Transplantation - Rhode Island Medical Society · Robert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian 100 LETTERS TO THE EDITOR 101 IMAGES IN MEDICINE – Post-transplant

Volume 90 No. 3 March 2007

�Transplantation

69VOLUME 90 NO. 3 MARCH 2007

Medicine and Health/Rhode Island (USPS 464-820), a monthly publication, is owned and published by the Rhode Island Medical Society, 235Promenade St., Suite 500, Providence, RI 02908, Phone: (401) 331-3207. Single copies $5.00, individual subscriptions $50.00 per year, and $100per year for institutional subscriptions. Published articles represent opinions of the authors and do not necessarily reflect the official policy of the Rhode IslandMedical Society, unless clearly specified. Advertisements do not imply sponsorship or endorsement by the Rhode Island Medical Society. Periodicals postagepaid at Providence, Rhode Island. ISSN 1086-5462. POSTMASTER: Send address changes to Medicine and Health/Rhode Island, 235 Promenade St.,Suite 500, Providence, RI 02908. Classified Information: RI Medical Journal Marketing Department, P.O. Box 91055, Johnston, RI 02919,phone: (401) 383-4711, fax: (401) 383-4477, e-mail: [email protected]. Production/Layout Design: John Teehan, e-mail: [email protected].

UNDER THE JOINTEDITORIAL SPONSORSHIP OF:

Brown Medical SchoolEli Y. Adashi, MD, Dean of Medicine& Biological Science

Rhode Island Department of HealthDavid R. Gifford, MD, MPH, Director

Quality Partners of Rhode IslandRichard W. Besdine, MD, ChiefMedical Officer

Rhode Island Medical SocietyBarry W. Wall, MD, President

EDITORIAL STAFFJoseph H. Friedman, MD

Editor-in-ChiefJoan M. Retsinas, PhD

Managing EditorStanley M. Aronson, MD, MPH

Editor Emeritus

EDITORIAL BOARDStanley M. Aronson, MD, MPHJay S. Buechner, PhDJohn J. Cronan, MDJames P. Crowley, MDEdward R. Feller, MDJohn P. Fulton, PhDPeter A. Hollmann, MDSharon L. Marable, MD, MPHAnthony E. Mega, MDMarguerite A. Neill, MDFrank J. Schaberg, Jr., MDLawrence W. Vernaglia, JD, MPHNewell E. Warde, PhD

OFFICERSBarry W. Wall, MD

PresidentK. Nicholas Tsiongas, MD, MPH

President-ElectDiane R. Siedlecki, MD

Vice PresidentMargaret A. Sun, MD

SecretaryMark S. Ridlen, MD

TreasurerKathleen Fitzgerald, MD

Immediate Past President

DISTRICT & COUNTY PRESIDENTSGeoffrey R. Hamilton, MD

Bristol County Medical SocietyHerbert J. Brennan, DO

Kent County Medical SocietyRafael E. Padilla, MD

Pawtucket Medical AssociationPatrick J. Sweeney, MD, MPH, PhD

Providence Medical AssociationNitin S. Damle, MD

Washington County Medical SocietyJacques L. Bonnet-Eymard, MD

Woonsocket District Medical Society

RHODE ISLANDPUBLICATION OF THE RHODE ISLAND MEDICAL SOCIETY

Medicine � Health VOLUME 90 NO. 3 March 2007

COMMENTARIES

70 Summing UpJoseph H. Friedman, MD

71 Euphemisms, Dysphemisms and BlasphemyStanley M. Aronson, MD

CONTRIBUTIONS

SPECIAL ISSUE: TRANSPLANTATIONGuest Editor: Paul Morrissey, MD

72 Solid Organ Transplantation – OverviewKevin Tan, MD, and Paul Morrissey, MD

76 Transplantation at Rhode Island Hospital: A Decade of CommitmentPaul Morrissey, MD

78 Pediatric Renal Transplantation – Historic and Current PerspectivesM. Khurram Faizan, MD, and Andrew S. Brem, MD

80 Immunosuppression Strategies In Kidney TransplantationsAngelito Yango, MD, and Amit Johnsingh, MD

84 Considerations for the Inpatient Care of Solid Organ RecipientsKevin M. Lowery, MD, and Reginald Y. Gohh, MD

89 Is There a Rational Solution to the Kidney Shortage?Anthony P. Monaco, MD

91 The National Organ Transplantation Breakthrough Collaborative –A Rhode Island Hospital Perspective

Kevin M. Dushay, MD, FCCP, and Suzanne Duni Walker, Esq, RN, BSN

COLUMNS

94 GERIATRICS FOR THE PRACTICING PHYSICIAN – The Assessment and Management ofFalls Among Older Adults Living In the CommunityMichael P. Gerardo, DO

96 HEALTH BY NUMBERS – Classification of Emergency Department Visits: How ManyAre Necessary?Jay S. Buechner, PhD, and Karen A. Williams, MPH

98 PUBLIC HEALTH BRIEFING – Bloodborne Pathogen Transmission Potential FromNeurological PinwheelsRobert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian

100 LETTERS TO THE EDITOR

101 IMAGES IN MEDICINE – Post-transplant Lymphoproliferative Disorder FollowingRenal TransplantCourtney A. Woodfield, MD

102 PHYSICIAN’S LEXICON – The Vocabulary of Paralysis in Anglo-Saxon EnglandJames T. McIlwain, MD

102 Vital Statistics

104 March Heritage

Cover: “After Life,” 17-inch wooden box, com-posed of mixed media mish-mash of materials,by Melissa Ferreira, a Providence artist whoteaches part-time in the IllustrationDepartmentat Rhode Island School of Design. “When notmaking commissioned pieces for clients, I createobjects and images that interpret these spectacu-lar human bodies of ours—inside and out—but in ways that resemble physiological modelsfrom the Middle Ages rather than the informedimaging we have today.” www.melissaferreira.net.

This issue is being mailed to selected physicians who are not members ofthe Rhode Island Medical Society. The expanded mailing has been madepossible by a grant from the Ultimate Gift Fund, Transplant Services, RhodeIsland Hospital.

70MEDICINE & HEALTH/RHODE ISLAND

Summing Up�

Commentaries

This is the 99th column that I’ve writtenfor Medicine & Health/Rhode Island, andI hope to keep supplying them, one permonth. It might seem that a summingup would be better suited for the 100th

column, or when I retire from this posi-tion; however, I’ve always written an“April fool’s” column, which will be the100th, making a serious venture inoppor-tune, and I’m not planning on steppingdown from this position for a while yet.Since being editor-in-chief of this jour-nal is not the most highly sought afterposition, it is unlikely that I will be forcedfrom the job by an unexpected palaceintrigue. What “palace?” What sort of an“intrigue?”

This journal is a small venture. It issent to the thousand plus members of theRIMS and is given free to all Brownmedical students. Some medical librariessubscribe, because they have contractualarrangements with other libraries in theircollaborative “systems” to subscribe to alldesignated journals. The contents of ourjournal are included in Index Medicusand therefore in Pub Med, so all the ar-ticles show up in literature searches.

The journal’s work is done almostentirely by the managing editor, JoanRetsinas, and myself. Stan Aronson,Brown Medical School’s founding deanand editor-in-chief emeritus of this jour-nal, writes a monthly column related tomedicine in history, a half column on theetymology of medical terminology, andedits my columns. The editors are unpaid.

The journal is subsidized by theRIMS, the RI Department of Health,Brown Medical School and the RI Qual-ity Partners. In a recent survey of RIMSmembers, the journal received a surpris-ing recognition as being one of severalaspects of the medical society that theyliked. It is not clear if Brown medical stu-dents share that enthusiasm, as they’ve notbeen surveyed. Having taught Brownmedical students for many years, I canstate that no student ever asked me if Iwas the same Joseph Friedman who edits

the medical journal. Nor has any studentevery quoted or asked about an article.

Aside from writing my column, whatdo I do? Mainly two things. The mostimportant is to recruit guest editors. Mostof our issues are devoted to single topics(e.g., autism, brain stimulation, atrial fi-brillation, etc). I therefore need to thinkof topics that I believe will be of interestto most of our readers. I then try to findsomeone in the medical community whocan pull together enough authors cover-ing enough topics to make a full issuepossible. I try, whenever possible, to high-light an area that Rhode Islanders excelin, but for which we may not be known.Sometimes a new service comes to RhodeIsland but local doctors, unaware, con-tinue sending their patients to Boston orelsewhere, not knowing that the serviceis readily available here. The authors aregenerally located in RI or have recentlymoved from Rhode Island and are col-laborating with Rhode Islanders. Some-times I ask someone to review recent ad-vances, with reference to services avail-able in RI, in a discipline, such as cardi-ology, urology or radiology.

We receive some unsolicited mate-rial, but not a lot. We encourage these.The journal is a good venue for fellows,residents and students to begin their pub-lishing careers. Our turn-around time isunrivaled, and the chances for publica-tion are higher than in national journals.When I began to edit the journal, Dr.Aronson, who had been editor for overten prior years, told me that he woulddefine me as successful when I was ableto reject a submission as unworthy. Thathurdle was crossed long ago. However,in the case of student and trainee sub-missions, we try to work with the authorsto improve the article sufficiently to meritpublication. Generally this is possible.

It may not seem so difficult to getthis done. And generally it’s not, but it isa never-ending surprise how often doc-tors will not return phone calls, e-mailsor even letters. You’d think that as editor-

in-chief of any journal, let alone the statejournal of a very small place, I’d receivesome “respect.” But no. Even juniorpeople ignore me. I used to think thatbad manners in doctors was a uniquelyHarvard quality, but Brown doctors, per-haps believing this is a desirable IvyLeague tradition, confusing bad mannerswith eminence, seem to be emulatingtheir more famous colleagues. I recentlyreceived several manuscripts from authorswho clearly had never even scanned thejournal and had no idea of what articlesin the journal should look like, anotherform of disrespect. But for people whodo read the journal it appears to be get-ting more favorable reviews. And theMedical Society is happy with its mem-bers’ feedback.

We endeavor to “advertise” local ac-tivities. We have a policy of publishingbook reviews of every book with a RIauthor, if the book is brought to our at-tention. Almost none have been. We wel-come purveyors of new tests, new treat-ments or new ideas to write scholarly ar-ticles to educate the community, andmake their own expertise known. Wewelcome letters to the editor. We havepublished few because we haven’t re-ceived many.

Our goal is to keep our local doc-tors informed about what’s going on inRhode Island. We aim to encourageyoung doctors to make observations andthen publish them. A scholarly medicalgroup raises community standards. Thetrip to Boston is not too long, but it’s noteasy and parking’s worse. Our goal is tohelp our community make that trip un-necessary.

– JOSEPH H. FRIEDMAN, MD


Euphemisms, Dysphemisms and Blasphemy�

Politeness often impels us to choose a congenial synonymwhen a more accurate term, sometimes vulgar, might offend thelistener. Thus we may perspire rather than sweat, call a funeraldirector a grief therapist, call a military retreat a tactical deploy-ment or refer to a recently deceased individual as the dearly de-parted rather than one who has kicked the bucket, bought thefarm or assumed room temperature.

The Greeks had a word for such a benevolent transforma-tion: euphemos, meaning a good word; in English, euphemism.[And blasphemy to define its opposite.] The English language isnow thoroughly saturated with relaxing, socially sanctionedphrases to temper the harshness of reality by employing circum-locution instead of brevity, clarity and directness. Given the gen-erous plasticity of our language, unreality may now be cloakedin the guise of reality and madness with the aura of sanity. Graf-fiti, for example, has been called authentic, socially-relevant art,garbage dumps are referred to as sanitary landfills, nuclear bombsrenamed as radiation enhancement devices and homeland resi-dents are now called natives, indigenous nationals or aborigines,depending upon the degree to which they have been colonized.

Dysphemism, the antonym of euphemism, defines verbiagethat is intentionally and unduly offensive rather than merelyquaintly descriptive or quietly obfuscating. Dysphemic terms areparticularly employed in sports journalism where, for example,the losing team may be annihilated, trounced or slaughteredbut rarely just defeated.

Euphemisms, when consciously used to conceal the truth,are now called doublespeak as a silent homage to George Orwell’snewspeak and doublethink. Nor is doublespeak confined to thevocabulary of used car salesmen [when used cars are called pre-owned vehicles] or real estate agents who now rename downpayments as “initial investments” and “rural settings” to hide longdriveways that require snow plowing in the winter.

Some euphemisms can bring humor into the choice of ac-ceptable synonyms. Fishermen off the coast of New England havesometimes been call “cod fathers,” a cowboy in the Midwest mayjokingly be renamed as a “bovine attendant,” those who stealbooks from college libraries are identified, in Freudian English,as “victims of bibliomania” and a botanical garden may be la-beled as “plant parenthood.”

Euphemisms are standard props in the language of govern-ment, the military, certainly newspaper columns and the domainsof sex and bodily functions [it is a sad day for spontaneous lovewhen foreplay is paraphrased as an “antecedent to interpersonaltransaction.”] The National Committee on Public Doublespeak,headed by Professor William Lambdin, has found such euphe-misms as “escalated interpersonal altercation” for domestic mur-der, “plural relations” for the apartheid activities in South Africa,“personal flotation device” for a life-saver and “involuntarily lei-sured” for the unemployed.

In terms of governmental activities, for example, state mur-der is called “capital punishment” or “judicially sanctioned ex-ecution”; neither of these semantic alternatives, of course, lessensthe end-result of the action. If, in reporting deaths due to mili-tary action, the word “kill” seems offensive, there are more be-nign substitutes such as “neutralize,” “pacify,” “victim of collat-eral action” or “ one who is terminated with prejudice.”

Many figures of speech modify the character and endur-ance of the message: such methods as irony, understatement,metaphor, allegory, hyperbole [often employed in advertising oras an inflation of job-titles], periphrasis, word deformation [sub-stituting a modified word such as “darn” instead of “damn”] allin the interests of degrading truth as an option rather than arequirement.

Consider, for example, a recent story from the Maine De-partment of Health and Human Resources. During the 2000 –2004 interval, there were 22,516 automobile accidents on theMaine roads involving feral animals; and 3,400 of these weremotor vehicle collisions with moose. These collisions resulted in1,583 injuries to humans and 17 deaths. The moose casualtyrate, of course, was substantially higher. Most of these accidentstook place after dark, particularly during the moose mating sea-son of September and October.

The Maine Department of Motor Vehicles has recentlyundertaken a number of measures to lessen this problem. First,by clearing much of the underbrush lining the highways andthus improving driver vision, particularly at night. Second, byplacing road signs where there have been frequent moose-ve-hicle collisions, under the presumption that either the drivers orthe moose are literate. And third, by moose herd management.[The Department defines “herd management” as the increasedissuance of moose-hunting permits, by state sanction, in thosestate areas with the highest frequencies of moose-vehicle colli-sions.]

It is comforting to know that the estimated 29,000 mooseof Maine are not mindlessly slaughtered, savagely hunted downor indiscriminately struck by motor vehicles but are having theirnumbers scientifically diminished through “herd management.”Mercy and the art of bureaucratic euphemisms are not dead.

– STANLEY M. ARONSON, MD


Solid Organ Transplation – OverviewKevin Tan, MD, and Paul Morrissey, MD�

Solid organ transplantation is the treatmentof choice for many patients with end-stage organ failure from a wide variety ofcauses. This area of medicine has ad-vanced over the last 50 years, improvingpatient survival and quality of life. Themain problem today is not allograft re-jection or infectious complications aftertransplantation, but the limited supply oforgans that prohibits broader applicationof this therapy. (Figure 1, Table 1) De-spite an ever-increasing number of trans-plants performed yearly, the waiting listoutpaces the modest incremental im-provements in deceased organ donation.

The United Network for OrganTransplant (UNOS) tracks transplanta-tion statistics in the United States undercontract from the federal government.1

The Organ Procurement and Transplan-tation Network (OPTN) is the unifiedtransplant network established by theUnited States Congress under the 1984

National Organ Transplant Act (NOTA),to be operated by a private, non-profitorganization under federal contract.UNOS was awarded the OPTN contractto administer the OPTN under contractwith the Health Resources and ServicesAdministration of the US Departmentof Health and Human Services (HHS).The primary goals of the OPTN are to(1) ensure the effectiveness, efficiency andequity of organ sharing and (2) increasethe supply of donated organs available fortransplantation. The national waiting listwas 25% greater than the number oftransplants recorded in 1988 and morethan 50% greater by 1994. The tre-mendous clinical success of transplanta-tion has created disparity in the numberof patients waiting for transplantationand the availability of organs for trans-plant. In November 2006, there wereover 93,000 listed candidates for organtransplant. UNOS’s efforts to improve

organ donation are discussed in a sepa-rate chapter in this issue.

ORGAN DONATIONThe practice and terminology of or-

gan donation have changed over the de-cades. The term “organ harvest” was re-placed by “organ procurement” and mostrecently by “organ recovery.” In the earlydays of transplantation asystolic deceaseddonors were the primary source of organs.The concept of brain death arose in1968, first as a medical definition arrivedat by a Harvard colloquium and later asthe legal equivalent of death. Throughthe early 1990s brain dead donors wereprimarily standard criteria donors(young, previously healthy with good or-gan function). As the gap between thesupply and demand for organs grew, themargins of acceptability were extendedto include donors with reduced functionand high-risk characteristics (prisoners,history of drug use, and history of can-cer, e.g.); so called marginal and ex-panded criteria donors (older, depressedorgan function). Recently there has beena re-emergence of cardiopulmonary ar-rested donors, referred to as donationafter cardiac death (DCD). Today thesedonors, all with severe irreversible braininjury, undergo end-of-life standardpractices (extubation, discontinuation ofIV fluids and vasopressors) with recoveryof organs (usually kidneys and liver) af-ter a five-minute documentation of ces-sation of cardiopulmonary function. AtRhode Island Hospital, 55 kidney trans-plants have been performed from DCDdonors.

The vast majority of solid organs areprocured from deceased donors with in-tact circulation and a clinical diagnosisof brain death. These donors have eitherdied from traumatic brain injury, cere-brovascular accidents or secondary CNSinjury (e.g., anoxia). Since 1988, the num-ber of donors who died from motor ve-hicle collision or gunshot wound hassteadily declined while the number ofdonors who died from primary centralnervous events has increased.2 The rea-sons for this include improved identifi-

Figure 1. Solid Organ Transplantations Performed in the United States versusGrowth of the Transplant Waiting List (all organs)


cation and referral of older donors, in-creased acceptance of older donors bytransplant units, and improved automo-bile and handgun safety in the UnitedStates. There are in fact fewer youngdonors available than in years past ratherthan donors being overlooked or fami-lies refusing consent at higher rates lim-iting access to such donors.3

The transplant community in theUnited States has embraced living dona-tion as a source of organs.1 Worldwidepractices vary greatly with nearly all kid-neys transplanted in Japan and Koreacoming from live donors, a distinct mi-nority of kidneys from live donors in Eu-rope and an increasing number of kid-neys (now over 40%) of kidneys from liv-ing donors in the United States. In 2001,for the first time ever, the number of liv-ing donors in the United States (6607)exceeded the number of deceased donors(6100). Living donors may be related orunrelated to the recipient. Unrelateddonors include spouses, distant relatives,friends, co-workers and altruistic strang-ers. The number of organs procuredfrom living donors has plateaued in re-cent years. Live donors primarily donatea kidney (6647 in 2004), but also includeliver (323), partial lung (24) and infre-quently intestine (6) or pancreas (2) do-nors.

Just over 40 % of transplanted kidneysnationwide come from living donors. Com-pared to deceased kidneys, kidneys fromliving donors demonstrate superior long-term outcomes. (Tables 2 and 3) The ob-servation that the results for living unrelatedkidney donors were equivalent to living-re-lated (and more closely HLA matched)revolutionized the field. The most com-mon living unrelated kidney donor is aspouse; more commonly a wife as men out-number women with end-stage renal dis-ease and women make up a disproportion-ate percentage of altruistic donors. Inter-estingly, this analysis showed that the rateof graft survival at 3 years was higher forkidneys from spousal donors than for de-ceased transplants (85% versus 70%) de-spite a greater degree of HLA mismatch-ing. The improved function of kidneysfrom living unrelated donors comparedwith deceased donors is attributed to im-proved organ quality, reduced ischemia-reperfusion injury, the absence of systemicaberrations due to brain death and reduced

cold ischemic time. These data also provedthat HLA matching is of minor significance.Indeed only five criteria are essential forsuccessful live donor transplantation: (1)overall good health, (2) normal renal func-tion, (3) ABO compatibility, (4) HLA(crossmatch) compatibility, and (5) a will-ing donor free of undue coercion. For fur-ther information potential donors may re-fer to http://www.lifespan.org/rih/services/transplant/donor/.

OUTCOMES OF TRANSPLANTSInitially patient survival was poor;

however there were few medical alterna-tives. The technology of dialysis was ru-dimentary, and most patients fairedpoorly. The early experience with car-diac transplantation illustrates this point.Following the publicity of the first suc-cessful heart transplant in South Africaand the first successful heart transplantin the United States one month later un-der the direction of Norman Shumwayat Stanford, surgeons performed 167cardiac transplant procedures at 58 cen-ters over the next two years. While thetechnical aspects of cardiac transplanta-tion were within the capabilities of manysurgeons, clinical and immunological as-

pects of patient care were poorly under-stood; and most patients died within afew weeks of surgery. The initial enthu-siasm of the cardiac surgery communitywas tempered by the familiar nemeses oftransplantation - rejection and infection.In the ensuing decade approximately 20-30 heart transplant operations were per-formed annually, one-third of them atStanford University. Long-term survivorswere rare. Only 35% of cardiac trans-plant recipients survived 3 months.4 Thischanged with the introduction ofcyclosporine in the early 1980s. Thegreater specificity of this agent controlledacute rejection with fewer morbid sideeffects than prednisone. Favorable re-sults were rapidly achieved for kidney,liver, heart and pancreas transplantation.Both short term and long term survivalrates improved. According to the 2005OPTN/SRTR report, one-year survivalwas highest for kidneys and pancreas re-cipients, which ranged from 94.6 to97.9%. One-year and five-year survivalsare impressively high. (Tables 2 and 3)

Graft survival rates are generallylower than patient survival rates becausepatients may receive a second transplantor be supported by an alternative therapy


(dialysis). Of note, five-year patient sur-vival is considerably better than allograftsurvival for kidney recipients, highlight-ing two important points: first, in theevent of loss of allograft function patientsmay return to dialysis; second, one-halfof all allografts are lost to chronic allograftnephropathy (formerly termed chronicrejection) with the recipient considerablyoutliving the functional allograft. Nota-bly, 15% of the patients waiting for a kid-ney transplant have already lost one pre-vious kidney. Kidneys transplanted froma live donor source result in superior long-term function. (Table 3)

KIDNEY TRANSPLANTATIONTransplantation is the treatment of

choice for patient with end-stage renaldisease (ESRD), providing longer sur-vival, superior quality of life and reducedmedical expenses compared with dialy-sis. There are very few absolutecontraindications to kidney transplant,therefore most patients younger than age60 and many under the age of 70 withESRD should be considered for trans-plant evaluation. Nevertheless, only oneof every six patients with ESRD is on thewaiting list for a kidney transplant. Mostare excluded because of advanced ageand prohibitive co-morbid medical con-ditions. The survival advantage aftertransplant compared with continued di-alysis has been shown for all age groupsand all causes of ESRD; the greatest ad-vantage is for diabetic patients.5 Allograftsurvival for deceased donor and livingdonor transplants averages 65 and 80%at 5 years and 45 and 65% at 10 years,respectively.

PANCREAS TRANSPLANTATIONSuccessful pancreas transplant re-

sults in insulin independence andeuglycemia, as well as the halt of progres-sion in diabetic retinopathy, neuropathyand notable improvements ingastroparesis. Most importantly, pancreastransplantation substantially enhances thepatient’s quality of life and obviates theneed for glucose monitoring and insulinadministration. In accomplishingeuglycemia, pancreas transplantationbecomes the optimal therapy for dia-betic, ESRD patients with hypoglycemicunawareness.

The major drawback for pancreas

transplant is the need for immunosup-pression, considered by most an unaccept-able trade-off with the need for chronicinsulin therapy. Therefore, pancreastransplantation is performed in diabeticpatients with kidney failure who are can-didates for a kidney transplant and willrequire immunosuppressive drug to pre-vent kidney rejection. The options forpancreas transplant are (1) deceased do-nor, simultaneous pancreas-kidney trans-plant (SPK), (2) living donor kidneytransplant, followed by a deceased donorpancreas transplant and far less com-monly (3) a pancreas transplant alone(PTA).

LIVER TRANSPLANTLiver transplant is the treatment of

choice for patient with acute fulminantand chronic liver failure. Patient survivalat one year posttransplant has increasedfrom 30% in the early 1980s to morethan 80% at present. This has led to anincrease in number of liver transplantsperformed (approximately 2000 in1990, 4000 in 1997 and over 6000 lastyear). In 2005, 6443 liver transplantswere performed among over 16,000people on the waiting list. Most of thisgrowth was achieved through the moreaggressive pursuit and recovery of de-ceased donor organs with a lesser contri-bution (about 5%) from living donors.Live liver donors include left lateral seg-mentectomy in parent-to-child transplan-tation and right hepatectomy for adult-to-adult liver transplantation (AALT).The donor mortality for AALT (0.5-1.0%) introduced appropriate caution inadopting this procedure; there were 519living liver segment donors in 2001, how-ever there have been only 330 on aver-age in the past five years.2

The leading indication for livertransplant is cirrhosis caused by non-cholestatic liver disease, primarily due tochronic hepatitis C virus (HCV) and al-

cohol. The proportion of active patientson the waiting list with non-cholestaticchronic liver disease has been increasing.In 1995, 65% of patients waiting forliver transplantation had cirrhosis second-ary to a non-cholestatic liver disease. In2004, this had increased to 72% prima-rily driven by patients with HCV (40%of all listed patients). In 2004, cholestaticliver disease (sclerosing cholangitis, pri-mary biliary cirrhosis), acute hepatic ne-crosis, biliary atresia, and metabolic liverdisorders accounted for 11%, 4.5%,1.7%, and 1.5% of patients on the ac-tive liver transplant waiting list, respec-tively.

In the United States there are over120 centers performing liver transplan-tation, including eight in New England(Hartford Hospital, UMMC, Yale,Lahey and four centers in Boston). Ap-proximately 8-12 people from Rhode Is-land receive a liver transplant each year.Given the proximity to other centers ouradministrators and we have not pursuedliver transplantation at Rhode IslandHospital. Such a pursuit would requireenormous resources including more ICUbeds, specialists in hepatology and pa-thology and dedicated teams in anesthe-siology and nursing. It appears that thenumber of liver transplants would be in-sufficient to maintain satisfactory skills foroptimal transplant care.

THORACIC ORGAN TRANSPLANTATIONHeart transplantation is generally

performed in patients with life expect-ancy less than one year. From 1995 to2004, the number of patients on theheart waiting list declined, primarily areflection of the decline in the percent-age of transplant candidates with a coro-nary artery disease classification. This mayreflect better outcomes resulting fromimprovements in medical, interventional,and surgical treatments for coronary dis-ease. The number of heart donors hasremained stable over recent years, withapproximately 2000-2200 heart trans-plants performed annually, of which 20%are in children. The most common causeis ischemic or dilated cardiomyopathy,follow by valvular disease and congenitalheart disease. Lung transplantation isnewer field than heart transplantation.Currently, chronic obstructive pulmo-nary disease (COPD) is the most com-

…15% of thepatients waiting for

a kidneytransplanted havealready lost oneprevious kidney.


mon indication, followed by pulmonaryfibrosis, cystic fibrosis, primary pulmo-nary hypertension and alpha-1 antit-rypsin deficiency. There are three majorapproaches: single-lung, bilateral sequen-tial lung transplant and transplantationof lobes from living donors (less than 25cases annually). For six consecutive years,the number of patients on the active wait-ing list for a heart-lung transplant hasdecreased, from a high of 179 patientsin 1998 to only 83 in 2004. Most wait-ing list patients for heart-lung transplan-tation (81%) were adults older than 18years. The most common diagnoses werecongenital heart disease (35%), primarypulmonary hypertension (18%), and cys-tic fibrosis.

INTESTINAL TRANSPLANTIntestinal transplantation is the least

frequently performed solid organ trans-plant and associated with the highest re-jection rates and lowest graft survival. Itis reserved for patient with poor intesti-nal function who cannot be maintainedon parenteral nutrition (TPN), or thosewith TPN-associated complications, in-cluding hepatic dysfunction. There isevidence that the majority of patientswith progressive organ failure are re-ferred to transplant centers at a laterstage of their disease. As a result theClinical Practice Committee of theAmerican Society of Transplantation hasmade the following recommendations:(1) early referral to a transplant centerfor patients with organ insufficiency, (2)close cooperation with the primary caredoctor regarding follow-up and appro-priate referral to the transplant centerwith disease progression and (3) regu-lar communication about any changesin the condition of patient that affecteligibility for transplantation.6

Transplantation of the intestine, ei-ther isolated or in combination with otherabdominal organs, is being performedwith increasing success. The number ofpatients who received a small intestinetransplant has gradually increased overthe past 10 years from 46 in 1995 to 152in 2004. In 2004, 443 patients werealive with a functioning intestine graft.These numbers point to the need forhighly specialized care for these complexpatients.

THE ECONOMICS OFTRANSPLANTATION

Funding sources for organ trans-plantation include private health insur-ance, Medicare, Medicaid and the Vet-erans Administration system. Additionalfunding is available through charitableorganizations, advocacy groups, and pre-scription drug assistance programs. Thelatter includes programs established byprivate drug companies and a variety ofstate-funded initiatives. Residents ofRhode Island for at least one year priorto the date of the transplant operationand with a household income less than$66,309.82 are eligible for moniesthrough the Rhode Island Organ Trans-plant Fund. After the recipient’s insurerhas made payment, any remaining costsare considered for reimbursement.

Organ transplantation costs, on av-erage, $250,000 for liver, $150,000 forheart and $80,000 for kidney (deceasedor live donor). Obtaining health insur-ance is a prerequisite for patients withorgan failure. Insurance coverage is notavailable to undocumented aliens andorgan transplantation is denied unless theindividual can cover the cost of transplan-tation or the money is raised thoroughcharitable appeals.

Kidney transplantation is more cost-effective than hemodialysis for the Medi-care program. The initially higher costs oftransplantation are fully recouped byMedicare within three years after surgery.Unfortunately, Medicare coverage forimmunosuppressants ends 36 months af-ter transplantation. At that time patientsmust obtain private insurance, qualify forMedicaid or enter patient assistance pro-grams to obtain funds for transplant im-munosuppression; the yearly cost rangesfrom $2000 – $12,000.

The Medicaid Program requiresstates to cover “categorically needy indi-viduals,” which typically includes low-income families with children and preg-nant women. A second category, Medi-cally Needy, allows one to subtract medi-cal expenses from income. A “spenddown” is the process of using medicalexpenses to reduce income to the levelthat qualifies for Medicaid. Throughthese mechanisms the majority of peoplewith end-stage organ failure obtain cov-erage for transplantation.

CONCLUSIONThis overview demonstrates that the

field of transplantation continues to im-prove as a surgical (technical) and medi-cal discipline. Improvements in the pre-and post-transplant care of patients withorgan failure and the continued progressin immunosuppression make this one ofthe most exciting areas in clinical medi-cine. Undoubtedly, improvements willcontinue in this “new” field, which cel-ebrated its 50th anniversary in 2004.7

REFERENCES1. Organ Procurement and Transplantation Network.

www.optn.org. Accessed November 20, 2006.2. 2005 OPTN/SRTR report. www.ustransplant.org.

Accessed November 20, 2006.3. Hauptman PJ, O’Connor KJ. Procurement and

allocation of solid organs for transplantation.NEJM 1997; 336: 422.

4. Pennock JL, Oyer PE, et al. Cardiac transplanta-tion in perspective for the future. J ThoracCardiovasc Surg 1982; 83:168.

5. Wolfe RA, Ashby VB, et al. Comparison of mor-tality in all patients on dialysis. NEJM 1999; 341:1725.

6. Guidelines for referral and management of pa-tients eligible for solid organ transplantation.Transplantation 2001; 71: 1189.

7. Sayegh MH, Carpenter CB. Transplantation 50years later—progress, challenges, and promises.NEJM 2004; 351: 2761.

Kevin Tan, MD, is a resident in sur-gery, Rhode Island Hospital.

Paul Morrissey, MD, is Associate Pro-fessor of Surgery, Brown Medical School,and Division of Organ Transplantation,Rhode Island Hospital.

CORRESPONDENCE:Paul Morrissey, MDRhode Island Hospital APC 921593 Eddy StreetProvidence RI 02903phone: 401-444-5285E-mail: [email protected]


Transplantation at Rhode Island Hospital:A Decade of Commitment

Paul Morrissey, MD�

Kidney transplantation for residents ofRhode Island has a long and interestinghistory. After training at the Peter BentBrigham, Joseph Chazan, MD, openedthe first dialysis unit in Rhode Island in1970. The unit was established at theRhode Island Hospital and shortly there-after the first freestanding unit was openedin the “six corners” location in East Provi-dence. Shortly thereafter a transplant unitwas established at the Miriam Hospital.Robert Hopkins performed six kidneytransplants between 1973 and 1975. Theprogram closed thereafter. For the next 21years patients were referred to transplantcenters in Boston and Connecticut fortransplantation. Tony Monaco, MD, atthe New England Deaconess Hospital,transplanted the majority of Rhode Island-ers with end-stage renal disease. With theencouragement of Joseph Chazan in thecommunity and the assistance of PeterKing, MD, Lance Dworkin, MD, andKirby Bland, MD, then Chief of Surgery,a transplant program was established atthe Rhode Island Hospital in 1996. Theprogram was first a satellite of the NEDHwith Reg Gohh, MD, serving as medicaldirector and Bette Hopkins, RN, as Trans-plant Coordinator. Pre- and post-trans-plant patients from Rhode Island werecared for at the clinic. In March 1997,the first transplants were performed froma deceased donor in Rhode Island; in June

the first living related transplant was un-dertaken. I joined the program at thattime and since then we have expanded toinclude specialists in infectious disease, psy-chiatry, social work, pharmacology, nutri-tion and research programs. Since 2004,the Transplant Team includes 9 physicians,5 nurses, 7 allied health care professionalsand 5 office assistants. Transplant volumeis shown in Figure 1.

ORGAN DONATION AND THE LOCALWAITING LIST

As the only Level 1 Trauma Centerin the state, Rhode Island Hospital is thepredominant site for deceased organ do-nation. In the past 10 years, 239 kidneyswere recovered at Rhode Island Hospital,compared with 14 at Kent, 8 at Roger Wil-liams and 4 each at Miriam and NewportHospitals. These stark differences are re-lated to differing patient populations withconditions that result in organ donor po-tential – trauma, cerebrovascular accidentsand other causes of irreversible brain in-jury or brain death. The majority of kid-neys recovered in Rhode Island are trans-planted within the state as allocation inNew England is heavily biased toward ge-ography. Rhode Island Hospital is consis-tently a leader in deceased organ dona-tion in the region. (Table 1) Our surgicalgroup is assigned primary responsibility forkidney recovery throughout Rhode Is-

land; often we also recover the liver andpancreas for use within the region or na-tionally. Rhode Island Hospital was thefourth center in New England to adopt apolicy for donation after cardiac death(kidney recovery after withdrawal of me-chanical ventilation in patients with dev-astating head injury) and such donors haveprovided a valuable source of kidneys(n=63) for transplantation.

Just over 45 % (296/640) of trans-planted kidneys at Rhode Island Hospitalcome from living donors. Most are fromrelatives. The most common living unre-lated kidney donor is a friend (n=35), fol-lowed by a spouse or fiancé (34); morecommonly a wife (22) as men outnumberwomen with end-stage renal disease andwomen always make up a disproportion-ate percentage of living donors. In 1999,our program became one of the first inthe country to accept a stranger(nondirected, altruistic) donor. We nowboast, on behalf of our generous donors,the second largest reported series of GoodSamaritan and nondirected donors (22)in the United States. 1 The University ofMinnesota has the most (around 40).

With these strong efforts in livingand deceased donor organ donation, thelatter elaborated in greater detail by KevinDushay, MD, in an accompanying ar-ticle, the wait-list for kidney transplanta-tion in Rhode Island is shorter than atYale and the Boston programs. Even so,we have a crucial need. Rhode Islandpatients on the active UNOS wait list in-clude: kidney (128), pancreas (22), liver(92), heart (18) and lung (12).


KIDNEY TRANSPLANTATIONTransplantation is the treatment of

choice for patients with end-stage renaldisease (ESRD), providing better patientsurvival, superior quality of life and re-duced medical expenses compared withdialysis. There are very few absolutecontraindications to kidney transplant,therefore most patients younger than age60 and many under the age of 70 withESRD should be considered for trans-plant evaluation. In fact, only one of ev-ery six patients with ESRD is on the wait-ing list for a kidney transplant (153 pa-tients of 950 on chronic dialysis in RhodeIsland). Most are excluded because ofadvanced age and prohibitive co-morbidconditions.

Kidney allograft survival rates arelower than patient survival as recipientswith a failed kidney allograft may receivea second transplant or return to dialysis.Our overall patient and graft survival isshown in Table 2. The majority of deathswere due to sepsis and cardiovascularcauses, particularly in the subgroup ofolder recipients.2 Additional allograftlosses were due to chronic allograft neph-ropathy, infection (BK virus, e.g.), andallograft rejection often related to medi-cation nonadherence. This occurrence,whether related to psychological illness,economic hardships or immaturity, is anunfortunate consequence of the need forchronic immunosuppression.3

PANCREASTRANSPLANTATION

Successful pancreastransplant results in in-sulin independence andsubstantially enhancesthe patient’s quality oflife. Therefore, pancreastransplantation is theoptimal therapy for dia-

betic, ESRD patients with hypoglycemicunawareness. For many patients with dia-betes and renal failure the opportunity fordeceased donor kidney-pancreas will pro-vide optimal survival and quality of life.4

The options for pancreas transplant aredeceased donor, simultaneous pancreas-kidney transplant (SPK) and living donorkidney transplant; followed by deceased do-nor pancreas transplant—pancreas afterkidney (PAK) transplantation. To date, 24patients with ESRD and diabetes have re-ceived a pancreas transplant (19 PAK, 5SPK) since 2002. With a mean follow-upof 30 months, 23 patients are alive with afunctioning kidney and 15 (62%) are in-sulin-free. As islet cell transplantation,xenotransplantation and optimal insulinpump technologies continue to require re-finement, pancreas transplantation for pa-tients with diabetes who already require im-munosuppression for a kidney allograft re-mains an appealing option.

REFERENCES1. Morrissey PE, Dube C, et al. Good Samaritan

kidney donation. Transplantation 2005; 80:1369.

2. Morrissey PE, Yango A. Renal transplantation:older recipients and donors. Clin Geriatr Med2006; 22: 687.

3. Morrissey PE, Flynn M, Lin S. Medication non-compliance and its implications in transplant re-cipients. Drugs 2007; in press.

4. Reddy KS, Stablein D, et al. Long-term survivalfollowing simultaneous kidney-pancreas trans-plantation versus kidney transplantation alone inpatients with type 1 diabetes mellitus and renalfailure. Am J Kidney Dis 2003; 41: 464.

Paul Morrissey, MD, is Associate Pro-fessor of Surgery, Brown Medical School, andDivision of Organ Transplantation, RhodeIsland Hospital.

CORRESPONDENCE:Paul Morrissey, MDRhode Island Hospital APC 921593 Eddy StreetProvidence RI 02903Phone: (401)E-mail: [email protected]


Pediatric Renal Transplantation –Historic and Current Perspectives

M. Khurram Faizan, MD, and Andrew S. Brem, MD

�Renal transplantation is the preferredmode of therapy for pediatric patientswith chronic kidney disease. Successfulkidney transplantation offers childrenwith end stage renal disease (ESRD) theopportunity for normalization of growthand development. Obstructive uropathyand associated renal dysplasia remain thecommonest causes of ESRD in the pedi-atric age group.1, 2 According to theUnited Network of Organ Sharing(UNOS) database, approximately 700pediatric renal transplants are performedeach year. Since 1988, a total of 13,163successful pediatric renal transplants havebeen carried out in the United States(www.unos.org).

Pediatric centers in Minnesota andCalifornia were the first to offer kidneytransplantation to children with endstage renal failure in the late 1960s.Those pioneering pediatricnephrologists and transplant surgeonsrecognized that renal failure in childrenwas a functional death sentence3 sincechronic dialysis was not readily availableat that time. Immunosup-pression was primitive,kidney donors were few,and medical insurancecovering the expense wasnot always available. TheCongressional passage ofthe Medicare End StageRenal Disease entitlementprogram in 1973 funda-mentally changed the dy-namic by, at the least,guaranteeing payment forthe transplant. Other pe-diatric centers soon beganoffering transplant serviceswith the assurance thattheir expenses would bedefrayed. Pediatric dialy-sis services also improvedwith Medicare funding,but chronic dialysis treat-ment could never fullycompensate for the mul-tiple medical and psycho-social problems associated

with renal failure. Over the next twenty-five to thirty years, advances in immu-nosuppression, living donor transplan-tation, and changes in deceased donororgan allocation criteria have establishedkidney transplantation as the treatmentof choice for children with chronic re-nal failure.

PEDIATRIC RENALTRANSPLANTATION PROGRAM ATRHODE ISLAND HOSPITAL

The Rhode Island Hospital initiatedits own kidney transplant program in1997. Prior to that time, all adult andpediatric patients were required to travelout of state for renal transplantation.Our pediatric transplant program waslaunched in 1998 with an 11-year oldboy receiving a kidney from his mother.Since then, 20 patients ranging from 2to 18 years have received 21 renal trans-plants. (Table 1) Approximately 60% ofthese renal transplants were done withliving donors. In contrast to adult expe-rience, living donor transplants are more

common than deceased donor trans-plants for pediatric patients.4 Outcomesin our program have compared favorablyto national data4 with 100% patient sur-vival and a one-year graft survival of 95%.The one loss was due to recurrent dis-ease (focal segmental glomerulosclerosis),a known risk factor.5 The relatively smallnumbers of pediatric transplants reflectthe low incidence of ESRD in children -approximately 2 to 3 cases per millionpopulation.

UNIQUE ASPECTS OF PEDIATRICEND STAGE RENAL DISEASE ANDRENAL TRANSPLANTATION

Children undergoing long-term di-alysis face a multitude of problems.Chronic dialysis although life-saving, isnot a panacea. Clearance of excess fluidand waste products by dialysis is cyclicand not the same for all toxins. Chil-dren on dialysis often have limited ap-petites especially given necessary dietaryrestrictions. With inadequate caloricintake, normal growth is unlikely. Ad-

SLE = Systemic Lupus Erthematosus, FSGS = Focal Segmental Glomerulosclerosis,RPGN = Rapidly Progressive Glomerulonephritis, PCKD = Polycystic Kidney Disease.


ditionally, multiple medications areneeded to augment the dialysis treat-ments including erythropoietin for con-trol of anemia and calcium supplementswith 1,25 (OH)2 vitamin D to ensureproper bone mineralization. From apsycho-social perspective, the time re-quired to undergo hemodialysis, usually3 to 4 hours for three sessions per week,imposes a heavy hardship on childrenremoving them from the usual childhoodactivities of school and play. Workingparents also have the burdens of trans-portation and caretaking. Families per-forming peritoneal dialysis (PD) athome must care for a sick child and dealwith the infectious and nutritional com-plications of PD. Successful renal trans-plantation in children allows for resto-ration of growth and development, im-provement in school performance andcognitive abilities, an increase in thephysical activity level, and allows fami-lies to lead a more normal life with theirchildren at home.

Parents are often ready and willingto serve as candidates for living donortransplantation when their own childrenare involved as patients. The UnitedNetwork for Organ Sharing (UNOS)also has recognized the special needs ofchildren with ESRD and favors allocat-ing deceased donor organs to childrenunder 18 years of age when possible.These two advantages increase organavailability and most children fortu-nately now spend a relatively brief timeundergoing dialysis prior to transplan-tation. Currently, most transplant cen-ters in the United States use an immu-nosuppressive regimen in pediatric pa-tients that mimics their adult counter-parts. However, a few centers have at-tempted to minimize the use of post-transplant steroids in children due totheir negative effect on growth. Unfor-tunately, teenagers comprise the high-est risk of acute transplant rejectionamongst any age group (including bothchildren and adults). This is due to a highrate of medical non-compliance seen inthis age group.

Pediatric renal transplantation is alabor-intensive exercise with attendantpitfalls and potential complications.Kidneys from adult donors are preferredeven for the youngest patients. Thismeans that the patient needs appropri-

ate volume expansion in the operatingroom to prevent hypo-perfusion andthrombosis. Young patients often me-tabolize immunosuppressive medica-tions more quickly than adults and re-quire close monitoring of drug levels inthe post-operative period. Hypertensionboth from medications and/or fromprior volume expansion is a frequentlyencountered problem. In the short-term, we accept higher blood pressuresin transplant patients as long as they areasymptomatic to avoid the risk of throm-bosis in the graft. The risk of infectionis ever present in children post-trans-plant; the infections come from outsideexposures or can be inadvertently ac-quired from the donor in the transplantprocess.

More mundane issues surface inour patients as time passes. Immuniza-tions often have been deferred and needto be considered. As a rule, most trans-plant centers, including our own, do notrecommend giving attenuated live virusvaccines to patients. Patients frequentlyare concerned about their delayed lin-ear growth, which resulted from priorrenal failure. Fortunately, newer im-mune-modulating protocols now limitglucocorticoid exposure6 and many chil-dren will resume a normal growth ve-locity or even exhibit “catch up” growthafter transplant. We encourage patientsto begin regular exercise once theirwounds are healed. Regular exercise foras little as 30 minutes a day helps pa-tients lower their risk for hypertension,excessive weight gain, and diabetes posttransplant.

CONCLUSIONSActive participation and cooperation

of the parents are necessary to ensure thatchildren receive prescribed drugs regu-

larly and maintain clinical follow-up af-ter transplantation. A multi-disciplinaryapproach is essential, with the pediatricrenal transplant team comprising oftransplant surgeons, pediatricnephrologists, social workers, transplantcoordinators, nurses and counselors toensure a successful outcome post-trans-plant. Most pediatric patients do very wellin the United States with a five-year graftsurvival of about 82% and a five-yearpatient survival of 92%.

REFERENCES1. Lewy JE. Treatment of children in the U.S. with

end-stage renal disease (ESRD). Med Arch 2001;55:201-2.

2. Seikaly MG, Ho PL, et al. Chronic renal insuffi-ciency in children. Pediatr Nephrol 2003; 18:796-804. Epub 2003 Jun 14.

3. McDonald SP, Craig JC. Long-term survival ofchildren with end-stage renal disease. NEJM2004; 350:2654-62.

4. Long-term graft survival in pediatric renal trans-plant patients based upon primary disease. Trans-plantation 2006; 82:100.

5. Baum MA, Ho M, et al. Outcome of renal trans-plantation in adolescents with focal segmentalglomerulosclerosis. Pediatr Transplant 2002;6:488-92.

6. Halloran PF. Immunosuppressive drugs for kid-ney transplantation. NEJM 2004; 351:2715-29.

M. Khurram Faizan, MD, is Clini-cal Assistant Professor of Pediatrics, BrownMedical School.

Andrew S. Brem, MD, is Professor ofPediatrics, Brown Medical School.

CORRESPONDENCEM. Khurram Faizan, MDSection of Pediatric NephrologyRhode Island Hospital APC 942593 Eddy StreetProvidence RI 02903phone: (401) 444-5672e-mail: [email protected]

Most pediatricpatients do very

well in the UnitedStates with a five-year graft survival

of about 82% and afive-year patientsurvival of 92%.


Immunosuppression Strategies in Kidney TransplantationAngelito Yango, MD, and Amit Johnsingh, MD

�The development of immunosuppressivedrugs heralded new and exciting possi-bilities in kidney transplantation. Morethan half a century ago, initial attemptsat kidney transplantation resulted in im-munologic destruction of the graftwithin a few weeks and eventual deathof the recipient from renal failure, leav-ing little hope for optimism. Such senti-ment changed, however, with the suc-cessful non-twin kidney transplantationin the late 1950s at the Peter BentBrigham Hospital.1 Previously theBrigham team and groups in France hadperformed successful kidney transplantsamong identical twins. Overcoming im-munologic barriers between geneticallydissimilar individuals by immunosup-pression, however, ranks as this group’sgreatest achievement.

Equipped with the knowledge thatrejection was an immunologic phenom-enon, efforts were taken to weaken theimmune system. Prior to the publicationof acquired tolerance, Medawar and oth-ers reported on the immunosuppressiveeffects of total body irradiation and of thenewly synthesized hormonecoricosteroids. In 1952, Frank Dixon re-ported in the Journal of Immunology thatx-rays could depress immune responsive-ness. The first use of clinical immunosup-pression was at the Peter Bent BrighamHospital (1958 - 1960), using total bodyirradiation with subsequent reconstitutionby a bone marrow allograft. Protocols werederived from experimental studies con-ducted by Joseph Murray and others inskin grafted

rabbits. It was suggested that

by infusing donor specific lymphoid cellsinto a recipient depleted of its own lym-phocyte by irradiation, one might createa “chimeric” subject tolerant of organs andtissues from the donor of the allogeneicmarrow. The initial cases were associatedwith short-term success and a high rate ofcomplications related

to the transplant op-

eration, renal failure or bone marrow sup-pression. One patient with profoundthrombocytopenia succumbed to

bleed-

ing complications one month after renaltransplantation. Two

postoperative biop-

sies and the kidney at autopsy failed to

demonstrate any evidence of rejection. Inthe group’s sixth case, the protocol wasmodified for a living related renal trans-plant from a fraternal twin. A lack of

iden-

tity was clinically apparent and immuno-logic disparity was proven by preoperativeand

postoperative skin grafts that were rap-

idly rejected. Given the closeness of therelation, 450 Gray of total body irradia-tion, a reduction from earlier transplants,was administered eight days preopera-tively. The

allograft was accepted repre-

senting the first successful living relatedrenal transplant under immunosuppres-sion.1 French surgeons soon replicated thesuccessful protocol, first in the identicalsetting of living related renal fraternaltwins and a year later in a sister-to-brother

combination. Several other long-term suc-cesses were reported with protocols withtotal body irradiation; and Jean Ham-burger, founding president of the Inter-national Society of Nephrology, showedthat further radiation could reverse acuterejection in the allograft. This strategywas soon widely applied at Denver, UCLA,University of Minnesota, Edinburgh,Hammersmith, the Massachusetts Gen-eral Hospital and the Medical College ofVirginia. The following year, a secondstrategy in clinical immunosuppressionarose from the development of 6-mercap-topurine in the laboratory. Subsequently,azathioprine was developed in collabora-tion with clinicians interested in transplan-tation and applied to the clinical arenaafter careful experiments in animal mod-els conducted by Sir Roy Calne while a

visiting fellow in the laboratory of JosephMurray.

Significant progress has been madein surgical techniques as well as medicalmanagement of renal transplant recipi-ents. Advances in transplant immunol-ogy paved the way for the developmentof immunosuppressive agents that are in-tegral to successful allograft function.With the use of azathioprine and corti-costeroids in combination, the average 1-year graft survival was less than 35%. Thisimproved to 50% with the use ofpolyclonal antibodies that were producedin laboratories and animal facilities asso-ciated with the individual transplant cen-ters. The next major breakthrough oc-curred with the identification of potentimmunosuppression from a product of asoil fungus identified in the Arctic Circle.This compound, cyclosporine A, wasoriginally purified in an effort to identifyantifungal medications by Sandoz Labo-ratories in Basel Switzerland.Cyclosporine, it turns out, had weak an-tifungal properties, but was fortuitouslynoted to suppress immune function in ahemagglutinin assay. This wonderfulagent may have been lost to clinical medi-cine had it not been for the self-experi-mentation of Jean Borel and H. Stahelin.The oral bioavailability of thisendecapeptide was so poor that its im-munosuppressive properties were lost invivo. However, by dissolving the com-pound in oil prior to ingestion the scien-tists were able to detect significantlygreater levels in their serum. Roy Calne,now at Cambridge, took the compoundto the transplant laboratory and then tothe clinic and proved its efficacy as animmunosuppressive agent.2 Refinementsin clinical immunosuppression with thecombination of cyclosporine, azathio-prine and prednisone set the stage formodern immunosuppression with 1-yearallograft survival approaching 80%. Thecurrent state of the art immunosuppres-sion regimens have now achieved 1-yearpatient and graft survival rates of greaterthan 95% and 88%, respectively.

In this brief review we will focus oncurrent immunosuppressive regimens in

The next majorbreakthrough

occurred with theidentification

of potentimmunosuppressionfrom a product of a

soil fungus identifiedin the Arctic Circle.


use as well as evolving strategies and regi-mens in renal transplantation.

In general, allograft rejection is me-diated by activated T lymphocytes, whichinfiltrate the graft leading to inflamma-tion and eventual destruction. The bestimmunosuppressive drugs target T cellactivation, cytokine production and pro-liferation. This is achieved by combiningtwo to three drugs that act at differentstages of T cell activation. Following kid-ney transplantation, immunosuppressionis typically administered in three distinctphases.

INDUCTION IMMUNOSUPPRESSIONThis phase involves intense immu-

nosuppression in the immediate posttransplant period when the risk of acuterejection is at its highest. Typically, stan-dard immunosuppressive drugs used inthe maintenance phase are also given athigher doses. For patients at high risk forrejection, such as those who are highlysensitized or have had previous organtransplants, the immunosuppression maybe further intensified by the administra-tion of anti-T cell antibodies. These anti-bodies act by binding to specific lympho-cyte cell surface receptors causing lym-phocyte depletion by way of phagocyto-sis or complement-mediated cell lysis.

T cell depleting antibodies includethe polyclonal antilymphocyte antibod-ies – equine ATGAM (Pharmacia) andrabbit ATG (Thymoglobulin, Genzyme)and the monoclonal antibodies OKT3(Ortho Pharmaceutical) andAlemtuzumab (Campath, Genzyme).

Currently, Thymoglobulin is the pre-ferred agent for induction, being supe-rior to ATGAM in reversing acute rejec-tion.3 The use of anti T-cell antibodypreparations does come with a price. It isassociated with profound and prolongedlymphopenia risking serious opportunis-tic infections, bone marrow suppressionand malignancy. Therefore, inductiontherapy should be reserved for patientsat high risk of acute rejection or admin-istered as a strategy to reduce mainte-nance immunosuppression.

For patients who are at low risk forearly acute rejection, such as the elderlyand unsensitized first-time recipients, onemay elect to withhold induction therapy.Alternatively, one may use a nondepletingantibody that is specific only to activatedT-lymphocytes. The prototypes for thisclass of agents are basiliximab (Simulect,Novartis) and daclizumab (Zenapax,Roche), which block interleukin-2 recep-tors expressed in activated T-cells. Sincethese drugs do not affect resting T cells,they do not deplete T cells and have mini-mal side effects.

MAINTENANCEIMMUNOSUPPRESSION

Following the initial phase of avidimmunosuppression, patients begin amaintenance regimen to prevent late al-lograft rejection. Over the last decade,transplant immunosuppressive therapyhas focused on T-cell specific immuno-suppression including tacrolimus,mycophenolate mofetil and sirolimus;each proven more efficacious than the

nonspecific agents azathio-prine and prednisone. In themaintenance phase differentclasses of immunosuppressiveagents are prescribed to tar-get different stages in T cellactivation. The major combi-nation used in most centers,including ours, is a calcineurininhibitor (cyclosporine ortacrolimus) augmented by anantiproliferative agent (aza-thioprine or mycophenolatemofetil) and corticosteroids.(Table 1)

Calcineurin inhibitors(cyclosporine or tacrolimus)remain the cornerstone ofimmunosuppression in renal

transplantation. They act by inhibitingcalcineurin, a key enzyme in T cell acti-vation. Cyclosporine (CsA; Neoral;Sandimmune; Novartis) was first intro-duced in the 1980s and brought aboutsignificant reduction in acute rejectionrates and dramatic improvement in oneyear cadaveric graft survival rates from50% to 80%. In 1999, Tacrolimus(Prograf; Astellas), a macrolide antibioticwas approved for kidney transplantationand was shown in large multicenter trialsto be superior to cyclosporine in prevent-ing acute rejection.4 By 2004 tacrolimuswas the calcineurin inhibitor used by80% of kidney transplant recipients.

Because the mechanism of action issimilar, cyclosporine and tacrolimus can-not be used synergistically. In addition,while both drugs are equally nephrotoxic,their side effect profiles are distinct fromone another. For example, tacrolimus ismore neurotoxic and likely to induce posttransplant diabetes. On the other hand,compared to cyclosporine, tacrolimus isless likely to induce hypertension, hyper-lipidemia, hirsutism and gingival hyper-trophy. Familiarity with these toxicities isimportant as the decision to choose onedrug over the other is influenced by thedrug’s side effect profile - avoiding CsAin adolescents or tacrolimus in Type IIdiabetes mellitus, for example.

Antiproliferative agents are key ad-juncts in transplant immunosuppressionbased on their ability to curb immuneresponse by inhibiting proliferation ofactivated T and B cells. Azathioprine(Imuran, Prometheus), an inhibitor of


nucleotide synthesis, has been used inrenal transplantation since 1962.Mycophenolate mofetil (MMF)(CellCept, Roche), a potent inhibitor ofthe de novo pathway for purine synthe-sis was introduced in 1995 and quicklygained wide acceptance based on its su-periority to azathioprine in preventingacute rejection when combined with ei-ther cyclosporine or tacrolimus.5 As such,the use of azathioprine has significantlydeclined and the combination oftacrolimus and MMF (with or withoutcorticosteroids) is the preferred combi-nation after kidney transplantation inmost centers.

Major side effects of MMF are gas-trointestinal and hematologic. Diarrheacan occur in up to one third of patientsand maybe associated with nausea, bloat-ing and vomiting. Although MMF spe-cifically targets lymphocytes, leukopenia,anemia and thrombocytopenia may alsooccur. These side effects generally re-spond to dose reduction. Recently, anenteric-coated mycophenolic acid hasbeen introduced to reduce gastrointesti-nal symptoms associated withmycophenolate mofetil. Thus far the newagent has shown equal efficacy withMMF but failed to reduce GI com-plaints, implying that the toxicity is re-lated to the systemic levels of the activecompound mycophenolic acid ratherthan a local effect.

Sirolimus (Rapamune, Wyeth) is alsoa macrolide antibiotic, discovered in a soilsample on Easter Island and named forthe indigenous population, the Rapanui.The drug, approved by the FDA in 1999for use in prophylaxis of rejection in re-nal transplant patients,6 is structurallysimilar to tacrolimus, but its action is dis-tinct from that of the calcineurin inhibi-tors. Sirolimus inhibits signal transduc-tion pathways resulting in inhibition ofT-cell proliferation.

The major side effects of rapamycinare myelosuppression and hyperlipi-demia. The main advantage of sirolimusover calcineurin inhibitors is its lack ofnephrotoxicity. This drug has been usedeither as primary therapy (calcineurininhibitor avoidance) or to facilitate with-drawal of calcineurin inhibitor. However,as a primary agent sirolimus showed dis-appointingly higher rates of rejection andsignificant problems with wound healing.

Corticosteroids are nonspecificanti-inflammatory agents that partiallydisrupt activation of T cells and mac-rophages by inhibiting key cytokines inthe inflammatory cascade. These drugshave been a key part of our immuno-suppressive regimen since the 1960sand continue to be used in combina-tion with newer agents although atmuch lower doses. Corticosteroids areassociated with a myriad of side effectsthat increase the risk of serious cardio-vascular disease and other morbidities.These include hypertension,dyslipidemia, glucose intolerance, os-teoporosis and weight gain to name afew. These serious adverse effectsprompted earlier attempts at steroidwithdrawal after kidney transplanta-tion. However, investigators noted asubstantial increase in acute rejectionrates prompting reluctance in adaptingsuch protocols. More recently, underthe protection of stronger inductionimmunosuppression, favorable resultshave been achieved with rapid steroidwithdrawal within the first week aftertransplantation or with complete ste-roid avoidance. Corticosteroids, oncethe mainstay of transplant immunosup-pression, are now usually used in smalldoses (< 0.1 mg/kg/d) or not at all.

TREATMENT OF ESTABLISHEDREJECTION

Acute rejection is a major risk fac-tor for reduced short- and long-termgraft survival. These episodes reflect in-adequate immunosuppression eitherfrom aggressive weaning of immunosup-pression or patient noncompliance. Inmost cases, the patient is asymptomatic;the only clue being a precipitous rise inthe serum creatinine. Definitive diagno-sis rests on a tissue biopsy and treatmentinvolves intensifying immunosuppres-sion by giving high doses of corticoster-oids, increasing the doses of mainte-nance therapy and converting to morepotent agents such as tacrolimus andMMF. In more aggressive cases, use ofanti-T cell antibodies may be indicated.Recent data show a significant drop inboth early and late acute rejection rates,a trend largely attributed to the intro-duction of new and more potent immu-nosuppressive agents.

TRENDSFor many years, the transplant com-

munity relied on very potent immuno-suppression to prevent rejection with thenotion that the benefits from heavy im-munosuppression far outweigh the risks.However, despite impressive reduction inacute rejection rates, there have been onlymodest improvements in long term graftoutcomes. The main causes of late allograftfailure are chronic allograft damage(chronic nephropathy, coronaryvasculopathy, recurrent HCV, e.g.) anddeath from cardiovascular disease, whichis exacerbated by chronic immunosup-pression. Immunosuppressive medica-tions promote infection, glucose intoler-ance, dyslipidemia and nephrotoxicity.Hence, there is at present a shift in focustowards striking a balance between ad-equate immunosuppression on one handand minimization of adverse effects onthe other.

The development of newer immu-nosuppressive agents has substantiallyincreased treatment options. In the pipe-line are drugs that selectively inhibit onlyT cells that react to donor antigens thus,achieving a state of donor specific toler-ance while maintaining a fully functionalimmune system. Other agents that arebeing developed are those that selectivelyblock accessory molecules crucial in therecruitment of inflammatory cells into theallograft; as well as agents that alter T-celltrafficking by driving T-cells into lym-phoid tissues and away from the graft.7

How these newer agents will apply toclinical practice remains to be seen.

Newer strategies are also emerging.The concept of “one size fits all” has beenabandoned for a more individualizedapproach, taking into account thepatient’s immunologic and comorbidrisks. While maintaining low rejectionrates remains crucial in the early stagesof engraftment, minimizing immuno-suppression after 6-12 months is as im-portant in improving long term out-comes. The availability of newer agentshas substantially increased treatment op-tions and potential combinations allow-ing greater flexibility in tailoring immu-nosuppression based on the patient’sclinical profile. To this objective, severalstrategies such as tolerance induction (per-manent acceptance of the graft withoutneed for chronic immunosuppression),


early minimization of steroid exposure oreven complete avoidance, minimizingexposure to calcineurin inhibitors, utili-zation of highly potent induction therapyfollowed by low dose immunosuppressionmonotherapy are all being actively pur-sued. Valuable data from all these trialsare accumulating; from this flurry of newinformation there is optimism for im-proved long-term patient outcomes.These evolving protocols and optionshighlight the requirement for lifelongfollow-up of allograft recipients by a teamof transplant specialists.

REFERENCES1. Merrill JP, Murray JE, et al. Successful homotrans-

plantation of the kidney between nonidenticaltwins. NEJM 1960;262:1251.

2. Calne RY, White DJ, et al. Cyclosporine A in pa-tients receiving renal allografts from cadaver do-nors. Lancet 1978; 2: 1323-7.

3. Gaber AO, First MR, et al. Results of the doubleblind, randomized, multicenter, phase III clinicaltrial of thymoglobulin versus ATGAM in the treat-ment of acute graft rejection episodes after renaltransplantation. Transplantation 1998; 66: 29-37.

4. Mayer A, Dmitrewski J, et al. Multicenter ran-domized trial comparing tacrolimus (FK506) andcyclosporine in the prevention of renal allograftrejection. Transplantation 1997; 64: 436-43.

5. The Tricontinental Mycophenolate Mofetil Re-nal Transplantation Study Group A. A blinded,randomized, clinical trial of mycophenolatemofetil for the prevention of acute rejection incadaveric renal transplantation. Transplantation1996; 61: 1029-37.

6. Kahan BD. The Rapamune US Study Group.Efficacy of sirolimus compared with azathioprinefor reduction of acute renal allograft rejection.Lancet 2000; 356: 194-202.

7. Hardinger KL, Koch MJ, Brennan D. Current andfuture immunosuppressive strategies in renal trans-plantation. Pharmacotherapy 2004; 24:1159-76.

Angelito Yango, MD, is Assistant Pro-fessor of Medicine, Brown Medical School.

Amit Johnsingh, MD, is a Renal Fel-low, Brown Medical School.

CORRESPONDENCEAngelito Yango, MDRhode Island Hospital APC 921593 Eddy StreetProvidence RI 02903phone: (401) 444-8345E-mail: [email protected]


Considerations for the Inpatient Care ofSolid Organ Recipients

Kevin M. Lowery, MD, and Reginald Y. Gohh, MD

�Advances in the management of patientswith solid organ transplants and improve-ments in immunosuppression have re-sulted in prolonged patient and allograftsurvival. These advancements have, inturn, led to an increase in the number ofpatients undergoing solid organ trans-plantation: in 2005, over 28,000 patientsin the United States received a solid or-gan transplant. 1 Because the majority sur-vive more than 10 years after transplan-tation, physicians in all fields will care forthese patients in their practices. Whilemost interactions will likely involve out-patient evaluations and procedures, theseencounters will offer the largest varietyof challenges in the inpatient setting.Most transplant centers utilize a team ap-proach to managing post-transplant pa-tients. This “team” often includes, but isnot limited to, transplant surgeons, medi-cal sub-specialists in the transplantedorgan’s field, infectious disease specialists,pharmacists, social workers, and nurses.While close interaction with this trans-plant team remains of utmost importancein all aspects of allograft recipient’s care,it is important that all physicians becomefamiliar with the select facets of medicine

that this growing population presents.This article will summarize these chal-lenges and review the most recent rec-ommendations for the inpatient manage-ment of solid organ recipients.

Many physicians have some educa-tion related to solid organ transplanta-tion, but few have sufficient experienceto adjust immunosuppressive agents. Inmost instances, maintenance of thepatient’s oral immunosuppressive medi-cation is preferred; however, several cir-cumstances may arise where this is eithernot necessary or not an option. Whethera plan of care for a clinical situation or apre-test precaution, inpatients frequentlyare required to maintain a Nothing PerOral (NPO) status. When an NPO sta-tus is expected to be minimal in duration(less than 12 hours), it is often accept-able to withhold the administration oforal immunosuppressive agents until thestatus is changed and re-start with theprescribed dosing schedule at that time.For longer durations, however, conver-sion to an intravenous (IV) preparationis recommended. Corticosteroids,cyclosporine, tacrolimus, azathioprine,and mycophenolate mofetil are all avail-

able as IV preparations. Sirolimus is notavailable in IV form in the United States,and can either be transiently discontin-ued or supplanted with increased IV dos-ing of other immunosuppressive medi-cations when oral administration is notfeasible. Furthermore, it may be neces-sary to temporarily discontinue all immu-nosuppressive medications in circum-stances where it is felt a more robust im-mune response may alter a life-threaten-ing situation. Although no specificguidelines are available for medical man-agement in these situations, there is someevidence that the upsurge of cytokinesassociated with sepsis and severe illnessmay protect against allograft rejection.2

In such instances, clinical monitoring isof chief importance, as immunosuppres-sion should be reintroduced as soon asthe clinical recovery begins to avoid al-lograft rejection.

The dosing and administration ofimmunosuppressive medications in theinpatient setting can also be potentiallyproblematic with regards to poly-phar-macy. While immunosuppressive regi-mens will vary, calcineurin inhibitors(CNI) remain a mainstay for the major-


ity of solid organ transplant recipients.The two CNIs in use today (cyclosporineand tacrolimus) and the antimetabolitedrug sirolimus are primarily metabolizedand eliminated by the cytochrome P450-IIIA4 enzyme system. Therefore, pa-tients utilizing these medications are athigh-risk for numerous drug interactions.Use of medications that induce or inhibitthe cytochrome P450 system are not con-traindicated for these patients, but closemonitoring of organ function as well ascyclosporine, tacrolimus, or sirolimus lev-els should be maintained when introduc-ing or discontinuing such medications.Additionally, many medications may in-hibit or enhance absorption of immuno-suppressive medications and alter the lev-els of these medications. (Table 1)

Cardiovascular disease (CVD) re-mains a major cause of morbidity in or-gan transplant recipients and remains theleading cause of death among kidney al-lograft recipients.3 The elevated risk ofCVD in this population is due to a varietyof factors related to both pre-existing (pre-transplant) risk factors as well as variablesspecific to the post-transplant setting. Inrenal allograft recipients, the pre-trans-plantation prevalence of hypertension,diabetes mellitus, hypercholesterolemia,and obesity are 80%, 55%, 60%, and30% respectively.4 Additionally, a num-ber of these CVD risk factors are associ-ated with or exacerbated by immunosup-pressive drugs. Calcineurin inhibitors andcorticosteroids are associated with an in-creased risk of hypertension, diabetes mel-litus, and lipid abnormalities and sirolimuscommonly causes hyperlipidemia .5, 6

While mortality secondary to CVD in non-renal solid organ allograft recipients islower than renal allograft recipients, thecomplications seen with these immunosup-pressive agents is universal, and the preva-lence of CVD will likely rise in these popu-lations as well with longer allograft surviv-als being seen today.

Corticosteroids and CNI predisposepatients to developing post-transplanta-tion diabetes mellitus (PTDM). Corti-costeroids impair insulin production, im-pede the activation of the glucose/FFAcycle, impair glucose uptake in the mus-culature, and decrease the number andaffinity of insulin receptors.7 Thecalcineurin inhibitors, cyclosporine andtacrolimus, are postulated to diminish beta

cell insulin production through inhibitionof specific cellular proteins.8 WhilePTDM can be treated similarly to Type IIdiabetes mellitus, special considerations re-garding contraindications or potential sideeffects of the available oral agents must bemade. Impaired liver or renal functionmay pose increased risks of hypoglycemiawith sulfonylurea agents, and arecontraindications, along with congestiveheart failure, for use of metformin. Giventhe limitations of oral agents, and the nec-essary exposure to immunosuppressivemedications, a majority of patients withPTDM eventually require exogenous in-sulin treatment.8 During episodes whereimmunosuppressive doses (in particularcorticosteroids) are altered, large variationsin blood glucose levels can be expected anddiligence in monitoring is of paramountimportance.

Because most transplant recipientsare maintained on corticosteroids, adre-nal insufficiency is a theoretical concernin the inpatient setting, but rarely a prac-tical one. Since the current standard ofcare for routine maintenance immuno-suppression generally involves relativelylow corticosteroid doses (5-10mg of pred-nisone daily) patients usually have suffi-cient reserve to respond to stress. Severalprospective studies demonstrated thataugmentation of baseline steroid doses invarious settings of stress (sepsis, surgery,metabolic abnormalities) is unnecessaryand may not entirely be benign.9-11 How-ever, if the patient has signs or symptomsof adrenal insufficiency, the use of high-dose steroids (50-100 mg of hydrocorti-sone every 8 hours) should be initiatedwith a return to baseline dosage over aperiod of 2-3 days as clinical status per-mits.

Although, when available, renaltransplantation remains the treatment ofchoice for end-stage renal disease, trans-plantation usually falls short of replac-ing renal function to normal levels. Theaverage glomerular filtration rate of kid-

ney transplant recipients rarely exceeds50 mL/min/2.73m2 as estimated by anequation derived from the Modificationof Diet in Renal Disease (MDRD)study.12 Recipients of other solid organtransplants are at risk for diminishedrenal function as well; most likely a re-sult of the nephrotoxicity related tolong-term exposure to immunosuppres-sive agents, in particular calcineurin in-hibitors. Approximately 32% of heartrecipients, 20% of lung recipients, and18% of liver recipients have chronickidney disease (CKD) at 5 years post-transplantation; and up to 29% of theseindividuals will eventually require someform of renal replacement therapy.13 Inan inpatient setting, this underlyingCKD may predispose patients to fluidand electrolyte abnormalities and totoxic accumulation of anesthetic or an-algesic medications. It is important toalso keep in mind that renal allograftslose their innate ability to autoregulaterenal blood flow due to functional den-ervation of a transplanted kidney, thuspredisposing these patients to episodesof ischemic acute renal failure.

Infection remains one of the mostcommon complications of immunosup-pressive therapy. Since the vulnerabilityto infection is related to both pathogenicexposure and the overall immunosup-pressive state, the risk for developing spe-cific types of infections is dependent onthe time period post-transplant. Imme-diately post-transplant, patients will bemost at risk for pathogens commonlyseen in non-immunosuppressed surgicalpatients. From 1-6 months post-trans-plant, while immunosuppression dosingremains relatively high, viral and oppor-tunistic infections become more preva-lent. The majority of patients receiveprophylaxis against cytomegalovirus(valganciclovir), pneumocystis carinii andnocardia (TMP-SMZ) and fungal infec-tion during this period. Beyond sixmonths, for patients with stable allograftfunction and lower immunosuppressiveregimens, infections seen in the generalpopulation are again most common, al-though viral pathogens can appear at anytime and the clinical course for viral andbacterial infections is often prolonged.14

As a result, these patients often require alonger duration of antibiotics and antivi-ral medications.

…most physicianswill likely at some

point be involved inthe routine care of

such patients.




Immunosuppression also predis-poses all transplant recipients to delayedwound healing as a result of diminishedtensile strength and tissue integrity. Evenat low doses, corticosteroids impair tissueintegrity and are associated with capillaryand tissue friability.15, 16 For this reason,it is recommended that skin staples bekept in place 2-3 times longer in thetransplant recipient and many transplantsurgeons recommend the use of nonab-sorbable sutures whenever possible. Re-cent information has implicated the useof sirolimus with delayed wound healingin the immediate post-transplantationsetting when compared to the use oftacrolimus.17 No data are available thusfar as to whether or not this increasedpropensity toward delayed wound heal-ing with sirolimus carries over to subse-quent surgeries, but this should be con-sidered in these situations.

In conclusion, the number of solidorgan transplant recipients in the UnitedStates is steadily increasing. As a result,most physicians will likely at some pointbe involved in the routine care of suchpatients. While close involvement of ateam of transplant specialists during theseinteractions remains the standard for care

of all such patients, it is important thatall physicians obtain a general under-standing of the unique aspects of carepresented by this population.

REFERENCES1. Organ Procurement and Transplantation Network.

www.optn.org. Accessed October 26, 2006.2. Burke GW, Ciancio G, et al. Association of

interleukin-10 with rejection-sparing effect inseptic kidney transplant recipients. Transplanta-tion 1996; 61: 1114-6.

3. Foley RN, Parfrey PS, Sarnak MJ. Clinical epide-miology of cardiovascular disease in chronic renaldisease. Am J Kidney Dis 1998; 32: S112-9.

4. Ojo AO. Cardiovascular complications after re-nal transplantation and their prevention. Trans-plantation 2006; 82: 603-11.

5. Kasiske BL. Epidemiology of cardiovascular dis-ease after renal transplantation. Transplantation2001; 72: S5-8.

6. Brattstrom C, Wilczek HE, et al.Hypertriglyceridemia in renal transplant recipi-ents treated with sirolimus. Transplantation Pro-ceedings 1998; 30: 3950-1.

7. Bialas MC, Routledge PA. Adverse effects of cor-ticosteroids. Adverse Drug Reactions ToxicologicalReviews 1998; 17: 227-35.

8. Montori VM, Velosa JA, et al. Posttransplantationdiabetes. Diabetes Care 2002; 25: 583-92.

9. Bromberg JS, Alfrey EJ, et al. Adrenal suppressionand steroid supplementation in renal transplantpatients. Transplantation 1991; 51: 385-90.

10. Glowniak JV, Loriaux DL. A double-blind studyof perioperative steroid requirements in secondaryadrenal insufficiency. Surgery 1997; 121: 123-9.

11. Kehlet H, Binder C. Adrenocortical function andclinical course during and after surgery inunsupplemented glucocorticoid-treated patients.Brit Med J 1973; 2: 147-9.

12. Poge U, Gerhardt T, et al. MDRD equations forestimation of GFR in renal transplant recipients.Am J Transplantation 2005; 5: 1306-11.

13. Ojo AO, Held PJ, et al. Chronic renal failure aftertransplantation of a nonrenal organ. NEJM 2003;349: 931-40.

14. Fishman JA, Rubin RH. Infection in organ-trans-plant recipients. NEJM 1998; 338: 1741-51.

15. Anstead GM. Steroids, retinoids and woundhealing. Adv Wound Care 1998; 11: 277-85.

16. Meadows EC, Prudden JF. A study of the influ-ence of adrenal steroids on the strength of healingwounds. Surgery 1953; 33: 841-8.

17. Dean PG, Lung WJ, et al. Wound-healing com-plications after kidney transplantation. Transplan-tation 2004; 77: 1555-61.

Kevin M. Lowery, MD, is a RenalFellow, Brown Medical School.

Reginald Y. Gohh, MD, is AssociateProfessor of Medicine, Brown MedicalSchool.

CORRESPONDENCEReginald Gohh, MDRhode Island Hospital APC 921593 Eddy StreetProvidence RI 02903phone: 401-444-8345E-mail: [email protected]


Is There a Rational Solution to the Kidney Shortage?Anthony P. Monaco, MD

�The treatment of mortal and morbiddiseases with organ replacement is oneof the great medical miracles of the 20th

century. This is particularly true in thecase of kidney transplantation, the com-monest solid organ transplant, wheretransplantation produces not only a bet-ter quality of life, but also prolongs lon-gevity compared to dialysis.1 This happycircumstance has dramatically increasedthe number of patients eligible for kid-ney transplantation but at the same timehas underscored the severe shortage ofkidneys for transplantation. Less than15% of some 70,000 Americans on thekidney waiting list in 2005 receivedtransplants; by 2010 the waiting list willexceed 100,000.2 As a direct conse-quence of the kidney shortage, waitingtimes on dialysis, already 5-10 years insome regions of the country, continue toincrease, leading to increased dialysis-as-sociated cardiovascular morbidities andmortality in those patients who are even-tually transplanted.3 Sadly annual deathrates on the dialysis waiting list have in-creased by almost 25% over the past fouryears.4

In the face of this kidney shortagethere have been only modest increases inthe number of deceased donor (DD) kid-neys in recent years, essentially achievedby using so-called marginal donors, i.e.,extended criteria donors (older, hyper-tensive donors frequently dying of cere-brovascular causes) and donors after car-diac death (donors who expire withoutcontrolled cardiorespiratory support),both circumstances contributing to kid-neys of lesser quality. Recently, the USDepartment of Health and Human Ser-vices initiated the Organ DonationBreakthrough Collaborative, a nationaldrive to increase the number of deceaseddonors. This effort will have the addi-tional benefit of increasing the availabil-ity of non-renal solid organ transplantsas well as kidneys. It is estimated that onlyapproximately 50% of eligible deceaseddonors eventually come to organ dona-tion.5 There has been a more substantialincrease in the use of living kidney do-nors: in the past year living donor kidney

transplants exceeded those for deceaseddonors. The dramatic improvement ineffective immunosuppression has elimi-nated the need for reduced histocompat-ibility (consanguinous living related do-nor-recipient pairs); in landmark studiesby Terasaki et al6 kidney transplants fromfriends, spouses, lovers, and other unre-lated donors survived as well as living re-lated donor kidneys. The risks of donornephrectomy (perioperative morality of0.03% and morbidity of <2%) are wellestablished and generally well accepted.2

The number of living kidney donorstransplanted now approaches 40-50% inmany programs. Every effort is employedto utilize appropriate willing donors. Anumber of thoughtful, well-intentionedstrategies have been implemented.7

Thus, totally altruistic donors—uniqueindividuals who volunteer to donate a kid-ney to any deserving person—are nowconsidered acceptable (after appropriatepsychological evaluation). Similarly, ex-changes (swaps) between one or moreABO-incompatible living-donor recipi-ent-donor pairs or crossmatch incompat-ible pairs (or even combinations thereof )have been pursued. Dr. Paul Morrisseyof our Rhode Island Transplant Grouphas been a national leader in these twoconcepts. These maneuvers add a fewadditional transplants to all programs,but their overall effect in extending thedonor pool, in my experience, is limited.

Advances in basic science researchthat would facilitate generation andgrowth of human solid organs (kidneys)in vitro and/or permit transplantation ofxenogeneic organs are no doubt yearsaway. The extraordinary effectiveness ofkidney transplantation, especially livingkidney transplants, to cure kidney diseasefor a very long time has brought intoprime focus the need to consider possiblealternatives in the form of rewards and/or financial compensation to expand thedonor pool.2,8,9 Financial compensation(as opposed to reimbursement for ex-penses incurred or loss of income) fororgan donation has been strictly prohib-ited in the United States by the NationalOrgan Transplant Act (NOTA) which

prohibits any person to acquire any hu-man organ for valuable consideration(money) for use in human transplanta-tion or face fines and imprisonment.This legislation was well intentioned, andbasically was designed to protect the poorand disenfranchised from potentially dan-gerous and unhealthy exploitation by un-scrupulous middlemen and avariciousbrokers. Such legislation has been quiteeffective in the United States, but an ex-tensive black market to obtain living do-nor kidneys—many of marginal quality,transplanted under less than optimal con-ditions, frequently by surgeons of limitedquality and experience—has flourishedin a number of countries around theworld.10 The number of American pa-tients that utilize these organ black mar-kets has grown; the presence of such pa-tients seeking post-transplant care is nowcommonplace in most American pro-grams.

Government prohibition of the un-regulated sale of kidneys and other or-gans to protect the poor from exploita-tion is appropriate and certainly justified.On the other hand, the idea that anytype of gain, reward, or compensation—financial or otherwise—for organ dona-tion is unethical and inherently undesir-able does not necessarily follow. Rewardsfor doing good, for making self-sacrifices,for taking personal risks to help others inone’s family, community, or country areevident in every fabric of modern West-ern society. Numerous examples can begiven but perhaps the most obvious ex-ample in the United States is voluntarymilitary service. The overwhelming ma-jority of volunteers for the United Statesmilitary are motivated by idealism andpatriotism, but they are also encouragedto volunteer with inducements of paidcollege educations, enlistment bonuses,reenlistment bonuses, and substantial fi-nancial recovery for injury or mortality.11

It is not surprising that minority groupmembers with limited financial resourcesare numerically disproportionately rep-resented in the military. Likewise, signifi-cant numbers of non-citizen immigrantsvolunteer for military service, eventually


being rewarded for their service byAmerican citizenship (a route taken bymy own father in World War I). Thus,the concept of encouraging and reward-ing acts of self-sacrifice and personal risktaking to help others—acts essentiallymotivated by love, altruism, idealism,patriotism or the like—with valuable con-siderations (money, etc.) is unequivocallyestablished and considered ethically ac-ceptable, even with the realization thatmore poorer people will undertake self-sacrifice and personal risk in part to gainthe financial rewards.

It is accepted that donor evaluationand workup, operative and postoperativecare should be covered by the recipient’smedical insurance. Also considered ac-ceptable is reimbursement of donors fortravel costs and lost wages. A recent pro-posal has suggested that donor benefitsalso include short-term (one year) termlife insurance (to cover possible operativemortality) and additional lifetime (Medi-care) medical insurance.2 The inclusionof a direct financial payment subsidy hasbeen considered exploitive and problem-atical.12 I think the biggest problem ininitiating a system of financial rewards forkidney/organ donation is the fact thatboth opponents12,13 and proponents 2,8 ofthe concept refer to this activity exclu-

sively as buying and selling organs. Buy-ing and selling implies financial negotia-tion between recipient (buyer) and do-nor (seller), suggests higher or lowerprices in the face of variations in valueand quality, and may involve middlemenor brokers. Certainly this is not desirable.We need a government regulated, scru-pulously supervised program in which aperson or his/her estate receives a fixedvaluable enhancement or reward for or-gan donation. Transplant pioneer, PaulTerasaki, MD of UCLA, suggested thatdonors be rewarded with a valuable goldmedal; the implication being that it couldbe kept or sold if so desired.14 I envisiona scheme in which a government insur-ance trust fund is established and admin-istered by a federal agency or commis-sion. A direct financial incentive wouldbe paid to both living donors and heirsof deceased donors as a reward or hono-rarium for organ donation. The rewardwould be dispersed by the federal agencyafter confirmation of organ donation,similar to the payment of an insurancepolicy. Importantly, in this era of expand-ing medical expenditures, the reduced fi-nancial burden of dialysis costs derivedfrom increased kidney transplantationwould make the program revenue neu-tral.

REFERENCES1. Wolfe RA, Ashby VB, et al. Comparison of mor-

tality in all patients on dialysis, patients on dialysisawaiting transplantation, and recipients of first ca-daveric transplant. NEJM 1999; 341: 1725-30.

2. Gaston RS, Danovitch GM, et al. Limiting finan-cial disincentives in live organ donation. Am J Trans-plant 2006; 6: 2458-555.

3. Meier-Kriesche HV, Kaplan B. Waiting time ondialysis as the strongest modifiable risk factor forrenal transplant outcomes. Transplantation 2002;74: 1377-81.

4. Merion RM, Ashby VB, et al. Deceased-donorcharacteristics and the survival benefit of kidneytransplantation. JAMA 2005; 294: 2726-33.

5. Sheehy E, Conrad SL, et al. Estimating the num-ber of potential organ donors in the United States.NEJM 2003; 349: 667-74.

6. Terasaki PI, Cecka JM, et al. High survival rates ofkidney transplants from spousal and living unre-lated donors. NEJM 1995; 333: 333-6.

7. Wessel D. Easing the kidney shortage. Wall Str J17 June 2004.

8. Friedman E, Friedman A. Payment for donor kid-neys. Kidney Int 2006; 69: 960-2.

9. Monaco AP. Rewards for organ donation. KidneyInt 2006; 69: 955-7.

10. Tilney NL. Transplant: From Myth to Reality. YaleUniversity Press, New Haven and London2003:364-74.

11. Brooke J. On the farthest US shores, Iraq is a wayto a dream. NY Times 31 July 2005.

12. Fox MD. The price is wrong:. Am J Transplant2006; 6: 2529-30.

13. Delmonico F. Commentary: The WHO resolu-tion on human organ and tissue transplantation.Transplantation 2005; 79: 639-40.

14. Terasaki PA. Congressional gold medal for trans-plant donors and families. Am J Transplant 2005;5: 1167.

Anthony P. Monaco, MD, is Professorof Surgery, Harvard Medical School, andDirector of Transplant Services, Rhode Is-land Hospital.

CORRESPONDENCEAnthony Monaco, MDRhode Island Hospital APC 921593 Eddy StreetProvidence, RI 02903Phone: (617) 632-9822e-mail: [email protected]


The National Organ Transplantation BreakthroughCollaborative – A Rhode Island Hospital Perspective

Kevin M. Dushay, MD, FCCP, and Suzanne Duni Walker, Esq, RN, BSN�

As of November 27, 2006, close to94,000 people in the United States werewaiting for organ transplants, comparedto fewer than 75,000 in 2000. The num-ber of patients dying while waiting fortransplants rose from 6,500 in 2000 to7,300 in 2004. In New England (Maine,New Hampshire, Vermont, Massachu-setts, Rhode Island, and Connecticut)nearly 4,000 individuals are wait-listedfor organ transplants; in Rhode Island thefigure is over 250. In 2004, only 51% ofpotential organ donors provided organsfor transplantation.1

This disparity spearheaded the firstOrgan Donation Breakthrough Collabo-rative (ODBC) in October 2003. Rep-resentatives of the US Department ofHealth and Human Services along withorgan transplantation and hospital pro-fessionals began a year-long program toachieve greater access to donor organs fortransplantation. A second Organ Dona-tion Breakthrough Collaborative fol-lowed, and over the past year, the firstOrgan Transplantation BreakthroughCollaborative (OTBC) was convened.Collaborative members have used tech-niques developed at the Institute forHealthcare Improvement under the di-rection of Donald M. Berwick, MD, todisseminate best practices for increasingboth the number of organ donors andthe number of organs procured per do-nor. Principally these changes involvedincreasing consent rates and relaxing ar-bitrary exclusion criteria when data indi-cate acceptable recipient and graft sur-vival rates.

Rhode Island Hospital/HasbroChildren’s Hospital, the only organ trans-plant center in Rhode Island, has been amember of all three breakthrough col-laborative sessions, represented by teamsconsisting of Rhode Island Hospital(RIH) and New England Organ Bank(NEOB) staff. The NEOB is the organprocurement organization (OPO) thatserves Rhode Island and most of NewEngland. This article is a report to theRhode Island medical community of theorgan donation and transplantation prac-tices that have been implemented overthe past year at RIH. We also describeopportunities for physicians to increasethe supply of donor organs.

HIGH LEVERAGE CHANGESThe ODBC, and later the OTBC,

stressed these goals: 1,2

1. Advocate Organ Donation as theMissionThose involved with the entire pro-cess, from identifying potential or-gan donors, to informing familiesabout the opportunity to provide apotentially life-saving organ dona-tion, to caring for the donor, mustbe enthusiastic about, committedto, and skilled in the practices oforgan donation.

2. Involve Senior Leadership to getResultsAt RIH, the Senior Vice Presidentof Medical Affairs, Boyd P. King,MD, attends the Organ Donation

Advisory Committee meetings, andmeets with its members to provideadministrative backing and support

3. Deploy a Self-Organizing OPO/Hospital TeamA Hospital Relations Coordinator(HRC), Suzanne Walker, Esq, RN,BSN, and two Family Service Co-ordinators (FSC), Leo Trevino andDarlene Fiotto, all employed by theNew England Organ Bank, workfrom an NEOB satellite officewithin the RIH complex to respondquickly to referrals of potential do-nors. In addition, they are valuableresources for information and edu-cation regarding organ donation.The HRC regularly analyzes hospi-tal-specific data through deathrecord reviews and “After ActionReviews” to identify missed oppor-tunities for organ donation. TheFSCs are trained requestors, as wellas liaisons to the community, meet-ing with religious and secular lead-ers and providing or coordinatingcommunity-directed educationalprograms. Completing the OPOteam are the NEOB Donation Co-ordinators (DCs), who provide on-site continuous management of theorgan donor and the donation pro-cess. The DC collaborates with thehealth care team in the critical careof the organ donor, including test-ing, requesting consults, and direct-ing therapy. At the same time, in con-junction with Newton-based Organ


Clinical Coordinators (OCC), theyare responsible for allocation andplacement of all recovered organs.The DCs coordinate the surgicalteams, technicians, operating roomstaff, and transplant centers.RIH has developed and is expand-ing a cadre of critical care nurseorgan donation champions, whoprovide education and support totheir colleagues. Furthermore,there are RIH respiratory therapistsand an Intensivist Physician Cham-pion who have designated them-selves as available for assistance inthe management of organ donors.RIH social workers join the OPO/Hospital organ donation team toprovide family support.

4. Practice Early Referral, Rapid Re-sponseFamilies are rarely prepared for endof life decisions when a loved one isa victim of trauma or a sudden neu-rologic event. Information oftenmust be presented several times.Success in obtaining consent fororgan donation is enhanced whenfamilies do not feel rushed byhealth-care professionals, when ex-pert, sensitive, and confident indi-viduals answer questions, and wheninformation is available at the timeit is requested.3

5. Master Effective RequestingStudies have shown that the high-est consent rates are achieved whenphysicians refer families to OPOpersonnel for discussion regardingthe opportunity to donate a lovedone’s organs. In addition, physiciansshould support the offer of organdonation as an opportunity to savea life, rather than as a legal require-ment at the time of a patient’s an-ticipated death.3 Physicians mustrecognize the possibility of an ap-pearance of a conflict of interest inthe family’s mind when they tell afamily that their loved one’s prog-nosis is poor and then speak of or-gan donation. First and foremost,families want to hear from theirdoctor that he or she is doing ev-erything possible for their lovedone. After an interval, the doctor

must ensure that the family under-stands that their loved one is notgoing to survive, before they are ap-proached regarding organ or tissuedonation, regardless of who is do-ing the requesting.

6. Implement Donation after Car-diac DeathThe number of brain-dead poten-tial donors has always been less thanthe number of patients waiting fortransplants. Even with optimal con-sent rates and optimal numbers oforgans procured, some patients willbe on waiting lists. Patients not suc-cumbing to brain death should stillhave the right to donate their or-gans to others who will otherwisedie. In addition, their families areentitled to the solace that comesfrom the donation of life-saving or-gans. However, many donor hospi-tals do not have policies to providethe option of donation after cardiacdeath to their patients who wish todo so. This is a disservice, not onlyto patients who wish to bestow thisgift, but to other patients whomight be recipients of that gift.

ACTIONS TAKEN OVER THE PASTYEAR AT RHODE ISLAND HOSPITAL

Clinical TriggersA set of criteria indicating a patient

is appropriate for referral to the NEOBhave been developed, printed on lami-nated pocket-sized cards, and distributedto staff in the Emergency Room andCritical Care Units. Any patient < 85years old with a Glasgow Coma Scale of= 4 due to neurologic insult, or in whomterminal extubation or no resuscitationstatus is being considered, is a potential

organ donor and should be discussedwith the NEOB (phone: 800-446-NEOB). The suitability of a donor or-gan depends on the prognosis of eachpotential recipient without it; therefore,the decision to reject a possible donororgan should be made in consultationwith transplant centers.

Donation Team HuddlesThese brief meetings, involving the

NEOB on-site coordinator(s), thepatient’s nurse and/or physician(s) and/or other healthcare providers, the unitsocial worker, and any other appropriateindividuals, are held as soon as possibleafter referral of a potential organ donor,and periodically thereafter, in order todetermine the best manner and timingfor approaching the family to discuss theopportunity for donation.

After Action ReviewsThese meetings review the course of

recent referrals to the NEOB. Previously,these meetings were held quarterly, butwill now be held weekly or biweekly sostaff will have a clear memory of cases.This will minimize the risk of losing sub-sequent donors to repeated suboptimalpractices.

Real Time Death RecordReviews

These reviews identify potential do-nors who were not referred to the NEOBat all. The patients’ healthcare providers areinformed of these missed opportunities.

Identify Physician/ClinicianChampions

For the most part, physicians com-mitted to increasing the number of do-nor organs are not born, they are made.Until recently, most OPOs had their DCsrelieve physicians of the responsibility ofcaring for their patients once they haddied and made the transition from pa-tient to organ donor. As a result, mostphysicians have little to no experiencecaring for patients following brain death.A profound series of pathophysiologicderangements occur in the brain deadpatient.4,5 Superimposed on the patho-physiology of brain death are the iatro-genic complications often present follow-ing unsuccessful resuscitation of the se-verely brain injured patient. The Organ

The patient shouldbe fully supported

until organ donationhas been absolutelyruled out if we are toreduce the numberof patients dying on

the waiting list.


Transplantation Breakthrough Collabo-rative has promoted the need to involveintensivists in the management of organdonors, based on data demonstratingmore organs transplanted per donorwhen intensivists care for donors, andwhen donor management guidelines arefollowed and achieved.6-8

Even prior to obtaining consent fororgan donation, physicians can potentiallyhelp increase the number of organs pro-cured per donor. Often physicians becomeless aggressive in patient management af-ter telling a family the patient’s poor prog-nosis and discussing the option of with-drawing cardiopulmonary support. Phy-sicians do not want to prolong the dyingprocess for the patient or the suffering ofthe family. However, the process of ob-taining consent for organ donation mayrequire multiple discussions extending overhours, even days. During this time, po-tential organ donors may fall into a “thera-peutic hole” with worsening hemodynam-ics, metabolic derangements, and failingorgans. Once consent for organ donationis obtained, the NEOB Donation Coor-dinator and/or physician may resume ag-gressive care only to find irreversible or-gan damage precluding donation. Thepatient should be fully supported untilorgan donation has been absolutely ruledout if we are to reduce the number of pa-tients dying on the waiting list.

RESULTSOver the years 2003, 2004, and

2005, the number of organ donors andorgan transplants in New England re-mained relatively stable, but at levelshigher than those in 2000 and earlier.(Table I) At the 2nd Annual NationalLearning Congress on Organ Donationand Transplantation in October 2006,the NEOB was recognized for its sus-tained high rate of Donation after Car-diac Death (DCD) donors over the pastyear, given a Donation Service Area per-formance award for outstanding perfor-mance in multiple aspects of organ do-nation, and a National ImprovementLeader Award. The staff of the NEOBdeveloped and implemented the secondlargest DCD program among 58 OPOsin the United States. At the same event,RIH won an Organ Donation Medal ofHonor for its high rate of obtaining con-sent for organ donations.

SUMMARYPatients needing organ transplants

still exceed the number of organs, andeach year some patients on waiting listsdie. A series of national collaborativemeetings identified practices shown toincrease organ donation consent rates andorgans procured per donor. A partner-ship between the NEOB and donor hos-pitals is important to achieve these goals.By following best practices set forth bythe Collaborative movement and put inplace by NEOB, physicians can increasethe supply of donor organs in New En-gland and nationally.

REFERENCES1. Organ Transplantation Breakthrough Collaborate

Charter, 2nd Annual National Learning Congresson Organ Donation & Transplantation. NewOrleans, LA, October 2006.

2. Organ Donation Breakthrough Collaborative,First Annual National Learning Congress. Pitts-burgh, PA, May 2005.

3. Siminoff LA, Gordon N, et al. Factors influenc-ing families’ consent for donation of solid organsfor transplantation. JAMA 2001; 286:71.

4. Szabó G. Physiologic changes after brain death. JHeart Lung Transplant 2004; 23: S223.

5. Wood KE, Becker BN, et al. Care of the potentialorgan donor. NEJM 2004; 351:2730.

6. Personal communication, Christopher C. Curran,Organ Operations, New England Organ Bank,Newton, Massachusetts.

7. Rosendale JD, Chabalewski FL, et al. Increasedtransplanted organs from the use of a standard-ized donor management protocol. Am J Trans-plant 2002; 2:761.

8. Rosendale JD, Kauffman M, et al. Aggressivepharmacologic donor management results in moretransplanted organs. Transplantation 2003;75:482.

9. Personal communication, Jim Bradley, Clinical In-formation Systems, New England Organ Bank,Newton, Massachusetts.

Kevin M. Dushay, MD, FCCP, is As-sistant Professor of Medicine, Brown Medi-cal School.

Suzanne Duni Walker, Esq, RN,BSN, is Hospital Relations Coordinator,New England Organ Bank.

CORRESPONDENCE:Kevin M. Dushay, MD, FCCPPulmonary, Critical Care & SleepDisorder MedicineRhode Island Hospital593 Eddy Street – APC 7Providence, RI 02903phone: 401-444-3565E-mail: [email protected]


The Assessment and Management of Falls Among OlderAdults Living In the Community

Michael P. Gerardo, DO

GERIATRICS FOR THEPRACTICING PHYSICIAN

A 78-year-old man presents to your officefor the first time. A review of his medicalrecord reveals a problem list that includeshypertension, atrial fibrillation, osteoar-thritis, depression and a previous transientischemic attack. His medication list in-cludes metoprolol, warfarin, acetami-nophen, omeprazole, escitalopram ox-alate, and aspirin. He tells you that al-though he has been educated on theproper use of his cane, and encouraged touse it, he does so intermittently; “when Ifeel off-balance.” He adds that his visionis not as good as it used to be. On moredirect questioning, he reports that he hasbeen afraid of falling since last winter. Hestumbled on a patch off ice and since thenhas noticed that he is not as quick or steadyon his feet as he would like.

This case illustrates the typical pre-sentation of older adults at risk of falling.The exact cause of falling is often difficultto pinpoint because numerous contribut-ing factors (such as age-related changes,diseases commonly occurring with aging,multiple co-morbidities and the medica-tions used to treat them) can be identifiedin an older adult. The goal of this editionof the column is to provide an evidenced-based approach to fall prevention. I be-gin with a discussion of the scope of theproblem facing clinicians, and proceed toa model for assessment and intervention;at the conclusion of this article are the well-established clinical guidelines for fall pre-vention among older adults living in thecommunity.

IMPACT & ETIOLOGYFalls represent an enormous psycho-

logical, social and financial cost to theindividual, family and society. It is esti-mated that more than one third of com-munity-dwelling persons age 65 or olderexperience a fall each year, that numberincreases to 50% among persons over the

Division of Geriatrics Quality Partners of RIDepartment of Medicine EDITED BY ANA C. TUYA, MD

tors for falling increases sharply after age70.7 Physicians should at least once a yearask older patients about any falls or thefear of falling. This yearly screen shouldinclude questions about and observationfor difficulties with balance or gait. The“Get-Up and Go” test is a short screen-ing tool that tests for balance and strength.It involves asking the patient to rise froma chair, walk ten feet, turn, return to thechair and sit. Performing the task longerthan 9 seconds confers a two-fold risk offalling. Difficulty with any part of thetest may increase risk as well. A timedscore that is greater than 30 seconds in-dicates that the patient is at high risk offalling, and will require assistance due toimpaired mobility. Those patients whohave not experienced a fall and do notexhibit any balance or gait difficultiesshould be encouraged by their physicianto participate in exercise programs thatinclude balance and strength training.

For those patients who have fallen,are afraid of falling, or exhibit difficul-ties with gait or balance, identifying rel-evant risk factors should be the first stepin fall prevention. The most successfulapproach to prevention has been a mul-tifactorial assessment for risk factors, fol-lowed by interventions targeting theidentified risk factors. It is estimated thatthis approach can reduce the risk of fall-ing by as much as 39% among older per-sons living in the community.11 The cli-nician should diagnose the underlyingcause or refer for an evaluation of a prob-lem with gait or balance. The most suc-cessful interventions studied in clinicaltrials include reducing psychoactivemedications; reviewing the medicationportfolio for inappropriate or unneces-sary medications; using physical or occu-pational therapy for strengthening, bal-ance and proper use of assistive devices;management of orthostatic hypotension;

age of 80.1,2 The sequelae from a fall areof important consequence. One in tenfalls results in a serious injury (e.g. frac-ture, subdural hematoma, soft tissue orhead injury).3 Falling is the leading causeof injury, and the 6th leading cause ofdeath among individuals over the age of65.4 Individuals may acquire disabilityfrom injury, fear of falling, or restrictionin ambulation, either self-imposed orimposed by family members to preventsubsequent falls. In addition to restric-tion in mobility, falls place a previouslyindependent person at risk of nursinghome placement.5,6 Falls account for 6%of urgent hospitalizations, and only 50%of those admitted to the hospital afterfalling are alive one year later.2

The majority of falls result from pre-disposing risk factors or acute perturba-tions to the limited physiologic reserve ofan older person.7 Impairments in balance,gait, vision and muscle strength increasethe risk of falling. In addition, depression,impaired cognition, postural hypotension,the use of four or more medications, andarthritis independently increase the risk offalling.3 Certain classes of drugs have aclear association with the risk of falling:serotonin reuptake inhibitors, tricyclicantidepressants, neuroleptic agents, ben-zodiazepines, anticonvulsants, class IA an-tiarrhythmic medications, and digoxin.8

Older persons can be particularly suscep-tible to falls during episodes of acute ill-ness or de-compensated chronic illness,and in the first month following hospitaldischarge.9 Environmental hazards, suchas rugs, improper footwear, poor lighting,and stairs have been associated with an in-creased risk of falling.3,10

ASSESSMENT & INTERVENTIONThe exact age at which to begin

screening for the risk of falling is uncer-tain; however, the prevalence of risk fac-


THE ANALYSES UPON WHICH THIS PUBLICATION IS BASED wereperformed under Contract Number 500-02-RI02, funded bythe Centers for Medicare & Medicaid Services, an agency ofthe U.S. Department of Health and Human Services. The con-tent of this publication does not necessarily reflect the viewsor policies of the Department of Health and Human Services,nor does mention of trade names, commercial products, ororganizations imply endorsement by the U.S. Government.The author assumes full responsibility for the accuracy andcompleteness of the ideas presented.

home safety evaluation for environmental hazards; and refer-ral for evaluation of visual impairments.12

GUIDELINES & RECOMMENDATIONSThe US Preventive Services Task Force (UPSTF) recom-

mends that all persons 75 years of age or older be counseledabout specific measures to reduce the risk of falling.13 Personsbetween the ages of 70 to 74 who have at least one risk factorfor falling should also receive the same counseling about riskreduction measures. The American Geriatrics Society, the Brit-ish Geriatrics Society and the American Academy of Orthope-dic Surgeons concertedly recommend that on a yearly basisclinicians should not only ask their older patients about anyfalls which occurred over the previous year, but also test gaitand balance. For those who screen positive by having eitherexperienced a fall or exhibit difficulty with gait or balance, it isrecommended that physicians perform a comprehensive assess-ment, followed by interventions targeting the identified riskfactors.14

Let us return to the patient described at the introductionof this column. This patient has experienced a fall and shouldundergo a comprehensive assessment for relevant risk factors.A detailed history reveals the following risk factors for falling:depression, arthritis, use of more than four medications, andimproper use of an assistive device. On physical exam, you con-firm visual impairment and difficulties with gait and balance,but do not document orthostasis. He does have atrial fibrilla-tion and the rate is well controlled with Metoprolol. His neu-rologic (proprioception, cognition, and muscle strength) ex-amination was found to be normal. After considering othercauses of gait disturbance and based on his musculoskeletalexamination, you suspect that his gait impairment, which re-quires the use of a cane, is due to degenerative joint disease.Based on this comprehensive assessment, a targeted interven-tion plan would include 1) referral to a physical therapist forgait, balance, and strength training and the proper use of anassistive device, 2) occupational therapy for a home safety evalu-ation to reduce the number of environmental hazards, and 3)an ophthalmologic exam. The medication portfolio was criti-cally evaluated, but the number of medications was not re-duced because the patient required all six medications to effec-tively manage his chronic illnesses; neither was dosage reduc-tion needed. A year later, after having complied with the rec-ommendations, the patient returns to your office and reportsgreater confidence in walking with his cane and no falls.

WEB BASED RESOURCESAmerican Geriatrics Society (http://www.americangeriatrics.org/

education/forum)Centers for Disease Control and Prevention (http://www.cdc.gov)National Institute on Aging (http://www.nia.nih.gov)

REFERENCES1. Bergland A., Wyller TB. Risk factors for serious fall-related injury in elderly

women living at home. Injury Prevention 2004; 10: 308-13.2. Sattin RW. Falls among older persons. Annual Rev Public Health 1992; 13:

489-508.3. Tinnetti ME, Doucette J, et. al. Risk factors for serious injury during falls by

older persons living in the community. J Ameri Griatrics Soc 1995; 43: 1214-21.

4. Centers for Disease Control and Prevention. Web-based Injury Statistics Queryand Reporting System (WISQARS) [database online]. National Center forInjury Prevention and Control, CD). 2001.

5. Tinnetti ME, William CS. The effect of falls and fall injuries on functioningin community-dwelling older persons. J Gerontol A Biological Medical Sciences1998; 53: M112-M9.

6. Tinnetti ME, William CS. Falls, injuries due to falls, and the risk of admissionto a nurisng home. NEJM 1997;1279-84.

7. Tinetti ME, Speechley M, Ginter SF. Risk factor for falls among elderly per-sons living in the community. NEJM 1988; 319: 1701-7.

8. Leipzig RM, Cummings RG. Tinetti ME. Drugs and falls in older people. JAmer Geriatric Society 1999; 47: 30-50.

9. Mahoney J, Sager M, Johnson J. Risk of falls after hospital discharge. J AmeriGeriatric Society 1994. 42: 269-74.

10. Tinnetti ME, Preventing falls in elderly persons. NEJM 2003; 348:42-9.11. Gillespie LD, Gillespie WJ, et. al. Interventions for preventing falls in elderly

people. Cochrane Database Systemic Review 2001; 3: CD000340.12. Tinnetti ME. Gordon C, et. al. Fall-risk evaluation and management, Geron-

tologist 2006. 46: 717-25.13. USPSTF, Guide to clinical preventive services: report of the U.S. Preventive

Services Task Force. Preventive Service Task Force. 1996, Baltimore: Williamand Wilkins: 659-85.

14. American Geriatrics Society, American Academy of Orthopaedic Surgeons Panelon Falls Prevention, Guide for the Prevention of Falls in Older Persons. J AmerGeriatric Society 2001. 49: 664-72.

Michael P. Gerardo, DO, is a Postdoctoral Research Fellowin Community Health, and a Clinical Fellow in Geriatric Medi-cine, Rhode Island and Miriam Hospitals.

8SOW-RI-GERIATRICS -032007


Classification of Emergency Department Visits:How Many Are Necessary?

Jay S. Buechner, PhD, and Karen A. Williams, MPH

RHODE ISLAND DEPARTMENT OF HEALTH • DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH EDITED BY JAY S. BUECHNER, PHD

In a recent year, hospital emergency departments (EDs) inRhode Island provided care to over 380,000 patients who didnot require subsequent admission to an inpatient or observa-tion bed.1 Many ED visits are for true emergencies that couldnot be treated in other health care settings, but there has beenmuch discussion among providers, payers, and policy makerson whether some of these patients could have been treated inless intensive and more appropriate settings, had those settingsbeen available, and whether additional ED visits could havebeen avoided had the patient’s primary care been adequate. Arecent study has classified ED visits based on whether they aremedical emergencies, whether they require care from an emer-gency department, and whether they are preventable or avoid-able with adequate primary care.2 The results of this studyhave been applied to emergency department visit data fromhospitals in Rhode Island for presentation here.

METHODSUnder licensure regulations, the eleven acute-care gen-

eral hospitals and two psychiatric facilities in Rhode Island re-port to the Department of Health a defined set of data itemson each emergency department visit beginning with visits oc-curring January 1, 2005. The data reported includes patient-level demographic and clinical information. This analysis cov-ers ED visits occurring January 1 – December 31, 2005 and islimited to ED visits not resulting in admission to the hospital.Due to complexities in the manner in which hospitals reportED data, the data presented here are subject to change as meth-ods to distinguish ED visits that result in inpatient admission atacute-care facilities from those that do not are improved.

Billings, et al., reviewed approximately 5,700 medicalrecords of ED visits in New York and classified them accordingto three standards – (1) emergent cases vs. non-emergent cases,

(2) cases requiring a level of careprovided only by a hospital EDvs. cases treatable in a primarycare setting, and (3) cases thatwere preventable or avoidablewith adequate primary care vs.those not preventable or avoid-able.2 (Figure 1) Cases where thefirst-listed diagnosis was injury,mental health-related, or alcoholor drug-related were not classi-fied. The algorithm resultingfrom that study has been appliedto the ED visit data submitted

from Rhode Island hospitals for calendar year 2005to produce the estimates presented here. (The Cen-ter for Health and Public Service Research at NewYork University makes available a computer programfor use with ED databases,3 and that program wasadapted for use with Rhode Island ED data.)

RESULTSIn 2005, there were 382,247 visits to EDs in

Rhode Island’s acute-care general and psychiatric hos-pitals that did not result in an inpatient stay. Of these,an estimated 44% were in one of the three categoriesindicating the ED visit was either unnecessary or avoid-able, including 19.8% non-emergent cases, 18.8%emergent cases not requiring the facilities of a hospitalED, and 5.4% emergent cases requiring the facilitiesof a hospital ED but preventable or avoidable withadequate primary care. (Figure 2) Of the remaining56% of visits, the majority were for injuries, and a smallproportion were related to mental health and substance

Figure 1. Classification of emergency department visits

Figure 2. Emergency department visits by classification category,Rhode Island, 2005


abuse. Approximately 10% fell into categories that could not beclassified according to the Billings scheme.

The proportion of ED visits that fell into one of the threecategories representing unnecessary or avoidable utilization ofthe ED varied with patient characteristics. Higher than averageproportions were seen among patients who resided in one of thesix core cities in Rhode Island (47.1%), who were enrolled in thestate’s Medicaid Program (49.9%), or who were Hispanic(50.4%), Black (47.7%), or Asian (47.2%). (Figure 3) The low-est proportions were seen among those who were uninsured(41.7%), who lived outside the core cities (41.9%), who hadprivate insurance coverage (42.6%), or who were White (42.6%).

DISCUSSIONThe Billings algorithm classified just over half (54.4%) of ED

visits at Rhode Island hospitals that did not result in an inpatientadmission by whether they were emergent, treatable in a primarycare setting, and preventable or avoidable with adequate primarycare. Fewer than one-fifth of the classified visits were classified asemergent, not treatable in a primary care setting, and not prevent-able or avoidable with adequate primary care. The remaining vis-its can be looked at as an upper-bound estimate of the volume ofED visits in Rhode Island that may be avoidable or treated in othersettings under the right circumstances.

There are clearly some caveats needed in applying the Bill-ings methodology to Rhode Island ED data. The classificationscheme is based on medical record reviews of 5,700 ED visitsduring 1994 and 1999 in Bronx Borough, New York City, whereaccess to medical care and patterns of care may be much differ-ent than in Rhode Island in 2005. In addition, the data fromthe 5,700 examined records were used to apportion visits with659 different principal diagnosis codes, so that most proportionsused in the algorithm are based on small numbers of cases andtherefore may be imprecise. However, the algorithm is useful in

providing a working estimate to inform changesin policy and operation that may result in bettercare and better outcomes for these patients.Hospital emergency departments have an impor-tant role in ambulatory care, but other care set-tings are better organized to provide continuityof care, patient education, and management ofchronic conditions, all of which are hallmarks ofa good primary care system.

REFERENCES1. Williams KA, Buechner JS. Utilization of hospital emer-gency departments, Rhode Island 2005. Medicine & Health /Rhode Island 2006;89:415-6.2. Billings J, Parikh N, Mijanovich T. Emergency depart-ment use in New York City: a substitute for primary care? IssueBrief. The Commonwealth Fund. November 2000.3. http://www.nyu.edu/wagner/chpsr/index.html?p=25.Accessed February 6, 2007.

Jay S. Buechner, PhD, is Chief, Center forHealth Data and Analysis, and Assistant Profes-sor of Community Health, Brown Medical School.

Karen A. Williams, MPH, is Public Health Epi-demiologist, Center for Health Data and Analysis.

Figure 3. Percent of emergency department visits that are non-emergent,primary-care treatable, or preventable/avoidable, by selected patient characteristics,

Rhode Island, 2005


Bloodborne Pathogen Transmission Potential FromNeurological Pinwheels

Robert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian

DAVID GIFFORD, MD, MPH, DIRECTOR OF HEALTH

RHODE ISLAND DEPARTMENT OF HEALTH EDITED BY JOHN P. FULTON, PHD

The Occupational Safety and Health Administration (OSHA)defines contaminated sharps as “….any contaminated objectthat can penetrate the skin including, but not limited to, needles,scalpels, broken glass, broken capillary tubes and exposed endsof dental wires.” [29 CFR 1910.1030(a)]

As such the classic neurological pinwheel qualifies as asharp. Thus, the use of the neurologic pinwheel for neuro-

logic testing must be considered a potential vehicle for person-to-person spread of blood borne pathogens such as HIV, Hepa-titis B and Hepatitis C. Moreover, with as many as 20 pins perpinwheel the risk is further increased. Fortunately, disposableand or sterilizable devices exist. Examples include theCleanWheel trademark ®, Cronin pinwheel ™ and others*.

The reusable safety pin should also be considered a po-tentially contaminated sharp. Although the specific risk foriatrogenic transmission of Hepatitis B, C, and HIV with theuse of these neurologic testing instruments has not been clearlydefined it is clear that the use of nondisposable or unsterilizedreusable pinwheel devices or pins is inconsistent with OSHAregulations which exist to protect both patients and caregivers.

* This reference to named products should not be misconstrued as an endorse-ment for any specific product by the RI Department of Health.

REFERENCESOccupational Safety and Health Standards. Toxic and hazardous substances.

Bloodborne pathogens. 29 CFR 1910.1030(a)http://osha.gov/SLTC/bloodbornepathogens/index.htmlDurham D, Wasserburger J. Disposable needles should be the only instrument used

to test sensation in neurologic examinations. West J Med 1997. 166:216-7.http://www.pubmedcentral.nih.gov/tocrender.fcgi?iid=124762

Robert S. Crausman, MD, MMS, is Chief AdministrativeOfficer, RI Board of Medical Licensure and Discipline, RhodeIsland Department of Health, and Associate Professor of Medi-cine, Brown Medical School.

Utpala Bandy, MD, MPH, is Assistant Medical Director,Center for Epidemiology, Rhode Island Department of Health.

Linda Julian is Complaint Investigator, Health Services Regu-lation, Rhode Island Department of Health.

CORRESPONDENCERobert S. Crausman MDChief Administrative OfficerRI Board Medical Licensure and Discipline3 Capitol HillProvidence RI 02908e-mail: [email protected]

Figure 2 – Neurologic pinwheel

Figure 1. Lower extremity of a patient demonstrating tissue damageafter neurologic examination using a pinwheel device



� Call for Manuscripts: Choosing a Specialty �

What made you want to be a pathologist? a urologist? an orthopedic surgeon?

Medicine & Health/Rhode Island plans to feature articles from physicians, describinghow they chose their areas of expertise—including articles from physicians who haveswitched specialties. Please e-mail manuscripts (maximum 1200 words) to Joan Retsinas(e-mail: [email protected]).

Letters to the EditorTO THE EDITOR,

I am sorry that you stifled your opinion on house of-ficer dress codes in the face of your daughter’s naïve ideaof youthful feminist freedom. [January 2007] This is theprecise situation in which the gray heads must stick to theirguns.

Those of us actively engaged in teaching have a pro-prietary interest in the overall education of our medicalstudents and residents. This includes professional appear-ance and behavior as much as how to do a physical examor close an abdomen. Dress is as much a part of patientinteraction as interviewing skills and empathy. I would bejust as remiss allowing my charges to dress inappropriatelyon the wards as wearing street clothes in the OR.

The doctor-patient relationship is primarily one ofextraordinary trust on the part of the patient. We must doeverything in our power to make sure that the level of re-spect accorded our patients is not besmirched by somemisguided paean to individual expression or the currentmodern fashion. We must lead by example and guidance,regardless of the discomfort it may bring.

– STEPHEN E GLINICK, MD

TO THE EDITOR,Dr. Joseph Friedman’s stimulating and insightful com-

mentary, “Dreams In Neurological Diseases,” [December,2006 ] reminded me of the widespread interest in dreamsand dreaming in American culture in the 20th Century,expressed by poets and by composers and lyricists who havepondered the fearful, hopeful, painful, wistful, happy, sadand other Freudian complexities of the dream state in manypopular songs. A representative but not comprehensivelist would include the following :

I’ll See You In My DreamsDream A Little Dream Of MeWhen My Dreamboat Comes HomeDream Dancing (one of Cole Porter’s best)Don’t Believe Everything You Dream (music by the

talented Jimmy McHugh and cautionary lyricby Harold Adamson)

All I Do Is Dream Of You (the whole night through)Lights Out (Close Your Eyes And Dream Of Me)Dreamin’ Of You (sung by the popular Selena)I Dreamed A DreamOut Of My Dreams (and in to your arms).

Lyrics by Oscar Hammerstein, from “Oklahoma”

Modern poet John Berryman (1914-1972) receiveduniversal acclaim for his “The Dream Songs” (Pulitzer Prize,1964), an expression of his lifelong struggles with literarycreativity, alcoholism, sexual promiscuity, failed marriages,depression, and suicide attempts (finally successful in 1972,when he jumped off a bridge in Minneapolis). These po-etic dream songs would have given Dr. Freud much to con-template.

Compliments to Dr. Friedman for his interesting essay.

– MELVIN HERSHKOWITZ, MD


Post-transplant Lymphoproliferative DisorderFollowing Renal Transplant

Courtney A. Woodfield, MD

Images In Medicine

A 46 year-old male 8 months status post renal transplantfor autosomal dominant polycystic kidney disease presented tothe emergency department with fever and was found to havenormal renal function. An enhanced CT examination of theabdomen and pelvis demonstrated a homogeneous soft tissueattenuation mass (arrow Figure 1) centered on the hilum andencasing the central vessels of a right lower quadrant doublepediatric (en bloc) cadaveric transplant. Ultrasound guidedpercutaneous biopsy of the perinephric mass confirmed post-transplant lymphoproliferative disorder (PTLD), polyclonalsubtype. The patient was treated with decreased immunosup-pression with subsequent mass regression on follow up CTimaging.

PTLD is a spectrum of lymphoid disorders resulting fromimmunosuppression after organ transplantation, ranging fromB-cell hyperplasia to aggressive (usually B-cell) lymphoma.PTLD is associated with Ebstein-Barr virus infection of recipi-ent B-cells with unopposed B-cell proliferation. Any nodal orextranodal site may be involved.1

Imaging plays an important role in the detection and di-agnosis of PTLD as early lesions have a better prognosis andcan often be managed with immunosuppression alone. Moreadvanced PTLD lymphoma has a poorer prognosis with needfor chemotherapy.

PTLD of the transplant kidney typically manifests as a hi-lar-centered mass or less commonly as a diffuse, low attenua-tion infiltrative process of the kidney. (Figure 2) Imaging evalu-ation of renal transplants usually begins with ultrasound whichcan depict PTLD as hypoechoic mass(es) adjacent to the trans-plant kidney. CT or MRI is useful for indeterminate ultra-sound exams and for establishing the size and extent of disease.Figure 3 is an enhanced axial T1-weighted fat saturated MRimage of renal transplant PTLD with enhancing soft tissue massof the renal hilum (long arrow) encasing the right iliac vessels.The low signal transplant ureter is also dilated (short arrow).

.CORRESPONDENCE

Courtney A. Woodfield, MDDepartment of Diagnostic ImagingBrown Medical Schoole-mail:[email protected]

REFERENCES1. Kew CE, Lopez-Ben R, et al. Postransplant lymphoproliferative disorder local-

ized near the allograft in renal transplantation. Transplantation 2000;68:809-14.

2. Scarsbrook AF, Warakaulle DR, et al. Post-transplantation lymphoproliferativedisorder. Clin Radiol 2005;60:47-55.


The Vocabulary of Paralysis in Anglo-Saxon England�

Physician’s Lexicon

Number (a)249189

414046

Number (a) Rates (b) YPLL (c)2,757 257.7 4276.02,281 213.2 6,364.0**

446 41.7 680.0445 41.6 6,857.5469 43.8 352.5

Reporting Period

12 Months Ending with March 2006March2006

UnderlyingCause of Death

Live BirthsDeaths

Infant DeathsNeonatal Deaths

MarriagesDivorces

Induced TerminationsSpontaneous Fetal Deaths

Under 20 weeks gestation20+ weeks gestation

Number Number Rates1,155 12,996 12.1*

783 9,850 9.2*(4) (89) 6.8#(2) (70) 5.4#

986 7,129 6.7*269 3,130 2.9*433 4,792 368.7#

86 921 70.9#(71) (862) 66.3#(15) (59) 4.5#

Reporting Period12 Months Ending with

September 2006September

2006Vital Events

Rhode Island MonthlyVital Statistics Report

Provisional OccurrenceData from the

Division of Vital Records

(a) Cause of death statistics were derived fromthe underlying cause of death reported byphysicians on death certificates.

(b) Rates per 100,000 estimated population of1,069,725

(c) Years of Potential Life Lost (YPLL)

Note: Totals represent vital events which occurred in RhodeIsland for the reporting periods listed above. Monthly pro-visional totals should be analyzed with caution because thenumbers may be small and subject to seasonal variation.

* Rates per 1,000 estimated population# Rates per 1,000 live births** Excludes 2 deaths of unknown age

RHODE ISLAND DEPARTMENT OF HEALTH

DAVID GIFFORD, MD, MPHDIRECTOR OF HEALTH EDITED BY COLLEEN FONTANA, STATE REGISTRAR

V ITAL STATISTICS

Diseases of the HeartMalignant Neoplasms

Cerebrovascular DiseasesInjuries (Accidents/Suicide/Homicde)

COPD

Old English, the ancestor of the languagewe speak today, was first written downabout thirteen hundred years ago bypeople we call the Anglo-Saxons. Sur-viving Old English texts from this period,including some medical leechbooks orlæcebocas, are rich in terms associated withparalysis, many of which we hear echoedin our own speech and others which havefallen from the language or are scarcelyrecognizable. Although paralysin, a bor-rowing from Greek via Latin, occurs insome Old English texts, the most com-mon term for paralysis was lyftadl, mean-ing weak disease. The first element ofthis word is derived from Old English lef,weak, and is related to our word for theweaker hand in those who are dextrals.(The right hand in Old English was theswithere, the stronger.) Adl had the gen-eral meaning of ailment or sickness, and

occurs in the vivid Old English expres-sion for hemiplegia, healfdead adl. Thisis paralysis that comes “on the right halfof the body or the left where the sinewsare powerless,” as one of the Anglo-Saxonleechbooks describes it. Old Englishseonu, sinew, was used indiscriminately forwhat are now called nerves, tendons andligaments. In this the Anglo-Saxon au-thors differed little from their Latin mod-els who used nervus in the same way.

That lyftadl could also include lossof sensation is reflected in other terms ap-plied to a paralyzed part such as aslapenor adeadod, much as we might say a limbfeels asleep or dead. These terms may alsohave been used for paralytic stroke, alongwith aslegen, which has the basic mean-ing of stricken and is an ancestor of ourwords slay and slain. One instance ofGreek apoplexia is glossed by Old English

færdeath, sudden death, suggesting thattreatment could often be futile, asHippocrates had discerned. Paralysismight also leave one spæcleas or sufferingfrom dumbnes, although this seems tohave been blamed primarily on paralysisof the tongue, a very old and persistentnotion. Depressed skull fracture follow-ing a blow to the brægenpanne could alsocause one to go silent.

The prevailing explanation for pa-ralysis, including healfdead adl, was thatharmful humors, yfel wæta, clogged pre-sumptive channels in the sinews by whichthe brægen communicated with the restof the body and vice versa. Treatmentwas directed at removing the offendinghumors from the paralyzed part by ap-plication of healing sealfas and other plas-

(continued on page 102)


a d v e r t i s e m e n t


�

�

�

�VOLUME 1 PER YEAR $2.00NUMBER 1 SINGLE COPY, 25 CENTSPROVIDENCE, R.I., JANUARY, 1917

The Official Organ of the Rhode Island Medical SocietyIssued Monthly under the direction of the Publications Committee

ters, while purging them from the entire body by a clænsung.The latter could be effected by an appropriate blodlæting, byprovoking emesis with the aid of a spiwdrenc, or, if the face wasinvolved, by drawing the yfel wæta from the head through thenose and mouth with special concoctions and causing the pa-tient to sneeze, gefnesan.

Those left permanently impaired by paralysis and forcedto hobble or pull themselves along the ground were calledcreopere, crypel, or, most evocatively, eorthcrypel, all words re-lated semantically to the notion of creeping. The lama and thehealt could perambulate with the aid of a crycc and includednot only the partially paralyzed but those, for example, madelimleas by traumatic injury. The most gravely impaired werethe beddridan, destined to ‘ride’ their beds until freed by deathor the intervention of a saint.

– JAMES T. MCILWAIN, MD

James T. McIlwain, MD, is Professor of Medical ScienceEmeritus, Brown Medical School.

(continued from page 100)

NINETY YEARS AGO, MARCH 1917In “A Study of Empyema or Pyothorax,” John W. Keefe, MD,

FACS, bemoaned the “lack of investigating interest on the part ofthe profession at large.” He cited a high mortality, even “for thisenlightened age.” “The cases of so-called recovery with a deformedchest, a displaced heart, or a curved spine, an impaired functionof lung or diaphragm, make the word ‘recovery’ a travesty.”

In “Hookworm Disease in Rhode Island, Alex M. Bur-gess, MD, and Perry D. Meader, ScM, discussed the state’s 8diagnosed patients: 4 had lived in Providence for 2 years, 1 for1 year, 2 had recently arrived, and 1 had probably lived in RIfor at least 2 years, but had returned to his native Portugal.Because of the chilly winter temperatures, the authors werenot concerned about contagion.

Harry S. Bernstein, MD, Consulting Pathologist, contrib-uted “Case of Tuberculous Meningitis” [from the MedicalClinic of St. Joseph’s Hospital]. A 14 year-old girl arrived atthe hospital in a coma. Her medical history included whoop-ing cough, measles at age 2, chicken pox at age 5, diphtheria atage 8, bronchitis at age 13. Ten days prior to admission, shefelt drowsy and weak. Two days later, she complained of severeheadaches. Soon afterward, she started vomiting, became in-continent. Three days after admission, she died. The physi-cians considered poliomyelitis and encephalitis in the differen-tial diagnosis; a lumbar puncture excluded infections due topyogenic organisms. To know the “character of the infection,”the author inoculated 2 guinea pigs with a centrifugalized speci-men of spinal fluid. The author concluded: “It is difficult todistinguish tuberculous meningitis from acute poliomyelitis …”

FIFTY YEARS AGO, MARCH 1957Anthony V. Migliaccio, MD, and J. Robert Bowen, MD,

in “Tears of the Mesentery,” discussed 6 such patients treated atRhode Island Hospital in the past 15 years. (One patient died.)

Anthony Carditi, MD, in “Rheumatic Carditis in late AdultLife,” discussed 3 cases (ages 54, 64, and 70). He stressed the impor-tance of early diagnosis: “…underlying atherosclerotic or inactiverheumative heart disease itself may confuse the clinical picture.”

J. Merrill Gibson, Jr, MD, discussed “Breast Carcinomawith Pregnancy or Lactation,” a rare occurrence (2% of breastcancer patients), with a poor prognosis (5-year survival 17%).The basic treatment was the same for patients, regardless ofpregnancy: biopsy and radical mastectomy; but the decisionsrevolved around timing and termination. Five-year survivalsalmost doubled when the pregnancies were terminated.

An Editorial supported “chemical testing of motorists al-leged to have driven vehicles while under the influence of al-cohol.” The Rhode Island Council on Highway Safety hadintroduced such legislation in the General Assembly.

TWENTY-FIVE YEAS AGO, MARCH 1982In a “Current Commentary” column, Paul T. Welch, MD,

asked readers to support “A Uniform Determination of Death Act.”For the past five years, the General Assembly had shelved those bills.

Rebecca Silliman, MD, Mary Ann Passero, MD, David Kaplan,MD, Mary Condry, RN, Constance Pass, Philip Robzyk, MichaelPassero, MD, contributed “Acute Cardio-respiratory Morbidity, AirQuality, Temperature and Pollen Concentration in RI.” They citedthe results from a study that suggested a relationship between airpollutants and temperature and the incidence of bronchospasm.The study sample included all patients admitted to Roger WilliamsGeneral Hospital or treated as an outpatient with complaints ofcardiopulmonary disease, during the warm months of 1980.

David H. Nichols, MD, FACS, FACOG, in “ClinicalPelvic Anatomy, the Types of Genital Prolapse and the Choiceof Operation for Repair, “ advised: “In most instances a trans-vaginal operation is indicated.”

Figure 1 in the article entitled “Biohybrid Limbs: NewMaterials and New Properties,” (p.4) of the January 2007issue was not credited. The scanning electron micrographimages were courtesy of J. Dennis Bobyn, PhD, Jo MillerOrthopaedic Research Laboratory, Montreal GeneralHospital, McGill University.

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Transplantation - Rhode Island Medical Society · Robert S. Crausman, MD, MMS, Utpala Bandy, MD, MPH, and Linda Julian 100 LETTERS TO THE EDITOR 101 IMAGES IN MEDICINE – Post-transplant