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Biomedical subjects

J A Jansen

Publications and source records attributed to J A Jansen.

At least 127 records · Page 7Linked to original sources

Absence of interaction between tiagabine, a new antiepileptic drug, and the benzodiazepine triazolam.

In a randomised, double blind, placebo-controlled, four-period cross-over study in 12 healthy volunteers, the potential pharmacodynamic and pharmacokinetic interactions between the new antiepileptic drug, tiagabine, and the benzodiazepine, triazolam, were investigated. A single dose of tiagabine HCl 10 mg did not enhance the sedative or cognitive effects of a single dose of the benzodiazepine triazolam 0.125 mg, although the time-course of the effects was prolonged. Furthermore, tiagabine did not produce any statistically significant effects on the pharmacokinetics of triazolam. Similarly, the pharmacokinetics of tiagabine were not modified by triazolam. Tiagabine was well tolerated when administered alone or with triazolam.

Adolescent↗

Tiagabine: absence of kinetic or dynamic interactions with ethanol.

Tiagabine is a new antiepileptic drug that inhibits the uptake of gamma-aminobutyric acid into neurons and glia. This double-blind, placebo-controlled study investigated the effect of multiple doses of tiagabine on the adverse cognitive effects produced by a single dose of ethanol in 20 healthy volunteers. The effects of each drug on the pharmaco-kinetics of the other were also determined. Compared with placebo, tiagabine produced no statistically significant effects on digit vigilance speed (primary assessment variable) or accuracy, choice reaction time, immediate or delayed word recall, delayed word recognition speed or sensitivity, visual tracking, body sway, or subjective measures of alertness, calmness, and contentment. There was no evidence of a pharmacodynamic interaction between tiagabine and ethanol with respect to these variables. The pharmacokinetic parameters of tiagabine and ethanol (maximum plasma concentration [Cmax], time to Cmax and area under the plasma concentration-time curve) were unchanged during concomitant administration. Adverse events, which mainly affected the central nervous system, occurred with a similar incidence during tiagabine and placebo administration and were more common after the administration of ethanol. There appears to be no need for additional caution regarding driving or operating machinery when ethanol is administered to patients taking tiagabine.

Adult↗

The effect of a subcutaneous silicone rubber implant with shallow surface microgrooves on the surrounding tissues in rabbits.

It has been suggested that during wound healing microtextured surfaces can alter events at the interface between implant surface surface and surrounding tissues. To investigate this phenomenon, smooth and microtextured silicone rubber implants were implanted subcutaneously in rabbits for 3, 7, 42, and 84 days. The textured implants possessed parallel surface microgrooves and ridges with a width of 2.0, 5.0, and 10.0 microns. All grooves had a depth of approximately 0.5 microns. SEM observation showed fibroblasts, erythrocytes, lymphocytes, macrophages, fibrin, and collagen on all implant surfaces after 3 and 7 days. After 42 and 84 days only little collagen, a small number of fibroblasts, but no inflammatory cells were seen on the implant surfaces. The fibroblasts were not oriented along the surface grooves on all textured surfaces. Three-dimensional reconstruction of CLSM images and LM images showed no significant differences between the thickness of the capsules surrounding the smooth and those surrounding the microgrooved implants. In contrast LM did show a significantly lower number of inflammatory cells and a significantly higher number of blood vessels in the capsules surrounding the microgrooved implants. Differences between the 2.0, 5.0, and 10.0 microns grooved implants were not detected. Our results concerning the capsule thickness suggest that the depth of our grooves was not sufficient to facilitate mechanical interlocking, but the cause for the observed differences in inflammatory response and number of blood vessels remains unclear.

Animals↗

The effect of Ca-P plasma-sprayed coatings on the initial bone healing of oral implants: an experimental study in the goat.

The response of bone of low density to uncoated, fluorapatite (FA), hydroxyapatite (HA), and hydroxyapatite heat treated (HAHT) plasma-sprayed coated implants was investigated 3 and 6 months after installation. Forty-eight threaded implants of commercially pure titanium were inserted into the maxilla of twelve goats according to a split-plot design. One goat died shortly after installation of the implants, five goats were sacrificed 3 months after installation, and the other six goats 6 months after installation. Histological evaluation revealed no difference in bone reaction between the 3- and 6-month implantation periods. In addition, probably due to the wide inter- and intra-animal variability, no significant difference between the 3- and the 6-month periods could be observed in the histomorphometrical measurements performed. Further, no significant differences were found in bone reaction among the various implant materials. Finally, qualitatively it appeared that all coatings showed reduction in coating thickness and that such reductions were most pronounced for the HA coatings.

Animals↗

A histological and histomorphometrical evaluation of the application of screw-designed calciumphosphate (Ca-P)-coated implants in the cancellous maxillary bone of the goat.

Various studies already have shown that the occurrence of oral implant failure is higher in the maxilla than in the mandible. To learn whether Ca-P coatings can improve the success rate of oral implants in the maxilla, three different plasma-sprayed, Ca-P-coated, self-tapping Brånemark implants were inserted in the trabecular bone of the maxilla. Before the insertion of the implants, the two first upper premolars of 16 goats were bilaterally extracted. Four months later, each animal received four types of implants: three different Ca-P-coated types and one uncoated. After an endosseous period of 6 months, the implants were provided with permucosal abutments. Four months later the animals were killed. At the end of the experiment, it appeared that 10 of the 16 installed noncoated implants had failed while of the 48 Ca-P-coated implants, only 6 had failed. All successful implants were retrieved and prepared for histomorphometrical evaluation of the bone and gingiva response. The Ca-P-coated implants showed a significantly greater percentage of bone in contact with the implant surface compared with the uncoated implants. The length of the epithelium was not significantly different for the coated compared to the uncoated implants, but the connective tissue was significantly thicker for the noncoated implants than for the Ca-P-coated implants. Also, measurements revealed that all coatings showed reduction in thickness. On the basis of these findings, we concluded that the application of Ca-P coatings (1) improves the bone-implant reaction, although all coatings reduced in thickness, and (2) is of benefit during the healing period in less mineralized trabecular bone.

Animals↗

Mechanical and histologic evaluation of Ca-P plasma-spray and magnetron sputter-coated implants in trabecular bone of the goat.

To aim of this study was to investigate the bone response to calcium phosphate (Ca-P) plasma-spray and radiofrequency magnetron sputter-coated implants with comparable roughness. Therefore, tapered conical screw designed implants were installed in the trabecular bone of the femurs of nine goats. They were provided with two types of coatings, a plasma-spray dual coating of fluorapatite and hydroxyapatite (FA/HA-PS) and a titanium plasma-spray coating, covered with an amorphous Ca-P magnetron sputtercoating (TPS/Ca-P-a). These implants were evaluated histologically and mechanically after 3 months of implantation. A well-controlled method to apply and measure a torsional force to load the screw-type implants to the point of failure was introduced. All implants healed uneventful and were well fixed. No significant difference (Student t test, p > 0.05) for the torsional failure force was measured for both type of coatings. Nevertheless, SEM revealed differently situated fracture planes. Light microscopy showed intimate bone-implanted contact for both types of coatings; original drill margins were still visible. A lamellar type of bone with some remodeling lacunae was shown. Histomorphometry revealed a higher percentage of bone contact for the FA/HA-PS-coated implants (students t test, p < 0.05). Measurement of the amount of bone revealed more bone mass around TPS/Ca-P-a-coated implants (analysis of variance and Turkey multiple comparison, p < 0.05).

Animals↗

Influence of rapid heating with infrared radiation on RF magnetron-sputtered calcium phosphate coatings.

This study evaluated the effect of rapid heating with infrared radiation on the physico-chemical and morphological properties of radio frequent (RF) magnetron-sputtered calcium phosphate (Ca-P) coatings. About 2.5 microm thick Ca-P coatings were deposited on titanium disks and cylinders. These specimens were left untreated or were heat treated by infrared radiation at 300, 400, 500, 600, and 700 degrees C for 4, 7, 11, 17, and 24 s. Subsequently, the specimens were immersed in simulated body fluid (SBF) for 1 day, 1 week, and 5 weeks. X-ray diffraction measurements showed that heating at 500 degrees C or higher resulted in an increase of coating crystallinity. In addition, FT-IR measurements revealed the appearance of OH peaks in the spectra of samples treated at 500-700 degrees C. Electron probe microanalysis showed that after 5 weeks of immersion about 40-50% of the coatings heat treated at 500 and 600 degrees C was maintained. The coatings heat treated at 700 degrees C showed no dissolution at all. On the other hand, as-coated and 300 degrees C treated films were dissolved within 1 day. Scanning electron microscopy of the samples showed that directly after heat treatment no apparent cracks were present in the coatings. On the basis of these findings, we conclude that rapid heating with infrared radiation around 600 degrees C is the best heat treatment for RF magnetron-sputtered coatings.

Biocompatible Materials↗

The pharmacokinetics of tiagabine in healthy elderly volunteers and elderly patients with epilepsy.

The pharmacokinetics of tiagabine after single-dose (8 mg) and multiple-dose (3 mg, three-times daily for four days) administration of tiagabine HCl were investigated in healthy elderly volunteers (n = 8; Group 1), elderly patients with epilepsy receiving at least one hepatic enzyme-inducing antiepileptic drug (AED) (n = 8; Group 2), and healthy young volunteers (n = 8; Group 3). Participants were matched by gender, age (Groups 1 and 2), alcohol intake, body weight, and whether they smoked tobacco. The pharmacokinetic parameters of tiagabine following single- and multiple-dose administration were similar in both healthy elderly and young volunteers except for a small but significant difference in the area under the concentration-time curve after multiple-doses (103 +/- 29 ng.hr/mL/mg in the elderly versus 72 +/- 20 ng.hr/mL/mg in younger participants). This is not expected to have any clinical relevance because of the large intersubject variability in this parameter. In contrast, and as expected, the pharmacokinetics of tiagabine were altered in the presence of enzyme-inducing antiepileptic drugs: Time to reach maximum plasma concentration, area under the concentration-time curve, and elimination half-lives were significantly lower (e.g. 39 +/- 13 ng.hr/mL/mg for AUC after multiple-dose) compared with corresponding values in the healthy volunteers. These findings suggest that adjusting the dose of tiagabine on the basis of the age of the patient is not necessary, although, irrespective of age, higher doses and/or more frequent administrations will be required in patients taking concomitant enzyme-inducing antiepileptic drugs.

Adult↗

Wound healing phenomena in titanium fibre mesh: the influence of the length of implantation.

In previous experiments a new type of percutaneous device for implantation in soft tissue was designed, containing a sintered titanium fibre mesh. The devices are inserted by a so-called "two-phase' surgical technique with an intervening healing period of 3 months between insertion of the subcutaneous and percutaneous parts. From a clinical point of view, this time interval is too long. The aim of this study was to investigate whether it was possible to reduce the intervening healing period. The implants were inserted in the backs of nine goats. In each goat, six implants were placed with intervals of 1 week. Consequently, at the end of the experiment, in each goat six implants were present with implantation periods ranging from 1 to 6 weeks. After 6 weeks, the animals were killed and the implants with surrounding tissue were processed histologically. Analysis demonstrated that during the first 2 weeks an inflammatory response was present. Thereafter, no difference in tissue response was found between the various implantation periods. In conclusion, the experiment suggests that for titanium mesh percutaneous devices a 3-week healing period is sufficient between the installation of the subcutaneous and percutaneous parts.

Animals↗

Stability of radiofrequency magnetron sputtered calcium phosphate coatings under cyclically loaded conditions.

The stability of radiofrequency (RF) magnetron sputtered calcium phosphate was studied under cyclically loaded conditions. The coatings were deposited on titanium bars and tested in either dry or wet conditions X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and Fourier transform infrared (FTIR) spectroscopy were used to characterize the as-sputtered and tested coatings. XRD demonstrated that the amorphous structure after annealing at 650 C changed into a crystalline apatite structure. The residual stresses were determined by the XRD cos 2 i/i method. These residual film stresses were influenced by the coating conditions and the crystalline sputtered coating showed the presence of compressive stresses. SEM demonstrated that, after cyclic loading conditions in air, the crystalline sputter-coated Ti-6A1-4V bars showed a partial coating loss. Furthermore, in wet conditions (simulated body fluid) only the heat-treated sputter-coated bars appeared to be stable. On the other hand, the amorphous coating only showed signs of delamination in the more highly stressed regions, while in the less stressed regions a Ca-P precipitate was formed. On the basis of these results we conclude that calcium phosphate coatings subjected to cyclic loading conditions show an important difference in fatigue behaviour when tested in either dry or wet conditions.

Absorptiometry, Photon↗

Assessment of bone surrounding implants in goats: ex vivo measurements by dual X-ray absorptiometry.

The aim of the present study is to determine the possibility of measuring the bone mineral density (BMD) around implants by dual energy X-ray absorptiometry (DEXA). Therefore, the trabecular BMD was measured close to 127-600 microns and at a distance from various uncoated and Ca-P-coated implants inserted into the femoral condyle of goals. The implants were left in situ for 12 weeks. In addition, the bone-implant interface was evaluated histologically. For comparative reasons the BMD of non-implanted lateral and medial femoral condyles was also measured. The reproducibility of the measurements, expressed as a coefficient of variation, was found to be 0.44%. Moreover, the regions closest to the implants exhibited a higher BMD than all other regions, and the regions located in the medial condyle showed a higher BMD than the lateral condylar regions. Although the histological sections of the implants in the medial condyle demonstrated more bone contact with the coated than with the uncoated implants, a higher density was measured around the uncoated implants. The results regarding the non-implanted condyles indicated a higher density in the medial than in the lateral condyle. In view of these results, we conclude that BMD around dental implants depends on the location of the implant and that DEXA appears to be an excellent tool for analysing bone-implant reactions.

Absorptiometry, Photon↗

An animal study on the bone behaviour of Ca-P-coated implants: influence of implant location.

Four different implant materials were installed into the mandibular corner of goats to investigate the trabecular bone response in a mainly unloaded model. The implants were installed using a standardized technique and were left in situ for 12 weeks. One goat had to be sacrificed after surgery because of a broken rib; the other animals healed uneventfully. After sacrifice of the animals, the bone response to the uncoated and the three different Ca-P implants was evaluated histologically and histomorphometrically. Four sections of each implant were evaluated; two were located in the cortical and two in the trabecular bone. Of the 44 retrieved implants, 20 implants appeared to be installed partially in the mandibular canal, as clearly visible on the X-rays. These implants were not used in the histomorphometrical measurements. Histological evaluation showed that the trabecular and cortical bone reactions were similar; there was no significant difference in the percentage of bone contact nor in the amount of bone in contact with the implants. In conclusion this study showed that the mandibular corner is an unsatisfactory model for the installation of implants because of anatomical restrictions. Also, the experiment remained inconclusive about the influence of loading conditions on bone behaviour. Nevertheless, the histological results confirmed the bioactive properties of Ca-P coatings.

Journal Article↗

Initial interfacial healing events around calcium phosphate (Ca-P) coated oral implants.

The bone response to different calcium phosphate (Ca-P) coated and non-coated titanium implants was evaluated in a goat animal model. Two types of Ca-P coatings have been investigated: an experimental plasma-spray bilayered Ca-P coating (FA-HA) and an amorphous RF magnetron sputter coating (Ca-P-a). Fifty-four conical screw shaped implants were inserted in the lateral and medial femoral condyles of 18 Saanen goats. After implantation periods of 3, 12 and 24 days, the bone-implant interface was evaluated histologically and histomorphometrically. Light microscopical evaluation revealed that bone formation on the Ca-P coated implants proceeded faster. At 24 days higher percentages of bone contact were measured for both Ca-P coated implants than for non-coated implants. However, this difference was only significant for the FA-HA coated implants. On basis of these findings, we concluded that Ca-P coatings show improved bone response due to an initial difference in bone cell response.

Animals↗

Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus.

A novel antiepileptic drug, tiagabine ((R)-N-[4,4-di-(3-methylthien-2-yl) but-3-enyl] nipecotic acid hydrochloride), was studied in rats in order to determine its efficacy in preventing seizures, seizure-induced neuronal damage and impairment of spatial memory in the perforant pathway stimulation model of status epilepticus. In pilot experiments, administration of tiagabine (50, 100 or 200 mg/kg/day) with subcutaneously implanted Alzet osmotic pumps led to a dose-dependent increase in tiagabine concentrations in the serum and brain. Two days of tiagabine treatment at a dose range of 50-200 mg/kg/day did not change the levels of gamma-aminobutyric acid (GABA), glutamate or aspartate in cisternal cerebrospinal fluid (CSF) compared to the controls. In the pentylenetetrazol test, the maximal anticonvulsive effect of tiagabine administered via osmotic pumps was achieved already with a dose of 50 mg/kg/day. In the perforant pathway model of status epilepticus, subchronic treatment with tiagabine (Alzet pumps, 50 mg/kg/day) completely prevented the appearance of generalized clonic seizures during stimulation (P < 0.001). In the same rats, tiagabine treatment reduced the loss of pyramidal cells in the CA3c and CA1 fields of the hippocampus (P < 0.05) but not the loss of somatostatin immunoreactive neurons in the hilus. Two weeks after perforant pathway stimulation, the tiagabine-treated rats performed better in the Morris water-maze test than the vehicle-treated rats did (P < 0.001). Our results show that tiagabine treatment reduces the severity of seizures in the perforant pathway stimulation model of status epilepticus. Possibly associated with the reduction in seizure number and severity, tiagabine treatment also reduced seizure-induced damage to pyramidal cells in the hippocampus as well as the impairment of the spatial memory associated with hippocampal damage.

Animals↗

Evaluation of plasma-spray and magnetron-sputter Ca-P-coated implants: an in vivo experiment using rabbits.

The bone response to different plasma-spray and magnetron-sputter calcium phosphate (Ca-P)-coated implants was evaluated in a rabbit animal model. Four types of Ca-P coatings have been investigated: a plasma-spray Ca-P coating (HA-PS), a heat-treated plasma-spray Ca-P coating (HA-PS/ht), an amorphous magnetron-sputter coating (Ca-P-a), and a crystalline magnetron-sputter coating (CA-P-c). Seventy-two specially designed cylindrical implants were inserted in the lateral and medial femoral condyles of 18 New Zealand White rabbits. The four differently coated implants were positioned in one animal according to a split-plot design. After implantation periods of 3, 6, and 9 weeks, the bone-implant interface was evaluated histologically. Besides descriptive light microscopical evaluation, quantitative histomorphometrical measurements were done to determine bone contact and the amount of bone surrounding the implant-bone interface. Light microscopical examination revealed that all types of coatings followed the same process of bone healing. Measurements of bone contact at 6 and 9 weeks did not reveal significant differences between the various coatings. For the amount of bone, in a circular region at a certain distance from the implant, the Ca-P-c-coated implants showed a significantly greater amount of bone after 6 weeks of implantation than did the other three Ca-P coatings. At 9 weeks this difference could no longer be measured. On the basis of these findings we concluded that magnetron-sputtered Ca-P coatings show the same process of bone healing as the plasma-sprayed Ca-P coatings when inserted into the trabecular femoral bone of rabbits.

Animals↗

Quantitative analysis of fibroblast morphology on microgrooved surfaces with various groove and ridge dimensions.

Fibroblasts have been shown to respond to substratum surface roughness. The change in cell size, shape and orientation of rat dermal fibroblasts (RDF) was therefore studied using smooth and microtextured silicone rubber substrata. The microtextured substrata possessed parallel surface microgrooves that ranged in width from 1.0 to 10.0 microns, and were separated by ridges of 1.0 to 10.0 microns. The grooves were either 0.45 or 1.00 microns deep. Prior to incubation, the substrata were cleaned and given a radio frequency glow discharge treatment. After surface evaluation with scanning electron microscopy and confocal laser scanning microscopy, RDF were incubated on these substrata for 5 days. During this period of incubation, the RDF were photographed on days 1, 2, 3, 4, and 5, using phase contrast microscopy. Digital image analysis of these images revealed that on surfaces with a ridge width < or = 4.0 microns, cells were highly orientated (< 10 degrees) and elongated along the surface grooves. Protrusions contacting the ridges specifically could be seen. If the ridge width was larger than 4.0 microns, cellular orientation was random (approximately 45 degrees) and the shape of the RDF became more circular. Furthermore, results showed that the ridge width is the most important parameter, since varying the groove width and groove depth did not affect the RDF size, shape, nor the angle of cellular orientation.

Animals↗

Tissue reaction to Dacron velour and titanium fibre mesh used for anchorage of percutaneous devices.

Dacron velour is often used to anchor a percutaneous device, like the catheter used in peritoneal dialysis. However, exit-site infections complicate this method of dialysis and are supposed to be related to the design of the catheter. In animal experiments, a percutaneous device provided with a titanium fibre mesh to anchor the implant was not affected by infectious complications. The purpose of this study was to compare the differences in soft tissue reaction to Dacron velour and titanium fibre mesh under the same experimental conditions. Therefore, we placed implants, provided with either Dacron or titanium mesh, subcutaneously in the dorsum of goats. The implants were left in situ for 4 months. Histological and histomorphological evaluations were performed. It was found that the soft tissue response inside the Dacron was mainly inflammatory, while the titanium mesh evoked good biocompatible behaviour. We concluded that the limited fibrous tissue ingrowth into the Dacron cuff has to be the reason for the observed high failure incidence of a percutaneous device.

Administration, Cutaneous↗