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PubMed1986

Nuclear morphometry as an important prognostic factor in stage I renal cell carcinoma.

Although 60% of Stage I renal carcinoma patients die from tumor within 5 years postoperatively, a considerable percentage survive that period. Nuclear grading can help to predict the outcome, but many of the patients are Grade 2, and the prognosis of this subclass is uncertain. Therefore, nuclear morphometry was carried out in 41 patients with Stage I renal cell carcinoma. Of these, 24 died within 5 years and 17 have survived that period. Using a mean nuclear area of 32 micron 2 as the decision threshold, none of the 24 short-term survivors are below that threshold and three of the long-term survivors exceed that value (18% false-positives) (99% confidence limit). Separate analysis with sets for learning and testing and Grade 2 patients gave similar results. The results show the essential prognostic value of morphometry in this set of patients with Stage I renal cell carcinoma.

Adult↗

PubMed1989

The role of morphometry in predicting prognosis in pancreatic islet cell tumors.

Morphometry of 31 pancreatic islet cell tumors was examined to determine the value of this technique in assessing tumor behavior. Patients were followed for a mean period of 5.1 years (range, 1 month-14 years) after diagnosis. Initially 17 localized and nine metastatic tumors were studied. Discriminant analysis was carried out on these cases and identified nuclear/cytoplasmic ratio and number of nuclei/mm2 as the significant discriminatory features. These were combined to derive a classification rule which was capable of correctly identifying localized and metastatic tumors in 92% of cases. The classification rule was applied subsequently to an additional five test cases, all of which were classified successfully. The failure of increased nuclear size and pleomorphism to correlate with malignancy in these tumors was confirmed. Tumors which metastasized had significantly greater gross diameters than localized lesions, but overlap existed. Mitotic counts were not a helpful discriminatory feature. Morphometry may be useful in improving histologic assessment of pancreatic islet cell tumor behavior.

Adenoma, Islet Cell↗

PubMed1991

Correlation of nuclear morphometry with progression of breast cancer.

Alterations in nuclear structure are the morphologic hallmark of cancer diagnosis. Nuclear size, shape, chromatin pattern, and nucleolar size and number have all been reported to change in breast cancer. Attempts to quantify nuclear alterations to establish grading systems, predict prognosis, and/or set guidelines for therapy have met with varied success. Therefore, the authors quantified the changes that occur with breast cancer with nuclear morphology in several different groups of patients: normal controls, intraductal carcinoma, invasive ductal carcinoma with negative nodes at mastectomy, and invasive ductal carcinoma with positive lymph nodes. Pleomorphism as measured by both nuclear area and intrasample variation increased with invasive histology and metastatic breast cancer. It is still unclear whether node-negative Stage II breast cancer requires adjuvant therapy. This issue would be less complicated if it were possible to identify those women at high risk of recurrence. Therefore, the authors retrospectively identified 30 women with node-negative Stage II infiltrating ductal carcinoma with a long follow-up period of 6 to 12 years. Computer-assisted morphometry of nuclei in routine hematoxylin and eosin-stained pathologic slides was done using the DynaCell Analysis System in a blinded fashion. DynaCell measures 15 nuclear parameters, including perimeter, area volume, roundness, and ellipticity. Although nuclear area and variance were related to breast cancer progression, nuclear morphometry did not predict successfully which patients would have recurrent disease in the women with Stage II, node-negative lesions at the time of mastectomy.

Adult↗

PubMed1988

Renal vascular histology and morphometry in systemic sclerosis. A case-control autopsy study.

An autopsy case-control study of renal vascular histology and morphometry in systemic sclerosis (scleroderma) was performed. Thirty-five of 70 systemic sclerosis cases had renal tissue available for study: 26 had diffuse cutaneous involvement (9 with "renal crisis" and 17 without) and 9 had limited cutaneous disease (CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias]). Age-matched (within 10 years) and sex-matched controls with renal specimens were obtained. New sections were cut from tissue blocks, and morphometry was completed using a Zeiss Image Analyzer. Using analysis of variance, the intimal area (Ai) was significantly increased (intimal thickening) in small and medium-sized arteries of patients with diffuse scleroderma and in small arteries of CREST patients, compared with those in controls, while a decreased medial area (Am) was seen consistently in all groups. The proportion of the vessel wall occupied by intima (Ai:[Ai + Am]) was significantly greater in all vessel size groups in patients with diffuse scleroderma compared with that in controls. The percentage of luminal occlusion was greatest in patients with diffuse disease with renal crisis. These same patients had severe edematous and mucinous intimal thickening in small and medium vessels, often in association with fibrinoid necrosis. We conclude that renal vascular structural changes are an integral part of systemic sclerosis. However, the significant differences between diffuse scleroderma patients and CREST syndrome patients, for both intimal thickening and percentage of luminal occlusion, suggest that the arterial disease in these 2 patient subsets is distinctive.

Calcinosis↗

PubMed1992

The value of nuclear morphometry in the management of patients with colorectal polyps that contain invasive adenocarcinoma.

Haggitt's classification is a useful guide in the management of patients with large bowel polyps which contain invasive adenocarcinoma in that patients with levels 1 to 3 require no operation. Nuclear morphometry has been shown to be a useful prognostic discriminant for patients with invasive carcinoma of the large bowel. The nuclear shape factor of 44 polyps with invasive carcinoma was studied to determine whether this parameter was of value to define those patients with Haggitt level 4 who should have a resection. The shape factor of 50 interphase nuclei was obtained through the use of image analysis by tracing the nuclear profiles as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. Our previous experience showed a nuclear shape factor greater than 0.84 was associated with a poor outcome. The overall mean shape factor was 0.71 (0.59-0.85). There was a tendency for the patients with residual disease to have values in the upper range. Our findings suggest that nuclear morphometry fails to add any predictive information in this clinical situation.

Adenocarcinoma↗

PubMed1976

The morphometry of the glomerular epithelial cell and its foot processes after the injection of bovine serum albumin or egg albumin.

The intraperitoneal injection of 1 g of bovine serum albumin daily for 5 days was shown by electron-microscope morphometry to cause swelling of the glomerular epithelial cells and very severe loss of foot processes. However, these changes were found in only 70 per cent. of glomeruli and the other 30 per cent. remained normal. After 7 days' recovery following five daily injections of 1 g of bovine serum albumin, the swelling of the glomerular epithelial cells had subsided and the foot process reappeared. These changes were accompanied by severe proteinuria which resolved only slowly when the injections were stopped. After daily injections of 0-8 g of egg albumin for 5 days there was no swelling of the glomerular epithelial cells and only very slight loss of foot processes detectable only by morphometry. There was a less severe proteinuria than after injections of bovine serum albumin and it resolved more rapidly when injections were stopped. It is suggested that these differences arise from the fact that bovine serum albumin is reabsorbed by the glomerular epithelial cell but egg albumin is not. Two of four rats allowed to recover for 7 days after five daily injections of 1 g of bovine serum albumin had unusual glomerular lesions.

Animals↗

PubMed1987

Whole embryo morphometry in teratogen screening.

Current methodology in embryo evaluation involves qualitative assessment of razor blade and paraffin serial sections. Presently, no one has applied existing computerized morphometric techniques to examine embryos. A technique has been developed that enables investigators to section embryos at 150 mu, thereby greatly reducing the number of sections and making morphometric analysis possible. This type of analysis permits the precise volumetric determination of several developing organ systems. The aim of this study was to evaluate the feasibility and sensitivity of whole embryo morphometry in teratogen screening. Cadmium chloride, a well-established teratogen, was chosen because of its ability to induce exencephaly in approximately one-half of offspring while having no observable effects on the remaining exposed embryos. It was found that both exencephalic and normal-appearing cadmium-exposed embryos had significantly smaller total cellular, neuroepithelial, otic vesicle, optic assembly, limb bud, and cardiac mesenchyme volumes when compared to controls. Also, the neuroepithelial volume of the exencephalic embryos was significantly smaller than the normal-appearing cadmium-exposed embryos. These results suggest that in addition to inducing exencephaly, cadmium chloride has an overall inhibitory effect on embryonic growth. We have shown that whole embryo morphometry is a sensitive means of evaluating embryonic growth that permitted determination of cadmium-induced aberrations not discernable by currently employed techniques. In light of these results, we feel this technique shows promise for future investigations of known and suspected teratogens.

Animals↗

PubMed1976

Morphology, morphometry and electron microscopy of HeLa cells infected with bovine Mycoplasma.

The host-parasite relationship of HeLa M cells artificially infected with a bovine species of Mycoplasma was studied by light microscopy, transmission electron microscopy and scanning electron microscopy. The use of morphometry to quantitate some of the findings was explored. The parasites were seen in locations extracellular to the cell surface. The detection of small numbers of organisms by light microscopy was well demonstrated by use of the flurescent antibody technique. Scanning electron microscopy proved to be an excellent method for revealing the surface details of cell-parasite morphology. Ultra-thin sections showed that the parasites are aligned mostly parallel to the plasma membrane of the host cell but separated by a gap of 10nm. Morphometry indicated an average of 69 organisms per cell surface occupying 1.7% of the surface area. An increase of 26% in diameter of the HeLa cells, possibly as a result of infection, was observed.

Biometry↗

PubMed1978

Ultrastructure and morphometry of ACTH-producing cell in the rat anterior pituitary gland stimulated by lysin-vasopressin and prostaglandin E1.

The aim of this study was to investigate the qualitative and quantitative changes of ACTH-cells in the rat after application of a specific and a non-specific stimulus. A CRF-analog (lysin-vasopressin) and a prostaglandin (prostaglandin E1) were used. 40 rats were injected lysin-vasopressin or prostaglandin E1, respectively, for 4 weeks. The pituitary glands were investigated by means of light microscopy, electron microscopy and morphometry. Activation of the ACTH-cells could be observed after use of both substances, the effect of lysin-vasopressin being more intense than that of prostaglandin E1. Enlargement of the nucleus, the cytoplasm and the organelles involved in hormone-production and -transport were found and verified by morphometry. Additionally an increase in number of the cells could be demonstrated. Prostaglandin influenced not only ACTH-cells, but also other cells of the anterior pituitary.

Adrenocorticotropic Hormone↗

PubMed1985

Studies on urinary bladder carcinoma by morphometry, flow cytometry, and light microscopic malignancy grading with special reference to grade II tumours.

Biopsies from 28 patients with urinary bladder carcinoma were investigated by flow cytometry and morphometry. Histopathological grading on 1.5 microns thick glycol methacrylate sections was also performed. Nuclear profile areas, nuclear volume densities and mitotic indices were usually larger in the higher grades of malignancy. All grade I tumours were diploid and all grade III tumours were aneuploid. Out of 13 grade II tumours 8 were diploid and 5 aneuploid. In these latter five cases nuclear profile areas were at the high end of the spectrum. The data show that flow cytometry and morphometry could be a valuable tool in the diagnosis of urinary bladder carcinoma. Our data also suggest that a subdivision of the grade II tumours might be possible and meaningful in the assessment of prognosis.

Adult↗

PubMed1991

Correlation of nuclear morphometry and DNA ploidy in rectal cancer.

Several investigators have used morphometric measurements to determine differences in the nuclear size and shape of normal and neoplastic colorectal tissue. Changes in nuclear morphometric parameters have also been shown to correlate with prognosis in a variety of noncolorectal cancers. The association of nuclear morphometry with prognostic indicators in rectal cancer has not been well studied. Measurements of the nuclear area, perimeter, longest cord, and circularity factor from 39 primary rectal adenocarcinomas were compared with DNA content, degree of tumor differentiation, Dukes' class, and patient survival. Nuclear circularity was found to correlate with DNA ploidy. Nondiploid tumors with a DNA index greater than 1.3 had significantly more circular nuclei than tumors with diploid or near-diploid DNA content. There was no correlation between nuclear morphometry and Dukes' class or patient survival. Significant increases in DNA content of rectal cancers appear to be reflected by measurable changes in nuclear shape. Nuclear morphometric measurements may provide useful information in the study of the progression of neoplastic changes in colorectal cancer.

Actuarial Analysis↗

PubMed1992

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.

Animal Nutritional Physiological Phenomena↗

PubMed1989

Sample size and statistical power in the hierarchical analysis of variance: applications in morphometry of the nervous system.

Analysis of variance is commonly used in morphometry in order to ascertain differences in parameters between several populations. Failure to detect significant differences between populations (type II error) may be due to suboptimal sampling and lead to erroneous conclusions; the concept of statistical power allows one to avoid such failures by means of an adequate sampling. Several examples are given in the morphometry of the nervous system, showing the use of the power of a hierarchical analysis of variance test for the choice of appropriate sample and subsample sizes. In the first case chosen, neuronal densities in the human visual cortex, we find the number of observations to be of little effect. For dendritic spine densities in the visual cortex of mice and humans, the effect is somewhat larger. A substantial effect is shown in our last example, dendritic segmental lengths in monkey lateral geniculate nucleus. It is in the nature of the hierarchical model that sample size is always more important than subsample size. The relative weight to be attributed to subsample size thus depends on the relative magnitude of the between observations variance compared to the between individuals variance.

Aging↗

PubMedDate not supplied

Perfused capillary morphometry in the senescent brain.

This study compared quantitative indices of capillary morphometry in the perfused vs. total capillary bed of conscious young (8-10 month old) and senescent (28-33 month old) rat brains. The total capillary bed was identified through alkaline phosphatase staining of tissue sections cut from specific brain regions. The perfused capillary bed was identified by the presence of fluorescein isothiocyanate (FITC) dextran in the microvessels. Average capillary volume fraction, VV (mm3/mm3, mean +/- S.E.M.) was 0.040 +/- 0.002 and 0.033 +/- 0.001 in the total capillary bed of the young and old animals, respectively. These values were not statistically different. Perfused VV averaged 0.020 +/- 0.001 and 0.017 +/- 0.001 mm3/mm3 in the young and old animals, respectively. Average perfused VV was 50% in the young and 49% in the senescent rat brains. Young and senescent brains utilize similar proportions of their "capillary reserves." In the areas examined in the brains of young animals, differences were found in the percentage of capillary volume/mm3, VV, and surface area/mm3, SV, perfused which were not present in old animals. The structural and neurochemical changes noted by others in the brain during aging were not related to alterations in indices of average and regional total or perfused cerebral capillary bed morphometry. However, differences in percent perfused VV, SV, length, LV, and number, Na, present in the younger rat brains were not present in the senescent rat brains.

Aging↗

PubMedDate not supplied

The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney in rats.

Experiments were performed to investigate the effects of lindane and linuron on calcium metabolism, femur morphometry and nephrotoxicity. Long-Evans hooded rats were dosed daily for 10 weeks with 0, 10 or 20 mg lindane or 10, 20 or 40 mg linuron/kg body weight beginning at weaning. Lindane significantly decreased urinary calcium concentration, serum alkaline phosphatase concentration and the cross-sectional medullary area of the bone. Lindane was nephrotoxic at both dose levels as demonstrated by elevated kidney weights, kidney-to-body-weight ratios, urinary LDH, tubule regeneration and hyaline droplet degeneration. Linuron significantly reduced medullary cross-sectional area at the 2 higher dose levels and decreased the total femur cross-sectional area at the highest dose level in the absence of effects on calcium excretion. Femur density and strength were also significantly reduced at the highest dose level of linuron. Neither compound affected the serum concentrations of parathyroid hormone or 1,25-dihydroxy Vitamin D-3. Both linuron and lindane exposure significantly increased serum cholesterol concentrations and reduced serum triglyceride concentrations. Both compounds affected calcium metabolism and/or bone morphometry but possibly by different mechanisms since the effects were not the same.

Alkaline Phosphatase↗

PubMed1991

Ultrastructural morphometry of human leucocytes in health and disease.

In this review, the literature on ultrastructural morphometry of each of the main types of human blood leucocytes has been considered, together with the technical and numerical procedures essential for valid analysis. Quantitative data have been reported for these cell types in health and comparisons have been made with those in disease states. In monocytes, and in macrophages developing from them, subtle ultrastructural differences have been detected and quantitated in malignant lymphoma; as the mononuclear phagocytes were not themselves neoplastic, the changes may have related to defects in host defence. Change in the ultrastructural characteristics of leukaemic monoblasts have also been reported. Lymphocytes and malignant lymphoid cells have been extensively investigated: differences between different types and subsets have been shown to be present in both normal lymphocytes and their malignant counterparts in leukemias and lymphomas. Particular attention has been paid to morphometric assessment of nuclear shape and size in these disorders and to its possible value as a diagnostic tool. Granulocytes have so far been the subject of few morphometric studies, although in hypereosinophilic syndrome, cellular changes have been defined and have thrown light on the abnormal pattern of degranulation. There have also been scattered reports on the cells of acute myelogenous leukaemia. The use of computers and sophisticated statistical packages has greatly facilitated the application of multiple comparison procedures and has permitted discriminant analysis to be carried out where appropriate. This review shows that ultrastructural morphometry of leucocytes will have an increasing application in clinical pathology.

Granulocytes↗

PubMed1991

Correlation of endometrial histology, morphometry, and ultrasound appearance after different stimulation protocols for in vitro fertilization.

The role of endometrial factors in controlling embryo implantation is poorly understood. In the present study, histopathology and morphometry were used to investigate differences in endometrial appearance seen by ultrasound (US) in 107 in vitro fertilization patients receiving different superovulation regimens. Seventy-seven patients received clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 30 buserelin acetate down regulation/hMG. All patients received an endometrial US at the time of embryo transfer (ET). Endometrial biopsies were taken from 17 women (12 CC/hMG, 5 buserelin acetate/hMG) with fertilization failure at the time when ET would normally have occurred. The morphometry results showed that endometrial glandular volume 2 days after oocyte retrieval was significantly reduced after CC/hMG compared with buserelin acetate/hMG, despite the fact that histopathological dating was similar for both groups. In addition, significant differences in endometrial thickness and echogenicity between CC/hMG and buserelin acetate/hMG were evident by US.

Adult↗

PubMed1989

A comparison of nuclear morphometry and Gleason grade as a predictor of prognosis in stage A2 prostate cancer: a critical analysis.

The natural history of stage A2 prostate cancer is unknown. Previous studies from this institution have shown that, without treatment, a third of the men with clinically localized stage A2 prostatic adenocarcinoma will have disease progression within 4 years. Presently, most patients who present with stage A2 prostate cancer receive surgical or radiation therapy. The degree of differentiation of the tumor (Gleason score) presently is used to predict the prognosis among patients with clinically localized prostate cancer. The Gleason score does well to predict the prognosis for patients with scores of 2 to 4 and 8 to 10. Unfortunately, the majority of patients fall within the range of Gleason scores of 5 to 7. Better methods are needed to predict which patients diagnosed with stage A2 prostate cancer have a high probability of disease progression. Several studies have reported that morphometrically determined nuclear shape descriptors provided accurate separation of these patients that was superior to Gleason grading methods. To evaluate critically the usefulness of nuclear morphometry for prediction of prognosis we developed a system. The Hopkins Morphometry System, that calculated and compared 15 different shape descriptors that were analyzed by 17 different statistical tests. We tested this system on 18 untreated patients with stage A2 prostate cancer with an average followup of 10.5 years (range 5 to 18 years). For each patient 17 statistical analyses of the 15 shape descriptors (255 total) were evaluated and 50 analyses (50 of 255, 19.6%), including average nuclear roundness factor, provided significant separation (p less than 0.01) of the patients on the basis of outcome, whereas the Gleason score (p equals 0.076) did not. The best separation (p less than 0.01) was provided by the lower quartile analysis of the ellipticity shape descriptor.

Adenocarcinoma↗