Diagnostic significance of deep T-wave inversion induced by exercise testing in patients with suspected coronary artery disease.
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Biomedical subjects
Publications and source records attributed to Y Yonezawa.
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Sera from different mammalian species displayed great differences in mitogenic activity, as measured by stimulation of DNA synthesis in BALB/c 3T3 cells (3T3 cells). Among the sera examined, fetal bovine serum was least active, and increasing activity was detected in calf serum, human serum, rat serum and mouse serum, in that order. Rat and mouse sera exhibited extremely high mitogenic activity with 3T3 cells, but when TIG-1 human fetal lung fibroblasts were used for the DNA assay instead, the activity levels of all of the sera were lower, and the differences between them were smaller. To determine the reasons for these differences, the heparin-binding growth factors in each serum were separated on a heparin affinity column. Five peaks of DNA-stimulating activity were obtained. Three of these were found in all sera examined, with both 3T3 cells and TIG-1 cells. Two other peaks were found only with 3T3 cells; one was peculiar to rat and mouse sera, with extremely high activity in the rat, and the other was specific to fetal serum. The dependence of the activity of these peaks on the cells used for the test was confirmed using normal rat lung fibroblasts and immortalized rat kidney cells. These findings adequately explain the species-specific differences in mitogenic activity of whole sera, and the variation in activity depending on the cells used for assay of DNA synthesis.
The purpose of this study was to noninvasively differentiate in patients with reduced global left ventricular function between those with idiopathic dilated cardiomyopathy (IDC) and coronary artery disease (CAD). Clinical features and findings of dipyridamole thallium-201 imaging in 55 consecutive patients with IDC were compared with those in 77 with CAD. Left ventricular ejection fraction was similar between the 2 groups (34 +/- 16% vs 39 +/- 7%). Patients with IDC had lower incidences of ischemic chest pain (11 vs 79%; p less than 0.0001), electrocardiographic evidence of myocardial infarction (24 vs 82%; p less than 0.0001), and reversible defects (4 vs 57%; p less than 0.0001) than did those with CAD. The lowest percent thallium uptake in the initial imaging was less with CAD than IDC (30 +/- 15% vs 59 +/- 10%; p less than 0.001). Patterns of perfusion defects were classified as: no defects, multiple small defects and large defects. Of patients with IDC, 15 had no defects, 19 had multiple small defects, and 21 had large defects, whereas all those with CAD had large defects (p less than 0.0001). Stepwise discriminant analysis, using chest pain and electrocardiography, revealed sensitivity of 89%, specificity of 87%, accuracy of 88%, and positive predictive value of 83% in the identification of patients with IDC.(ABSTRACT TRUNCATED AT 250 WORDS)
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Since we have found previously that adult donor skin fibroblasts (TIG-114) migrated more slowly in serum-depleted medium than in medium supplemented with 10% FBS, we tried to identify a factor(s) which promotes fibroblast migration from the edge of a denuded area in a monolayer. In medium supplemented with 10% FBS, the effects of both suramin, a competitor of growth factors at the receptor level, and monensin, an inhibitor of the secretion of extracellular matrix, were examined. Both substances suppressed cell migration, suggesting that growth factors and matrix substances are important for cell migration. Then, we examined the effects of growth factors and extracellular matrix on fibroblast migration in serum-free medium. Platelet-derived growth factor (PDGF), basic fibroblast growth factor, acidic fibroblast growth factor, and transforming growth factor-beta did not stimulate cell migration. Type I collagen, plasma fibronectin, and heparin also did not promote cell migration. However, the combination of PDGF and type I collagen did promote cell migration. Addition of anti-PDGF antibody reduced the stimulatory effect induced by the combination of PDGF and type I collagen. These results suggest that the copresence of growth factors and extracellular matrix regulates fibroblast migration into a denuded area in a monolayer.
The migration of human lung and skin fibroblasts was determined during in vitro aging and in vivo cellular senescence by measuring their migration from the edge of a denuded area of a monolayer. The migration of human fetal lung fibroblasts (TIG-1 and TIG-3) decreased only very slightly with increasing passage, whereas the migration of human fetal skin fibroblasts (TIG-3S) declined gradually: the difference in cell migratory ability between early and late passages was significant (P less than 0.05). The migratory patterns of skin fibroblasts from adult and elderly donors were also similar to that of fetal skin fibroblasts. Next, the migratory abilities of fibroblast lines from adult and elderly donor groups were compared, using relatively early passaged cells. The migratory ability of the elderly-donor skin fibroblast lines was significantly lower (P less than 0.05) than that of the adult-donor skin fibroblast lines. Addition of suramin and monensin suppressed the migration of fibroblasts from fetal, adult and elderly donors, which implies that fibroblast migration is regulated by growth factors and matrix substances. The relationships between the age-dependent decline of migratory ability, growth factors and the extracellular matrix are discussed.
In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400 micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.
A decline is usually observed in the myocardial uptake of thallium-201 in delayed imaging compared with initial imaging. In patients with severe coronary artery disease (CAD), the uptake is sometimes higher in the delayed than in the initial imaging, which is expressed as negative washout rate. To evaluate the diagnostic implications of this negative washout rate the findings of dipyridamole thallium scintigraphy in 582 patients with coronary artery disease were evaluated. The negative washout rate was present in 201 of 582 patients (35%). It had a significant association with high grade coronary artery narrowing of > or = 90%. Sensitivity in detecting patients with this high grade narrowing by negative washout rate was 48%, its specificity was 93%, and its positive predictive value was 94%. Sensitivity to detect individual coronary artery narrowing of > or = 90% did not decrease according to the extent of CAD, with the highest detection in the left anterior descending coronary artery and the lowest in the left circumflex coronary artery. Since patients with high grade coronary narrowing often require coronary intervention, the results of this study suggest the diagnostic importance of negative washout rate in the identification of the particular subset of patients with CAD.
To elucidate the prognosis of elderly patients with asymptomatic aortic stenosis (AS) and to assess the timing of aortic valve replacement (AVR), 21 asymptomatic patients (8 men, 13 women, mean age: 75 +/- 8 years (54-89 years)), who had Doppler echocardiographic evidence of a significant aortic pressure gradient of greater than 40 mmHg (mean gradient: 75 +/- 31 mmHg), were followed for 33 +/- 10 months. During the follow-up, there were 4 cardiac events (2 cardiac deaths, 2 late AVRs), and 2 non-cardiac deaths (cerebro-vascular accidents). Among 15 survivors, 13 patients were in NYHA class I--II, and the remaining 2 patients were found to have malignant disease. Compared to the 17 patients without cardiac events, those with cardiac events had significantly larger CTR (58 +/- 6% vs. 53 +/- 3%; p less than 0.01), although there were no significant difference in electrocardiographic LVH, echocardiographic LV mass, and Doppler pressure gradient between the two groups. The prevalence of the development of cardiac symptoms during the follow-up was not high (12%) in patients without cardiac events. Among 4 patients with cardiac events, one patient who was 89 years-old at diagnosis died of heart failure, one patient had fatal myocardial infarction which seemed to be unrelated to AS, and two patients had successful late AVR because of new heart failure. The low incidence of fatal cardiac events in asymptomatic patients with aortic stenosis and the relatively high possibility of developing non-cardiac events in elderly patients indicate that the decision-making for AVR should not be solely based upon the pressure gradient detected by Doppler echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine whether the orientation of the major orifice of a mitral tilting disc prosthesis affects hemodynamics, intracavitary blood flow patterns were studied in 45 patients with well-functioning Björk-Shiley mitral prosthesis using color Doppler flow imaging. The major orifice was oriented towards the septum in 23 patients (12 men, 11 women, age 58 +/- 11 years; group S), and towards the posterior wall in 22 patients (8 men, 14 women, age 55 +/- 9 years; group P). 1) The left ventricular end-diastolic dimensions (S: 4.8 +/- 0.9 cm, P: 5.2 +/- 1.0 cm), end-systolic dimensions (S: 3.6 +/- 0.9 cm, P: 3.8 +/- 1.2 cm), and left atrial dimensions (S: 5.0 +/- 1.0 cm, P: 4.7 +/- 0.9 cm) did not differ significantly between the 2 groups. 2) The peak mitral flow velocities (S: 1.43 +/- 0.38 m/sec, P: 1.43 +/- 0.27 m/sec), pressure gradients (S: 8.5 +/- 4.0 mmHg, P: 8.4 +/- 3.1 mmHg), and pressure half-times (S: 94.0 +/- 19.0 msec, P: 86.5 +/- 21.7 msec) did not differ significantly between the 2 groups. 3) Although mitral regurgitation was detected in 8 patients (35%) in the S group and in 2 patients (9%) in the P group, hemodynamically significant regurgitation was detected in only 4 patients in the S group (3 mild, one moderate). 4) The patients in the S group had reversed intracavitary blood flow; mitral flow was first directed towards the left ventricular outflow tract during diastole, while the outflow pattern was displaced into the left ventricular inflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)
In an attempt to predict high risk myocardial infarction, we studied 201 patients with Q wave infarction with dipyridamole-loading thallium-201 myocardial perfusion scintigraphy (D-MPS), left ventriculography, coronary angiography and treadmill exercise testing. The results of these tests were related to the use of initial PTCA or CABG, and the occurrence of cardiac deaths and nonfatal cardiac events during a mean follow-up period of 39 months. Three high risk parameters were identified by D-MPS; partial redistribution, diffuse slow washout, and extensive fixed defects. The patients were categorized into 3 groups according to the numbers of high risk parameters: group A (n = 50), patients with 2 or more high risk parameters; group B (n = 95), patients with one high risk parameter; group C (n = 56), patients without a high risk parameter. The prevalence of 3-, 2-, and one- or insignificant vessel disease was 72, 20 and 8% in group A, 15, 16, and 69% in group B, and 5, 13 and 82% in group C, respectively. Initial PTCA or CABG was performed in 42% of the patients in group A, 5% of the patients in group B, and 2% of the patients in group C. Among medically-treated patients, cardiac deaths occurred in 31% in group A, 4% in group B, and in none in group C. Nonfatal cardiac events occurred in 24, 12, and 4%, respectively. Coronary angiography revealed 3-vessel disease in 53 patients, 2-vessel disease in 32, and one-vessel disease or insignificant lesions in 116 patients. Initial PTCA or CABG was performed in 45% of the patients with 3-vessel disease, 6% of those with 2-vessel disease and 1% of those with one-vessel disease. Among medically-treated patients, cardiac deaths occurred in 31% with 3-vessel disease, 7% with 2-vessel disease, and in 2% with one-vessel disease. Nonfatal cardiac events occurred in 17, 10, and 3%, respectively.
A radio multichannel telemetry system has been developed for use with chronically instrumented, unrestrained, small animals. The system can simultaneously record autonomic neural signals, blood flow velocity, blood pressure, and ECG. The system is time-multiplexed and pulse width modulation (PWM)/FM device, which employs two sampling frequencies. The system is designed with 10 standard low power integrated circuits, a 3 terminal voltage regulator, and a transistor. The size is 53 x 42 x 20 mm, and the weight, including two batteries is 40 grams. The system is powered by two lithium cells, which provide 60 hours of continuous operation.
To evaluate the usefulness of dipyridamole thallium scintigraphy with low-level exercise for the identification of left main (LM) coronary artery disease (CAD), 466 consecutive patients with CAD were studied. Thirty-eight patients (8%) had LM stenosis (diameter narrowing greater than or equal to 50%). The LM scintigraphic pattern was present in 9 of 38 patients with LMCAD and 38 of 428 CAD patients without LMCAD (24 vs 9%; p less than 0.005). This pattern was present in 6 of 9 patients with LMCAD without right CAD and in only 3 of 29 patients with LM and right CAD (67 vs 10%; p = 0.0005). Patients with LMCAD had a higher incidence of premature cessation of low-level exercise (53 vs 21%; p less than 0.0001), chest pain (68 vs 48%; p less than 0.02), blood pressure decrease of greater than or equal to 20 mm Hg (44 vs 16%; p less than 0.002) and greater ST depression (0.17 +/- 0.13 vs 0.06 +/- 0.10 mV; p less than 0.001) during dipyridamole loading than patients without LMCAD. Stepwise discriminant analysis revealed that the LM scintigraphic pattern and markers of ischemia during dipyridamole loading best identified (p less than 0.0001) patients with LMCAD without right CAD (sensitivity 67%, specificity 91%), but this predictability is no better than the LM scintigraphic pattern alone. The combination of clinical markers of ischemia during dipyridamole loading and scintigraphic findings of diffuse slow washout, extensive fixed defects and the LM pattern best identified (p less than 0.0001) patients with LM and right CAD (sensitivity 72%, specificity 80%).(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the prognostic significance of thallium-201 perfusion defects in patients with idiopathic dilated cardiomyopathy (IDC), 43 patients underwent thallium scintigraphy in addition to clinical, echocardiographic, angiographic and hemodynamic evaluation. Eleven patients had no significant thallium perfusion abnormality, 19 had multiple small defects and 13 had a large defect. During 3.2 +/- 2.2 years, 14 patients had disease-related mortality. The patients who died had a higher incidence of ventricular tachycardia (71 vs 31%; p less than 0.02), increased cardiothoracic ratio (60 +/- 6 vs 54 +/- 6; p = 0.005), decreased fractional shortening (11 +/- 6 vs 15 +/- 5; p less than 0.05), increased pulmonary wedge pressure (15 +/- 7 vs 10 +/- 6 mm Hg; p = 0.05), increased left ventricular end-diastolic pressure (21 +/- 8 vs 14 +/- 6 mm Hg; p = 0.02) and abnormal thallium perfusion defects (13 of 14 vs 16 of 26; p less than 0.05) compared with survivors. Age, gender, left ventricular end-systolic and end-diastolic dimensions, cardiac index and ejection fraction were not statistically different in the survivors versus the patients who died. Kaplan-Meier survival estimates at 1, 3 and 5 years were 100% in patients without significant perfusion abnormality; 89, 77 and 64%, respectively, in patients with multiple small defects; and 84, 76 and 30%, respectively, in patients with a large defect (p less than 0.025 by log rank test).(ABSTRACT TRUNCATED AT 250 WORDS)
An equation for dissolution from the whole surface of a nondisintegrating single component tablet under the sink condition was derived. Also, equations for several dissolution manners of the tablet under the sink condition were derived in the postulation of the dominant dissolution rate constant which determines the dissolution manner. The applicability or validity of these equations were examined by the dissolution measurements with nondisintegrating single component tablets. About one-tenth the amount of the amount needed to saturate the solution was used to prepare a tablet, and dissolution measurements were carried out with the tablet whose flat or side surface was masked with an adhesive tape in accordance with the conditions for derivation of equations. Among the derived equations, dissolution from the whole surface of a tablet was expressed by a form similar to the cube root law equation for particles. Hence, a single component tablet compressed by the use of a suitable amount was thought to behave like a single crystal. Also, equations derived for several dissolution manners were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystal's habit and its dissolution property, and the extended applicability was examined by converting the crystal into a simplified or idealized form, i.e., rectangle or plate.
To determine whether a change in the size of a scintigraphic perfusion defect is of prognostic significance in dilated cardiomyopathy (DCM), we performed thallium-201 myocardial scintigraphy twice for each of 13 patients with mean intervals of 45 +/- 18 months. Seven patients showed clinical deterioration (Group D) during the follow-up period of 58 +/- 22 months; whereas, 6 patients improved clinically as well as echocardiographically (LVDd < or = 5.5 cm and %FS > or = 20%) (Group I). 1. The initial scintigraphy showed that 3 patients had large defects (LD), 2 had multiple small defects (MSD) and 2 had no defects (NL) in Group D. Among 6 patients in Group I, one had LD, 3 had MSD and 2 had NL. 2. The second scintigraphy showed that in 5 patients in Group D, the defects were progressively enlarged and in the remaining 2 who had no defects at the initial scintigraphy, new defects developed (MSD). Among 6 patients in Group I, no patient had enlargement of defects. In 4 patients with defects (1LD, 3MSD), the sizes in their defects reduced. 3. At the initial study, all 7 patients in Group D fitted NYHA functional class III-IV; while, in Group I, 4 of the 6 patients fitted class III-IV and 2 patients class II. In the second study, all 7 patients in Group D remained in class III-IV; whereas, all 6 patients in Group I fitted class I-II. Five of the 7 patients in Group D died of heart failure after the second study.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the significance of diffuse slow washout (DSW) in dipyridamole loading thallium-201 myocardial perfusion scintigraphy, 382 patients were studied. DSW were observed in 69 (24%) of 285 patients with perfusion defects, 5 (5%) of 97 patients without perfusion defects. There was significant relation between DSW and perfusion defects (p less than 0.01). Coronary angiography showed multivessel disease in 84% single vessel disease in 12% of patients with DSW and multivessel disease in 28%, single vessel disease in 50% of patients without DSW. During a mean follow up period of 29 months, initial CABG or PTCA were done in 41%, cardiac death occurred in 12%, nonfatal cardiac events occurred in 7% of patients with DSW and perfusion defects. In patients without DSW, initial CABG or PTCA were done in 11%, cardiac death occurred in 7%, nonfatal cardiac events occurred in 5%. Patients without perfusion defects had good prognosis regardless of the presence or absence of DSW. In conclusion, DSW indicates serious cardiac ischemia in patients with perfusion defects. DSW does not indicate cardiac ischemia in patients without perfusion defects.
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