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Biomedical subjects

F Lapierre

Publications and source records attributed to F Lapierre.

At least 37 records · Page 2Linked to original sources

Matrix metalloproteinase inhibitors: a structure-activity study.

Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

Chromatography, High Pressure Liquid↗

[Approach to severe functional deficiencies: evaluating the efficacy of a special multidisciplinary consultation].

A global approach is required to evaluate severe functional deficits. We have developed a multidisciplinary consultation and assessed its usefulness after one year. A total of 62 patients were evaluated (mean age 35 years), usually for neurological functional deficit (50%). Among the 62 patients, surgery was proposed in 72.6% (operations performed in 66%). Others were managed with non-surgical procedures or abstention. The functional outcome as assessed by patients and physicians was poor (or no result) for 6%, fair for 15%, good or very good for 79%. These results suggest that such a multidisciplinary approach is worth being pursued. Some adjustments for psychological dysfunction may further improve outcomes.

Adolescent↗

EBIC-guidelines for management of severe head injury in adults. European Brain Injury Consortium.

Guidelines for the management of severe head injury in adults as evolved by the European Brain Injury Consortium are presented and discussed. The importance of preventing and treating secondary insults is emphasized and the principles on which treatment is based are reviewed. Guidelines presented are of a pragmatic nature, based on consensus and expert opinion, covering the treatment from accident site to intensive care unit. Specific aspects pertaining to the conduct of clinical trials in head injury are highlighted. The adopted approach is further discussed in relation to other approaches to the development of guidelines, such as evidence based analysis.

Adult↗

[Neurinomas-neurofibromas].

Among primary nerve sheath tumors, schwannomas and neurinomas are the most common. While the schwannomas (neurilemomas) originate in schwann cells, neurofibromas arise from all the constitutive parts of the nerve. The behavior of each tumor is quite different and only neurofibromas may present malignant transformation, especially when arising in patients with Von Recklinghausen disease (NF1 with multiple neurofibromas).

Humans↗

[Evaluating the efficacy of a multidisciplinary approach of severe functional deficits].

Therapeutic indications aimed at improving function in handicapped persons are difficult to establish as the expected result of a given technique may vary. We have developed a multidisiplinary approach for handicapped persons. Our assessment of this activity which has concerned 62 patients from October 1995 to October 1996 is promising and encourages us to continue this type of attitude. Forty-six of the 58 persons evaluated stated they were well satisfied or very well satisfied with the management of their case and outcome was worse in none of the patients.

Adolescent↗

Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties.

Structural features of heparin potentially important for heparanase-inhibitory activity were examined by measuring the ability of heparin derivatives to affect the degradation of [3H]acetylated heparan sulphate by tumor cell heparanases. IC50 values were determined using an assay which distinguished degraded from undegraded substrate by precipitation of the latter with cetylpyridinium chloride (CPC). Removal of heparin's 2-O-sulphate and 3-O-sulphate groups enhanced heparanase-inhibitory activity (50%). Removal of its carboxyl groups slightly lowered the activity (18%), while combining the treatments abolished the activity. At least one negative charge on the iduronic acid/idose moiety, therefore, is necessary for heparanase-inhibitory activity. Replacing heparin's N-sulphate groups with N-acetyl groups reduced its activity (37%). Comparing this heparin derivative with 2,3-O-desulphated heparin, the placement of sulphate groups appears important for activity since the two structures have similar nominal linear charge density. In addition, unsubstituted uronic acids are nonessential for inhibition since their modification (periodate-oxidation/borohydride-reduction) enhanced rather than reduced heparanase-inhibitory activity. The most effective heparanase inhibitors (2,3-O-desulphated heparin, and [periodate-oxidized, borohydride-reduced] heparin) were tested in the chick chorioallantoic membrane (CAM) bioassay for anti-angiogenic activity and found to be at least as efficacious as heparin. 2,3-O-desulphated heparin also significantly decreased the tumor growth of a subcutaneous human pancreatic (Ca-Pan-2) adenocarcinoma in nude mice and prolonged the survival times of C57BL/6N mice in a B16-F10 melanoma experimental lung metastasis assay.

Animals↗

[Evolutive morphology of the olfactory bulb in man and certain non-human mammals].

Human and comparative anatomy of the olfactory lobe and the anterior floor was studied in 241 patients and 27 specimens (2 human fetuses, 4 specimens from adult humans, 11 non human primates and 10 carnivorous mammals). Macroscopic morphology and imaging data (CT-scan, 3D) reconstruction and magnetic resonance imaging) were obtained at the same time. The results obtained provide radiographic knowledge of the olfactory bulb ontogenesis and a basis for recognizing inborn or acquired pathology of the olfactory bulb. Evidence was also obtained for distinguishing between macrosmatic and microsmatic criteria in mammals.

Adolescent↗

Quantification and assessment of carotid artery lesions: degree of stenosis and plaque volume.

Various methods were developed for the quantification of the degree of stenosis: B-mode imaging, CW Doppler with spectral analysis, PW-duplex, and color-flow imaging. The degree of stenosis can be evaluated using transverse views of the carotid in conventional B-mode imaging. The diameters of the residual lumen (Ds) and the external diameter (De) of the artery at the same level are measured and the degree of stenosis (in area) is calculated. Two different Doppler methods have been designed and validated for the quantification of the stenosis degree. The first one is based on the determination of the maximal velocity inside the stenosis and requires the use of a duplex device. The second one, based on the quantification of the hemodynamic disturbances at the outlet of the stenosis, can be used either with a duplex system or with a continuous-wave Doppler system (pencil probe). The color display mode facilitates the determination of the residual lumen and therefore contributes to making the B-mode method more accurate. Moreover, it provides a visualization of the blood flow which avoids most of the misinterpretations of B-mode or Doppler data. Several classification systems based on subjective or semi-quantitative criteria (morphological or hemodynamic) were used to identify different grades of stenosis (< 40%, 40% to 60%, 60% to 90%, etc.) These classifications provide an evaluation of the degree of stenosis accurate enough to discuss the possibility of performing an endarterectomy on a symptomatic patient. When the surgical treatment seems to be inappropriate, the patient is treated medically; the follow-up of the lesion (ie, every 6 months) requires a more precise evaluation of the plaque changes than does stenosis classification. Several parameters have been designed and validated for the quantification of the degree of stenosis by ultrasound. These parameters, whether measured with the B-mode and color image or with the Doppler spectrum, allow quantification of the stenosis degree in percentage of lumen reduction with a precision of approximately +/- 10%. Such a quantitative assessment of carotid lesions for a long period of time may be very helpful in evaluating the beneficial effects of medical treatment or in detecting any significant increase of the stenosis that could lead to surgical treatment. A new method for the plaque volume assessment has been recently validated. The plaque volume index expressed in mm3 is calculated from longitudinal and transversal B mode views of the bifurcation.

Blood Flow Velocity↗

[Cerebral metastases of testicular neoplasms. Apropos of 2 cases and review of the literature].

The authors report two cases of brain metastasis of a testicular cancer in two young men. In the first case the histology was an embryonal carcinoma, in the second the association of a seminoma and a teratocarcinoma. The first patient was submitted to chemotherapy, neurosurgery and radiotherapy. The second one to chemotherapy alone. The survival time was respectively of 16 and 58 months. It looked interesting to review the different treatments and their indications in this extremely severe pathology to define the interest of surgery and radiotherapy, and the different prognostic factors. In the literature, among the various treatment, the role of chemotherapy is widely emphasized. The prognosis remains desperately bad when several brain metastasis exist, or if a brain metastasis develops during chemotherapy.

Adult↗

Discitis after lumbar disc surgery. Features of "aseptic" and "septic" forms.

Two major types of postoperative discitis have been previously described: septic discitis and "avascular" or "chemical" discitis. Percutaneous discal biopsy is an important way of distinguishing these entities. In a retrospective study of 25 cases of postoperative discitis, three groups have been analyzed with bacteriologic and histologic tests: a group of nine patients (group A) with positive discal bacteriologic cultures; a group of eight patients (group B) with typical septic histologic tests but negative bacteriologic discal procedures; and a group of eight patients (group C) in whom the histologic picture was reminiscent of a mechanical process. No group was unique in any clinical and radiologic parameter. Group A and group B were quite similar in biological features, but group C had erythrocyte sedimentation rate and C-reactive protein serum levels significantly lower than groups A and B (P less than 0.01). After 4 weeks, these differences were still present. This study confirms that there are two main features of postoperative discitis that can be recognized by histologic and biological tests, allowing for different treatments.

Biopsy↗

[Cranioplasties using free femoral osteo-periostal flaps].

Injuries, osteomyelitis, tumors are responsible of large skull defects. Their management is difficult. Three post traumatic and post infectious defects were repaired with an osteoperiostic flap taken from the internal face of the femur. A large defect due to the removal of a metastatic tumor was repaired with an iliac osseous flap. The choice of the donor site depends on the defect size (the femur provides a flap of 13 cm x 8 cm, the iliac bone a flap of 17 x 17 cm). The three head injured patients had a range of six previous unsuccessful surgical attempts using polymerised material or bone grafts. The post operative course in the post traumatic patients was uneventful, the domestic result good, the periostic consolidation less than three months. The free flap seems a good method for the management of risky cases.

Bone Transplantation↗

[Effect of age on the number and size of myelinated nervous fibers. A qualitative and quantitative study in the rat].

The number and the average diameter of the myelinated fibers have been recorded in the both medial gastrocnemius nerves in the rat. The study concerned foetus at the end of the intra-uterine life as well as old rats (24 months). It seemed the absolute necessity to collect these data before studying the consequences of age on nervous regeneration. Electron microscopy was used in very small samples, photonic microscopy in bigger ones. The first myelinated fibers appear during the first day of life. Their number becomes steady around 2 months of live. But their diameter changes and increases until the end of the 6th month. In pubescent animals, the global variations between the two sides are negligible (average right number 260 +/- 8 fibers, average left 258 +/- 12, average right diameter 1.7 +/- 0.7 microns, average left diameter 7.1 +/- 0.6 microns).

Aging↗

[Effect of age on the number and size of myelinated nerve fibers. A study after localized freezing on section-suture of the sciatic nerve in the pubescent rat].

The regeneration of the myelinated fibers has been studied after a localized congelation or a section followed by an immediate suture in the left sciatic nerve of rats aged of 1 1/2, 3, 6, 12, 18 and 24 months at the moment of the operation. The regenerated fibers has been observed in the left internal gastrocnemius nerve, the right nerve being considered as the sham. For each nerve, the number and the caliber of the myelinated nerves has been systematically registered at standard levels allowing to calculate the average diameter of the fibers, their repartition and to draw their histogram. The results seem to prove that the potential of regeneration is correlated to the age, the velocity and intensity of the axonal growth decreasing in the old age. This potential of regeneration remains during the whole life. The integrity of the schwannian membranes considerably facilitates the nervous fibers regeneration, their interruption is a major obstacle to the axonal regrowth.

Aging↗

[Cranioplasties using a free osteoperiostic femoral vascularized flap].

The management of large defects after head injury, osteomyelitis or both is usually solved by the use of bone grafts, polymerised material or metallic prosthesis. The post-operative course is often frustrating when those materials are close to the frontal sinus leading to the removal of this material. For these reasons, we decided to use free periostic flaps for the management of these skull defects. The flap comes from the internal part of the femur creating no other defect in the body. Three patients with post infectious and post traumatic skull defects have been operated. The postoperative course was uneventful, the cosmetic result good and the protection of the cranial content effective after three months. Of these three patients one had eleven previous attempts of repair for his defect. This method seems to be a good one for those risky cases, and somewhat better than the use of great omentum transfer sometimes associated with bone grafts.

Adult↗