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A Chevrier

Publications and source records attributed to A Chevrier.

18 recordsLinked to original sources

Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects.

OBJECTIVE: Marrow-stimulation techniques are used by surgeons to repair cartilage lesions although consistent regeneration of hyaline cartilage is rare. We have shown previously that autologous blood can be mixed with a polymer solution containing chitosan in a glycerol phosphate (GP) buffer (chitosan-GP), and that implantation of this polymer/blood composite onto marrow-stimulated chondral defects in rabbit and sheep leads to the synthesis of more chondral repair tissue with greater hyaline character compared to marrow-stimulation alone. In the current study, we examined the modulation of cell recruitment and repair tissue characteristics at early post-surgical time points (from day 1 to 56) in a rabbit model to elucidate potential mechanisms behind this improved repair outcome. DESIGN: Thirty-three skeletally mature New Zealand White rabbits underwent bilateral arthrotomies, with each trochlea receiving a cartilage defect (3.5 mm x 4.5mm) bearing four microdrill holes (0.9 mm diameter, approximately 4 mm deep) into the subchondral bone. One defect per rabbit was treated with a chitosan-GP/blood implant, while the other defect was left as a microdrilled control. Repair tissues were stained by histochemistry, for collagen types I, II, and X by immunohistochemistry and analyzed using quantitative stereological tools. RESULTS: Histological analyses demonstrated that control defects followed a typical healing sequence observed previously in marrow-stimulation animal models while chitosan-GP/blood implants led to three significant modifications in the healing sequence at early stages: (1) increased inflammatory and marrow-derived stromal cell recruitment to the microdrill holes, (2) increased vascularization of the provisional repair tissue in the microdrill holes, and (3) increased intramembranous bone formation and subchondral bone remodeling (BR). CONCLUSIONS: These results suggest that the greater levels of provisional tissue vascularization and BR activity are main factors supporting improved cartilage repair when chitosan-GP/blood implants are applied to marrow-stimulated cartilage lesions.

Animals↗

Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects.

OBJECTIVE: We have previously shown that microfractured ovine defects are repaired with more hyaline cartilage when the defect is treated with in situ-solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with autologous whole blood. The objectives of this study were (1) to characterize chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation model in order to determine the effects of the chitosan-GP/blood implant and of debridement on the formation of incipient cartilage repair tissue. METHODS: Blood clots were characterized by histology and in vitro clot retraction tests. Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were pierced with four microdrill holes and filled with a chitosan-GP/blood implant or allowed to bleed freely as a control. At 1 day post-surgery, initial defects were characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral repair tissues between or through the drill holes were evaluated by histology, histomorphometry, collagen type II expression, and stereology (n=16). RESULTS: Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the formation of a more integrated and hyaline repair tissue above a more porous and vascularized subchondral bone plate compared to drilling alone. Correlation analysis of repair tissue between the drill holes revealed that the absence of calcified cartilage and the presence of a porous subchondral bone plate were predictors of greater repair tissue integration with subchondral bone (P<0.005), and of a higher total O'Driscoll score (P<0.005 and P<0.01, respectively). CONCLUSIONS: Chitosan-GP/blood implants applied in conjunction with drilling, compared to drilling alone, elicited a more hyaline and integrated repair tissue associated with a porous subchondral bone replete with blood vessels. Concomitant regeneration of a vascularized bone plate during cartilage repair could provide progenitors, anabolic factors and nutrients that aid in the formation of hyaline cartilage.

Animals↗

Soluble recombinant neprilysin induces aggrecanase-mediated cleavage of aggrecan in cartilage explant cultures.

Neprilysin (neutral endopeptidase, enkephalinase, CALLA, CD10, NEP) is a regulatory Zn metallopeptidase expressed in the brush border membranes of the kidney and has been found in porcine chondrocytes and rat articular cartilage as well as other cell types and tissues. Although its function in cartilage is not currently known, previous observations of high levels of NEP enzymatic activity in the synovial fluid of arthritic patients and on the chondrocyte membranes of human osteoarthritic cartilage have led to the hypothesis that NEP is involved in the inflammation or degradation pathways in articular cartilage. Our study localized endogenous NEP to the membranes of mature bovine articular chondrocytes in a tissue explant model and demonstrated that the addition of soluble recombinant NEP (sNEP) to the culture medium of bovine cartilage explants leads to the degradation of aggrecan through the action of aggrecanase. A 6-day exposure to sNEP was necessary to initiate the degradation, suggesting that the chondrocytes were responding in a delayed manner to an altered composition of regulatory peptides. This NEP-induced degradation was completely inhibited by the NEP inhibitors thiorphan and phosphoramidon. These results suggest that NEP is present as a transmembrane enzyme on articular chondrocytes where it can cleave regulatory peptides and lead to the induction of aggrecanase.

Aggrecans↗

High frequency acoustic parameters of human and bovine articular cartilage following experimentally-induced matrix degradation.

Matrix degradation and proteoglycan loss in articular cartilag eare features of early osteoarthritis. To determine the effect of matrix degradation and proteoglycan loss on ultrasound propagation in cartilage, we used papain and interleukin-1alpha to degrade the matrix proteoglycans of human and bovine cartilage samples, respectively. There is also minor collagen alteration associated with these chemical degradation methods. We compared the speed of sound and frequency dependent attenuation (20-40 MHz) of control and experimental paired samples. We found that a loss of matrix proteoglycans and collagen disruption resulted in a 20-30% increase in the frequency dependent attenuation and a 2% decrease in the speed of sound in both human and bovine cartilage. We conclude that the frequency dependent attenuation and speed of sound in articular cartilage are sensitive to experimental modification of the matrix proteoglycans and collagen. These findings suggest that ultrasound can potentially be used to detect morphologic changes in articular cartilage associated with the progression of osteoarthritis.

Adult↗

[Li-Fraumeni syndrome: update, new data and guidelines for clinical management].

The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children and young adults, and characterized by a wide spectrum of tumors, including soft-tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal breast cancers. In most of the families, LFS results from germline mutations of the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were identified in affected families. The LFS working group recommendations are the following: (i) positive testing (screening for a germline TP53 mutation in a patient with a tumor) can be offered both to children and adults in the context of genetic counseling associated to psychological support, to confirm the diagnosis of LFS on a molecular basis. This will allow to offer to the patient a regular clinical review in order to avoid a delay to the diagnosis of another tumor; (ii) the 3 indications for positive testing are: a proband with a tumor belonging to the narrow LFS spectrum and developed before age 36 and, at least, first- or second-degree relative with a LFS spectrum tumor, before age 46, or a patient with multiple primary tumors, 2 of which belonging to the narrow LFS spectrum, the first being developed before 36 or a child with an adenocortical tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young age of onset of the LFS tumors the prognosis of some tumors, the impossibility to ensure an efficient early detection and the risk for mutation carriers to develop multiple primary tumors justify that prenatal diagnosis might be considered in affected families.

Adult↗

Role of equalisation mammography of dense breasts.

Parenchymal patterns characteristic of dense breasts are known to degrade the mammographic detection of small breast cancers and microcalcifications. This arises from large variations in exposure of the film, resulting in reduced image contrast over areas of suboptimal exposure. Based on sensitometric measurements of mammograms from a typical patient population, it is shown that over 60% of a typical mammogram in Wolfe's DY classification was found to be exposed suboptimally, suggesting a significant margin for improving mammography for these patients. In order to address this problem, a prototype mammographic version of scanning equalisation radiography (MSER) has been developed, which delivers a patient-specific spatially non-uniform distribution of breast exposure, adjusted to maintain optimal film exposure and contrast over the entire mammogram. Anthropomorphic phantom MSER images show a marked improvement in subjective image quality relative to conventional mammograms, while exhibiting a similar radiation risk. The detection of small microcalcifications and fibrils over clinically significant breast densities is found to be improved by factors eight and four, respectively. Such a system may be clinically practical through the use of multiple-beam equalisation methods with available X-ray tube technology.

Breast Neoplasms↗

Neuroendocrine primary small cell carcinoma of the breast. Report of a case and review of the literature.

One case of breast neuroendocrine primary small cell carcinoma with light microscopic and immunohistochemical findings is reported. The patient died of unrelated disease 21 months after diagnosis and treatment by modified radical mastectomy, radiotherapy and subsequent chemotherapy. Immunohistochemical studies revealed cytokeratin and neuroendocrine markers (chromogranin, neuron-specific enolase) immunostaining on tumoral cells. Expression for neuropeptides (met-enkephalin, leu-enkephalin, beta-endorphin) and CALLA antigen was found. Based on this case report and six other previously reported cases, breast neuroendocrine primary small cell carcinoma appears to be a very aggressive tumor for which no firm conclusions regarding treatment can be drawn.

Aged↗

Expression of opioid peptides in cells and stroma of human breast cancer and adenofibromas.

The expression of beta-endorphin, Met-enkephalin and Leu-enkephalin was studied in 63 malignant and benign human breast tumors using immunohistochemical methods. Among invasive ductal carcinomas, 93% were positive for beta-endorphin, 87% for Leu-enkephalin and 90% for Met-enkephalin, in both the tumor stroma and the cell bodies. Enkephalin was predominant in cells, whereas endorphin was predominant in stroma. Nearly the same distribution was found in adenofibromas. In pericancerous normal tissue, neuropeptides were predominantly expressed in the stroma. Although the neuropeptide expression is not cancer-specific, it could be cancer-related, since the results suggest that the neuropeptide expression could reflect the host response to cancer cells and not only the cancer cell activity. The possibility of a direct action of the nervous system on stroma reaction and then on cancer cells is discussed.

Adenofibroma↗

Tetracosactrin vs. methylprednisolone in the prevention of emesis in patients receiving FEC regimen for breast cancer.

0.5 mg tetracosactrin is considered to be equivalent to 40 mg methylprednisolone with regard to the induced cortisol secretion. 97 female breast cancer patients who received their first two FEC courses (epirubicin 50-75 mg/m2, 5-fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2) entered this randomised crossover study (76 had previously received an adjuvant treatment); tetracosactrin was administered intramuscularly and methylprednisolone intravenously immediately before chemotherapy administration. The tolerability was evaluated using a diary card during 5 days and patients were asked for their preference at the end of the two cycles. There was no difference either for vomiting (dry heaves were included) or nausea between the two treatments (the analysis was performed on day 1, the worse day of days 2 and 3 and the worse day of days 4 and 5). At day 1, 49% of the patients experienced no or mild nausea after tetracosactrin and 62% after methylprednisolone (not significant) (first period analysis); a complete control of vomiting (including dry heaves) was observed in 49% of the patients after tetracosactrin and 53% after methylprednisolone (not significant). No difference was observed between patients with or without previous chemotherapy. However, slightly more patients preferred tetracosactrin (P = 0.048).

Antineoplastic Combined Chemotherapy Protocols↗

[Some insights on the history of children's drawings].

Both children's use of drawings and their interpretation in psychopathology have a history and even a pre-history. The author comments on the few drawn documents he could gather concerning the latter. He examines the birth of children drawings in psychology, psychiatry and education at the end of the XIXth century and the turn of the XXth. He finally recalls the first traces of its use by psychoanalysis, mainly in France. Some excursi are joined relative to the conditions of discovery of pre-historic art, to the relationship between modern art and child "primitivism", and to the themes of child drawings within cartoons.

Art↗

Inhibition of active E rosette forming T lymphocytes by hyaluronic acid. Evidence of a receptor for hyaluronic acid on a lymphocyte subpopulation.

Previous studies have shown the inhibition of active E rosette forming T lymphocytes by a mesenchyme associated antigen. Recent results clearly indicated that this antigen consisted in the association of a glycoprotein named hyaluronectin with hyaluronic acid. Using the active E rosette technique of Wybran and Fudenberg, we have studied the action of hyaluronic acid on T lymphocytes. We obtained evidence of the partial inhibition of active E rosette formation by hyaluronic acid in 19 of 25 healthy subjects. Among them, inhibition percentage was 45 +/- 4. This inhibition remained significant at a concentration of 22.5 micrograms/ml hyaluronic acid. Hyaluronic acid was labelled with peroxidase by the glutaraldehyde technique: 17 +/- 7% lymphocytes were stained by this preparation. The preincubation of peroxydase labelled hyaluronic acid by brain hyaluronectin lowered this staining. This is in agreement with the presence of hyaluronectin on a subpopulation of lymphocytes as it was shown by immunofluorescence techniques. In conclusion, a receptor for hyaluronic acid (hyaluronectin) was detected on a proportion of lymphocytes. These results suggest that hyaluronic acid could have an immunosuppressive activity.

Humans↗

Inhibition of the active E-rosette-forming T lymphocytes by a mesenchyme associated antigen.

Using the active E-rosette method, we have obtained evidence for the inhibition of their formation by a mesenchyme associated antigen (MAA) which was found in human tumors. After incubation of lymphocytes with MAA, the active E-rosette percentage in 28 healthy donors fell from 22.4 +/- 3.5 to 11.3 +/- 2.8. This inhibition was studied for different concentrations of MAA and remained significant for 22.5 microgram/ml. In vivo implication of this inhibition is discussed.

Animals↗

Isolation and characterization of a mesenchyme associated antigen from dimethylbenzanthracene induced rat fibrosarcoma.

Using an antiserum directed against human neurospecific antigen and the indirect immunofluorescence technique, we have obtained evidence for the presence of a mesenchyme associated cross-reacting antigen (MAA) in the dimethylbenzanthracene induced fibrosarcoma of the rat. This antigen has been purified from this tumor and compared with the antigen associated with the human nervous system and that associated with the nervous system of the rat. An anti-rat MAA antiserum has been obtained. It has cytotoxic activity against cultured fibrosarcoma cells as measured by release of radioactivity. This antigen can be considered as a marker of fibrosarcomas.

9,10-Dimethyl-1,2-benzanthracene↗