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Biomedical subjects

P Aebischer

Publications and source records attributed to P Aebischer.

At least 145 records · Page 8Linked to original sources

Transplantation of neural tissue in polymer capsules.

Neural tissue reaction to permselective polymer capsules and the feasibility of encapsulated neural tissue transplantation were evaluated in a rat model for a period of 1-12 weeks. Polymer implants in the central nervous system were generally well tolerated. The brain reaction to the synthetic material was minimal and did not disturb normal brain architectonics. Embryonic mouse mesencephalon enclosed in a polymer capsule remained morphologically intact for at least 12 weeks in the parietal cortex of rats. We conclude that the immunoprotection provided by a permselective polymer membrane encapsulating neural tissue is compatible with diffusional exchange of nutrients and metabolites. Polymer encapsulation may provide an alternative for the problem of immunorejection in transplantation of neural tissues.

Animals↗

Tissue reaction to fabrics coated with turbostratic carbon: subcutaneous versus vascular implants.

A technique allowing the deposition of an adherent thin film of turbostratic, high-density carbon on heat-sensitive polymers was recently developed. The biological response to this biomaterial on yarns and fabrics of the type used in cardiovascular surgery has been studied. Polyester yarns, knitted Dacron sheets and knitted uncrimped Dacron vascular grafts were coated with a thin film (less than 1 micron) of turbostratic carbon using a physical vapour deposition process. Coated and control discs of knitted material, as well as coated and uncoated yarns, were implanted in pairs in the subcutaneous tissue of mice, using for each type of implant two cohorts of 12 animals, with observation periods of 4 and 8 wks respectively. Vascular grafts (8 cm long, 8 mm i.d.) coated with carbon on the luminal side only, were implanted for 12 wks in the infrarenal aortic position in six dogs, and compared to uncoated Dacron grafts of the same dimensions inserted in the same location and for the same duration in the infrarenal aortic position in six control animals. With subcutaneous implants, there was no significant difference in the tissue reaction to either coated or uncoated patches. In contrast, the vascular grafts, all of which were patent upon retrieval, showed a much lower extent of thrombosis on the blood-exposure surface in the case of carbon-coated Dacron, as compared to the luminal surface of control prostheses. The internal capsule (tissue formed between the polymer fabric and the blood interface) was thinner in carbon-coated grafts than in control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experience with fully bioresorbable aortic grafts in the dog.

Reorganization of the arterial wall through natural processes on the resorption of a totally bioresorbable graft was investigated in dogs with Vicryl prostheses coated with two different blends of bioresorbable polyesters capable of slowing down considerably the disintegration of a Vicryl fabric in vivo. The prostheses (8 to 9 mm in internal diameter, 8 to 10 cm long) were implanted in the infrarenal aortic position for up to 24 weeks. All 18 animals implanted with coated prostheses survived, whereas one animal implanted with an uncoated Vicryl prosthesis died because of early rupture of the graft. Patent tubular conduits were present in 14 animals at the time of retrieval. On resorption of the synthetic polymers, the tissue layers that formed on both sides of the prosthetic material either fused or remained separated, depending on the polymer used as a retardant coating. We conclude that polymer composition influences the repair process and that a fully resorbable vascular graft can function effectively in a canine model, provided that tissue organization is sufficiently advanced by the time the prosthesis has lost its mechanical integrity. Further studies are needed to document the performance of the newly formed blood conduit over extended periods, in hypertensive subjects, and when presented with a bacterial challenge.

Absorption↗

Piezoelectric guidance channels enhance regeneration in the mouse sciatic nerve after axotomy.

Piezoelectric nerve guidance channels made of polyvinylidene fluoride (PVDF) were evaluated in a transected mouse sciatic nerve model. Poled PVDF channels were compared to unpoled PVDF channels after 4 and 12 weeks of implantation. In all animals, the proximal and distal nerve stumps were bridged by a continuous nerve cable. Nerves regenerated in poled channels contained a higher number of myelinated axons than those regenerated in unpoled channels at both time periods. We conclude that piezoelectric nerve guidance channels enhance peripheral nerve regeneration and provide a tool to investigate the influence of electrical activity on nerve regeneration.

Animals↗

Collagen- and laminin-containing gels impede peripheral nerve regeneration through semipermeable nerve guidance channels.

Semipermeable guidance channels were filled with saline, collagen-, or laminin-containing gels and used to repair a 4-mm sciatic nerve gap in mice. After 12 weeks, nerve cables regenerated in gel-filled channels displayed fewer myelinated axons than saline-filled channels. Remnants of the exogenous substrates were still in evidence, in amounts related to the initial collagen or laminin gel concentration. The impairment of nerve regeneration by collagen or laminin-containing gels suggests that the regenerative environment created within semipermeable channels is not improved by the addition of growth substrates in a gel form.

Animals↗

SYNDROC: microcomputer based differential diagnosis of malformation patterns.

The differential diagnosis of human malformation patterns is difficult because of their great number and low occurrence. To compensate for deficiencies in experience, the authors have developed a microcomputer based differential diagnosis for dysmorphic syndromes. Written in PL/I-80 and using a MDBS III data base containing more than 700 signs and 300 syndromes, the algorithm of SYNDROC, the program's name, is built on three different approaches. An initial differential diagnosis is given by a pseudo-Bayesian method. Its refinement is possible through an heuristic approach, and undiagnosed cases are stored for subsequent Boolean retrieval, thus permitting the recognition of new dysmorphic disorders. The reliability of the program was tested in a retrospective study based on 100 dysmorphic cases. The results showed a 95% agreement between the first two diagnoses suggested by SYNDROC and the diagnosis made by experienced geneticists.

Abnormalities, Multiple↗

Does renal failure induce a decrease in cyclosporine blood concentrations?

Blood Cys concentrations were monitored twice weekly by RIA in nine patients undergoing renal transplantation. The Cys dose was adapted to obtain blood values between 100-400ng/ml. A negative correlation was found between plasma creatinine and blood Cys, even in those patients in whom the oral dosage was not changed (r = 0.65, n = 23, p less than 0.001). In vitro studies showed no effect of uraemic blood on Cys measurement. It seems probable that uraemia induces changes in distribution volume and/or gastrointestinal absorption of the drug. Careful monitoring of Cys during uraemia is therefore warranted.

Adult↗

The activity of pars compacta neurons of the monkey substantia nigra is depressed by apomorphine.

In the substantia nigra of anesthetized and awake monkeys, presumptive dopamine cells of the pars compacta were electrophysiologically discriminated against non-dopaminergic cells of the pars reticulata by their lower discharge rate (0.5-8 vs 20-130 imp./s), their longer impulse duration (means 2.05 vs 0.92 ms), and their exclusive depression following systemic injection of the dopamine agonist apomorphine (24 out of 30 compacta neurons at 0.05-0.1 mg/kg s.c.).

Action Potentials↗

[An example of applied data processing in medicine: medical management in a dialysis center].

An application of computers to haemodialysis units is presented. In fact these centers are characterised by an enormous amount of data which should benefit from computerization, and therefore in the haemodialysis unit of the Cantonal Hospital, Fribourg, a program has been developed to handle medical data. This program, as far as we know the only one of its kind in Switzerland, has already been in use for the last 9 months. Swiftly, surely and simply it allows storage and retrieval of all the administrative and medical data of each patient. Facility of data retrieval, graphic data display and automatic data evaluation has been found to improve clinical management of patients. It also considerably facilitates scientific work. Once the adaptation period is over it permits definite time savings. We are convinced that, after the necessary period of introduction, computers can be of considerable help in medical care.

Computers↗

Photoimmobilization of a bioactive laminin fragment and pattern-guided selective neuronal cell attachment.

To attain light-dependent functionalization of biocompatible materials, a photolabel-derivatized, bioactive laminin fragment has been synthesized, chemically characterized, and photoimmobilized. Covalent high-resolution patterning of the laminin fragment CDPGYIGSR to hydroxylated fluorinated ethylene propylene (FEP-OH), poly(vinyl alcohol), and glycophase glass has been achieved. The synthetic peptide CDPGYIGSR was thermochemically coupled to either N-[m-[3-(trifluoromethyl)-diazirin-3-yl]phenyl]-4-maleimidobuty ramide or 4-maleimidobenzophenone. Photolabel-derivatized peptides were radiolabeled, and 20 and 300 microns-sized patterns were visualized by autoradiography. The biospecific interaction of photoimmobilized laminin fragments with cells was investigated by analyzing the selective attachment of NG 108-15 neuroblastoma x glioma cells which bear CDPGYIGSR-specific cell surface receptors. On photopatterned FEP-OH membranes NG 108-15 cells differentiated in serum-supplemented media within 1 day. Specific attachment to the immobilized oligopeptide CDPGYIGSR was assessed in serum-free media with competitive binding studies, showing an 82% decrease in cell adherence after the cell receptors were blocked with soluble CDPGYIGSR.

Amino Acid Sequence↗

Control of water flux in a bioartificial kidney.

UC-PK1 cells were grown to confluence on microporous microcellulose membranes in order to test the feasibility of using transmembrane pressure (TMP) for controlling connective water transport in a bioartificial kidney. TMP was applied on either the apical or basal aspect of the polarized cell layer, while the fluid compartments on both sides of the membrane were perfused with tissue culture medium in a miniature flow chamber. The cell monolayer did not allow filtration in the apical to basal direction when positive TMP up to 30 mmHg was applied on the apical side. Application of positive TMP on the basal side led to measurable ultrafiltration. The hydraulic permeability, L(p), of the cell-seeded membranes was found to be increasing with time, reaching a steady state value after 60 min. There was a strong positive correlation between L(p) and applied TMP. For a constant TMP, L(p) was found to be independent of the shear rate between 2.6 and 10.5 sec-1. When positive pressure was changed abruptly back from the basal to apical site, the ultrafiltration rate decreased to zero within seconds. Morphologic studies suggest that the tight junctions between cells were broken by TMP applied on the basolateral aspect of the cell monolayer. It is concluded that, basolateral TMP may be used to control water flux in a bioartificial kidney.

Animals↗

Microencapsulated bovine chromaffin cells in vitro: effect of density and coseeding with a NGF-releasing cell line.

Immobilization of discrete cell clusters within a partially crosslinked matrix prevents reaggregation of primary tissues and may provide a means for long-term maintenance of encapsulated cells. Dissociated bovine adrenal chromaffin (BAC) cells were suspended throughout crosslinked polyanionic microspheres previously shown to be selectively permeable. Microcapsules approximately 500 microns in diameter were seeded with: 1) three different densities of BAC cells; and 2) BAC cells suspended in Matrigel or coseeded with a genetically modified nerve growth factor (NGF)-releasing fibroblast cell line. Each group was analyzed in vitro at 1, 4 and 8 weeks for spontaneous and potassium-evoked release of catecholamines, and maintained in vitro for up to 12 weeks for morphological observations. Over time, release of norepinephrine (NE) and epinephrine (EPI) diminished, while dopamine (DA) remained constant from the monoseeded capsules. In the coseeded group, an increase in potassium-evoked release of DA was observed from 1 to 4 weeks, and remained at that level up to 8 weeks. Encapsulated chromaffin cells retained a rounded morphology typical of undifferentiated cells. Intact chromaffin cells with well preserved and abundant secretory granules were observed ultrastructurally after 4 weeks in vitro. Small neurites from the chromaffin cells in the coseeded group were observed at 4 weeks with light microscopy, and up to 12 weeks with electron microscopy. Under static incubation conditions, 1 mM D-amphetamine resulted in a significant increase in the output of NE and DA from the coseeded capsules 8 weeks post-implantation, as compared to microcapsules loaded with chromaffin cells alone. Encapsulation within an immobilization matrix allows manipulation of the internal environment, thereby providing the ability to pre-treat cells with various factors in a non-invasive manner, which may enhance long-term cellular viability.

Animals↗

Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically engineered xenogeneic cells.

A phase I/II clinical trial has been performed in 12 amyotrophic lateral sclerosis (ALS) patients to evaluate the safety and tolerability of intrathecal implants of encapsulated genetically engineered baby hamster kidney (BHK) cells releasing human ciliary neurotrophic factor (CNTF). These patients have been assessed for a possible intrathecal or systemic immune response against the implanted xenogeneic cells. Hundreds of pg CNTF/ml could be detected for several weeks in the cerebrospinal fluid (CSF) of 9 out of 12 patients, in 2 patients up to 20 weeks after capsule implantation. Slightly elevated leukocyte counts were observed in 6 patients. Clear evidence for a delayed humoral immune response was found in the CSF of only 3 patients out of 12 (patients #4, #6, and #10). Characterization of the antigen(s) recognized by the antibodies present in these CSF samples allowed to identify bovine fetuin as the main antigenic component. The defined medium used for maintaining the capsules in vitro before implantation contains bovine fetuin. Fetuin may therefore still be adsorbed to the surface of the cells and/or the polymer membrane, or be present in the medium surrounding the encapsulated cells at the time of implantation. Because of the insufficient availability of CSF samples, as well as the relatively poor sensitivity of the assays used, a weak humoral immune response against components of the implanted cells themselves cannot be excluded. However, the present study demonstrates that encapsulated xenogeneic cells implanted intrathecally can survive for up to 20 weeks in the absence of immunosuppression and that neither CNTF nor the presence of antibodies against bovine fetuin elicit any adverse side effects in the implanted patients.

Adult↗