Dartmouth Medical School Research Articles

The acidosis paradox: asphyxial brain injury without coincident acidemia

The acidosis paradox: asphyxial brain injury without coincident acidemia

Putting a cap on reinitiation

The transcription apparatus barely gets started before shutting itself down, according to Lawrence Myers (Dartmouth Medical School, Hanover, NH), Paul Tempst (Memorial Sloan-Kettering Cancer Center, New York, NY), and colleagues. Figure Native and recombinant capping enzymes block transcription in vitro. The authors have found that the two yeast mRNA capping enzymes, Cet1p and Ceg1p, are potent in vitro inhibitors of transcription. Cet1p, stimulated by its Ceg1p binding partner, stalled transcription by blocking reinitiation at already activated promoters. Conversely, elimination of Cet1p in vivo stimulated transcription. Although Cet1p is the first general repressor found to act at reinitiation, this step is well suited for transcription inhibition. “If 100 transcripts are made from a promoter,” says Myers, “only one is made at initiation—the remaining 99 are made by reinitiation.” A block by the capping enzyme could ensure that RNA polymerase does not make more transcripts than can be properly processed. It is still unclear how capping enzymes block reinitiation. Possibly, the interaction of Cet1p with proteins in the reinitiation scaffold may prevent further polymerase subunits from entering. The inhibition must be lifted to allow multiple rounds of transcription. Here, Myers speculates that the final step of capping (methylation, which does not occur in the in vitro system) might release repression and allow reinitiation. ▪ Reference: Myers, L., et al. 2002. Mol. Cell. 10:883–894. [PubMed]

Shameless: The visionary life of Mary Gove Nichols

Shameless: The Visionary Life of Mary Gove Nichols. By Jean L. Silver-- Isenstadt. (Baltimore: Johns Hopkins University Press, 2002. Pp. xii, 342. Illustrations. Cloth, $24.95.) Shameless is the first book-length biography to chronicle the amazing life of Mary Gove Nichols, health and sex reformer who was in the public eye, on the public stage, and in the public prints for two decades, starting in 1838. This forceful advocate for women's freedom has long deserved far more prominent place in our histories of antebellum reform and women's rights, and Jean Silver-Isenstadt restores her to that prominence in an artfully written book that is pleasure to read. This is the biography that Mary Gove Nichols and her husband Dr. Thomas L. Nichols expected, anticipated, indeed probably ached to have. They had formidably sure sense of their own fame, and why it eluded them for so long is an interesting question. The two show up in cameo roles in number of excellent books on nineteenth-century social movements. But no one, until now, has advanced our biographical knowledge of Mary Gove Nichols beyond the basic outlines. Silver-Isenstadt, who holds an M.D. as well as Ph.D., brings to the project firm foundation in medicine, which is helpful for understanding woman who from her adolescent years studied medical books with obsessive intensity. With sure hand, Silver-Isenstadt appraises the health scene of the 1840s and makes sense of this determined woman's professional rise as medical specialist. When Mary Gove made her 1838 lecturing debut in towns across the Northeast on the subject of women's anatomy and physiology, only handful of women were public lecturers. Her immodest topics-tight lacing, reproduction, and marital sex-drew ridicule from the press and disownment from her Quaker meeting. In 1840 she edited health journal based on the teachings of the diet and sex reformer Sylvester Graham; in many ways, Gove appears to have been female Graham, espousing his anti-sex and anti-meat regimens. Her first pamphlet publication, in 1839, addressed the solitary vice (i.e., masturbation) in females. By 1845 she was committed to the water cure and secured her first posts as paid medical practitioner, seeing women patients, teaching classes, and writing for the Water-Cure Journal. In 1847, Mary Gove- disaffected and separated wife of the churlish Hiram Gove-met Thomas Low Nichols. Mary Gove, Nichols was journalist and editor with strong medical interests. During an early stint at Dartmouth Medical School, he heard Sylvester Graham lecture and adopted his dietary program. Like trains on parallel tracks, Thomas and Mary would spend the next fourteen years [1834-48] living two versions of the same experience (111). And when their trains hooked up, in their 1848 marriage, the two became unstoppable. Over the next ten years, this ambitious couple established several health schools, issued regular periodical, and published half dozen books. Their critique of the sexual system moved in new directions, too, as they relocated to Modem Times on Long Island, joined forces with Stephen Pearl Andrews, and wrote three remarkable books that attacked indissoluble marriage and were widely regarded as promoting Free Love. In this same time period, Mary's talents as medium blossomed, and Spiritualism became central to the Nicholses' lives. And then, quite suddenly, the two converted to Catholicism in 1857, dropped from the reform scene, and in 1861 moved to England, citing moral objections to the Civil War. Silver-Isenstadt notes compelling reasons why these two once-notorious reformers have not gotten their due: they disappeared to England, they passed through many movements instead of sticking with consistent set of allies, their free love program was a liability that made other reformers shun them, and their turnabout conversion has disappointed scholars (8). She offers an intriguing psychological explanation for Mary Gove Nichols's embrace of Catholicism: that baptism and devotion to the Virgin Mary cleansed this woman of an early dread of sex, product of her hateful marriage to Hiram Gove. …

Maternal hypothyroidism and cognitive development of the offspring.

*Department of Pediatrics, Dartmouth Medical School, Lebanon, New Hampshire, USA; and †Department of Medicine, University of Massachusetts Medical School, State Laboratory Institute, Boston, Massachusetts, USA. Correspondence to R. Z. Klein, MD, Department of Pediatrics, Dartmouth Medical School, Lebanon, NH 03756, USA; e-mail: [email protected]

An efficient and effective teaching model for ambulatory education.

Teaching and learning in the ambulatory setting have been described as inefficient, variable, and unpredictable. A model of ambulatory teaching that was piloted in three settings (1973-1981 in a university-affiliated outpatient clinic in Portland, Oregon, 1996-2000 in a community outpatient clinic, and 2000-2001 in an outpatient clinic serving Dartmouth Medical School's teaching hospital) that combines a system of education and a system of patient care is presented. Fully integrating learners into the office practice using creative scheduling, pre-rotation learning, and learner competence certification enabled the learners to provide care in roles traditionally fulfilled by physicians and nurses. Practice redesign made learners active members of the patient care team by involving them in such tasks as patient intake, histories and physicals, patient education, and monitoring of patient progress between visits. So that learners can be active members of the patient care team on the first day of clinic, pre-training is provided by the clerkship or residency so that they are able to competently provide care in the time available. To assure effective education, teaching and learning times are explicitly scheduled by parallel booking of patients for the learner and the preceptor at the same time. In the pilot settings this teaching model maintained or improved preceptor productivity and on-time efficiency compared with these outcomes of traditional scheduling. The time spent alone with patients, in direct observation by preceptors, and for scheduled case discussion was appreciated by learners. Increased satisfaction was enjoyed by learners, teachers, clinic staff, and patients. Barriers to implementation include too few examining rooms, inability to manipulate patient appointment schedules, and learners' not being present in a teaching clinic all the time.

Neonatal Intensive Care: Costs vs Results

Although the United States spends more on neonatal intensive care than Australia, Canada, and the United Kingdom, newborns in each country have similar rates of survival, Dartmouth Medical School researchers have found.

Angiogenesis

Annals of the New York Academy of SciencesVolume 961, Issue 1 p. 249-250 Angiogenesis Initiation and Maintenance MARK J. POST, Corresponding Author MARK J. POST Associate Professor of Medicine and Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USAAddress for correspondence: Mark J. Post, Associate Professor of Medicine and Physiology, Dartmouth Medical School, Hanover, NH 03755, USA. Voice: 603-650-3903; fax: 603-650-6130; [email protected].Search for more papers by this author MARK J. POST, Corresponding Author MARK J. POST Associate Professor of Medicine and Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USAAddress for correspondence: Mark J. Post, Associate Professor of Medicine and Physiology, Dartmouth Medical School, Hanover, NH 03755, USA. Voice: 603-650-3903; fax: 603-650-6130; [email protected].Search for more papers by this author First published: 24 January 2006 https://doi.org/10.1111/j.1749-6632.2002.tb03093.xCitations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume961, Issue1REPARATIVE MEDICINE: GROWING TISSUES AND ORGANSJune 2002Pages 249-250 RelatedInformation

A method for pulsed carbon dioxide laser treatment of epidermal nevi

J Am Acad Dermatol 2002;46:554-6.

Editorial overview

Correspondence to John C. Baldwin, MD, Vice-President for Health Affairs, Dartmouth College; Professor of Surgery (Cardiothoracic) and Dean, Dartmouth Medical School

Newfound RNA suggests a hidden complexity inside cells

It started with worms that would not grow up. In early 1990s, Victor Ambros and his colleagues were conducting a gene hunt. In particular, they were searching for gene that was mutated in a perplexing strain of Caenorhabditis elegans, small nematode whose development many biologists study. This genetic change Ambros hunted had apparently disrupted worms' developmental timing. In normal strains, worms pass through four larval stages as they mature into fertile adults. But members of mutant strain get stuck at first stage. They would molt, but instead of moving on to second larval stage, they simply repeated first stage. The larvae kept growing larger but never became fullfledged adults. Ambros' team painstakingly homed in on gene responsible by adding pieces of DNA from normal C. elegans back into mutant worms. If a DNA sequence restored full development, it presumably harbored a working copy of gene that's defective in mutants, reasoned investigators. In 1993 at Dartmouth Medical School in Hanover, N.H., hard work of Ambros and his colleagues paid off with elusive gene's discovery. It was a heroic detective story, says Sean Eddy of Howard Hughes Medical Institute at Washington University in St. Louis. The story had a surprise ending, too. Unlike most genes, one identified by Ambros' group doesn't encode a protein. It spawns a small molecule of RNA-a chemical relative of DNA-that somehow turns off other genes that play a role in worm development. This odd finding stood alone until a few years ago, when a team led by Gary Ruvkun of Massachusetts General Hospital in Boston found a gene that controls C. elegans' transition from fourth larval stage to adulthood. This gene also creates RNA that regulates expression of worm Although Ambros hadn't found genes in other organisms similar to one he'd identified in C. elegans, Ruvkun and his colleagues discovered that many animals have versions of this second RNA-encoding worm gene. His team found such genes in flies, mollusks, fish, and even people. The researchers speculated that RNA produced by gene is a universal regulator of animal development, perhaps an important controller of a caterpillar's metamorphosis into a butterfly and a tadpole's into a frog. Inspired by such research, biologists have now begun to systematically look for so-called RNA genes. DNA whose final product is RNA instead of protein. Several groups, including one led by Eddy, recently surveyed DNA of bacterium Escherichia coli and uncovered dozens of such Just a few months ago, Ambros' team and two other research groups reported that worms, flies, and people contain dozens of previously undetected genes that spawn RNA instead of protein. These investigators argue that many intensive searches for protein-coding genes have ignored or missed genes for small, stable RNA molecules that have cellular functions. The RNA genes found so far are just tip of a huge iceberg, says Ruvkun. The biologist goes as far as to compare RNA-gene findings to a humbling discovery on a much larger scale. Astronomers studying effects of gravity on galaxies found to their astonishment that universe contains large quantities of so-called dark matter, mass that still eludes observation. In Oct. 26, 2001 SCIENCE, Ruvkun speculates that the number of genes in tiny RNA world may turn out to be very large, numbering in hundreds or even thousands in each genome. Tiny RNA genes may be biological equivalent of dark matter-all around us but almost escaping detection. RNA genes have already attracted commercial interest: A biotech firm is testing whether some of newfound bacterial RNAs play a role during infection and might therefore be targets for new antibiotics. If that's not provocative enough, some scientists suggest that RNA regulation of gene activity and other cellular processes could explain diversity and complexity of plants and animals as compared with bacteria.

The American Association for Vascular Surgery: Advocate for independence

The American Association for Vascular Surgery: Advocate for independence

The American Association for Vascular Surgery: Advocate for independence

The American Association for Vascular Surgery: Advocate for independence

Carleton B. Chapman, MD, MPH

Carleton B. Chapman, who made important contributions in 4 areas of medicine, died in Hanover, New Hampshire, on December 10, 2000. These areas included cardiovascular medicine and research, medical education, philanthropy, and medical history and ethics. His career can be separated temporally into periods when he focused on each of these areas, although he was active in all of them throughout his career. Dr Chapman was born on June 11, 1915, in Sycamore, Alabama (the same small community that produced Tinsley Harrison). He attended public schools in Talladega and graduated from Talladega High School. He was a precociously talented concert organist during his school years, and he seriously considered a career in music. Although he ultimately chose medicine, he maintained his passion for playing the organ throughout his life. He entered Davidson College in 1932 as a liberal arts major, where he became President of the Student Body and a member of Phi Beta Kappa. By the time of his graduation in 1936, he had developed an interest in human physiology, which he pursued at Oxford University after being awarded a Rhodes Scholarship. As a student of St Johns College, Oxford, from 1936 to 1939, he received his BA and MA degrees in Physiology. During that time, he worked with the famous respiratory and exercise physiologist Professor C.G. Douglas. He returned to the United States in 1939 and completed medical school at Harvard, where he received his MD in 1941 and his MPH in 1944. His training in Internal Medicine and Cardiology was received at Boston City Hospital from 1941 to 1944. From 1944 to 1946, he was in the Public Health Service and was stationed first in the Middle East and then in China and Indonesia. In 1946, he returned to Harvard and did a second …

Anemia of the critically ill: “Acute” anemia of chronic disease*

Dartmouth Medical School Dartmouth-Hitchcock Medical Center Lebanon, NH Vanderbilt University School of Medicine VA Medical Center Nashville, TN * This article first appeared in Critical Care Medicine 2000; 28:3098–3099. Supported, in part, by Ortho Biotech Inc. Address requests for reprints to: Howard L. Corwin, MD, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756-0001.

Endoscopically Assisted, Intraorally Approached Corrective Rhinoplasty

Discussion by Mark B. Constantian, M.D. From the Department of Surgery, Plastic Surgery, St. Joseph Hospital and Southern New Hampshire Regional Medical Center and Dartmouth Medical School. Received for publication January 9, 2001. Mark B. Constantian, M.D. 19 Tyler Street Nashua, N.H. 03060

Medicare Reform Bill Seeks Mental Health Parity

Medicare Reform Bill Seeks Mental Health Parity

Comorbid ADHD/Depression Treated with Bupropion SR

A trial of bupropion sustained release (SR) was conducted in 24 adolescents (ages 11-16 years) with ADHD and either major depressive disorder or dysthymic disorder at the Department of Psychiatry, Dartmouth Medical School, Hanover, NH.

IN MEMORIAM: LAWRENCE KILHAM, 1910–2000

Lawrence Kilham died at his home in Lyme, New Hampshire, on 21 September 2000. Born 10 August 1910 in Brookline, Massachusetts, Lawrence grew up in Massachusetts and New Hampshire. He graduated from Harvard University with a bachelor's degree in history and literature in 1932, earned a master's degree in biology from Harvard in 1935, and an M.D. from Harvard Medical School in 1940. While serving as an intern in Cleveland, Ohio, he met his wife, Jane, a fellow intern. Both went to England early in World War II, and Lawrence served in field hospitals under General George Patton. After leaving the Army in 1945, Lawrence returned to graduate school doing virology research and teaching epidemiology. From 1949 to 1960, he worked as a research virologist. He joined the faculty at Dartmouth Medical School in 1961, where he remained until he retired in 1978. Lawrence Kilham was widely recognized for his research with viruses and infectious diseases, publishing nearly 150 articles and discovering a new group of viruses with single-stranded DNA. At first his interest in birds was recreational, stemming from a lifelong quest for solitude and nature that led him to identify with Henry David Thoreau and to seek wild places. After his marriage, his wife Jane shared his quests and often illustrated his articles and books; to better learn from nature, they went their own ways in the field, coming back together every few hours to share their observations. By the early 1950s, Lawrence was serious about birds, joining both the AOU and the Wilson Ornithological Society in 1952. It was while doing viral research in Uganda in 1954-1955, that he developed a research interest in bird behavior. From that point on, his work with the behavior of birds and mammals, an avocation, became a passion that led to more than 90 publications in the ornithological and behavioral literature. I suspect that for him, the joy of birds relieved the pressures of teaching and laboratory work. For his ornithological contributions, he was made an Elective Member of the AOU in 1962, and a Fellow in 1974. Truly Lawrence Kilham successfully lived two outstanding careers in science! In addition to his journal articles, he published four books relating to his studies of nature: Never Enough of Nature (1977, Droll Yankees Inc., Foster, Rhode Island); On Watching Birds (1979, Chelsea Green Publishing Company, Chelsea, Vermont), reissued as A Naturalist's Field Guide (1981, Stackpole Books, Harrisburg, Pennsylvania); Life History Studies of Woodpeckers of Eastern North America (1983, Publications of the Nuttall Ornithological Club, no. 20); and The American Crow and the Common Raven (1989, Texas A & M University Press, College Station, Texas). For On Watching Birds he was awarded the John Burroughs Medal for outstanding nature writing in 1988. Although he studied a great diversity of birds, Lawrence Kilham is best known for his work with woodpeckers. Indeed, it is difficult to find a major study on the behavioral ecology of woodpeckers that was not influenced by Kilham's work. Much ornithological research today is problem oriented; some remain species oriented; his work was often individual oriented! His research was not couched in systematic

Dartmouth Medical School.

Dartmouth Medical School.

Current medicolegal and confidentiality issues in large, multicenter research programs.

The convenience of fast computers and the Internet have encouraged large collaborative research efforts by allowing transfers of data from multiple sites to a single data repository; however, standards for managing data security are needed to protect the confidentiality of participants. Through Dartmouth Medical School, in 1996-1998, the authors conducted a medicolegal analysis of federal laws, state statutes, and institutional policies in eight states and three different types of health care settings, which are part of a breast cancer surveillance consortium contributing data electronically to a centralized data repository. They learned that a variety of state and federal laws are available to protect confidentiality of professional and lay research participants. The strongest protection available is the Federal Certificate of Confidentiality, which supersedes state statutory protection, has been tested in court, and extends protection from forced disclosure (in litigation) to health care providers as well as patients. This paper describes the careful planning necessary to ensure adequate legal protection and data security, which must include a comprehensive understanding of state and federal protections applicable to medical research. Researchers must also develop rules or guidelines to ensure appropriate collection, use, and sharing of data. Finally, systems for the storage of both paper and electronic records must be as secure as possible.