Biomedical subjects

N L Fazzalari

Publications and source records attributed to N L Fazzalari.

At least 19 recordsLinked to original sources

PubMed1997

Quantitative analysis of trabecular morphogenesis in the human costochondral junction during the postnatal period in normal subjects.

BACKGROUND: Quantitative histomorphometric features of the bone growth plate in the human rib have been investigated in infants, ranging in age from 3-36 weeks (mean 18.6 weeks) to provide data currently not available. METHODS: Measurements were taken in each histological zone of the growth plate. Data from 20 cases were pooled and parameters describing the characteristic features of trabecular bone calculated using morphometric formulae. The measurements were made from the resting zone of the cartilage to the secondary spongiosa, 3.78 mm from the starting point. RESULTS: Cartilage volume fraction decreased from 78% in the resting zone to a bone volume fraction of between 20% and 30% in the secondary cancellous bone. Cartilage matrix surface increased rapidly in the cartilage and bone mineral surface declined in correspondence with the development of primary bone. The distance between chondrocyte lacunae was observed to decrease throughout the cartilage to a transverse septa thickness of 18 microns in the hypertrophic zone. A rapid increase in trabecular thickness to 128 microns was observed in the primary spongiosa, the secondary spongiosa ranging between 137 microns and 168 microns. Spacing, chondrocyte profile transverse diameter, increased to 30 microns in the hypertrophic zone, following which an increase in trabecular separation to 347 microns was observed in the primary spongiosa. The number of transverse intervals between individual chondrocyte lacunae was observed to increase in the cartilage to a maximum of 21.3 cartilaginous or mineralised septa per mm of growth plate length in the hypertrophic zone. Trabeculae in the metaphysis then decreased in number to approximately 1.5 trabeculae per mm in the secondary spongiosa. CONCLUSIONS: These data thus provide new insight into the development of trabecular structure during growth and normal values for the comparison of tissue from skeletal dysplasias and growth disorders.

Achondroplasia↗

PubMed1997

Fractal properties of subchondral cancellous bone in severe osteoarthritis of the hip.

Primary osteoarthritis of the hip results in changes to the architecture of subchondral cancellous bone. These changes in architecture occur through the action of osteoclasts and osteoblasts in selectively removing and adding bone. The quantitative description of the bone architecture helps in understanding the etiology of primary osteoarthritis. Fractal analysis is a method for describing complex shapes, which is expressed numerically as the fractal dimension. A box counting method was used, where the perimeter of binary profiles of cancellous bone samples was measured for different box sizes. The fractal dimension was the absolute value of the slope of the straight line segments from the plot of the log number of boxes versus the log box size. Cancellous bone samples from two subchondral regions, superior and inferomedial, to the fovea were analyzed from primary severe osteoarthritic specimens taken following total hip replacement surgery (n = 19, aged 51-80 years) and autopsy controls (n = 25, aged 18-90 years). There were three straight line segments identified on the log-log plot, for each subject, indicating a fractal dimension over three different ranges of scale. The results show that in the superior region there is a highly significant difference between the groups (p < 0.0001) for fractal 1 and pivot point 2. The histomorphometry shows significant differences for bone volume/total volume, bone surface/total volume, trabecular separation, and osteoid surface/total volume between groups. In the inferomedial region fractal 1 and fractal 2 are significantly different. For the histomorphometry, trabecular thickness and eroded surface/total volume are significantly different between the groups. The pivot points, i.e., the box size at which the fractal dimension changes, were of similar magnitude to the trabecular thickness and trabecular separation. These data suggest that the fractal geometry analysis of cancellous bone identifies architectural features not easily recognized by conventional bone histomorphometry. The fractal dimension is a descriptor of bone structure which simplifies the description of a complex structure and enables changes in cancellous bone architecture, due to disease, to be identified.

Adolescent↗

PubMed1996

Enzyme replacement therapy in a feline model of Maroteaux-Lamy syndrome.

We report studies that suggest enzyme replacement therapy will result in a significant reduction in disease progression and tissue pathology in patients with Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). A feline model for MPS VI was used to evaluate tissue distribution and clinical efficacy of three forms of recombinant human N-acetylgalactosamine-4-sulfatase (rh4S, EC 3.1.6.1). Intravenously administered rh4S was rapidly cleared from circulation. The majority of rh4S was distributed to liver, but was also detected in most other tissues. Tissue half-life was approximately 2-4 d. Three MPS VI cats given regular intravenous infusions of rh4S for up to 20 mo showed variable reduction of storage vacuoles in Kupffer cells and connective tissues, however cartilage chondrocytes remained vacuolated. Vertebral bone mineral volume was improved in two MPS VI cats in which therapy was initiated before skeletal maturity, and increased bone volume appeared to correlate with earlier age of onset of therapy. One cat showed greater mobility in response to therapy.

Animals↗

PubMed1996

Fractal dimension and architecture of trabecular bone.

The fractal dimension of trabecular bone was determined for biopsies from the proximal femur of 25 subjects undergoing hip arthroplasty. The average age was 67.7 years. A binary profile of the trabecular bone in the biopsy was obtained from a digitized image. A program written for the Quantimet 520 performed the fractal analysis. The fractal dimension was calculated for each specimen, using boxes whose sides ranged from 65 to 1000 microns in length. The mean fractal dimension for the 25 subjects was 1.195 +/- 0.064 and shows that in Euclidean terms the surface extent of trabecular bone is indeterminate. The Quantimet 520 was also used to perform bone histomorphometric measurements. These were bone volume/total volume (BV/TV) (per cent) = 11.05 +/- 4.38, bone surface/total volume (BS/TV) (mm2/mm3) = 1.90 +/- 0.51, trabecular thickness (Tb.Th) (mm) = 0.12 +/- 0.03, trabecular spacing (Tb.Sp) (mm) = 1.03 +/- 0.36, and trabecular number (Tb.N) (number/mm) = 0.95 +/- 0.25. Pearsons' correlation coefficients showed a statistically significant relationship between the fractal dimension and all the histomorphometric parameters, with BV/TV (r = 0.85, P < 0.0001), BS/TV (r = 0.74, P < 0.0001), Tb.Th (r = 0.50, P < 0.02), Tb.Sp (r = -0.81, P < 0.0001), and Tb.N (r = 0.76, P < 0.0001). This method for calculating fractal dimension shows that trabecular bone exhibits fractal properties over a defined box size, which is within the dimensions of a structural unit for trabecular bone. Therefore, the fractal dimension of trabecular bone provides a measure which does not rely on Euclidean descriptors in order to describe a complex geometry.

Adult↗

PubMed1996

Adaptive changes in trabecular architecture in relation to functional strain patterns and disuse.

Principal strains and their orientation, determined from in vivo and in situ strains recorded from the lateral cortical surface of the calcaneus of potoroos (a small marsupial) during treadmill exercise and tension applied via the Achilles tendon, were compared with the underlying trabecular architecture and its alignment to test Wolff's "trajectorial theory" of trabecular alignment. In vivo and in situ principal compressive strains (-800 to -2000 mu e) were found to be aligned (mean 161 +/- 7 degrees) close to the preferred alignment (160 degrees) of underlying trabeculae within the calcaneal metaphysis [a second trabecular arcade was closely aligned (70 degrees) with the direction (71 degrees) of principal tensile strain]. This finding represents quantitative verification of Wolff's trajectorial theory of trabecular alignment. These trabecular alignments, as measured by trabecular anisotropy (TbAn, the ratio of horizontal: vertical intercepts), remained unchanged (p > 0.05) after 8 weeks of disuse. However, trabecular bone volume fraction (BV/TV, -35%), trabecular thickness (TbTh, -25%), and trabecular number (TbN, -16%) were reduced for the tenotomized calcaneii relative to their contralateral controls (p < 0.001 to < 0.003). The reduction in trabecular number was associated with a corresponding increase in trabecular spacing (TbSp, +30%). Together, these results suggest that once trabecular alignment is established during growth (along the directions of principal strain during locomotion), it is not altered when functional strains are removed.

Adaptation, Physiological↗

PubMed1994

The relationship between head-neck-shaft angle, calcar width, articular cartilage thickness and bone volume in arthrosis of the hip.

The thickness of articular cartilage and the macroscopic and morphometric characteristics of bone in the proximal femur were assessed in a group of 28 surgically-treated patients with advanced idiopathic osteoarthrosis, and compared with the findings in a group of 16 non-arthrotic femora obtained at autopsy. In arthrosis, the BMI was increased, cartilage thickness at two principal stress sites was found to be significantly reduced, and the femoral head-neck-shaft angle was reduced. The calcar width of the cortical bone in the femur was unchanged. Bone volume was increased at the principal compressive region and diminished at both of the tensile regions. Regression analysis showed that in arthrosis calcar width was dependent on BMI and bone volume in the medial principal compressive region of the proximal femur. Furthermore, the volume of bone medial to the greater trochanter was significantly correlated with BMI.

Aged↗

PubMed1994

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↗

PubMed1993

Trabecular microfracture.

Healing trabecular microfractures are a common feature in cancellous bone. These lesions, when observed in macerated cancellous bone slices, measure about 500 microns in diameter and surround fractures in trabeculae with microcallus. Whether microcallus is a structure acting primarily as a transient brace, preventing relative movement of the fragmented segments and enabling the trabecula to heal, or whether it is a permanent buttress reducing the stress on the fractured strut, preventing the healing process, is not known. Microfractures are the result of normal physical activity. Hence, the widespread occurrence of trabecular microfracture in cancellous bone implies that a reasonable rate of microfracture is physiologically tolerable. There are three putative effects for trabecular microfracture. One is that, in response to impulse loading, cancellous subchondral bone increases its rigidity due to osteosclerosis resulting from bone formed around microfractures. Another hypothesis is that, if sufficient trabecular microfractures occur, they will compromise the trabecular structure of the vertebra and the proximal femur leading to osteoporotic fracture. By inducing remodeling changes, microfractures have an effect on the maintenance of joint structure. There are two histological patterns for microfractures: an early stage, when actively forming woven bone is bridging the fracture; and a more common late stage, when woven bone is inactive. Femoral studies fail to demonstrate that an increasing number of healed or healing microfractures in osteoarthrosis causes the increase of bone in the head of femur. Only one study has reported a significant increase in the number of trabecular microfractures in osteoarthritic femoral heads compared with normal controls. This significant increase was in patients taking antiinflammatory drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗

PubMed1993

Direct calculation of the surface-to-volume ratio for human cancellous bone.

There are many diseases which cause detrimental changes in the trabecular structure of cancellous bone, leading to mechanical failure of the tissue. One approach to understanding the mechanisms of these diseases is to create idealized models that recreate the morphology of the tissue. This paper presents a partial development of such a model. Further histological methods must be developed before a complete definition of morphologically valid models is possible. In a histological section of cancellous bone, the orientation and length of the trabecular surfaces determine how a line drawn across the bone section will intersect the bone-marrow interface. The distribution of the average length between intersections for a set of parallel lines is defined as the mean intercept length distribution. In this paper, the average surface morphology and volume of the average structure of cancellous bone is determined from an examination of the mean intercept length. The average structure of cancellous bone contains a repeated structural element (SE). As a result, the basic bone structure is analogous to a brick wall made from many similar bricks. For a group of 107 specimens, a strong relationship between structural element volume (SE.V) and bone volume fraction (BV/TV) is demonstrated, SE.V = 0.017 kappa (BV/TV)-2.05 mm3, R2 = 0.93, with kappa a model-dependent constant. For the same specimens, the structural element surface (SE.S) showed the relationship, SE.S = 0.144 kappa (BV/TV)-1.35, R2 = 0.92. As a result of the inverse square dependence of structural element volume on bone volume fraction, it is predicted that cancellous bone strength is inversely proportional to structural element volume.

Adult↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1987

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↗