presenting cells (macrophages) with T-cells. I chose tuberculosis as a disease model. When you start to study infectious agents, like tuberculosis, you always have the issue that many people are exposed but only some get the disease. Over the years I’ve done studies, starting at the Cleveland Clinic and going to Uganda and Mexico City, where I’ve tried to understand the immunologic concomitance of tuberculosis. I started doing international research because, when you want to study a disease like tuberculosis you need to go to a place where tuberculosis is common and where a number of individuals are relatively healthy except for the prevalence of tuberculosis.

IMpact: Could you please quantify how much tuberculosis there is in the world for our readers who might not know?

Dr. Ellner: There are two million deaths from tuberculosis in the world annually. Ninety-five per cent of the cases are in developing nations, and 99% of the deaths are in developing nations. In the next ten to twenty years we’re likely to see major changes in the way we treat tuberculosis as a result of scientific advances.

IMpact: At some point in your career HIV became very prevalent. At what point did you decide that you didn’t want to completely change your research, but that you wanted to start incorporating HIV research into it?

Dr. Ellner: I was mid-career when HIV came along. I was one of the few people who was studying tuberculosis, and therefore I got more funding. I did go through a period where I had to decide if I wanted to stay in tuberculosis research or change to HIV. One of the reasons I stayed with tuberculosis was because I was an immunologist, not a virologist, and it seemed to me that I didn’t have the right to start work in HIV. I began to look at the impact of HIV on tuberculosis and vice versa.

IMpact: Some of the work you did regarding HIV was revolutionary. Could you tell us about the HIV vaccine study you did in Uganda?

Dr. Ellner: We did a very small HIV vaccine study. At the time the strain used in HIV vaccines was the North American strain, which was also known as clave B (a certain class of HIV), but we began using the strains endogenous to Uganda (clave A and D). The question was whether you could use a clave B vaccine to protect against the endogenous strains in Uganda. My role in the vaccine trial was mostly as a middle person. I developed very strong collegial collaborations with both scientists and public health officials in Uganda, so I was able to “broker” the vaccine trial there. My role became quite complicated because there were lots of ethical questions that arose, including the fact that we were testing a clave B vaccine in a country where that particular clave didn’t occur. It took three years before we could vaccinate the first person. I made it a point to be there for the whole study of 40 people. It was actually a proof of concept; we weren’t trying to find out if the vaccine was effective in preventing HIV, we were really just trying to see if any cross-reactivity occurred.

IMpact: Was there any cross-reactivity?

Dr. Ellner: Yes there was. We were working with an interesting vaccine; it was attenuated canary pox. At that time it looked to be a very promising vaccine because canary pox could infect mammalian cells but it couldn’t replicate. It could express the antigens on the surface of mammalian cells. One of the hurdles in AIDS vaccine development was to induce a CD8 response. Unfortunately, the vaccine studies (ours and others) showed that the vaccine only produced CD8 response in a small fraction of those who were immunized. This vaccine is no longer the leading candidate for large scale trials.

IMpact: Many researchers have a disease focus. Is it important for a medical student who is interested in research to figure out what disease or area they would be interested in researching?

Dr. Ellner: No, I think that the main goal should be to get yourself the best basic scientific training you can. With it, you can study a wide array of diseases, but without it, you’re very limited in terms of what you can do scientifically.

For example, take a disease like Multiple Sclerosis (MS). For fifty years investigators have tried every scientific approach, and we still don’t know a lot about its pathogenesis. As a student, or a physician, or even an MD, PhD with just your clinical training, you’re probably not going to have much of an impact, when all these great minds before you couldn’t figure it out. On the other hand, if you have really good basic science training, and if the area you train in is relevant to MS studies, then you can apply it to the disease.

IMpact: What advice would you like to give to students who want to go into internal medicine?

Dr. Ellner: Sometimes students think about their careers and base their decisions on what’s popular now. One thing we can be certain of is that medicine changes. I think the most important thing is for students to follow their own interests and take opportunities as they arise, rather than imagining that they can plan everything out in advance.

For instance, I started to work in tuberculosis because of my own scientific interests, not because of a real understanding within myself of how much of a problem tuberculosis was in the world. Then AIDS came along and changed so many things. Tuberculosis became regarded as much more of a public health problem in the US, whereas before AIDS it was not. Because of HIV, the US government had an interest in setting up collaborative projects in developing countries. So they set up a program, and one of my mentors, a Nobel Laureate in internal medicine, was very eager to get involved in training students in AIDS research. At this time both he and I were at Case Western. By chance, there were a couple of people at Case Western who had been volunteering in Uganda and my mentor then went on an initial visit to Uganda. As a Nobel Laureate (which he had won during his fellowship), he had never written a grant in his life but all doors were open to him, so he asked me to come along and help him.

This really changed my life. I wasn’t very sophisticated in what it took to develop collaborations internationally. As is usually the case, naiveté was an advantage. I got involved in a situation which was very complicated and where a skeptic would say that there’s very little chance of success, but timing is everything. Early on we got to do some studies and the program we had just grew and grew.

IMpact: So it seems like there was a lot of chance on your side?

Dr. Ellner: If you choose to go into private practice your career remains pretty much the same over time. An academic career, however, has various phases and it’s more likely that you’ll be influenced by serendipity and external events, and you might end up in places you never would have imagined while you were in medical school.

When I was a child, Africa was a forbidden continent. I never dreamed that I would visit there, let alone work there.

One of the reasons I came to work in Cleveland, however, is that there are very important problems in our inner cities. Devoting a big chunk of my life to improving health in other countries without trying to have a hand in doing something positive in my own country began to wear thin. I thought that maybe I could do something and have some positive impact by coming to NJMS in Newark, because there is a lot of HIV in the community.

IMpact: If a student wants to do internal medicine and is considering doing international health, would you recommend infectious disease to them as a fellowship?

Dr. Ellner: There are international studies related to areas other than infectious disease, but infectious diseases cause tremendous morbidity and mortality and are more amenable to intervention. In Uganda, for example, it would be nice to do something about hypertension or heart disease, but there’s no facility in the country to do a cardiac catheterization. For someone from Uganda to get a coronary artery bypass, they would have to go to India, UK, or the US. There are areas of health that have not been addressed because they are so costly. In infectious disease, however, if you have a vaccine, you can have a great deal of impact with little cost. Bill Gates has said that if an effective AIDS vaccine becomes available, he will use all his resources to make it available worldwide.

IMpact: What do you see as the top three diseases that could be cured by vaccines in the next 20 years?

Dr. Ellner: Malaria, Tuberculosis, and HIV.

IMpact: What would you say to medical students who are not choosing internal medicine as a career choice due to decreased salary, difficulty dealing with managed care, and lifestyle issues?

Dr. Ellner: I don’t have any easy answers to broad societal issues. I think if you want to do internal medicine, you can do it. There are many areas of the country that are underserved. The costs of malpractice insurance for internal medicine practice are much less than other areas of medicine, such as ob-gyn. I think more residents are choosing specialty training, but the pendulum shifts. There was greater interest in primary care, and now there is more subspecialty interest. There are many physicians who have received subspecialty training who are now practicing general internal medicine. I think training in infectious disease is particularly useful.

In terms of the financial consequences of career decisions, I think they receive a little too much play. Most people don’t choose medicine as a career because compensation is the biggest issue. I think it requires a little bit of soul searching as to why you chose a career in medicine and what your overall goals are. Do you want to take care of patients? Do you want to work in underserved communities? Do you want to work in affluent communities? There’s nothing wrong with that; someone has to take care of affluent people.

Many students already have a strong interest in nephrology, or cardiology, or whatever. My advice is to pursue whatever interests you most—even if you’re not sure exactly why it interests you—as opposed to trying to imagine where medicine will be 10 to 20 years from now. For example, right now within internal medicine, gastroenterology is a very popular specialty. If you come back 10 years from now, it’s possible that virtual colonoscopy will replace actual colonoscopy and we’ll have over-trained gastroenterologists. You never know. If you’re trying to get ahead of the wave, there are changes in internal medicine that I can see and others that I cannot. My advice is to follow your inclination. Hopefully profitability is not a major motivator for most medical students.

IMpact: So where do you see the field of internal medicine growing, expanding, or changing in the next 20 years?

Dr. Ellner: I think that there will probably be more pharmacogenomics. Therapy will probably be individualized based on the patient’s genomic structure. We’ll have a lot more information about whether someone is likely to respond or have adverse events than we currently do. I also think that there will be new diagnostic techniques so we’ll use approaches such as micro-arrays to try to diagnose tumors and infectious diseases. A lot of the current approaches might be extinct.

IMpact: So where do you see the field of infectious disease growing, expanding, or changing in the next 20 years?

Dr. Ellner: About 25 or 30 years ago, it was said that there was no longer a reason to train anyone in infectious diseases. Public perception was infectious disease had been conquered in the US. At that time, infectious disease was becoming too cerebral—then HIV came along. There’s a whole new chapter of infectious disease which is driven by acute medicine with new approaches to understand, prevent, and treat.

Infectious disease is one of those specialties perfect for those who have an interest in research because it allows them to still see patients clinically and also have a laboratory. If your interest is in dealing with diseases where the etiological agent can be identified and there’s a possibility of curing and/or preventing the disease, there will always be opportunities in infectious disease. I would definitely consider infectious disease as one of the bench-top to bedside specialties.

IMpact: Is there anything else you’d like to tell our medical student readers?

Dr. Ellner: Some of the genuine needs in global health are not evident to students as they go to college, then to medical school, then to residency, and ultimately make their career choices. I think that every student should try to have an experience in a developing country. Travel is one thing, but to actually be engaged in something related to your profession in a developing nation is different because it can make you rethink your career choice. I think almost every individual who came to work with us in Uganda had a life or career changing experience. I would encourage people, particularly in medical school, where you have some flexibility in your schedule, to try to do something internationally.

Internal Medicine Interest Group of the Month: State University of New York, Upstate Medical University at Syracuse

The key to our vibrant Internal Medicine Interest Group (IMIG) at State University of New York (SUNY), Upstate Medical University at Syracuse resides in the keenly motivated and creative group officers, in association with highly supportive group advisors, all of whom have eagerly contributed their various skills to the novel approach we have instituted this year in promoting careers in internal medicine. The IMIG officers are: Sara Grethlein MD, FACP and David Duggan, MD, FACP (Faculty Advisors); James J. Calloway (President); Anita Sargent (Chief Editor of The Pulse); Sherin Varghese (Vice President); Cynthia Lien (Treasurer/Coordinator); Tiffany Denepitiya (Secretary); and Yung Lyou (Webmaster). Joining the ACP as Medical Student Members and employing the use of ACP funding for group activities has also proven to be an invaluable resource.

Rather than merely repeating what has been done in past years, we have consented as a group to create fresh ideas for giving students exposure to internal medicine careers. Early in the year we conducted table conferences featuring physicians from different internal medicine subspecialties who offered invaluable information on the requirements and lifestyle considerations of each. During December 2005 we hosted the highly successful First Annual Winter Holiday Concert at Upstate, in which we brought together faculty and students while promoting an awareness of careers in internal medicine. As an added bonus, the video recording of the concert played throughout our University Hospital, most notably bringing smiles to the faces of inpatients in the pediatric wards during the holiday season. We are currently in the planning stages for our next event, “Cardiology in 2006: Prevention and Transplantation,” featuring an alumnus of Upstate, John Bisognano, MD, FACP.

We have developed our own signature publication, The Pulse, that features high-quality articles by medical students in conjunction with faculty physicians. Our publication has proven to be the most efficient manner for our group to connect with the student body. The Pulse highlights current health topics important to internal medicine physicians and the innovative research done by students and faculty at Upstate. We also feature medical case studies, internal medicine subspecialty columns, and interviews with patients, physicians, and residents.

In an attempt to give greater exposure to our group and to form connections with other IMIGs, we have taken the initiative to establish our own group website. We have aimed to set a precedent that will continue to inspire the minds of future internal medicine physicians at Upstate for years to come.

James J. Calloway and Anita Sargent, SUNY Upstate Medical University at Syracuse

Congratulations to the Winners of the Medical School Awards Program!

At the Associates and Medical Students Recognition Reception, held Saturday, April 8, 2006 during Annual Session, the following seven schools were honored for their outstanding efforts to increase Medical Student Membership in the American College of Physicians. The awards program recognized schools that increased their Medical Student Membership in the College by 15% or more of their student body from July 1, 2005 through March 15, 2006. Certificates of Merit were awarded to:

University of Utah (28.3% increase)
Florida State University (23.7% increase)
Memorial University of Newfoundland (18.8% increase)
Wright State University (18.4% increase)
University of South Carolina (18.3% increase)
University of Hawaii (17.4% increase)
State University of New York at Stony Brook (15.4% increase)

The two top winners, University of Utah and Florida State University, were also awarded cash prizes of $300 and $200, respectively, in support of internal medicine interest group activities.

The Medical School Awards Program, sponsored by the Council of Student Members, is in its seventh year. For more information about this program, please contact Patty Moore, Medical Student Coordinator, by phone at (800) 523-1546 ext. 2749 or by e-mail at pmoore@acponline.org.

MKSAP for Students 3 – Question 1

A 66-year-old woman is evaluated for 6 months of intermittent substernal chest discomfort. This discomfort is characterized as heaviness that lasts approximately 15 minutes and is provoked by emotional stress and sometimes by physical exertion, and is not related to meals or relieved by antacids. She is taking no medications.

On physical examination, she is thin, with a pulse rate of 60/min, respiration rate of 12/min, and blood pressure of 136/86 mm Hg. Her lungs are clear, and the chest wall is nontender to palpation. Cardiac examination reveals a normal apical impulse, an S4, decreased intensity of the S1, and a paradoxically split S2. The remainder of the examination is normal.

The patient's electrocardiogram is shown.

Which of the following findings is present on the electrocardiogram?

( A ) Left bundle-branch block
( B ) Right bundle-branch block
( C ) First-degree atrioventricular block
( D ) Second-degree atrioventricular block
( E ) Third-degree (complete) atrioventricular block

MKSAP for Students 3 – Question 2

A 53-year-old woman with hypertension and a 12-year history of type 2 diabetes mellitus is evaluated for antihypertensive drug therapy. She is overweight, but has lost 4.4 kg (10 lb) on a heart-healthy, low-sodium diet. Her blood pressure is 158/90 mm Hg. Her hemoglobin A1c is 8.6%, serum creatinine is 1.4 mg/dL, and blood urea nitrogen level is 28 mg/dL.

Which of the following agents should be included in this patient's initial drug therapy?

( A ) Amlodipine
( B ) Hydrochlorothiazide
( C ) Metoprolol
( D ) Ramipril
( E ) Transdermal clonidine

MKSAP Answer 1

Answer = A

Educational Objective: Diagnose left bundle-branch block

This patient has a left bundle-branch block. The salient features of left bundle-branch block include a QS or rS deflection in lead V1 and monophasic R waves in leads I, V5, and V6. The usual small Q waves in V6 and I that reflect septal depolarization are absent in left bundle-branch block. Right bundle-branch block is characterized by an M-shaped QRS complex in V1; a wide S wave in V6; and a wide S wave in lead I. First-degree atrioventricular block is associated with a PR interval exceeding 0.20 seconds. Second-degree atrioventricular block is established when not all beats are conducted from the atria to the ventricles (“dropped beats”). It is recognized in the tracing by the presence of isolated P waves that are not followed by a QRS complex. Complete heart block is characterized by complete absence of conduction from the atria to the ventricles; the P waves and the QRS complexes are completely independent of each other.

In this case, the importance of the left bundle-branch block is related to the proper selection of tests to evaluate the patient's chest pain. This patient has atypical chest pain and an intermediate pretest likelihood of coronary artery disease, and is an appropriate candidate for further noninvasive evaluation. However, treadmill exercise electrocardiography cannot be interpreted in the presence of a left bundle-branch block. The usual exercise-induced ST segment depression that is diagnostic of ischemia cannot be observed in the presence of this conduction abnormality.

Further evaluation of this patient should be done with an imaging modality, such as radionuclide perfusion imaging, using a vasodilator stressor, such as adenosine or dipyridamole.

References

Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, et al. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol. 2002;40:1531-40.

MKSAP Answer 2

Answer = D

Educational Objective: Recognize the importance of prescribing an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker to treat hypertension in a patient with diabetes.

This patient has two risk factors that favor the use of an angiotensin-converting enzyme inhibitor (ACE) or possibly an angiotensin receptor blocker (ARB): diabetes mellitus and elevated serum creatinine. The HOPE trial in diabetics (MICRO-HOPE) and other data in patients with hypertension show the benefit of an ACE inhibitor for reducing the incidence of vascular events in patients with diabetes. The LIFE trial showed a reduction in the incidence of clinical events in patients with hypertension and diabetes who were treated with losartan (an ARB) compared with those who were treated with atenolol. Furthermore, both of these classes of agents have been shown to slow the progression of renal disease in patients with diabetes and proteinuria. There has been no progressive trial comparing the two classes of agents. Because they may sometimes worsen the serum creatinine level, they must be initiated carefully in patients who have azotemia. Both ÿ-blockers and calcium channel blockers are appropriate agents for use in patients with diabetes, but not as first-line therapy. Similarly, randomized trials strongly support the efficacy of thiazide diuretics in patients with hypertension (ALLHAT); however, these agents offer no specific benefits in patients with diabetes. Clonidine offers no vascular or renal protection.

References

Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145-53.

Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:1004-10.

Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355:253-9. Erratum in: Lancet 2000;356:860.

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-97.

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