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Biomedical subjects

M Gerritsen

Publications and source records attributed to M Gerritsen.

At least 19 recordsLinked to original sources
PubMed2002

[Subcutaneously implantable glucose sensors in patients with diabetes mellitus; still many problems].

Despite considerable scientific efforts, no clinical method is currently available for the continuous monitoring of glucose in subcutaneous tissue fluid. In general, good results were obtained during in-vitro experiments with various implantable glucose sensors. However, after implantation these devices exhibited a progressive loss of sensor function. It is evident that the tissue reaction to the implanted sensor, especially the interactions at the sensor-tissue interface, plays an important role in this loss of function. Adequate strategies to improve in-vivo sensor performance can only be developed if there is a better understanding of the processes involved in sensor inactivation.

Biosensing Techniques↗
PubMed2001

Influence of inflammatory cells and serum on the performance of implantable glucose sensors.

The objective of this investigation was to evaluate the influence of polymorphonuclear granulocytes on the performance of uncoated and cellulose acetate/Nafion coated amperometric glucose sensors in vitro. The response of these sensors was also investigated in serum. Uncoated and coated sensors showed lower sensitivities to glucose, with a significant drift in sensor output upon exposure to serum or leukocytes. Although the use of a coating resulted in higher sensitivity, the progressive loss of output was not completely prevented. Stimulated granulocytes were shown to excrete components, probably catalase and myeloperoxidase, which consumed the hydrogen peroxide formed by the oxidation of glucose. In addition, adsorbed serum proteins formed a diffusional barrier for glucose. Furthermore, serum was found to contain low-molecular weight components that alone inhibited glucose oxidase activity. Based on preliminary electrochemical results, we postulate that rabbit serum contains oxidizing substrates that compete with molecular oxygen for the acceptance of electrons from the oxidized enzyme. Consequently, future efforts should be aimed at elucidating the mechanisms involved in the interference of unknown serum components with electron transfer. In addition, further investigations have to be performed to develop an outer membrane that minimizes protein adsorption as well as the actions of inflammatory cells.

Animals↗
PubMed2001

Splenic abscess caused by Peptostreptococcus species, diagnosed with the aid of abdominal computerized tomography and treated with percutaneous drainage and antibiotics: a case report.

We describe herein a 63-year-old patient with a splenic abscess due to Peptostreptococcus spp., diagnosed with the aid of abdominal computerised tomography and treated with ultra-sound guided percutaneous drainage and antibiotics. The bacteriological characteristics of splenic abscesses are discussed.

Abscess↗
PubMed2001

A percutaneous device as model to study the in vivo performance of implantable amperometric glucose sensors.

Glucose kinetics were investigated in subcutaneous tissue of rabbits, in which a percutaneous device was implanted. The device was used for collection of tissue fluid and as carrier of an amperometric glucose sensor. Changes in glycaemia were reflected in subcutaneous tissue fluid. However, a limited number of responses of the implanted sensors were observed. Histologic evaluation showed thin fibrous capsules surrounding the implants. Accumulations of inflammatory cells were observed inside the subcutaneous chamber. The experiments again showed that changes in blood glucose concentration can be measured in subcutaneous tissue fluid collected with a percutaneous device. Nevertheless, implanted glucose sensors could not reliably monitor these changes. Supported by our histological observations and sufficient in vitro performance, we suppose that the cellular reaction to the sensor plays an important role in this poor in vivo performance. In combination with adsorption of tissue fluid proteins, this results in a reversible deactivation of implanted sensors. The exact mechanisms involved in this process are currently unknown and need further investigation.

Journal Article↗
PubMed2001

[Snijders-Oomen Nonverbal Intelligence Test: useful for the elderly?].

The feasibility of the SON-R 5 1/2-17, a non-verbal intelligence test for deaf children, was investigated in a group of older adults, with a view to the future use of the test in older neurological patients. In a group of 58 healthy elderly persons intelligence was measured with the SON, the Raven Progressive Matrices and a Dutch reading test. The subjects were also asked for their subjective judgements of the tests. The SON-R 5 1/2-17 appears to be a user-friendly test. The high correlations between the subtests, and between the SON and other measures of intelligence suggest that the SON is a valid test for measuring fluid intelligence in elderly persons. The existing norms are not suitable when the SON is used in elderly people, new norms for adults should therefore be developed.

Aged↗
PubMed2000

Wound healing around bone-anchored percutaneous devices in experimental diabetes mellitus.

The objective of this investigation was to study the influence of impaired wound healing on the tissue response to bone-anchored percutaneous devices. For this reason, diabetes mellitus was induced in rabbits with alloxan. Untreated rabbits were used as controls. Skin-penetrating titanium implants were inserted in the tibial bone of diabetic and healthy animals. The enossal part of half of the implants was provided with a thin magnetron-sputtered calcium-phosphate coating. The soft-tissue and bone response was evaluated clinically, histologically, and histomorphometrically. We did not observe more infectious complications in diabetic animals. Furthermore, histological analysis revealed no differences in soft-tissue response between diabetic and healthy animals. A close bone-implant contact was observed for all implants. Nevertheless, the density of cortical bone around the implants was clearly lower in diabetic animals compared with control animals. In control rabbits, but not diabetic animals, coated implants showed more downgrowth of bone into the marrow cavity than uncoated ones. In general, diabetes mellitus was shown to have no adverse effect on the clinical performance of the percutaneous devices. We think that this is due to the good fixation of the implants in diabetic as well as control animals. Therefore, we conclude that the presence of impaired healing in chronic health disorders like diabetes is no contra-indication for the anchorage of percutaneous implants in cortical bone.

Animals↗
PubMed2000

The influence of impaired wound healing on the tissue reaction to percutaneous devices using titanium fiber mesh anchorage.

The objective of this investigation was to study the influence of impaired wound healing on the soft-tissue response to percutaneous devices using titanium fiber mesh anchorage. For this reason, diabetes mellitus was induced in rabbits with alloxan. Untreated rabbits were used as controls. Two implant types were inserted subcutaneously: two-stage percutaneous devices as well as separate titanium fiber mesh sheets. The soft-tissue response to both implants was assessed by clinical, histologic, and histomorphometric evaluation. Clinically, we observed a higher number of infectious complications around percutaneous implants in diabetic animals. Histologic and histomorphometric analyses revealed that severe diabetes effected matrix maturation and delayed neovascularization (p<0.05). We also observed higher numbers of inflammatory cells in the mesh porosity of percutaneous implants in severely diabetic animals (p = 0.09). Our results indicate that severe, uncontrolled diabetes negatively influences the maturity and neovascularization of connective tissue inside the fiber mesh porosity. The higher number of infectious complications in diabetic animals suggests that the presence of impaired healing conditions facilitates infection around skin penetrating devices.

Animals↗
PubMed2000

Biocompatibility evaluation of sol-gel coatings for subcutaneously implantable glucose sensors.

The objective of the current investigation is to determine the soft-tissue biocompatibility of sol-gel matrices which can be used to optimize the properties of implantable glucose sensors. The biocompatibility of sol-gel matrices with heparin, dextran sulphate, Nafion, polyethylene glycol, and polystyrene sulphonate was examined in vitro in simulated body fluid and with cell culture experiments using human dermal fibroblasts. Finally, an in vivo study was performed. Therefore, sol-gel coated polystyrene discs were inserted subcutaneously in the back of rabbits. After 4 and 12 weeks, the implants with surrounding tissue were retrieved and processed histologically. In simulated body fluid, the formation of a granular calcium phosphate precipitate was observed. Cell proliferation on polyethylene glycol, Nafion, and heparin coated substrates was comparable to control samples and significantly higher than on dextran sulphate and polystyrene sulphate coated substrates. Light microscopic evaluation of the retrieved in vivo samples showed a fair tissue reaction to all materials. Histomorphometric analysis demonstrated that there were no differences in tissue response to the different sol-gel coatings. In conclusion, sol-gel matrices exhibit a fair biocompatibility both in vitro and in vivo. These results will form the basis for further research into the real merits of sol-gel coatings in optimizing the properties of subcutaneously implantable glucose sensors.

Animals↗
PubMed2000

A percutaneous device to study glucose kinetics in subcutaneous tissue fluid.

In the current study subcutaneous glucose kinetics were investigated in tissue fluid collected with a percutaneous device (PD). PDs containing a subcutaneous tissue chamber were implanted subcutaneously in New Zealand white rabbits. Sintered titanium fiber mesh sheets were used for subcutaneous anchorage of the PD. The bottom of the subcutaneous tissue chamber was either covered with a titanium fiber mesh sheet, a cellulose acetate membrane, or left uncovered. Subcutaneous glucose kinetics were determined after injection of octreotide and glucagon. The tissue reaction to the implants was evaluated histologically. No dynamic relationship was observed between glycaemia and subcutaneous tissue fluid glucose for all membrane covered devices. Histological evaluation showed that the presence of a seroma cavity in combination with obstruction of the membrane prevented adjustment of the subcutaneous glucose concentration in response to changes in glycaemia. In the uncovered devices, on the other hand, changes in glycaemia were reflected in subcutaneous tissue fluid. Our results prove that it is possible to measure changes in the glucose concentration in subcutaneous tissue fluid collected with a percutaneous device. Therefore, we conclude that a percutaneous device has an application as model to study the in vivo performance of implantable glucose sensors. The use of porous membranes in such devices has to be avoided.

Journal Article↗
PubMed1999

Performance of subcutaneously implanted glucose sensors for continuous monitoring.

Despite a considerable amount of research attributed to the development of an implantable glucose sensor, to date there is no clinically applicable concept for continuous glucose monitoring. Investigations to validate the subcutaneous tissue for continuous glucose sensing mostly comprised short-term implantations of glucose sensors. Most implanted glucose sensors showed a significant drift in sensitivity over the implantation period. This bioinstability was not to be expected from the in vitro performance of the sensors. In this paper, the influence of possible failure mechanisms on the poor in vivo performance of subcutaneously implanted glucose sensors is reviewed.

Animals↗
PubMed1999

Role of tumor necrosis factor and interferon gamma in endotoxin-induced E-selectin expression.

Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), potent inflammatory cytokines, are released by macrophages during endotoxin shock. However, the contribution of these cytokines to endotoxin-induced inflammation has not been defined. The expression of E-selectin, measured using the dual radiolabeled monoclonal antibody (mAb) technique, was monitored in different tissues of endotoxin-challenged wild-type and IFN-gamma-deficient mice receiving a mAb to TNF-alpha (TN3). A significant elevation in E-selectin expression occurred in all tissues of wild-type mice challenged with endotoxin. Injection of TN3 in wild-type mice significantly attenuated the endotoxin-induced up-regulation of E-selectin in all tissues (p < .05) except the pancreas. The level of reduction in endotoxin-induced E-selectin expression ranged between 30% in the stomach to 60% in the small intestine. E-selectin expression in endotoxin-challenged, IFN-gamma-deficient mice was significantly reduced in the small and large intestines, when compared with endotoxin-challenged wild-type mice. Although IFN-gamma deficiency had no effect on E-selectin expression in other tissues, administration of TN3 to endotoxin-challenged, IFN-gamma-deficient mice significantly reduced E-selectin expression to levels observed in endotoxin-challenged, wild-type mice that received TN3. These findings indicate that TNF-alpha is essential for achievement of maximal E-selectin expression in most vascular beds during endotoxemia, whereas the contribution of IFN-gamma is largely confined to the small intestine.

Animals↗
PubMed1999

Quantification of murine endothelial cell adhesion molecules in solid tumors.

Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-alpha-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-alpha was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-alpha, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.

Animals↗
PubMed1998

Evaluation of the tissue reaction to a percutaneous access device using titanium fibre mesh anchorage in goats.

The tissue reaction to a percutaneous access device, applicable as a carrier for an implantable glucose sensor, was evaluated in goats. Titanium fibre mesh structures were used for anchorage of the device in superficial as well as deeper soft-tissue locations. The percutaneous part was subcutaneously anchored with a fibre mesh sheet. The distal part was placed intraperitoneally and anchored in deeper soft-tissue layers using a fibre mesh cuff. All implants showed good healing with the surrounding tissue. Histological evaluation showed that the subcutaneous fibre mesh sheets and peritoneal fibre mesh cuffs were filled with immature connective tissue, generally free of inflammation. Problems concerning disconnection of the silicone catheter from the titanium holding element and filling of part of the peritoneal fibre mesh cuff with silicone glue have to be overcome by more appropriate preclinical testing and improved implant design. Our results demonstrate that titanium fibre mesh structures can be used effectively for soft-tissue anchorage of percutaneous access devices. A sufficient ingrowth of connective tissue was obtained in superficial as well as in deeper soft-tissue layers. The access device could have application as a carrier for an implantable glucose sensor for glucose monitoring in different tissue compartments.

Journal Article↗
PubMed1997

Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse.

The dual radiolabeled mAb technique was used to quantify the constitutive and induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the microvasculature of different organs of the mouse. The constitutive expression of both adhesion molecules varied significantly between tissues, with ICAM-1 levels consistently higher than VCAM-1 in all tissues studied. Following systemic administration of endotoxin (LPS), an increased surface expression of both adhesion molecules occurred in most organs, with the largest increases for ICAM-1 (2 to 3x increase) noted in the heart, small intestine, and brain, while heart and small intestine exhibited the largest increases in LPS-induced VCAM-1 expression (2 to 5x increase). These responses occurred in the face of an unaltered expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in all tissues. TNF-alpha also elicited an increased expression of both adhesion molecules, with initial increases noted at 2 to 5 h, peak levels at 5 to 9 h, and a sustained elevation above baseline at 24 h. The TNF-alpha-induced increases in both ICAM-1 and VCAM-1 were dose dependent, with significant up-regulation noted at 5 microg/kg and maximal increases occurring at 10 to 25 microg/kg. These studies indicate that while there are significant quantitative differences in constitutive and induced expression of murine ICAM-1 and VCAM-1, the kinetics and dose-response characteristics of the two adhesion molecules to TNF-alpha are qualitatively similar.

Animals↗
PubMed1995

Palliative chemotherapy with CMF after the same adjuvant regimen for breast cancer. The Breast Cancer Study Group.

BACKGROUND: The results of palliative chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with advanced breast cancer who received adjuvant therapy with the same regimen were investigated. RESULTS: Of 47 patients, 14 (30%) achieved an objective remission (median duration 9.5, range 5-21 months) and 8 (17%) stabilisation of disease (median duration 6, range 3-17 months). Objective remissions were observed in premenopausal as well as in postmenopausal women, in patients with all categories of dominant localisation of disease and regardless of the oestradiol receptor status of the primary tumour or eventual previous endocrine therapy. One of 4 and 13 of 43 patients who started palliative chemotherapy within or later than 12 months after the last adjuvant course obtained an objective remission. The median survival time from start of therapy of all treated patients was 12 (range 1-40) months. Patients with an objective remission or stable disease and patients with progressive disease had a median survival time of 20 (range 6-40) and 6 (range 1-35) months respectively (p < 0.0001). CONCLUSIONS: Palliative treatment with CMF should not be rejected for patients who have relapsed after adjuvant chemotherapy with the same modality.

Adult↗
PubMed1994

Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines.

PURPOSE: Although a number of bioreductive agents are substrates for purified DT-diaphorase the role of this enzyme in either activation or detoxification of these agents in the whole cell is unclear. The aim of this study was to determine the role of DT-diaphorase in the metabolic activation of EO9 under both aerobic and hypoxic conditions. METHODS AND MATERIALS: A panel of lung cancer cell lines was used and drug sensitivity was determined by clonogenic or tetrazolium-dye-based assays. Activities of DT-diaphorase, cytochrome P450 and cytochrome b5 reductase were determined spectrophotometrically by following the reduction of cytochrome c. RESULTS: Small-cell lung cancer cell lines showed a 600-fold range in DT-diaphorase activities but levels were much higher in three of the four non-small-cell lines. Activities of cytochromes P450 and b5 reductase were much lower than those of DT-diaphorase and showed much less variation between cell lines. There was no relationship between the activities of any of the enzymes and aerobic sensitivity to SR 4233, BCNU and cis-platin. Under aerobic conditions there was a clear correlation between DT-diaphorase activity and sensitivity to EO9. The small-cell lines were much more resistant to EO9 than the DT-diaphorase rich non-small-cell lines. A doxorubicin resistant variant of one of the small-cell lines (H69LX10) did not show cross resistance to EO9 but did show a small degree (3-fold) of cross resistance to SR 4233. Under hypoxic conditions, cell lines with high levels of DT-diaphorase showed only a small increase in sensitivity to EO9 (1.5-7 fold); cell lines with low levels of activity showed a 10-37-fold increase in sensitivity. CONCLUSION: These results suggest that under hypoxic conditions, EO9 is metabolized by 1-electron reducing enzymes to a toxic species. This reduction product is oxygen sensitive but a similar degree of activation is obtained under aerobic conditions in cell lines with high levels of 2-electron reducing DT-diaphorase.

Antineoplastic Agents↗
PubMed1994

DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9.

Aerobic sensitivity to indoloquinone EO9 has been shown to correlate with cellular levels of the two-electron reducing enzyme DT-diaphorase. However, little is known about the relative roles of one- and two-electron reducing enzymes in the hypoxic cytotoxicity of EO9. We have characterised a panel of 23 human tumour cell lines for both bioreductive enzyme activities and aerobic sensitivity to EO9. Eight cell lines were then selected for a comparison of aerobic and hypoxic sensitivities. Activities of DT-diaphorase showed a wide range (> 10,000-fold), while activities of the one-electron reducing cytochrome b5 and cytochrome P450 reductases were generally lower and showed only a 15- and 25-fold range respectively. The aerobic cytotoxicity of EO9 was clearly related to the cellular levels of DT-diaphorase (r = 0.87), with higher levels giving increased sensitivity, but not to the levels of one-electron reducing enzymes. In contrast, there was no relationship between sensitivity to BCNU, cisplatin or the bioreductive agent SR 4233 (tirapazamine) and activities of any of these reducing enzymes. Under hypoxic conditions sensitivity to EO9 was markedly increased in cell lines with low levels of DT-diaphorase activity, while cell lines with high levels show only a small increase in sensitivity. This is reflected by a clear correlation (r = 0.98) between cellular DT-diaphorase activity and the ratio of aerobic to hypoxic sensitivity to EO9. However, we have now for the first time demonstrated an inverse correlation (r = 0.93) between the cellular activity of DT-diaphorase and hypoxic sensitivity to EO9, that is sensitivity decreases with increasing DT-diaphorase activity. Moreover, this correlation was lost when cells were exposed to drug in the presence of dicoumarol, supporting an involvement of DT-diaphorase in this relationship. These observations question the previously straightforward role for DT-diaphorase in the metabolic activation of EO9. Whereas DT-diaphorase is associated with increased toxicity in air, it appears to reduce the cytotoxicity of EO9 in hypoxic conditions. This suggests either that the one-electron reduction product of EO9 metabolism, the semiquinone, is more toxic than the two-electron reduction product, the hydroquinone, or that the hydroquinone is not cytotoxic and aerobic toxicity is due to the transient appearance of the semiquinone upon back oxidation of the hydroquinone.

Aerobiosis↗