I N S I D E

Chairman’s Message ................................................. 2

Profile, Endocrinology ............................................... 2

Faculty Promotions and Appointments .................. 2

Biodefense and Emerging Pathogens ..................... 3

Barrington Primary Care ........................................... 3

Biomedical Ethics .................................................... 4-5

Doctors/Researchers Participate In AIDS Ride ....... 5

Improving ICU Care in Rhode Island ....................... 6

Research Awards ........................................................ 7

Grand Rounds ............................................................. 8

O c t o b e r 2 0 0 5 • V o l u m e 6 • I s s u e 4 • P u b l i s h e d Q u a r t e r l y

www.brownmedicine.org

Letter from Dean Eli AdashiDear Friends,After nine months as dean of medicine and biological sciences, I am pleased by theprogress made and am eager to continue to refine a vision for Brown Medical Schooland its teaching hospital partners. I remain keen to realize our collective potential. Ilook to the Department of Medicine, to its proud tradition, its bright future and itsvisionary leadership, as a key partner in the road ahead. I consider myself privileged tobe working with Dr. Edward J. Wing as well as with his division chiefs, faculty, andtrainees.

Since arriving in January, I have made it a point of meeting with faculty; staff;undergraduate, graduate, medical and postdoctoral students; alumni and friends; and,of course, the leadership of our teaching hospital partners. I work continually tounderstand the nature of the issues and to identify priorities most in need of attention.Our agenda is undeniably ambitious, but I have no doubt that if we align and optimizeour skills, talents, energy, and expertise, there is little we cannot accomplish.

On the administrative front I have undertaken a restructuring of the deanery, includingthe appointment of Dr. Phillip A. Gruppuso as associate dean of medical education; ofDr. Stephen R. Smith as associate dean of virtual curriculum; and of Mr. John M. Deeleyas executive dean for administration. We are also moving forward with the creation ofnew positions with an eye toward enhancing our research enterprise and serving faculty

and students throughout our life and health sciences community. Specifically, three new deanships will be dedicated to graduateand postdoctoral studies, cross-disciplinary sciences, and translational science.

In the educational realm, we are making great strides in redesigning the curriculum, which we intend to be innovative, modern,relevant, and highly integrated. The “early bird” in this regard is the newly implemented “Doctoring” course for first- andsecond-years, in which students are exposed to the outpatient clinical setting in their very first week of school. Among its novelfeatures, the new curricular plan will emphasize flexibility so that early on, students may pursue their own specialized interestsin medicine. I believe that the result of this reform effort will be yet anothereducational product we can characterize as a “Brown Med original.” Work has alsobegun to upgrade the teaching and student spaces in the Biomedical Center and toaccentuate Brown Medical School’s identity through improved signage.

With our teaching hospital partners, we have established Partnership Boards topromote collaboration and programmatic coordination. The Boards meet regularlyand constitute excellent venues for open communication. We are also striving –together – to establish a network of reciprocating Institutional Review Boards so asto minimize impediments to multilateral collaboration. Further, we are in the midstof recruiting the inaugural permanent chair of the Department of EmergencyMedicine, a position we hope to fill before the end of the calendar year.

In closing, I would like to thank one and all for the support I have received and forthe warm welcome. I applaud the Department of Medicine for its continued excellencein education, research and clinical care and look forward to working closely withyou all on an ongoing basis.

Best,

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Chairman’s MessageEdward J. Wing, MD

There are exciting newinitiatives in the Department ofMedicine, which will occur, inthe next year. Dr. Frank Basile’sprimary care practice group ofeight physicians will be movingfrom the MOC on DudleyStreet to a new leased buildingon Providence’s East Side, at285 Governor Street. This is a

12,000 square foot building that will provide anoutstanding new site for multi-specialty care. Not onlywill primary care physicians have their own practiceslocated there, but specialties such as Cardiology,Dermatology, GI, General Surgery, Infectious Disease,Nephrology, Podiatry, and Pulmonary will be available.This exciting new practice site with convenient parkingand a remarkable location will be opening in December.

The Department is currently in the middle of a searchfor a new director of the Division of Hematology/Oncology. Dr. Ed Wittels and Dr. Fred Schiffman havedone a commendable job running the Division and theCancer center. The new individual will be the permanentDirector of Hematology/Oncology and will hold theCalabresi Chair. We currently have six candidates whoare coming through for the first visit. These areindividuals from distinguished institutions, includingour own, Harvard, Northwestern, Cleveland, andPittsburgh. The new Director will take the reins of analready exceptional division. He/She will be chargedwith growing the clinical specialties in oncology andhematology as well as developing both clinical and basicresearch. Our international programs continue to grow.Drs. Sid Braman and Muhanned Abu-Hijleh and I visitedJordan recently to sign an agreement to exchangepulmonary fellows. This will add a new dimension toour existing international programs in Africa, Cambodiaand India in addition to providing opportunities forboth clinical and research.

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Haiyan Xu, MD, PhD, recently joined the Departmentof Medicine as an assistant professor of medicine in theDivision of Endocrinology, Diabetes and Metabolism.Dr. Xu received her MD and MS degrees from BeijingMedical University. She obtained her Ph.D. from HarvardUniversity where she was the recipient of the Edgar HaberAward in Biological Sciences and the Medical Sigma XiHarvard-Radcliffe Chapter Scientific Recognition Award.She was a researcher in the Department of MetabolicDisease Biology at Millennium Pharmaceuticals, Inc,before moving to the Metabolic Disease ResearchDivision of Abbott Laboratories.

Dr. Xu’s research interests have centered on themechanisms of obesity related insulin resistance and type2 diabetes. Her work is particularly focused on thecorrelation of adipose inflammation and insulin signalingin obesity, novel factors in the regulation of adiposeenergy metabolism, and the control mechanisms ofhepatic gluconeogenesis. Her discovery of obesity-induced macrophage infiltration in adipose tissuerevealed a new mechanism contributing to the systemicinflammatory state observed in obese and diabeticpatients. This work was selected as one of the milestonediscoveries in the 80-year publication history of theJournal of Clinical Investigation. Dr. Xu’s currentresearch projectsinclude studies on thetriggering factorsresponsible foro b e s i t y - i n d u c e dadipose macrophageinfiltration, the rolesof novel AMP relatedkinases in adipocytebiology, and the effectsof two phosphataseson insulin signaling inliver and adiposetissue.

Endocrinology

Faculty Promotions and AppointmentsMemorial Hospital of Rhode Island

Hematology/OncologyHumera Khurshid, MD, BMBS, Assistant Professor

Rhode Island HospitalCardiologyGong Xin Liu, M.D., Ph.D., Assistant Professor ofMedicine (Research)

NephrologyAngelito Yango, MD, Assistant Professor

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Research Spotlight

to an NIAID Biodefense initiative,experiments are also underway todevelop a DNA-based vaccine and animmunization strategy to elicitprotective mucosal immunity (ADeGroot, collaborator). The efficacy ofresultant vaccine candidates will betested in “humanized,” HLA class I andclass II double-transgenic micechallenged with aerosolized F.tularensis.

In addition to these studies, substantialeffort in our laboratory is dedicated todelineating the factors that effectclearance of bacteria from thebloodstream and their elimination in theliver. Previously, we reported thatefficient elimination depends upon thecomplex interaction of resident tissuemacrophages (Kupffer cells) that line theliver sinusoids and bactericidalneutrophils, which accumulate rapidlyin the liver in response to infection (EJWing, collaborator). To our knowledge,these studies represent the firstdocumented evidence to indicate thatthe critical function of Kupffer cells mayrelate far more to their ability toregulate the proinflammatory orantimicrobial activities of other celltypes (e.g., neutrophils in this instance)

than to their own capacity to ingest andkill microorganisms.

The ability of Kupffer cells to modulatethe biological activity of other cells issupported by our recent studiesdemonstrating the Kupffer cell-dependent abrogation of cholestatic liverinjury in a mouse model (TF Tracy, Jr.,collaborator). Hepatocellular apoptosisand necrosis were exacerbated in Kupffercell-depleted or IL-6-deficient micefollowing ligation of the common bileduct. Recombinant IL-6 administered atthe time of surgery reversed the severeliver damage seen otherwise in Kupffercell-depleted animals, thus demonstratingthe critical role of IL-6 in protection.Similarly, invariant (i)NKT cells (a uniqueT cell population characterized by itsability to recognize glycolipids ratherthan peptides of host cell origin) alleviateliver injury in this model. Relative towild-type animals, iNKT cell-deficientmice exhibit increased liver damagefollowing bile duct ligation (L Brossay,collaborator). This latter finding suggeststhe principal function of hepatic iNKTcells may be to moderate inflammationand suppress tissue injury rather than tomediate innate immunity to bacterialpathogens as broadly speculated in theliterature.

Biodefense and Emerging PathogensStephen Gregory, MD

F r a n c i s e l l atularensis, thecausative agent oftularemia, is one ofthe most infectiousbacteria known toman, as few as 10organisms cancause fatal disease.

Aerosolized F. tularensis represents apotentially dangerous biological weapondue to its high degree of infectivity, easeof dissemination and capacity to causesevere illness. No safe vaccine ispresently available for general use.Currently, our laboratory is conductingexperiments to determine the factorsthat effect protective immunity topneumonic tularemia using laser capturemicrodissection (LCM) to isolaterelevant immune cell populations fromthe lungs of immunized and non-immunized mice infected with F.tularensis, and DNA microarray andreal-time RT-PCR analyses tocharacterize gene expression. Thesignificance of specific gene products tohost defenses will be determined bytreating mice with sequence-specificsiRNA to knock-down gene expressionand product synthesis (A Ayala and BRamratnam, collaborators). In response

Barrington Primary CareThe University Medicine Foundation primary care site located on the Wampanoag Trail in East Providence was initiallystarted by Dr. Edward J. Stulik in 1990 as part of the Rhode Island Hospital Foundation. Dr. Stefano L. Cazzanigajoined the practice in 1994. Both physicians are board certified in Internal Medicine. The physicians actively admitpatients to Rhode Island Hospital. They attend their patients while in the hospital and also at various nursing homesin the area. The doctors are both involved in teaching activities at Brown Medical School.

Their office is located in the Barrington Medical Building with ample free parking. Because the building also houses aLifespan Laboratory and a RI Medical Imaging Facility, this UMF site is able to provide high quality health care in alocation convenient for the East Bay residents of Barrington, Warren, Bristol, East Providence and Seekonk,Massachusetts.

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Historically taught in the form ofSocratic dialogue and questioning,

medical ethics education has become arigorous discipline with bothphilosophical grounding and practicalapplication to real world medicalsituations. The Center for BiomedicalEthics oversees education in medicalethics in the clerkships for the medicalstudents and for those in the Brown-affiliated Internal Medicine trainingprograms. The Center was founded bynoted medical ethicist and formerBrown Philosophy professor Dan Brockand nurtured by former BMS AssociateDean of Medicine (Humanities andSocial Sciences) Ed Beiser. Tom Bledsoe

� It is 4 a.m. and you are the senior resident on theovernight shift in the Respiratory Intensive Care Unit.One of your patients was taken off the respirator thatafternoon after a long conversation with her familyabout her prospects and her previously expressed wishesabout her care. She has been breathing agonally for closeto eight hours. Her family at the bedside asks you tojoin them in the hall and son wonders whether wecouldn’t just give a little more morphine to “relieve hersuffering.”

� You are starting a new month on the medical serviceand inherit an elderly patient with advanced dementiawho has been rehospitalized with another aspirationpneumonia. The intern informs you her unemployedson (who lives in the home she owns) is the familyspokesperson and has told the team to continue allaggressive life-support measures.

� You are a medical student starting the third month ofyour medicine clerkship and are secure in the knowledgethat your new patient, while quite ill, has had a chanceto make known to you his wishes regarding end-of-lifecare and a preferred surrogate decision maker, shouldone become necessary, and that you’ve documentedthese in the medical record. You’ve even helped guidehim through the Rhode Island statutory advancedirective form.

Biomedical Ethics in The Brown Medicine Clerkships and TrainingProgramsTom Bledsoe, MDInterim DirectorCenter for Biomedical Ethics, Brown Medical School

Dr. Tom Bledsoe lectures medical students and residents at Rhode Island Hospital.

MD is currently Interim Director and isassisted by Michael Felder DO, JayBaruch MD, Deirdre Fearon MD, BarryWall MD, Ed Forman MD and RosalindLadd PhD. Drs. Bledsoe, Felder andBaruch are responsible for teaching inthe medicine programs at Rhode IslandHospital, the Miriam Hospital, the VAMedical Center and at MemorialHospital.

We have four basic goals in teachingmedical ethics:First, the students and residents shouldknow the basic facts underlyingcommon ethical dilemmas. Many of themost problematic areas of medical ethics

since its inception as a field in the 1960’s,such as deciding for others andwithholding and withdrawing care at theend of life, now have fairly wellestablished lines of thought as well asprocedures and even legal standards. Anexample is the development of theRhode Island advance directive form(available on-line at http://www.lifespan.org/Services/Ethics/DPAHC/. There are points of knowledgeabout who can make decisions for othersand how those decisions should bemade. There are points of knowledge

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about the elements of informed decision-making that can be a usefulguide to medical professionals in discussing testing and treatment optionswith their patients.

The second goal is that the students and residents be able to recognizethe ethical dimension present in all medical interactions and specificallyto recognize ethical conflict. Decisions about care for a patient withAlzheimer’s disease and dementia cannot be made on a purely “medi-cal” level. Is it “best” to treat the pneumonia, or to treat only for comfort?Even a new prescription for hypertension involves ethical aspects. Is thepatient aware of the cost of this medication? How much does he or sheneed to know about possible side effects?

The third goal is that the students and residents develop a practice stylethat incorporates “preventive ethics.” How can this ethical dilemma beavoided next time a similar clinical situation arises? An important aspectof this goal is nurturing and developing ethical sensitivity. As the studentsand residents enter the medical field and encounter new situations, theyare frequently made uncomfortable or uneasy by situations. All too often,the demands of a hectic training program allow them to simply moveon; the rotation is over and the situation passes (or is swept under therug). This goal involves using those experiences and learning from them.

The fourth goal is a variation on the famous “Primum non nocere,”and is “Primum non tacere,” which means “first, be not silent.” Thereis real risk to patients in silence in the setting of ethical conflict, and themost sensitive student or resident may do his or her patients a greatservice by speaking up and seeking open discussion, either to the teamor to the institutional ethics committee. There is also great risk for thetrainee, for seeing ethical breaches in the practice of medicine andremaining silent greatly raises the risk of burnout and departure fromthe practice of clinical medicine.

The students have a defined curriculum in ethics on the medicineclerkship and have sessions on advance directives and surrogate decision-making, informed consent and on medical error. Every month on themedical service includes a “ward ethics rounds.” These resident andstudent sessions allow the medical teams to bring forward ethicalsituations or conflicts they have encountered on the wards for opendiscussion, community ethical deliberation and problem solving. Thepreventive ethics review is incorporated here.

In addition, both categorical and primary care residents have sessionsdevoted to medical ethics in the ambulatory block months (which are)dedicated to the goals of medicine and models of the doctor-patientrelationship, informed consent, confidentiality, physician as gatekeeperand other outpatient ethical issues and topics.

A classic conundrum in medical ethics is whether creating ethicalphysicians is possible, or whether it is the admissions office’sresponsibility to accept ethical individuals, who then are trained asphysicians. We believe that our trainees are ethical, but that they needto be taught to trust their instincts when a medical situation makesthem uncomfortable, that they need to know where to turn for help andguidance in these situations, and that the ethical practice of medicinegives them the best hope for a long, satisfying and rewarding career inmedicine.

Doctors/ResearchersParticipate In AIDS RideKelly McGarry, MDDrs. Laura Ofstead and Kelly McGarry (both ofGeneral Internal Medicine) and Meg Hebert(General Internal Medicine Research Unit)completed a 5-day, 500-mile bike ride betweenSeptember 7-11th, 2005. RIDE FAR (Ride ForAIDS Resources), as it is known, was created in1989 by Brown University graduate, artist andillustrator, Suzy Becker, to raise money andawareness for HIV/AIDS. 100% of the proceedsgo to support the cause. Not a single dollar goesto overhead expenses.

Thus far RIDE FAR 9 has raised over $100,000this year alone. This year’s money will go to anAIDS organization in Namibia, Project Informin California and 1/3 of the money will go to alocal organization designated by each of theriders. Laura, Kelly and Meg all donated theirmoney to AIDS Care Ocean State. Anyonewishing to contribute can still do so by mailing atax-deductible contribution to RIDE FAR 9 andsending it to one of the riders above c/o GeneralInternal Medicine, Rhode Island Hospital, JaneBrown Ground, Suite 0100, Providence, RI,02903. Kelly, Laura and Meg wish to thank thosewho have already generously given.

Left to right - Shellie Sylvia, Laura Ofstead,Kelly McGarry, Meg Hebert

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Improving ICU Care in Rhode Island: A Collaborative Statewide EffortLynn McNicoll, MD, FRCPC, Vera A. De Palo, MD, Cathy E. Duquette, Ph.D., RN, Laura L. Adams, R.N.

Recent literature has shown thatintensive care unit (ICU) care andoutcomes can be significantly improvedby implementing evidence-basedpractices.1 Implementing five evidence-based practices could prevent 167,819ICU deaths nationally.2 Studies haveshown that 17% of ICU patients suffera serious adverse event and are fourtimes more likely to die or have higherhospital costs.3,4 Last winter, the RhodeIsland Quality Institute, along withQuality Partners of Rhode Island (RI)and the Hospital Association of RI,developed a project plan for the RI ICUCollaborative and embarked on thequest to obtain financial support tobring successful strategies for improvingICU care to the entire state of RI. Thetwo larger health care insurers of RI,Blue Cross Blue Shield of Rhode Islandand United Healthcare, have generouslyagreed to sponsor the statewide programmanagement and hospitals have agreedto support internal program costs forparticipation. The RI ICU Collaborativelaunched officially in September 2005.

Three states - Michigan, Maryland, andNew Jersey – have implemented similarcollaboratives with excellent results. Inthe Michigan collaborative, 31% havefive or more months with no ventilatorassociated pneumonia and 31% havefive or more months with no catheter-

related blood stream infections.5

Mortality and length of stay werereduced by 46.7% and 47.3%respectively. Building on the experienceand lessons learned from these statecollaboratives and using the expertisefrom Johns Hopkins University, andtools from Voluntary HospitalAssociation’s (VHA) Transforming Carein the ICU project, the RI ICUCollaborative hopes to achieve similarresults.

RI currently has 11 general acute carehospitals that have one or more adultICUs. These hospitals include a total of16 adult intensive care units across theState with the total capacity of 263 beds,distributed as shown in Table 1.

This Collaborative aims to improve carefor hospitalized ICU patients specificallyto reduce length of stay and reducecomplications and associated costs byimplementing and evaluating one ormore of the following in the adult ICUsetting in hospitals in RI: ComprehensiveUnit-based Safety Program (CUSP) toimprove patient safety culture, catheterrelated blood stream infections,ventilator care, and sepsis care. Further,this Collaborative seeks to improveefficiency, change culture, improvestaffing, and subsequently, improvepatient, family, and staff satisfaction.

In addition to the benefits of improvedcare provided to patients who need orreceive ICU care, hospitals and directcare providers will benefit from; trainingin the science of safety and modernimprovement techniques; a SafetyCulture Survey; and sharing, learning,and practicing strategies in a safe,supportive environment. Conservativecost savings estimates for ventilator-associated pneumonia preventionapproach $6.3 million.

This Collaborative is designed to beconsistent with other applicable patientsafety and quality improvementprograms; the Institute for HealthcareImprovement (IHI), the JointCommission of Accredited HealthcareOrganizations (JCAHO) requirements,and CMS requirements.

Hospital ICUs represent care areas withgreat opportunity to prevent medicaldeath and reduce cost. While hospitalsin RI have already taken steps toimprove care in the ICU setting,participation in this Collaborative willenable hospitals to learn from otherstates that have demonstrated dramaticimprovement in ICU care, allowhospitals to share best practices andlessons learned, and improve the qualityof ICU care provided to all RhodeIslanders.

Table 1.Hospital Number Percentage of 2003 Percentage

Adult ICU Beds Total ICU Beds ICU Patient Total VolumeStatewide Volume Statewide

Kent 15 5.7% 918 5.8%Landmark 8 3.0% 506 3.2%Memorial 18 6.8% 745 4.7%Miriam 35 13.3% 1405 8.8%

Newport 10 3.8% 620 3.9%Rhode Island 122 46.4% 7674 48.1%

Roger Williams 14 5.3% 1613 10.1%South County 8 3.0% 598 3.8%St. Joseph’s 15 5.7% 784 4.9%

VA Medical Center 8 3.0% 392 2.5%Westerly 10 3.8% 689 4.3%

Total 263 100.0% 15,944 100.0%

Lynn McNicoll, MD, FRCPC is the clinical consultant to Quality Partners ofRhode Island for the hospital quality indicators and Assistant Professor at theBrown University School of Medicine.Vera A. De Palo, MD, is the director of the medical ICU at Memorial Hospitalof Rhode Island and Associate Professor of Medicine at the Brown UniversitySchool of Medicine.Cathy E. Duquette, Ph.D., RN is Senior Vice President at the HospitalAssociation of Rhode Island and is Clinical Assistant Professor of CommunityHealth at Brown University.Laura L. Adams is President and Chief Executive Officer of the Rhode IslandQuality Institute.

REFERENCES1. Institute of Medicine: To err is human. Washington, DC, National Academies Press, 19992. Pronovost PJ, Rinke ML, Emery K, et al: Interventions to reduce mortality among patientstreated in intensive care units. Journal of Critical Care. 2004; 19(3): 158-164.3. Andrews LB, Stocking C, Krizek T, et al. An alternative strategy for studying adverse events inmedical care. Lancet. 1997; 349(9048):309-313.4. Iezzoni LI, Ash AS, Shwartz M, et al: Predicting who dies depends on how severity ismeasured. Annals of Internal Medicine. 1995; 123(10): 763-7705. Sean Berenholtz, personal communication, March 28, 2005.

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Research AwardsDAWN ABBOTT, MD, in the division ofCardiology, was awarded $40,000 in fundingfrom the American College of Cardiology fora project titled ‘Prognostic AngiographicFindings in Patients with Acute CoronarySyndromes (ACS) Undergoing PercutaneousCoronary Intervention (PCI).’ The project willdevelop a database of angiographic variablessuch as extent of coronary heart diseases,coronary flow, ulceration, thrombus,calcification, and the presence of coronarycollateral circulation. An analysis of thesevariables will hopefully help guide thetreatment plan for patients with ACSundergoing PCI.

JANE CARTER MD, in the division ofInfectious Diseases has received funding fromthe Centers of Disease Control via a five yearsubcontract averaging $32,000 direct cost peryear with Indiana University for the‘Presidential Expansion Project for AIDS Relief(PEPFAR).’ Dr. Carter is using these funds torebuild the infrastructure for diagnosis andtreatment of TB in the western regions ofKenya. She will also develop diagnostic andtreatment algorithms for respiratory infectionsas well as noninfectious complications of HIV/AIDS including the ongoing development ofthe fiber optic bronchoscope program at MoiTeaching and Referral Hospital in Kenya.

SUSAN CU-UVIN, MD, in the division ofInfectious Diseases has received a K-24‘Midcareer Investigator Award in PatientOriented-Research’ from the NationalInstitutes of Health. This five-year awardaveraging $136,700 direct cost per year isgiven to highly successful patient-orientedresearchers with a proven track record inresearch and teaching. The funds are intendedto provide salary support and other fundingto provide Dr. Cu-Uvin with the dedicated timeand effort to mentor junior investigators inresearch. Dr. Cu-uvin’s nationally recognizedexpertise on critical issues related to HIV inwomen including HIV treatment andprevention provides the framework andspecificity of her mentoring role.

JI SU LI, PHD in the division of Gastroenter-ology, has received a funding from the NationalInstitutes of Health for an R-21 two yearproject averaging $150,500 direct cost per year‘Molecular Targets for Interruption ofHepadnavirus Infection.’ The specific aims ofthis project are to 1) investigate the molecularbasis whereby p120 (a duck Hepatitis B(DBHV) pre-S envelope-interacting protein)mediates DBHV infection. 2) Determine thecontribution of proprotein covertases toDBHV infectivity. 3) Evaluate p120 as well asp170 (another DBHV pre-S envelope-interact-ing protein) as molecular targets forintervention of DBHV infection. The hope isthat these studies will contribute to the under-standing of the early events of hepadnavirusinfection and may lead to the development ofnovel antiviral strategies for prevention of HBVinduced liver cancer.

EDUARDO NILLNI, PHD, in the division ofEndocrinology, has received a competingcontinuation R01 four-year grant averaging$200,000 direct cost per year from theNational Institutes of Health for a project titled‘ProTRH Gene Transcription and Biosynthesisof Leptin.’ Continuing the previously fundedwork on leptin, the laboratory will further testthe interactions that exist between the leptininduced direct and indirect pathway onactivation of thyrotropin-releasing hormone(TRH) neurons and characterize how thissubset of TRH neurons then acts on theHypothalamic-Pituitary-Thyroid axis, utilizingan in vivo model.

BHARAT RAMRATNAM MD, division ofInfectious Diseases, has been awarded an R01five-year award averaging $279,900 direct costper year from the National Institutes of Healthfor a project titled ‘Overcoming HIV-1Resistance to RNA Interference.’ The grantfocuses on the therapeutic potential of RNAinterference (RNAi) in preventingcervicovaginal HIV-1 transmission. Thedetailed specific aims are to 1) design optimizedshort interfering RNA (siRNA) targetingCCR5 and determine their gene splicing

kinetics in the cervicovaginal mucosa oftransgenic mice. 2) Determine whether serialsiRNA mediated knock down of cervicovaginalexpression leads to prolonged CCR5knockdown. 3) Use RNAi to define theepithelial factors associated with HIV-1transmission.

JOSIAH RICH, MD, in the division ofInfectious Diseases, has received an R01 five-year award averaging $250,000 direct cost peryear from the National Institutes of Health forthe project ‘Opiate Replacement Therapy atRelease from Incarceration.’ This grant willevaluate the effectiveness of initiating opiatereplacement therapy prior to release fromincarceration on reducing HIV risk behaviors.A randomized controlled trial will determinewhether initiating opiate replacement therapyprior to release from prison is a more effectivestrategy than referral to methadone treatmentprograms at the time of release fromincarceration. The effects on reducing HIV riskbehaviors, reducing recidivism, and drugtreatment attendance will be studied todetermine the value of this treatmentmethodology.

ALAN ROSMARIN, MD, in the division ofMedical Oncology, has received an R01 four-year award averaging $250,000 direct cost peryear funded by the National Institutes of Healthtitled ‘GABP Transcription Factor in MyeloidDifferentiation.’ The goal of the proposal is tocomprehensively characterize the role of thetranscription factor GA-Binding Protein(GABP) in myeloid differentiation and geneexpression. GABP is one of a limited numberof transcription factors that regulate myeloidcells. Defects in transcription factors areassociated with acute myelogenous leukemia.The studies will test the following hypotheses:1) GABP mediates an alternative pathway togranulocytic differentiation. 2) GABPparticipates in an enhancesome – a multiproteincomplex that regulates myeloid gene expression.3) GABP is required for granulocytic survivaland/or differentiation and it will define themechanisms by which GABP drives myeloid celldevelopment.

The Department of Medicine Newsletter

is published quarterly.

To submit an article or provide information

contact Denise Lavely-O’Hara at 444-5127,

e-mail to dlavely-ohara@Lifespan.org or

contact Dan Bryant at 444-6893,

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Department of Medicine Grand Rounds – Tuesday Mornings at 8:00 AMGeorge Auditorium, Rhode Island Hospital • Lecture Hall, The Miriam Hospital (teleconferenced from RIH) • Room 653, VA Medical Center (teleconferenced from RIH)

Office of the Chairman of MedicineRhode Island Hospital593 Eddy StreetProvidence, RI 02903

October 2005

8

October 18, 2005: The Kameny Lecture“Mobility in the Older Adult: Clinical Value to Medical Generalists and

Specialists”Stephanie A. Studenski, M.D., MPH, Staff Physician, VA Pittsburgh

GRECC, Professor, Department of Medicine, Division of Geriatrics,Professor, Schools of Allied Health and Nursing (secondaryappointments), University of Pittsburgh, Pittsburgh, Pennsylvania

October 25, 2005: Morbidity & Mortality ConferenceCase 1: “A 40-year-old woman with syncope and respiratory distress form

sudden cardiogenic shock”Presenter: Kevin Dushay, M.D., Pulmonary/Critical Care MedicinePanelists: Leonard Mermel, D.O., Infectious Diseases; Philip Stockwell,

M.D., CardiologyCase 2: “A 27-year-old male with fevers, right upper quadrant pain and

fulminant hepatic failure”Presenter: James Butera, M.D., Hematology/OncologyPanelists: Kittichai Promrat, M.D., Gastroenterology

November 1, 2005: “Teaching in the Office”

Edward H. Wagner, M.D., MPH, FACP, Director, W.A. MacColl Institute for HealthcareInnovation, Group Health Cooperative of Puget Sound, Adjunct Professor, Universityof North Carolina at Chapel Hill School of Public Health, Department of Epidemiology

November 8, 2005: Endocrine UpdateGeetha Gopalakrishnan, M.D., Assistant Professor of Medicine,

Brown Medical SchoolMarc Laufgraben, M.D., Clinical Assistant Professor of Medicine,

Brown Medical School

November 15, 2005: Morbidity & Mortality Conference

November 22, 2005: Nephrology Update

November 29, 2005: Guest Lecture

December 6, 2005: Morbidity & Mortality Conference

December 13, 2005: 2nd Annual Paul Calabresi Memorial Lecture“Cancer Drug Discovery: What have we accomplished with targeted

therapy?”Bruce A. Chabner, M.D., Professor of Medicine, Chief, Hematology/

Oncology, Clinical Director, Cancer Center, Massachusetts GeneralHospital

December 20, 2005: Gastroenterology Update“Endoscopic Ultrasound”Sripathi Kethu, M.D., Assistant Professor of Medicine,

Brown Medical School“Photodynamic Therapy”Fadlallah Habr, M.D., Assistant Professor of Medicine,

Brown Medical School

December 27, 2005: CANCELED - HAPPY HOLIDAY

• The Rhode Island Hospital fully intends to comply with the legal requirements of theAmericans with Disabilities Act. If any participant of this conference is in need ofaccommodation, please contact the Rhode Island Hospital CME office at (401) 444-4260.

• Rhode Island Hospital Continuing Medical Education has reviewed this activity’s speakerdisclosures and resolved all identified conflicts of interest, if applicable.

• The Department of Medicine Grand Rounds series is supported by an unrestrictededucational fund as contributed by: Abbott Laboratories, Hoechst Marion Roussel, Merck& Co., The Liposome Company, Parke-Davis, Schering, Pfizer, Wyeth-Ayerst Laboratories,Eli Lilly and Company, Berlex Laboratories, AstraZeneca.