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T Oostendorp

Publications and source records attributed to T Oostendorp.

15 recordsLinked to original sources

The effect of blood flow on oxygen extraction pressures calculated in a model of pointlike erythrocyte sources for rat heart.

A mathematical description of pericapillary oxygen gradients that takes into account the particulate nature of blood is possible in terms of erythrocytes as pointlike sources. The formulation in terms of quasi-stationary sources [1] is extended to account for moving erythrocytes. The extended model is semianalytical and can be used to estimate the extraction pressure (EP), which quantifies the effect on partial pressure of oxygen (pO2) in the tissue far from the erythrocytes. Simulations have been done for rat heart muscle tissue around a capillary. For low hematocrit (Hct; 20%) and low blood velocity EP is highest, higher than the pO2 drop in a surrounding typical tissue cylinder. This means that the impediment to O2 release close to the capillary can be larger than that to transport further into the tissue. Increasing the hematocrit decreases EP, that is, it facilitates O2 release. Increasing the blood velocity decreases EP at low Hct values but has the opposite effect at high Hct values (> 35%). For zero velocity, results are the same as with the quasi-stationary model.

Animals

The effect of separate red blood cells on capillary tissue oxygenation calculated with a numerical model.

In simplified models that describe large quantities of capillaries the capillary content is considered to be homogeneous for oxygen transport; but, in reality, the capillaries contain discrete red blood cells (RBCs), and this discreteness will affect oxygen transport from the capillary to the tissue. This was previously investigated with an analytical model, where RBCs were modelled as point-like sources. A numerical approach is used in this investigation, and the results are compared with the analytical model. In both models the effect of the particulate nature of blood depends on the haematocrit and on the RBC velocity. There is only a minor difference between the two models. For rat hearts, the correction factor used in this study, the extraction pressure, can be up to 3 kPa (23 mmHg).

Animals

Mathematical model of erythrocytes as point-like sources.

A new approach to investigate the effect of pericapillary gradients, caused by the particulate nature of blood, on oxygen partial pressure (pO2) in tissue is presented. The blood erythrocytes are modeled as point-like sources, which makes the system independent of the geometry of the erythrocytes. This model is semi-analytical and is developed to estimate the pO2 far from the erythrocytes. It does so through calculation of the extraction pressure, which accounts for the capillary oxygen drop as compared to homogeneous blood. It is particularly useful to estimate pO2 in regions where the oxygen concentration is low. Simulations have been performed for a cylindrical tissue geometry and parameters are chosen for rat heart muscle. In accordance with the literature, for a fixed total oxygen supply low hematocrit values result in a lower pO2 at the border of the tissue cylinder than high values do. Also a decrease in hematocrit results in higher values for the extraction pressure. Finally, it was found that the effect of the particulate nature of blood is most distinct at low hematocrit values.

Animals

Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse.

The vascularisation and perfusion of seven subcutaneously xenografted human glioma lines established from surgical specimens has been analysed using an anti-collagen type IV antibody to visualise the vascular walls in combination with a perfusion marker (Hoechst 33342). A computer-based digital image processing system was employed for quantitative analysis of the parameters. The vascular architecture of individual tumours belonging to the same tumour line showed a consistent similarity, while substantial differences occurred between the various tumour lines derived from different patients. Despite the presence of a large inter-tumour variation in vascular area as a proportion of the tumour area, this vascular parameter clearly showed tumour line-specific characteristics. The perfused fraction of the tumour vessels also showed a large inter-tumour variation for all tumour lines ranging from 20% to 85%, but the majority of tumours of all lines had perfusion fractions of more than 55%. Despite large variation, the perfused vascular area as a proportion of the tumour cross-sectional area exhibited clear tumour line-specific tendencies. These observations suggest that consistent differences in vascular parameters are present between glioma xenograft lines, although the tumour lines all originated from histologically similar human high-grade gliomas. These differences may have important consequences for treatment and clinical behaviour of this type of tumour.

Adult

Identifying electrode failures with cochlear implant generated surface potentials.

A procedure for measuring surface potentials called electrode-by-electrode (E-E) mapping is described that can detect the nonintermittent malfunctioning of the implanted receiver and electrode array of multichannel cochlear implants, such as the Cochlear (Nucleus) device. E-E mapping is based on the sequential stimulation of all paired combinations of electrodes. The recorded waveforms were averaged and all peak-to-peak amplitudes were combined into one graph for a comprehensive check on open circuit or short-circuited electrodes. Normative data from 21 patients are given. E-E mapping detected electrode failure in three patients whose behavioral thresholds were in agreement with hardware problems, including one case of overstimulation at high stimulus levels. In one patient who was suffering from overstimulation without any deviant thresholds, no failure could be detected. The procedure takes about a quarter of an hour and the stimulus amplitude needed is below threshold for most patients, which makes it especially useful in children. An informative partial E-E map can be made during implantation and requires virtually no extra theater time.

Adult

Cochlear implant generated surface potentials: current spread and side effects.

Surface potentials were recorded in 16 users of the Cochlear (Nucleus) Mini System 22 in order to investigate the current flow resulting from the sequential stimulation of all paired combinations of 22 electrodes. In almost all patients the amplitude of the surface potentials increased with the distance between the stimulating electrodes along the scala tympani and decreased with the distance between the basal electrode and the round window. However, in two patients whose cause of deafness was otosclerosis, the largest surface potentials were seen when the stimulation was applied to electrodes which were approximately half a cochlear turn apart. These highly regular patterns suggested two different pathways for the currents that generated surface potentials: (1) through the fluid along the scala and not through the dense cochlear bone, leaving the cochlea only at the basally located openings; (2) through the very permeable cochlear bone in the case of otosclerosis. Stimulation of any electrodes that caused facial twitching and/or unpleasant sensations in the head (four patients) did not give rise to abnormal surface potential amplitudes. Two patients who suffered from frequent threshold and comfort level changes were tested repeatedly. As the recorded amplitudes did not change significantly over time, neurophysiological changes were a more likely cause than fluctuations of the stimulator output.

Adult

The potential distribution generated by surface electrodes in inhomogeneous volume conductors of arbitrary shape.

The use of the boundary element technique in the computation of the potential distribution within isotropic inhomogeneous volume conductors of arbitrary shape set up by current injected through surface electrodes is presented. The derived algorithm is validated by comparing its solution to analytical solutions in the case of a concentric bipolar electrode configuration on a homogeneous, spherical volume conductor. This problem is essentially a mixed boundary value problem. It is shown that approximations by treating this problem as a Neumann problem, which have recently appeared in the literature, are valid for remote field points only. Applications to the modeling of the field of cardiac defibrillation electrodes are presented.

Algorithms

Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies.

The expression of cytokeratins (CKs) in human lung cancer was studied using chain-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 18, and 19. When applied to adenocarcinomas (ACs) of the lung, high levels of CKs 7, 8, 18, and 19 were detected in all tumors, while CK 4 was found in high concentrations in some ACs. CK 10 and 13 were completely absent, or only present in low numbers of cells. Small cell lung cancers (SCLCs) and lung carcinoids contained CK 18 and sometimes 8 and 19, but no CK 7 in most cases. Three out of four tumors, histologically classified as SCLC, and expressing CK 7 in a variable number of cells were found by electron microscopic studies to contain regions with AC and/or squamous cell carcinoma (SQC) differentiation. The monoclonal antibody specific for CK 7 can therefore possibly help to distinguish AC differentiation within SCLC. CKs 10 and 13 were completely absent in SCLCs and lung carcinoids, while few CK 4-positive cells were found in some SCLCs and in one lung carcinoid. Within SQCs the monoclonal antibodies revealed a pronounced heterogeneity in CK expression. CKs 4, 7, 8, 10, 13, 18, and 19 could be detected, although not evenly distributed among all tumor cells. Highly differentiated SQCs expressed high levels of the CKs specific for squamoid differentiation, i.e., CKs 4, 10, and 13 in variable numbers of cells. With decreasing histologically detectable SQC differentiation these markers were gradually lost, while the number of cells containing CKs 7, 8, 18, and 19 increased. Application of this panel of monoclonal antibodies can therefore distinguish not only the main subtypes of lung cancer, but can also indicate the degree of differentiation and the degree of heterogeneity. These findings can be used as a diagnostic aid in lung tumor pathology, which may have an impact on treatment and prognosis.

Antibodies, Monoclonal

Spontaneous changes in intermediate filament protein expression patterns in lung cancer cell lines.

The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings.

Carcinoma, Small Cell

Immunocytochemical detection of human lung cancer heterogeneity using antibodies to epithelial, neuronal, and neuroendocrine antigens.

Lung cancers were investigated for their heterogeneity as expressed by their immunoreactivity for cytokeratins and neurofilament proteins, as well as for the neuroendocrine differentiation antigen MOC-1. Using broadly cross-reacting antibodies, cytokeratins were detected in nearly all cases of lung carcinomas. Keratinization could be detected only in cases of moderately to well-differentiated squamous cell carcinoma (SQC) using a monoclonal antibody to cytokeratin 10, while a monoclonal antibody reactive with cytokeratin 18, and specific for glandular epithelia, reacted with adenocarcinomas, small cell lung carcinomas (SCLC), and lung carcinoids. In SQC this antibody could detect non-squamous cell differentiation, showing increasing numbers of positive cells with decrease of histologically detectable SQC differentiation. Cells positive for neurofilaments were demonstrated in some of the poorly differentiated SQCs and in some of the cases of SCLC, possibly representing the variant type of SCLC. Also in some of the lung carcinoids neurofilament proteins were present, colocalizing with cytokeratins. MOC-1 was present in all SCLC and lung carcinoids. This antibody could also detect neuroendocrine differentiation in all combined small cell carcinomas, in one poorly differentiated adenocarcinoma, and in about 30% of the poorly differentiated SQCs. Therefore, lung cancer heterogeneity can be detected using a panel of well-defined antibodies to intermediate filaments in combination with the MOC-1 antibody. The use of these antibodies in diagnosis can have prognostic significance and can lead to a more selective therapeutic approach.

Adenocarcinoma

Detection of epithelial- and neural type of intermediate filament proteins in human lung tumors.

Five different types of lung cancers, i.e. squamous cell carcinomas, adenocarcinomas, small cell lung carcinomas, carcinoids and adenoid cystic carcinomas were examined for their intermediate filament constituents, with special emphasis on the different cytokeratin polypeptides and neurofilament proteins. Polyclonal as well as monoclonal antibodies to these proteins were used in immunocytochemical techniques applied to both tumor frozen sections and paraffin sections. Squamous cell carcinomas and adenocarcinomas could be shown to contain cytokeratins, which could be detected in both frozen sections and paraffin sections. Also small cell lung carcinoma (SCLC) and carcinoid lung tumors showed a positive staining reaction with polyclonal and monoclonal (cyto)keratin antibodies, but were negative with neurofilament antibodies, with the exception of one case of lung carcinoid, which co-expressed neurofilaments and cytokeratins. We have used antibodies to cytokeratin polypeptides, to neurofilament proteins and to a neuroendocrine related membrane antigen (MOC-1) to further subclassify heterogeneously composed squamous cell carcinomas. Using a monoclonal antibody to cytokeratin 18, normally present in glandular tissues and adenocarcinomas, we observed that more than 90% of the squamous cell carcinomas examined can be stained with this antibody. The percentage of tumor cells, however, positive for cytokeratin 18 varies between 1 and 100%. In these same tumors a monoclonal antibody to skin keratins, which is known to react specifically with keratinizing cells, also stained variable numbers of tumor cells. This finding confirms the presence of (keratinizing) squamous cell carcinoma elements in these tumors. Our data show that most lung tumors, heretofore considered pure squamous cell carcinomas, should be considered biologically adenosquamous carcinomas. Also areas positive with MOC-1 were found in these tumors, suggesting the presence of squamous cell carcinomas with neuroendocrine differentiation. Furthermore, in some poorly differentiated squamous cell carcinomas areas with neurofilament positive cells were detected, suggesting a neural differentiation within these neoplasms. Adenoid cystic carcinomas are shown to co-express cytokeratins and vimentin in the tumor cells. This phenomenon can be used to identify such tumors and to distinguish them from other lung tumors.

Adenocarcinoma

[Localization of brain electric sources in patients with focal epilepsy].

In this paper we discuss a non-invasive method to localize neural electrical sources using EEG data. In this method, the human head is modelled by a set of four concentric spheres with different conductivities which represent the scalp, the skull, the CSF and the brain or by three triangulated surfaces which approximate the exact head shape (in this model we do not consider the CSF layer) using NMR images. In this case the computer effort is very high, since the calculations imply thousands of equations. Therefore, the number of research groups working with this improved model, in the world, is very small. In both models, we assume that the neural source is a current dipole. This makes the model suitable for cases where the active brain areas are limited and localized. We discuss some error factors associated with the method, as the geometry of the head, the conductivity of the different layers and the number of electrodes used in the EEG measurements. Comparing the more realistic head model, with the spherical one we often have differences of 1-2 cm. However, we can reach even more pronounced differences in the frontal areas. Concerning the skull conductivity, we realized that it could introduce errors of 1-2 cm. We observed that at least 50 electrodes should be used only since 21 electrodes could imply errors of about 0.5 cm. The method was applied, both in the spherical version and the realistic one, to clinical cases of focal epileptic patients. The results are discussed in terms of the other clinical information available and they are coherent with the remaining clinical data.

Adolescent