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Biomedical subjects

W F Shen

Publications and source records attributed to W F Shen.

At least 37 records · Page 2Linked to original sources

Prognostic importance of left ventricular diastolic filling velocity profiles in dilated cardiomyopathy.

To determine the prognostic importance of pulsed Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcome of 58 patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction was analysed. During a mean follow-up period of 31.2 +/- 12.8 months, 23 died of either progressive pump failure or sudden death. Peak early filling velocity (E) was higher and late atrial filling velocity (A) lower in nonsurvivors than in survivors. The E/A ratio was higher and the deceleration time (DT) of early diastole shorter in nonsurvivors. The mortality was significantly higher in patients with an E/A ratio > 2 or a DT < 150 ms than in those without. Repeated Doppler echocardiographic examinations in 31 of 35 survivors after intense treatment showed decreased E, increased A, reduced E/A ratio and prolonged DT in 18 patients with clinical functional improvement, whereas these measurements were unaltered in the remaining 13 patients whose functional status was unchanged or deteriorated. This study suggests that pulsed Doppler-derived left ventricular diastolic filling variables may be important predictors of outcome in dilated cardiomyopathy and provide useful measures in observing the effects of therapy during long-term follow-up of the patients.

Adolescent↗

Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines.

We have previously reported that certain genes of the HOX2 cluster of homeobox genes on human chromosome 17 are specifically expressed in human leukemic cell lines with erythroid potential, suggesting that these genes are involved in hematopoietic differentiation. We now show that the expression of the HOX 2.2 gene decreases during erythropoietin-induced differentiation of the erythroid cell line MB02. In order to study the role of the HOX 2.2 homeobox gene in hematopoiesis, vectors producing sense or antisense transcripts were introduced into K562 and HEL cells, pluripotent lines with erythroid and myeloid features. Overexpression of HOX 2.2 is associated with loss of erythroid features in both lines and an increase in certain myelomonocytic markers in K562 cells. Expression of antisense HOX 2.2 is associated with an increase in erythroid features in HEL cells and a mild decrease in myeloid characteristics in K562 cells. Overexpression of the adjacent HOX 2.1 gene in K562 cells does not produce similar phenotype changes. These data demonstrate that modulation of a specific HOX 2 homeobox gene can change the phenotype of somatic cells and suggest that certain HOX 2 genes play a role in blood cell differentiation.

Blotting, Northern↗

Prognostic significance of Doppler-derived left ventricular diastolic filling variables in dilated cardiomyopathy.

To determine the prognostic significance of pulsed wave Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcomes of 62 consecutive patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction were analyzed. All patients had echocardiographic left ventricular end-diastolic dimension > or = 6.0 cm, fractional shortening < 25%, increased E pointseptal separation, and diffuse hypokinesia or akinesia. During a mean follow-up period of 30.5 +/- 13.9 months, 27 patients experienced cardiac events: 23 died of either progressive pump failure or an episode of sudden death and four required cardiac transplantation because of refractory heart failure. Peak early filling velocity (78 +/- 23 cm/sec vs 65 +/- 25 cm/sec; p < 0.03) was higher and late atrial filing velocity (34 +/- 13 cm/sec vs 55 +/- 19 cm/sec; p < 0.001) was lower in patients with cardiac events than in cardiac event-free survivors. The ratio of early to late transmitral filling velocities was higher (2.6 +/- 1.2 vs 1.5 +/- 1.3; p < 0.001), and the deceleration time of early diastole was shorter (133 +/- 48 msec vs 175 +/- 71 msec; p < 0.001) in patients with cardiac events. The cardiac event rate was significantly higher in patients with an early to late filling velocity ratio greater than 2 (77% vs 19%; p < 0.001) or a deceleration time less than 150 msec (58% vs 23%; p < 0.05) than in those without. Stepwise multivariate regression analysis revealed that the pattern of transmitral early to late filling velocity ratio was the only significant independent Doppler echocardiographic predictor of outcome for these patients. Repeat Doppler echocardiographic examinations, which were performed in 31 survivors after intensive treatment (mean, 38.6 +/- 6.5 months), showed that early filling velocity was decreased (55 +/- 20 cm/sec vs 75 +/- 25 cm/sec; p < 0.02), late atrial filling velocity was increased (74 +/- 27 cm/sec vs 57 +/- 21 cm/sec; p < 0.01), early to late filling velocity ratio was reduced (0.8 +/- 0.3 vs 1.7 +/- 1.3; p < 0.001), and deceleration time was prolonged (227 +/- 60 msec vs 167 +/- 82 msec; p < 0.01) in 18 patients with clinical functional improvement, whereas these measurements were unaltered in the remaining 13 patients whose functional status was unchanged or had deteriorated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Left ventricular aneurysm and prognosis in patients with first acute transmural anterior myocardial infarction and isolated left anterior descending artery disease.

To determine the clinical and angiographic factors responsible for left ventricular aneurysm formation and the prognosis of patients with aneurysm, 79 patients with a first acute transmural anterior myocardial infarction and angiographically documented isolated left anterior descending artery disease were retrospectively evaluated. Presence of large infarct size and left ventricular volumes, reduced left ventricular function, and evidence of clinical functional impairment were more common in patients with aneurysm (n = 31) than in those without (n = 48). Patients with aneurysm often had total occlusion of the proximal left anterior descending artery without collateral vessels on angiography. During a mean follow-up of 53 months, 10 patients with and three without aneurysm died (P less than 0.01). Compared to survivors with or without aneurysm, the nonsurvivors were older, had significantly larger infarct size and left ventricular volumes and poor systolic function. The incidence of total occlusion of the left anterior descending artery without collaterals was higher in nonsurvivors. In patients with aneurysm, stepwise multivariate analysis revealed that left ventricular ejection fraction and the status of left anterior descending artery obstruction and collaterals were independent predictors of mortality. The study indicates that in patients with a first acute transmural anterior myocardial infarction and isolated anterior descending artery disease, left ventricular aneurysm often results from a large infarct caused by total occlusion of the proximal left anterior descending artery without collateral supply to the infarct region. The reduced survival rate for patients with aneurysm is primarily related to severe global left ventricular dysfunction which may be determined by assessing the residual flow to the infarct region.

Adult↗

Assessment of severity of mitral regurgitation by measuring regurgitant jet width at its origin with transesophageal Doppler color flow imaging.

BACKGROUND: The ability of transesophageal color Doppler echocardiography to provide high-resolution images of both cardiac structure and blood flow in real time is advantageous for many clinical purposes. This study was performed to determine the utility of the regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging in the assessment of severity of mitral regurgitation. METHODS AND RESULTS: Sixty-three consecutive patients with mitral regurgitation underwent transesophageal color Doppler examination, and the diameter of regurgitant jet at its origin was measured. Both right and left cardiac catheterizations were performed within 24 hours of Doppler studies, and angiographic grading of mitral regurgitation and regurgitant stroke volume were evaluated. There was a close relation between the jet diameter at its origin measured by transesophageal Doppler color flow imaging and the angiographic grade of mitral regurgitation (r = 0.86, p less than 0.001). A jet diameter of 5.5 mm or more identified severe mitral regurgitation (grade III or IV) with a sensitivity of 92%, specificity of 92%, and positive and negative predictive values of 88% and 95%, respectively. In 31 patients with isolated mitral regurgitation, the jet diameter correlated well with the regurgitant stroke volume determined by a combined hemodynamic-angiographic method (r = 0.85, p less than 0.001). A jet diameter of 5.5 mm or more identified a regurgitant stroke volume of 60 ml or more with a sensitivity of 88%, specificity of 93%, and positive and negative predictive values of 94% and 87%, respectively. CONCLUSIONS: The regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging provides a simple and useful method of measuring the severity of mitral regurgitation, and it may allow differentiation between mild and severe mitral regurgitation.

Angiocardiography↗

Alternative splicing of the HOX 2.2 homeobox gene in human hematopoietic cells and murine embryonic and adult tissues.

The HOX 2.2 homeobox gene is expressed in human hematopoietic cell lines with erythroid features (W.-F. Shen, et al, Proc. Natl. Acad. Sci. 86, 8536-8540, 1989). Both human and murine Hox 2.2 genes contain a single 1 kb intron which interrupts the sequence encoding the proposed homeobox protein. Four human erythroleukemia cell lines express the spliced, homeobox-coding transcript as the major form of message, and variable low amounts of unspliced HOX 2.2 mRNAs. Murine embryonic tissues and adult kidney and uterus contain approximately equal amounts of transcripts containing this intron and mRNAs from which the intron has been excised. The spliced transcript encodes a 224 amino acid homeobox protein, while the unspliced transcript would potentially encode a 140 residue protein containing the same N-terminal sequence but lacking the homeodomain.

Amino Acid Sequence↗

Relationship between electrocardiographic patterns and angiographic features in isolated left circumflex coronary artery disease.

The relation of electrocardiographic (ECG) patterns to clinical and angiographic features was assessed in 89 patients with isolated left circumflex coronary artery (LCx) disease (46 with and 43 without myocardial infarction). ECG abnormalities were present in 75 patients; there were isolated Q waves in 20, an abnormal R wave in lead V1 with or without inferior and/or lateral Q waves in 21, and isolated ST-T wave changes in 34 cases. Inferior abnormalities on the electrocardiogram were similar in patients with proximal or distal stenoses of the LCx, but an abnormal R wave in lead V1 correlated with proximal LCx stenosis (p less than 0.01). Lateral abnormalities were more common in stenoses of the obtuse marginal branch and proximal LCx than in distal stenosis (all p less than 0.01). Compared with patients without myocardial infarction with or without ST-T-wave changes and those with infarction without an abnormal R wave in lead V1, patients with LCx-related infarction and an abnormal R wave in lead V1 associated with inferior and/or lateral Q waves had larger left ventricular end-diastolic and end-systolic volumes, lower ejection fraction, higher incidence of total occlusion of proximal LCx without collateral vessels, and more cardiac events during follow-up. This study suggests that an abnormal R wave in lead V1 associated with lateral abnormalities on the standard electrocardiogram may be clinically useful in predicting proximal LCx stenosis and identifying a subset of postinfarction patients with left ventricular dysfunction due to a large infarct size.

Adult↗

The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein.

The t(10;14)(q24;q11) chromosomal translocation found in malignant cells of 5-10% of patients with T-cell acute lymphoblastic leukemia (T-ALL) involves the T-cell receptor delta chain gene on chromosome 14 and a breakpoint cluster region on chromosome 10. The candidate proto-oncogene tcl-3, thought to be involved in the pathogenesis of t(10;14) T-ALL, was cloned and found to be elevated in expression in leukemic cells harboring the t(10;14) translocation. Sequence analysis revealed that tcl-3 is a new homeobox-containing gene. Comparison of the tcl-3 cDNA and its 5' genomic sequences with DNA sequences from the t(10;14) translocation breakpoints showed that this gene is structurally altered in four patients with t(10;14)(q24;q11) T-ALL. These findings suggest that homeobox-containing genes that normally act as transcription factors may contribute to T-cell leukemogenesis when abnormally expressed.

Amino Acid Sequence↗

Determination of left ventricular inflow by pulsed Doppler echocardiography: influence of mitral orifice area and blood velocity measurements.

Pulsed Doppler echocardiography was performed in 30 patients to assess the influence of mitral orifice area and velocity on the determination of mitral stroke volume and inflow. Aortic forward stroke volume and outflow were measured at the centre of the aortic annulus, and compared with mitral flow measurements calculated by three methods. Both mitral stroke volume and inflow derived from an instantaneous velocity-area method showed an excellent correlation with aortic flow measurements. The other two methods, which determined mitral stroke volume and inflow based on a mean mitral valve area and diastolic velocity integral, significantly underestimated mitral flow measurements. This study indicates that the instantaneous velocity-area method offers a reliable means for quantitating left ventricular inflow.

Adult↗

Assessment of severity of aortic regurgitation by M-mode colour Doppler flow imaging.

To assess the value of measuring the aortic regurgitant jet diameter at its origin by M-mode colour Doppler imaging, 82 patients with aortic regurgitation underwent, within 72 h of each other, colour Doppler examination and angiography. After excluding one patient without colour Doppler aortic regurgitation and five with a highly eccentric regurgitant jet, we found a close relationship between the jet diameter at its origin measured by M-mode colour Doppler and the angiographic grade of aortic regurgitation (r = 0.88). A jet diameter greater than or equal to 12 mm identified severe aortic regurgitation (grade III or IV) with a sensitivity of 86.4% and a specificity of 94.4%. In 38 patients, the jet diameter correlated well with the regurgitant fraction measured by a combined haemodynamic-angiographic method (r = 0.88). A jet diameter greater than or equal to 12 mm identified a regurgitant fraction greater than or equal to 40% with a sensitivity of 88.2% and a specificity of 95.2%. This study indicates that the size of the regurgitant jet diameter at its origin measured by M-mode colour Doppler provides a simple and useful measure of the severity of aortic regurgitation. It may allow differentiation between mild or moderate and severe aortic regurgitation and evaluation of regurgitant fraction.

Angiography↗

End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed Doppler echocardiography: a new predictor of the aortic regurgitant fraction.

End diastolic flow velocity just beneath the aortic isthmus was measured within 72 hours of cardiac catheterisation by pulsed Doppler echocardiography in 30 controls and 61 patients with aortic regurgitation. The end diastolic flow velocity was determined at the peak R wave on a simultaneously recorded electrocardiogram. In all controls there was no reverse flow at the end diastole beneath the aortic isthmus. In patients with aortic regurgitation the end diastolic flow velocity correlated well with the angiographic grade of regurgitation (r = 0.81) and regurgitant fraction (r = 0.82). The mean (SD) values were 6.3 (5.2), 12.2 (4.3), 22.1 (5.7), and 34.3 (9.3) cm/s for patients with regurgitant fraction of less than 20%, between 20% and 40%, between 41% and 60%, and greater than 60%, respectively. An end diastolic flow velocity of greater than 18 cm/s predicted a regurgitant fraction of greater than or equal to 40% with a sensitivity of 88.5% and a specificity of 96%. The study suggests that the pulsed Doppler derived end diastolic flow velocity is a useful index in the routine non-invasive assessment of the severity of aortic regurgitation.

Adult↗

Non-invasive measurement of the regurgitant fraction by pulsed Doppler echocardiography in isolated pure mitral regurgitation.

OBJECTIVE: To assess the usefulness of pulsed Doppler echocardiography as a method of measuring the regurgitant fraction in patients with mitral regurgitation. PATIENTS AND METHODS: Twenty controls and 27 patients with isolated mitral regurgitation underwent Doppler studies. In the patients the study was performed within 48 hours of cardiac catheterisation. Aortic outflow was measured in the centre of the aortic annulus, and mitral inflow was derived from the flow velocity at the tip of the leaflets and the area of the elliptical mitral opening. The regurgitant fraction was calculated as the difference between the two flows divided by the mtiral inflow. RESULTS: In the 20 controls the two flows were almost identical (mitral inflow, 4.44 (SD 0.88) l/min; aortic outflow, 4.58 (SD 0.84) l/min), with a mean regurgitant fraction of 4.2 (SD 8.4)%. In patients with mitral regurgitation, the mitral inflow was significantly higher than the aortic outflow (8.8 (3.6) v 4.3 (1.1) l/min). In most patients the Doppler-derived regurgitant fraction (45.8 (19.2)%) accorded closely with the regurgitant fraction (41.3 (SD 17.8)%) determined by the haemodynamic technique. CONCLUSION: Pulsed Doppler echocardiography, with an instantaneous velocity-valve area method for calculating mitral inflow, reliably measured the severity of regurgitation in patients with mitral regurgitation.

Adult↗

Angiographic prediction of cardiac events after first acute transmural myocardial infarction. A prospective study of 108 patients.

108 patients with acute myocardial infarction (MI), aged 70 years or younger, underwent left ventriculography and coronary arteriography (mean one month) after infarction and were followed up for an average period of 22 months (range 5-47 months). The contribution of angiographic variables to a first cardiac event (death, recurrent infarction, coronary artery bypass grafting or congestive heart failure) was evaluated with Kaplan-Meier survival curve analysis and long-rank test. Patients with cardiac events had left ventricular dilation, systolic dysfunction, multivessel coronary disease and lack of residual flow to the infarct region. Multivariate analysis showed that left ventricular end-systolic volume (P less than 0.001), end-diastolic volume (P less than 0.01) and the number of the diseased coronary vessels (P less than 0.05) were of significance in predicting the outcome. This prospective study indicates that in survivors of first acute transmural MI, cardiac catheterization performed one month after infarction can provide additive prognostic information that can be used to stratify risk.

Adult↗

[Relationship between electrocardiographic pattern and angiographic findings in inferior myocardial infarction].

The relationship between electrocardiographic pattern and angiographic features was assessed in 86 patients with inferior myocardial infarction. Although the occurrence of inferior Q wave was similar in patients with isolated left circumflex (LCX) or right coronary artery (RCA) occlusion, lateral Q wave and abnormal R wave in lead V1 were more frequent in the former. In patients with LCX-related infarction, abnormal R wave in lead V1 associated with inferior and/or lateral Q waves may indicate left ventricular dysfunction, total occlusion of the LCX without collateral circulation, and high cardiac event rate during longterm follow-up.

Adult↗

Myocardial infarction due to isolated left circumflex or right coronary artery occlusion.

The electrocardiographic (ECG) patterns related to clinical spectrum and angiographic features were assessed in 41 patients with first myocardial infarction due to isolated left circumflex coronary artery (LCX) occlusion, and compared to those in 45 patients with right coronary artery (RCA)-related infarction. The occurrence of inferior Q waves was similar in patients with LCX and RCA occlusion, but lateral Q waves and an abnormal R wave in lead V1 were more frequently seen in patients with LCX-related infarction (46% vs 7% and 51% vs 4%, respectively). Compared with patients with LCX-related infarction without an abnormal R wave in lead V1 and those with RCA occlusion, patients with LCX-related infarction and an abnormal R wave in lead V1 associated with inferior and/or lateral Q waves had larger left ventricular end-diastolic and end-systolic volumes, lower ejection fraction, higher incidence of total occlusion of a dominant LCX without collaterals, and more cardiac events during follow-up. The study suggests that the presence of lateral Q waves and an abnormal R wave in lead V1 after myocardial infarction may be a useful marker of LCX occlusion, and that patients with LCX-related infarction may have different status of left ventricular function depending on the size of circulation and the status of residual flow to the infarct region during LCX occlusion.

Coronary Angiography↗

Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction.

Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗