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Biomedical subjects

M Maly

Publications and source records attributed to M Maly.

6 recordsLinked to original sources
PubMed1997

Lamotrigine pharmacokinetics in patients receiving felbamate.

Drug interactions can significantly complicate the management of patients receiving multiple medications. It is essential therefore that potential pharmcokinetic interactions be evaluated as new antiepileptic medications are introduced. Lamotrigine (LTG) is a recently marketed medication whose pharmacokinetics are significantly influenced by concomitant drugs. Felbamate (FBM), another relatively new antiepileptic agent has been associated with multiple interactions including both enzyme induction and inhibition. The purpose of the present pilot study was to evaluate potential differences in lamotrigine kinetics in six patients concomitantly receiving FBM compared to five patients receiving lamotrigine as monotherapy. There was no statistically significant differences in either apparent LTG oral clearance (0.026 +/- 0.005 vs. 0.024 +/- 0.01 l/kg per h, respectively), or in mean elimination half-life (33.7 +/- 7.5 vs. 40.2 +/- 15.05 h, respectively). Oral clearance values in our patients are also consistent with data reported previously in the literature. Data from this pilot study suggest that a marked effect of FBM upon lamotrigine pharmacokinetics is unlikely.

Adult↗
PubMed1994

Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration.

Valproic acid (VPA) may cause impaired platelet function, thrombocytopenia and, occasionally, severe bleeding. Controversy exists both as to the mechanism of this alteration in hemostasis and as to whether these adverse effects are either dose-related or idiosyncratic. Previous investigations have focused primarily on pediatric patients who commonly were receiving multiple anticonvulsant medications. We evaluated a cohort of 27 adult patients with epilepsy who were receiving VPA monotherapy and compared them with age-matched controls to determine whether a correlation exists between platelet count, function, bleeding time, levels of von Willebrand's factor antigen, and VPA dose or plasma concentration. VPA patients had significantly lower platelet counts and longer bleeding times than did controls (p < 0.05). Platelet count was inversely correlated to VPA dose and both free and total VPA concentration (p < 0.01). There was no significant difference in levels of von Willebrand's factor antigen between patients and controls. We assessed platelet aggregation by measurement of whole-blood platelet aggregation and release with agonists including adenosine diphosphate, thrombin, collagen, arachidonic acid, and ristocetin. VPA patients had significant decreases in platelet aggregation values compared with controls. There were significant differences in collagen, arachidonic acid, and adenosine diphosphate release and aggregation between groups that correlated to both VPA dose (p < 0.01) and concentration (p < 0.05). Prolongation of bleeding time was significantly correlated to both VPA dose and concentration. Our data suggest a significant relationship between impaired platelet function and both VPA dose and plasma concentration.

Adult↗
PubMed1992

Microscopy of bone cells, bone tissue, and bone healing around implants.

Newer methods of scanning microscopy using both light and electrons are particularly relevant to the study of bone cells, bone matrix organization, matrix mineralization, bone modeling and remodeling, and the adaptation of cells and matrix to implants. Most of such studies are conducted on retrieved implants, at least after the death of the related tissue. Because the retention of the tissue-implant relationship in such preserved tissue is crucial for critical evaluation of the implant, methods based on the study of flat surfaces of embedded tissue blocks are very important. Using electrons, the backscattered electrons in a scanning electron microscope can be employed to evaluate mean atomic number (density) and cathodoluminescence can identify polymers and fluorescent labels. Using light, confocal microscopical techniques permit the examination of layers deep to the block face. Confocal reflected and fluorescence methods allow the study of cell behavior upon both transparent and opaque substrates in the laboratory. Examples of the above are presented and interpretation problems discussed. Current experiments are aimed at enabling the study of bone wound healing and bone adaptation to implanted materials in vivo, through the implantation of optical quality windows and/or newly conceived and designed microscopical objective lenses.

Animals↗
PubMedDate not supplied

Vital confocal microscopy in bone.

We wished to exploit confocal microscopy for high spatial and temporal resolution vital microscopy in bone. To this end, we evolved implants with glass windows supported in titanium, which were placed in the medial proximal tibial plateau of the rabbit, and special small, self-focussing objectives (dry 10/0.25, water immersion 20/0.45, and oil immersion 45/0.65 and 120/1.0) which mated and matched to the conical window entrance section of the metal components. At intervals of up to 21 months after implant healing, these lenses were used to study live tissue using two genera of confocal microscope: multiple aperture disc, tandem scanning, microscopes for observation in reflection, and video rate confocal laser scanning microscopes for recording, mainly in the fluorescence mode. The latter allowed the study of a variety of intravenously administered substances, including fluorescein, fluorescein-dextrans, fluorescent microspheres, acridine orange, DASPMI, calcein, and tetracycline. We were able to remove blood, stain cells with fluorescent markers, and replace them into the circulation. Calcein and tetracycline bind to the mineral front in bone: this labelling was studied in progress. We observed that both substances partition and remain for long periods (at least days) in adipocytes. Further characterisation of the system used both confocal fluorescence and scanning electron microscopy methods in the study of retrieved implants. These studies showed that the subimplant cortical bone remodelled to a less compact structure with a rich microvasculature extremely close to bone. The points of attachment of bone to glass were found to involve coarse fibres, with the matrix containing large numbers of large cells: some of this tissue was cartilage and some immature bone. An amorphous, mineralised matrix was in immediate contact with glass. The results provide further confirmation of the general utility of high-scan speed confocal methodology in physiology.

Adipocytes↗