Nava Blum

Coronary artery disease: Are men and women created equal?

BACKGROUND Ischemic heart disease in women is a difficult issue in cardiovascular medicine, mainly because of our lack of understanding of the early-stage mechanisms and symptoms. A better and earlier understanding of the pathophysiology of coronary artery disease (CAD) in women will enable us to detect ischemic heart disease earlier and prevent adverse clinical outcomes. OBJECTIVES The aims of this article were to describe the phenomenon of ischemic heart disease in women, increase awareness of the difference between men and women in relation to ischemic heart disease, improve our understanding of the mechanisms that cause this difference, and identify new approaches for better and earlier detection and treatment of CAD in women. METHODS We conducted a search of the PubMed database for double-blind studies on the mechanistic pathways of CAD in women published in English within the past 10 years and epidemiologic studies published since 1970. Search terms included women and coronary artery disease and ischemic heart disease in women. RESULTS The literature search revealed 30 peer-reviewed articles pertaining to this issue. The incidence of CAD was markedly lower in women <60 years of age than in older women. After 60 years of age, the rate of CAD increased and reached the rate seen among men by the 8th decade of life. The gender difference in atherosclerosis in the coronary tree was particularly large in patients <55 years of age and remained large at older ages. The gender difference in the coronary bed was strikingly larger than in other vascular beds. Intensive risk-factor modification had a similar effect on plaque progression in both men and women. Coronary endothelial dysfunction appeared to be related to cardiovascular morbidity and mortality in women as well as in men, and because endothelial dysfunction could be modified, it appeared that the prognosis could be improved by appropriate management. A strong association was found between body mass index (BMI) and metabolic status, but only the metabolic syndrome was associated with CAD. Physical activity was independently associated with fewer risk factors, less CAD, and fewer adverse events in women; however, obesity was not associated with these outcomes. CONCLUSIONS Results of the identified studies suggest that reduction of risk factors is a common approach to fighting heart disease in both sexes. It appears that for women, weight and BMI are not as important as previously thought, but physical exercise and fitness are very important and can change risk factors and clinical outcomes more than any other known intervention. Data suggest that global inflammation may play an important role in women and may predict cardiovascular outcome in women much better than the traditional risk factors that have been used and proved for men.

Oliver Wendell Holmes (1809-1894) and Ignaz Philipp Semmelweis (1818-1865): preventing the transmission of puerperal fever.

IN THE EARLY TO MIDnineteenth century in Europe and America, thousands of young women died from childbed fever, also known as puerperal fever, a disease rampant in the charity maternity clinics of the time.1 Women were generally affected within the first three days after childbirth. The disease progressed rapidly and caused acute symptoms of severe abdominal pain, fever, and debility. Therapy usually involved bloodletting, but with or without this treatment the disease was often fatal. Perhaps Jane Seymour, the third wife of Englands King Henry VIII, was the most famous victim of puerperal fever. She died two weeks after giving birth to Henrys only surviving son, the future Edward VI of England. Two heroes in the fight against puerperal fever were Oliver Wendell Holmes and Ignaz Philipp Semmelweis. If Holmes now stands in Semmelweiss shadow, it is because Holmess own medical reputation was largely eclipsed by the brilliant success he achieved in the fields of literature, poetry, and popular lectures.2 In the late nineteenth and early twentieth centuries, Holmess literary and poetic works were reprinted in hundreds of editions by American and British publishers. Even his own profession came to value him more as a professor and poet than as a fearless and outspoken defender of the life and health of childbearing women. In the late nineteenth century, Oliver Wendell Holmes was so popular that his image and lines from his poetry and prose appeared on items such as this calendar, as well as games, postcards, and gift books. Courtesy of Marilyn Barth and the National Library of Medicine, National Institutes of Health, Bethesda, MD. Semmelwei s Defender of Motherhood. Courtesy of the National Library of Medicine, National Institutes of Health, Bethesda, MD. Born into a family whose ancestors had distinguished themselves in both literature and medicine, Holmes attended Harvard University and also studied at the prestigious medical schools of Paris. After two and a half years, he returned to the United States and received his medical degree from Harvard in 1836. He maintained a small medical practice for 12 years but found that his main interests lay in teaching and research. Hearing of the death of a physician one week after performing a postmortem exam on a woman who had died of puerperal fever, Holmes began a thorough investigation and read a paper on “The Contagiousness of Puerperal Fever” before the Boston Society for Medical Improvement in 1843. Because the paper was published in the New England Quarterly Journal of Medicine and Surgery,3 a journal with a very small circulation which ceased publication after only one year, it went largely unnoticed until it was republished in 1855 as a booklet entitled Puerperal Fever, as a Private Pestilence.4 Holmes argued the controversial view that physicians with unwashed hands were responsible for transmitting puerperal fever from patient to patient. Holmes was promptly attacked by the leading Philadelphia obstetrician, Charles D. Meigs, who derided his arguments as the “jejeune and fizzenless dreamings” of a sophomoric writer, and declared that any practitioner who met with epidemic cases of puerperal fever was simply “unlucky.”5 A few years later, Semmelweis took up the struggle in Europe to persuade other physicians of the contagiousness of puerperal fever. Semmelweis completed his MD degree at the University of Vienna in 1844. In 1846, he was appointed assistant to Johannes Klein in the maternity clinic of the Vienna General Hospital. Semmelweis was puzzled to discover that the First Clinic of the Hospital had a much higher maternal mortality rate (10%) than the Second Clinic (less than 4%). The only difference he could find between the two clinics was that the first was used to train medical students whereas the second trained midwives. When his friend and colleague, Professor Jakob Kolletschka, died from septicemia from a finger injury acquired from a postmortem examination on a woman who had died of puerperal fever, Semmelweis concluded that he and his fellow physicians were carrying “cadaverous particles” from the autopsy rooms to the patients they examined in the First Clinic. The midwives, who were not involved in autopsies, had no such contact with corpses or “cadaverous particles.” Semmelweis began to insist that anyone attending autopsies scrub their hands in chloride of lime before entering the maternity wards. The maternal mortality rate immediately fell to that of the Second Clinic.6 Semmelweis soon became the focus of a fierce power struggle within the Vienna medical faculty as his work became the subject of a bitter dispute among European obstetricians. His arguments ran contrary to the disease theories of the time, that infections were due to “miasmas” or “bad air,” or to the balance of humors within a patients body. In 1861, Semmelweis published Die Atiologie, der Begriff und die Prophylaxis des Kindbettfiebers [The Etiology, Concept, and Prophylaxis of Childbed Fever].7 When his book was either ignored or ridiculed, Semmelweis began to denounce prominent European obstetricians as irresponsible murderers. He became depressed and started drinking; his public behavior became irritating and embarrassing to his professional colleagues and to his family. In 1865 he was deceived into entering an insane asylum and when he tried to escape, he was severely beaten by guards. A gangrenous wound to his hand, probably caused by the beating, led to his untimely death two weeks later. Thanks to the work of Holmes and Semmelweis, the gradual acceptance of sterile procedures, and to a variety of other factors such as improved environmental conditions, better overall obstetrical care, and the availability of antibiotics, puerperal fever has become rare in developed countries. In time, with sufficient organization, political will, and dedication, maternal mortality will be very rare in all parts of the world.

Howard A. Rusk (1901–1989) From Military Medicine to Comprehensive Rehabilitation

HOWARD ARCHIBALD RUSK, MD, is generally recognized as the “father of comprehensive rehabilitation.” In comprehensive rehabilitation, those suffering disabilities that result from illness, injury, or congenital defect are given therapy and training designed to help them to live and work in the community to the best of their abilities. Rusk initially developed this field as a contribution to military medicine during World War II and later broadened it in application to the civilian population. The excerpts reprinted here were taken from his engaging and often humorous autobiography in which he relates the many adventures involved in his life’s work. Rusk was born on April 9, 1901, to Augusta Eastin Shipp and Michael Yost in Brookfield, Missouri. He received his undergraduate degree from the University of Missouri in 1923, then earned his medical degree at the University of Pennsylvania two years later. He returned to Missouri for a one-year internship at St Lukes Hospital in St Louis, married Gladys Houx, and began a private practice in internal medicine. In the early 1930s, he had his own office with a staff of seven—two doctors and five nurses—as well as technical and secretarial staff. In April 1937, Rusk became the second internist in the United States to pass the rigid examination required for membership in the newly created American Board of Internal Medicine.1 In 1932, the first of Rusk’s many articles began to appear in various medical journals. These early papers dealt with the therapeutic use of potassium in treatment of obesity and certain allergies.2 With the entrance of the United States into World War II in 1942, Rusk left private practice to join the US Air Force as a major and was stationed as Chief of Medical Services at Jefferson Barracks in St Louis. There he began to establish a broad and comprehensive program of rehabilitation for his injured patients. It began with a patient who complained when a spider’s web was cleaned from the ceiling above his bed; watching the spider spin his web was, the patient said, his only form of entertainment. Rusk realized that men who were sitting around bored and wasting time during their convalescence needed purposeful activities, and he began offering a series of classes. Eventually, he developed an integrated rehabilitation program with equal emphasis on physical reconditioning, psychological readjustment, and vocational training. Rusk’s program was remarkably successful, and the US Air Force subsequently established a whole series of special convalescent hospitals. Similar programs were later adopted by the US Army as “reconditioning” and by the US Navy as “rehabilitation.” The convalescent hospitals’ staffs were enlarged to include physical therapists, educators, athletic trainers, occupational therapists, social service workers, personal counselors, and vocational guidance experts who worked as a team to treat the needs of the “whole man.” Rehabilitation began the moment the acute illness or surgery terminated. After World War II, Rusk joined the faculty of the New York University School of Medicine and formed a facility for the rehabilitation of individuals with disabilities. Rusk first convinced the medical school at New York University to free up some wards in Bellevue and Goldwater hospitals to rehabilitate civilians. In 1946, Rusk was appointed professor and chairman of a new Department of Physical Medicine and Rehabilitation at New York University College of Medicine, and there he established the first comprehensive medical training program in rehabilitation in the world. In 1951 Rusk opened the Institute of Medical Rehabilitation at New York University and served as its director for 33 years. In 1984, New York University honored Rusk by renaming the facility the Howard A. Rusk Institute of Rehabilitation Medicine. The Rusk Institute today is the largest university-affiliated center devoted entirely to care, research, and training in rehabilitative medicine.3,4 Rusk founded the World Rehabilitation Fund in 1955, which has developed programs for professionals in 110 countries and trained more than 2000 physicians and other health specialists in rehabilitation. Rusk also served on many government panels and commissions and wrote several books and numerous articles. For two decades he served as a contributing editor to The New York Times and published a weekly column on medical issues and rehabilitation. He traveled around the world on behalf of the United Nations and other international organizations. He even worked as a team with Jihan el-Sadat, wife of Egyptian President Anwar el-Sadat, and Aliza Begin, wife of Israeli Prime Minister Menachem Begin, to create a program of cooperation on rehabilitation medicine between Israel and Egypt, announced in Cairo in 1979.5 Rusk was a great supporter of the disabled and argued passionately for the rights of the disabled to contribute to society. He campaigned for medical rehabilitation as a public health issue and argued that the control of many infectious diseases, the consequent lengthening of the lifespan, the aging of the population, and the shift in emphasis from infectious to chronic diseases meant that chronic physical and mental disabilities would continue to increase.6–8 He believed that rehabilitation for all those with disabilities was essential to the health and happiness of the population. Rusk’s ideas and new ways of thinking transformed the response to disability in the fields of public health and welfare and made it possible to rehabilitate millions of people with disabilities and help them to achieve healthier lives.9,10 Among Rusk’s awards were the Distinguished Service Medal, USA, and Lasker Awards in international rehabilitation, medical journalism, and public health. Rusk ended his autobiography with the words, “To believe in rehabilitation is to believe in humanity.”

Critical Shortcomings at Walter Reed Army Medical Center Create Doubt

This photograph shows an amputee soldier undergoing occupational therapy at the Walter Reed Army Medical Center (Walter Reed) in the early 1950s. Walter Reed was then well known for its comprehensive approach to rehabilitation based on the patients physical, vocational, social, and emotional capacities, leading to the maximum recovery of injured and disabled military personnel.1 An amputee soldier undergoing occupational therapy at the Walter Reed National Army Medical Center, 1952. Source. National Library of Medicine, Bethesda, MD. Since 1909, Walter Reed has healed American soldiers, presidents, and international visitors. The medical center was established to integrate patient care, teaching, and research, and to provide the highest standard of care to American servicemen.2 The center is named after Major Walter Reed (1851–1902), one of the brightest stars of the US Armys Medical Department. He was responsible for identifying the means of transmission of yellow fever and developing the protective practices—clearing mosquito breeding grounds, covering water supplies, using mosquito nets, and installing sewers—that enabled workers to finish building the Panama Canal.3 Major William Cline Borden (1858–1934), Reeds colleague and friend, spent six years after Reeds death trying to persuade the army to build a new general hospital in the District of Columbia and to name it for Reed. It was Bordens dream to combine the Army Medical School, the Army Medical Museum, the surgeon generals library, and a new hospital facility into a single campus. In 1905, Congress provided funds to build the hospital, which admitted its first patients in 1909. The hospital expanded very rapidly during World War I and again in World War II. Hundreds of thousands of soldiers were treated at Walter Reed during World War II and the Korean and Vietnam wars.4 Throughout the years, Walter Reed added additional facilities: the Walter Reed Institute of Research, the Armed Forces Institute of Pathology, the Army Physical Disability Agency, and several smaller units. Today, Walter Reed continues to serve the military community and admits approximately 16000 patients a year. The troubles at Walter Reed began during the wars in Iraq and Afghanistan. In August 2004, the Department of Veterans Affairs conducted focus group interviews with seriously wounded soldiers recuperating at the center. These revealed that many veterans of the wars in Iraq and Afghanistan had become frustrated, confused, and angry while dealing with the hospitals bureaucracy.5 One year later, the Pentagons Base Realignment and Closure Commission (BRAC) proposed shutting Walter Reed and moving much of its staff and services to the National Naval Medical Center in Bethesda, Maryland. The commission argued that Walter Reed was showing its age: “Kids coming back from Iraq and Afghanistan, all of them in harms way, deserve to come back to 21st century medical care,” said BRAC chairman Anthony Principi.6 In February 2007, the Washington Post published a series of articles documenting the poor living quarters and bureaucratic breakdowns endured by wounded soldiers returning from Iraq and Afghanistan. These soldiers lived in dilapidated buildings on the Walter Reeds campus and faced nightmarish tangles of red tape as they tried to secure ongoing care.7,8 President George W. Bush appointed a bipartisan commission, led by former Senate majority leader Bob Dole and former Secretary of Health and Human Services Donna E. Shalala, to investigate. The commissions report made six broad recommendations, including the creation of “recovery coordinators” to assist each seriously injured service member in navigating the heath care system, restructuring the disability and compensation systems, and improving the prevention, diagnosis, and treatment of posttraumatic stress disorder and traumatic brain injury.9 An independent review group appointed by US Secretary of Defense Robert Gates submitted a report, Rebuilding the Trust, in April 2007 that concluded many elements had combined to create the “perfect storm” of resource mismanagement at Walter Reed.10 These elements included the decision of the BRAC to close Walter Reed, pressure to outsource traditional military service functions through A-76 (an Office of Management and Budget A-76 circular requires competitions with the private sector for many governmental positions), and military-to-civilian personnel conversions. Coming at the same time as increasing numbers of wounded soldiers returned from Iraq and Afghanistan, this confluence of events increased the probability for the failures and shortcomings at Walter Reed. As Rebuilding the Trust put it: Additionally, inadequate facilities; leadership inattention; failure to meet processing guidelines; conflicting interpretations of laws, rules and regulations (long conditioned by lack of bureaucratic energy to clarify and simplify); and conflicting budget pressures, created their own impact and collectively brewed to feed the storm.10 The government continues to debate what to do with Walter Reed in the long term. The cost of retrofitting the existing medical center would likely be higher than that of building a new facility, but the war spending bill11 recently passed by the House would bar funds from being used to shutter Walter Reed. General Richard A. Cody, the Army Vice Chief of Staff, has suggested the proposed closing be reexamined while the Iraq war continues. Will the end of the Iraq war be the end of Walter Reed Army Medical Center?

“No Good Deed Goes Unpunished”: Ignaz Semmelweis and the Story of Puerperal Fever

Ignác Fülöp Semmelweis was born almost 200 years ago, in 1818, to a well-to-do middle class Hungarian family. He started law school in 1837, switched to medicine a year later, and graduated in 1844.

Professor Natan Goldblum: The Pioneer Producer of the Inactivated Poliomyelitis Vaccine in Israel

A PANDEMIC OF POLIOMYELITIS struck Israel in the early 1950s and created an urgent need for immunization against the disease. By 1956, there were 5835 cases of poliomyelitis, 85% to 90% of whom were children aged 5 years and younger.1 This pandemic began in part as a result of the massive immigration of Jews from post-war Europe and Middle Eastern and North African countries, which doubled the Israeli population within 3 years. It is possible that the virus was imported from these countries. In addition, the crowded, unsanitary conditions in the immigrant temporary camps facilitated the fast spread of the virus among the population.

High serum lactate level may predict death within 24 hours

Abstract Background: Unexpected death within 24 hours of admission is a real challenge for the clinician in the emergency room. How to diagnose these patients and the right approach to prevent sudden death with 24 hours is still an enigma. The aims of our study were to find the independent factors that may affect the clinical outcome in the first 24 hours of admission to the hospital. Methods: We performed a retrospective study defining unexpected death within 24 hours of admission in our Department of Medicine in the last 6 years. We found 43 patients who died within 24 hours of admission, and compared their clinical and biochemical characteristics to 6055 consecutive patients who were admitted in that period of time and did not die within the first 24 hours of admission. The parameters that were used include gender, age, temperature, clinical and laboratory criteria for SIRS, arterial blood lactate, and arterial blood pH. Results: Most of the patients who died within 24 hours had sepsis with SIRS. These patients were older (78.6±14.7 vs. 65.2±20.2 years [p<.0001]), had higher lactate levels (8.0±4.8 vs. 2.1±1.8mmol/L[p<.0001]), and lower pH (7.2±0.2 vs. 7.4±0.1 [p<.0001]). Logistic regression analysis found that lactate was the strongest independent parameter to predict death within 24 hours of admission (OR1.366 [95% CI 1.235-1.512]), followed by old age (OR 1.048 [95% CI 1.048-1.075] and low arterial blood pH (OR 0.007 [CI <0.001-0.147]). When gender was analyzed, pH was not an independent variable in females (only in males). Conclusions: The significant independent variable that predicted death within 24 hours of admission was arterial blood lactate level on admission. Older age was also an independent variable; low pH affected only males, but was a less dominant variable. We suggest use of arterial blood lactate level on admission as a bio-marker in patients with suspected sepsis admitted to the hospital for risk assessment and prediction of death within 24 hours of admission.

The First Mental Hospital in China

AFTER MORE THAN 25 YEARS of planning and fundraising, American medical missionaries opened the first mental hospital in China in 1898. In 19th century China, the mentally ill were usually confined by their families in a dark room of the house, essentially neglected.1 If left to wander in the streets, they were often mocked and laughed at, and sometimes stoned. If they did anything wrong, they could be arrested and thrown into prison. Because the mentally ill were largely invisible, some missionaries argued that mental illness was not as prevalent in China as in Europe or the United States. John G. Kerr, MD (1824–1901), an American Presbyterian medical missionary, disagreed—and he worked long and hard to change the treatment of the mentally ill. Kerr had trained at Jefferson Medical College in Philadelphia and went to Canton, China (now Guangzhou), in 1854. For more than 40 years, he ran the Ophthalmic Hospital in Canton, which treated almost one million patients.2 He also trained 150 Chinese medical students, including Sun Yat-Sen, who would become the first president of the Chinese republic. Kerr translated 34 volumes of Materia Medica into Chinese and published many of his own articles and treatises. In 1887, he became the first president of the Medical Missionary Association of China. As president, Kerr presented his plan for a mental asylum to the Medical Missionary Association. He was strongly supported by Professor Edward P. Thwing of the American Presbyterian Mission, who read a paper at the Shanghai Medical Convention in 1890 on “Western methods with insane Chinese.”3 In it, Thwing noted that he and Kerr had visited a number of wealthy citizens of Hong Kong and Canton and appealed to them for funds to open a mental hospital to bring relief to their suffering kinsmen; these citizens had listened politely but declined to do anything. But Thwing was not deterred; the demands of humanity required a mental hospital—whether or not the Chinese themselves wanted one. “We ask, not what they want, but what they need,” he wrote. “The heathen do not ask for bibles and missionaries, but they need them all the same.”3(p399) The same logic applied: the Chinese did not want, but needed, a mental hospital. The Medical Missionary Association agreed, in 1890, to support the proposal, despite doubts and objections from some of its members. In 1891, Kerr bought three acres of land in Canton, at his own expense, and started a dispensary. In 1894, he received unexpected help from a former medical missionary who gave him the money to erect a building on the site. By 1897, the hospital, with 24 rooms, was ready; in February 1898, the first patient was admitted.4 Kerr said that most of the patients were brought to him in chains; his descriptions suggest that, at that time, the insane were often treated as harshly as lepers. The first patient admitted had been chained for three years to a stone in such a way that he had been unable to take a single step and had lost the power of walking.5 The second patient, a woman, was found with a chain around her neck, the end of which was fastened to the floor behind her. John G. Kerr Refuge for the Insane, Canton, China Source. Courtesy of the National Library of Medicine. When he opened his Refuge for the Insane, Kerr declared some new principles: first, insane patients were ill and should not be blamed for their actions; second, they were in a hospital, not a prison; and third, they must be treated as human beings, not as animals. He pledged to conduct a course of treatment based on persuasion rather than force, on freedom rather than restraint, and on a healthy outdoor life with a maximum of rest, warm baths, and kindness. He also wanted to provide patients with gainful employment wherever possible. The directors of the Canton refuge worked closely with local Chinese officials and local police, who did not know how to handle insane people and were glad to refer them in large numbers to the refuge.6 Chinese officials paid the refuge an annual allowance for taking care of the patients. Local families also brought in patients, and some were sent from Hong Kong by the British authorities. The hospital was eventually expanded to 500 beds, and it operated with considerable success until it finally closed in 1937.

Blum et al. Respond

We thank Tulchinsky for commenting on and for expanding the discussion of Natan Goldblums contributions. We are aware that he was involved in many important projects, such as the one Tulchinsky mentions, but because of space limitations, we had to focus on only one aspect of his work—the first steps in producing the inactivated poliomyelitis vaccine in the 1950s. We are pleased to have more of Goldblums significant projects brought to the attention of our readers.

The St John Eye Hospital: A Bridge for Peace

The article offers information on the Saint John Eye Hospital in east Jerusalem. It is stated to be a bridge for peace in a world at war. It serves as the main center for specialized eye care in the West Bank, Gaza, and east Jerusalem. The eye hospital started in 1882, and was then located in Ottoman Empire Jerusalem. It closed in 1914, during World War I, but reopened in 1919. It is said to be the only public hospital in the region specializing in ophthalmology. It is stated to place a high priority on training local doctors and nurses. Patients are predominantly Palestinians. The hospital operates a number of satellite clinics in areas where public services are not easily available. It works to eliminate the main causes of preventable blindness.