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Biomedical subjects

N L Fazzalari

Publications and source records attributed to N L Fazzalari.

At least 19 recordsLinked to original sources

Cancellous bone structure analysis using image analysis.

The application of image analysis techniques for the analysis of histology are developing rapidly particularly where it is possible to prepare high contrast histology sections. Bone histology is one such instance, bone matrix can be stained with van Geisen. This preparation is particularly suitable for image segmentation using grey level threshold detection. This study has quantified the bias and random error that can be attributed to pixel sizing and the threshold detection level. Also, the influence of the working magnification and the intra and inter observer variability on the reproducibility and reliability of image analysis results. The study has analysed vertebral cancellous bone structure in vertebrae with low bone volume (5.53%) and high bone volume (20.85%) at a range of magnification (x4 to x640). Data were collected at various machine settings and at different times by the machine operators. Data were analysed using Student's paired t-test. Variation from the optimum threshold detection level significantly influences the magnitude of bone volume, bone mineral surface and trabecular thickness measurements. Bone mineral surface measurement increases as the working magnification increases, identifying the fractal nature of cancellous bone. Operator bias is less than 5% though random error can be as high as 13%. Image analysis can be very efficient and make quantitative tissue analyses more accessible to scientists interested in studies of comparative pathology. This study shows that reproducible and reliable data for the analysis of cancellous bone structure can be obtained by the application of a clearly defined operating protocol and adequate operator training.

Bone and Bones

Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis.

Twenty-four cytologic features, previously reported to be useful in the distinction of malignant mesothelioma, adenocarcinoma, and benign mesothelial proliferation in serous effusions were assessed. Forty-four cases of malignant mesotheliomas, 46 cases of metastatic adenocarcinomas, and 30 cases of benign mesothelial proliferations were examined for these parameters. When these cytologic features were subjected to a stepwise logistic regression analysis, five features were selected to distinguish malignant mesothelioma from adenocarcinoma. These were true papillary aggregates, multinucleation with atypia, cell-to-cell apposition, acinus-like structures, and balloon-like vacuolation, the latter two features being characteristic of adenocarcinoma. The four variables selected to distinguish malignant mesothelioma from benign mesothelial proliferations were nuclear pleomorphism, macronucleoli, cell-in-cell engulfment, and monolayer cell groups, the latter being a feature of benign proliferations. Using these selected variables, the logistic model correctly predicted 95.4% of cases of malignant mesothelioma versus 100% of adenocarcinoma and 100% of malignant mesotheliomas versus 90% of benign mesothelial proliferations. The results of regression analysis suggest that many of the previously described cytologic features are not important diagnostic discriminators.

Adenocarcinoma

Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.

Aged

Microfractures in coxarthrosis.

We examined the subchondral bone architecture of the femoral head in relation to trabecular microfracture. Three groups of femoral head specimens were studied. Twenty-eight specimens taken during hip replacement had grade III or IV arthrosis (70 +/- 8 years). From autopsy, 40 femoral heads were obtained, 18 in a group greater than 50 years of age (72 +/- 10 years) and 22 in a group less than 50 years of age (25 +/- 11 years). None of these 40 heads had worse than grade II arthrosis. Coronal slices of the femoral heads were macerated and examined under a dissecting microscope to count trabecular microfractures. For bone histomorphometry, blocks were taken from the subchondral principal compressive and tensile trabeculae. The bone volume, trabecular thickness, and marrow space were quantified. In the subchondral principal compressive region, the arthrotic group had more bone volume, thicker trabeculae, similar trabecular space, and trabecular microfractures when compared with the group greater than 50 years old. In the tensile region, there were no differences except for decreased trabecular microfracture number in the arthrotic group. With the thinnest trabeculae in the compressive region occurring in the greater than 50 years old group, the trabeculae of the younger age group have thinned with age, but with the onset of arthrosis, the thinning is overtaken by pathologic thickening of trabeculae.

Adult

Age-related changes in femoral trabecular bone in arthrosis.

Age-related changes in the cancellous bone in selected regions of the proximal femur and iliac crest were assessed. An arthrosis group and a control cadaver group, partitioned into subjects younger and older than aged 50 years, were compared. The control group comprised 69 heads of femur and iliac crest samples. The arthrosis group comprised 28 consecutive heads of femur affected by primary arthrosis and an iliac crest biopsy taken during hip arthroplasty. Cancellous bone was sampled from four selected regions in the proximal femur. Histomorphometric estimates of percentage bone volume were determined using image analysis. In the young controls the bone volume was higher than that in the old controls for all the regions. In the arthrosis group the bone volume was higher than that of the old controls except for the subchondral principal tensile and medial to the greater trochanter regions. The old controls had regression of bone volume on age for the subchondral and medial principal compressive regions and the iliac crest. The arthrosis group had a minimal dependence of bone volume on age. Our study showed that primary arthrosis modulates the age dependence of bone volume in the proximal femur.

Adult

Mathematical modelling of trabecular bone structure: the evaluation of analytical and quantified surface to volume relationships in the femoral head and iliac crest.

The three-dimensional architecture of trabecular bone has structural trends related to physical function as described by Wolff's law. Mathematical modelling provides a means of analysing these structures through the use of simplified representations. A single measure of mineralized bone volume per unit volume of structure (Vv) and the surface area of mineralized bone per unit volume of structure (Sv) does not identify a particular architecture in any detail; the way in which Sv changes in relation to Vv does provide this information as the structure remodels. A series of structures using the elements of plates and rods were created. The rates of change of Sv with respect to Vv for trabecular structures give insight into differences in such models. Structures in the femoral head and iliac crest were analysed by power curve regression. In the principal compressive region, just above the medial cortex, advanced osteoarthritis was associated with a preferential loss of rods from the normal trabecular structure, resulting in a more plate-like architecture. The iliac crest remodelling that takes place in the osteoporotic appears to be the result of a generalised bone loss with some of the thinner elements of the structure being removed completely, resulting in an increase in unit cell dimension. The consequence of changing unit cell size has a major impact on surface availability for osteoblastic and osteoclastic activity. The simple plate model as a basis for the stereological analysis of trabecular structures is therefore limited because of the mixed plate and rod nature of trabecular architecture.

Anthropometry

Comparative study of iliac crest and proximal femur histomorphometry in normal patients.

The relation between the bone histomorphometric profile of the iliac crest and regions of the proximal femur was investigated. In the proximal femur four blocks were selected, representing the subchondral principal compressive (SPC) and tensile (SPT) regions, the zone near the medial cortex in the principal compressive region (MPC), and the zone medial to the greater trochanter (MGT). Undecalcified tissue sections stained by the von Kossa silver method and counterstained with haematoxylin and eosin were used for quantitation. The SPT region was most representative of the iliac bone profile, in particular the structural parameters of mineralised bone, trabecular thickness, and trabecular spacing and resorption surface. Most parameters in the regions studied showed inconsistent and variable results when compared with those of the iliac crest. There was only a weak association, therefore, between the histomorphometric parameters of the iliac crest and the proximal femur despite the appeal of the use of the iliac biopsy specimen as a simple clinical test.

Adolescent

Trabecular microfractures. Nature and distribution in the proximal femur.

The nature and distribution of healing trabecular microfractures (TMF) of femoral heads were studied in 50 autopsy specimens, 30 patients with osteoarthritis (OA) of the hip and 45 patients with subcapital fractures of the femoral neck (SFFN). Macerated coronal slices were examined with a dissecting microscope, and the TMFs were identified where there was callus formation, either nodular or smooth. The number of TMFs did not differ significantly in the SFFN and age-matched control groups. The number of TMFs in the OA group was lower than in SFFN and age-matched control groups. The numbers of nodular TMFs in the control and SFFN groups did not differ significantly but were fewer in the OA group. Smooth TMFs were present in similar numbers in OA, control, and SFFN groups. The ratio of the nodular to smooth TMFs regressed with age. The greater proportion of nodular TMFs in older patients was indicative of an early stage of woven bone callus formation. In all three groups (excluding controls younger than 50 years of age), TMFs tended to appear some distance from the midpoint of the trabeculae. The number of TMFs in trabeculae parallel and perpendicular to the direction of principal stress was similar in all three groups.

Adult

Use of morphometry in cytological preparations for diagnosing follicular non-Hodgkin's lymphomas.

Morphometric techniques were applied to cytocentrifuge smears from 27 patients with histologically confirmed follicular non-Hodgkin's lymphoma to determine the usefulness of this method in diagnosis. Analysis of quantitative data confirmed that most subtypes were classified correctly on the basis of the proportion of large cells, small cleaved, and large non-cleaved cells, and nuclear, nucleolar, and cytoplasmic features. Morphometry is a more objective and reproducible technique than manual cell counting methods, and the use of cytocentrifuge smears has several advantages compared with conventional histological sectioning. Data derived with the aid of morphometry may be of value in follow up clinicopathological studies.

Cell Count

Lymph node cellular morphology: comparative study of imprints and cytocentrifuge smears.

To assess the usefulness of the lymph node imprint technique in quantitating cell types a comparative study using cytocentrifuge smears as controls was undertaken. The cell dimensions and distribution of cell types were compared in 12 patients with non-Hodgkin's lymphoma (NHL) using semi-automated image analysis. The results show that the imprint procedure introduces selective bias in favour of certain cell types; moreover, certain cell measurements, such as nuclear shape, are easier to see on cytocentrifuge smears. The imprint technique compares unfavourably with cytocentrifuge smears when precise quantitation of cell types is required.

Cell Nucleolus

Quantitation of nuclear shape in non-Hodgkin's lymphoma. Alternate shape descriptors.

The nuclear contour index (NCI) has been used extensively to quantitate cellular shape in non-Hodgkin's lymphoma (NHL). This disease entity has a mixed cellular component, with nuclei exhibiting a spectrum of shapes; the main disadvantage of conventional shape descriptors, such as NCI, is that similar values are assigned to these widely divergent shapes. In this study, two alternative shape indices, measures of convexity-concavity (C-C) and slimness (SL), were assessed to determine their suitability as shape descriptors. To achieve this, the contours of lymphoid cells in cytologic preparations of NHL were quantitated by means of semiautomated image analysis. C-C was able to identify nuclear clefts, with the values obtained by this index reflecting the number and depth of invaginations present; this index was unaffected by ellipsoid shapes. SL was able to describe ellipsoid profiles, irrespective of the presence of nuclear clefts; the index also characterized indentations, although precise identification of this form of invagination was difficult. This study confirms the usefulness of these indices in the characterization of nuclear shape; utilization of these shape descriptors enhances the accuracy of more-objective approaches to the morphologic classification of lymphoid lesions.

Cell Nucleus

Osteoarthritis of the hip. Possible protective and causative roles of trabecular microfractures in the head of the femur.

In contrast to the large volume of data on the cartilage and synovial fluid changes, there has been relatively little investigation of the involvement of bone in the genesis of osteoarthritis (OA). Previous researchers have hypothesized that OA follows stiffening of subchondral bone through trabecular microfractures. Although it is widely recognized that marked changes in the subchondral bone are a consistent feature of advanced OA, the nature of the changes in the bone in OA has not received significant attention. The heads of the femur from 67 patients who had joint replacement for advanced OA and 66 autopsy controls without discernible joint disease were examined microscopically to ascertain the number and distribution of trabecular microfractures in coronal slabs and to quantify the mineralization and thickness of trabecular bone in a principal compressive zone. There was a reduction in the number of trabecular microfractures in OA patients, compared with the controls, with a lack of correlation between numbers of microfractures and age in OA patients. There was no evidence for the hypothesis that increased numbers of microfractures led to the increase of bone to support the view that microfractures play a role in maintaining OA joint structure. Structural changes produced relatively sclerotic and porotic groups of OA and two subgroups of the sclerotic group.

Adolescent

Lymphoid aggregates in the guinea pig large bowel: development of quantitation techniques for number, volume and distribution.

A technique for assessing the number, distribution and volume of the lymphoid aggregates (LA) in the guinea pig large bowel is described. Aggregates could be visualised macroscopically after immersion of the bowel in 10% acetic acid and their number and distribution recorded by tracing on plastic sheets. Serial sections through a sample of 13 LA showed that they were ellipsoidal and this was confirmed by mathematical comparison with hypothetical ellipsoids. In practice, only the length and width of each LA could be measured but, using the sample of 13 LA, it was established that regression analysis enabled the volumes of all except the smallest LA to be predicted accurately from the knowledge of length and width alone.

Acetates

Histomorphometric changes in the trabecular structure of a selected stress region in the femur in patients with osteoarthritis and fracture of the femoral neck.

Histomorphometric changes in the trabecular structure of the principal compressive stress region in the femur in patients with osteoarthritis and fracture of the femoral neck are described. Femoral heads were obtained from patients who had surgery for the treatment of femoral neck fracture or total hip replacement for advanced osteoarthritis. Blocks from the principal compressive region of a coronal slice were sampled systematically to prepare 10 microns sections for automated analysis. There was no significant difference in the mineral bone content of the osteoarthritic (OA) and fractured neck of femur (FNOF) cases or between males and females for each group. The regression of mineralized bone on age was significant for OA data, showing a decrease in mineralized bone volume with age, whereas there was no significant relationship for the FNOF data. Surface density was significantly lower in the OA group than in the FNOF group despite the fact there is no difference in the mineralized bone. The regression of surface density on age was not statistically significant in both groups, although regression of surface density on the mineralized bone was significant for both groups and demonstrated that OA cases generated less surface than FNOF cases for the same amount of mineralized bone volume. The trabeculae in OA were significantly thicker than in FNOF, and spacing in OA was significantly greater than in FNOF. The regression of trabecular thickness and spacing on age was not significant for either OA or FNOF. For OA, thickness and spacing showed a significant regression on the mineralized bone volume, positive and negative, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Changes in bone histoquantitative parameters and histochemical staining reactions for aluminium in a group of patients with chronic renal failure following a reduction in the aluminium concentration of the haemodialysis fluid.

Bone biopsies from a group of 16 patients in chronic renal failure treated by intermittent haemodialysis were available for histoquantitative and histochemical assessment before and after the introduction of reverse osmosis treatment of the dialysis fluid. This treatment reduced the aluminium concentration of the fluid from 1.15 mg/l to less than 0.06 mg/l. After the changeover there was an increase in the extent of calcification fronts. Overall, there was a decrease in the histochemical staining reactions for aluminium, although a few cases showed increased reactions. A large percentage of cases showing decreased reactions also had decreased osteoid volumes. It is concluded that reduction of the concentration of aluminium in the dialysis fluid is associated with an improvement in mineralisation state, and this is further evidence of the importance of minimising the aluminium burden of patients with chronic renal failure.

Aluminum

Three dimensional reconstruction of the left ventricle from four anatomically defined apical two-dimensional echocardiographic views.

A method is described for three dimensional reconstruction of the left ventricle which uses four anatomically defined apical views. It is shown that the algorithms developed for reconstruction and volume estimation provide accurate results when applied to planar views with accurately defined boundaries. The linear regression equation was y = -6.32 + 1.04x, with SEE = +/- 3.4 ml, r = 0.999. For both "in vitro" and "in vivo" studies this method is found to be better than various geometrical models used to estimate volumes from two dimensional tomographic or projection views. The linear regression equation of in vitro fluid volume on volume estimate is y = 8.44 + 0.68x, with SEE = +/- 4.9 ml, r = 0.988. For pooled end diastolic and end systolic volumes (EDV and ESV) determined by three dimensional reconstruction (3-DR) and angiography the linear regression equation is y = 54.50 + 0.50x, with SEE = +/- 33.5 ml, r = 0.670. For stroke volume (SV), the regression equation is y = 21.10 + 0.40x, with SEE = +/- 12.8 ml, r = 0.750, and for ejection fraction (EF) it is y = 1.10 + 0.70x, with SEE = +/- 7.8%, r = 0.840. In patients with ischemic heart disease, the method presented is shown to be better than existing methods of volume estimation. Three dimensional perspective images can be plotted in any orientation as a visual aid to the cardiologist. In vivo studies demonstrate the feasibility of 3-DR, from anatomically defined apical views, in the clinical setting.

Cardiac Volume

A study of the first heart sound spectra in normal anesthetized cats: possible origins and chest wall influences.

Heart sound recordings were taken from cats. The heart sounds were recorded directly from the chest wall and through an esophageal tube. The phono transducer and the esophageal tube were both placed over the base of the heart. Ultrasound M-mode, or motion-mode, recordings were taken to study the mitral valve dynamics. After analogue to digital conversion, electrocardiogram gated first heart sounds of each phono record were analyzed by the fast Fourier transform to obtain a frequency spectrum. Relative energies in 15 Hz bandwidths up to 150 Hz were correlated with the mitral valve closing velocity of the anterior mitral leaflet, obtained from the M-mode echocardiograms. The closing velocity correlated best with the energy in the 30-45 Hz bandwidth and 60-75 Hz bandwidth for the externally and internally monitored phonocardiogram respectively. The chest wall acted as a low pass filter, that is, the wall favoured the transmission of low frequencies and the energy transmitted decreased as wall thickness increased.

Anesthesia

Bone histoquantitative findings and histochemical staining reactions for aluminium in chronic renal failure patients treated with haemodialysis fluids containing high and low concentrations of aluminium.

A total of 112 undecalcified bone biopsies from 67 patients under treatment for chronic renal failure by maintenance haemodialysis was available for retrospective study. The patients were divided into three groups. Group I (15 cases) had been dialysed for the majority of the time in their own homes with a fluid containing a low concentration of aluminium. Group II (28 cases) had been dialysed exclusively in hospital (prior to 1978) with a fluid containing a high concentration of aluminium and group III (24 cases) had been treated exclusively in hospital (from 1978 onwards) with a fluid of low aluminium concentration. The tissues from these groups were subjected to histoquantitative assessment and stained by a histochemical technique to demonstrate aluminium salt. In group II, 71.4% of cases showed positive aluminium staining reactions (at the osteoid/mineralised tissue interface) compared to 26.6% in group I and 37.5% in group III. Staining reactions were also more extensive in group II cases. The osteoid volume was significantly increased and the calcification front extents significantly decreased in group II compared to both groups I and III. A comparison of histochemically positive with negative cases in each group showed a significantly increased osteoid volume and significantly decreased calcification fronts in the positive cases. It was, therefore, concluded that haemodialysis against a fluid containing a high concentration of aluminium leads to intraosseous aluminium accumulation of greater degree in a larger number of patients than a fluid with low aluminium content and that there is an accompanying osteomalacia manifest by an increase in osteoid volume together with diminution in the extent of the calcification fronts.

Adult