Endothelial Nitric Oxide Synthase Gene Polymorphisms at Heart of High-Altitude Pulmonary Edema
Polymorphisms, or changes in the base pairs of the gene that encodes for endothelial nitric oxide (NO) synthase (the enzyme responsible for NO synthesis), are associated with high-altitude pulmonary edema and the pulmonary hypertension that accompanies it, according to a group of Japanese researchers from Shinsu University School of Medicine in Matsumoto, Japan, in this week’s issue of Circulation (Circulation. 2002;106:826–830OpenUrl).
Studies of 41 patients susceptible to high-altitude pulmonary edema and 51 health controls revealed that 2 polymorphisms of the NO synthase gene were found more frequently in the group that was susceptible to the high-altitude disorder than in the health controls (all of whom were climbers). Eleven of the susceptible group carried both polymorphisms, whereas no one in the control group had both. The polymorphisms were identified as a Glu298Asp variant and the 27 bp VNTR. Both are found in the endothelial NO synthase gene. Although the researchers, led by Yunden Droma, MD, feel that their study confirms a genetic basis involving impaired NO synthesis in the lungs of a person with high-altitude pulmonary edema, they also said the work calls for a more comprehensive genetic approach that uses linkage analysis and other tools of that discipline.
In an accompanying editorial (Circulation. 2002;106:768–769), A.J. Marian, MD, of Baylor College of Medicine and Eric Boerwinkle, MD, of The University of Texas Medical School at Houston noted: “Although the report by Droma et al provides important and novel observations that deserve replication and further analysis by others, the study has limitations that also deserve attention.”
They went on to point out that the sample size was small and that chance variations are possible. However, they complimented the researchers on their tenacity in sampling all available cases and identifying controls who were also exposed to high-altitude conditions. “It is necessary for others with similar opportunities to replicate and validate their findings in other populations,” they noted.
They also noted that the researchers did not provide functional data to support the associations and “to substantiate differential effects” of the NO synthase alleles. They warned that, “the results of the present study should be interpreted with caution and considered provisional pending confirmation in additional studies and evidence of supportive functional data.”
They wrote, “There is little doubt that genes are major determinants of susceptibility to disease, clinical outcome, and response to therapy. What remains less clear is whether we can reliably identify the underlying specific genes and gene mutations.” Three elements are necessary for genetic association studies to be accepted finally, they said. Those are adequate sample size, replication of the findings, and functional data.
“Until these criteria are met, the results of genetic association studies, including the results of Droma et al, should be considered provocative but preliminary,” the authors concluded.
Soluble Intracellular Adhesion Molecule-1 Associated With Rapid Atherosclerosis
Levels of soluble intracellular adhesion molecule-1 (sICAM-1) were higher in men who developed peripheral artery disease than they were in those who did not, according to authors of an intriguing report in this week’s issue of Circulation (Circulation. 2002;106:820–825OpenUrl).
Three researchers, Aruna D. Pradhan, MD, MPH, Nader Rifai, PhD, and Paul M. Ridker, MD, MPH, from The Brigham and Women’s Hospital and the Harvard Medical School in Boston, Mass, evaluated the relationship between baseline levels of sICAM-l, soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease during a 9-year follow-up period. They found that sICAM-1 levels were significantly higher at baseline among men who developed peripheral artery disease. However, they did not find a significant increase in sVCAM-1.
In their discussion, the authors noted that the men who developed peripheral arterial disease were the most likely to have traditional coronary risk factors at baseline. They noted that the chronic disease process called atherosclerosis involves both cellular and humoral inflammatory responses of which leukocyte recruitment is one. ICAM-1 and VCAM-1 facilitate this process.
“These data, while confirming the association between endothelial activation, inflammation, and systemic atherosclerosis, raise the possibility that cellular immune mechanisms and the associated temporal sequence of events in clinical PAD (peripheral arterial disease) progression may differ from those related to acute coronary occlusion,” the authors wrote.
Senate Nixes Amendment That Would Have Capped Damage Awards in Malpractice Suits
On July 30, 2002, the US Senate rejected an amendment to a generic drug bill that would have put a ceiling on damages awarded in malpractice suits against physicians and insurers, according to the July 31, 2002, issue of CongressDaily/AM. The generic drug bill passed the body—an attempt to give patients more access to cheaper generic drugs, according to the August 4, 2002 issue of AAMC STAT—new from the Association of American Medical Colleges.
The amendment would have limited punitive damages in malpractice suits to twice the compensatory damages. It required that half of the punitive damages go to state activities and also restricted the amount of attorney fees.
The bill would have capped noneconomic damages at $250 000. Republicans favored the bill, whereas Democrats said that it gave special consideration to the insurance industry at the expense of victims. President Bush had called on Congress to cap such awards.
New Surgeon General Approved in Senate
Richard Carmona, MD, an emergency physician, has been confirmed as US Surgeon General, after his qualifications were strictly scrutinized during committee hearings, according to the July 24, 2002, issue of The Arizona Daily Star.
Dr Carmona succeeds David Satcher, MD, a Clinton appointee whose term expired last February. Dr Carmona said he intends to follow the lead of previous surgeons general who used their offices as a “bully pulpit” from which they fought for a variety of public health issues. They opposed smoking, pushed for more treatment and prevention efforts in the area of AIDS/HIV, advocated that the nation get moving to reduce obesity and type II diabetes. In the past, surgeons general have demonstrated a surprising degree of independence. C. Everett Koop, MD, a pediatric surgeon, was expected to maintain a hard antiabortion line. He never compromised his own beliefs, but he surprised Congress and the health establishment by coming out strongly in favor of developing treatments and vaccines to prevent AIDS. He also came out in favor of measures to prevent the spread of HIV, including the use of condoms.
Dr Carmona will be commissioned as a three-star admiral in the public health corps. In a released statement, US Health and Human Services Secretary Tommy Thompson said: “Dr Carmona will be a strong and vigorous leader in our efforts to combat chronic conditions and lead this nation to better health.”