Biomedical subjects

R T Lee

Publications and source records attributed to R T Lee.

At least 127 records · Page 7Linked to original sources

PubMed1994

Relationship of aortic regurgitant velocity slope and pressure half-time to severity of aortic regurgitation under changing haemodynamic conditions.

The slope and pressure half-time of the aortic regurgitant velocity spectrum have been used as non-invasive markers of regurgitant severity. Recent in vitro and theoretical work, however, has suggested a confounding effect of systemic vascular resistance and left ventricular compliance on these parameters. To study this situation in vivo, we have investigated the determinants of the aortic regurgitant velocity profile in an animal model of aortic regurgitation in which the regurgitation was induced surgically and in which the afterload was varied pharmacologically. Specifically, we examined the relationship of slope and pressure half-time of the aortic regurgitant velocity profile to the severity of aortic regurgitation under varying conditions of afterload using multilinear analysis. Slope varied directly with regurgitant orifice area and inversely with systemic vascular resistance and both left ventricular and aortic compliance (all P < 0.001). Pressure half-time related to these variables in the opposite direction. When the regurgitant orifice was variable in size, slope related directly (P < 0.001) and half-time inversely to the severity of the aortic regurgitation (the clinically expected response). In contrast, when the regurgitant orifice area was constant, slope varied inversely (P < 0.001) and half-time varied directly (P < 0.07) with the severity of the aortic regurgitation. Following nitroprusside infusion, slope tended to increase (P = 0.08) and pressure half-time tended to shorten (P = 0.08) despite a significant reduction in the regurgitant fraction (P = 0.009). Similarly, following dopamine infusion, a significant increase in regurgitant fraction (P = 0.01) was associated with a slight fall in aortic regurgitation slope and a lengthening of the half-time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

An external aortic root device for decreasing aortic regurgitation: in vitro and in vivo animal studies.

OBJECTIVES: The purpose of this study was to determine if a device placed externally around the aortic root decreases regurgitant flow in acute aortic regurgitation. BACKGROUND: Aortic regurgitant flow is dependent on central aortic pressure and the aortic root and leaflet geometry. It may be possible to decrease aortic regurgitant severity by reducing aortic root size or dimension changes. METHODS: Aortic regurgitation was created in eight calf heart specimens suspended in a continuous flow system. Retrograde and antegrade aortic flow and distending aortic pressure were measured at baseline and after placement of an external aortic device at the level of the aortic annulus. In two additional specimens, the incompetent aortic valve was visualized fiberoptically before and after placement of the external device. Acute aortic regurgitation was created surgically in four live calves by excising a portion of the aortic leaflets. Antegrade and retrograde flow, left ventricular pressure, and central aortic pressure were measured at baseline, after creation of aortic regurgitation, and after placement of the external device. RESULTS: In the in vitro calf specimens, regurgitant flow decreased from 46.9 cc/sec to 15.1 cc/sec (66.0% +/- 21.8% decrease) after placement of the external device (p < 0.001). The regurgitant orifice area decreased from 0.13 +/- 0.04 cm2 to 0.04 +/- 0.02 cm2 after device placement (p < 0.001). Antegrade flow was reduced to a smaller extent (20.0% +/- 19.2% decrease) by the device (p < 0.05). Placement of the device around the aorta resulted in improved coaptation of the leaflets with a marked reduction in defect size by endoscopic visualization. Use of the external aortic device was associated with improvement in aortic regurgitant severity in three of four calves with surgically created aortic regurgitation. CONCLUSIONS: In these preliminary studies, acute experimental aortic regurgitant severity is decreased by the use of an external aortic device, probably due to reduction in aortic annular dimension changes and improved aortic leaflet apposition. Further studies are needed to determine the effectiveness of this device in chronic aortic regurgitation.

Animals↗

PubMed1994

Mechanical properties of model atherosclerotic lesion lipid pools.

Structural analysis of atherosclerotic coronary arteries has suggested that stress concentrations are associated with plaque rupture and that these stress concentrations are critically dependent on the geometry and mechanical properties of the fibrous cap and lipid pool. Recent clinical trials of lipid-lowering therapy have shown a significant reduction in cardiac events associated with plaque rupture perhaps because of the changing composition of subintimal lipid pools. To test the hypothesis that changes in lipid composition can change the mechanical properties of lipid pools, we measured the dynamic shear moduli of combinations of cholesterol monohydrate crystals, phospholipids, and triglycerides similar to those found in atherosclerotic lesions. Increasing the cholesterol monohydrate concentration from 0% to 50% increased the real component of the dynamic shear modulus (storage modulus or stiffness) by 4.5 times at a frequency of 1 Hz (P < .001). All specimens demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.1 to 3 Hz. We conclude that the stiffness of model atherosclerotic plaque lipid pools is related to the concentration of cholesterol monohydrate crystals. Because the relative concentration of cholesterol monohydrate increases during early regression of experimental atherosclerosis, the resultant stiffening of the lipid pool may reduce stresses in plaque caps. However, the magnitude of the contribution of changing lipid stiffness to the reduction of cardiac events seen in clinical studies is unclear.

Arteriosclerosis↗

PubMed1994

Dynamic nature of the aortic regurgitant orifice area during diastole in patients with chronic aortic regurgitation.

BACKGROUND: The effective aortic regurgitant orifice area varies with aortic pressure in animal models of acute aortic regurgitation. The purpose of this study was to determine whether the aortic regurgitant orifice area changes during diastole in patients with chronic aortic regurgitation. METHODS AND RESULTS: Two-dimensional and Doppler echocardiography were performed immediately before and after magnetic resonance velocity mapping using a cine phase contrast sequence in 17 patients with chronic aortic regurgitation. ECG-gated continuous-wave Doppler velocity time integrals and magnetic resonance flow rates were measured 16 times per cardiac cycle. The mean aortic regurgitant orifice area (centimeters squared) was calculated by the continuity equation. The regurgitant orifice area was also determined for each diastolic acquisition interval. Changes in the regurgitant orifice area during diastole were modeled using an asymptotic exponential decay model to determine the static and dynamic components of the orifice. The regurgitant orifice area increased directly with regurgitant fraction (y[cm2] = 0.0072[cm2/%]*x[%]-0.0409[cm2]; r = .86, P < .0001). In 15 of 17 (88%) patients, the regurgitant orifice area decreased during diastole. The dynamic component of the regurgitant orifice area decreased with increasing regurgitant fraction (y[%] = -0.98x[%]+96.9[%]; r = -.90, P < .0001). There were no significant differences in heart rate, systolic or diastolic blood pressures, or continuous-wave Doppler velocity time integrals measured before or after the magnetic resonance examination. CONCLUSIONS: The effective regurgitant orifice area decreases during diastole in patients with chronic aortic regurgitation. This phenomenon should be considered when evaluating aortic regurgitant severity.

Aortic Valve↗

PubMed1994

Birth-related upper brachial plexus injuries in infants: operative and nonoperative approaches.

Advances in intraoperative neuroelectrodiagnostic testing and microneurosurgical techniques have made it possible to accurately explore the brachial plexus of neonates. Since 1987, we have followed 250 infants with birth-related brachial plexus injuries, and successful operations have been completed on more than 70 infants. Fifty infants who underwent surgery have been followed for more than 18 months. Based on these accumulated data and historical data, this review describes both nonoperative and operative approaches to the treatment of birth-related brachial plexus injuries.

Arm↗

PubMed1994

The benefits of post-surgical orthodontic treatment.

Orthodontic therapy is best carried out in a normal skeletal and soft tissue environment. In patients requiring orthognathic surgery, it is suggested that there are advantages in correcting the skeletal and soft tissue elements as early as possible, and to orthodontically control the occlusion post-operatively. This results in a shorter overall treatment time due to more biologically favourable tooth movement, more predictable occlusal results and better management by the orthodontist. The clinical benefits of post-operative orthodontics are outlined.

Humans↗

PubMed1993

Effects of histamine type 2-receptor antagonists cimetidine and famotidine on left ventricular systolic function in chronic congestive heart failure.

Twelve patients with stable congestive heart failure and left ventricular dysfunction were enrolled in a double-blind, randomized crossover trial of famotidine, cimetidine and placebo to determine whether histamine type 2 (H2) antagonists adversely affect left ventricular systolic performance. Two-dimensional echocardiograms were obtained at baseline, after 4 days of oral treatment with standard doses of famotidine and cimetidine, and placebo, and at the conclusion of the trial. The baseline mean ejection fraction was 19 +/- 7%. The changes in ejection fraction were +2 +/- 11% (95% confidence interval [CI] -5 to 9%) with famotidine, +3 +/- 10% (95% CI -3 to 10%) with cimetidine, and -3 +/- 7% (95% CI -8 to 2%) with placebo. There were no significant differences in changes in ejection fraction among the 3 experimental treatments (p = 0.22; analysis of variance). The changes in end-systolic wall stress/volume ratios from baseline were +6 +/- 21% (95% CI -6 to 18%) for famotidine, +8 +/- 29% (95% CI -8 to 25%) for cimetidine, and +2% +/- 29% (95% CI -15 to 18%) for placebo (p = 0.69; analysis of variance). No patient had a worsening of symptoms during therapy. Despite previous reports that H2 antagonists may depress left ventricular systolic function, at standard doses these agents result in no decrease in left ventricular systolic function in patients with chronic congestive heart failure.

Aged↗

PubMed1993

Computational structural analysis based on intravascular ultrasound imaging before in vitro angioplasty: prediction of plaque fracture locations.

OBJECTIVES: This in vitro study was designed to test the hypothesis that a structural analysis based on intravascular ultrasound images of atherosclerotic vessels obtained before angioplasty can be used to predict plaque fracture locations and balloon pressures required to cause fracture. BACKGROUND: Intravascular ultrasound imaging performed before interventional procedures has potential for providing information useful for guiding therapeutic strategies. METHODS: Intravascular imaging was performed on 16 atherosclerotic human iliac vessel segments obtained freshly at autopsy; balloon angioplasty was then performed with 1-min inflations at 2 atm, increasing in 2-atm increments until fracture of the lumen surface occurred. Fracture locations were confirmed by histopathologic examination. Structural analysis of these images was performed with a large strain finite element analysis of the image that calculated the distribution of stress in the vessel with 2 atm of lumen pressure. RESULTS: Structural analysis demonstrated a total of 30 high circumferential stress regions in the vessels (mean 1.9 high stress regions/vessel). A total of 18 plaque fractures occurred in the 16 vessel segments. Of the 17 fractures that occurred in the 15 specimens with regions of high circumferential stress, 14 (82%) occurred at a high stress region (p < 0.0001). However, there was no significant relation between the peak stresses estimated by structural analysis and the ultimate balloon inflation pressure required to cause fracture. CONCLUSIONS: Structural analysis based on intravascular ultrasound imaging performed before in vitro balloon angioplasty can predict the locations of plaque fracture that usually accompany angioplasty. However, these data suggest that intravascular ultrasound may not be useful for predicting the ultimate balloon inflation pressure necessary to cause fracture, possibly because of the variable fracture properties and microscopic structure of atherosclerotic tissues.

Angioplasty, Balloon↗

PubMed1993

Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion.

Data from a non-randomised study have hinted that in patients with acute pulmonary embolism (PE), thrombolysis followed by heparin more rapidly reverses right-ventricular dysfunction and restores pulmonary tissue perfusion than does heparin alone. We have pursued this idea in a randomised protocol. 46 haemodynamically stable patients were randomised to recombinant tissue plasminogen activator (alteplase, rt-PA) 100 mg over 2 h followed by intravenous heparin and 55 to heparin alone. Right-ventricular wall motion was assessed qualitatively, and right-ventricular end diastolic area was estimated by planimetry from echocardiograms at baseline and at 3 and 24 hours. Pulmonary perfusion scans were obtained at baseline and 24 hours. In 39% of rt-PA patients but in only 17% of heparin alone patients right-ventricular wall motion at 24 hours had improved from baseline and in 2% and 17%, respectively, it worsened (p = 0.005). rt-PA patients also had a significant decrease in right-ventricular end-diastolic area during the 24 hours after randomisation and a significant absolute improvement in pulmonary perfusion (14.6% vs 1.5%). No clinical episodes of recurrent PE were noted among rt-PA patients, but there were 2 fatal and 3 non-fatal clinically suspected recurrent PEs within 14 days in patients randomised to heparin alone. rt-PA rapidly improves right-ventricular function and pulmonary perfusion among patients with PE and may lead to a lower rate of adverse clinical outcomes.

Acute Disease↗

PubMed1993

Allopurinol protects the bowel from necrosis caused by indomethacin and temporary intestinal ischemia in mice.

The present study was undertaken to evaluate if allopurinol administration protects mice from bowel necrosis caused by temporary intestinal ischemia followed by indomethacin (INDO). We have previously reported that ischemia (15-minute occlusion of superior mesenteric vessels) followed by intravenous (i.v.) INDO caused significant bowel necrosis in CD-1 mice. Ischemia or INDO alone did not cause necrosis. To investigate protective measures against necrosis, we used CD-1 mice, 25 to 30 g. Forty-four animals were gavage fed 1 mL of water for 7 days and 32 animals were gavage fed 10 mg/kg allopurinol for 7 days. On the seventh day all animals were anesthetized and the superior mesenteric vessels occluded for 15 to 20 minutes, followed by i.v. INDO (0.5 mg/kg) once daily for 3 days. Animals who died were examined for bowel necrosis and all animals were killed 7 days after surgery and necropsied. Of the 44 saline-fed animals, 12 developed bowel necrosis (27%). Of the 32 allopurinol-fed animals, 1 developed necrosis (3%). The result of Fisher's exact two-tailed test was P = .006. Pretreatment with oral allopurinol significantly protects the mice from developing bowel necrosis when the mesenteric vessels are temporarily occluded and INDO is administered. Allopurinol may prevent reperfusion injury by inhibiting formation of xanthine oxidase generated, oxygen-derived free radicals and may be valuable in pretreating premature infants with patent ductus arteriosus who have had an ischemic episode in whom INDO use is contemplated.

Allopurinol↗

PubMed1993

Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations of the beta-myosin heavy chain gene.

OBJECTIVES: The purpose of this study was to determine the spectrum of left ventricular hypertrophy and ventricular morphology in adults with hypertrophic cardiomyopathy due to mutations of the beta-myosin heavy-chain gene. BACKGROUND: Although echocardiography is an important test in diagnosing hypertrophic cardiomyopathy, the lack of an independent diagnostic criterion has been an obstacle in determining the full echocardiographic spectrum of this disease. Mutations in the beta-myosin heavy chain gene occur in approximately 50% of familial cases; in members of families with a known mutation, the diagnosis can be made with certainty. METHODS: Echocardiograms from 39 genetically affected and 30 genetically unaffected adult family members over age 16 years from 10 families were analyzed. Left ventricular wall thickness was measured at 10 separate locations, and the presence of systolic anterior motion of the mitral valve, right ventricular hypertrophy and left ventricular morphology was evaluated independently by three separate observers without knowledge of the genetic diagnosis. RESULTS: The mean maximal wall thickness in the genetically affected group was 24 +/- 8 mm (range 11 to 40), compared with 11 +/- 2 mm (range 7 to 16) in the unaffected group (p < 0.0001). Systolic anterior motion of the mitral valve or chordae tendineae with or without leaflet-septal contact was present in 62% of the affected group and in none of the unaffected group. The morphologic finding of reversed septal curvature was present in 79% of the affected group and in none of the unaffected group. Seventy-seven percent of patients in the affected group had a septal/free wall ratio > or = 1.3 compared with 6% in the unaffected group, with a septal/posterior wall ratio > or = 1.3 associated with only a 55% probability of being affected. CONCLUSIONS: The two-dimensional echocardiographic spectrum of hypertrophic cardiomyopathy in a genetically defined adult population is broad. Previous echocardiographic criteria may be too strict to diagnose the disease in some patients who are genetically affected and therefore at risk for adverse events related to the disease. Ultimately, genetic testing may supersede echocardiography in diagnosing hypertrophic cardiomyopathy.

Adolescent↗

PubMed1993

Influence of jet impingement on color Doppler parameters of aortic regurgitation.

In vitro studies have demonstrated that the characteristics of a color Doppler jet are influenced by a number of factors including jet eccentricity and jet impingement. To explore the relationship of a jet impingement and aortic regurgitant color Doppler jet parameters, jet area, width, and length were measured from apical echocardiographic views of 84 patients 4 +/- 11 days prior to catheterization and compared to angiographic grade. An impinging color jet contacted the interventricular septum or mitral valve beneath the aortic valve in the imaging plane and a nonimpinging jet did not contact the septum or mitral valve in the imaging plane. As expected, the percentage of patients with impinging jets increased with aortic regurgitation angiographic grade. Neither left ventricular chamber dimensions nor the presence of an aortic prosthesis significantly influenced the color Doppler variables. For a given angiographic grade of aortic regurgitation, impinging jets were associated with larger color Doppler jet widths (P less than 0.05) and areas (P = 0.001) than nonimpinging jets. The color Doppler area and length increased significantly with angiographic grade for nonimpinging jets (P less than 0.05) but not for impinging jets. Impinging jets are associated with larger color Doppler widths and areas than nonimpinging jets for a given grade of aortic regurgitation, possibly because of the effect of jet deflection toward an adjacent wall. Jet impinging should be considered when using color Doppler techniques to evaluate aortic regurgitation.

Aged↗

PubMed1993

Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation.

BACKGROUND: Although rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial. METHODS AND RESULTS: To test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a single stress concentration region of more than 2,250 mm Hg. In seven of 12 lethal lesions (58%), rupture occurred in the region of maximum circumferential stress; in 10 of the 12 lethal lesions (83%), rupture occurred in a region where computed stress was more than 2,250 mm Hg. CONCLUSIONS: These data suggest that concentrations of circumferential tensile stress in the atherosclerotic plaque may play an important role in plaque rupture and myocardial infarction. However, plaque rupture may not always occur at the region of highest stress, suggesting that local variations in plaque material properties contribute to plaque rupture.

Aged↗

PubMed1992

Microcalorimetric study of wheat germ agglutinin binding to N-acetylglucosamine and its oligomers.

The energetics of association of wheat germ agglutinin (WGA) with N-acetylglucosamine (GlcNAc) and its beta(1,4) oligomers have been measured using isothermal titration calorimetry. Association constants of 0.4, 5.3, 11.1, 12.3, and 19.1 mM-1 and enthalpies of binding of -6.1, -15.6, -19.4, -19.3, and -18.2 kcal mol-1 were obtained at 26 degrees C for the titration of WGA with GlcNAc, (GlcNAc)2, (GlcNAc)3, (GlcNAc)4, and (GlcNAc)5, respectively. The term T delta S was always of negative value, indicating that the binding process is enthalpically driven. Titrations of WGA performed at pH 4.5 did not differ significantly from those performed at pH 7.0, suggesting that no groups with a pKa in this range are directly involved in the binding event. Also, performing the titration in a buffer system with a higher enthalpy of protonation did not change the enthalpy of binding confirming that there is no net protonation or deprotonation when WGA binds GlcNAc residues at pH 7. A model of four independent binding sites was found to adequately describe the binding curves, except in the case of (GlcNAc)4 which exhibited positive cooperativity. The energetic values are discussed within the context of the structure of the WGA-(GlcNAc)2 complex.

Acetylglucosamine↗

PubMed1992

Ligand binding characteristics of the major mistletoe lectin.

Carbohydrate binding specificity of the galactose-specific, major lectin of mistletoe extract (ML-1) was studied by an inhibition assay using monosaccharides, monosaccharide derivatives, disaccharides, and compounds containing multiple galactosyl terminals. The results indicate that 1) both alpha- and beta-galactosyl residues are recognized equally well; 2) each of the hydroxyl groups of galactose contributes to varying degrees to the binding process, the 4-OH being the most important and the 6-OH the least important hydroxyl group; 3) disaccharide sequences of Gal beta 2Gal and Gal beta 3Gal have much higher affinity than galactose, whereas affinity of all other Gal-disaccharides is only slightly better than galactose; 4) macromolecular ligands having 10 or more terminal galactosyl residues have 500-fold higher affinity than Gal; and 5) a group on ML-1 with pK alpha of 4.8 appears to be involved in the binding of ligand.

Binding Sites↗

PubMed1992

Multivalent ligand binding by serum mannose-binding protein.

The serum-type mannose-binding protein (MBP) is a defense molecule that has carbohydrate-dependent bactericidal effects. It shares with mammalian and chicken hepatic lectins similarity in the primary structure of the carbohydrate-recognition domain, as well as the ligand-binding mode: a high affinity (KD approximately nM) is generated by clustering of approximately 30 terminal target sugar residues on a macromolecule, such as bovine serum albumin, although the individual monosaccharides have low affinity (KD 0.1-1 mM). On the other hand, MBP does not manifest any significant affinity enhancement toward small, di- and trivalent ligands, in contrast to the hepatic lectins whose affinity toward divalent ligands of comparable structures increased from 100- to 1000-fold. Such differences may be explained on the basis of different subunit organization between the hepatic lectins and MBP.

Acute-Phase Proteins↗

PubMed1992

Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.

A human cDNA encoding a galactokinase (EC 2.7.1.6) was isolated by complementation of a galactokinase-deficient (gal1-) strain of Saccharomyces cerevisiae. This cDNA encodes a predicted protein of 458 amino acids with 29% identity to galactokinase of Saccharomyces carlsbergensis. Previous studies have mapped a human galactokinase gene (GK1) to chromosome 17q23-25, closely linked to thymidine kinase. The galactokinase gene that we have isolated (GK2) is located on chromosome 15. The relationship between the disease locus for galactokinase deficiency galactosemia, which is responsible for cataracts in newborns and possibly presenile cataracts in adults, and the two galactokinase loci is unknown.

Amino Acid Sequence↗

PubMed1992

Relation between Doppler color flow variables and invasively determined jet variables in patients with aortic regurgitation.

OBJECTIVES: The purpose of this study was to test the hypothesis that invasively derived jet variables including regurgitant orifice area and momentum determine the characteristics of Doppler color flow jets in patients with aortic regurgitation. BACKGROUND: In vitro studies have demonstrated that the velocity distribution of a regurgitant jet is best characterized by the momentum of the jet, which incorporates orifice area and velocity of flow through the orifice. METHODS: Peak jet momentum, peak flow rate and regurgitant orifice area were determined with intraaortic Doppler catheter and cardiac catheterization techniques in 22 patients with chronic aortic regurgitation. These invasively derived variables were compared with apical and parasternal long-axis Doppler color echocardiographic variables obtained in the catheterization laboratory. RESULTS: Jet momentum increased significantly with the angiographic grade of regurgitation. The apical color jet area of aortic regurgitation increased linearly with jet momentum and regurgitant orifice area in vivo, but the correlations were only moderately good (r = 0.63 and 0.65, respectively). Color jet length also increased linearly with jet momentum and with regurgitant orifice area. There was only a trend for Doppler color jet width to increase with all invasively derived jet variables. CONCLUSIONS: Whereas jet area by Doppler color flow imaging is directly related to both orifice area and jet momentum in vivo, Doppler color variables measured in planes normal to the orifice do not correlate well enough with either jet momentum or regurgitant orifice area to predict jet flow variables in patients with aortic regurgitation. It is likely that the important influence of adjacent boundaries will limit the use of the velocity distribution of aortic regurgitant jets for determining the severity of disease.

Aortic Valve Insufficiency↗