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1.
Circulation ; 95(6): 1577-84, 1997 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-9118528

RESUMEN

BACKGROUND: 99mTc glucarate has recently been reported to be an infarct-avid agent. The feasibility of imaging with 99mTc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered 111In anti-myosin. METHODS AND RESULTS: Four groups of six rabbits each were studied. The left anterior descending coronary artery (LAD) was kept persistently occluded (n = 6) or reperfused after 40 minutes (n = 6) in rabbits. After confirmation of LAD occlusion by 201Tl scintigraphy, a mixture of 99mTc glucarate (15.7 +/- 1.6 mCi) and 111In anti-myosin (0.53 +/- 0.03 mCi) was administered intravenously. Another group of rabbits (n = 6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of 99mTc glucarate for the ischemic myocardium. The remaining 6 rabbits with reperfused myocardial infarction were used for the assessment of subcellular localization of 99mTc glucarate. 99mTc glucarate cleared rapidly from circulation (elimination t1/2, 36 minutes). Infarcts were visualized within 10 minutes in reperfused and within 30 minutes in nonreperfused coronary territories after intravenous administration. 111In anti-myosin delineated reperfused infarcts within 1 to 3 hours, but no uptake was seen in persistently occluded rabbits. 99mTc glucarate uptake in reperfused and nonreperfused infarct centers was 28 and 12 times greater, respectively, than that in normal myocardium (P = .0001). A direct correlation between glucarate and anti-myosin localization (r = .60 for nonreperfused; 0.76 for reperfused; P < .0001) was observed. Ischemic hearts showed no glucarate uptake. Subcellularly, 99mTc glucarate localized predominantly in the nuclear fraction of the infarct, with lesser extents in the mitochondrial and cytoplasmic fractions. CONCLUSIONS: Noninvasive imaging of myocardial infarcts with 99mTc glucarate is possible within minutes in persistently occluded or reperfused myocardial infarcts. Early detectability results from the rapid blood clearance and high avidity of glucarate for the acutely necrotic myocardial tissue.


Asunto(s)
Ácido Glucárico/análogos & derivados , Infarto del Miocardio/diagnóstico por imagen , Compuestos de Organotecnecio , Animales , Anticuerpos Monoclonales/farmacocinética , Ácido Glucárico/farmacocinética , Radioisótopos de Indio , Infarto del Miocardio/metabolismo , Reperfusión Miocárdica , Miosinas/inmunología , Compuestos de Organotecnecio/farmacocinética , Conejos , Cintigrafía , Fracciones Subcelulares/metabolismo , Distribución Tisular
2.
Circulation ; 94(1): 73-82, 1996 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-8964121

RESUMEN

BACKGROUND: Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis. METHODS AND RESULTS: Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%. CONCLUSIONS: In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.


Asunto(s)
Ecocardiografía , Miocarditis/diagnóstico por imagen , Miocarditis/microbiología , Fiebre Reumática/diagnóstico por imagen , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Ecocardiografía Doppler en Color , Femenino , Estudios de Seguimiento , Humanos , Masculino , Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Miocarditis/fisiopatología , Recurrencia , Fiebre Reumática/fisiopatología , Función Ventricular Izquierda
3.
Circulation ; 92(3): 474-84, 1995 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-7634463

RESUMEN

BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.


Asunto(s)
Anticuerpos Monoclonales , Arteriosclerosis/diagnóstico por imagen , Fragmentos Fab de Inmunoglobulinas , Radioisótopos de Indio , Músculo Liso Vascular/inmunología , Animales , Anticuerpos Monoclonales/aislamiento & purificación , Arteriosclerosis/inmunología , Arteriosclerosis/patología , División Celular/inmunología , Diseño de Fármacos , Humanos , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/inmunología , Ratones , Músculo Liso Vascular/patología , Polímeros , Conejos , Cintigrafía , Proteínas Recombinantes de Fusión/inmunología
4.
Brain Behav Evol ; 19(3-4): 144-54, 1981.
Artículo en Inglés | MEDLINE | ID: mdl-7326573

RESUMEN

The retinas of 14 ecologically diverse species of Anolis lizards have been examined neuroanatomically. Both central and temporal foveas were observed in each eye of all species: however, the two foveas differed with regard to a number of structural and morphological characteristics. All central foveas were deep and convexiclivate, while temporal foveas were shallower and more variable both in shape and retinal location across species. Central foveas had higher cell densities and a broader foveal clivus than did temporal foveas both within and across species. As eye size increased across species, densities of receptor nuclei per visual degree2 (vis. deg.2) increased more rapidly than did ganglion cell densities/vis, deg.2 in the central fovea. In contrast, both cell types increased at approximately the same rate in the temporal fovea as eye size increased. Several of these relationships have been previously reported for diurnal birds of prey, which are also bifoveate. of stomach contents revealed that Anolis species which feed upon small prey items have temporal foveas with a relatively deep clivus. Foveal characteristics may influence both species typical foraging behaviors and the type of prey which can be effectively utilized by a given species.


Asunto(s)
Fóvea Central/anatomía & histología , Lagartos/anatomía & histología , Mácula Lútea/anatomía & histología , Percepción Visual/fisiología , Animales , Recuento de Células , Masculino , Neuronas/ultraestructura , Células Fotorreceptoras/anatomía & histología , Conducta Predatoria/fisiología , Retina/anatomía & histología , Especificidad de la Especie , Vías Visuales/anatomía & histología
5.
Proc Natl Acad Sci U S A ; 77(7): 4185-7, 1980 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16592851

RESUMEN

Data on the foraging microhabitats of British birds are reanalyzed with the aim of understanding how fluctuations in resource abundance affect niche relationships and community structure. At Marley Wood, overlap in the foraging sites of resident bird species increased during the late spring and summer and decreased during the fall and winter. Among bird species coexisting in the pine forests at Thetford Chase, spatial overlap and spatial niche widths were positively correlated with food abundance over a 4-year period. These results suggest that in variable environments similarity in spatial niches is an inverse function of the intensity of competition for food. As food supplies drop, consumer species must apparently occupy increasingly different foraging areas in order to coexist. In less variable environments, however, resource stability may allow finer partitioning of the available foraging space and greater spatial overlap within a given foraging area. The results of this paper also suggest a reinterpretation of MacArthur's study of resource partitioning among warbler species in the boreal forests of New England. Rather than providing an instance of niche segregation in order to avoid intense competition, MacArthur's warblers may actually represent another example of increased spatial similarity when food resources are abundant and competition is reduced.

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