Duke University Medical School Research Articles

First person profile: Lori J. Pierce, MD: First African American, first female radiation oncologist to serve as American Society of Clinical Oncology president makes equity her theme.

First person profile: Lori J. Pierce, MD: First African American, first female radiation oncologist to serve as American Society of Clinical Oncology president makes equity her theme.

News, Programs, Publications, and Awards

News, Programs, Publications, and Awards

An Interview with Robert Califf.

In the late 1970s, when Robert Califf was in medical school, the heart was still a kind of medical terra incognita. Most cardiologists believed that a class of untimely heartbeats, known as premature ventricular contractions (PVCs), could predict sudden cardiac death. During his third year at Duke University Medical School, Califf, and his colleagues, showed that impaired left ventricular function was the true culprit. A few years later, as new clot-busting agents were being developed, Califf, by then a Duke faculty member, and colleagues predicted that one of the drugs, tissue plasminogen activator (tPA), would be most effective when followed immediately by angioplasty. They ran a multicenter clinical trial—the first of a series collectively known as Thrombolysis and Angioplasty in Myocardial Infarction (TAMI)—which showed the opposite: waiting to do the artery-opening procedure led to better outcomes. Inspired by the power of clinical trials to topple even his own beliefs, Califf embarked, with colleagues, on an ambitious series of groundbreaking trials comparing tPA and another clot-buster, streptokinase. The study—known as the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO)—established the superiority of tPA and also Califf's reputation as one of the most creative clinical scientists of his generation. In 1995, he founded the Duke Clinical Research Institute, which has grown to become one of the world's largest academic research organizations, having enrolled more than 1.2 million participants in 65 countries and with over 1300 employees. Admired for his ability to bring people from academia and clinical medicine together with members of industry—a connection that caused some to object when he was later nominated by President Obama for the post of Commissioner of the Food and Drug Administration (FDA)—Califf is also one of the top 10 most cited medical authors. Until recently, he continued to see patients …

Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study

1 MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, UK 2 Departments of Psychology and Neuroscience, Duke University, Durham, NC, USA 3 Psychiatry and Behavioral Sciences, Duke University Medical School, Durham, NC, USA 4 Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA 5 Dunedin Multidisciplinary Health and Development Research Unit, Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand 6 Duke Transdisciplinary Prevention Research Center, Center for Child and Family Policy, Duke University, Durham, NC, USA

George S. Eisenbarth: Insulin and Type 1 Diabetes

George S. Eisenbarth, MD, PhD, could be considered a natural conduit in the research of type 1 diabetes (T1D) and the fields of endocrinology and immunology. His recognition of T1D as a chronic autoimmune disease has advanced the field toward prediction, prevention, and clinical trials. His focus on insulin as the key autoantigen in islet autoimmunity unraveled the molecular basis of the insulin autoimmune response, leading to experimental antigen-specific therapies that are presently approaching clinical translation and represent a model approach for the treatment of human T1D and other autoimmune diseases. George Eisenbarth was born in 1947, in Brooklyn, New York, to a working-class family of German ancestry. He graduated from Grover Cleveland High School in 1965 and won a Pulitzer Scholarship to Columbia University in New York City. His father feared the scholarship was some sort of scam that would not fully cover tuition, and he had to be convinced to let Eisenbarth enter the program. Eisenbarth obtained a BA degree from Columbia in 1969, followed by his PhD (Physiology-Pharmacology, 1974) and MD (1975) degrees from Duke University Medical School. As a PhD-MD student, Eisenbarth worked under the mentorship of Dr. Harold Lebovitz. According to Dr. Lebovitz, once Eisenbarth joined his laboratory, everyone else started working for him! Eisenbarth did not become a leader over time, he always was one. Dr. Eisenbarth married his wife Frieda, and they had two children, Stephanie and Stephen, who are both successful in their careers. Nothing gave him more pride than his daughter becoming an immunologist and a productive researcher at Yale University. He was a loving husband, caring father, and proud grandfather. His treasures were family, friends, and his work. Always kind and polite, he was loved and respected by all who knew him and by the many he touched. Gifted with …

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

Huntington's Disease and Behavioral Dyscontrol

Huntington's Disease and Behavioral Dyscontrol

FDA advisers wary of expanding quetiapine use

FDA advisers who met in April to discuss broadening the labeling of Seroquel XR, AstraZeneca’s extended-release formulation of quetiapine fumarate, unanimously agreed that the drug should not be used as a first-line monotherapy for major depressive disorder (MDD) or generalized anxiety disorder (GAD). “I just don’t think that the long-term risks have been adequately characterized,” said Duke University Medical School cardiologist Robert Harrington, 1 of 10 experts commissioned by FDA to vote on whether to expand the drug’s labeling. Harrington was particularly concerned about metabolic effects associated with the drug’s use, including weight gain, dyslipidemia, and blood-glucose abnormalities. Other advisers expressed concern about tardive dyskinesia, a sometimes-irreversible movement disorder associated with the use of atypical antipsychotics like quetiapine. The group also discussed recent research linking the use of anti-psychotic medications to sudden cardiac death. There was near-unanimous assent among the panelists that quetiapine is effective for the treatment of MDD and GAD. And the group agreed, by a 2:1 margin, that quetiapine is safe as an adjunctive treatment in patients with MDD.

Psychiatric Manifestations in Churg-Strauss Syndrome

Back to table of contents Previous article Next article LETTERFull AccessPsychiatric Manifestations in Churg-Strauss SyndromeTih-Shih Lee M.D., Ph.D.,Tih-Shih Lee M.D., Ph.D.Search for more papers by this author,Published Online:1 Apr 2009AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Churg-Strauss syndrome is a systemic small-vessel necrotizing vasculitis characterized by asthma, hypereosinophilia, granulomas, and pathological involvement of the heart, kidneys, and CNS. 1 Various neurological manifestations have been described, with peripheral neuropathy being the most common. 2 Central nervous system involvement has been reported in 13% of Churg-Strauss syndrome patients. 3 However an extensive literature search did not reveal any case reports of psychiatric symptoms associated with Churg-Strauss syndrome. Here we present a case of Churg-Strauss syndrome with cognitive and psychotic symptoms, describe our management approach, and briefly discuss pathophysiology. Case Report A 70-year-old man presented to the emergency department with an asthmatic attack and was also found to be acutely confused and agitated. He had a prior history of occasional asthma attacks over the past 2 years. For this admission, he was noted to have marked hypereosinophilia—absolute eosinophil count was 4.71×10 9 (normal 0.04–0.44×10 9 ) and 28.3% (normal 0.6%). Antineutrophil cytoplasmic antibodies were positive. There was no renal impairment but the patient was noted to have dilated cardiomyopathy. Diagnosis of Churg-Strauss syndrome was made based on the American College of Rheumatology criteria. The psychiatric consultant noted paranoid delusions about visitors to the hospital following him around and debt collectors hounding him. Further history from the patient’s family revealed that he had been admitted to another hospital 2 years prior with a first episode of delirium which resolved spontaneously. Moreover they reported that he was markedly more forgetful over the preceding 2 years and that he had become increasingly paranoid about neighbors and debt collectors. They verified that he did not have outstanding debts. Mental status examination revealed an alert, responsive man who was oriented to place and person but not to time. He denied feeling depressed and any past or current auditory hallucinations. He had fixed non-bizarre paranoid delusions. His Mini-Mental State Examination score was 22. He was unable to cooperate with further neuropsychological testing. There were no focal neurologic findings. A head CT showed bilateral cerebral lacunae consistent with thromboembolic disease. He was treated with high dose prednisone, 30 mg/day, which was tapered during the hospitalization. His psychiatric symptoms predated the introduction of prednisone. The absolute eosinophil count decreased to 0.57×10 9 and 5.9% within 2 weeks of commencing steroids. Given the absence of literature on psychiatric manifestations of Churg-Strauss syndrome and treatment, our approach was symptom management. He was started on risperidone, 1 mg twice a day, and he became markedly less agitated. His paranoid delusions persisted but to much lesser degree. However his cognitive functioning remained unchanged. Eventually he was discharged in stable condition with prednisolone, 10 mg/day, and risperidone, 1 mg twice a day. In consultation with his physicians, we decided that aggressive treatment using high dose steroids may modulate the primary disease process and perhaps arrest or slow down the cognitive deterioration while we closely monitored him for steroid-associated psychiatric symptoms. He was stable on outpatient follow-up with pulmonology, rheumatology, and psychiatry.Discussion Churg-Strauss syndrome is known to affect the CNS, but psychiatric symptoms have not been specifically reported in the literature. Keogh 4 suggested that CNS involvement was the one clinical manifestation that correlated closely with antineutrophil cytoplasmic antibody status. Like other vasculitides, damage is likely be a result of thromboembolic phenomenon; the hypereosinophilia itself could possibly be neurotoxic, 5 or the underlying etiologic cause of Churg-Strauss syndrome could account for neuronal damage. Further investigation is warranted to elucidate the pathophysiology and management of neuropsychiatric sequelae in Churg-Strauss syndrome and similar vasculitic diseases. Department of Psychiatry and Behavioral Science, Duke University Medical School, Durham, NC

Live Everyday to the Full

Dr. Michelle Lau emigrated from Hong Kong to the United States in 1994. She graduated from UC Berkeley with Highest Honor in Molecular and Cell Biology (Genetics). She graduated from Duke University Medical School in 2004. During her medical school years, she was awarded Clinical Research Training Program Fellowship at the National Institutes of Health. Her research in bone marrow transplant was published in the journal Blood. She is also the regional director of Asian Pacific American Medical Student Association (APAMSA). She then completed her residency in Internal Medicine at Washington University Barnes Jewish Hospital. Her work in sickle cell disease was presented in the American College of Physician Missouri Annual Conference. She is currently finishing her fellowship in Hematology/Oncology at Harvard’s teaching hospital,Beth Israel Deaconess Medical Center. She is honored in this year’s Cambridge Who’s Who list. She is currently performing research on Cancer and Asian Americans.

The Diseased Body: Resources for Scholarly Inquiry in the Duke University History of Medicine Collections

This article examines the holdings of the Duke University Medical School Library's History of Medicine Collections, including the Trent Collection. It provides a generalized topical description of the collections' contents, as well as an exploration of specific resources that can be used to study the diseased body in medieval and early modern Europe. Bibliographic notations direct the nonspecialist to further readings on the subject.

J. William Littler, MD, 1915–2005

J. William Littler, MD, one of the founders of the specialty of hand surgery, former director of the hand surgery service of the St. Luke’s-Roosevelt Hospital Center, and mentor to several generations of American and international hand surgeons, died on February 27, 2005, in Providence, Rhode Island. He had sustained a head injury in a fall in late October 2004. He was 89 years old and he lived a major part of his life in New York City. Dr. Littler was a legend in the field of hand surgery—a true renaissance man who aptly applied a rich background in the classics, mathematics, and engineering with the keen eye of an accomplished artist, to teaching and innovation in upper-extremity surgery. He edited several classic textbooks in hand reconstruction and published over 70 original articles, many of which defined the basic principles in hand surgery: sensory neurovascular island transfers, reconstruction for the absent thumb, and tendon transfers for nerve-damaged arms and hands. His contributions to hand surgery are so fundamental and so fully assimilated into the basic principles of structure and function of the hand, that little thought is given to who originally described them. Dr. Littler was born in Manlius in upstate New York, October 7, 1915, the son of James H. and Adelaide Littler. At age 8 he attended weekend art classes at Syracuse University College of Fine Arts and at 16 he built and flew his own glider. He attended Duke University Medical School, graduating with honors in 1942. His internship was at Johns Hopkins Hospital, where he was awarded the William Halstead Fellowship; however, his formal training was interrupted by World War II. He joined the U.S. Army and was eventually stationed at Cushing Army Hospital outside Boston. He was assigned to the orthopedic service, which was subsequently designated as one of several centers for the late care and reconstruction of upper-extremity injuries. At war’s end he volunteered to complete many complex hand reconstruction procedures on Valley Forge Army Hospital patients. While there, he developed many of the reconstruction principles and techniques that are still in use today. After the war Dr. Littler, although a recognized authority on upper-extremity reconstruction, completed a plastic surgery residency under Jerome Webster, MD, at Columbia University. In 1952 he set up practice at Roosevelt Hospital in New York City and founded a hand surgery fellowship program that continues to this day. Many of the more than 100 graduates have presided over national hand, orthopedic, and plastic societies and have chaired academic departments in these specialties throughout the United States and abroad. The Professor, as he was affectionately known by his students, had a remarkable ability to make rapid, clear sketches as he spoke, making his subject clear and easily remembered. The hallmark of his numerous prestigious national and international lectureships were his remarkable illustrations. His drawings appear in all major hand, plastic, and orthopedic texts and are regarded as classics in hand reconstruction. His sketches have also graced the napkins and tablecloths of many restaurants here and abroad. Dr. Littler was one of the last surviving founding members of the American Society for Surgery of the Hand. He was also a founding member of the Group d’Etude de la Main (GEM) and Sociedad de Cirugia de la Mano del Caribe. Dr. Littler was also a member of the American College of Surgeons, the American Association of Plastic Surgeons, the British Society for Surgery of the Hand, and the Societe International de Chirurgie Orthopedique et de Traumatologie. He was Emeritus Professor of Surgery (Plastic) at Columbia College of Physicians and Surgeons in New York City. Dr. Littler is survived by his daughter, Anne, of Paradise Valley, Nevada; a brother, Ted, in Providence, Rhode Island; his long-time secretary, Joyce Jones Wells; and the Members of the Littler-Eaton Society. At his request there are to be no memorial funds or services in his name.

With the help of giants.

A childhood fascination with animals, plants, and insects was aided and abetted by many giants, beginning with my parents. The Bronx High School of Science and the City College of New York (CCNY) made a solid and priceless grounding in chemistry and biology available free of charge. Abe Mazur at CCNY revealed the wonders of biochemistry and illustrated that it was possible to pursue these wonders while being paid to do so. He also directed me to Duke University Medical School for PhD work under the tutelage of Phil Handler. With the exception of a sabbatical year at Harvard with Frank Westheimer, my entire career has been spent at Duke serving under three fine and supportive chairmen: Handler, Hill, and Raetz. The premier discoveries to emanate from my laboratory have been the sulfite oxidase, the several superoxide dismutases, the manganese catalase, and the catalase/peroxidase. Many other topics piqued my interest and resulted in ~ 400 publications. Herein I have recounted some of the circumstances surrounding that work and named a few of the people involved. The first 20 years I worked happily at the bench and the next 35 years just as happily facilitating the work of younger people. It has been so rewarding that I wish for nothing more than to be allowed to keep at it.

The early history of orthopaedic surgery in Philadelphia. 1976.

Alfred Rives Shands, Jr, MD (1899-1981) Alfred Rives Shands, Jr. (Fig 1) was born in Washington DC. His father was the first orthopaedist to practice in the district. When he was 14 years of age, his father, Alfred R. Shands, Sr., was president of the American Orthopaedic Association. The young man graduated from the University of Virginia in 1918 and enrolled in Johns Hopkins Medical School. He remained at Johns Hopkins Hospital for surgical and orthopaedic training until 1927. He returned to Washington, DC to join his father in practice until 1930 when he was invited to Duke University Medical School to initiate the Department of Orthopaedic Surgery and the orthopaedic residency program. In 1937, Shands left Duke University to become Medical Director of the Alfred I. duPont Institute in Wilmington, DE.Fig 1: Alfred R. Shands, Jr, MD (Reprinted with permission from J Bone Joint Surg 64A:314-315, 1982).His first task at the institute was to plan and supervise the construction of a children's orthopaedic hospital on the grounds of Nemours, the estate of Alfred I. duPont. The hospital was completed in 1940 and Shands became Surgeon in Chief, a position he held until 1962. He remained Medical Director of the institute until 1969. During World War II, Shands served as the senior consultant for orthopaedics for the United States Air Force. Shands made many contributions to the care of children who are crippled, which are reflected in his numerous publications. His Handbook of Orthopaedic Surgery became an important educational resource, nine editions were published. Perhaps his greatest contribution to orthopaedics was his essential role in the formation of the Orthopaedic Research and Education Foundation, and his support of the Orthopaedic Research Society. He was honored by elected positions in various orthopaedic and other groups. He was a recipient of numerous honorary memberships and honorary degrees. His distinguished presence was noted at the annual meetings of orthopaedic societies, where he was especially friendly and encouraging to the young investigators. As a historian, Shands will be remembered for his article about the development of orthopaedics as a specialty in the United States. Many historic articles were published in The Early Orthopaedic Surgeons of America.1 The following article is an example of his historic scholarship. Leonard F. Peltier, MD, PhD

Problem-based learning: A method of integrating basic science with introduction to clinical skills in a medical curriculum

Integrating basic science and clinical sciences frequently meets obstacles. At my university we have in the past introduced clinical material into the first year Physiology course by inviting selected clinicians to give so called clinical correlation conferences, whose topic was coordinated with the Physiology schedule. The success of these depended on the willingness of our clinical colleagues to speak at first-year level, and to concentrate on the pathophysiology (rather than diagnosis and management) of the they presented. More recently Duke University Medical School joined the ranks of the schools using Problem-Based Learning as a tool in the first year curriculum. Groups of 6-8 students get together for a whole afternoon once a week. One basic science and one clinical teacher is assigned to facilitate the work of each group of students, but the bulk of the work is done by the students themselves. The group is presented with a clinical case, and is given the task to solve it. This involves not just arriving at a diagnosis, but also reviewing relevant physiology, biochemistry, pathology, bacteriology, as well as social and psychological problems. The cases are fabricated, synthetized from actual clinical material, by the staff of the Department of Family and Community Medicine. This year (1994) the Physiology staff was consulted for the construction of the to be presented in the period during which the Medical Physiology course is given. The case is presented to the group by patients, who are in fact actors: either acting students in training, or amateurs. The students interview the patient'; the has previously been coached on the answers to be given, and the emotional attitudes to be displayed. Genuine laboratory data concerning the case are available upon request. The student group must decide which laboratory tests to order'. After the patient interview the tasks are divided among the members of the group, who then have three or four weeks to research the library, interview staff, or use any other means to assemble the information, which then is shared and discussed in detail during the weekly meetings. Having used this method for several year, we at Duke University are of the opinion that this method of teaching is a very valuable and popular addition to the curriculum, but it does not replace the more traditional lectures and laboratory classes.

Prayer and Health During Pregnancy

Department of Family and Community Medicine, Eastern Virginia Medical School, Norfolk, Virginia; Departments of Psychiatry and Medicine, Northwestern University Medical School, Chicago, Illinois; and Department of Psychiatry, Duke University Medical School, Durham, North Carolina

M. Stephen Mahaley, Jr., M.D., Ph.D., 1932-1992.

M OSrS Stephen (Steve) Mahaley, Jr., one of our most prominent nationally and internationally respected neurosurgeons and cancer researchers, died prematurely at his home in Maggie Valley, North Carolina, on March 8, 1992. During his illness he received letters and visits from many colleagues who held his accomplishments in high esteem, as well as from nurses, patients, former students, and friends who shared his interests in birding and hiking. I knew Steve closely from both a personal and professional standpoint. I first met him in 1963 when I transferred to Duke University Medical School, at which time he was already one of the star students of two of the most eminent neurosurgeons in the country at that period Dr. Barnes Woodhall, who ultimately became Dean of Duke University Medical School and Chancellor of the University, and Dr. Guy Odom, then Chief of Neurosurgery at Duke. Steve, a true son of the South, attended Charlotte College and Wake Forest College in North Carolina and graduated from Duke University with his M.D. in 1959. He had already developed an interest in neurosurgery by graduation, but that same year he obtained a Ph.D. as well, a practice that was to become a nationally prominent educational component of Duke. His successes led Dr. Woodhall and other senior administrators at Duke to formally develop one of the first M.D.-Ph.D. programs for training physician-scientists in the nation. Steve chose his Ph.D. work in anatomy because, at that time, he and Drs. Odom and Woodhall were performing some of the first arterial infusions of chemotherapy for brain tumors in the country. Steve went on to complete an internship and residency in neurosurgery at Duke in 1965; during the research time of his residency, he won the prestigious Residency Research Award from the American Academy of Neurological Surgeons, the first of many awards that were to come to him during his career. He received numerous other national and international awards throughout his career. He was a member of Phi Beta Kappa and Alpha Omega Alpha, and was very proud to be the founder and a member of the Odom-Woodhall M. Stephen Mahaley, Jr., M.D., Ph.D., 1932-1992

Complication-specific management of postoperative care after cardiac transplantation

Coronary Artery Disease 1992, 3:797–805 From the Department of Surgery, Duke University Medical School, Durham, NC, USA.

Book reviews

This lavishly illustrated book, running to some 700 pages, is a six-author work from Duke University Medical School. It is the second edition of an established work and is now very comprehensive, having been expanded to take account of the development of digital angiography, the introduction of new angiographic contrast agents and the blossoming of interventional angiography.

Davison of Duke: His Reminiscences

Two devoted students have collected the reminiscences of Wilburt Cornell Davison, first dean and pediatrician at Duke University Medical School. In addition to the autobiographical material, much of which is devoted to Davison's pre-Duke years, Jay Arena (an early leader in poison control) and John McGovern (a pediatric allergist) have assembled 100 pages of correspondence (largely between Davison and the editors), eulogies, and obituaries. What emerges from the volume is the lively spirit and charm of the dean called Dave, whose motivating force Arena and McGovern believe was indispensible to the building and growth of Duke. William Osler figured prominently in Davison's training. Osler advised Davison's studies while the American was a Rhodes Scholar at Oxford University (1913-1915), guided his clinical initiation at the Radcliffe Infirmary, and frequently selected Davison's reading material. On Osler's recommendation, he was admitted as a fourth-year student at Johns Hopkins in 1916, and there is