Biological terrorism: understanding the threat, preparation, and medical response.

The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all. Political factors--and possibly biotechnology--have changed that. As we enter the new millennium, national, state, and local governments in the United States are preparing for what is now called "not if, but when" biological terrorism. In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health-care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of disease, no matter what the cause of the disease.

New technologies in medicine: biotechnology and nanotechnology.

In February 1997, researchers created Dolly, a lamb cloned from the DNA of an adult sheep. This was supposed to be impossible (or at least generations away), but suddenly it was here--a clone of a higher mammal. Whatever Dolly's ultimate significance, she conclusively demonstrated the growing power of biotechnology. Many have come to the conclusion that advances in biotechnology will fundamentally transform medicine during the coming decade. Society is in the midst of a technical revolution that will have the same relevance as the development of the printing press, the internal combustion engine, and the microprocessor. Computers have become the key tools in the accelerating progress that is occurring in the field of biotechnology. At the same time, genetic, evolutionary, and other biologic processes are providing new models for the development of computer hardware and software. Today represents the early stages of what has been called the "bionic convergence": the convergence of the biologic revolution with the information revolution, the joining of biology with electronics. Virtually everything that is important to health care practitioners and patients--diagnostic techniques, means of understanding disease causes, methods of treatment, approaches to prevention, health care facility design, medical education, and legal and ethical issues--will be changed by the revolutions currently underway in the fields of biotechnology and genetic medicine. The following monograph includes several forecasts about a range of possible opportunities that may have enormous effects on health care during the next century. These forecasts address the potential impacts of biotechnology on disease detection and diagnosis, treatment, prevention, nanotechnology, and other areas of medical significance. Every area of beneficiary care will be affected as the changes implied by these forecasts begin to develop. Beneficiary care will continue to see the emergence of a "forecast, prevent, and manage" paradigm. The emphasis will be on disease prevention, health promotion, and the creation of healthy communities. New diagnostic and treatment opportunities will be available as a consequence of breakthroughs in genetic medicine. The health care system will view health as a whole, as a person's overall sense of well-being--an entity that encompasses much more than the absence of symptoms.

Telemedicine: a new dimension in the practice of medicine.

Telemedicine has drawn increasing attention as one of the emerging service delivery vehicles running on the information highway. Until recently, the adoption of telemedicine has been discouraged by the cost of telecommunications and equipment and by the lack of infrastructure, standards, and evidence of cost-effectiveness and cultural acceptance. Although there have been attempts to reduce costs by making use of computer communication networks, they were technically limited by slow network speed and the lack of real-time audio/video compression technology. Ongoing technologic advances in telecommunications, imaging, multimedia computers, and information systems are making interactive telemedicine increasingly possible as high-speed video, voice, and data services are brought to large segments of the general population. The current synergy between health reform initiatives, which are redefining how health care services are accessed and delivered, and advances in technologies that support telemedicine has resulted in a proliferation of telemedicine projects. However, there is still no proof that telemedicine is necessarily cost-effective for a broad set of applications. Each prospective application requires its own business case analysis. Within the current environment, the development of a telemedicine strategy should be based on a sound knowledge of the current and future potential of telemedicine to improve health care access and quality while containing and possibly reducing health care costs.

Operation Joint Endeavor in Bosnia: telemedicine systems and case reports.

OBJECTIVE: For the last several years the U.S. Department of Defense (DoD) has operated a telemedicine test bed at the U.S. Army Medical Research and Material Command's Medical Advanced Technology Management Office. The goal of this test bed is to reengineer the military health service system from the most forward deployed forces to tertiary care teaching medical centers within the United States by exploiting emerging telemedicine technologies. METHODS: The test bed has conducted numerous proof-of-concept telemedicine demonstrations as part of military exercises and in support of real-world troop deployments. The most ambitious of those demonstrations is Primetime III, an ongoing effort to provide telemedicine and other advanced technology support to medical units supporting Operation Joint Endeavor in Bosnia. RESULTS: Several of the first instances of the clinical use of the Primetime III systems are presented as case reports in this paper. These reports demonstrate capabilities and limitations of telemedicine. CONCLUSION: The Primetime III system demonstrates the technical ability to provide current telecommunications capabilities to medical units stationed in the remote, austere, difficult-to-serve environment of Bosnia. Telemedicine capabilities cannot be used without adequate training, operations, and sustainment support. Video consultations have eliminated the need for some evacuations. The system has successfully augmented the clinical capability of physicians assigned to these medical units. Fullest clinical utilization of telemedicine technologies requires adjustment of conventional clinical practice patterns.

A quality assurance model of operative mortality in coronary artery surgery.

Quality assurance in coronary artery bypass grafting (CABG) surgery requires a comparison of operative mortality against an accepted standard of care. Raw mortality statistics are unacceptable in this context, and risk factor analysis is essential. However, this principle has not been adequately demonstrated in previous reports. Our goal in this study was to develop a risk model of accepted CABG mortality and illustrate its proper use in coronary artery surgery. The model was derived from a Bayesian analysis of 6,630 patients undergoing CABG in the Coronary Artery Surgery Study (CASS) registry. Age, sex, ventricular function, previous myocardial infarction, extent of coronary artery disease, unstable angina, and surgical priority were used by the model to sort patients into risk categories. From January 1984 through December 1987, 840 patients underwent isolated CABG at our hospital. With raw mortality data, the 3.9% (33/840) mortality of our patients was significantly different from the 2.3% (153/6,630) CASS mortality (p less than 0.001). When our patients were entered into the CASS model for risk stratification, however, our CABG mortality conformed to the CASS experience. These results illustrate the fallacy of using raw mortality statistics for interinstitutional comparisons. This type of risk model is a fundamental element of CABG quality assurance.

Asymptomatic left main coronary artery disease and silent myocardial ischemia.

Gathering data on the prognosis, detection, and natural history of asymptomatic left main coronary artery disease with silent myocardial ischemia is difficult. Epidemiologic studies of unexpected death and postmortem studies on silent myocardial infarction suggest this entity to be common. We reviewed 89 consecutive patients with left main coronary artery disease (LMD), defined as 50% or greater reduction of luminal diameter. Of this group, 10 patients (11%) were asymptomatic (ALMD) and 79 patients (88%) were symptomatic (SLMD). All 10 ALMD patients were men, with a mean age of 53 years (range 40 to 65). Treadmill tests (TMT) were performed for: ECG abnormalities six; pre-jogging evaluation two; risk factor evaluation two. The TMT within 9 minutes showed 2 mm or greater ST depression in seven (70%) and 1 to 2 mm in three (30%). Similar TMT results were obtained in the SLMD group, although two patients had negative responses. The degree of stenosis of the left main coronary artery and the frequency of three-vessel disease were similar in both groups. The ejection fraction (EF) and contractile pattern of the left ventricle (LV) were normal in all 10 ALMD patients, but the left ventricular end-diastolic pressure (LVEDP) was abnormal in three (70%). In the SLMD group, 51 (64%) had an abnormal ejection fraction, 50 (65%) had wall motion abnormalities, and 25 (32%) had an abnormal LVEDP.

Medical success in El Salvador.

American medicine is respected worldwide, and our ability to respond with aid is beyond that of any nation. While we cannot administer aid indiscriminately, our ability to provide swift, effective humanitarian aid is one way in which we can demonstrate that we are truly relevant in the Third World. Recent United States experience in El Salvador proves this point. In 1983, when the Army was sending the first medical mobile training team to El Salvador, the mortality rate of wounded Salvadorian soldiers was 45%. As a result of U.S. military medical assistance, over the past four years the mortality rate of the wounded decreased to 5%. Activities of the Army Medical Department in El Salvador are an excellent example of efficient use of military medicine in low intensity conflict.

Use of a Bayesian statistical model for risk assessment in coronary artery surgery.

A computerized statistical model based on the theorem of Bayes was developed to predict mortality after coronary artery bypass grafting. From January, 1984, to April, 1987, at our hospital, 700 patients underwent isolated coronary artery bypass grafting. The presence or absence of 20 risk factors was determined for each patient. The first 300 patients formed the initial database of the Bayesian predictive model, and the remaining 400 patients were prospectively evaluated in four groups of 100 each. Each group was prospectively evaluated and then incorporated into the database to update the model. There was good agreement between predicted and observed results. Bayesian theory is particularly suited to this task because it (1) accommodates multiple risk factors, (2) is tailored to one's specific practice, (3) determines individual, rather than group, prognosis, and (4) can be updated with time to compensate for a changing patient population. These flexible attributes are especially valuable in light of recent changes in the coronary artery bypass graft patient profile.

A comparison of patients with endoscopic esophageal perforations and patients with Boerhaave's syndrome.

A review was conducted to ascertain whether patients who suffered spontaneous postemetic esophageal rupture (Boerhaave's syndrome) experienced higher morbidity and mortality than patients who had endoscopic iatrogenic esophageal perforations. Review of the records of three medical centers from 1960 to 1985 identified 11 patients with Boerhaave's syndrome (group B) and 19 with iatrogenic perforations (group E). In group B, four patients were diagnosed greater than 24 h after perforation. Nine were treated surgically; of these one died. Two group B patients who were treated conservatively survived. In group E, only four patients were diagnosed greater than 24 h after perforation. Of 19 patients, 15 were treated surgically and four, medically. In group E, three patients died (one surgically and two conservatively treated). This study suggests that there is little difference in mortality between the two groups of patients as long as the diagnosis is made early and therapy is instituted promptly.

Serum creatine kinase and lactate dehydrogenase isoenzyme levels in patients after major esophageal surgery, esophageal dilation, and acute myocardial infarction.

All three isoenzymes of creatine kinase (CK), including MB, the fraction used in diagnosing acute myocardial infarction (AMI), have been found in the esophagus. Clinical reports suggest that injuries to the esophagus can cause changes in peripheral serum CK. This prospective study was designed to delineate whether esophageal dilation or major esophageal surgery would cause changes in serum CK and lactate dehydrogenase isoenzymes that might be consistent with the diagnosis of an AMI. Two groups of patients admitted to a coronary care unit were used as controls: patients with electrocardiographically proved AMI and those who had chest pain but who had AMI ruled out by sequential electrocardiograms. The coronary care unit patients had serum enzymes determined on admission, then every 8 hours for four samples, and then daily for 3 days. The surgical patients had determinations preoperatively, in recovery, every 8 hours for four samples, and daily for 5 days. The patients who had esophageal dilations had serum enzyme levels drawn before the procedure and every 8 hours for 2 days after dilation. Serum total CK and lactate dehydrogenase levels were determined by automated spectrophotometry. Isoenzyme levels were determined by agarose gel electrophoresis. The data suggest that small serum CK-MB bands that may be generated by esophageal surgery or dilation can be differentiated from those seen in AMI and that AMI can be confirmed by simultaneous analysis of serum lactate dehydrogenase isoenzymes.

Prevention of ventricular fibrillation after myocardial revascularization.

Ventricular fibrillation during reperfusion after aortic cross-clamping for coronary artery bypass grafting may cause subendocardial injury. We investigated the use of lidocaine to prevent ventricular fibrillation during this period. In a blind, prospective, randomized trial, 91 consecutive patients undergoing elective coronary artery bypass graft procedures were given lidocaine (2 mg/kg) or normal saline immediately before removal of the aortic cross-clamp. The groups were similar with respect to demographic, clinical, and intraoperative variables. Myocardial preservation techniques were similar in both groups. Of 47 patients receiving lidocaine, 38 recovered a supraventricular rhythm without ventricular fibrillation, compared with only 5 of 44 patients in the control group (p less than .001). When ventricular fibrillation occurred, patients in the control group required a greater number of direct-current countershocks (2.31 versus 1.86) to convert to sinus rhythm. Transient heart block, requiring temporary pacing, developed in 3 patients in the lidocaine group, compared with 1 patient in the control group. There was no significant difference between the groups in the requirement for perioperative inotropic support (6 of 47 versus 6 of 44) or the number of myocardial infarctions (2 of 47 versus 1 of 44), and there were no deaths in either group. Lidocaine infusion immediately before removal of the aortic cross-clamp significantly reduces the incidence of ventricular fibrillation during the reperfusion period after cardiopulmonary bypass.

Changes in serum creatine kinase and lactate dehydrogenase caused by acute perioperative myocardial infarction and by transatrial cardiac surgical procedures.

A prospective clinical study was conducted to ascertain if a patient's postoperative elevation in serum creatine kinase MB isoenzyme coupled with determination of the lactate dehydrogenase1/lactate dehydrogenase2 ratio could differentiate whether atrial or ventricular myocardium was the source of these changes. Animal studies have shown that atrial myocardium is as rich a source of creatine kinase MB as is ventricular myocardium. Atrial myocardium has a lactate dehydrogenase1/lactate dehydrogenase2 ratio less than 1.00, whereas in ventricular myocardium the ratio is greater than 1.00. Sixty-four patients were assigned to six groups on the basis of serial electrocardiograms and vectorcardiograms by a cardiologist who was unaware of their clinical courses. The control group (Group 1) consisted of 16 patients admitted to the coronary care unit who had no electrocardiographic changes. Three surgical groups without electrocardiographic or vectorcardiographic evidence of perioperative myocardial infarction were studied: 10 patients undergoing routine coronary artery bypass procedures (Group 2), six adults undergoing repair of secundum atrial septal defect (Group 3), and 13 patients having mitral valve replacement (Group 4). Two groups of surgical patients who had acute perioperative transmural myocardial infarctions confirmed by serial electrocardiograms and vectorcardiograms were studied: 15 patients (Group 5) who had elective coronary artery bypass procedures and four (Group 6) who had mitral valve replacement. This study suggests that serum creatine kinase MB levels in excess of 50 IU/L on the postoperative day 1 and day 2 samples coupled with serum lactate dehydrogenase1/lactate dehydrogenase2 ratios greater than 1.00 on the postoperative day 2 and day 3 samples support the diagnosis of acute myocardial infarction. Patient groups undergoing procedures necessitating atriotomies had average elevations in serum creatine kinase MB and in the lactate dehydrogenase1/lactate dehydrogenase2 ratio, but these were significantly less than those seen when acute perioperative myocardial infarction had occurred.

The use of computed tomography in the evaluation of mediastinal masses.

A retrospective analysis was conducted to ascertain whether computed tomography had increased diagnostic accuracy while decreasing the number of tests needed in the preoperative assessment of patients with mediastinal masses. A total of 42 patients were entered into the study: Fifteen patients were evaluated before the advent of computed tomography (No CT) and 27 patients had computed tomography during their evaluation (CT). The No CT group comprised 10 male and five female patients (2:1 ratio); the age range was 8 months to 61 years. The CT group included 15 male and 12 female patients (1.25:1.0 ratio), the age range being 21 to 70 years. In each group, both invasive and noninvasive studies were done. Although the CT group had 40 noninvasive tests, 27 were computed tomographic scans. The additional 13 noninvasive tests and the five invasive tests added no significant diagnostic information. In the No CT group, preoperative evaluation as to the cystic or solid nature of the mass was correct only four of 13 times (31%). In the CT group, 22 of 25 patients had accurate assessment as to the cystic or solid nature of the lesions (88%). In addition, extension of the mass into other structures, consistent with malignancy, was correctly diagnosed preoperatively in nine of the patients in the CT group. Two had extension of the mass at operation not preoperatively diagnosed (82% accuracy). None of the No CT group was given an assessment of possible mass extension preoperatively. The results suggest that mediastinal masses can be evaluated by computed tomography with a high degree of accuracy for predicting the nature, size, location, and involvement of other organs by the mass. The use of other tests before resection generally yields little additional information.

Evaluation of serum creatine kinase and lactate dehydrogenase in experimental myocardial infarction, atriotomies, and thoracotomies.

Myocardial infarction causes elevation of the serum myocardial-associated isoenzyme of creatine kinase (CK-MB) and a serum isoenzyme of lactate dehydrogenase (LDH1). Since atrial myocardium has as much CK-MB as ventricular myocardium, surgical manipulation of the atrium could cause elevation of serum CK-MB in the postoperative period. The distribution of LDH isoenzymes is different between atrial and ventricular myocardium. Hence, surgical procedures on the atrium could, theoretically, cause different changes in serum LDH isoenzymes than those seen after acute myocardial infarction. This study was conducted to ascertain whether surgical manipulation of the atrium could cause changes in these two serum enzyme systems that might be confused with those seen after acute myocardial infarction. Right thoracotomies were performed on 20 dogs. Each dog then was assigned randomly to one of four groups: thoracotomy (control), placement of atrial pursestring sutures, atriotomy, or acute perioperative myocardial infarction. Serum total and isoenzyme distributions of CK and LDH were measured for 48 hours in all animals. The results suggest that significant elevations of serum CK-MB occurred even after small atriotomies. Confirmation of a ventricular myocardial origin of postoperative serum CK-MB bands was obtained by analysis of serum LDH isoenzymes in that the ratio of LDH1 to LDH2 and the absolute value of serum LDH1 became elevated only after acute perioperative myocardial infarction and not after atriotomy.

Rib fracture healing in experimental flail chest.

Sixteen dogs were placed under general anesthesia and flail segments of the left chest were created by transecting ribs 7,8,9, and 10 anteriorly and posteriorly. Fractures were 10 cm apart so that a 10-cm flail segment encompassing four ribs was created. In Group I, the control (N = 5), the chest wall muscles were closed without any stabilization of the fractures. Group II (N = 5) had stabilization of both anterior and posterior fracture sites by polypropylene sutures. Group III (N = 6) had stabilization of the fractures in ribs 7 and 8 with 2.5-cm bone grafts taken from the left fourth rib. Ribs 9 and 10 were stabilized by polypropylene sutures. The study established a canine model for flail chest. It also showed that strut stabilization of rib fractures with bone grafts promotes better healing than suture stabilization. It suggests that using bone grafts taken from another rib to stabilize flail segments may be unsatisfactory since the rib used as a donor showed no signs of regeneration at 30 days.