Faculty Bibliography

Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. Eight major clusters of related genotypes were identified in M. tuberculosis sensu stricto, including a single cluster representing organisms responsible for several large outbreaks in the United States and Asia. All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis are distinct, deeply branching genotypic complexes whose extant members did not emerge directly from one another in the recent past. sSNP genotyping rapidly delineates relationships among closely related strains of pathogenic microbes and allows construction of genetic frameworks for examining the distribution of biomedically relevant traits such as virulence, transmissibility, and host range

Yet for all of Kennedy's suffering, the ailments did not incapacitate him, [Robert Dallek] concluded. In fact, he said, while Kennedy sometimes complained of grogginess, detailed transcripts of tape- recorded conversations during the Cuban missile crisis in 1962 and other times show the president as lucid and in firm command. For many years, Kennedy's back problems were largely attributed to injuries suffered when his Navy patrol boat, PT-109, was sunk in World War II. In fact, he had back pain before that. Dallek said his vertebrae may have begun degenerating as a result of the steroids he may have taken for intestinal problems in the late 1930s. The records show that Kennedy had 'a tremendous proclivity for infections,' [Jeffrey A. Kelman] said, contradicting [Janet G. Travell]'s assertion in 1960 that Kennedy had 'a better than average resistance to infection' and 'astounding vitality.'

The trend has been building for years but has only now been confirmed through more refined statistical methods and improved reporting of infection with HIV, the virus that causes AIDS. The world figures largely reflect the epidemic in sub-Saharan Africa, the world's worst-affected area, where nearly 1 in 11 adults is infected. There, women account for 58 percent of infections. Whether the ratio of women to men will continue to increase depends on unpredictable factors. If the AIDS epidemic explodes in Asia, men can be expected to make up a larger percentage of those infected worldwide, because among infected people there, the male- female ratio ranges from about 2 to 1, in Thailand, to 8 to 1, in China, Dr. Neff Walker, a U.N. epidemiologist, said in a telephone interview from Geneva. Of the 38.6 million adults living with HIV worldwide, 19.2 million are women. Of the 4.2 million adults newly infected this year, 2 million are women. Women accounted for 1.2 million of the world's 2.5 million adult deaths from AIDS this year

Of the 38.6 million adults living with H.I.V. worldwide, 19.2 million are women. These figures include both those who are infected with H.I.V. and those who have AIDS. Of the 4.2 million adults newly infected this year, 2 million are women. Women accounted for 1.2 million of the 2.5 million deaths from AIDS in the world this year. In addition, 3.2 million children have H.I.V. Dr. [Peter Piot] described success in fighting H.I.V., where it has occurred, to prevention programs that have fostered a number of behavioral changes: postponing the age of first sexual intercourse; increasing the use of condoms; having fewer sex partners and fewer encounters with prostitutes; and improving education and access to H.I.V. tests. The United Nations reports that women now make up about half of H.I.V.-positive adults worldwide, mainly because of the large numbers of H.I.V.-positive women in sub-Saharan Africa. That region accounts for about 70 percent of all H.I.V./AIDS cases

Whether the ratio of women to men will continue to increase depends on unpredictable factors. If the AIDS epidemic explodes in Asia, men can be expected to make up a larger percentage of those infected worldwide, because among infected people there, the male- female ratio ranges from about 2-to-1 in Thailand to 8-to-1 in China, Dr. Neff Walker, an epidemiologist at the United Nations, said in a telephone interview from Geneva. Of the 38.6 million adults living with HIV worldwide, 19.2 million are women. Of the 4.2 million adults newly infected this year, 2 million are women. Women accounted for 1.2 million of the 2.5 million deaths from AIDS in the world this year. From 1991 to the present, 92.9 percent of AIDS cases reported in the county were male and 7.1 percent female, [Michael Bursaw] said. In that time, 10,682 new AIDS cases in males were reported, 819 in females

A presumed reason for the difference in death rates was that patients did not benefit from the application of several kinds of recommended therapies. Where the guidelines called for ACE inhibitor drugs to reduce the risk of death, the study found their use was 40 percent in the ''lagging'' hospitals compared to 70 percent in the ''leading'' hospitals. And where guidelines called for cholesterol lowering drugs, the use was 58 percent in lagging hospitals compared with 80 percent in leading ones. Similarly, use of aspirin was 73 percent compared with 93 percent, and efforts to stop smoking 7 percent compared with 65 percent. Some doctors do not follow guidelines because they fail to keep up with medical advances. Others fail to communicate critical information from guidelines to patients well enough. Still other doctors dismiss guidelines as cookbook medicine, partly in the belief that medicine is more an art than a science. But as the lifesaving benefits of following guidelines becomes better documented, such doctors are increasingly being challenged by the question: would they fly with a pilot who did not use a checklist before takeoff? Clearly, guidelines cannot completely replace physician judgment for many reasons. One is that many patients, particularly the elderly, are afflicted with more than a single disease, and that situation requires modification of guidelines. Another is that many patients do not fit the rigid criteria used in selecting the participants in clinical trials, and disagreement may arise as to whether the findings can be extrapolated to them. So the trials and guidelines do not answer all the questions doctors face in everyday practice

There were no heart attacks or deaths among the 200 participants in the study, because they had implanted defibrillators, which monitor heart rhythms and deliver electric shocks to restore normal heartbeat when they detect life-threatening abnormalities. Two of the authors -- Dr. Jonathan S. Steinberg, chief of cardiology at St. Luke's-Roosevelt Hospital in Manhattan, and Dr. Marcin Kowalski, a resident at St. Luke's -- said the findings documented persistence of increased psychological stress after Sept. 11 and showed compelling evidence of its effects on the heart. The researchers scrutinized the electrocardiograms stored in the device for evidence of two life-threatening abnormal rhythms -- ventricular tachycardia and ventricular fibrillation. The device is programmed to deliver a shock when either of these rhythms develops. (The researchers did not study the rate of arrhythmias that were not life threatening.)

If the new findings hold up in further testing, use of the filter may make angioplasty a preferred procedure among many of the estimated 200,000 Americans who undergo carotid artery surgery each year, said Dr. Jay S. Yadav of the Cleveland Clinic, who led the study. Particles that break away from the buildup of fatty deposits in the carotids are a leading cause of the 730,000 strokes that occur in this country each year. After inflating a balloon to open the clogged artery -- just as doctors do in angioplasty to open up blocked arteries in the heart -- doctors insert a tiny metal tube called a stent to help keep the artery open. The carotid stent is made of flexible nickel and titanium so it can change shape as the artery pulses. Because new fatty deposits and tissue can form on the stents and then block a repaired artery, researchers have reported significant progress in reducing the frequency of such complications by coating the tubes with various drugs. But Dr. Yadav said the role of coated stents in carotid angioplasty was not known