Diagnose chest pain for less with early risk stratification and SPECT imaging protocol.

Why waste time in the diagnosis of chest pain? A diagnostic strategy of SPECT imaging and exercise tolerance testing halves the medical resources required to rule out heart attacks, a small-scale study shows. A key to success is having a clear-cut system for identifying lower-risk patients, the study's lead author says.

An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial.

STUDY OBJECTIVE: Conventional emergency department testing strategies for patients with chest pain often do not provide unequivocal diagnosis of acute coronary syndromes. This study was conducted to determine whether the routine use of single photon emission computed tomography (SPECT) imaging at rest and early exercise stress testing to assess intermediate-risk patients with chest pain and no ECG evidence of acute ischemia will lead to earlier discharges, more discriminate use of coronary angiography, and an overall reduction in average costs of care with no adverse clinical outcomes. METHODS: All patients in this study had technetium 99m tetrofosmin SPECT imaging at rest and were randomly assigned to either a conventional (results of the imaging test blinded to the physician) or perfusion imaging-guided (results of the imaging test unblinded to the physician) strategy. Patients in the conventional arm were treated at their physician's discretion. Patients in the perfusion imaging-guided arm were treated according to a predefined protocol based on SPECT imaging test results: coronary angiography after a positive scan result and exercise treadmill testing after a negative scan result. Study endpoints consisted of total in-hospital costs and length of stay. Hospital costs were calculated using hospital department-specific Medicare cost/charge ratios. Length of stay was calculated as total hospital room days billed (regular and intensive care). RESULTS: We enrolled 46 patients, 9 with acute myocardial infarctions. Patients randomly assigned to the perfusion imaging-guided arm had $1,843 (95% confidence interval [CI] $431 to $6,171) lower median in-hospital costs and 2.0-day (95% CI 1.0 to 3.0 days) shorter median lengths of stay but similar rates of in-hospital and 30-day follow up events as patients in the conventional arm. CONCLUSION: An ED chest pain diagnostic strategy incorporating acute resting (99m)Tc tetrofosmin SPECT imaging and early exercise stress testing may lead to reduced in-hospital costs and decreased length of stay for patients with acute chest pain and nondiagnostic ECGs.

Entoptic foveal avascular zone measurement and diabetic retinopathy.

BACKGROUND: Entoptic visualization of the foveal avascular zone (FAZ) provides a noninvasive method for measurement of the FAZ. To determine if repeatability of measurement with this technique is good enough to monitor changes in diabetic retinopathy, we quantify (1) the repeatability of entoptic FAZ measurement in healthy subjects and (2) the relationship between measured FAZ diameter and the severity of retinopathy. METHODS: (1) To determine FAZ measurement repeatability, 10 healthy adults entoptically measured their FAZ diameters in 11 separate testing sessions. (2) In a separate experiment, 53 patients with varying levels of diabetic retinopathy and 21 control subjects used a vascular entoptoscope to measure their FAZ diameters. RESULTS: The disease-related increase in FAZ diameter is large (approximately 400 microm) compared to the repeatability of the entoptic measurement within a subject (SD approximately 35 microm). CONCLUSION: Entoptic measurements have the repeatability necessary to reliably monitor increases in FAZ diameter of the magnitude of those induced by diabetes.

Clinical value of acute rest technetium-99m tetrofosmin tomographic myocardial perfusion imaging in patients with acute chest pain and nondiagnostic electrocardiograms.

OBJECTIVES: We sought to evaluate the clinical use and cost-analysis of acute rest technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomographic (SPECT) myocardial perfusion imaging in patients with chest pain and a normal electrocardiogram (ECG). BACKGROUND: Current approaches used in emergency departments (EDs) for treating patients presenting with chest pain and a nondiagnostic ECG result in poor resource utilization. METHODS: Three hundred fifty-seven patients presenting to six centers with symptoms suggestive of myocardial ischemia and a nondiagnostic ECG underwent Tc-99m tetrofosmin SPECT during or within 6 h of symptoms. Follow-up evaluation was performed during the hospital period and 30 days after discharge. All entry ECGs, SPECT images and cardiac events were reviewed in blinded manner and were not available to the admitting physicians. RESULTS: By consensus interpretation, 204 images (57%) were normal, and 153 were abnormal (43%). Of 20 patients (6%) with an acute myocardial infarction (MI) during the hospital period, 18 had abnormal images (sensitivity 90%), whereas only 2 had normal images (negative predictive value 99%). Multiple logistic regression analysis demonstrated abnormal SPECT imaging to be the best predictor of MI and significantly better than clinical data. Using a normal SPECT image as a criterion not to admit patients would result in a 57% reduction in hospital admissions, with a mean cost savings per patient of $4,258. CONCLUSIONS: Abnormal rest Tc-99m tetrofosmin SPECT imaging accurately predicts acute MI in patients with symptoms and a nondiagnostic ECG, whereas a normal study is associated with a very low cardiac event rate. The use of acute rest SPECT imaging in the ED can substantially and safely reduce the number of unnecessary hospital admissions.

Potential cost effectiveness of initial myocardial perfusion imaging for assessment of emergency department patients with chest pain.

Previous investigations have confirmed the diagnostic and predictive usefulness of initial single-photon emission computed tomography (SPECT) myocardial perfusion imaging using technetium-99m sestamibi in the evaluation of emergency department patients with chest pain. Patients with a normal SPECT perfusion scan performed during chest pain have an excellent short-term prognosis, and may be candidates for expeditious cardiac evaluation or outpatient management. However, there are limited data regarding the cost effectiveness of this technique. This analysis models the potential cost effectiveness of this procedure. In the current investigation we compared 2 model strategies for management of emergency department patients with typical chest pain and a normal or nondiagnostic electrocardiogram (ECG). In 1 model strategy, (the technetium-99m sestamibi SPECT myocardial perfusion imaging [SCAN] strategy), the decision whether to admit or discharge a patient from the emergency department is based on results of initial technetium-99m sestamibi SPECT myocardial imaging. Patients with normal scans are discharged; others are admitted. In the second model strategy, (the NO SCAN strategy), the decision whether or not to admit a patient is based on a combination of clinical and electrocardiographic variables. Patients with > or = 3 cardiac risk factors or an abnormal ECG are admitted; others are discharged. Adverse cardiac events were prospectively defined as cardiac death, nonfatal myocardial infarction, or the need for acute coronary intervention. Costs were assigned using data derived from 102 patients who underwent SPECT myocardial perfusion imaging and an additional 107 emergency department patients with ongoing chest pain who either underwent or were eligible for initial SPECT myocardial perfusion imaging. Mean (+/- SE) costs were highest among hospital admitted patients who experienced an adverse cardiac event ($21,375 +/- $2,733) and lowest in patients discharged from the emergency department ($715 +/- 71). Mean costs per patient of the SCAN strategy and NO SCAN strategy were $5,019 versus $6,051, respectively. These results were stable in a sensitivity analysis across a range of costs and predictive values. Thus, the SCAN model strategy for initial management of emergency department patients with typical ongoing angina and a normal or nondiagnostic ECG using initial myocardial perfusion imaging with technetium-99m sestamibi appears to be safe, accurate, and potentially cost effective. Validation of these preliminary retrospective observations will require further prospective investigation.

The early diagnosis and treatment of non-ST-segment elevation acute ischemic syndromes: the need for a new approach.

The diagnosis and treatment of ST-segment elevation myocardial infarction (MI) has been well defined by many multicenter trials. However, the treatment and diagnosis of non-ST-segment elevation MI is much less understood. Single photon emission computerized tomographic perfusion imaging shows great promise in risk-stratifying patients into low-risk and high-risk subsets when 12-lead ECG and initial cardiac enzymes are normal or nondiagnostic. Early exercise stress testing may be important in further risk-stratifying patients whose chest pain has resolved or who have low risk perfusion scans in the emergency department. The role of two-dimensional echocardiography in non-ST-segment elevation MI is currently under investigation.

Ninety-day follow-up of patients in the emergency department with chest pain who undergo initial single-photon emission computed tomographic perfusion scintigraphy with technetium 99m-labeled sestamibi.

BACKGROUND: Patients in the emergency department with typical chest pain and a normal or nondiagnostic electrocardiogram have a 10% to 20% risk of nonfatal myocardial infarction. These patients can be stratified into groups of very low and very high risk for inpatient adverse cardiac events on the basis of initial 99mTc-labeled sestamibi single-photon emission computed tomographic (SPECT) perfusion imaging performed during symptoms. However, the intermediate or posthospital discharge prognosis of such patients has not been reported. METHODS AND RESULTS: Patients (n = 150) with typical chest pain (based on a semiquantitative chest pain questionnaire) and a normal or nondiagnostic electrocardiogram underwent injection of 15 to 45 mCi 99mTc-labeled sestamibi injected during symptoms. Ninety-day follow-up history (telephone questionnaire and review of medical records) was obtained in 140 patients, and follow-up electrocardiography was performed in 72 patients. Cardiac events (death, nonfatal myocardial infarction, thrombolysis, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting) occurred before hospital discharge in 33 patients (18%), and these patients were excluded from further analysis. At follow-up, two (8%) of 25 patients with an abnormal initial scintigram and none of 87 patients with a normal scan had cardiac events (p = 0.008). CONCLUSIONS: In patients with typical angina and a normal or nondiagnostic electrocardiogram, initial SPECT scintigraphy allows early accurate risk stratification. The previously observed excellent inpatient prognosis of patients with a normal scintigram appears to extend for at least 90 days of follow-up. These observations may provide a rational basis for safe and cost-effective outpatient evaluation of selected patients in the emergency department with typical angina, a normal or nondiagnostic electrocardiogram, and a normal initial 99mTc-labeled SPECT perfusion scintigram performed during symptoms.

Technetium-99m sestamibi myocardial perfusion imaging in the emergency room evaluation of chest pain.

OBJECTIVES: The purpose of this investigation was to evaluate the practicality and short-term predictive value of acute myocardial perfusion imaging with technetium-99m sestamibi in emergency room patients with typical angina and a normal or nondiagnostic electrocardiogram (ECG). BACKGROUND: Accuracy of emergency room chest pain assessment may be improved when clinical and ECG variables are used in conjunction with acute thallium-201 myocardial perfusion imaging. Technetium-99m sestamibi is a new radioisotope that is taken up by the myocardium in proportion to blood flow, but unlike thallium-201, it redistributes minimally after injection. Technetium-99m sestamibi can thus be injected during chest pain, and images acquired 1 to 2 h later (when patients have been clinically stabilized) will confirm whether abnormalities of perfusion were present at the time of injection. METHODS: One hundred two emergency room patients with typical angina (on the basis of a standardized angina questionnaire) and a normal or nondiagnostic ECG had a technetium-99m sestamibi injection during symptoms and were followed up for occurrence of adverse cardiac events (cardiac death, nonfatal myocardial infarction, coronary angioplasty, coronary surgery or coronary thrombolysis). RESULTS: Univariate predictors of cardiac events included the presence of three or more coronary risk factors (p = 0.009, risk ratio 3.3) and an abnormal or equivocal acute technetium-99m sestamibi scan (p = 0.0001, risk ratio 13.9). Multivariate regression analysis identified an abnormal perfusion image as the only independent predictor of adverse cardiac events (p = 0.009). Of 70 patients with a normal perfusion scan, only 1 had a cardiac event compared with 15 patients with equivocal scans or 17 patients with abnormal scans, with a cardiac event rate of 13% and 71%, respectively (p = 0.0004). CONCLUSIONS: Initial myocardial perfusion imaging with technetium-99m sestamibi when applied in emergency room patients with typical angina and a normal or nondiagnostic ECG appears to be highly accurate in distinguishing between low and high risk subjects.

Posterior subluxations of the medial and lateral tibiofemoral compartments. An in vitro ligament sectioning study in cadaveric knees.

We report for the first time the abnormal increases in posterior subluxation of the medial and lateral tibial plateaus after sectioning the posterolateral structures and posterior cruciate ligament. We applied specific forces and moments to the knees of seven cadaveric whole lower limbs and measured the position of the tibia at which the ligaments and the geometry of the joint limited motion. Removal of only the posterolateral structures resulted in an average increase in posterior translation of the lateral tibial plateau of 8.0 mm (range, 5.7 to 10.6) at 30 degrees of flexion over the intact state (P < 0.01), but no significant increase at 90 degrees of flexion (mean, 2.7 mm). Knees with underlying physiologic cruciate ligament laxity (high anterior/posterior displacement in the intact knee) had the greatest lateral tibial plateau subluxation (P < 0.01). There was no abnormal posterior translation of the medial tibial plateau. After sectioning the posterior cruciate ligament and the posterolateral structures, statistically significant increases in posterior translation of both the medial and lateral tibial plateaus occurred at 30 degrees and 90 degrees of flexion (P < 0.01). The increase in posterior translation of the lateral tibial plateau over the intact state averaged 17.8 and 23.5 mm at 30 degrees and 90 degrees of flexion, respectively; for the medial tibial plateau this increase averaged 7.6 and 12.3 mm at 30 degrees and 90 degrees of flexion, respectively. The diagnosis of abnormal tibiofemoral rotatory subluxations requires knowledge of the anteroposterior direction and magnitude of each tibial plateau under both low flexion and high flexion knee angle positions.

Development of a culturally appropriate food guide for pregnant Caribbean immigrants in the United States.

Communities with large Caribbean immigrant populations in Boston, Mass, have alarmingly high rates of both infant mortality and low-birth-weight infants. Although the federally funded Special Supplemental Food Program for Women, Infants, and Children (WIC) has been shown to increase infant birth weight and reduce fetal mortality, observations made in this study show that pregnant Caribbean immigrants who enrolled in WIC did not receive comprehensive, culturally appropriate nutrition counseling. Public health nutritionists and other health care providers used the Basic Four food group model as the basis for their dietary recommendations. The Basic Four model, however, is culturally biased and does not accommodate the food habits of the Caribbean immigrant. Furthermore, it does not adequately address the needs of pregnant women who are either lactose malabsorbers or vegetarians. Using ethnographic and nutrition science research methods, two culturally appropriate food guides were developed to accommodate the food practices of pregnant women from Haiti and the English-speaking Caribbean. The guides group foods into three categories: growth, protection, and energy. The guides not only include cultural foods but allow for the Recommended Dietary Allowance (RDA) for calcium to be met by nondairy sources and the RDA for protein to be met by vegetable sources. This study suggests that the Basic Four system is an inadequate model for Caribbean immigrants and that it is possible and necessary to construct culturally appropriate food guides that meet the US RDAs.

Development of a culturally appropriate food guide for pregnant Caribbean immigrants in the United States

Communities with large Caribbean immigrant populations in Boston, Mass, have alarmingly high rates of both infant mortality and low-birth-weight infants. Although the federally funded Special Supplemental Food Program for Women, Infants, and Children (WIC) has been shown to increase infant birth weight and reduce fetal mortality, observations made in this study show that pregnant Caribbean immigrants who enrolled in WIC did not receive comprehensive, culturally appropriate nutrition counseling. Public health model as the basis for their dietary recommendations. The Basic Four model, however, is culturally biased and does not accomodate the food habits of the Caribbean immigrant. Furthermore, it does not adequately address the needs of pregnant women who are either lactose malabsorbers or vegetarians. Using ethnographic and nutrition science research methods, two culturally appropriate food guides were developed to accomodate the food practices of pregnant women from Haiti and the English-speaking Caribbean. The guides group food into three categories: growth, protection, and energy. The guides not only include cultural foods but allow for the Recommended Dietary Allowance (RDA) for calcium to be met by nondairy sources and the RDA for protein to be met by vegetable sources. This study suggests that the Basic Four system is an inadequate model for Caribbean immigrants and that it is possible and necessary to construct culturally appropriate food guides that meet the US RDAs. (AU)

Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis.

The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

Detection of activated proto-oncogenes in N-nitrosodiethylamine-induced liver tumors: a comparison between B6C3F1 mice and Fischer 344 rats.

DNA from B6C3F1 mouse and Fischer 344 rat liver tumors induced by N-nitrosodiethylamine (DEN) were examined for the ability to induce morphological transformation of NIH3T3 cells. DNAs from 14 of 33 of the mouse liver tumors induced by a single injection of DEN at 12 or 15 days of age were positive in this assay while DNA from only one of 28 DEN-induced rat liver tumors was active. Southern blot analysis of the NIH3T3 transformants derived from the mouse liver tumors revealed amplified and/or rearranged restriction fragments homologous to the H-ras proto-oncogene. DNA from two independent foci induced by the rat tumor DNA did not hybridize to probes for members of the ras gene family or c-raf. Activating mutations in the H-ras genes from the DEN-induced mouse liver tumors were characterized by selective oligonucleotide hybridization and the detection of a new XbaI restriction site by Southern blot analysis. In activated H-ras genes from the DEN-induced mouse liver tumor DNA, seven of 14 had a CG----AT transversion at the first base of the 61st codon, three of 14 had an AT----GC transition and four of 14 had the AT----TA transversion at the second base of codon 61. This spectrum of mutations is very similar to that recently observed in activated H-ras genes found in spontaneously occurring B6C3F1 mouse liver tumors. Taken together, the data suggest that the DEN-induced rat and mouse liver carcinogenesis may involve genetic targets other than or in addition to the H-ras gene.