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Biomedical subjects

C Alexandre

Publications and source records attributed to C Alexandre.

At least 145 records · Page 8Linked to original sources

Cytomorphometry of osteoclasts.

Tartrate resistant acid phosphatase (TRAP) is considered as an enzyme marker for osteoclasts and their precursors. A cytomorphometric study of the osteoclastic population was made after TRAP staining on transiliac bone biopsies from 10 human volunteers, and the diameter of each TRAP positive profile was determined with an automatic image analyser. The frequency distribution of the cell diameter followed a lognormal law. TRAP positive cells along bone trabeculae belong to a homogeneous osteoclastic population.

Acid Phosphatase↗

Histologic evidence of an abnormal bone remodeling in B-cell malignancies other than multiple myeloma.

In a prospective study of the quantitative bone changes induced by B-cell cancers other than multiple myeloma (MM), but including chronic lymphocytic leukemia (CLL; n = 8), hairy cell leukemia (HCL; n = 3), and Waldenström disease (WD; n = 7), an abnormal bone remodeling close to malignant cells was found in 80% of the patients. This was observed more frequently in cases of diffuse, but not nodular, bone marrow involvement by tumor cells. More particularly, excessive bone resorption (a major feature of MM) associated with a normal to low bone formation (i.e., uncoupling bone disease) was the most frequent feature and in the same range of that observed in overt MM. However, as opposed to MM, this bone resorption was characteristically mediated by small mononucleated osteoclasts (i.e., microresorption). The same phenomena of abnormal bone remodeling, the uncoupling process, excessive bone resorption, and above all microresorption were confirmed by the detailed bone study of five cases of B-cell cancers other than MM presenting lytic bone lesions and hypercalcemia. The current findings are important for clarifying the biology of these B-cell malignant diseases, and also could be of diagnostic and prognostic value.

Adult↗

Hypocalcemia response following calcitonin administration: lack of correlation with osteoclast number determined after histoenzymologic identification in osteoporosis.

The relationship between calcitonin-induced hypocalcemia and histomorphometric parameters of bone resorption was examined in iliac crest biopsies of 30 osteoporotic patients aged 55-86 years all of whom had received a single injection of 100 UI of salmon calcitonin. Number of osteoclasts and active resorption surfaces were determined after histoenzymologic staining based on osteoclastic tartrate resistant acid phosphatase content. No significant correlation could be demonstrated between the drop of hypocalcemia and the different histomorphometric parameters. It can be concluded that the calcitonin test is useless in osteoporosis.

Aged↗

Effects of a one-year administration of phosphate and intermittent calcitonin on bone-forming and bone-resorbing cells in involutional osteoporosis: a histomorphometric study.

The bone histomorphometric effects of intermittent phosphate and calcitonin therapy during 1 year were analyzed in 15 involutional osteoporotic patients. Phosphate was administered continuously (1.5 g/day) and calcitonin was injected during 5 days every third week (50 IU/day). The bone cell response was analyzed in two separate groups, according to the amount of trabecular bone present in the iliac bone biopsy: patients with trabecular bone volume (TBV) beyond the histomorphometric spontaneous fracture threshold (0.16 mm3/mm3) (group 1; 11 patients) and patients with TBV above this threshold (group 2; 4 patients). In group 1, the treatment significantly increased TBV from 0.113 +/- 0.025 to 0.156 +/- 0.046 mm3/mm3 by thickening the existing trabeculae rather than by creating new trabeculae; stimulation of bone formation rate (+ 50%) and significant reduction in active trabecular resorption surfaces (from 0.021 +/- 0.013 to 0.010 +/- 0.006 mm2/mm2; P less than .05) may have led to positive bone balance. In group 2, TBV was not changed because of the treatment's relative inefficiency for reducing the bone-resorbing cell activity, leading to likely persistent negative bone balance. Cortical thickness did not change in either group. This study confirms the positive effectiveness of continuous treatment with phosphate and intermittent calcitonin during 1 year on bone balance in involutional osteoporosis with low amount of bone. The lack of response in patients with normal amount of bone must be verified before raising the hypothesis of different bone cell activity and before anticipating the therapeutic response according to local bone mass besides bone remodeling status in osteoporosis.

Aged↗

Improved algorithms for automatic bone histomorphometry on a numerized image analysis system.

Quantitative histological methods have proved to be the most effective methods in bone disease research. Faster and more accurate techniques are currently needed. We have developed a simple digitized image analysis system which allows accurate measurements of trabecular bone mass. The algorithm is based on the 'four-connected sets' mathematical theory. Given a numerized image displayed by a CCD camera, the algorithm recognizes all possible four-connected sets and provides area measurements. The first procedure automatically eliminates small, irrelevant profiles (wrinkles, cell nuclei, etc.) while larger profiles are erased interactively. The second procedure similarly erases the artefactual defects within the trabeculae (artefactual cracks or empty osteocytic lacunae). The method was shown to be very accurate and time-saving.

Algorithms↗

Trabecular bone remodeling after seven days of weightlessness exposure (BIOCOSMOS 1667).

Seven male rats were exposed to 7 days of weightlessness in the Soviet mission COSMOS 1667 and compared with seven control rats by bone histomorphometric methods. In proximal tibial metaphysis, the trabecular bone volume was markedly reduced in flight animals. Trabeculae were decreased in number and thickness; this probably leads to alteration of bone mechanical properties. Formation activity (reflected by measurements of osteoid seams) was decreased at trabecular and endosteal levels. Resorption activity (estimated by count of osteoclast number and active resorption surfaces using a histoenzymologic method) remained unchanged. The imbalance between these cellular activities appears to be responsible for the loss of trabecular bone mass. In proximal femoral metaphysis, measurements were performed in an area located under the muscular insertions. The trabecular bone volume, despite a slight decrease in flight rats, was not significantly different from that of control rats. Furthermore, osteoclastic and osteoid parameters were unchanged. Differential responses between these two long bones need additional investigations. In thoracic and lumbar vertebrae no detectable change in bone mass and bone resorption parameters was found.

Animals↗

Spatial distribution of trabeculae in iliac bone from 145 osteoporotic females.

145 women showing clinical and radiological signs of involutional osteoporosis of the spine were biopsed at the ilium for histomorphometric analysis of bone mass including trabecular bone volume and parameters reflecting the spatial distribution of bony elements (mean trabecular plate thickness, density and separation). Results were compared with an age-matched population of 22 healthy females. Postmenopausal osteoporotics (i.e. younger than 75 years) were characterized by a significant reduction in trabecular bone volume, plate density and thickness, while senile osteoporotics (i.e. older than 75 years) did not exhibit any difference with controls. 51% of the osteoporotic patients had a trabecular bone volume higher than the spontaneous vertebral crush threshold defined by Meunier. Osteoporotic patients with trabecular bone volume under the vertebral crush threshold had a significant decrease in all trabecular parameters. On the opposite, patients with trabecular bone volume above the vertebral crush threshold had only a significant decrease in the number of trabeculae. A negative correlation was found between age and plate density in both osteoporotic patients and controls. A linear correlation was found between trabecular bone volume and plate density, but thickness and density of trabecular plates were not correlated. This study confirms that involutional osteoporosis is not only a decreased bone mass disorder. A modified spatial distribution of trabeculae or a mechanically less resistant bone matrix could be additional factors.

Aged↗

[Male sterility. Experience of an andrologist].

Male sterility is taken as a paradigm for a new approach to andrology. Although known about since Antiquity, responsibility of man in conjugal sterility has only been recognized in the last half century. All the same, even to day, it is not always accepted: although apparently obsolete since women's sexual liberation, this denial often manifests itself in patients behaviour, as well as in their doctor's. Until now, as far as we know, no andrologist has taken into account this strange denial. The aim of this paper is to draw attention to the need for the andrologist to be aware of it in his approach to the sterile man. History of male sterility emphasizes the coexistence, since Antiquity, of two opposite preoccupations, those of doctors thoughtful of proving male sterility existence and those of philosophers, often determined to deny it. Steps of knowledge as well as social structures institutionalizing its dissembling are described. Sexual liberation which claimed to put and end to women's dependence on men is often illusory; acceptance of equality of sexes by men is often more apparent that real. At present, the medicalization of male sterility leads some patients and even some doctors to an activist behaviour which demonstrate their inability to accept even the concept of man sterility. In our opinion, to be an andrologist in the full sense of the word means not only to know the biology of reproduction and the progresses of research in this domain, but also and mainly to be aware of the permanence of prejudices and fantasies infallibly conveyed by the idea of sterility in every one, andrologist included.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[Effects of weightlessness on phospho-calcium metabolism and its hormonal regulation in man during the 51 G Franco-American space flight].

During the 51 G franco-american mission in weightlessness, calcium metabolism and hormonal regulation were analyzed in two astronauts (a male, a female) before (30,7 and 4 days) and after (0,2 and 5 days) the 7-day spaceflight. Calcium, phosphate, alkaline phosphatase, GLA protein, 25 hydro-vitamin D, 1-25 dihydroxyvitamin D, parathyroid hormone, 24 h urinary calcium, total, dialysable and nondialysable hydroxyproline and glycosaminoglycans (GAG) were measured in blood and urine. Only urinary parameters are increased after space flight. Blood parameters, in particular hormone measurements, are unchanged. The data indicate stimulation of resorptive activity which could result in bone matrix atrophy and demineralisation. On the contrary, no bone formation impairment is noted since alkaline phosphatase and GLA protein are unchanged. These changes are not dependent on hormonal variations. They could only reflect the mechanical bone adaptation to weightlessness.

Adult↗

[Relations between trabecular bone mass and the configuration in the space of the trabeculae of bone. Histomorphometric study of a population of 145 osteoporotic women].

145 women with involution osteoporosis and at least one vertebral compression noted on X-Rays, underwent a biopsy of the iliac wing and measurement of the mean cortical thickness, trabecular bony volume and parameters concerning the spatial configuration of bony trabecules (MTPT = Mean Trabecular Plate Thickness, MTPD = Mean Trabercular Plate Density, MTPS = Mean Trabecular Plate Separation), reflecting respectively the thickness, the density and the separation of the trabecules. The results were compared with those of a series of 22 control women of the same age. The post-menopausal osteoporotic patients present a decreased VTO, MTPD and MTPS with normal MTPT. Patients with senile osteoporosis show no difference as compared to the control patients of the same age. Half of the patients had a VTO higher than the spontaneous vertebral fracture threshold. Involution osteoporosis where the VTO exceeds the threshold present a significant decrease of the number of bony trabecules without decreased thickness. There is a negative correlation between age and the number of trabecules; a linear correlation between VTO and thickness, between VTO and trabecular density confirming the close relationship between mass and spatial configuration of the bone. There is a geometric configuration between density and separation of the trabecules, indicating a great sensitivity of the microstructural framework of disorganized trabecular bone. These data show that a decreased bony mass is not the only physiopathological mechanism observed during involution osteoporosis. Alterations of the spatial configuration of the trabecules or the mechanical resistance of the bony matrix are additional factors, the role of which might have been underestimated.

Aged↗

B cell malignancies presenting with unusual bone involvement and mimicking multiple myeloma. Study of nine cases.

Nine unusual cases of B cell malignancies presenting with lytic bone lesions on radiography and/or hypercalcemia, and mimicking multiple myeloma are reported in this study. These cases included acute lymphoblastic leukemia (one patient), non-Hodgkin's lymphoma (five patients), chronic lymphocytic leukemia (two patients), and Waldenström's disease (one patient). Quantitative bone biopsy performed in two patients (one with non-Hodgkin's lymphoma and one with Waldenström's disease) demonstrated a dramatic increase in osteoclastic resorption close to tumor cells in both cases, similar to or even more marked than that observed in multiple myeloma. Finally, significant production of bone resorbing activity was found in short-term liquid culture specimens of tumor cells in eight of the nine cases. These observations clearly indicate that in B cell disorders other than multiple myeloma, the malignant B cells can produce significant bone resorbing activity in vitro and result in excessive osteoclastic resorption and lytic bone lesions, frequent hypercalcemia, and an overall disease picture clinically mimicking multiple myeloma.

Adolescent↗

Effects of weightlessness on bone mass and osteoclast number in pregnant rats after a five-day spaceflight (COSMOS 1514).

Five pregnant growing rats were orbited for 5 days aboard the Soviet COSMOS 1514 biologic satellite. The bone effects of weightlessness were studied and compared to those of five pregnant rats kept in vivarium and five pregnant conditioned rats. Bone histomorphometric studies were performed to investigate the early effects of weightlessness in loaded (tibia-femur) and unloaded (thoracic and lumbar vertebrae) bones. A short exposure to weightlessness does not induce any change in bone mass and inner structure in either type of bone. In unloaded bones, the number of osteoclasts per square millimeter of the trabecular surface significantly increased when measured after histochemical demonstration of tartrate-resistant acid phosphatase. It is likely that a stimulation of bone resorption activity occurs in the trabeculae of unloaded bones during the early phase of a spaceflight. In tibia, osteoid seam thickness and total osteoclastic resorption surfaces at the endosteal level were not modified.

Acid Phosphatase↗

Bone embedding in pure methyl methacrylate at low temperature preserves enzyme activities.

Pure Methyl Methacrylate (MMA), a widely used embedding medium for undecalcified bone studies, was polymerized at low temperature (4 degrees C). MMA was prepared by a new purification procedure yielding a absolutely anhydrous and catalysed resin. The redox system benzoyle peroxide/NN-Dimethylanilin was used as the catalyzer-initiator system providing free radicals for the MMA chemical polymerization. Since the reaction is inhibited at -20 degrees C, complete infiltration of blocks is achieved within 3 d. Polymerization took place at +4 degrees C. The method provides undecalcified bone sections suitable for histomorphometric analysis of osteoid tissue, tetracycline bone labeling and Tartrate Resistant Acid Phosphatase. Enzyme histochemistry was shown to be possible in pure MMA embedded bones, when this low temperature embedding was used.

Alkaline Phosphatase↗

Inhibition of testosterone metabolism in the brain and cloacal gland of the quail by specific inhibitors and antihormones.

The effects of antioestrogens, antiandrogens and of various inhibitors of testosterone metabolism on testosterone metabolism in the quail hypothalamus and cloacal gland were studied by an in-vitro radioenzymatic assay. It was found that antioestrogens and antiandrogens generally had little or no effect on aromatase and 5 alpha- and 5 beta-reductases of testosterone, except when used at very high doses. The 5 alpha-reductase inhibitor, 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, inhibited both 5 alpha- and 5 beta-dihydrotestosterone production without markedly affecting aromatase activity. Surprisingly, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, inhibited not only the production of oestradiol but also that of 5 beta-dihydrotestosterone and, to a lesser extent, 5 alpha-dihydrotestosterone. These unexpected properties should be taken into account when interpreting the results of in-vivo experiments using these compounds.

Androgen Antagonists↗

Skeletal distribution and biochemical parameters of Paget's disease.

Quantitative bone scans were performed with 99mTc-EHDP in 170 untreated pagetic patients (93 men, 77 women; mean age, 65.4 years). The distribution of 863 pagetic skeletal locations was analyzed. Bone scans demonstrated 8.3% more pagetic sites than roentgenograms. The extent of Paget's disease was evaluated in each patient by a scintigraphic skeletal index. This index correlated with serum alkaline phosphatase (SAP) and urinary hydroxyproline (HyPro) levels, and also with hypocalcemic acute response to calcitonin. The correlation of SAP with an index of activity (extent index adjusted by uptake ratios) was better than with the nonadjusted index. Only 30.6% of pagetic sites were responsible for clinical symptoms. No correlation was found between age and skeletal index of the disease.

Adult↗