The last frontier in cardiovascular health: a landmark lecture for the XVII World Congress of the International Society for Heart Research.

Following World War II, Vannevar Bush described science as an "endless frontier" that should be made accessible to all Americans. Since then, cardiovascular health has improved markedly, largely because substantial investments in biomedical research led to numerous therapies and prevention strategies for cardiovascular disease. Despite these advances, however, science remains an endless frontier and we continue to face an infinite array of opportunities for improving cardiovascular health. A standard definition for "frontier" is the "farthermost limit of knowledge or achievement". The limits of our knowledge are expanding at an ever accelerated pace. Unfortunately, we do not always apply what we know, and therefore fail to achieve all we could. For example, we have known for two decades that heart attack patients benefit from beta-blockers, but even today, the drugs are not always prescribed. And, health disparities continue to exist among races and communities. Therefore, the "last frontier of cardiovascular health" is the translation and application of our knowledge to improve the cardiovascular health of all people. We will not reach the farthermost limit of achievement without new knowledge. But, in our zeal to expand our knowledge of cardiovascular diseases, we must remember to ensure that what we learn is rapidly applied to improve cardiovascular health.

Failure properties of suture anchors in the glenoid and the effects of cortical thickness.

The ultimate pullout strength and fatigue properties of a screw-design suture anchor implanted in the anterior glenoid rim were investigated and compared with results from a nonscrew-design suture anchor. Twenty-two cadaveric glenoids were harvested and one to two anchors were implanted in the superior and inferior quadrants. Fifty-seven Statak 3.5 anchors (Zimmer, Warsaw, IN) were tested and compared with results obtained in a previous study on 50 Mitek GII anchors (Mitek Products, Inc, Westwood, MA). The specimens were mounted on an Instron fatigue testing machine (Instron Corp, Canton, MA) and cycled between preselected minimum and maximum loads until pullout. The Mitek GII maintained a higher pullout strength than the Statak 3.5 after cyclic loading. Cortical thickness at the implantation sites was measured, and found to decrease monotonically from superior to inferior positions. The ultimate pullout strength, and subsequently the fatigue life, of both types of suture anchors depended directly on cortical thickness. The significantly lower performance of both anchors when placed inferiorly emphasizes the importance of correct anchor selection, number, and placement in this region. All anchors settled during the first 10 to 100 cycles, resulting in partial exposure of the implant. Intraoperative cycling of the anchors before suture tying may be necessary to achieve complete settling and prevent subsequent loss of coaptation between capsule and glenoid. The study shows that for the anchors to last 1,000 cycles or more, less than 50% of the theoretical ultimate pullout strength should be applied cyclically. With aggressive early rehabilitation exercises, this significant decrease in fixation strength could shift reconstruction failure from suture breakage or soft tissue tearing to anchor pullout.

Fatigue properties of suture anchors in anterior shoulder reconstructions: Mitek GII.

Suture anchors have simplified anterior capsule labral reconstruction. During rehabilitation the shoulder goes through many repetitions of range of motion exercises. These exercises will repetitively submaximally load the anchor and in theory should reduce the pullout strength of the suture anchor. No published reports exist on the fatigue strengths and properties of one of the most commonly used anchors: Mitek GII suture anchors. Fifty trials of cyclic submaximal load were done on 22 cadaveric glenoids with an average age of 66.8 years (range, 40 to 90 years). At two to three different sites on the same specimen, the anchors were inserted according to manufacturer's specifications. The anchors were tested to failure on a Instron 1331 servohydraulic mechanical testing system at 2 Hertz sinusoidal loading pattern using steel sutures and a predetermined load. There were 22 (44%) tests performed in the superior quadrant and 28 (56%) tests in the inferior quadrant. All anchors pulled out, and no wires broke. There were statistically significant differences between the superior and inferior portion of the glenoid with regard to number of cycles to failure at a given maximum load. The anchors underwent an average of 6,220 cycles before pullout at an average load of 162 N (SD = 73 N). In the superior quadrant, the average ultimate pullout strength was 237 N (SD = 42 N), whereas in the inferior quadrant the average ultimate pullout strength was 126 N (SD = 36 N). Hence, the ultimate pullout strength of the Mitek GII anchor was significantly higher (P < .002) in the superior quadrant than in the inferior quadrant. Using a least squares regression analysis, it was possible to predict the fatigue life of the superiorly and inferiorly placed suture anchors over a wide range of cycles. The R-squared values for trendlines showed good reliability (superior R2 = 0.55; inferior R2 = 0.28). The fatigue life curves for the two different quadrants were normalized using the ultimate pullout strength. This new, universal curve predicts the fatigue life of the Mitek GII anchor as a percentage of the ultimate pullout strength for any selected location. For a clinically relevant number of cycles, no more than approximately 40% to 50% of the ultimate pullout strength of the suture anchor can be cyclically applied to the anchor to guarantee a life for the duration of rehabilitation. For the entire system, the inferiorly placed anchors dictate the amount of cyclically applied load the system can experience without failing, and rehabilitation should be adjusted accordingly.

The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc. 99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with 99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and meso 99mTc-TMPAO isomers are efficiently trapped in brain.

Funding biomedical research: a common ground for concern?

Despite record levels of support, concerns over the ability of individual investigators to obtain funding for their research have been growing within the biomedical research community. The concerns have been focused almost exclusively upon the outcomes of funding decisions, and have ignored the pressures that produce them. Yet, it is those pressures that constitute our 'common ground for concern'. Resources committed in response to the pressures from special interest groups are unavailable for general competition based upon scientific merit. We in the biomedical research community must recognize that such self-interested efforts to dedicate resources undermine the integrity of the existing processes for making funding decisions. As a community, we should instead attempt to ensure that adequate resources are available to support the best quality research.

Increasing the number of competing awards at the National Heart, Lung, and Blood Institute: projections of a model.

In the mid 1980s, the National Heart, Lung, and Blood Institute (NHLBI) sought to extend the benefits of longer award terms to the research community by supporting requests for longer award terms that were scientifically justified. Although investigators welcomed the resultant increase in support stability, concerns were raised about the institute's ability to fund competing awards. A model was developed to assess alternative policies that might result in increased numbers of competing awards. Assuming that the NHLBI receives budget increases sufficient only to keep pace with inflation, the transitory effects of moving to the current policy of longer award terms should largely have passed by 1993. In the long term, the annual number of competing awards will exceed the average number funded between 1980 and 1983. To increase the annual number of competing awards over the long term would require either a reduction in the current percentage of five-year awards or an increase in the total number of active grants. A reduction in the current percentage of five-year awards would subject productive scientists to greater instability in their research support (that is, they would have to apply more frequently for grants) and would introduce greater variability in the number of competing awards available each year. A substantial increase in the total number of active NHLBI awards would be necessary to return the institute's competing awards to the levels of 1984 to 1988.

The vanishing lag from precept to practice.

Advances in biomedical research are being translated into clinical practice at a rate that is unprecedented, and yet there is reason to believe that the pace is accelerating. Current research directions offer great promise for improved methods of disease prevention and treatment. It is an especially satisfying time for young investigators who are just embarking on a career in research. They will experience both the gratification of discovery and the satisfaction of seeing their work contribute to improved public health.

Implants, transplants, and other parts of the medicine of the future.

Today, therapies that rely on adding something "more than natural" to the patient are a commonplace of medical practice. Although we may view such therapies as recent developments of biomedical science and engineering, they are actually the culmination of efforts to replicate, replace, and enhance parts of the human anatomy that date from the early days of recorded history. A review of some of those early efforts is an instructive way to begin. It helps us to appreciate that current developments at the forefront of biomedical science and engineering will soon transform the implants and transplants of today into the relatively primitive implants and transplants of the past. A discussion of the present state of implants and transplants follows. It is necessary to allow us to appreciate the great potential offered by current biomedical science and engineering for future developments in the therapies of the "more than natural." And then, finally, we can offer a present view of the implants, transplants, and other parts of the medicine of the future.

Research programs of the National Heart, Lung, and Blood Institute. Bethesda, Maryland, U.S.A.

While the NHLBI is authorized and funded by the United States government, the Institute recognizes that advances in the science related to the prevention, diagnosis, and treatment of cardiovascular, lung, and blood diseases and to the management and development of blood resources can be achieved most effectively through active participation in the international research enterprise. Through its policy of encouraging rapid publication and dissemination of the results of the research it sponsors and conducts, the Institute manifests its commitment to insuring that the associated public health benefits are shared as widely as possible. In addition to numerous informal contacts and exchanges of information the NHLBI actively pursues and participates in an extensive international network of collaborative arrangements. The Institute has established formal cooperative programs with 15 nations that span 5 continents, and participates in cooperative activities with another six. The benefits of such efforts are clear to the NHLBI and we hope to its partners as well. It is not just that international cooperation enables us to identify those aspects of the development of cardiovascular, lung, and blood diseases that are influenced by diet and culture and those that are not. Through continued international cooperation duplicative efforts can be avoided thereby effectively expanding the resources available to support the research that will reduce the international burden imposed by diseases of the heart, blood vessels, lung, and blood.

Dietary fiber intakes of nursing home residents and independent-living older adults.

Daily dietary fiber intakes were determined for two groups of older adults with significantly different bowel habits: nursing-home (NH) residents who habitually took laxatives and independent-living (IL) adults who took laxatives occasionally. Fiber intakes were calculated from neutral detergent fiber (NDF) and Southgate total dietary fiber values. IL subjects (n = 7) consumed on average 9.0 +/- 1.6 g NDF and 18.8 +/- 4.6 g total fiber daily. The NH menu provided a similar amount of NDF but more total fiber. NH residents (n = 6) consumed approximately 70-85% of the fiber served. When fiber intakes were expressed as energy, NH and IL subjects consumed similar amounts of NDF but IL subjects consumed less total fiber. Grain products were major fiber sources for both groups; IL subjects consumed more fiber from fruits. Comparisons of fiber intakes, bowel function, lifestyles, and medications suggest that dietary fiber is only part of the basis for inadequate large bowel function experienced by some elderly populations.