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Biomedical subjects

A de Vos

Publications and source records attributed to A de Vos.

11 recordsLinked to original sources
PubMed2002

Dynamic posturography using a new movable multidirectional platform driven by gravity.

Human upright balance control can be quantified using movable platforms driven by servo-controlled torque motors (dynamic posturography). We introduce a new movable platform driven by the force of gravity acting upon the platform and the subject standing on it. The platform consists of a 1 m2 metal plate, supported at each of its four corners by a cable and two magnets. Sudden release of the magnets on three sides of the platform (leaving one side attached) induces rotational perturbations in either the pitch or roll plane. Release of all magnets causes a purely vertical displacement. By varying the slack in the supporting cables, the platform can generate small (0.5 degrees ) to very destabilising (19 degrees ) rotations. Experiments in healthy subjects showed that the platform generated standardised and reproducible perturbations. The peak rotation velocity well exceeded the threshold required to elicit postural responses in the leg muscles. Onset latencies were comparable to those evoked by torque motor-driven platforms. Randomly mixed multidirectional perturbations of large amplitude forced the subject to use compensatory steps (easily possible on the large support surface), with little confounding influence of habituation. We conclude that this gravity-driven multidirectional platform provides a useful and versatile tool for dynamic posturography.

Adult↗
PubMed2001

Adaptive intrapatient dose escalation of cisplatin in patients with advanced head and neck cancer.

The purpose of this study was to explore the feasibility and toxicity of intrapatient dose adjustment using predefined levels of exposure to cisplatin, with the ultimate goal to further improve the antitumor activity of the treatment. The primary parameter for adaptive dosing was the level of platinum DNA adducts in peripheral white blood cells (WBC) and the secondary parameter the area under the curve (AUC) of unbound platinum in plasma, which were determined during the applied courses. Target levels had been defined in a previously performed pharmacologic study. The concept of adaptive dosing was tested in 16 patients with locally advanced head and neck (H/N) cancer who would receive six weekly courses of cisplatin at a starting dose level of 80 mg/m(2), which was previously investigated in a phase II study. Forty-seven percent of patients received a dose increase varying from 10 to 40%. Only two patients had exposure levels significantly below the defined target levels for DNA adducts and AUC. The majority of patients reached the defined target levels by modest dose increases of 10-20% during course 2. Relevant but reversible ototoxicity (temporary grade 3 in two patients) and renal toxicity (temporary grade 2 in two other patients) were observed. The pattern and severity of the toxicity was comparable to that encountered in the previous phase II study in H/N cancer patients. We conclude that the strategy of intrapatient dose adjustment for cisplatin is practically feasible in a research setting even when a short turn around time of 1 week is the limit for reporting results. Although in some patients the dose increase that had to be applied to reach target levels was substantial (up to 40%), this approach in H/N cancer patients is not expected to improve the response rate significantly, because these significantly underdosed patients represented only a small percentage of the investigated population. The great majority of patients needed only limited (10-20%) dose increases which very likely will not improve the response rate to a clinically significant extent. The outlined concept is currently being explored in other tumor types and schedules of cisplatin.

Adult↗
PubMed1993

Assessment of pupillary responses to light with IRIS.

With a newly developed method, IRIS, the potential usefulness of various parameters of pupillary reflexes for the assessment of autonomic nerve function was studied. Constriction latency decreased and dilatation latency increased significantly with higher intensities of light (P < 0.01 and P < 0.05, respectively). Thirteen subjects were tested twice one year apart in order to examine long-term intra-individual variability; no significant differences (all P > 0.3) were found. Reproducibility and reliability of hippus and pupil cycle time were lower than for the determination of constriction and dilatation latency. None of the parameters was correlated with age (all P > 0.3). We conclude that pupillary constriction and dilatation latency, assessed with IRIS, are the main dynamical parameters for the study of parasympathetic and sympathetic parts of the autonomic nervous system, that controls the pupillary system. Although a statical parameter, useful additional information may be obtained from the dark adapted pupil diameter. Hippus cycle time and pupil cycle time do not provide additional information and therefore cannot be recommended as standard tests for autonomic nerve function.

Adult↗
PubMed1991

Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera.

A monoclonal antibody and an affinity purified polyclonal antibody, both raised against recombinant human IL-6, have been employed in an ELISA procedure to quantitate human IL-6. Both antibodies were very potent in neutralizing the biological activity of recombinant as well as natural human IL-6. The monoclonal antibody was used as the capture antibody whilst the polyclonal antibody, in biotinylated form, was used as the detecting antibody in combination with a streptavidin horseradish peroxidase conjugate and a signal amplification system. The detection limit for natural as well as recombinant IL-6 was 1 pg/ml. A good correlation was found between the ELISA and the B9 biological assay when IL-6 was measured in crude culture supernatants, in synovial fluids of rheumatoid arthritis patients and in the sera of patients with diverse diseases. Immunoprecipitation of IL-6, produced by different cell types, such as monocytes, endothelial cells and smooth muscle cells or derived from biological fluids, such as the serum of a patient with septic shock or the synovial fluid of a rheumatoid arthritis patient, revealed in every case only molecules in the molecular weight range of 21,000-26,000.

Animals↗
PubMed1989

The pupillary light reflex in diabetes mellitus: evaluation of a newly developed infrared light reflection method.

Pupillary light reflexes were measured in 18 diabetic patients without clinical signs of neuropathy and in 18 control subjects, using a newly developed infrared light reflection technique called IRIS. This method has some important advantages. Apart from being non traumatic, it enables the recording of dynamic pupillary light reflexes simultaneously in both eyes. Furthermore, it has a large amplitude and time resolution (1 ms), permitting accurate determination of latency values. It was found that 78% of the diabetic patients show a significantly prolonged latency of the constriction reaction, while 39% of the diabetic patients show an abnormally prolonged dilatation latency. All patients with an abnormally prolonged dilatation latency also show a prolonged constriction latency. This finding suggests that in diabetes mellitus the parasympathetic system is affected before abnormalities of the sympathetic nervous system can be demonstrated. Assessment of the pupillary light reflex, using the sensitive IRIS method, is an easily applicable and reliable method for detection of subclinical autonomic nervous system dysfunction associated with diabetes mellitus. The method may also provide an objective tool for the assessment of therapy results in diabetic neuropathy.

Adult↗
PubMed1988

Crystallization of human c-H-ras oncogene products.

There is compelling evidence that cancer develops as a consequence of genetic changes (probably multiple) in some members of a selected set of cellular genes. DNA isolated from a variety of tumors, but not normal tissues, possesses the ability to malignantly transform non-tumorigenic cells. Many oncogenes responsible for such transformation have been isolated from transformed cell lines and animal and human tumors induced spontaneously, by virus, by chemical, or by radiation. The most commonly found transforming genes isolated from human tumor cells by DNA transfection assay are the ras gene family (c-H-ras, c-K-ras and N-ras). We report crystallization of several human c-H-ras oncogene proteins.

Crystallization↗
PubMed1987

Further studies on the standardization of neonatal bilirubin.

Certain problems in the standardization of direct-reading instruments (bilirubinometers) were investigated. It was shown that the combination of wavelength setting and choice of pH is very important with respect to the standard to be used. It is emphasized that in fact there is no synthetic bilirubin standard which can be used as primary standard. Reasons are given why the only pragmentic solution proved to be a pool of neonatal serum.

Adult↗
PubMedDate not supplied

Nerve fiber size-related block of action currents by phenytoin in mammalian nerve.

We investigated nerve fiber size-related actions of phenytoin (PHT) by applying the anticonvulsant on 2-mm-long stretches of desheathed whole nerves, excised from rat sural nerve. Compound action potentials (APs) were elicited by voltage pulses of increasing amplitude and recorded as monophasic action currents of the A alpha beta-type along the surface of the nerve. The area under the action current Q at supramaximal stimulation was reduced by 11 and 30% in solutions containing 10 and 100 microM PHT, respectively, similar to the reduction in peak action current. However, a greater reduction in Q induced by PHT was observed with smaller stimuli at both concentrations. This stimulus-dependent reduction was believed to originate from selective inhibition of the thicker nerve fibers. Using a mathematical model, we separated Q into contributions Q alpha of the alpha-fibers and Q beta of the beta-fibers. In solutions containing 10 microM PHT, Q alpha was reduced by 15% maximally, whereas Q beta was not affected. Both fiber types were reduced < or = 30% in the presence of 100 microM PHT, whereas the relations between Q alpha and Q beta, respectively, and stimulus voltage shifted along the voltage axis for 0.3 V, suggesting that the larger fibers in the A alpha beta-groups were more inhibited by PHT than the smaller ones. Abolition of the early phases of the compound action currents by PHT also indicated loss mainly of faster conducting nerve fibers. We conclude that primarily the larger fibers in the A alpha beta populations were inhibited by the anticonvulsant, strongly suggesting a differential mode of action by PHT on myelinated nerve fibers.

Action Potentials↗