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Nuclear morphometry in prognosis of renal adenocarcinoma.

Nuclear morphometry was carried out on 95 parenchymatous adenocarcinomas of the kidney treated by radical nephrectomy and hilar lymphadenectomy and followed up for at least five years. The study assessed nuclear area, nuclear perimeter, major diameter, nucleolar area, nuclear shape factor, and nuclear size. There was a significant statistical correlation between survival and the morphometric parameters and between the parameters themselves except for nuclear shape factor. The multiple regression proved that nuclear area is the factor which shows the greatest statistical significance for prognosis. Taking a mean nuclear area of 35 microns 2 allowed two prognostic groups to be established regardless of stage, with those below the threshold having a good prognosis and those above it having a poor prognosis: 96.7 percent of patients with a good prognosis survived after five years (60 months) compared with 17.2 percent of those with a poor prognosis.

Actuarial Analysis↗

Methodological problems in placental morphometry: apologia for the use of stereology based on sound sampling practice.

Several problem areas in morphometry of human and animal placentae are reviewed. Attention is given to methods of tissue processing (handling, mode of fixation, embedding, shrinkage) and sampling (of organs, tissue blocks, sections, micrographs). Principal sources of bias and sampling variability are identified and the crucial importance of randomized sampling is emphasized. Methods for obtaining structural quantities from sections are compared. The case is made for estimating absolute values (volumes, surface areas, lengths, numbers, thicknesses) using stereological principles rather than relying on planar data (profile areas, perimeter lengths, numbers, apparent thicknesses). Absolute values may be obtained simply and efficiently without resort to expensive measuring devices. Finally, morphological descriptors suitable for correlating with functional data or for comparing normal and diseased organs are surveyed.

Delivery, Obstetric↗

A useful programme in BASIC for axonal morphometry with introduction of new cytoskeletal parameters.

Interest in the structure of axons and quantification of their components has been growing over the last years. However, the existing literature contains few reports of available computer programmes to facilitate such studies. This paper presents a fully comprehensive BASIC programme for the morphometric analysis of electron micrographs of cross-sectional nerve fibres. From drawings of fibre and axonal contours and dots of the microtubules and neurofilaments, the programme calculates the following parameters: area, diameter and form factor of the fibres and axons, number and density of microtubules and neurofilaments, proportion between microtubules and neurofilaments (R-proportion), myelin thickness and the diameter of the axon relative to its sheath (g-ratio). The programme also introduces three new parameters to analyse the degree of uniformity of microtubule and neurofilament distribution: distances between microtubules and between neurofilaments, equilateral index and cytoskeletal intermingling index. The programme is written in Microsoft BASIC Interpreter for Apple Macintosh (Microsoft Corporation) but can be used on other computers. Although the programme has been tested on adult rat optic nerve fibres, it can be used for different projects concerning axonal morphometry.

Animals↗

Intrinsic and extrinsic factors collaborate to generate driving forces for neural tube formation in the chick: a study using morphometry and computerized three-dimensional reconstruction.

The formation of the neural tube, the rudiment of the entire central nervous system, is one of the earliest morphogenetic movements. The origin of the driving forces for this process remains uncertain, but recent studies suggest the involvement of both intrinsic and extrinsic factors. In the present study, we have used morphometry, analysis of stereopair photographs of whole embryos, and computerized three-dimensional reconstruction to investigate the factors which constitute the bulk of the driving forces for neural tube formation in the developing midbrain of Hamburger and Hamilton stages 5-9 chick embryos. Results support the notion that neural tube formation is driven by a coordinated interplay of intrinsic and extrinsic forces. Initial bending of the neural plate along the midline of the embryo and uplifting of the neural folds is accomplished primarily through the combined action of intrinsic forces (resulting from apical constriction of neuroepithelial cells) and extrinsic forces (mostly a passive consequence of head-fold formation). However, once in the uplifted position, curling over of neural folds and closure of the neural tube is driven largely by apical constriction-mediated (intrinsic) forces that are generated by cells in the midlateral walls of the forming neural tube.

Animals↗

Synaptic mitochondria and ageing: computer-assisted morphometry in rat cerebellar glomeruli.

The ultrastructural features of synaptic mitochondria have been investigated by means of computer-assisted morphometry in the cerebellar glomeruli of young, adult and old rats. The volume fraction occupied by mitochondria (volume density: Vv), the number of organelles/ microm(3) (numerical density: Nv), the average volume (V) and the average length (Sk) of the mitochondria were the parameters measured in electron microscopic photos taken at an enlargement of x 8000. Vv showed a lifespan constancy. Nv was increased in the adult group vs. the young, but it was decreased in old animals as compared with the other 2 groups of age studied. V and Sk showed the same age-dependent changes: a significant decrease in the adults and a significant increase in the old rats vs. the other groups analysed, respectively. We interpret these findings to represent age-dependent morphofunctional adaptations occurring at synaptic mitochondria as a response to actual energy demands from the synaptic connectivity they subserve. Although impaired, the dynamic morphology of synaptic mitochondria appears to be capable of consistent compensative ultrastructural rearrangements in the central nervous system of old individuals.

Journal Article↗

DATAPLOT: a graphical display package for bacterial morphometry and fluorimetry data.

A microbiological image processing system has been developed, which is used to determine both morphometry and fluorimetry data on (mainly faecal) bacteria. A special program for display of these data has been developed for this system. Besides probability density estimates of any one or two parameters and scatter plots of any two or three parameters in the distribution, it can generate scatter plots using the actual bacterial shapes, rather than arbitrary symbols. A particularly powerful feature of the program is the possibility to overlay a contour plot of the probability density distribution of the bacteria in parameter space, with a scatter plot of the actual bacterial shapes involved. In this paper, the program's organization, options, and the algorithms used are discussed.

Algorithms↗

Vertebral morphometry in diagnosis of spinal fractures.

Vertebral morphometry was performed on lateral thoracic and lumbar radiographs of 153 women with a preliminary diagnosis of spinal osteoporosis. Measurements included anterior and posterior vertebral height, width, area, wedge angle, percent reduction of anterior to posterior height (PRH) and percent difference in anterior height between adjoining vertebrae (PDAH). A vertebral fracture was identified if any of the measurements which control for interindividual variation in vertebral size (wedge angle, PRH, PDAH) were below the normal range. Among individuals with mild osteoporosis (0-2 fractures) PDAH identified 86% of the fractures and 95% of the individuals with fractures. Other measurements identified less than 71% of the fractures and less than 80% of the individuals with fractures. Although the results reflect a relative rather than a true sensitivity it appears that PDAH is the better diagnostic measurement for fractures in the earlier stages of spinal osteoporosis.

Aged↗

Comparison of in vivo and in vitro rat hepatic toxicity of coumarin and methyl analogues, and application of quantitative morphometry to toxicity in vivo.

The rat hepatic toxicity of coumarin and methyl analogues (3-,4-methyl coumarin and 3,4-dimethylcoumarin) has been determined in vivo and in vitro (freshly-isolated cells). Coumarin at a dose of approximately 1 mmol/kg produced clear histological evidence of centrilobular necrosis, while the methyl analogues at an equivalent dose were much less toxic. By use of a systematic random sampling protocol and quantitative morphometry it was determined that there was a lobar variation in the extent of hepatic damage but that this exhibited random inter-animal variation. The order of cytotoxicity in vitro was identical to that observed in vivo. In hepatocytes depleted of glutathione the toxicity of all four compounds was increased. This was particularly marked for the 3-methyl analogues, such that the order of toxicity was different to that observed in vivo and in hepatocytes not depleted of glutathione.

Animals↗

Ready evaluation of lung alveolar toxic damage with histological sections morphometry.

In this experiment we aimed at developping a method of ready evaluation of lung alveolar toxic damage using morphometric measurements. Swiss-Webster mice were treated with different doses of diquat (i.p.) and the left lung was fixed at 0, 3, and 5 days after treatment. The technique of morphometry of histological sections embedded in glycol methacrylate (GMA) was used to quantify possible modifications of alveolar cells. Quantitative evaluation includes: alveolar macrophages, polymorphonuclear cells, type II and intermediate pneumocytes. The results indicate a lung dose-dependent response, observed in both inflammatory and epithelial regeneration components of the alveolar primary reaction. This method could be used to readily evaluate the pulmonary toxic potential of any substance.

Animals↗

In vivo morphometry of planum temporale asymmetry in first-episode schizophrenia.

Magnetic resonance imaging is a promising tool for in vivo analysis of the neuropathology underlying schizophrenia. One of the most consistent features emerging from the majority of published studies is the lateralization of pathological findings, and this has led to hypotheses of impaired hemispheric specialization in schizophrenia. In previous work, we have validated morphometry of supratemporal language-related cortex using high-resolution magnetic resonance imaging and analyzed the relation of the so defined planum temporale to functional parameters of hemispheric specialization. In the present study, we examined planum temporale structural asymmetry in first-episode schizophrenics. Asymmetry coefficients obtained in these patients did not differ significantly from those in equally right-handed controls and were not correlated to standard psychopathological measures. These data are contrasted with other studies reporting lateralized brain pathology in schizophrenia with special emphasis on methodological considerations in neuroimaging procedures.

Adult↗

Nuclear morphometry in squamous cell carcinoma (SCC) of the tongue.

In the histological grading of oral squamous cell carcinoma (OSCC) nuclear features are very important. Nevertheless evaluation is usually performed in a subjective and not highly reproducible way. The aim of this work was to investigate the relationship between nuclear shape and survival in 30 cases of carcinoma of the tongue. All the patients were divided into two groups: short-term survival and long-term survival. Twenty nuclei for each tumour were submitted to a morphometrical study by the shape analytical morphometry (SAM) software system. It was thus possible to evaluate not only nuclear dimensions but also nuclear contour irregularities and nuclear shape asymmetries. Multivariate discriminant analysis (MDA) of the quantitative parameters obtained by the morphometrical study distinguished the patients of the two groups with only a 10% error; moreover successful cluster analysis was performed by using Fourier parameters. Both these sets of results were achieved mainly owing to the parameters for contour irregularities.

Adult↗

Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group.

Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve-fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy.

Aldehyde Reductase↗

Changes in the distribution of extracellular matrix vesicles during healing of rat tibial bone (computerized morphometry and electron microscopy).

A study of the distribution of extracellular matrix vesicles during the first 3 weeks of healing of adult rat tibial bone was performed by transmission electron microscopy in combination with computerized morphometry. Bone injury comprised removal of the marrow followed by regeneration of the tissue via a phase of primary mineralization. A total number of 39,498 vesicles were traced on electron micrographs and sorted according to their diameters, distance from the calcified front and types. The different vesicular types were defined as follows: (a) vesicles with electron lucent contents, i.e. "empty", (b) vesicles with amorphous electron opaque contents, i.e. "amorphic", (c) vesicles containing crystalline depositions, i.e. "crystal", and (d) vesicles containing crystalline structures with ruptured membranes i.e. "rupture". The vesicles were studied on the days 3, 6, 14 and 21 after bone injury. Most of the vesicles were concentrated between diameters of 0.07 and 0.17 micron. Most of the vesicles were found in a distance less than 3 microns from the calcified front. The sequence of changes of distances from the calcified front and of the vesicular diameters were recorded as follows: "rupture", "crystal", "amorphic" and "empty", the "rupture" type being the closet to the front and of the largest diameter in each day. The results of the present study confirm the accepted hypothesis on calcification via extracellular matrix vesicles. It is thought that the cell secretes "empty" vesicles that accumulate Ca and Pi forming amorphous calcium phosphate that is then converted to hydroxyapatite. This is followed by rupture of the vesicular membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differences in cortical bone in overloaded and underloaded femurs from ovariectomized rats: comparison of bone morphometry with torsional testing.

Osteopenia and mechanical incompetence are the defining features of osteoporosis, yet the effects of changes in bone structure on mechanical properties are not completely understood. The primary objective of this study was to determine if in a rodent model, changes in cortical bone structure, as measured by static morphometry, would correlate with functional properties, as measured by torsional testing. For this, cortical bone structure and stiffness were determined in overloaded and underloaded limbs in rats rendered ovarian hormone-deficient by ovariectomy (OVX). Rats were OVX and six weeks later a hind limb was immobilized by casting for an additional six weeks. In all cases the femur from the underloaded, casted limb was compared with that from the contralateral, overloaded limb. The success of this experimental protocol was confirmed by differences in femoral cancellous bone volume by microradiography and single photon absorptiometry, with the overloaded limb having a greater bone volume and bone mineral density than the contralateral, immobilized controls. Morphometric differences in the femoral diaphyseal cortical bone included greater endocortical perimeter and endocortical osteoclast surface, less cortical area, less minimum cortical width, and less minimum cortical width at fracture planes when the bones were tested for stiffness in the underloaded, compared with the contralateral, overloaded limbs. Using a torsional test, the ultimate torque to failure and stiffness were less in the underloaded femurs compared with the contralateral, overloaded femurs. These results emphasize the importance of mechanical loading on bones from a gonad-deficient animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Detection of abnormal visual cortex in children with amblyopia by voxel-based morphometry.

PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Thirteen children with amblyopia and 14 normally sighted children underwent magnetic resonance (MR) examination. The two groups were age-matched with a mean age of 5.8 years. In the amblyopia group, five children had strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the original 3-dimensional T1 brain images using the VBM module within the widely used analysis software package SPM2 (Welcome Department of Cognitive Neurology, London, United Kingdom). After normalization, segmentation, and smoothing of the images, comparison between amblyopic and control groups was derived for the gray matter of the entire brain using parametric statistics. RESULTS: The results of VBM analysis indicated that the amblyopic group had decreased gray matter density in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The radii of these regions ranged from 12 to 36 voxels. These abnormalities were consistent with morphologic changes in brain regions related to visual function. CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the visual cortex of children with amblyopia, which may indicate developmental abnormalities of visual cortex during the critical growth period.

Amblyopia↗

Impact of renal function on coronary plaque morphology and morphometry in patients with chronic renal insufficiency as determined by intravascular ultrasound volumetric analysis.

The aim of the present study was to use intravascular ultrasonography (IVUS) to assess plaque morphology and morphometry in patients with varying degrees of chronic renal insufficiency, including end-stage renal disease (ESRD) on dialysis replacement. Cardiovascular disease is the main cause of death for patients with chronic renal insufficiency, particularly in patients with ESRD. The impact of several degrees of renal insufficiency (including ESRD) on coronary plaque characteristics has not been determined. A total of 142 patients who underwent IVUS imaging of a de novo native coronary artery stenosis before percutaneous intervention were matched for age, gender, and diabetes and were grouped according to calculated creatinine clearance (CrCl): CrCl >70 ml/min (n = 39); CrCl 50 to 69 ml/min (n = 41); CrCl <50 ml/min, (n = 37), and ESRD (n = 25). Standard clinical, angiographic, and IVUS parameters were measured. The ESRD group had more African-American (p = 0.002) and hypertensive (p = 0.002) patients. No significant difference was found in any of the IVUS measurements among patients with CrCl >70, 50 to 69, and <50 ml/min: reference and lesion site arterial, lumen, and plaque areas and volumes, and arterial calcium (p = NS for all comparisons). Conversely, patients with ESRD had larger reference segment arterial and lumen areas and volumes; larger lesion site arterial, lumen, and plaque areas; and larger arcs of calcium (p <0.05 for all post hoc comparisons between patients with ESRD and patients with CrCl >70, 50 to 69, and <50 ml/min). Thus, chronic renal insufficiency in the absence of dialysis is not associated with increased reference segment or lesion site plaque burden and calcium. However, the transition to the need for dialysis is associated with progressive calcific atherosclerosis (larger lesion plaque area and calcium).

Aged↗

Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry.

BACKGROUND: Structural magnetic resonance imaging (MRI) studies of regions of interest in brain have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder (BD). Voxel-based morphometry (VBM) provides an unbiased survey of the brain, can identify novel brain areas, and validates previously hypothesized regions. We conducted both optimized VBM, comparing MRI gray matter volume, and traditional VBM, comparing MRI gray matter density, in 11 BD subjects and 31 healthy volunteers. To our knowledge, these are the first VBM analyses of BD. METHODS: Segmented MRI gray matter images were normalized into standardized stereotactic space, modulated to allow volumetric analysis (optimized only), smoothed, and compared at the voxel level with statistical parametric mapping. RESULTS: Optimized VBM showed that BD subjects had smaller volume in left ventromedial temporal cortex and bilateral cingulate cortex and larger volume in left insular/frontoparietal operculum cortex and left ventral occipitotemporal cortex. Traditional VBM showed that BD subjects had less gray matter density in left ventromedial temporal cortex and greater gray matter density in left insular/frontoparietal operculum cortex and bilateral thalamic cortex. Exploratory analyses suggest that these abnormalities might differ according to gender. CONCLUSIONS: Bipolar disorder is associated with volumetric and gray matter density changes that involve brain regions hypothesized to influence mood.

Adolescent↗

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.

BACKGROUND: Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI). METHODS: We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions. Twenty-six studies comprising volumetric measurements on up to 404 independent patients with bipolar disorder were included. A meta-analysis was carried out comparing the volumes of regions in bipolar disorder to comparison subjects using a random effects model. RESULTS: Patients with bipolar disorder had enlargement of the right lateral ventricle, but no other regional volumetric deviations which reached significance. Strong heterogeneity existed for several regions, including the third ventricle, left subgenual prefrontal cortex, bilateral amygdala and thalamus. CONCLUSIONS: Regional volume of most structures we studied is preserved in bipolar disorder as a whole, which was significantly associated only with right-sided ventricular enlargement. However the extensive heterogeneity detected indicates the need for further studies to establish if consistent regional brain volume deviation exists in bipolar disorder or in specific clinical subsets of the illness.

Algorithms↗