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Biomedical subjects

M B van Leeuwen

Publications and source records attributed to M B van Leeuwen.

10 recordsLinked to original sources

Biocompatibility of a novel tissue connector for fixation of tracheostoma valves and shunt valves.

Rehabilitation after laryngectomy often includes the use of a shunt valve and a tracheostoma valve to restore voice. To improve the fixation method of these valves, a new tissue connector has been developed, basically consisting of a ring that will be integrated into surrounding tracheal soft tissue. The valves can be placed in the ring. To test the principle of the tissue connector, a prototype consisting of a subcutaneous polypropylene mesh and a percutaneous titanium stylus was implanted into the backskin of 10 rats by a two-stage surgical procedure. We reasoned that if a firm connection can be realized with the skin, a firm connection with the trachea will also be possible. The subcutaneous part was implanted first, followed by the percutaneous part after 6 weeks. The complete tissue connector with surrounding tissue was removed 8 weeks later and examined histologically. The principle of the new tissue connector proved to be effective: hardly any epithelial downgrowth appeared, and adhesion of soft tissue was demonstrated. No infection or severe inflammation reaction was detected. The tissue connector seems appropriate for its intended use.

Administration, Cutaneous↗

Long-term evaluation of degradation and foreign-body reaction of subcutaneously implanted poly(DL-lactide-epsilon-caprolactone).

The aim of this study was to evaluate the degradation and foreign-body reaction of poly(DL-lactide-epsilon-caprolactone) (PLA85CL50) bars. This specific biomaterial is used for the construction of nerve guides, which can be used in the reconstruction of short nerve gaps. Subcutaneously implanted PLA85CL50 bars were harvested after implantation periods ranging from 3 to 12 months and evaluated for the rate of degradation and the degree of foreign-body reaction. It was observed that this copolymer degraded completely within 12 months and that no lactide or epsilon-caprolactone crystals were formed. Furthermore, we conclude that the foreign-body reaction of PLA85CL50 is very mild. These properties make the amorphous copolymer of DL-lactide and epsilon-caprolactone (50:50) suitable for the construction of nerve guides.

Administration, Cutaneous↗

Characterization of human larynx carcinoma cell lines HLaC'79 and HLaC'82: a common origin but diverged malignancies.

As part of a study on the relationship of tumour phenotype and behaviour, we have characterized two head and neck squamous cell carcinoma cell lines, derived from human laryngeal carcinomas and designated HLaC'79 and HLaC'82. Cytogenetic analysis revealed that HLaC'79 and HLaC'82 shared 10 major chromosome rearrangements indicating that the cell lines had a common origin. In the extremely complex chromosomal patterns, abnormalities were found in chromosomes 1, 3 (surplus 3q) and 5 (i(5p) x 2). Both cell lines displayed constitutive expression of vimentin and were capable of anchorage-independent growth in agarose gels. However, in spite of their common origin specific differences were found. Cells of HLaC'79 were spindle shaped and formed tumours in athymic mice. In contrast, cells of HLaC'82 had a compact morphology, contained less vimentin, were more contact inhibited and were not tumorigenic. These results indicate that malignant transformation in HLaC'82 was partially reversed.

Carcinoma, Squamous Cell↗

A correlative study of MR images and cryo-sections of the neonatal hip.

The complex anatomy of the neonatal hip is often difficult to image. Recently, magnetic resonance imaging (MRI) has been used to evaluate the normal and abnormal neonatal hip. We correlated the MRI scans of the hip of a newborn cadaver with multiplanar cryo-sections stained according to Mallory-Cason, to detail the anatomic structures of the normal hip joint space. In our experience, MRI was shown to provide excellent depiction of hip anatomy.

Hip Joint↗

A modified mallory-cason staining procedure for large cryosections.

The classic Mallory-Cason staining procedure has been modified for application to sections "on tape" obtained from large deep frozen tissue specimens. These 20 microns cryosections are collected on tape from a large heavy duty cryomicrotome. The stained sections provide anatomical details that are not revealed by other techniques. The merit of this procedure is found in the support of modern medical modalities, both for research and educational purposes.

Blood Cells↗

Floating on a water bath and mounting glycol methacrylate and hydroxypropyl methacrylate sections influence final dimensions.

This paper reports the dimensional changes occurring in the different steps of the histoprocessing of tissues for light microscopy. Two water-miscible methacrylates used for embedding, namely 2-hydroxyethyl methacrylate and 2-hydroxypropyl methacrylate, were investigated. It was found that during stretching on the water bath and in the mounting step considerable size changes occur, which are of the same magnitude as during the dehydration step of histoprocessing. The final dimensions of the sections and of microscopic images are dependent on the response to surface tension at the water surface and mounting of the glycol and hydroxypropyl methacrylate sections, respectively. Between the two resins under study, significant differences in the size of the resin sections, with and without embedded liver tissue, were found. It is shown that the temperature at which the sections are mounted is of great importance. These observations indicate the importance of standardizing histotechniques if morphometry is to be applied.

Acrylates↗

Glycol methacrylate embedding in histotechnology: the hematoxylin-eosin stain as a method for assessing the stability of glycol methacrylate sections.

Glycol methacrylate (GMA) samples containing inhibitor in the range of 200-300 ppm were included in a standard embedding mixture. The pH of the GMA samples was measured as a 10% solution of the sample in distilled water. The acidity of GMA due to methacrylic acid causes background staining of sections after basic dyes. The concentration of GMA and the amount of impurities such as methacrylic acid (MA) and ethylene glycol dimethacrylate (EDMA) were measured by gas chromatography. Distinct variations in purity were found among five samples of GMA. Sections derived from GMA samples containing more than 2% EDMA showed few, if any, minifolds after staining with hematoxylin and eosin and were more stable in alcoholic and basic solutions; sections from purer GMA showed minifolds and were less stable. Addition of crosslinkers, EDMA or triethylene glycol dimethacrylate (TEDMA) prevented these artifacts. Crosslinkers clearly influence dimensional changes in sections. Addition of crosslinkers to GMA samples containing minimal amounts of MA improved the results. The possibility of obtaining a high quality GMA embedding medium is discussed.

Acrylates↗

6-mercaptopurine: high-dose 24-h infusions in goats.

In vitro investigations have indicated the need for both prolonged exposure to 6-mercaptopurine (6MP) and the use of high concentrations to achieve maximal cell kill. After the customary oral administration the bioavailability of 6MP appeared to be low, and i.v. bolus injections resulted in short-lived high concentrations of 6MP, so prolonged infusions seemed rational. To test the feasibility of this approach 24-h infusions were given to goats. We used our improved HPLC method to quantitate 6MP and 6MP riboside (6MPR) in plasma, CSF, and urine. The concentrations of 6MPR were in excess of those of 6MP. Since 6MPR can easily be converted to 6MP, 6MPR acts as a depot for 6MP. Penetration of both 6MP and 6MPR into CSF was excellent. Of the total dose administered, 38% to 68% could be accounted for in the urine, with about equal amounts of 6MP and 6MPR. At doses of 20 and 10 mg kg-1 h-1 total concentrations of 6MP and 6MPR in excess of 100 microM were reached during 24-h infusions. However, all three experimental animals died due to toxicity. A dose of 2 mg kg-1 h-1 was tolerated; the total steady state concentration of 6MP and 6MPR in two experiments was about 10 microM. We conclude that the prolonged infusion of 6MP is feasible, and in view of the excellent penetration of 6MP and 6MPR into CSF, studies using prolonged infusions of thiopurines are warranted in man.

Administration, Oral↗

6-Thioguanine: high-dose 2-H infusions in goats.

6-Thioguanine (6TG) is poorly absorbed after oral administration. Bolus injections of 6TG result in high peak concentrations with relatively short-lived plasma concentrations. In vitro studies have shown the importance of prolonged exposure to 6TG. Therefore we administered 6TG by infusion at a dose rate of 2 mg/h over 2 h. In three goats we determined the plasma concentration-time curves of 6TG and its riboside (6TGR). A steady state was reached for 6TG and was almost reached for 6TGR within the 2 h of infusion. In one experiment we obtained several samples of CSF and observed good penetration of 6TG and 6TGR into CSF. Urinary excretion of 6TG and 6TGR was also quantitated. The amount of drug and metabolite excreted later than 4 h after the end of the infusion was negligible. By infusing 6TG, the problems of both erratic absorption after oral administration and acute renal toxicity after bolus injection, can be averted. In our opinion prolonged infusions of 6TG may be of advantage in humans suffering from actively proliferating malignant diseases, and thus should be studied.

Animals↗