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Morphometric analysis of atrioventricular septal defect with common valve orifice.

OBJECTIVES: We sought to analyze morphometric features of atrioventricular septal defect (AVSD) in autopsy specimens and to consider the developmental implications of obstruction in either ventricular outflow tract. BACKGROUND: Left ventricular outlet obstruction (LVO) is more prevalent in patients with Rastelli type A morphology. When tetralogy of Fallot (ToF) complicates this malformation, there is usually a free-floating superior bridging leaflet. The reasons for these associations are uncertain. METHODS: In 133 hearts with AVSD and common atrioventricular (AV) valve orifice, we measured the degrees of horizontal and anterior deviation of the great arteries from the AV valve, the diameters of the ventricular outlets and the great arteries and the degree of deficiency of the ventricular septum. RESULTS: In Rastelli type A morphology, the great arteries were deviated more leftward than in type C morphology (p < 0.01). Type A hearts also had a relatively small aorta, with a long and narrow subaortic tract. The presence of obstruction in either ventricular outlet was associated with a more oblique arrangement of the great arteries, with the pulmonary trunk being more leftward than in hearts without LVO (p < 0.01). In combination with ToF, the aorta was dextroposed and the pulmonary trunk was located more posteriorly (p < 0.01). No heart with type A morphology showed ToF (p < 0.01). CONCLUSIONS: The geometric arrangement of the great arteries correlated significantly with obstruction in either ventricular outflow tract and with the Rastelli subtypes. Malrotation of the developing outlet septum may be an embryologic factor producing obstruction, with horizontal deviation of the outlets also influencing the morphology of the superior bridging leaflet.

Aorta↗

Classification of colorectal adenomas with quantitative pathology. Evaluation of morphometry, stereology, mitotic counts and syntactic structure analysis.

In search for an objective classification rule for the morphologic changes in colorectal adenomas, the results of nuclear morphometry for assessing geometric characteristics of tumour nuclei, syntactic structure analysis for assessing the arrangement of nuclei in the epithelium, stereological assessment of glandular changes, and area weighted mitotic counts were evaluated in a multivariate analysis. The H&E stained tissue sections of 59 colorectal adenomas were studied, of which 20 showed mild, 20 moderate and 19 severe dysplasia, according to blind duplicate assessments by two pathologists. In a stepwise jackknifed discriminant analysis, the combination of variables was selected that could best discriminate the cases into the previously assessed grade of dysplasia. With the combination of two variables (minimum line length and inner gland surface density), 71% of the cases could be correctly classified according to the previously assessed grade. No cases with mild dysplasia were classified as severe dysplasia and vice versa. However, since the reproduction of subjectively assessed grade was not the ultimate goal, we aimed to discriminate the cases into two groups on the basis of measurements results alone, by means of a cluster analysis. These two groups would merely reflect the cases with major versus minor morphologic changes. The results of the cluster analysis showed that all mild dysplasia cases were allocated into the low grade cluster, and that the moderate dysplasia cases were divided over both the low grade and high grade cluster. Two severe dysplasia cases with borderline morphometric results were allocated into the low grade cluster, and the remaining 16 into the high grade cluster. It is concluded that objective evaluation of dysplasia in colorectal adenomas is possible by a combination of morphometric techniques. The results of the morphometric analyses seem to favor a two-grade classification system rather than a three-grade system.

Adenoma↗

[Computer-assisted geometric measuring technic in coronary angiography interval studies: results of initial angiograms of the International Nifedipine Trial of Anti-atherosclerotic Therapy (INTACT) study].

In 396 of 423 (93.6%) patients with mild to moderate coronary artery disease participating in a coronary angiographic follow-up trial, diameters of the epicardial coronary arteries were measured with an automatic contour detection system (CAAS). The underlying INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy), a prospective, placebo-controlled, randomized, double-blind multicenter trial, investigates the influence of the calcium antagonist nifedipine (80 mg/day) on the progression of coronary atherosclerosis over a three-year interval. The study is based on coronary angiograms repeated in identical projections after premedication with 10 mg isosorbide dinitrate sublingually. For quantitative analysis the coronary artery system was, in consideration of all anatomical variations, subdivided into 25 segments. In the first angiograms of the 396 patients evaluated up to April 1, 1988, altogether 5,425 different coronary segments could be analyzed over their entire length in one or more angiographic projections--on the average 13.7 +/- 2.8 segments per patient. Analysis parameters were the mean diameters of the entire segments and of the individual subsegments (about 5 mm in length). The 10 major proximal segments could be evaluated in 76-94% of patients respectively in more than two different angiographic projections on the average; in 0-13% of patients the respective segments were occluded. In 1-4% of patients the evaluation of these segments was prevented by poor film quality and in 1-16% of patients prevented by anatomical abnormalities (e.g., segment too short or too small). 184 segments were found occluded (RCA 42%, LAD 30%, CX 28%) and 909 mostly low-grade to moderate stenoses (RCA 34%, CX 32%, LAD 30%, left main 4%) were analyzed with a special algorithm. The following obstruction parameters were derived: minimal diameter, percentage severity, length, and plaque area. The present data demonstrate that in an angiographical multicenter follow-up study such as INTACT a nearly complete quantitative morphometric analysis of the visualized coronary artery system can indeed be obtained in virtually all angiograms when a computer-assisted contour detection system is applied.

Clinical Trials as Topic↗

Histamine-induced coronary spasm in regions of intimal thickening in miniature pigs: roles of serum cholesterol and spontaneous or induced intimal thickening.

The pathogenesis of histamine-induced coronary spasm was examined angiographically and morphometrically in Göttingen miniature pigs. In five of 36 consecutive pigs that were 4 to 5 months of age, coronary spasm was provoked by the intracoronary administration of histamine, and the left coronary arteries were examined histologically without endothelial denudation (group 1). Endothelial balloon denudation of the major branch of the left coronary artery was performed in 31 of 36 pigs and five died during the procedure. The remaining 26 pigs were randomly allotted to one of two groups, one fed a cholesterol-supplemented (group 2, n = 13) and one fed a regular low-cholesterol diet (group 3, n = 13). After 3 months, serum cholesterol increased significantly from 57 +/- 6 to 222 +/- 27 mg/dl (p less than .01) in group 2, but remained unchanged (48 +/- 5 to 55 +/- 6 mg/dl) in group 3. Percent narrowing of the coronary diameter induced by 10 micrograms/kg ic histamine after administration of the H2 blocker cimetidine (60 mg/kg iv) was 39 +/- 3% and 24 +/- 2% (p less than .05 between groups 2 and 3) at the nondenuded site and 78 +/- 3% and 74 +/- 4% at the denuded site in groups 2 and 3, respectively (p less than .01 between nondenuded and denuded sites). Histamine-induced percent narrowing of the coronary diameter after cimetidine in group 1, 2, and 3 pigs correlated well with the degree of intimal thickness on an exponential curve (r = .92, p less than .001). Since percent narrowing at the intact site was 27% (n = 19) in all three groups, predicted histamine-induced percent narrowing at the spastic site, applying the geometric theory, was 33 +/- 3%. Accordingly, enhanced constriction of the coronary artery with intimal thickening in response to histamine can largely be explained by the acquired hyperresponsiveness of the vascular wall to autacoids. This phenomena, not related to the level of serum cholesterol, may be uniquely linked to the basic pathology of evolution of atherosclerosis.

Animals↗

Fractal dimension can distinguish models and pharmacologic changes in liver fibrosis in rats.

Fractal analysis measures the complexity of geometric structures. The aim of this study was to evaluate the feasibility and accuracy of fractal analysis in liver fibrosis. A total of 77 rats were included: 10 sham, 46 with fibrosis secondary to bile duct ligation (BDL), and 21 with fibrosis due to CCl(4) intoxication. Measurements included the fractal dimension of Kolmogorov (D(k)), histologic lesions, the area of fibrosis by image analysis, liver hydroxyproline content, messenger RNA fibronectin, serum hyaluronate level, and portal pressure. Fibrotic rats were given placebo, octreotide, or O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO). Intraobserver agreement of D(k) was excellent with the intraclass (ic) correlation coefficient r(ic) = 0.91 (P <.0001) as well as the interobserver agreement with r(ic) = 0.88 (P <.001). D(k) was correlated with other measurements or markers of fibrosis: the area of fibrosis (r = 0.75; P <.0001), hydroxyproline content (r = 0.51; P <.001), serum hyaluronate level (r = 0.52; P <.001), and portal pressure (r = 0.52; P <.01). D(k) was significantly different between the 2 models of fibrosis (P <.0001), unlike the area of fibrosis, and this relationship was independent of other histologic lesions. The significant decrease in fibrosis observed with octreotide or V-PYRRO/NO was similarly reflected by D(k) or the area of fibrosis. The diagnostic accuracy for the fibrosis model was 97% with the 5 main measurements or markers of fibrosis studied, with D(k) isolated at the first step by stepwise analysis. In conclusion, fractal analysis is suitable for analyzing liver fibrosis and has excellent reproducibility. This is the only quantitative morphometric method that can discriminate among the models of fibrosis and is sensitive enough to detect pharmacologically induced changes in liver fibrosis.

Animals↗

Cell intercalation during notochord development in Xenopus laevis.

Morphometric data from scanning electron micrographs (SEM) of cells in intact embryos and high-resolution time-lapse recordings of cell behavior in cultured explants were used to analyze the cellular events underlying the morphogenesis of the notochord during gastrulation and neurulation of Xenopus laevis. The notochord becomes longer, narrower, and thicker as it changes its shape and arrangement and as more cells are added at the posterior end. The events of notochord development fall into three phases. In the first phase, occurring in the late gastrula, the cells of the notochord become distinct from those of the somitic mesoderm on either side. Boundaries form between the two tissues, as motile activity at the boundary is replaced by stabilizing lamelliform protrusions in the plane of the boundary. In the second phase, spanning the late gastrula and early neurula, cell intercalation causes the notochord to narrow, thicken, and lengthen. Its cells elongate and align mediolaterally as they rearrange. Both protrusive activity and its effectiveness are biased: the anterioposterior (AP) margins of the cells advance and retract but produce much less translocation than the more active left and right ends. The cell surfaces composing the lateral boundaries of the notochord remain inactive. In the last phase, lasting from the mid- to late neurula stage, the increasingly flattened cells spread at all their interior margins, transforming the notochord into a cylindrical structure resembling a stack of pizza slices. The notochord is also lengthened by the addition of cells to its posterior end from the circumblastoporal ring of mesoderm. Our results show that directional cell movements underlie cell intercalation and raise specific questions about the cell polarity, contact behavior, and mechanics underlying these movements. They also demonstrate that the notochord is built by several distinct but carefully coordinated processes, each working within a well-defined geometric and mechanical environment.

Animals↗

A morphometric approach to the study of human ovarian organogenesis.

This study deals with the morphometric approach used to describe the quantitative characteristics of human ovaries during their final histogenesis. Fixed ovaries ranging from the 20th fetal week to the 8th postnatal month were used. They were measured using a high precision caliper, were embedded in toto in epoxide resin, and systematically cut (1 microm-thick sections) orthogonal to the major axis of the organ. The surface areas were automatically measured, at low magnification, and ovarian volume was calculated using the Cavalieri method. The volume fractions of ovarian medulla, primitive cortical tissue, primordial, primary, secondary and Graafian follicles, and stroma were calculated by differential point counting at higher magnification. At the same magnification, the position of the different follicle categories in the cortex was estimated as percentage distance of the follicle from the cortico-medullary boundary. The number in unit cortex volume of the oocyte nuclei in primordial and primary follicles were derived by diameter analysis according to the Schwartz-Saltykov method, and the total follicle number for each ovary was obtained. The diameter of nuclear, cellular and follicular profiles of primary and primordial follicles in sections was also measured. Ovarian volume was about 30 mm3 at 20 fetal weeks and 287 mm3 at the 8th postnatal month, with a 9.5-fold increment. Irrespective of age, the cortex occupied most of the organs, ranging from 90% at 20 prenatal weeks (about 27 mm3) to 85% at 8 postnatal months (about 245 mm3). In the cortex, the interstitium or stroma intermingled with the germinal component: primitive cortical tissue was found in all ovaries, and its absolute volume remained unmodified between the 20th fetal week and birth. In the analyzed fetal stages, the total number of primordial follicles had its largest modification, with a 1.3-fold increment between the 20th-25th fetal weeks. Hereafter, the number increased at a slower rate (about 1.2 times between the 25th week and birth, 1.1 times between birth and the 8th postnatal month). The largest absolute volume of primordial follicles was found at birth. Follicular, oocyte and nuclear diameters increased during the intrauterine life, while after birth their dimensions did not modify further. Conversely, their spatial position in the cortex modified even after birth. In the 8-month old child nearly all germinal cells were comprised into follicles in different degrees of development, and the primitive cortical tissue was exhausted. A three-dimensional geometrical model of human ovary has also been elaborated to define the spatial organization of ovarian germinal and somatic components, and to allow the comparison of the present data to the "in-vivo" volumetric assessments.

Embryonic and Fetal Development↗