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Biomedical subjects

Z F Jaworski

Publications and source records attributed to Z F Jaworski.

At least 19 recordsLinked to original sources

Reversibility of nontraumatic disuse osteoporosis during its active phase.

The potential for the recovery of bone lost during the active phase of disuse osteoporosis, both in the diaphyseal compacta and metaphyseal spongiosa was tested in young adult and old Beagle dogs. Immobilization for up to 60 weeks was achieved by placing the forelimb in a spica cast and remobilization by removing it. Bone volume was estimated in the third metacarpus, radius, ulna and humerus at the mid-diaphysis and at the level of distal metaphyseal spongiosa in both forelimbs by radiography and histomorphometry. Measurements carried out on animals remobilized showed considerable recovery of the original bone loss. In both age groups, the residual deficits increased, however, with the duration of immobilization and were similar in the metaphyseal spongiosa and in the diaphyseal compacta. The old dogs which began the study with 10% less bone than the younger dogs, showed smaller proportional losses than the younger dogs but greater residual deficits, most evident in the diaphysis. In both age groups the distal, weight-bearing bones tended to show greater losses and also greater recovery both in diaphyseal compacta and the metaphyseal spongiosa. Thus, 28 weeks after cast removal following 32 weeks of immobilization the following findings were noted: In the third metacarpal diaphyseal compacta in the younger dogs, a 53.6% loss (mostly from the periosteal envelope) decreased to 16.3% (a 70% recovery) while in the older dogs a 37.6% loss (mostly from the endosteal envelope) decreased to 23% (a 40% recovery).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Periosteal stress-induced reactions resembling stress fractures. A radiologic and histologic study in dogs.

An external callus is always associated with so-called stress fractures, but a fracture line cannot always be demonstrated by radiologic means. In such instances it is assumed that an undisplaced fracture or microfracture must nevertheless exist for an external callus to form. In this experimental study, 18 beagles were immobilized in a shoulder spica for periods of time ranging from 6 to 32 weeks and then remobilized. At the time of sacrifice, which varied from four to 28 weeks after remobilization was started, eight showed on radiographs an external fusiform bone formation on the distal metacarpal metaphysis during the remobilization period without evidence of a fracture line. Serial histologic examination, in seven metacarpi, also failed to reveal the presence of any break in the bone's continuity. Although this does not exclude the accumulation of microdamage (mechanical fatigue) at such sites, there is sufficient evidence that the circumscribed periosteal reaction occurred at a site of increased stress in the absence of an actual fracture. Consequently, this condition is called a periosteal stress-induced reaction.

Animals↗

Lamellar bone turnover system and its effector organ.

Juxtaposition of cell kinetics in the asymmetric, self-renewing osteoclast and osteoblast populations in the evolving secondary Haversian systems, which are in neutral balance, disclosed their genetically determined fixed and flexible or variable properties, the latter controllable. These jointly controlled cell populations (coupling) at local and organ level, constitute the Effector Organ of Lamellar Bone Turnover Systems (EO LBTS). In part genetically preprogrammed, this system also responds during growth and maturity to environmental (mainly biomechanical) factors that adjust structure to function. Since the pattern of signals and stimuli generated within the bones under the conditions of mechanical loads differs during growth and maturity, the two major expressions of the LBTS (i.e., modeling of bones during growth and their remodeling during growth and maturity) can be explained by the appropriate response of its EO to those patterns. Since normal physical activity has a limited range and bones sustain more or less predictable deforming forces, the signals and stimuli so generated must preserve more or less similar patterns. Considering also the constraints on the system (constants of the EO LBTS), modeling and remodeling patterns, as well as the gross and microscopic organization of bones, would vary little from one individual to another under normal circumstances. For its proper function, the EO LBTS requires the presence in the cell environment of specific and nonspecific permissive factors (as any cell or tissue in the organism) and it may be influenced further by modulatory factors which link it with the system maintaining calcium ion homeostasis in the body fluids. Mechanical failure of the skeleton in metabolic bone disease can be explained by the alterations in the biochemical or biomechanical milieu due to disorders of other organs and systems which interfere with the primary (structural) function of the EO LBTS.

Adaptation, Physiological↗

Kinetics of osteoclasts and their nuclei in evolving secondary Haversian systems.

A study of osteoclast and osteoclast nuclear population kinetics within evolving secondary osteons was undertaken in young adult Beagle dogs. Autoradiographs of serial longitudinal rib biopsy sections taken from 1 hour to 15 days after tritiated thymidine injection were analysed as to the time and the rate of appearance of the labelled nuclei within the osteoclasts and their nuclei. Such systems contained an average of nine osteoclasts, each containing an average of nine nuclei. Labelled osteoclast nuclei first appeared within 24 hours, peaked at 10% at 4 days, and declined to 1% or less after 11.5 days more. Thus, the entry rate of new nuclei into (and their exit from) the population of osteoclast nuclei under steady state conditions approximates 8% per day. Therefore, the total mononuclear osteoclast population may be viewed as divided into functional units, i.e. osteoclasts. From the ratio of the osteoclast nuclei in the cutting cone to the number of osteoblasts in the closing cone (as well as from their rates of resorption and formation), it was deduced that the osteoclast per nucleus is approximately 20-40 times more efficient than the osteoblast. Because of the intrinsically different efficiencies and life spans of these two cell types, the rates of resorption and formation within evolving Haversian systems and the amounts of bone ultimately resorbed and formed by the system, are determined by the rate and duration of the respective precursor cell proliferation. It is at this level that factors which control the bone remodelling and balance must operate.

Animals↗

Study of cell kinetics within evolving secondary Haversian systems.

A study of the origin, proliferation rate and migration of cells within the secondary evolving Haversian systems was undertaken in young adult Beagle dogs. Autoradiographs of serial longitudinal sections prepared from rib biopsies taken from one hour to eleven days after the injection of tritiated thymidine were subjected to semiquantitative analysis as to the time of appearance, number, location and transformation of various labelled cells. Numerous labelled osteoblasts appeared early (at 14-24 hours) in the most proximal closing cone. With time, this zone was seen to have been left behind the advancing cutting cone and the successive generations of osteoblasts. The first labelled osteocytes were seen at nine days after injection, in the distal closing cone. Labelled nuclei within the osteoclasts were few and appeared late (none before 24 hours). It is apparent that each self renewing cell population within these systems (i.e. osteoclasts, osteoblasts and endothelial cells) derives from its own immediate precursor and evolves at its own speed. The mononuclear osteoclasts' precursors divide locally and infrequently and the turnover of osteoclastic nuclei appears to be slow; consequently their life span and that of the osteoclasts appears to be longer than the time of the observation, i.e. 11 days. The proliferation of osteoblasts' precursors and osteoblasts recruitment is rapid. The life span of osteoblasts was found to be indeterminate; some osteoblasts may become osteocytes within a few days while others may continue to deposit bone for several weeks. Since the recruitment of osteoclastic nuclei is slow while that of the osteoblasts is fast, it is unlikely that the osteoclasts in the sites of lamellar bone remodelling modulate into osteoblasts.

Animals↗

Pseudohypoparathyroidism and epilepsy: diagnostic value of computerized cranial tomography.

Computerized cranial tomograms (CCTs) unexpectedly showed bilateral symmetrical calcifications in the basal ganglia and frontal areas in two unrelated epileptic patients 12 and 13 years of age. The patients presented with a variety of seizures, some with focal features; these seizures were resistant to medication in the first case. Subsequent testing revealed hypocalcemia and other biochemical and radiologic features of pseudohypoparathyroidism, despite absence of the usual phenotypic features, tetanic symptoms, and positive family history. The CCT scan may provide the first clue to an underlying hypocalcemic disorder in an epileptic patient even when the skull X-ray is normal. Early detection of this metabolic condition by CCT scanning allows specific treatment to restore serum calcium levels to normal, which usually eliminates seizures and favors optimal cerebral functioning. Serial CCT scanning also provides a useful means for following the intracerebral calcifications, which remained unchanged after 1 and 2 years of normocalcemia in our 2 patients.

Adolescent↗

Bone loss in response to long-term immobilisation.

The histodynamic response to long-term "non-traumatic" immobilisation was studied in young adult Beagle dogs by means of radiomorphometry and histomorphometry, the right forelimb being encased in plaster and the left forelimb serving as a control. The dogs were killed at two, four, six, eight, twelve, sixteen, twenty, twenty-four, thirty-two and forty weeks and the third metacarpal, radius, ulna and humerus removed for analysis of the contributions of the periosteal, haversian and endosteal envelopes to the bone loss at the mid-diaphysis. The bone mass responded to long-term immobilisation in three stages. First there was a rapid initial loss of bone, reaching its maximum (some 16 per cent of original mass) at six weeks, to which all three bone envelopes, to some extent, contributed. A rapid reversal followed, the bone mass approaching the control values between eight and twelve weeks after immobilisation. A second stage of slower but longer lasting bone loss ended twenty-four to thirty-two weeks after immobilisation; the periosteal envelope was the main contributor (80 to 90 per cent of the total loss). The third stage was characterised by maintenance of the bone mass which had been reduced by some 30 to 50 per cent of original values. This pattern was qualitatively similar in all four bones but the distal bones lost more bone than the proximal bones. The extent of resorption surface and the total histologically "active" periosteal envelope increased parallel to the phases of bone loss. The linear mineralisation rate did not differ significantly between the experimental and control sides.

Animals↗

Impaired osteoclastic function and linear bone erosion rate in secondary hyperparathyroidism associated with chronic renal failure.

Osteoclastic function, as estimated by the speed with which the haversian cutting cones advance through the compacta of the rib (linear erosion) was found significantly decreased (27.97-SE 0.8 mu/day versus normal 43.61-SE 0.7 mu/day) in dogs rendered chronically uremic (BUN between 36-89 mg/100 ml). The cause of the impairment of osteoclasts' function was tentatively ascribed to the chronic excess of the circulating parathyroid hormone. A decrease in the linear erosion rate, such as observed in this study, will produce predictable morphological changes. As the time necessary to erode a cavity increases, so does the lifespan of cavities, their number and consequently the bone surface area (or in the bone section the perimeter length) covered by Howship's lacunae. Thus, the increased total bone erosion perimeter in secondary hyperparathyroidism associated with moderate uremia does not necessarily reflect an accelerated tissue level erosion rate or even bone loss. As the remodeling sites in both adult man and dog have a similar standard configuration and dimensions, these observations may be extrapolated to disease in man.

Alkaline Phosphatase↗