Mittwoch, Februar 29, 2012

Can Vitamin D Treat Pain?


 
 
 

From Medscape Medical News > Neurology

Can Vitamin D Treat Pain?

Pauline Anderson

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February 27, 2012 — Women with dysmenorrhea who take a single high dose of vitamin D suffer much less menstrual pain and have no need of pain medications for any reason for up to 2 months, a new study has found.

"To our knowledge, this is the first study investigating the effect of a single high dose of vitamin D in primary dysmenorrhea," wrote the study authors, led by Antonino Lasco, MD, from the Department of Internal Medicine, University of Messina, Italy.

"Our data support the use of cholecalciferol in these patients, especially when exhibiting low plasmatic levels of 25(OH)D [25-hydroxyvitamin D]," they write.

The study is published February 27 in the Archives of Internal Medicine.

Pain Trigger

Dysmenorrhea affects almost one half of menstruating women. The pelvic pain is believed to be triggered by excessive uterine production of prostaglandins, synthesized from omega-6 fatty acids before menses, that control vasoconstriction and uterine contractions.

According to the study authors, vitamin D may act as an anti-inflammatory and may regulate the expression of key genes involved in the prostaglandin pathway, causing decreased biological activity of prostaglandins.

The study included 40 women aged 18 to 40 years who had experienced at least 4 consecutive painful menstrual periods in the past 6 months and had a 25(OH)D serum level below the upper limit of the lowest quartile (<45 ng/mL). They were not taking calcium, vitamin D, oral contraceptives, or other medications, and they had not used an intrauterine contraceptive device during the previous 6 months.

The participants could use other means of birth control, however. They were also allowed to use nonsteroidal anti-inflammatory drugs (NSAIDs) as needed, but they had to record their use of these agents.

The women were randomly assigned to receive a single oral dose of 300,000 IUs of vitamin D (cholecalciferol) or placebo 5 days before the time they expected to begin their next menstrual period.

The primary outcome was intensity of menstrual pain as measured by a visual analog scale. The secondary outcome was use of NSAIDs.

After 2 months, baseline pain scores decreased 41% among women in the vitamin D group; there was no difference in scores among women taking placebo (P < .001). The greatest reduction in pain was among women in the vitamin D group who had the most severe pain at baseline (r = -0.76; P < .001)

During the study, none of the women in the vitamin D group needed NSAIDs to manage pain at 1 and 2 months, whereas 40% of those taking placebo used an NSAID at least once (P = .003).

Implications for Chronic Pain?

In an accompanying commentary, Elizabeth R. Bertone-Johnson, ScD, from the Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, and JoAnn E Manson, MD, from the Division of Preventive Medicine, Department of Epidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, said the study provides support for larger randomized trials of vitamin D for treating pain-related conditions in women.

Chronic widespread pain and fibromyalgia syndromes are more prevalent in women, "likely owing to the influence of sex steroid hormones," they write.

This future research, they write, must address several key issues.

"First, it is important to know how long reductions in pain associated with a single high-dose vitamin D therapy would persist and how often treatment would need to be repeated," the editorialists write. They point out that each dose would need to be effective for a lengthy period for average daily intake to remain below recommended upper limits.

Because many women will experience dysmenorrhea for several years until menopause, follow-up of participants in vitamin D trials must be extended to better evaluate adverse effects and to compare risks and benefits, they note.

The editorialists also note that it remains unknown whether vitamin D would improve dysmenorrhea pain in women with higher 25(OH)D levels.

"If these findings are confirmed in future randomized trials, vitamin D supplementation may become an important new treatment option for women who experience menstrual pain disorders," they conclude. "In the meantime, encouraging all women to obtain the recommended dietary allowance for vitamin D (≥600 IU/d for women of reproductive age), as well as screening for low serum 25(OH)D levels among women with other risk factors for vitamin D deficiency, would be a rational interim approach."

Pain Site

Approached for comment, Clifford Lo, MD, PhD, Director, Harvard Human Nutrition Program, and Medical Education Coordinator, Harvard Medical School Division of Nutrition, said that although the numbers were small, there was a convincing difference between the placebo and vitamin D groups in the study.

However, although it is plausible that vitamin D affects prostaglandins, the study did not specify which prostaglandin or which pain site might be involved, said Dr. Lo, whose research interests include vitamin D metabolism.

The study proposes an interesting possible mechanism, "but that's certainly not good enough for me to say that this is a good treatment for pain," said Dr. Lo. "It's very premature to say it's something we should use."

Pain associated with dysmenorrhea is generally subjective and not easily measured, he added. It is difficult to make conclusions about the effect an agent will have on pain when there is "no convincing biomarker" for the pain, as was the case with this study, said Dr. Lo.

The 300,000 IU dose of vitamin D used in the study is probably harmless if taken every month or 2, and even perhaps every week, but it could cause hypercalcemia if taken daily, said Dr. Lo. The typical vitamin D dose is 400 to 1000 IU/day.

Dr. Lo pointed out that because the participants in the study had vitamin D levels below 45 ng/mL, they were not exactly deficient in vitamin D to begin with. "Most people would say that you're not deficient until you're below 20 ng/ml," he said. "I would say that half the American population is below 30 ng/mL."

The study authors and editorialists have disclosed no relevant financial relationships.

Arch Intern Med. 2012;172:366-367, 367-369.

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Pauline Anderson

Pauline Anderson is a freelance writer for Medscape.

 
 
 
 
 
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Freitag, Februar 24, 2012

A Reader's Guide to 200 Years of the New England Journal of Medicine — NEJM


Perspective

200th Anniversary Article

A Reader's Guide to 200 Years of the New England Journal of Medicine

Allan M. Brandt, Ph.D.

N Engl J Med 2012; 366:1-7January 5, 2012

Comments open through December 31, 2012

Article
References
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Audio Interview

Interview with Allan Brandt on the first 200 years of the Journal as a window into the history of medicine, science, and society.

Interview with Allan Brandt on the first 200 years of the Journal as a window into the history of medicine, science, and society. (22:26)

With this issue, the New England Journal of Medicine marks its 200th anniversary. In January 1812, as the first issue came off the handset letterpress, few of its founders could have predicted such continuity and success. (See Figure 1Figure 1Illustration from "Cases of Organic Diseases of the Heart and Lungs," by John C. Warren, April 1, 1812, Issue of the Journal., from an 1812 issue.) John Collins Warren, the renowned Boston surgeon, his colleague James Jackson, a founder of Massachusetts General Hospital, and the small group of distinguished colleagues who joined them in starting the New England Journal of Medicine and Surgery, and the Collateral Branches of Science expressed modest and largely local aspirations for the enterprise. Boston, a growing urban center, and the wider New England environs had no medical journal of their own, although much medical knowledge and practice was considered region-specific. Although the name and format of the Journal would vary until 1928, 7 years after its ownership passed to the Massachusetts Medical Society, it remains the longest continuously published medical periodical in the world. The prospectus for the Journal, a call for papers issued in late 1811, explained the goals of Warren and his collaborators: "The editors have been encouraged to attempt this publication by the opinion, that a taste for medical literature has greatly increased in New England within a few years past. New methods of practice, good old ones which are not sufficiently known, and occasional investigations of the modes in common use, when thus distributed among our medical brethren in the country, will promote a disposition for inquiry and reflection, which cannot fail to produce the most happy results."1

At a time of intense debate and controversy regarding the causes of disease, the nature of therapeutics, and the basis of professional authority, the young Journal worked to steer a middle course. This was certainly advisable from a commercial point of view, since it could easily alienate diverse medical readers by endorsing a particular therapeutic system or theory. But this approach also established the ecumenical temper of the Journal, which based its early publications on a commitment to empirical observation and an outlook skeptical of conventional medical wisdoms. As the editors explained in 1837, "It has been a point of ambition with us . . . to make these pages the vehicle of useful intelligence, rather than the field of warfare. . . . The Journal is to all intents and purposes, designed to be a record of medical and surgical facts. It is the medium through which the profession may interchange sentiments and publish the results of their experience" (see Historical Journal Articles Cited).

Given the breadth of the Journal's interests and contributors over these past two centuries, it serves today as a remarkable resource for understanding the profound changes that have occurred in medicine. The Journal (now available electronically from its first issue onward) is not just a window on clinical medicine and scientific advance; it serves as a basis for investigating the history of medicine in all its complexity: it reflects the relationships of culture, society, economy, and politics to medical knowledge, practice, and the organization of health care. (An interactive timeline providing access to the Journal archives is available with the full text of this article at NEJM.org.) Encyclopedic in its breadth, the Journal has covered virtually every aspect of medical science and its evolution. Indeed, if it were the only source available to the medical historian, much could be recovered to reconstruct this period of seismic change and revolutionary shifts in knowledge and practice.

But despite this emphasis on the growing power of medical science to define and treat disease effectively, there are deep continuities within medicine that a review of the Journal reveals as well. A dive into the digital archive exposes a world of medicine and science radically different from today's, as well as a stability of orientation and approach to fundamental problems of disease in patients and populations.

The Enduring Problem of Disease

The observation and investigation of disease is perhaps the most salient consistent feature of the Journal. From the meticulous description of angina pectoris in the first issue to the early descriptions of AIDS in the early 1980s, there has been an ongoing recognition that therapeutic approaches must await the sharp articulation of symptoms. The first decades of the Journal's history reflected the intensive concern with the epidemics affecting New England and the new nation, and it was not unusual during the early years for authors to direct attention to the environment as a critical variable in the production of disease. John Gorham, an editor writing in 1828, offered a "Medical Report of the Weather and Prevalent diseases for the last Three months." Such articles may appear both quaint and humorous from our contemporary scientific perch, but they reveal a serious commitment to understanding more fully the vagaries of epidemic disease that could devastate town and country in short order. Furthermore, they offer a complex notion of causality that characterized much 19th-century medicine, in which disease was seen as the result of interactions of the patient's individual "constitution" with an ever-changing and often dangerous environment.2 By the late 20th century, many observers would renew concerns voiced more than a century earlier about the environment's relationship to disease.

In 1832, as cholera raged in New York City, the Journal published an article advocating immediate treatment upon diagnosis with 100 drops of laudanum "mixed with nearly as much of the spirit of essence of peppermint into a wineglass, and filled with brandy." The author cautioned against the use of bloodletting and cathartics (showing impressive therapeutic restraint, given their popularity). By the early 20th century, as epidemics of such infectious diseases as tuberculosis and smallpox receded, the Journal began to emphasize studies of the systemic chronic diseases, including cancer, heart disease, and diabetes, that would become so characteristic of disease patterns in the developed world. Thus, the Journal reflected the shifts in the burden of disease caused by forces typically beyond the reach of medical intervention.

Documenting Therapeutic Innovation

The Journal provides a powerful record of the course taken by medical science and its applications over a 200-year period. It quickly became a conduit for reporting new investigations and findings and for summarizing and disseminating evolving medical knowledge across the widest range of practice. After issuing favorable reports on bloodletting, herbal treatments, and other "heroic" practices of the early 19th century, the Journal began to reflect a growing skepticism toward such approaches. Authors increasingly pointed to the benefits of the healing powers of nature — vis medicatrix naturae — as physicians came to recognize some of the iatrogenic effects of their interventions that had previously been difficult to differentiate from the course of serious disease.3 Therapeutics based on ancient notions of humoral excess and depletion gave way to a renewed emphasis on empirical observation and experiment. The first demonstration of surgical anesthesia, conducted at Massachusetts General Hospital in 1846 in an amphitheater soon to be renamed the "Ether Dome," was first reported in the Journal (Figure 2Figure 2"First Operation under Ether," 1846, with Related Journal Report.). Others quickly began using ether in their practices. One surgeon wrote in the Journal, "I performed the amputation of an arm, the second under the use of ether, while the patient was dreaming of her harvest labors in Ireland, and felt grating but not painful sensations, `as if a reaping-hook was in her arm'" (1850).

The rise of the germ theory was vigorously debated in the Journal in the late 19th century. As one author noted, "Whether these organisms are of vegetable or animal origin, whether they are really the cause of the diseases they accompany, either by the activity which they exercise as living organisms, or by the products they give rise to, whether they are actually the contagious power, is a question still sub judice" (1871). But the idea of specific causes of specific diseases would come to dominate the pages of the Journal by the end of the century. By then, the decided advantages of "aseptic surgery," "aseptic midwifery," and other approaches to reducing infection had been demonstrated by the prevailing anecdotal logic of repeated case reports (Figure 3Figure 3"The General Arrangement of Surgeon, Assistants, Towels, Spray, &c., in an Operation Performed with Complete Aseptic Precautions," 1882.).4

The diagnostic opportunities inherent in the germ theory were apparent in a discussion of Paul Ehrlich's techniques for identifying the tubercle bacillus in sputum (1891). Early in the 20th century, Ehrlich's introduction of Salvarsan to treat syphilis heralded a new age of "magic-bullet" medicine, in which therapies would be identified and designed to target specific pathogens.5 Although the full therapeutic implications of these insights — frequently reported in the Journal — would be delayed until the introduction of antibiotics — notably, penicillin — in the 1940s, the revolutionary aspects of this approach to infection would not be lost on Journal readers. With germ theory, the scientific foundation for the use of vaccines, new and old, was at last demonstrated. Compulsory vaccination was a constant topic of debate in the Journal from its earliest years, as it remains in contemporary societies, conveying ongoing tensions between social mandates and individual liberties, the good of the many and the risks to the few.

The Journal would report many "firsts" in subsequent years, including the first major quantitative study linking smoking to lung cancer (1928), the introduction of the pulmonary artery catheter (1970), and early clinical descriptions of AIDS (1981). And breakthroughs reported elsewhere quickly found their way to the Journal. Insulin, for example, first described in the Journal of Laboratory and Clinical Medicine in 1922, received extensive review and discussion in the Journal later that year, and many articles analyzing its optimal use in diabetes followed.

Myriad new diagnostic technologies accompanied changes in the theory and treatment of disease. The Journal offers a window onto the rise of new medical technologies, from stethoscopes to improved tourniquets, from Wilhelm Roentgen's x-rays to magnetic resonance imaging and beyond. Technologies that probe and visualize the body represented a critical aspect of the development of modern medical practice and the conceptualization of pathologies. The focus on disease specificity and causal mechanism that emerged with the germ theory would ultimately drive research at the molecular and genetic level that continues to be reflected in the Journal.

The consistent editorial goal was to bring cutting-edge knowledge to a wide audience of clinicians in a timely way. As a result, the Journal followed a "synthetic" approach, incorporating sophisticated findings (from observation, experimentation, and the laboratory) into pragmatic clinical and population-based approaches to the amelioration of disease and its associated morbidity and mortality. But viewing the Journal merely as a "record" of medical "progress" would be to diminish its value in recovering a complex view of our medical past, often filled with conflicts, debates, and indicators of values and beliefs that transcended scientific developments.

Education and the Dissemination of Medical Knowledge

From the beginning, the Journal has critically covered essential debates about the character and quality of medical education. The editors considered one of their primary goals to be educating the profession, so assessment of medical school programs was in harmony with their mission; after all, these schools produced their readers. In the late 19th century, the Journal frequently noted the great inconsistencies in educational standards and quality. A decade before the publication of the Flexner reforms, prominent Boston physician Henry Bowditch anticipated many key aspects of the report when he called for linking medical education to universities, lengthening the course of study, and demanding deeper preparation in the sciences and wider domains of knowledge (1900). He argued for active learning to replace didactics, a theme that would echo through the debates about medical education. As late as 1900, when Bowditch proposed his reforms in the Journal, less than half the students at Harvard Medical School had completed a college education. After the publication of the Flexner Report in 1910 and the massive changes that followed, the Journal applauded the consolidation of medical education on a new scientific foundation.

But controversies about the relationship of scientific and clinical expertise, generalism and specialism, and the medical curriculum continued unabated in the Journal's pages. The recognition that new knowledge crowded the curriculum intensified the debates about medical education. "No individual can grasp all the facts of scientific interest. . . . The attempt to teach everything has been abandoned," noted the Journal in 1926. Given this reality, concerns frequently arose that clinical insight and the professional values of caregiving might be marginalized in the battles for time and authority in the curriculum. With increased emphasis on the basic sciences, some physicians lamented the loss of time at the bedside. "The number of formal lectures could be reduced and the teaching revitalized by more frequent contact with clinical material," one physician noted in the Journal in 1928.

Physicians frequently insisted that medicine was both an art and a science. In part, this claim reflected concerns already articulated in the late 19th and early 20th centuries that medicine's turn to a new science had alienated deeper humanistic values and concerns about the patient. These apprehensions would be reflected in debates about how best to prepare new generations of physicians. Even while the Journal voiced such anxieties, it continued to advocate aggressively for evidence-based practice long before the nomenclature "evidence-based medicine" came into vogue. "Only thus can medicine progress; only through observation and experiment can the world grow in wealth of knowledge," explained one editorial (1919). Simultaneously, however, the Journal repeatedly directed attention to the vagaries and values of the doctor–patient relationship (1935).

There was never a great distance between the Journal's interest in developments in medical education and its commitment to professional education. In 1895, Dr. Richard Cabot of Massachusetts General Hospital began using case records centered on postmortems, operative findings, and diagnostic uncertainty "in private quiz exercises at [his] office" (1939). At the turn of the 20th century, the Journal started publishing these "exercises" in clinical thinking under his editorial supervision. In 1923, the "Case Records of the Massachusetts General Hospital" became a special feature (Figure 4Figure 4Chest X-Ray Suggesting "a Pathological Process in the Lung Parenchyma, Most Marked in the Left Base," from the Journal's First Case Records of the Massachusetts General Hospital, October 25, 1923.) — and it continues today (1948). These "teaching cases" remained at the heart of the Journal's ongoing commitment to "continuing" medical education, even as the rigors of publishing peer-reviewed, statistically sophisticated original scientific findings moved to the fore.

Too Much to Know

With the radical expansion and shifting of the scientific basis of medicine at the turn of the 20th century, the Journal recorded growing interest in and concern about specialization. From a largely undifferentiated notion of medical training and expertise, many new and specific divisions of the medical profession developed.6 Whereas the Journal came to view specialization as the inevitable result of exploding medical knowledge, the creation of medical "specializm" was viewed with considerable skepticism and lamentation, if not outright hostility. Much ink was spilled in attempts to determine the relationship of general knowledge and practice to increasingly specific (and limited) areas of expertise. How would the "whole patient" be treated when specialties had divided the body into organ systems and medicine into categories of disease and authority over various technologies and techniques?

Although "general practitioner" was becoming a term of nostalgia, if not derision, commentators frequently pointed to the dilemmas of coordination implicit in the growth and division of medical knowledge. "With this specialization . . . are we not losing to a considerable degree our professional competence?" the Journal asked in 1924. "Are we not losing sight of that fundamental thread of truth that gives us a perspective of the real value of our work; that enables us to consider our patient as an individual and not a pathological unit of a human body or a representative of an age group?" Such concerns would reverberate through the Journal's second century; systematic expertise and notions of standardization displaced to a considerable degree the personal and intimate connections of local practice and continuity of care. "How much can the specialist know of home conditions, of family difficulties, and their relation to the case?" lamented a physician in 1923.

The simultaneous explosion of new knowledge and its fracturing into specialized fields posed particular issues for the Journal itself. With more and increasingly specialized papers arriving at its doorstep, the traditional board of editors could no longer critically evaluate their quality without wider consultation. Peer review now required identifying independent experts and soliciting their assessment of submissions.

The Permeable Boundaries of Science and Medicine

Despite the Journal's deep commitment to empirical reasoning and scientific rationality, cultural and political beliefs and values are ever apparent in its pages. In some instances, professional prerogatives and social assumptions are exposed. For example, when the introduction of women students at Harvard Medical School was debated in 1878, the Journal expressed concern: "It would . . . be impossible to avoid an indiscriminate mingling of the sexes in the dissecting or autopsy rooms, and in the amphitheatres, to witness exercises which justly have hitherto been thought of a character to be witnessed by one sex alone." Harvard would ultimately admit women in 1945, when the war caused a shortage of male candidates. In the 1950s, the Journal expressed regret that some women physicians with children "have found it impossible to carry on their practices" (1954).

Nowhere, perhaps, is the porous membrane of medicine and science seen more clearly than in the Journal's coverage of eugenics and mandatory sterilization in the early 20th century. Advocating for the sterilization of the "unfit," the Journal argued in 1928, "Sterilization of mental defectives seems, on first thought, like taking decided liberties with the individual. Viewed as a public health measure, however, it becomes apparent that it is a practical method of reducing the incidence of defectiveness and eventually preventing further deterioration of the race. It is more humane and practical than permanent segregation of the individual, it is simple and it is effective."

Most alarming was the admiration expressed for developments early during the Third Reich. The Journal announced in 1934, "Germany is perhaps the most progressive nation in restricting fecundity among its unfit. . . . In America it is probable that the sentiment of the people is not ready for the adoption of the German plan, and will be inclined to restrict compulsory sterilization to a small proportion of those who might properly be regarded as especially fit subjects of this treatment."

Of course, such pronouncements can only be fully understood through deeper investigation of their context, but they remind us that medicine and journals disseminating scientific knowledge are not immune from deeply held values or dangerous social and political forces. By the end of World War II, the Journal would utterly condemn Nazi science and medicine, noting the horrors inflicted on behalf of medical science in a totalitarian regime (1949). After the Holocaust, medical ethics would be radically reframed with a new emphasis on patient autonomy and informed consent. In 1966, anesthesiologist Henry Beecher published an exposé in the Journal of unethical research using human subjects that had previously appeared in major American medical journals (including the Journal). That article was an important contribution to the larger process of recognizing patients' rights — as research subjects and in clinical care. Beecher concluded, "It is absolutely essential to strive for [consent] for moral, sociologic and legal reasons."

Reflections on the Journal at 200

While the Journal embraced new science and the critical apparatus of peer review, it rejected a narrow notion of specialism, continuing to cover the widest range of contributions to medical knowledge. In an increasingly atomized medical world, the commitment to publish on cross-cutting educational, professional, ethical, and policy issues pulled together diverse readers, including physicians and other health care providers, public health experts, and policymakers, around issues that were often beyond their immediate expertise. The radical growth of teaching hospitals, federal funding for basic science and clinical research, and academic medical centers (all developments reflected in the Journal) have been crucially linked to the Journal's growth, stability, and success.

During the Journal's first 200 years of publication, medicine and health care moved from the social periphery to become dominant aspects of our science, culture, and economy. The Journal unquestionably owes its success and stability to this monumental shift in the status, authority, and impact of biomedicine. But the Journal has also played a critical role in these developments. By combining a commitment to publishing papers of scrupulous scientific merit across wide-ranging domains, with a recognition of the central questions and values uniting the profession, the Journal has remained true to its founders' vision. It has recognized that advances in medical science can finally be assessed only in the context of delivery, care, and outcome. The Journal reflects today, as at its inception, a view that medical science and its applications are fundamentally tied to patient care and public health. It therefore continues to draw a range of readers wider than Warren could have imagined. Today, the ability to disseminate publications so widely through digital technologies promises to bring innovations in medical knowledge to a new set of global constituents. The first hundred issues of Warren's journal were, of course, distributed on horseback.

No one having looked at the last 200 years of medicine — in which changes came so quickly and dramatically — would hazard a prediction about the next two decades, let alone the next two centuries. Nonetheless, as vast as these changes have been, there are substantial continuities in the nature of scientific inquiry, the care of the patient, and powerful questions concerning the public's health. Today we say that medicine is a "public good." But though their society, culture, skills, and science differed so profoundly from ours, those who started this Journal in 1812 undoubtedly understood that basic truth.

Browse all 200th Anniversary Articles.

Historical Journal Articles Cited.

New England Journal of Medicine and Surgery, and the Collateral Branches of Science

1812. Warren J. Remarks on Angina Pectoris. 1:1-11.

The Boston Medical and Surgical Journal

1828. Gorham J. Medical report of the weather and prevalent diseases for the last three months. 1:10-12.

1832. Editorials and Medical Intelligence. 6:401-2.

1837. Editorials and Medical Intelligence. 16:16-17.

1846. Bigelow HJ. Insensibility during surgical operations produced by inhalation. 35:309-17.

1850. Peirson AL. Anæsthetic agents. 42:229-32.

1871. Seaverns J. Recent advances in medicine and their influence on therapeutics. 85:113-20.

1878. Reports of Meetings. Female medical students at Harvard. 98:786-7.

1891. Ernst HC. Records for cases of tuberculosis treated with Koch's parataloid. 124:75.

1900. Bowditch HP. The medical school of the future. 142:445-53.

1919. Editorial. Science and medical teaching. 180:108-9.

1923. Phippen WG. The relation of the specialist to the general practitioner. 189:204-6.

1924. Specialism versus Competence. 190:475-6.

1926. Editorial. The teaching of medicine. 195:1124-5.

1928. Appel KE. Medical education: the retrospect of a recent graduate. 197:1265-7.

The New England Journal of Medicine

1928. Lombard HL, Doering CR. Cancer studies in Massachusetts: habits, characteristics and environment of individuals with and without cancer. 198:481-7.

1928. Editorial. Sterilization of defectives. 199:1225-6.

1934. Editorial. Sterilization and its possible accomplishments. 211:379-80.

1935. Henderson LJ. Physician and patient as a social system. 212:819-23.

1939. Mallory TB. Richard Clarke Cabot and the clinicopathologic conference. 220:880.

1948. The Case Records of the Massachusetts General Hospital. 239:690.

1949. Alexander L. Medical science under dictatorship. 241:39-47.

1954. Editorial. Practice of medicine by married women. 250:486.

1966. Beecher HK. Ethics and clinical research. 274:1354-60.

1970. Swan HJC, Ganz W, Forrester J, et al. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. 283:447-51.

1981. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. 305:1425-31.

1981. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia. 305:1431-8.

1981. Siegal FP, Lopez C, Hammer GS, et al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. 305:1439-44.

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

Source Information

From the Department of Global Health and Social Medicine, Harvard Medical School, Boston; and the Department of the History of Science and the Office of the Dean, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA.


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