Diagnostic accuracy of serum B-type natriuretic peptide for myocardial ischemia detection during exercise testing with spect perfusion imaging.

OBJECTIVE: To determine whether serum B-type natriuretic peptide measured at rest and peak exercise and DeltaBNP contribute to the predictive value and diagnostic accuracy of exercise test in the diagnosis of myocardial ischemia. BACKGROUND: Ventricular myocytes release BNP in response to increased wall stress that occurs in acute ischemia. During exercise testing, transient myocardial ischemia could also cause acute myocardial stress and changes in circulating BNP. METHODS: BNP was measured before and immediately after exercise testing with radionuclide imaging in 203 consecutive subjects referred for chest pain evaluation. Tested subjects were classified as ischemic and non-ischemic based on exercise results, and no ischemia, mild-moderate, and severe ischemia according to perfusion scan results. A logistic regression model, constructed of an ROC and an AUC (area under the curve), was used. RESULTS: Ischemic ECG changes (> or =1 mm, horizontal S-T shift) were detected in the treadmill exercise test in 127 subjects (62.6%), and 76 (37.4%) had neither ST segment shift nor chest pain. Baseline BNP was higher in the ischemic group compared to the non-ischemic group (p=0.044); peak BNP was also higher in the ischemic group (p=0.025), as was DeltaBNP (p=0.0126). Of these 127 subjects, 106 (52% of all) had abnormal perfusion scan results. In the ischemic group, the median baseline, peak exercise BNP, and DeltaBNP values from baseline to peak were higher than in the non-ischemic group. In the severe ischemic group these variables were approximately three-fold higher than in the mild-moderate ischemic group (p<0.0001 for baseline; p<0.0001 for peak; and p<0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were significantly higher in patients with previous myocardial infarction (p<0.001) and in patients treated with beta blockers; peak exercise BNP was higher in hypertensives and diabetics (p<0.05). The ROC convergence model showed that the AUC for peak-exercise BNP was best able to discriminate and predict severe ischemia and no ischemia, while DeltaBNP from rest to peak exercise discriminated best between mild-moderate and severe ischemia. CONCLUSIONS: Peak exercise BNP and DeltaBNP improved the sensitivity, specificity, positive likelihood ratio, predictive value, and diagnostic accuracy of severe ischemia detection during an exercise test. The contribution of BNP determination during exercise was, however, less impressive than previously reported by others.

Confidentiality in home and hospice nursing. Protecting vulnerable populations.

Nurses are taught early in their educational experience the importance of keeping confidential information they have learned about the people for whom they provide care. This article describes a scenario where confidentiality is breached and how the intended "good works" actually resulted in unintended harm.

Project EFECT: a case study of collaboration and cooperation. Education for Effective Collaborative Training.

Many service professionals have little opportunity during their educational experience to collaborate directly with others outside of their discipline or to have real-life experiences in teamwork and cooperation. Project EFECT provided laboratory experiences in area schools for students from 4 different disciplines to practice working together while delivering much needed services to at-risk school children.

Cultural basics and chronic illness.

Cultural factors have significant impact on the clinical encounter between health care professionals and their patient-families. A good continuing relationship is essential for successful management of chronic disease. Misunderstandings predicated on implicit cultural assumptions are a frequent potential hazard. This review outlines some possible problems and concludes by making eight suggestions for culturally sensitive and medically effective communication.

Educational outcomes and specialized accreditation.

Does the accreditation of a nursing education program make a difference in the performance of its graduates? This question was explored by comparing the performance of all graduates (N = 4114) from all specialized accredited and nonaccredited community college nursing programs in Maryland on licensure examinations to assess the differences on this standardized outcome measure of nursing knowledge. From 1987 to 1992 (the most recent year for which data were available), the results show that the performance by graduates of accredited programs was not typically better than those from nonaccredited programs, and there was a suggestion in 1 year that the reverse may be true. The implications of these findings for assurance of quality in nursing education and further research in outcome assessments are discussed.

The ubiquitin-activating enzyme, E1, is required for stress-induced lysosomal degradation of cellular proteins.

ts85, a cell line that harbors a mutant thermolabile ubiquitin-activating enzyme, E1, fails to degrade short lived proteins at the restrictive temperature (Ciechanover, A., Finley, D., and Varshavsky, A. (1984) Cell 37, 57-66). However, the involvement of the ubiquitin system in the degradation of long lived proteins (most cellular proteins fall in this category) has not been addressed. In the present study we show that upon shifting the mutant cells to the restrictive temperature, there is no change in the rate of degradation of long lived proteins. In contrast, shifting the wild-type cells (FM3A) to the high temperature is accompanied by a 2-fold increase in the rate of proteolysis of this group of proteins. This heat-induced accelerated degradation can be inhibited completely by NH4Cl and chloroquine. Similarly, exposure of the cells to starvation, a stimulus that activates the autophagic-lysosomal pathway, has no effect on the degradation of long lived proteins in the mutant cells after inactivation of E1. Under the same conditions, the degradation rate in the wild-type cells increases almost 4-fold. Analogous results were obtained using a different cell line that also harbors a thermolabile E1 (ts20 (Kulka, R. G., Raboy, B., Schuster, R., Parag, H. A., Diamond, G., Ciechanover, A., and Marcus, M. (1988) J. Biol. Chem. 263, 15726-15731)). Cycloheximide and 3-methyladenine, known inhibitors of formation of autophagic vacuoles, inhibit the heat-induced accelerated degradation of long lived proteins in wild-type cells. Taken together, the results suggest that 1) heat stress induces enhanced degradation of intracellular proteins; 2) the process occurs most probably in autophagic vacuoles; and 3) activation of ubiquitin is required for the formation of these vacuoles. As there is no change in the basal rate of degradation of intracellular proteins in the mutant cells at the restrictive temperature, it appears that the ubiquitin system is not involved in their breakdown.

The ubiquitin-activating enzyme is required for lysosomal degradation of cellular proteins under stress.

ts85, a cell-line that harbors a mutant thermolabile ubiquitin-activating enzyme, E1, fails to degrade short-lived proteins at the restrictive temperature (Ciechanover, A., Finley, D., and Varshavsky, A. (1984) Cell 37, 57-66). It is not known whether the ubiquitin system is also involved in the degradation of long-lived proteins. In the present study we show that upon shifting the mutant cells to the restrictive temperature, there is no change in the rate of degradation of long-lived proteins. In contrast, shifting the wild-type cells (FM3A) to the high temperature is accompanied by a 2-fold increase in the rate of proteolysis of this group of proteins. This heat-induced accelerated degradation can be completely inhibited by NH4Cl and chloroquine. Similarly, exposure of the cells to starvation, a stimulus that activates the autophagic-lysosomal pathway, has no effect on the degradation of long-lived proteins in the mutant cells following inactivation of E1. Under the same conditions, the degradation rate in the wild-type cells increases almost 4-fold. A revertant of the ts85 cells behaved in a similar manner to the wild-type cells. Analogous results were obtained using a different cell line that also harbors a thermolabile E1 (ts20) (Kulka, R. G. et al. (1988) J. Biol. Chem. 263, 15726-15731). Cycloheximide and 3-methyladenine, inhibitors of formation of autophagic vacuoles, suppress the heat-induced accelerated degradation in the wild-type cells. Taken together, the results suggest that: 1. heat stress induces enhanced degradation of intracellular proteins, 2. the process occurs most probably in autophagic vacuoles, 3. activation of ubiquitin is required for enhanced degradation to occur, and 4. the activation is involved most probably in formation of the autophagic vacuoles.

Purification, characterization, and rapid inactivation of thermolabile ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85.

Conjugation of ubiquitin to certain proteins can trigger their degradation in the in vitro reticulocyte system. In order to determine whether ubiquitin conjugation serves as an intermediate step in the turnover of cellular proteins in vivo, it is necessary to isolate proteolytic intermediates, i.e. ubiquitin-protein adducts of specific cellular proteins. While the steady-state level of conjugates of rapidly turning over proteins is relatively high, that of long-lived proteins is presumably extremely low, and therefore undetectable. Therefore, mutant cell lines with conditionally altered function(s) of the ubiquitin system can serve as powerful tools in studying the degradation of stable cellular proteins. We have characterized a temperature sensitive cell cycle arrest mutant cell (ts85) with a thermolabile ubiquitin-activating enzyme (E1; Finley, D., Ciechanover, A., and Varshavsky, A. (1984) Cell 37, 43-55). Following incubation at the restrictive temperature (39.5 degrees C), these cells fail to degrade short-lived proteins (Ciechanover, A., Finley, D., and Varshavsky, A. (1984) Cell 37, 57-66). However, involvement of the ubiquitin system in the turnover of long-lived proteins has not been addressed in these cells. A slow rate of inactivation of E1 in vivo, and significant rate of cell death following long incubation periods at the restrictive temperature, make this question difficult to address experimentally. In the present study we show that incubation of the cells for 1 h at 43 degrees C leads to rapid inactivation of ubiquitin conjugation in the intact mutant cell. Following heat treatment, the cells can be incubated at 39.5 degrees C for at least 6 h in order to study the possible involvement of the system in the turnover of long-lived cellular proteins. The viability of the cells is excellent at the end of the incubation. Following extraction, we have shown that inactivation occurs much more rapidly in the cell lysate in vitro than in the intact cell (t1/2 of 10 min compared to 4 h at 39.5 degrees C). The enzyme from both the mutant cell and the wild-type cell was purified to homogeneity. The molecular mass of the native enzyme from both cells is approximately 220 kDa with a subunit molecular mass of about 108 kDa. The structure of the enzyme is therefore very similar to that purified from rabbit reticulocytes. At the permissive temperature, the enzymes from both cells catalyze ATP-PPi and ATP-AMP exchange in similar kinetics. However, at the high temperature, the mutated enzyme is at least 7-fold less stable than the wild-type enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)