Selective adsorption of human CD4 T cells

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.     

F-18 deoxyglucose and stress N-13 ammonia positron emission tomography in anterior wall healed myocardial infarction

To evaluate myocardial blood flow and glucose utilization, N-13 ammonia (NH3) and F-18 deoxyglucose positron emission tomography scanning was performed in 22 patients with previous anterior wall myocardial infarction, using a high-resolution, multi-slice, whole-body scanner. The N-13 ammonia study was performed at rest and after exercise. The F-18 deoxyglucose study was performed at rest after fasting greater than 5 hours. The N-13 ammonia study revealed a hypoperfused area in 19 of the 22 patients (86%), that corresponded to the infarcted regions as diagnosed by electrocardiography, coronary arteriography and left ventriculography (21 patients). The hypoperfused areas expanded after exercise in 16 of 22 patients (73%). F-18 deoxyglucose uptake was observed in these hypoperfused areas, especially in patients with hypokinetic wall motion on left ventriculography and in exercise-induced hypoperfused areas. However, positron emission tomography demonstrated diffuse uptake of F-18 deoxyglucose in 3 of 8 patients with dyskinetic wall motion. Thus, metabolically active myocardium in infarcted areas or periinfarct ischemia can be visualized with F-18 deoxyglucose and stress N-13 ammonia studies.     

Exponential increases in pulmonary intravascular and extravascular fluid volumes by overperfusion with dextran 70 in anesthetized dogs

In the lung overperfused by dextran 70, it is not known how intravascular blood volume and extravascular water volume increase as a function of pulmonary microvascular pressure. To determine their characteristics, we produced an overperfusion state (high pressure and high blood flow) by infusing dextran 70 (100 ml/kg over 30 min) into 15 anesthetized dogs. Using the thermal and dye dilution technique, we simultaneously estimated the pulmonary blood volume (PBV) and the extravascular lung thermal volume (EVLTV), and correlated mathematically these variables with pulmonary artery end-diastolic pressure (PAEDP). Here, we defined PAEDP as the pulmonary microvascular pressure. From the values determined before, during and after dextran 70 infusion, we obtained the following exponential relations. PBV(ml/kg) = 30[1-0.902(e-0.021PAEDP(mmHg)) EVLTV(ml/kg) = 5.15(e0.027PAEDP (mmHg)) From these mathematical relations, we conclude that: (1) the pulmonary blood volume increases rapidly at low pressure and slowly at high pressure; and (2) the pulmonary extravascular water volume increases slowly at low pressure and then increases rapidly at high pressure. In addition, this equation indicates that the critical pressure from which the pulmonary extravascular water volume exceeds the upper limit of its normal volume is about 17 mmHg in PAEDP. Infusion of dextran 70 increased plasma macromolecular osmotic pressure from 20.8 +/- 0.6 (mean +/- SD) mmHg before infusion to 43.7 +/- 1.4 mmHg after infusion. Therefore, dextran 70 does not change the critical microvascular pressure against pulmonary edema.     

Two electrocardiographic patterns with or without transient T-wave inversion during recovery periods of variant anginal attacks

Continuous electrocardiographic recordings during anginal attacks in patients with variant angina were reviewed. Twenty-seven attacks in 15 patients were associated with transient T-wave inversion during recovery periods of angina (type A), while in another 69 attacks in 28 patients there was no T-wave inversion (type B). In none of the patients was there an ischemic T-wave inversion during angina-free periods. Both the maximum elevation (0.79 +/- 0.57 mV) and duration (5.3 +/- 1.2 min) of ST-segment deviation of type A attacks were significantly higher and longer than those of type B (0.44 +/- 0.27 mV, 2.8 +/- 1.4 min). Ten patients who had both type A and type B attacks one time or the other were selected for further evaluation. In these 10, the duration of ST-segment elevation was significantly longer during type A attacks (5.2 +/- 1.2 min, n = 18) than during type B attacks (2.7 +/- 1.2 min, n = 20) but there was no significant difference in the maximum ST-segment elevation. Giant U-wave inversion appeared in 15% of the type A attacks, but never in type B. Therefore, the T-wave abnormality related to ischemic episodes in patients with variant angina seems to be associated with more severe ischemia of longer duration than milder episodes of transient ischemia.     

Non-Q wave versus Q wave myocardial infarction: regional myocardial metabolism and blood flow assessed by positron emission tomography

This study compared regional myocardial blood flow at rest and during supine exercise as well as regional myocardial glucose utilization in the fasting condition in 22 patients, 11 with antecedent non-Q wave and 11 with antecedent Q wave infarction. With use of N-13 (nitrogen-13) ammonia and F-18 (fluorine-18) deoxyglucose as tracers of blood flow and exogenous glucose utilization and positron emission tomography, hypoperfused areas were noted at rest and during exercise in all 11 patients (100%) with Q wave infarction. Among the 11 patients with non-Q wave infarction such areas were noted in only 5 (45%) at rest and in 8 (73%) during exercise. Furthermore, segmentally enhanced F-18 deoxyglucose uptake corresponding to the infarcted areas (identified electrocardiographically) was seen in 10 (91%) of the 11 patients with non-Q wave infarction but in only 4 (36%) of the 11 patients with Q wave infarction (p less than 0.01). In conclusion, segmental F-18 deoxyglucose uptake as a possible sign of myocardial viability was seen more frequently in non-Q wave than in Q wave infarction and, importantly, regionally enhanced F-18 deoxyglucose uptake occurred even in the absence of segmental rest or exercise blood flow abnormalities, or both, in 5 (45%) of 11 patients with non-Q wave infarction.     

Coronary risk factors used to predict coronary artery disease by logistic regression analysis.

Risk factor analysis in coronary artery disease was conducted in 303 patients who underwent coronary arteriography to identify associations between personal characteristics and the prevalence of coronary heart disease. Age, sex, obesity, smoking, alcohol intake, hypertension, diabetes mellitus, serum uric acid, total cholesterol, LDL- and HDL-cholesterol, triglyceride, and atherogenic indices were statistically analyzed. All 13 variables were first compared between patients with positive and negative ergonovine tests. Only total cholesterol was significantly different, while significant differences in age, sex, history of diabetes, total cholesterol, LDL- and HDL-cholesterol, triglyceride and atherosclerotic indices were observed between patients with and without organic coronary artery stenosis. A multivariate analysis was performed, and the resulting equation was tested using the remaining patients. Logistic analysis of all 13 variables identified 5 (age, sex, diabetes mellitus, LDL- and HDL-cholesterol) which accounted for the differences between patients with and without significant coronary artery disease and that were validated in the test group. The sensitivity for prediction of coronary artery disease was 75.8%, specificity 68.5%, and predictive accuracy 71.5% in the test group. Thus, risk factor analysis appears to be very valuable in screening subjects with high-risk organic coronary stenosis and in optimizing the preventive and therapeutic modalities, but not in predicting vasospastic subjects.     

Exercise-induced angina provoked by aspirin administration in patients with variant angina

The effects of aspirin (4.0 g/day) given orally to eight patients with variant angina were observed. An exercise stress test performed in the morning was positive in two of seven patients during placebo administration, whereas a test performed in the afternoon at the same exercise work load resulted in negative findings. During aspirin administration, the afternoon exercise test repeatedly provoked anginal attacks associated with electrocardiographic changes (S-T segment elevation in five and S-T depression in two). Rate-pressure product at the end of the exercise test during aspirin administration was significantly lower than that during placebo administration (p <0.01). During aspirin administration, the frequency of angina increased markedly, and the attacks occurred not only during the night or early morning but also in the daytime in six of the eight patients. Our observations suggest that aspirin, in this large dose, reduces the capacity for exercise and provokes exercise-induced coronary arterial spasm in patients with variant angina.     

Significance of technetium-99m/thallium-201 overlap on simultaneous dual emission computed tomography in acute myocardial infarction

To examine the significance of technetium-99m pyrophosphate/thallium-201 scintigraphic overlap as an indicator of identifying early coronary reperfusion (less than or equal to 3 hours), 32 patients, in whom coronary recanalization was attempted for acute myocardial infarction (AMI), underwent myocardial imaging 3 days after the onset of AMI. The imaging was performed by simultaneous dual emission computed tomography, which allows simultaneous recording of technetium-99m pyrophosphate and thallium-201 images and comparison between both images in the same slice. The patients were separated into 3 groups: 9 patients in whom reperfusion was successful and showed scintigraphic overlap (group A), 12 with successful recanalization but no overlap (group B) and 11 with neither coronary reflow nor overlap (group C). No patient in whom reperfusion failed showed scintigraphic overlap (p less than 0.05). Groups A and B were comparable in age, infarct vessel, collateral circulation, residual coronary stenosis and cumulative release of creatine kinase-MB isoenzyme. However, compared with group B, group A had a shorter interval between onset of AMi and reflow (2.5 +/- 0.8 vs 4.8 +/- 1.3 hours, p less than 0.001). The presence of scintigraphic overlap identified early coronary reflow with a sensitivity of 80%, specificity of 91%, positive predictive accuracy of 89% and negative predictive accuracy of 83%. Thus, technetium-99m/thallium-201 overlap on dual emission computed tomography can be used as an index of documenting early recanalization and might reflect the presence of salvaged myocardium adjacent to the necrotic tissue.     

A problem intrinsic to the measurements of the pulmonary extravascular water volume by the thermal-dye technic with the sampling site in the bifurcation of the aorta. Thermal equilibrium with the aortic wall

When estimating the pulmonary extravascular water volume (PEWV) as the lung thermal volume (LTV), by the double indicator dilution technic using heat and indocyanine green (ICG), a part of the left ventricular wall comes to the thermal equilibrium, and this leads to an overestimation of PEWV, when the samplings are made in the aortic root. In a previous study from this laboratory, this overestimation was approximately 10% of the measured LTV in the aortic root. In the present study, we evaluated the extent to which the thermal equilibrium with the aortic wall would cause LTV to slightly overestimate PEWV. For this purpose, we injected a mixture of the indicators into the right atrium, and recorded the indicator dilution curves at the bifurcation of the aorta (AB). We then compared this LTV with the one calculated from the indicator dilution curves recorded simultaneously in the aortic root (Ao). We obtained the following results: Firstly, the values of cardiac output (CO) from the dye dilution curve and from the thermodilution curve at two sites, Ao and AB, were all in agreement. Secondly, LTV estimated in Ao (LTVAo) and LTV estimated in AB (LTVAB) were not the same, and their relationships were: LTVAB = 1.21 X LTVAo + 0.44 (ml/kg), n = 32, (r = 0.98, p less than 0.001) A close agreement of CO determined at two sites indicated that there was virtually no loss of heat between the two sampling sites, Ao and AB. An excess of LTVAB over LTVAo came to about 20%, and this excess appeared to be ascribable to the incorporation of the thermally equilibrated "volume" of the aortic wall. This finding appeared to be a challenge to the validity of estimating LTV when sampling the indicators in the distal abdominal aorta.     

Long-term evaluation of early repolarization syndrome (normal variant RS-T segment elevation).

The electrocardiograms of 65 patients with the "early repolarization syndrome" (normal variant of RS-T elevation) were analyzed to delineate the features and evaluate the natural history of this electrocardiographic entity. Maximal follow-up was 26 years. The syndrome was characterized by (1) an upward concave elevation of the RS-T segment with distinct or "embryonic" J waves, slurred downstroke of R waves or distinct J points or both; (2) RS-T segment elevation commonly encountered in the precordial leads and more distinct in these leads; (3) rapid QRS transition in the precordial leads with counterclockwise rotation; and (4) persistence of these characteristics for many years although some intraindividual changes were common. Less commonly found were (5) tall R and T waves in the precordial leads; (6) "labile" or "juvenile" T wave patterns; (7) "pseudo-R" waves; and (8) "isolated T negativity syndrome." These changes commonly simulate pericarditis, myocardial ischemia, left ventricular hypertrophy and right bundle branch block.