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Biomedical subjects

I A Simpson

Publications and source records attributed to I A Simpson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Comparative imaging techniques and models.

The explosion of high-resolution imaging technology in recent years has led to the increasing problem of choosing imaging modalities appropriate to specific clinical questions. In terms of structural information, for example, the relative benefits of ultrasound versus magnetic resonance imaging versus computed tomography scanning are often readily apparent, but in the related area of flow velocity imaging, difficulties may arise. These are perpetuated by the relative lack of information on the fundamental display characteristics of these imaging techniques. Much of this essential information can be acquired from in vitro modeling of the pressure and flow characteristics of a variety of pathologic lesions. The information obtained from such experimental investigation can provide a basis for a more rational approach to the interpretation of these imaging modalities in the clinical setting. We review the recent role of in vitro modeling for enhancing our understanding of the display characteristics of various imaging technologies, with particular emphasis on Doppler ultrasound and color Doppler flow mapping where in vitro modeling has been most extensively studied.

Coronary Circulation↗
PubMed1992

Intravascular ultrasound imaging of the coronary arteries: an in vitro evaluation of measurement of area of the lumen and atheroma characterisation.

OBJECTIVE: To assess the accuracy of measurement of area of the lumen, and sensitivity, and specificity of detection of atheroma in coronary arteries in vitro with a commercially available 20 MHz intravascular ultrasound system. SETTING: A teaching hospital department of cardiology with the support of the department of cardiovascular pathology. PROCEDURE: 10 segments of coronary artery were removed from cadaver hearts. Intravascular ultrasound imaging was performed at fixed levels and the vessels were then sectioned and photographed before histological preparation. An independent blinded observer measured luminal area and assessed the presence of atheroma on the intravascular ultrasound images of 76 vessel sections (304 quadrants). The sensitivity and specificity of detection of atheroma was assessed in comparison with the histologically prepared sections. Luminal areas from intravascular ultrasound, photographs of cross sections of the vessels and histological sections were compared with the technique of limits of agreement. RESULTS: Overall 36% of the 304 quadrants studied histologically had identifiable atheroma. Intravascular ultrasound sensitivity for atheroma was 0.593 and the specificity was 0.839. The positive predictive value was 0.674, and the relative risk 3.139. Values for area of the vessel lumen were on average 9.4 mm2 (confidence interval (CI) 8.6-10.2 mm2) larger than those measured from photographs and 10.7 (CI 9.8-11.6 mm2) larger than those measured from the histological sections. CONCLUSIONS: The intravascular ultrasound system assessed in this study significantly overestimated coronary vessel luminal area and had low sensitivity and specificity for detection of atheroma. Improvements in image resolution are required before this system can provide useful information on coronary artery size and morphology.

Coronary Artery Disease↗
PubMed1992

Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms.

BACKGROUND: Intraventricular conduction in hypertrophic cardiomyopathy (HCM) has been characterized to test the hypothesis that myofibrillar disarray will cause dispersion of activation throughout the ventricular myocardium. METHODS AND RESULTS: Of 37 patients with HCM, four had spontaneous ventricular fibrillation (VF), five had nonsustained ventricular tachycardia (VT), 13 had no risk factors, and 15 had a family history of sudden death. These patients and four controls were studied by pacing one site in the right ventricle and recording electrograms from three other right ventricular sites. These electrograms were high-pass filtered to emphasize small deflections due to activation of small bundles of myocytes close to the electrode. Intraventricular conduction curves were obtained with S1S2 coupling intervals decreasing in 1-msec steps from 479 msec to ventricular effective refractory period (VERP). These curves were repeated by pacing each RV site in turn and were characterized by two parameters: the point at which latency increased by 0.75 msec/20 msec reduction of the S1S2 coupling interval and an increase in electrogram duration between an S1S2 of 350 msec and VERP. Patients with VF, VT, and family history of sudden death had a mean increase in electrogram duration of 12.8 (2.9-32.3) msec versus 4.6 (-4.2 to 14.0) msec in low-risk patients and controls. Electrogram latency increased at an S1S2 of 363 msec in the VF group (342-386), 269 msec in the controls (266-279), and 326 msec in the non-VF group (260-399). Discriminant analysis separated VF patients from the remainder (p less than 0.0001) and VF, VT, and family history of sudden death patients from the low-risk and control groups (p less than 10(-6)). CONCLUSIONS: Patients with HCM who are at risk of sudden death have increased dispersion and inhomogeneity of intraventricular conduction, and this may create the conditions for reentry and arrhythmogenesis.

Adolescent↗
PubMed1992

Echocardiographic study of the morphology and growth of the aortic arch in the human fetus. Observations related to the prenatal diagnosis of coarctation.

BACKGROUND: In a study of normal and abnormal growth of the aorta before birth, high-resolution echocardiographic imaging of the aortic arch in 92 normal fetuses aged 16-38 weeks was used to establish normal values for aortic arch dimensions at varying gestational ages. METHODS AND RESULTS: From long-axis views of the aortic arch, the internal diameter of the aortic root, ascending aorta, transverse aortic arch, aortic isthmus, proximal descending thoracic aorta, and left common carotid artery were measured. Correlation coefficients for the diameter of each aortic arch segment when related to gestational age varied from r = 0.87 to r = 0.94 (p less than 0.001 for each), and growth curves were derived from the third and 97th percentiles around each linear regression analysis. In most of the fetuses, there was progressive tapering of the aortic arch, with the smallest diameter being at the isthmus. The ratio of the transverse aorta, isthmus, descending aorta, and aortic root to the ascending aorta remained relatively constant with gestational age, with mean values of 0.94, 0.81, 0.96, and 1.13, respectively. In five fetuses in whom a prenatal diagnosis of aortic coarctation was confirmed postnatally, transverse aortic and isthmic measurements fell on or below the third percentile for gestational age from the above data. In each case, the ratio of left common carotid artery to transverse aorta was greater than or equal to 0.73 compared with less than or equal to 0.62 for the 92 normal fetuses (mean ratios, 0.77 +/- 0.05 [SD] for coarctation versus 0.48 +/- 0.08 for normal fetuses; p less than or equal to 0.001). CONCLUSIONS: Use of normal growth curves for the developing aortic arch should facilitate the prenatal diagnosis of left heart and aortic arch abnormalities, particularly aortic coarctation, which until recently has been a difficult prenatal diagnosis to make with certainty.

Aorta, Thoracic↗
PubMed1991

Phosphorylation state of the GLUT4 isoform of the glucose transporter in subfractions of the rat adipose cell: effects of insulin, adenosine, and isoproterenol.

The acute effects of insulin, adenosine, and isoproterenol on the activity, subcellular distribution, and phosphorylation state of the GLUT4 glucose transporter isoform were investigated in rat adipocytes under conditions carefully controlled to monitor changes in cAMP-dependent protein kinase (A-kinase) activity. In contrast to GLUT1, which has not been shown to be phosphorylated even when cells are exposed to any of the above agents, GLUT4 was partially phosphorylated (0.1-0.2 mol/mol) when the activity of the A-kinase was suppressed, and remained unchanged in response to insulin. Isoproterenol elicited a 64% inhibition of insulin-stimulated glucose transport activity in the absence, but not the presence, of adenosine receptor agonists. However, in either the presence or the absence of agonists, A-kinase was activated as assessed by examining the phosphorylation of the major adipocyte A-kinase substrate, perilipin. Similarly, under either condition, phosphorylation of GLUT4 was enhanced 1.4-fold in the intracellular membranes, but no significant change was observed in the plasma membrane. In the absence of adenosine receptor agonists, isoproterenol exerted a small (14%) but significant inhibition of the insulin-induced translocation of GLUT4 but had no effect on the translocation of GLUT1. Thus, changes in the phosphorylation state and/or subcellular distribution of GLUT4 cannot account for the inhibition of insulin-stimulated glucose activity induced by isoproterenol.

Adenosine↗
PubMed1991

Role of protein kinase C in the regulation of glucose transport in the rat adipose cell. Translocation of glucose transporters without stimulation of glucose transport activity.

The possible role of protein kinase C in the regulation of glucose transport in the rat adipose cell has been examined. Both insulin and phorbol 12-myristate 13-acetate (PMA) stimulate 3-O-methylglucose transport in the intact cell ein association with the subcellular redistribution of glucose transporters from the low density microsomes to the plasma membranes, as assessed by cytochalasin B binding. In addition, the actions of insulin and PMA on glucose transport activity and glucose transporter redistribution are additive. Furthermore, PMA accelerates insulin's stimulation of glucose transport activity, reducing the t1/2 from 3.2 +/- 0.4 to 2.1 +/- 0.2 min (mean +/- S.E.). However, the effect of PMA on glucose transport activity is approximately 10% of that for insulin whereas its effect on glucose transporter redistribution is approximately 50% of the insulin response. Immunoblots of the GLUT1 and GLUT4 glucose transporter isoforms in subcellular membrane fractions also demonstrate that the translocations of GLUT1 in response to PMA and insulin are of similar magnitude whereas the translocation of GLUT4 in response to insulin is markedly greater than that in response to PMA. Thus, glucose transport activity in the intact cell with PMA and insulin correlates more closely with the appearance of GLUT4 in the plasma membrane than cytochalasin B-assayable glucose transporters. Although these data do not clarify the potential role of protein kinase C in the mechanism of insulin action, they do suggest that the mechanisms through which insulin and PMA stimulate glucose transport are distinct but interactive.

3-O-Methylglucose↗
PubMed1991

Subcellular distribution and phosphorylation state of insulin receptors from insulin- and isoproterenol-treated rat adipose cells.

Rat adipose cells treated with insulin followed by isoproterenol exhibit a change in glucose transporter intrinsic activity (lowered maximal activity) and a decrease in insulin sensitivity (rightward shift of the concentration-response curve) when assayed for 3-O-methylglucose transport. To investigate the latter phenomenon, the distribution and phosphorylation state of insulin receptors was examined. Isoproterenol augmented the effect of insulin to reduce cell surface receptors by 20-30%. These receptors were recovered in microsomal fractions. Isoproterenol also markedly reduced insulin-stimulated [32P]phosphate incorporation into the plasma membrane receptor beta-subunit. These effects may account for the effect of isoproterenol to decrease the sensitivity of the glucose transport response to insulin.

Adipose Tissue↗
PubMed1991

Transcoronary atrioventricular nodal modification using microvascular collagen.

Surgical and catheter based techniques for atrioventricular (AV) nodal modification have recently been described. Similarly, transcoronary embolization for the treatment of arrhythmias has recently emerged as a potentially useful approach. This report reviews our experience of a novel technique using embolization of the AV node with an inert agent, cross-linked collagen, for the treatment of AV nodal reentrant tachycardia. Three patients with refractory nodal tachycardia received 0.1-0.5 mL cross-linked collagen (2 mg/mL) delivered via a catheter placed within the nodal artery. All developed transient complete AV block with subsequent recovery of conduction. Two patients have had no further tachycardia and were noninducible at restudy. One patient required electrical modification because of recurrent symptoms. One patient sustained a limited posterior infarct due to back-spill of collagen into the distal right coronary artery. This novel technique provides an alternative approach to a cure for AV nodal tachycardia without producing long-term heart block.

Atrioventricular Node↗
PubMed1991

Alcohol ablation of atrioventricular conduction.

Transcoronary ablation of atrioventricular conduction by dehydrated alcohol was attempted in 14 patients with refractory atrial arrhythmias. Alcohol (0.5 or 1.0 ml) was delivered after selective catheterisation of the atrioventricular nodal artery in the 10 patients in whom the artery could be identified by cineangiography. The other four patients underwent electrical ablation when the nodal artery could not be catheterised. Temporary atrioventricular block induced by dilute contrast and cold saline (0.9%) confirmed that the catheter was in the correct position before the alcohol was delivered. In all 10 patients complete atrioventricular block developed after alcohol ablation. The block persisted in all four patients given 1.0 ml alcohol but not in four of the six given 0.5 ml. The mean (SD) creatine kinase (MB fraction) at four to six hours after ablation was 76.5 (49.5) IU after 1.0 ml and 75.5 (43.1) IU after 0.5 ml alcohol (normal less than 20 IU). The overall success rate of alcohol ablation in the whole group on an "intention to treat" basis was 43%. The procedure was a technical success in six of the 10 patients in whom the nodal artery was identified. Transcoronary alcohol ablation of atrioventricular conduction should be considered in patients in whom electrical techniques have been unsuccessful.

Aged↗
PubMed1991

Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography.

After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention.

Aged↗
PubMed1991

A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study.

While color Doppler flow mapping has yielded a quick and relatively sensitive method for visualizing the turbulent jets generated in valvular insufficiency, quantification of the degree of valvular insufficiency has been limited by the dependence of visualization of turbulent jets on hemodynamic as well as instrument-related factors. Color Doppler flow imaging, however, does have the capability of reliably showing the spatial relations of laminar flows. An area where flow accelerates proximal to a regurgitant orifice is commonly visualized on the left ventricular side of a mitral regurgitant orifice, especially when imaging is performed with high gain and a low pulse repetition frequency. This area of flow convergence, where the flow stream narrows symmetrically, can be quantified because velocity and the flow cross-sectional area change in inverse proportion along streamlines centered at the orifice. In this study, a gravity-driven constant-flow system with five sharp-edged diaphragm orifices (ranging from 2.9 to 12 mm in diameter) was imaged both parallel and perpendicular to the direction of flow through the orifice. Color Doppler flow images were produced by zero shifting so that the abrupt change in display color occurred at different velocities. This "aliasing boundary" with a known velocity and a measurable radial distance from the center of the orifice was used to determine an isovelocity hemisphere such that flow rate through the orifice was calculated as 2 pi r2 x Vr, where r is the radial distance from the center of the orifice to the color change and Vr is the velocity at which the color change was noted. Using Vr values from 54 to 14 cm/sec obtained with a 3.75-MHz transducer and from 75 to 18 cm/sec obtained with a 2.5-MHz transducer, we calculated flow rates and found them to correlate with measured flow rates (r = 0.94-0.99). The slope of the regression line was closest to unity when the lowest Vr and the correspondingly largest r were used in the calculation. The flow rates estimated from color Doppler flow imaging could also be used in conjunction with continuous-wave Doppler measurements of the maximal velocity of flow through the orifice to calculate orifice areas (r = 0.75-0.96 correlation with measured areas).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of pressure and volume of the receiving chamber on the spatial distribution of regurgitant jets as imaged by color Doppler flow mapping. An in vitro study.

Regurgitant jet dimensions imaged by color Doppler flow mapping have been used to evaluate the severity of valvular insufficiency in clinical studies. To study the effect of pressure and volume within the receiving chamber on the magnitude of spatial distribution of regurgitant jets assessed by color Doppler techniques, we designed a simple constant-flow model in which a jet was driven through a known orifice (1.5 mm2) into a compliant receiving chamber by a steady-flow pump. A distal tube at the outflow closed the system and maintained the volume of the chamber constant during pump operation. We varied flow rate from 60 to 270 ml/min into elastic balloons with different static compliances of 1, 2, 4.5, and 9 ml/mm Hg (pressures of 57, 28, 18, and 8 mm Hg, respectively); the balloons served as receiving chambers at the constant volume of 150 ml. We also evaluated the effect of different volumes of a receiving chamber (110, 130, and 150 ml and pressures of 5, 15, and 24 mm Hg) with a static compliance of 2 ml/mm Hg over the same range of flow rates. For each of the different balloons, jet area correlated linearly with the jet velocity across the orifice (r = 0.98, 0.99, 0.98, and 0.97) and also with flow rate (r = 0.97, 0.99, 0.98, and 0.99). At the same flow rate and volume of receiving chamber, however, the jet area imaged by color Doppler decreased as the pressure in the receiving chamber increased, although receiving-chamber volume was constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1991

Quantification of valvular regurgitation by Doppler echocardiography.

One of the widest uses of color Doppler echocardiography is for the quantification of valvular regurgitation. In this article we review the physics and instrumentation factors related to the most commonly applied method, that of planimetering areas of regurgitant jet spray within the receiving chamber, and relate features such as instrument gain, pulse repetition frequency, and important physical parameters such as receiving chamber compliance and driving pressure to the application of this method for precordial as well as transesophageal echocardiography. New approaches to the quantification of valvular insufficiency, such as measurement of the momentum of the jet and study of the acceleration flow in the proximal flow convergence region within the chamber of origin of an insufficiency jet and proximal to the orifice, are described and preliminary results given for a new method of quantification of volume flow across regurgitant orifices.

Compliance↗
PubMed1990

Cell surface labeling of glucose transporter isoform GLUT4 by bis-mannose photolabel. Correlation with stimulation of glucose transport in rat adipose cells by insulin and phorbol ester.

A new impermeant photoaffinity label has been used for identifying cell surface glucose transporters in isolated rat adipose cells. This compound is 2-N-4(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4- yloxy)-2- propylamine. We have used this reagent in combination with immunoprecipitation by specific antibodies against the GLUT4 and GLUT1 glucose transporter isoforms to estimate the relative abundance of these two transporters on the surface of the intact adipose cell following stimulation by insulin and phorbol 12-myristate 13-acetate (PMA). In the basal state, GLUT4 and GLUT1 are both present at the cell surface but GLUT4 is more abundant than GLUT1. In response to insulin, GLUT4 increases 15-20-fold and GLUT1 increases approximately 5-fold while 3-O-methyl-D-glucose transport is stimulated 20-30-fold. By contrast, PMA only induces a approximately 4-fold increase in GLUT4 while GLUT1 increases approximately 5-fold to the same level as seen with insulin. In addition, PMA stimulates 3-O-methyl-D-glucose transport approximately 3-fold to only 13% of the insulin-stimulated state. Thus GLUT4 is the major glucose transporter isoform under all conditions, and it is selectively and markedly enriched in response to insulin but not PMA which increases GLUT1 and GLUT4 equally. Furthermore, stimulation of glucose transport activity correlates closely with the appearance of GLUT4 on the cell surface in response to both insulin and PMA but does not correlate with the sum of GLUT1 and GLUT4 appearance. These results suggest that GLUT4 may be inherently more active than GLUT1 due to a higher TK (turnover/Km).

Adipose Tissue↗
PubMed1990

Insulin, oxytocin, and vasopressin stimulate protein kinase C activity in adipocyte plasma membranes.

Incubation of isolated rat adipocytes with insulin, vasopressin, or oxytocin increased plasma membrane-bound protein kinase C (PKC) activity by 100-400%. PKC activity was assayed by a procedure that is virtually background-free, thus permitting assay of protein kinase activity in highly diluted samples of solubilized membranes. Hormone-dependent increases in PKC activity were limited to plasma membranes. Stimulation of the kinase was half-maximal with 70 pM insulin, and the hormone effect was rapid. Oxytocin and vasopressin produced effects on PKC similar to insulin, but the magnitude of the vasopressin stimulation exhibited seasonal variations. Treatment of cells with phorbol 12-myristate 13-acetate (PMA) resulted in a loss of PKC activity from the cytosol and a gain in plasma membrane activity, indicative of translocation of the enzyme. With activity measurements it was not possible to determine if insulin stimulated a translocation of the kinase. However, Western blot analysis of plasma membranes with polyclonal antibodies directed against PKC suggest that at least some of the insulin-stimulated PKC activity resulted from enzyme translocation.

Adipose Tissue↗
PubMed1989

Doppler color flow mapping of simulated in vitro regurgitant jets: evaluation of the effects of orifice size and hemodynamic variables.

The spatial distribution of simulated regurgitant jets imaged by Doppler color flow mapping was evaluated under constant flow and pulsatile flow conditions. Jets were simulated through latex tubings of 3.2, 4.8, 6.35 and 7.9 mm by varying flow rates from 137 to 1,260 cc/min. Color jet area was linearly related to flow rate at each orifice (r = 0.96, SEE = 3.4; r = 0.99, SEE = 1.6; r = 0.97, SEE = 2.3; r = 0.97, SEE = 3.2, respectively), but significantly higher flow rates were required to maintain the same maximal spatial distribution of the jet at the larger regurgitant orifices. Constant flow jets were also simulated through needle orifices of 0.2, 0.5 and 1 mm, with a known total volume (5 cc) injected at varying flow rates and with differing absolute volumes injected at the same flow rate (0.2, 1.0 and 2.0 cc/s, respectively). Again, maximal color jet area was linearly related to flow rate at each orifice (r = 0.97, SEE = 2.3; r = 0.97, SEE = 2.4; r = 0.92, SEE = 3.9, respectively), but was not related to the absolute volume of regurgitation. Color encoding of regurgitant jets on Doppler color flow maps was demonstrated to be highly dependent on velocity and, hence, driving pressure, such that color encoding was obtained from a constant flow jet injected at a velocity of 4 m/s through an orifice of 0.04 mm diameter with flow rates as low as 0.008 cc/s. Mitral regurgitant jets were also simulated in a physiologic in vitro pulsatile flow model through three prosthetic valves with known regurgitant orifice sizes (0.2, 0.6 and 2.0 mm2). For each regurgitant orifice size, color jet area at each was linearly related to a regurgitant pressure drop (r = 0.98, SEE = 0.15; r = 0.97, SEE = 0.20; r = 0.97, SEE = 0.23, respectively), regurgitant stroke volume (r = 0.77, SEE = 0.55; r = 0.94, SEE = 0.30; r = 0.91, SEE = 0.41, respectively) and peak regurgitant flow rate (r = 0.98, SEE = 0.16; r = 0.97, SEE = 0.21; r = 0.93, SEE = 0.37, respectively), but the spatial distribution of the regurgitant jets was most highly dependent on the regurgitant pressure drop. Jet kinetic energy calculated from the summation of the individual pixel intensities integrated over the jet area was closely related to driving pressure (r = 0.84), but integration of the power mode area times pixel intensities provided the best estimation of regurgitant stroke volume (r = 0.80).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗