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Biomedical subjects

P Prevost

Publications and source records attributed to P Prevost.

At least 19 recordsLinked to original sources

[Coverage of heel tissue loss by two pediculated flaps in a single procedure].

We report the case of a traffic accident victim who suffered major tissue loss of the heal. We used two pediculated flaps to close the gap in a single procedure. The remaining tissue presented zones of necrosis from the plantar aspect to the posterior half of the calcaneum, up to the insertion of the calcaneus tendon, extending 5 cm on the posterior aspect of the heal. We decided to combine a medial plantar flap with a lateral supramalleolar flap. The thick medial plantar flap allowed cover of the calcaneum and sensitivity. The calcaneus tendon was covered with the lateral supramalleolar flap. The thickness of the flap was adapted to match the tissue defect. At six months, the patient had recovered walking function with satisfactory weight bearing on the heal. Flap sensitivity was satisfactory with no slipping phenomenon.

Accidents, Traffic↗

[Medial and volar approach to fractures of the base of the fifth metacarpus].

A medial and volar approach to the base of the fifth metacarpus for exposing finger joint fractures is described. The dorsal approach does not expose well the joint surface of the base of the fifth metacarpus, hindering reconstruction of this important articulation. Carpometacarpal mobility of the ulnar joints contributes significantly to ulnar stability and grip force. An inverted "J" incision is made along the hypothenar eminence. The insertion of the tendon of the extensor carpi ulnaris is identified and the anterior fibers are disinserted. Capsulotomy is performed in front of the anterior border of the extensor carpi ulnaris tendon. This approach exposes well the medial two-thirds of the base of the fifth metacarpus. There is no risk of injury to the ulnar vessels nor to the dorsal sensitive branch of the ulnar nerve.

Dissection↗

Control of erythropoietin secretion by doxycycline or mifepristone in mice bearing polymer-encapsulated engineered cells.

Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.

3T3 Cells↗

Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin-induced diabetic rat model.

The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in biocompatibility in the field of hemodialysis. Its use for the encapsulation of living cells has been already described, but this study is the first description of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic rats. The aim of this work is to evaluate the biocompatibility of the AN69 hydrogel by comparison of the efficacy of free versus encapsulated islets transplanted to balance diabetes. Pancreatic islets are isolated from adult male Lewis rats by a standard collagenase digestion and purified on Ficoll density gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69 collodion. The hollow fiber is filled with islets suspended in agarose at the final concentration of 10,000 islets/ml, closed with surgical clips and implanted. The recipients are rendered diabetic by intravenous injection of STZ. The experimental design includes 4 groups of 8 rats: group 1: control, group 2: diabetic rats intraperitoneally implanted with 6000 free islets, group 3: diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4: diabetic control. Weight and fasting glycemia are evaluated twice a week, diuresis once a week. After free islet implantation, rat survival is improved with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This tends to demonstrate the biocompatibility of AN69 and is the first step of the validation of the use of AN69 for living cell encapsulation.

Acrylic Resins↗

Standardization of procedure for efficient ex vivo gene transfer into porcine pancreatic islets with cationic liposomes.

BACKGROUND: New strategies to improve the outcome of encapsulated porcine islet transplantation may involve the transfer of gene sequences affecting islet viability. While adenoviral vectors appear as the most efficient gene transfer system so far established for islets, non-viral-based vectors are most likely to fulfill microbiological safety criteria and be retained in the clinical setting. Our aim was to standardize the procedures of gene transfer into adult porcine islets using cationic liposome DOTAP. METHODS: Porcine islets obtained by collagenase digestion and density gradient purification were lipofected with plasmids coding for luciferase or beta-galactosidase under the control of simian virus 40 or cytomegalovirus promoter. The following parameters were explored: exposure time to vector (1-48 hr), DNA amount (1-15 microg/500 islets), and DOTAP to DNA ratio (2-16). Reporter gene expression was determined 48-72 hr after lipofection. RESULTS: Efficiency and reproducibility of transfection were maximal with the following procedure: 3-hr exposure time followed by islet washing, 12 microg of DNA per 500 islets (150 microm equivalent), and DOTAP to DNA ratio of 12 microl/microg. Freshly isolated islets in large aliquots (n=4000 in 50-ml tubes) were efficiently transduced with this procedure, and distribution of gene expression was homogenous when islets were subsequently plated in 500-islet aliquots. Luciferase gene expression was detected for a minimum of 7 days after lipofection. Gene expression was also evident up to 4 weeks after islet transplantation beneath the kidney capsule of athymic mice. Transfection of islets using the beta-galactosidase vector yielded 25% positive islets. Islet viability was not adversely affected. CONCLUSIONS: This islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.

Animals↗

Epidemiological data on Staphylococcus aureus strains producing synergohymenotropic toxins.

DNA hybridisation of 309 consecutive Staphylococcus aureus clinical isolates with oligonucleotide probes specific for genes encoding Panton-Valentine leucocidin (luk-PV) and gamma-haemolysin (hlg) revealed that 99% of randomly selected strains carried the hlg locus whereas only 2% harboured the luk-PV as well as the hlg loci. Only 1% of the strains did not possess either gene. In a clinical prospective study of independent S. aureus strains, 58 Panton-Valentine leucocidin (PVL)-producing isolates were shown to be responsible for primary skin infections, mainly furuncles (86%). Phage susceptibility patterns and pulsed field gel electrophoresis (PFGE) profiles of DNA were shown to be polymorphic epidemiological markers of PVL-producing strains. In eight patients with recurrent furuncles, the PVL-producing strains isolated either from furuncles or from the anterior nares were considered to be identical in each based upon phage sensitivity profiles or PFGE patterns.

Aged↗

In vitro potency testing of inactivated biologics: current situation in the E.E.C.

A whole series of regulations are currently being implemented in the European Economic Community in the field of biologics that are complementing the European Pharmacopoeia and widening its field of application. The object of these new regulations is to ensure a very high level of safety and efficacy, but unfortunately, they tend towards the increased use of animals for testing purposes. However, for ethical, economic and practical reasons, the number of animals used must be reduced which makes the development of in vitro tests an important issue. In vitro testing is complicated since inactivated products are often adsorbed onto aluminum hydroxide or presented as an emulsion, and tests are easier to carry out prior to final blending operations. It is suggested that in-process controls can replace finished product controls when batch-to-batch consistency has been formerly validated, a quality assurance system has been adopted, and that system is regularly subjected to a suitable inspection procedure. The new inspection system applied in the United Kingdom should facilitate progress in this field and lead to a parametric release system. To avoid future problems, it is particularly important that efforts be made now for the harmonization of new techniques between Europe and the United States.

Animal Testing Alternatives↗

Multifactorial analysis of the outcome of 6430 cadaver kidney grafts.

A total of 6430 cadaver kidney grafts performed within the network of France-Transplant between 1 January 1978 and 1 January 1989 were analyzed. Each case was examined comprehensively in regard to 12 variables. A multifactorial analysis (Cox regression) was used to determine the degree of association between each covariate and the outcome of the graft. The results were evaluated by calculating relative risks of graft failure for each variable. A total of seven covariates appeared to influence graft survival significantly: the period of transplantation (P = 10(-8)), retransplantations (P = 0.003), age and sex of the donor (P = 0.003 and 0.009 respectively), duration of pretransplant dialysis (P = 0.03), pretransplant sensitization to HLA antigens (P = 0.05), and matching for HLA-A, -B, and -DR loci (P = 0.03). This last parameter has previously been reported as influencing the outcome of the graft in seven out of eight international studies carried out using similar methodology.

Adolescent↗

[Course of chronic paranoid delusions during pregnancy and post-partum].

In order to analyse the evolution of the mental state of patient suffering from chronic delirium, during their pregnancy and the postpartum period, we researched the medical history of some pregnant women about 50 pregnancies. It appears that the period preceding the birth is calm in the great majority of cases. However the delirium reappears in the days following the birth in a brutal fashion in nearly a third of the cases. No malformation in the child is found, but we should note there was one case of infanticide and one young baby was abandoned in the street. The delirium, often concerning the identity or the theft of the child, has necessitated the hospitalisation. The termination of psychotropic drugs is justified during the months of pregnancy. However it often brings with it, an end to psychiatric follow up and the absence of any return to treatment, which seems necessary to us immediately after the birth.

Delusions↗

[Informational structure of the national registry of bone marrow donor volunteers].

Successful Bone Marrow Transplantations with unrelated donors can be performed providing that donor and recipient are totally HLA-A, B, DR identical. To find such a suitable donor it is necessary to type a large pool of volunteers for HLA in histocompatibility laboratories. We have built a network of 36 micro-computers AT 286 for updating local files and for translating data to the national file of donors maintained on a main computer (VAX 8250). The main computer communicates regularly using modems with local computers in order to update data and exchange information. After one year of functioning, users are well satisfied with the computers system which locates regularly potential donors for recipients waiting for a graft.

Bone Marrow Transplantation↗