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Biomedical subjects

J G Miller

Publications and source records attributed to J G Miller.

At least 145 records · Page 8Linked to original sources

Applicability of ultrasonic tissue characterization for longitudinal assessment and differentiation of calcification and fibrosis in cardiomyopathy.

Progress in tissue characterization of myocardium with ultrasound suggests that quantitative recognition of ischemic or scarred tissue will be achieved. Despite the increasing recognition and importance of cardiomyopathy, its diagnosis generally requires invasive procedures such as cardiac catheterization and biopsy. To investigate methods that permit the characterization of longitudinal cardiomyopathic changes that might ultimately be extended for noninvasive studies in patients, quantitative ultrasonic methods were utilized for in vitro tissue characterization of hearts from Syrian hamsters of selected age of either 2 to 3 or 5 to 7 months. Normal hamsters were used as controls. Myocardial sites (n = 600) from the young Syrian hamsters exhibited values (+/- standard error) of integrated ultrasonic backscatter averaging -53.87 +/- 0.26 dB, which were significantly different from values (n = 500) in age-matched control hamsters (-58.07 +/- 0.08 dB; p less than 0.001). Cardiomyopathic hearts from older animals exhibited backscatter values (n = 500 sites) averaging -50.87 +/- 0.22 dB, again significantly different from values (n = 300 sites) in age-matched control hamsters (-55.91 +/- 0.11 dB; p less than 0.001). In addition, ultrasonic attenuation was significantly different for hearts from the control and cardiomyopathic hamsters of both age ranges. The results correlated with sequential calcification and fibrosis characteristics assessed histopathologically. This study indicates that quantitative characterization of myocardium with ultrasound may permit longitudinal assessment of cardiomyopathic changes in diverse disease entities and their response to therapy.

Age Factors↗

Culture and development of everyday social explanation.

The impact of cultural meaning systems on the development of everyday social explanation is explored in a cross-cultural investigation undertaken among Indian and American adults and children (ages 8, 11, and 15 year). It is demonstrated that at older ages Americans make greater reference to general dispositions and less reference to contextual factors in explanation than do Hindus . References to general dispositions also undergo a much greater developmental increase among Americans than among Hindus , whereas references to contextual factors show the opposite pattern of developmental change. Evidence suggests that these cross-cultural and developmental differences result from contrasting cultural conceptions of the person acquired over development in the two cultures rather than from cognitive., experiential, or informational differences between attributors . Discussion focuses on theoretical implications of such a demonstration for understanding: (a) the importance of integrating semantic with structural considerations in theories of social attribution, (b) the need to develop nonteleological frameworks for interpreting age and cultural diversity in conceptualization, and (c) the role of cultural communication in the acquisition of everyday social knowledge.

Adolescent↗

Regional differences in the cyclic variation of myocardial backscatter that parallel regional differences in contractile performance.

Previous reports from our laboratory indicate that ultrasonic backscatter from myocardium exhibits a cyclic variation during the cardiac cycle that is reduced sharply by ischemia, a process which impairs both systolic contraction and diastolic relaxation. These results suggest that the cyclic variation of backscatter may be related to the cyclic variation of the contractile performance of the myocardium. Because contractile performance of the left ventricle is known to exhibit regional variability, the present study was undertaken to determine whether such regional differences in contractile performance are paralleled by differences in the magnitude of the cyclic variation of ultrasonic backscatter. Measurements obtained from representative zones of three regions of the hearts of ten open-chest dogs indicate that the magnitude of the cyclic pattern of variation of backscatter parallels the regional differences in contractile performance throughout the left ventricle with the maximum variation (5.5 +/- 0.9 dB peak-to-peak amplitude) occurring at the apex, intermediate values (4.3 +/- 0.8 dB) at the midwall, and minimum (0.5 +/- 1.0 dB) at the base. These results suggest that the ultrasonic backscatter may be sensitive to the regional myocardial contractile performance.

Animals↗

Effects of myocardial contraction on ultrasonic backscatter before and after ischemia.

To determine whether contraction and relaxation influence quantitative myocardial ultrasonic backscatter we measured systolic and diastolic integrated backscatter separately in 10 pentobarbital-anesthetized dogs with defined, paced heart rates, before and after coronary occlusion. Data were acquired from intramural sites by coupling a broadband 5-MHz transducer to the left ventricular epicardium. Integrated backscatter was obtained from seven sequential ECG gated intervals throughout the cardiac cycle over the frequencies of 2.5-7.5 MHz and referenced to values obtained with a steel reflector. Before coronary occlusion myocardium in all dogs exhibited a decrease in integrated backscatter from end diastole to end systole (P less than 0.05) in control zones and in zones destined to become ischemic (P less than 0.05). Thirty minutes after occlusion integrated backscatter did not change in control zones but was elevated in ischemic zones with blunting of the diastolic-to-systolic variation. Thus myocardium undergoing contraction exhibits a decrease in integrated backscatter, and measurement of integrated backscatter at end systole differentiates ischemic from normal myocardium.

Analysis of Variance↗

Attenuation estimation in reflection: progress and prospects.

This monograph presents a tutorial review of the current state-of-the-art in ultrasonic attenuation estimation in reflection. Clinical indications which provide the motivation for attempting in vivo attenuation estimation are discussed. Frequency and time domain techniques and their respective tradeoffs and problems are presented. Finally, current clinical results obtained with the various techniques are summarized and further areas of study are suggested.

Female↗

Properties of amino acid transport in preimplantation rabbit embryos.

The kinetics, specificity, time dependency, Na+ dependency, and exchange behavior of the uptake of methionine, as a model for the uptake of the neutral amino acids, was investigated in rabbit eggs, morulae, and 6-day blastocysts. Uptake by the blastocyst was physically resolved into components representing uptake into the cellular and cavity compartments. The kinetic data for all material, except the cellular compartment of the blastocyst, could be described mathematically by the parallel activity of a saturable and a linear transport system. The Km decreased from 91 microM in the unfertilized egg to 38 microM in the fertilized egg to 13 microM in the 69-hr morula. The Km of uptake into blastocysts was 131 microM. The Vmax of uptake into the whole blastocyst was calculated to be about 5000 times that of uptake into the egg. Competition of methionine uptake by other amino acids indicated that the egg had somewhat more "L-like" transport specificity than subsequent developmental stages, while the system(s) in the blastocyst were reactive with most neutral amino acids. Uptake into the egg, 69-hr morula, and the cellular compartment of the blastocyst reached a steady state with time, in contrast to uptake into the 76-hr morula and the cavity compartment of the blastocyst. Compatible with this, was the observation that eggs and 69-hr morula, but not blastocysts, exhibited considerable efflux into amino acid-containing media. The cavity compartment of the blastocyst may, however, act as a reservoir of amino acids for the cellular compartment. The Na+ dependency of transport was unchanged throughout the developmental period studied in this investigation.

Animals↗

Disordered thinking in schizophrenia: intermingling and loss of set.

In a study of schizophrenic thought pathology, potential loss of set and intermingling were examined. The responses of 36 acute psychiatric patients who showed intermingling were analyzed. Intermingling, frequently seen in the speech and thinking of schizophrenic patients, involves the blending of personal material from one's experiences into one's thinking and communication, leading to bizarre and inappropriate speech. The results indicated that intermingling frequently leads to some loss of goal-directed thinking, but not usually to complete loss of set. Patients adopt new sets based partly on the original topic and partly on their own personal idiosyncratic concerns. The apparent "looseness" of schizophrenic patients is based on thematic shifts to idiosyncratic ideas, often from the beginning of their responses, rather than on word-to-word associative looseness. Intermingling of personal concerns typically occurs in a nonfragmented fashion. Schizophrenics and other psychotic patients show significantly more intermingling of personal material in open and undisguised fashion, as though they do not recognize how inappropriate their intermingling appears. The results suggest that although the intrusion of personal material is task inappropriate, it still represents a form of systematic, goal-oriented thinking.

Adult↗

Changes in myocardial backscatter throughout the cardiac cycle.

This investigation was performed to identify and quantify systematic variations of myocardial ultrasonic backscatter throughout the cardiac cycle. Using a broadband 5 MHz focused transducer coupled to the epicardial surface of the left ventricle in dogs, backscatter measurements were obtained from each of 7 intervals (windows) of 34 milliseconds duration evenly distributed throughout the cardiac cycle and referenced to backscatter from a steel reflector. Values of integrated backscatter obtained demonstrated a consistent and reproducible pattern throughout the cardiac cycle characterized by elevated values at end-diastole and significantly lower values at end-systole. The average maximum difference was 3.5 dB.

Animals↗

Cardiac ultrasonic tissue characterization.

This new variation on an old technique can actually define the physical state of a tissue--not merely visualize its size and motion. Clinical use awaits technologic refinements, but potential applications include noninvasive detection of amyloid protein, of myofibrillar disorientation characteristic of idiopathic hypertrophic subaortic stenosis, and of various kinds of vascular pathology.

Animals↗

Detection of cardiomyopathic changes induced by doxorubicin based on quantitative analysis of ultrasonic backscatter.

Ultrasonic measurements are valuable in characterizing cardiac dimensions and structure. Recently, analysis of ultrasonic properties of tissue has proved useful in detecting morphologic changes such as those accompanying myocardial infarction. This study was undertaken to determine whether acoustic properties of tissue can be utilized to detect cardiomyopathic changes as well. Cardiomyopathy was induced by prolonged administration of doxorubicin (Adriamycin) (1.2 mg/kg twice weekly) in 25 rabbits and results were compared with those in normal control rabbits, housed identically. The 15 surviving treated animals were killed at selected intervals to 10 to 18 weeks after initiation of drug administration and the hearts were analyzed for collagen content based on hydroxyproline. Regional ultrasonic backscatter was assessed with a frequency-averaging procedure to minimize effects of phase cancellation and with an independent method employing spectral display over the frequency range of 1 to 11 megahertz from which an index of backscatter at a single frequency (2.25 megahertz) could be calculated. In hearts from treated animals, collagen content was significantly increased (p less than 0.05). Integrated ultrasonic backscatter was markedly increased (by more than 500 percent, that is, equivalent to 7 decibels) in fibrotic regions and significantly, although less markedly, in myopathic regions without marked collagen deposition. Thus, increased backscatter correlated with collagen deposition. Backscatter at 2.25 megahertz was significantly increased (by more than 500 percent, that is, equivalent to 7 decibels) in fibrotic regions. These results indicate that alterations in acoustic properties occur in cardiomyopathic tissue and that such alterations can be detected with the use of reflected ultrasound. Accordingly, assessment of integrated backscatter offers a promising approach for early clinical detection and characterization of evolution of cardiomyopathy induced by doxorubicin or of other causes.

Animals↗

Relationship between collagen and ultrasonic backscatter in myocardial tissue.

The relationship between ultrasonic backscatter and collagen concentration estimated on the basis of hydroxyproline concentration was examined in hearts from normal dogs and in hearts from dogs subjected to ischemic injury by coronary occlusion as an approach toward elucidating the physical mechanisms underlying the scattering of ultrasound by soft tissue. Ultrasonic backscatter was found to increase significantly in regions of ischemic injury studied 5--17 weeks following occlusion. The average backscatter coefficient was six time larger in regions of infarct studied 8--10 weeks after occlusion than that in regions of infarct studied 5--6 weeks after occlusion. In contrast, the average hydroxyproline concentration, a quantitative index of molecular collagen content, for regions of infarct was only about 25% larger at 8--10 weeks compared with that at 5--6 weeks after occlusion. These results may suggest that the magnitude of ultrasonic scattering in regions of remote myocardial infarct is sensitive not only to the concentration of molecular collagen but also to the organizational state of this structural protein. In addition, the results of this study may indicate that scattering represents a small fraction of the total attenuation coefficient in a biological system exhibiting either low collagen concentration (normal myocardium) or significant collagen concentration (scarred myocardium).

Animals↗

Effects of myocardial ischemia on quantitative ultrasonic backscatter and identification of responsible determinants.

Quantitative characterization of myocardial properties represent a rapidly emerging area of echocardiographic investigation. Because measurement of the ultrasonic integrated backscatter is theoretically applicable to analysis in vivo with reflected ultrasound, this study was performed to develop and evaluate a suitable method for measurement of quantitative backscatter in vivo. In view of the desirability of characterizing ischemic myocardium noninvasively, the study was performed with animal preparations simulating myocardial ischemia in humans. In one series of open-chest dogs, integrated backscatter among 22 ischemic regions was increased by 200% (P less than 0.01) compared to values in control regions within 1 hour after coronary occlusion and by 400% (-45.1 +/- 0.7 dB compared to -50.9 +/- 0.4 dB) (P less than 0.001) within 6 hours. In a second series of open-chest dogs, ischemia was quantified with 141Ce microspheres, and mean integrated backscatter was found to increase (280% of control) (P less than 0.01) in regions with flow less than 20% of control 2 hours following coronary occlusion. Additional studies with perfused hearts revealed two determinants of the increased ultrasonic backscatter observed: (1) an increase in cardiac fluid content reflected by the wet-to-dry weight ratio, and (2) the contributions of formed elements in whole blood. The results indicate that ultrasonic integrated backscatter distinguishes severely ischemic from nonischemic myocardium in vivo in open-chest animals. Because it was possible to obtain these results in the reflection mode, potential extension of the approach to clinical applications is promising.

Animals↗

Margaret Mead.

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Anthropology↗