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Biomedical subjects

W E Hopkins

Publications and source records attributed to W E Hopkins.

At least 19 recordsLinked to original sources
PubMed2000

Ethane sulfonate metabolite of alachlor: assessment of oncogenic potential based on metabolic and mechanistic considerations.

Chronic administration of alachlor has been shown to produce neoplastic responses in the nasal turbinate mucosa, glandular stomach mucosa, and thyroid follicular epithelium of rats. Subsequent studies have shown that specific metabolic activation of alachlor is required for nasal tumor formation, and that non-genotoxic, threshold-sensitive processes produce all three tumors. The herbicide alachlor is degraded in the soil by microbial action to the tertiary ethane sulfonate metabolite (ESA). The acute and subchronic toxicity of ESA is very low, and the metabolite did not produce developmental toxicity or genotoxicity. The studies described here were conducted to determine whether ESA shares a common mechanism of oncogenicity with alachlor in rats. Specifically, we studied ESA's pharmacokinetics and ability to produce changes that are causally associated with the oncogenicity of alachlor. These studies demonstrated that ESA was poorly absorbed and underwent minor metabolism, which contrasted with the significant absorption and substantial metabolism observed with alachlor. ESA was also excreted more quickly than alachlor and showed no evidence of accumulation in the nasal turbinates, a site of oncogenicity for alachlor in the rat. In addition, ESA did not elicit the characteristic preneoplastic changes observed in the development of alachlor-induced nasal, stomach, and thyroid tumors. The results of these studies support the conclusion that ESA does not share a common oncogenic mechanism with alachlor and would not be expected to produce the same oncogenic responses observed following chronic alachlor exposure in rats.

Acetamides↗
PubMed1997

Paradoxical relationship between N-terminal proatrial natriuretic peptide and filling pressure in adults with cyanotic congenital heart disease.

BACKGROUND: Many adults with cyanotic congenital heart disease are characterized by reduced ventricular filling pressures and decreased systemic oxygen transport. Data from animals suggest that hypoxia can induce synthesis and secretion of atrial natriuretic peptide. METHODS AND RESULTS: We measured plasma N-terminal (1-98) proatrial natriuretic peptide (proANP) in 26 cyanotic adults and 28 noncyanotic control subjects. Resting arterial oxygen saturation was significantly lower and hemoglobin concentration and hematocrit significantly greater in cyanotic patients than in control subjects (82+/-6 versus 96+/-3%, 19.7+/-2.2 versus 14.7+/-2.1 g/dL, and 59.0+/-8.5% versus 44.3+/-5.2%, respectively, P<.0001 in all cases). Four cyanotic patients had evidence of iron deficiency. Plasma proANP levels were elevated in cyanotic patients compared with control subjects (1828+/-1147 versus 689+/-343 pmol/L, P<.0001). Comparison of resting arterial oxygen saturation and proANP levels demonstrated an inverse linear relationship between the two measures (r=-.70, P<.0001). There was a significant linear relationship between both hemoglobin concentration and hematocrit and proANP levels as well (r=.53, P=.0003 and r=.48, P=.002, respectively). Cyanotic patients had lower mean right atrial pressures than the control subjects (4+/-3 versus 7+/-2 mm Hg, P=.005), and there were inverse logarithmic relationships between proANP levels and systemic cardiac index (r=-.82, P=.0002), systemic oxygen transport (r=-.68, P=.005), and mixed venous oxygen saturation (r=-.79, P<.0001). CONCLUSIONS: Adults with cyanotic congenital heart disease are characterized by increased levels of plasma proANP. The increased atrial natriuretic peptide most likely results in extracellular and plasma volume depletion and reduced systemic oxygen transport. Measures designed to increase ventricular filling may improve quality of life of these patients.

Adolescent↗
PubMed1996

Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome.

BACKGROUND: To date, lung or heart-lung transplantation remains the only definitive treatment for most adults with severe primary pulmonary hypertension or Eisenmenger syndrome. Although the hemodynamic derangements and clinical history of adults with severe primary pulmonary hypertension have been well documented, those of adults with Eisenmenger syndrome have not. METHODS: We evaluated hemodynamics and nontransplantation survival of 100 adults with severe pulmonary hypertension (34 +/- 9 years, 73 women and 27 men; 57 with primary pulmonary hypertension, 37 with Eisenmenger syndrome, and six with a previously repaired congenital heart defect) followed up by the lung transplant or adult congenital heart services at Washington University. RESULTS: Despite a trend toward greater pulmonary artery pressures (107 +/- 20 versus 97 +/- 21 mm Hg, p = 0.06), patients with Eisenmenger syndrome had greater systemic cardiac indexes (2.7 +/- 0.6 versus 2.2 +/- 0.8 L/min/m2, p < 0.05) and lower mean right atrial pressures (5 +/- 2 versus 12 +/- 5 mm Hg, p < 0.0001) than patients with primary pulmonary hypertension. Four (11%) patients with Eisenmenger syndrome died and eight (22%) received transplants during the follow-up interval; 13 (23%) patients with primary pulmonary hypertension died, and 31 (54%) received transplants over the same interval. Actuarial survival of patients who did not receive transplants was 97% at 1 year, 89% at 2 years, and 77% at 3 years for patients with Eisenmenger syndrome and 77%, 69%, and 35%, respectively, for patients with primary pulmonary hypertension. Data on hemodynamics from a small number of patients with a previously repaired heart defect and severe pulmonary hypertension were similar to those from patients with primary pulmonary hypertension. CONCLUSIONS: Our data suggest that adults with Eisenmenger syndrome have a more favorable hemodynamic profile and prognosis than adults with primary pulmonary hypertension.

Adolescent↗
PubMed1995

Usefulness of dobutamine stress echocardiography for the prospective identification of the physiologic significance of coronary narrowings of moderate severity in patients undergoing evaluation for percutaneous transluminal coronary angioplasty.

Dobutamine stress echocardiography (DSE) was performed after coronary angiography to evaluate the need to perform percutaneous transluminal coronary angioplasty (PTCA) for 46 stenoses of moderate severity (50% to 80%) in 46 patients. Patients were divided into 2 groups according to the DSE results in the distribution of the coronary artery with the lesion of moderate severity: group I (n = 32) were those without inducible myocardial ischemia; PTCA was not performed. Group II (n = 14) were those who exhibited myocardial ischemia; PTCA was performed in 12. The 2 groups were comparable in terms of clinical characteristics. Follow-up DSE was performed < or = 48 hours after PTCA, at 3 months, and 6 to 12 months after the first DSE. In group I at 3 months, DSE results were still negative in the distribution of the vessel with the moderately severe lesion in 24 patients; only 1 patient had a positive result, and 8 patients who refused DSE remained clinically stable. At 6 to 12 months (mean 7 +/- 2), 26 patients had negative study results; 3 patients who refused follow-up DSE remained clinically stable. In group II, 12 of 14 patients with inducible ischemia on the initial DSE underwent PTCA. Early follow-up DSE (< or = 48 hours) was negative in 7, and 4 had persistent inducible wall motion abnormalities in the myocardium subtended by the coronary artery in which the PTCA had been performed; 1 study was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Transesophageal echocardiography in the detection of cardiovascular sources of peripheral vascular embolism.

The purpose of this study was to determine the impact of transesophageal echocardiography (TEE) on the management of patients with peripheral vascular emboli. We prospectively evaluated the role of TEE in 15 patients with documented peripheral emboli and no evidence of occlusive peripheral vascular disease. The patients were divided in two groups for analysis: group 1 (n = 8) had no clinical evidence of heart disease and group 2 (n = 7) had clinically significant heart disease. TEE provided information regarding the source of embolism in four (50%) patients in group 1, and these findings significantly affected the management of all. Three patients underwent thoracic surgery to remove the source of embolism (aortic valve mass in one and a thrombus in the descending thoracic aorta in two); the other patients was treated with thrombolytic agents. TEE findings had high diagnostic value in all patients in group 2, but the results had a possible effect on clinical management in only two of these patients. TEE provides diagnostic information in most patients with peripheral vascular emboli and this information has a significant influence on management, particularly in those without clinically evident heart disease. TEE should be performed in all patients with documented peripheral embolism.

Adult↗
PubMed1995

Intravenous albunex during dobutamine stress echocardiography: enhanced localization of left ventricular endocardial borders.

Albunex is an intravenous contrast agent that opacifies the left ventricle (LV). This study evaluated the effect of Albunex on the enhancement of LV endocardial border localization during dobutamine stress echocardiography (DSE). Albunex was infused in 30 patients at baseline and with low- and high-dosage dobutamine. Apical two- and four-chamber views were divided into six segments each, and enhancement of LV border localization was compared with precontrast images graded as follows: 0 = none; 1 = faint; or 2 = optimal. The mean grade and percentage of segments with optimal localization of LV endocardial borders were determined. There was a significant increase in enhancement with low- and high-dosage dobutamine when compared with baseline. Of 179 segments with suboptimal enhancement at baseline, 137 (77%) became optimal during DSE with Albunex. We conclude that Albunex improves localization of LV endocardial borders and that this localization is enhanced during DSE.

Aged↗
PubMed1995

Right ventricular dysfunction in low output syndrome after cardiac operations: assessment by transesophageal echocardiography.

BACKGROUND: Low output syndrome after cardiac operations is associated with high morbidity and mortality rates. The contribution of right ventricular dysfunction to this syndrome has not been fully characterized. The purpose of this study was to evaluate the utility of transesophageal echocardiography to identify the frequency and the in-hospital mortality from right ventricular dysfunction in patients with this syndrome. METHODS: Seventy-five consecutive patients undergoing transesophageal echocardiography for low output syndrome early after cardiac operations were evaluated. The findings from transesophageal echocardiography were correlated with the type of surgical procedure, cross-clamp time, right heart hemodynamics, and coronary angiography. RESULTS: Right ventricular systolic dysfunction occurred in 36 patients (42%); in 17 patients it was isolated and in 19 patients it occurred in combination with left ventricular dysfunction. Postoperative right ventricular dysfunction was not uniformly associated with important right coronary artery disease or with prolonged ischemic time during cardiopulmonary bypass. Hemodynamic data were not useful to distinguish the group with postoperative right ventricular dysfunction. Patients with right ventricular dysfunction had a high (44%) in-hospital mortality rate. CONCLUSIONS: Right ventricular dysfunction occurs frequently in patients with low output syndrome after cardiac operations and is associated with a high in-hospital mortality rate. Better understanding of the mechanisms causing postoperative right ventricular dysfunction may provide insight for preventing this complication.

Adult↗
PubMed1995

Severe pulmonary hypertension in congenital heart disease: a review of Eisenmenger syndrome.

Patients with Eisenmenger syndrome are characterized by severe irreversible pulmonary hypertension and reversed central shunt. In the past, congestive heart failure was generally considered common and prognosis poor. However, newer information suggests that congestive heart failure is uncommon and that the natural survival of patients with Eisenmenger syndrome is better than survival achieved with transplantation. In this review, I discuss who gets Eisenmenger syndrome, when they get it, why they get it, and what the consequences are for adults with the disorder.

Adult↗
PubMed1995

A new mask filter cartridge used to determine applicator inhalation exposure to an alachlor herbicide (Lasso) during normal spraying operations.

A filter cartridge with a low air-flow resistance was designed for use on a modified half-face respirator worn during the application of alachlor (Lasso) herbicide. The filter trapped large concentrations of alachlor while retaining the ability to trap small respirable droplets. Moreover, alachlor could be recovered from the disassembled cartridge and analyzed by conventional methods. The test cartridges were used in combination with conventional personal air samplers to determine whether the filters trapped more alachlor when compared with personal samplers and to determine accurately the amount of alachlor reaching the breathing zone. Farmers sprayed alachlor in the form of alachlor (N = 7) or alachlor mixed with other herbicides or surfactant (N = 15). An average of 4 x 10(-2) mg or 2 x 10(-4) mg/kg of applied alachlor reached the respirator filters. This concentration was 10-fold higher than the alachlor recovered from the personal samplers. The new filter cartridge is better for determining the amount of alachlor reaching the breathing zone, and there is a low potential for significant inhalation exposure to alachlor during normal spraying operations.

Acetamides↗
PubMed1995

Multiplane transesophageal echocardiographic doppler imaging accurately determines cardiac output measurements in critically ill patients.

OBJECTIVES: To compare cardiac output and stroke volume measured by multiplane transesophageal Doppler echocardiography with that measured by the thermodilution technique. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Cardiac surgery and myocardial infarction intensive care units. PATIENTS: Twenty-nine patients, mean age (+/- SD) 67 +/- 8 years. Nineteen had undergone open heart surgery and 10 had suffered acute myocardial infarction. METHODS: Cardiac output and stroke volume were measured simultaneously by the thermodilution technique and multiplane transesophageal Doppler echocardiography via the transgastric view (119 +/- 8 degrees) with the sample volume positioned at the level of the left ventricular outflow tract. RESULTS: Stroke volume and cardiac output measurements were obtained in 29 of 33 patients (88%). Mean values were 50 +/- 13 mL and 4.8 +/- 1.3 L/min by Doppler and 51 +/- 14 mL and 4.9 +/- 1.4 L/min by thermodilution (r = 0.90, r = 0.91, p < 0.001). The mean differences in values obtained with the two techniques were 1 +/- 6 mL (2 +/- 12%) and 0.1 +/- 0.7 L/min (2 +/- 12%). CONCLUSIONS: Multiplane transesophageal echocardiography enhances the ability to estimate accurately cardiac output and stroke volume by providing new access to left ventricular outflow tract in critically ill patients.

Aged↗
PubMed1994

Quantitative ultrasonic tissue characterization of myocardium in cyanotic adults with an unrepaired congenital heart defect.

Adults with nonrestrictive ventricular septal defects have chronic hypoxemia that may lead to alterations in myocardial structure and function. Ultrasonic integrated backscatter provides quantitative assessment of myocardial acoustic properties that are altered by myocardial ischemia, fibrosis, and edema. Sixteen patients (age 31 +/- 10 years) with a nonrestrictive ventricular septal defect were studied using 2-dimensional and M-mode echocardiography with integrated backscatter imaging to determine the cyclic variation of integrated backscatter in the right ventricular free wall, ventricular septum, and left ventricular posterior wall. Cyclic variation of integrated backscatter in the right ventricular free wall and interventricular septum in patients was significantly less than that in control subjects (4.1 +/- 0.8 vs 4.9 +/- 1.0 decibels [dB], p = 0.02, and 3.8 +/- 1.2 vs 4.8 +/- 1.1 dB, p = 0.004, respectively). There was no difference between mean cyclic variation of integrated backscatter in the left ventricular posterior wall in patients and that in control subjects (4.7 +/- 1.3 vs 4.8 +/- 1.1 dB, p = NS, respectively). However, values < 4.0 dB were noted in 38% of patients compared with 15% of control subjects. Biventricular systolic function was normal in all but 1 patient. There was no correlation between backscatter and either wall thickness or percent wall thickening from the 3 regions. Histologic analysis of myocardial tissue in 3 patients revealed interstitial and replacement fibrosis. Adults with nonrestrictive ventricular septal defects exhibit alterations in tissue-acoustic properties detectable by integrated backscatter imaging despite preserved systolic function and wall thickening.

Adult↗
PubMed1994

Initial clinical experience with a miniature biplane transesophageal echocardiographic probe in adults.

Transesophageal echocardiography (TEE) is now routinely used in cardiovascular medicine. With improved technology the size of TEE probes has increased. Recently there has been interest in using smaller probes for adult TEE. We used a miniature 32-element, phased array biplane probe in 20 consecutive adults who underwent clinically indicated TEE evaluation. The miniature biplane probe was easily inserted without complication in all patients including one with thrombocytopenia and one with an esophageal stricture. Subjectively the probe was easier to insert and better tolerated by patients than standard adult TEE probes. High quality images of near-, mid-, and far-field structures were obtained in a majority of patients. Color Doppler identified mitral regurgitation in 12 (60%) patients, tricuspid regurgitation in ten (50%) patients, and aortic insufficiency in five (25%) patients. The miniature biplane TEE probe used in this study enhanced patient comfort without significant loss of image quality.

Adult↗
PubMed1993

Right and left ventricular area and function determined by two-dimensional echocardiography in adults with the Eisenmenger syndrome from a variety of congenital anomalies.

The Eisenmenger syndrome has been associated with right ventricular (RV) enlargement and systolic dysfunction. However, little attention has been directed toward potentially characteristic changes in left ventricular (LV) dimensions or function. Therefore, 2-dimensional echocardiography (short-axis-papillary muscle level) was performed in 24 adults (mean age 33 +/- 7 years) with Eisenmenger syndrome to evaluate RV and LV size and function. A significant correlation was found between RV and LV end-diastolic areas (r = 0.96; regression slope 1.06), and fractional area change (r = 0.88; regression slope 1.03) in patients with a nonrestrictive ventricular septal defect (VSD) (n = 15). In contrast, in patients with Eisenmenger syndrome but no VSD (n = 9), RV and LV end-diastolic areas (r = 0.68; regression slope 0.10), and fractional area change (r = 0.08; regression slope -0.09) were discordant. RV function was preserved in most patients with a VSD, and mean RV fractional area change was significantly greater than in those without a VSD (0.50 +/- 0.13 vs 0.18 +/- 0.08; p < 0.001). No significant difference was apparent in these 2 groups (patients with and without a VSD) with respect to age, pulmonary artery systolic pressure, partial arterial oxygen pressure or hematocrit. Thus, the results indicate a relation between biventricular chamber dimensions and systolic function that is dependent on the nature and locus of the primary intracardiac defect responsible for the Eisenmenger syndrome.

Adult↗
PubMed1993

Comparison of color flow imaging and peripheral venous saline contrast during transesophageal echocardiography to evaluate right-to-left shunt at the atrial level.

Intravenous injections of agitated saline (contrast) are used to identify right-to-left atrial shunt during transesophageal echocardiography (TEE). Color flow imaging (CFI) with TEE can be used to detect left-to-right atrial shunt but its application to detect right-to-left shunt is not known. We performed CFI and contrast during TEE in 72 patients for detection of right-to-left shunt. Frame-by-frame review of CFI demonstrated discrete laminar jets of the left side of the atrial septum at the lower or upper margin of the fossa ovalis (FO) in 41 (57%) of 72; only 22 had positive contrast. Timing of shunts was late diastolic or early systolic and not related to pulmonary venous inflow. The length of the FO at end-systole was greater in those with positive CFI compared to negative CFI (13.5 +/- 5 vs 11 +/- 4 mm, P = 0.02). CFI was positive for right-to-left shunt in ten of 14 with atrial septal aneurysms. Contrast was positive for right-to-left shunt in 29 (40%) of 72; all but six had positive CFI. The degree of left atrial opacification was minimal in 19 and moderate to severe in ten. FO size was greater in positive versus negative contrast (14 +/- 4 vs 11 +/- 5 mm, P = 0.02). Contrast was positive for shunt in ten of 14 with septal aneurysms. Thus, right-to-left atrial shunt more often occurs with increased FO size and septal aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗