Temperature and pressure dependence of the luminescence of Eu(2+)-doped fluoride crystals Ba(x)Sr(1-x)F(2) (x = 0, 0.3, 0.5 and 1): experiment and model.

This paper summarizes experimental evidence of anomalous luminescence in Eu(2+)-doped fluoride crystals Ba(x)Sr(1-x)F(2) (x = 0, 0.3, 0.5 and 1). Luminescence, luminescence excitation spectra and luminescence kinetics obtained at ambient and high hydrostatic pressure at various temperatures are discussed. Hydrostatic pressure was shown to cause a redshift of normal [Formula: see text] emission and anomalous luminescence. The experimental data shows the existence of temperature- and pressure-induced spectral transformations where the anomalous luminescence is replaced by normal emission of Eu(2+) centers. We present a model that predicts a strong electron-lattice coupling of the trapped excitons as well as the pressure effect of the spectral transformation from anomalous to normal emission.

Contra-directional two-beam coupling by use of a single input beam in an iron-doped lithium niobate multimode fiber.

Experimental results are presented for 1,800 contra-directional two-beam coupling (TBC) measurements in a single crystal fiber of LiNbO8:Fe using a single incident beam and its Fresnel reflection off the back surface of the fiber. To our knowledge, this is the first time that volume gratings have been written in a fiber using this beam coupling geometry. At small f-numbers, the TBC efficiency has been predicted to decrease in bulk LiNbO3:Fe due to the erasure of the weak gratings by the dark conductivity. We present experimental results validating the published theory and show experimentally that confinement of the interfering beams in a fiber geometry overcomes this limitation.

Genetics of allergic disease: evidence for organ-specific susceptibility genes.

BACKGROUND: While previous studies have probed the genetics of asthma and serum IgE levels, there have been no studies on the genetics of allergic conjunctivitis. This paper describes the initial phase of a genetic study of allergic conjunctivitis. METHODS: Approximately 117 families with probands with allergic conjunctivitis were recruited generating 245 affected sib pairs. Each family member completed a detailed questionnaire on atopic symptoms, and results from skin testing were obtained. Genomic DNA was extracted and genotyped using thirty-five polymorphic markers spanning human chromosomes 5, 6, 11, 12, 16 and 17. Heritability was assessed using the POINTER program, and nonparametric linkage analysis using the BETA program. RESULTS: Evidence for genetic linkage of allergic conjunctivitis was obtained for chromosomes 5, 16 and 17. Weak linkage was detected for chromosome 6 when studies were restricted to specific allergens. No evidence for linkage was detected for chromosomes 11 and 12. CONCLUSIONS: Consistent with heritability analysis discussed in this paper, genetic linkage for allergic conjunctivitis is shown to differ from that reported for atopic asthma. This indicates that there are likely to be organ-specific disease susceptibility genes, which together with general atopy genes target the allergic response to specific mucosal tissues.

Lack of lung hemorrhage in humans after intraoperative transesophageal echocardiography with ultrasound exposure conditions similar to those causing lung hemorrhage in laboratory animals.

This study investigated the phenomenon of ultrasonically induced lung hemorrhage in humans. Multiple experimental laboratories have shown that diagnostic ultrasound exposure can cause hemorrhage in the lungs of laboratory animals. The left lung of 50 patients (6 women, 44 men, mean age 61 years) was observed directly by the surgeon after routine intraoperative transesophageal echocardiography was performed. From manufacturer specifications the maximum derated intensity in the sound field of the system used was 186 W/cm2, the maximum derated rarefactional acoustic pressure was 2.4 MPa, and the maximum mechanical index was 1.3. The lowest frequency used was 3.5 MHz. This exposure exceeds the threshold found for surface lung hemorrhage seen on gross observation of laboratory animals. No hemorrhage was noted on any lung surface by the surgeon on gross observation. We conclude that clinical transesophageal echocardiography, even at field levels a little greater than the reported thresholds for lung hemorrhage in laboratory animals, did not cause surface lung hemorrhage apparent on gross observation. These negative results support the conclusion that the human lung is not markedly more sensitive to ultrasound exposure than that of other mammals.

Effect of acoustic cavitation on platelets in the presence of an echo-contrast agent.

A suspension of human platelets in autologous plasma or buffer solution with and without a microbubble echo-contrast agent was exposed in vitro to 730 W/cm2 (ISPPA) ultrasound pulses of duration 40-160 microseconds at 1 MHz and 20-Hz pulse repetition frequency. Inertial cavitation occurring within the samples was monitored during the exposures and a measure of average cavitational activity was calculated for each 5-min exposure. This quantity, with the other acoustic parameters, accounted for up to 75% of the variation in the destruction of platelets as measured by Coulter counter and 83.5% of the release of bound radiolabel using a multiple-interaction statistical model. When the echo-contrast agent was absent, negligible cavitation occurred and the amount of platelet destruction was statistically indistinguishable from sham (no-ultrasound) exposures. Therefore, microbubble echo-contrast agents may interact with ultrasound to cause platelet lysis through the mechanism of inertial cavitation.

Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study.

OBJECTIVES: The CarboMedics, Duromedics, Sorin Bicarbon and the St. Jude Medical valves are bileaflet mechanical prostheses of modern but different design. Choosing a valve with the best hemodynamic profile is of clinical importance in patients with small ventricles and a small mitral annulus. METHODS: The hemodynamic performance of these valves in the mitral position was compared in 76 asymptomatic, ambulatory patients with normally functioning prosthesis and left ventricle, using Doppler echocardiography. Of the 76 patients studied, 22 had the CarboMedics, 16 had the Duromedics, 17 had the Sorin Bicarbon and 21 had the St. Jude prosthesis. The patients ages ranged from 18 to 81 years. There were 44 women and 32 men. The time from implantation to echocardiographic study ranged from 1 to 55 months. RESULTS: The echocardiographic study was performed earlier after surgery in the Sorin Bicarbon group. There was no significant difference in women/man ratio, incidence of atrial fibrillation, left ventricular or left atrial diameters between the four groups. The mean prosthesis size was significantly smaller for Sorin Bicarbon and Duromedics valves compared to the CarboMedics and the St. Jude valves (mean+/-SD, 27.2+/-1.3, 27.1+/-1.1 and 30.0+/-1.9 and 30.0+/-2.7 mm, respectively, P<0.001). Despite its smaller size the Sorin Bicarbon valve had significantly larger effective valve area by Doppler compared to the CarboMedics valve (290+/-40 vs 250+/-60 mm2, respectively, P=0.014). The ratio of effective valve area to prosthesis size was significantly larger for the Sorin Bicarbon valve when compared with any other type of prosthesis. CONCLUSIONS: (1) The Sorin Bicarbon bileaflet valve offered the best hemodynamic results that may be explained by the valve's large leaflet opening angle and small thickness of the leaflets. (2) Since the Sorin Bicarbon is the newest bileaflet valve, durability of this valve remains uncertain.

Correlation of ultrasound-induced hemolysis with cavitation detector output in vitro.

A 20-MHz passive acoustic detector was used to quantify the amount of transient acoustic cavitation occurring in a sample exposed to intense pulsed ultrasound. A dilute suspension of human erythrocytes with and without a microbubble echo-contrast agent was exposed in vitro to 500 W/cm2 (SPPA) ultrasound of center frequency 1 MHz and tone burst duration 20, 100, 200, 500 and 1000 microseconds at a pulse repetition frequency of 20 Hz. Inertial cavitation occurring within the sample, as measured by the temporal average of the detector output, correlated well with hemolysis, suggesting that violent bubble collapse is responsible for cell damage. The result also raises the prospect of cavitation monitoring as a possible predictor of adverse bioeffects when echo-contrast agents are used clinically.

Hemolysis in vivo from exposure to pulsed ultrasound.

Ultrasonically induced hemolysis in vivo when a commercial ultrasound contrast agent, Albunex, was present in the blood. Murine hearts were exposed for 5 min at either 1.15 or 2.35 MHz with a pulse length of 10 microseconds and pulse repetition frequency of 100 Hz. During the exposure period, four boluses of Albunex were injected into a tail vein for a total of approximately 0.1 mL of Albunex. Following exposure, blood was collected by heart puncture and centrifuged, and the plasma was analyzed for hemoglobin concentration. With Albunex present in the blood, the threshold for hemolysis at 1.15 MHz was 3.0 +/- 0.8 MPa (mean +/- SD) peak positive pressure (approximately 1.9 MPa negative pressure, approximately 180 W cm-2 pulse average intensity). For the highest exposure levels (10 MPa peak positive pressure at the surface of the animal), the mean value for hemolysis was approximately 4% at 1.15 MHz and 0.46% at 2.35 MHz, i.e., the threshold at 2.35 MHz is > 10 MPa peak positive pressure. In contrast, hemolysis in control mice receiving saline injections at 10 MPa or sham-exposed (0 MPa) mice receiving Albunex was approximately 0.4%.

Albunex Does Not Increase the Sensitivity of the Lung to Pulsed Ultrasound.

If cavitation in the vasculature of the lung is the physical mechanism responsible for lung hemorrhage, then addition of cavitation nuclei to the blood should enhance the bioeffect. To test the cavitation hypothesis, the extent of lung hemorrhage in mice injected with the echocontrast agent, Albunex(R), was compared to lung hemorrhage in animals injected with saline. Animals were exposed for 5 minutes to 1.1-MHz pulsed ultrasound (10 µs pulse length, 100-Hz pulse repetition frequency) at a peak positive pressure at the surface of the animal of 2 MPa. This exposure is approximately twice the threshold pressure amplitude for lung hemorrhage. Lesion areas did not differ significantly in the two groups of animals and were approximately equal to the lesion area in uninjected mice from an earlier study where acoustic exposures were the same. Neither this study nor a related study of hemolysis in vivo suggests that use of Albunex in echocardiographic procedures increases the risk of bioeffects.

Effect of static pressure on acoustic transmittance of Albunex microbubble suspensions.

Albunex (ALX), an albumin-stabilized microbubble echo contrast agent, is sensitive to pressures similar to those produced by the heart. The tested hypothesis was that the acoustic transmittance of ALX suspensions will increase with increasing hydrostatic pressure (Ps). The test involved an acoustic setup analogous to a spectrophotometer. The acoustic transmittance of microbubble suspensions was strongly Ps dependent. Transmittance at 1 MHz was essentially zero at ambient pressure, increasing to approximately 50%, approximately 63%, and nearly 100% at Ps of 80, 120, and 400 mm Hg, respectively. The ultrasound pulses used to interrogate samples were without measurable effect on the acoustic transmittance of suspensions maintained at ambient pressure during experimental measurements. The data indicate that many of the microbubbles are destroyed at Ps comparable to those produced by the heart.

Food and Drug Administration ultrasound device regulation: the output display standard, the "mechanical index," and ultrasound safety.

The Food and Drug Administration has recently revised its guidelines regarding acoustic output on diagnostic ultrasound equipment to allow a new track for manufacturers to achieve approval to market diagnostic ultrasound equipment. It would move for the first time toward regulating instrumental output based on scientific bioeffect data. It would allow increased instrumental output in certain modes and at the same time mandate on-screen labeling of a "thermal index" or "mechanical index," coupled with a user education program on the significance of these indexes. The increased instrumental output allowed by these new guidelines may benefit adult echocardiography by allowing slightly more penetration and higher frequency/better resolution. However, a tradeoff is that echocardiographers need to understand more about how to perform an examination to decrease unnecessary patient exposure to ultrasound and more about ultrasound bioeffects, such as the theoretical potential for cavitation-related adverse effects in certain circumstances.

Effect of pressure on echocardiographic videodensity from sonicated albumin: an in vitro model.

The effect of different pressures (0, 10, 30, 60, 80, 100, 120, or 180 mm Hg) on the ultrasound contrast effect obtained from sonicated albumin was evaluated by videodensity decay curves in an in vitro model immersed in a water tank. Decay rates and half-times were calculated from the videodensity decay curves at each pressure. A significant (P < 0.0001) relation was found between contrast disappearance and pressure: the higher the pressure the more rapid the contrast disappearance. Release of pressure did not result in contrast reappearance. Contrast decrease with pressure may result from microbubble destruction or alteration in acoustic properties by pressure. These findings may help explain the limited success of sonicated albumin for systemic ultrasonographic arteriography and myocardial perfusion imaging after intravenous injection. An ideal contrast agent for contrast echo studies should be stable at physiologic pressures.

Digital subtraction myocardial contrast echocardiography: design and application of a new analysis program for myocardial perfusion imaging.

Myocardial contrast echocardiography may provide important physiologic information on myocardial perfusion. Most current analysis programs use manual frame grabbing and selecting of the area of interest. This is time-consuming and not highly reproducible. A system for automatic analysis of myocardial contrast echocardiographic studies was developed and evaluated. The program acquires an electrocardiographically gated sequence of end-diastolic images with a frame grabber in a personal computer. The baseline image is subtracted and the videodensity versus time contrast curve parameters are calculated on-line. Fast color-coded analysis is done automatically with a running square window that covers the entire image. A second mode of contrast analysis allows manual selection of multiple regions of interest. The program was evaluated with contrast echo data from open-chest dogs and two demonstrative patients. This myocardial contrast analytic package is an inexpensive, rapid, flexible, convenient, and reproducible on-line method that facilitates myocardial contrast echocardiographic analysis.

Ultrasound accelerates urokinase-induced thrombolysis and reperfusion.

We have shown that ultrasound accelerates TPA-induced thrombolysis in vitro as assessed by release of labeled fibrinogen from radioactive labeled clots. Others have shown that ultrasound shortens the time to recanalization of TPA treated thrombi in animal models. The aim of this study was to test the hypothesis that ultrasound enhances thrombolysis and reperfusion by using urokinase in an in vitro flow system. An in vitro flow system of a branching tubing circuit was developed. Flow in one branch was obstructed by a thrombus. Five control clots were exposed to continuous wave ultrasound at a frequency of 1 MHz and intensity of 2.5 W/cm2 only without any thrombolytic agent (group 1). Twenty clots were exposed to a bolus of 80,000 U of urokinase and randomized to either ultrasound exposure (group 2) or to urokinase only without ultrasound (group 3). Flow distal to the clot and the rate of release of radiolabeled fibrin were used as indexes of reperfusion and thrombolysis, respectively. Exposure to ultrasound significantly accelerated urokinase-mediated reperfusion, with 40.6% +/- 11.8% of maximal flow in group 2 versus 1.3% +/- 0.7% in group 3, p < 0.0015 after 25 min. The maximal difference in flow between groups 2 and 3 was achieved at 40 minutes (67.4% +/- 11.1% vs 13.1% +/- 5.6%, p < 0.0009). Thrombolysis was significantly higher after 25 minutes of ultrasound exposure (24.1% +/- 4.6% in the ultrasound-treated group vs 9.7% +/- 3.5% in group 3, p < 0.013). The maximal difference in thrombolysis between groups 2 and 3 was 60 minutes. (52.5% +/- 5.1% vs 18.7% +/- 6.2%, p < 0.00015).(ABSTRACT TRUNCATED AT 250 WORDS)

Right-sided valvular pathology and rheumatic fever.

This paper discusses some of the recent advances in the evaluation and treatment of right-sided cardiac pathology, and reviews the more general subject of rheumatic fever, with particular emphasis on diagnosis and possible genetic influences. A comprehensive assessment of these topics is not intended; rather, interesting features and recently published long-term outcome data of more common right heart abnormalities are summarized.

Does external ultrasound accelerate thrombolysis? Results from a rabbit model.

BACKGROUND: Prior in vitro and in vivo studies have reported that external ultrasound accelerates thrombolysis at intensities too low to have a direct effect on clot dissolution in the absence of a thrombolytic agent. The present study was undertaken to examine the ultrasound effect on thrombolysis and reocclusion in a rabbit thrombosis model. METHODS AND RESULTS: Blood clots were produced in a femoral artery segment with endothelial damage and distal stenosis. Recombinant tissue-type plasminogen activator (rTPA) was infused at 30 micrograms.kg-1.min-1 for 60 minutes. Femoral artery flow was measured every 5 minutes for 2 hours. Rabbits were randomized to four groups with continuous wave ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin (+US/-US/+Asp/-Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2. In seven of eight and five of five rabbits given rTPA and -US/-Asp or -US/+Asp, respectively, reflow was observed, persisting to the end of the observation period. In five of nine and four of five rabbits given rTPA and +US/-Asp or +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently observed in five of five and two of four of these rabbits, respectively. Overall, femoral artery patency was worse and reocclusion occurred more often when ultrasound was added to rTPA (P = .002 by nonparametric ANOVA). However, initial reflow occurred more rapidly with ultrasound exposure (21 +/- 10 and 33 +/- 6 minutes for the +US/+Asp and +US/-Asp groups, respectively) compared with without ultrasound (46 +/- 13 and 74 +/- 14 minutes for the -US/+Asp and -US/-Asp groups, respectively) (P = .03 by ANOVA). CONCLUSIONS: Although time to initial reflow was shortened by ultrasound, it was associated with less reperfusion and more reocclusion in this model. A possible explanation for these results is ultrasound-induced platelet activation counterbalancing its thrombolysis-accelerating effect.

Quantitative myocardial ultrasonic integrated backscatter measurements during contrast injections.

We and others have shown that normal myocardium exhibits 4 to 5 dB diastolic-to-systolic cyclic variation (CV) of integrated backscatter. To investigate the effect of intramyocardial contrast on integrated backscatter, we injected 5% sonicated albumin, containing microbubbles in the range of 5 microns in diameter, into the left atrium in nine open-chest dogs. The dogs were anesthetized and placed in the right lateral decubitus position on a specially designed table with a cutout allowing ultrasound imaging from below. Ultrasonic data was obtained from the right precordium by use of a prototype M-mode integrated backscatter system implemented in a commercially available two-dimensional system. Usable data were obtained in eight of nine dogs. Integrated backscatter increased up to 13 dB after contrast injections. There was a significantly decreased CV of integrated backscatter during myocardial contrast in all eight dogs. The mean level of CV of integrated backscatter for the eight dogs decreased from 4.7 dB (530 beats analyzed) without contrast to 2.8 dB during contrast (436 beats analyzed). There was a trend to greater CV at higher levels of contrast. Septal excursion, as measured by M-mode echocardiography simultaneously with integrated backscatter by the same ultrasound beam, was similar with and without contrast (mean 8.2 vs 8.3 mm). Thus left atrium contrast injection produces quantitatively measurable integrated backscatter effects. Cyclic variation of integrated backscatter decreases with contrast. However, at higher contrast levels the decrease tends to be smaller. These effects should be considered during quantitative tissue characterization and myocardial contrast studies.

Feasibility of recanalization of human coronary arteries using high-intensity ultrasound.

To investigate the feasibility of ultrasonic recanalization of obstructed human coronary arteries in vitro, high-intensity ultrasound was applied to 16 coronary arteries obtained at autopsy, using a prototype instrument enabling insonification through a catheter tip. It was a 119 cm long, 0.95 mm thick wire in an 8Fr catheter connected to an external ultrasonic transformer and power generator. A 5 MHz phased-array 2-dimensional echocardiography instrument was used to determine minimal luminal diameter and percent diameter narrowing before and after ultrasound application. The ultrasonic energy was delivered at 21.5 kHz and with a 52 +/- 19 micrometer average amplitude of tip displacement. The mean percent luminal diameter narrowing, flow rate and mean pressure gradient before ultrasound exposure were 74 +/- 11%, 97 +/- 61 ml/min, and 92 +/- 18 mm Hg, respectively. After recanalization, the mean percent luminal diameter narrowing decreased to 45 +/- 17% (p < 0.001), the mean flow rate increased to 84 +/- 92 ml/min (p < 0.001), and the mean pressure gradient was reduced to 45 +/- 24 mm Hg (p < 0.001). Of the debris particles, 95% had a diameter < 9 microns (range 5 to 12). Arterial perforation occurred in 5 of 16 arteries (31%) and all 5 occurred due to stiff wire manipulation and without ultrasound application. Mechanical fracture of the wire occurred in 8 cases (50%). No signs of thermal injury were found on histology. Thus, ultrasonic recanalization of human coronary arteries in vitro is feasible. It may reduce obstruction and improve blood flow. Debris sizes are sufficiently small to minimize the hazard of peripheral embolization.

Transthoracic and transesophageal echocardiographic sizing of the aortic annulus to determine prosthesis size.

To assess the accuracy of 2-dimensional echocardiography versus transesophageal echocardiography (TEE) in predicting aortic annulus diameter, and to determine which part of the cardiac cycle should be used for measuring the size of the aortic valve prosthesis in patients undergoing aortic valve replacement, the aortic annulus was measured retrospectively in a blinded fashion in a group of 94 patients who had undergone aortic valve replacement: 66 had preoperative transthoracic echocardiography (TTE), 69 had intraoperative TEE, and 41 had both. Accuracy of measurements was calculated by the mean biases (differences between annular size by echo and actual valve size chosen by intraoperative mechanical sizing of the aortic annulus). TTE was compared with TEE and end-diastolic (ED) measurements with end-systolic (ES) measurements. The mean biases +/- SD were -1.7 +/- 3.4 mm by TTE-ES versus -0.9 +/- 3.5 mm by TEE-ES measurements (p = NS), and +0.03 +/- 3 mm by TTE-ED versus +0.5 +/- 2.8 mm by TEE-ED (p = NS). Examination of the magnitudes of the biases gave the same result. ED measurements were found to have a smaller amount of bias than ES measurements, both by TTE and by TEE: -1.7 +/- 3.4 mm by TTE-ES versus +0.03 +/- 3 mm by TTE-ED (p = 0.0001) and -0.9 +/- 3.5 mm by TEE-ES versus +0.5 +/- 2.8 mm by TEE-ED (p = 0.0001). Examination of the magnitudes of the biases also gave the same result.(ABSTRACT TRUNCATED AT 250 WORDS)