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Biomedical subjects

A Zwart

Publications and source records attributed to A Zwart.

At least 37 records · Page 2Linked to original sources
PubMed1989

Nasal tumours in rats after severe injury to the nasal mucosa and prolonged exposure to 10 ppm formaldehyde.

To study the significance of damage to the nasal mucosa for the induction of nasal tumours by formaldehyde in rats, a long-term inhalation study was conducted in which male rats with severely damaged or undamaged nose were exposed 6 h/day for 5 days/week to 0, 0.1, 1.0 or 10 ppm formaldehyde vapour for 28 months, or for 3 months followed by a 25-month observation period. The damage to the nasal mucosa was induced by bilateral intranasal electrocoagulation. The total number of rats used was 720, 480 with damaged and 240 with intact nose. Compound-related degenerative, inflammatory and hyperplastic changes of the nasal respiratory and olfactory mucosa were invariably observed when rats with intact nose were exposed to 10 ppm but not when exposed to 1.0 or 0.1 ppm formaldehyde. Nasal electrocoagulation increased the incidences of formaldehyde-induced rhinitis, hyper- and metaplasia of the respiratory epithelium, and degeneration and hyper- and metaplasia of the olfactory epithelium. In addition, exposure to 10 ppm formaldehyde for 28 months produced nasal squamous cell carcinomas in rats with damaged nose (15/58) but not in rats with intact nose. Three months of exposure to 10 ppm formaldehyde or exposure to 0.1 or 1.0 ppm formaldehyde for 28 months had no such effect. It was concluded that severe damage to the nasal mucosa may contribute to the induction of nasal tumours by formaldehyde.

Animals↗
PubMed1989

The excretion of highly soluble gases by the lung in man.

The excretion (E) of inert gases by the lung depends on, among other things, their blood-gas partition coefficients (lambda). According to conventional gas exchange models, E should increase with increasing lambda. However, recent models that take into account the tidal character of breathing and the buffering capacity of lung tissue predict that E will show a minimum in the range of large lambda values (lambda greater than 10). Further, this local minimum should shift to larger lambda values in exercise conditions as compared to rest conditions. The aim of this study is to verify this predicted behaviour of E. The experiments were carried out with seven healthy subjects at rest and at three work loads (50 W, 100 W and 150 W) on a bicycle ergometer. The behaviour of E was determined from the results of a simultaneous washin of four tracer gases: ethyl acetate (lambda approximately 75), acetone (lambda approximately 330), ethanol (lambda approximately 2000) and acetic acid (lambda approximately 20000). The washin lasted 4 min, and E was calculated from E = 1 - PE-/PI, where PI and PE- are the partial pressures of the tracer gas in inspired and mixed expired gas determined from the recordings obtained during the last minute of washin. PI and PE- were measured with a mass spectrometer. Comparison of the E values of the four gases shows that at rest a minimum value for E is found for acetone. In exercise conditions, however, the smallest E value is found for the more soluble ethanol or acetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1989

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylene↗
PubMed1989

Diffusion-limited gas mixing in the lung and its consequences for transpulmonary gas transport.

The ratio of alveolar ventilations of He and SF6 (VA,He/VA,SF6) was determined in 7 healthy male subjects at rest and at three different levels of exercise on a bicycle ergometer (75, 150 and 225 W). This ratio was calculated from the ratio of the specific ventilations for these gases which were obtained from the decay of the end-tidal partial pressures of He and SF6 during a simultaneous, multiple-breath washout. In all experiments, VA for He was larger than VA for SF6. On the average, VA,He/VA,SF6 was equal to 1.09, and the mean values of this ratio at rest and at the three levels of exercise were not significantly different. Therefore, the difference in VA for He and SF6 (VA,He-VA,SF6) increased with increasing work load. Further, we used the mean value obtained for VA,He/VA,SF6 to calculate the ratio of excretion values (E1/E2) for pairs of hypothetical tracer gases with equal blood-gas partition coefficients and with different diffusivities in the gas phase. E1/E2 ranged from unity for lambda = 0 to about 1.08 for lambda = 10. At a given lambda, E1/E2 decreased with increasing ventilation-perfusion ratio of the lung. Thus, the difference between the excretion values of light and heavy tracer gases will be most pronounced under rest conditions and for gases that are well soluble in blood.

Adult↗
PubMed1989

Determination of concentration-time-mortality relationships versus LC50s according to OECD guideline 403.

The effect of decreasing the number of animals on the accuracy of estimated concentration-time-mortality relationships and the LC50 values derived from these was investigated by means of simulation methods. Studies of NH3, Cl2, H2S, and COCl2 were made using 5 rats per sex per group. Mortality rates were analysed in 500 new data sets obtained by randomly removing 4 rats/sex/group from the original data sets. It was concluded that the concentration-time-mortality relationship and the LC50 values can be determined over a 5-10-fold time range using one rat/sex/group. The resulting 5 and 95 percentiles compare favourably with the 90% confidence limits when determining a LC50 according to OECD guideline 403. When using concentration-time-mortality relationships, additional information can be obtained which can be used in inhalation hazard risk assessment.

Administration, Inhalation↗
PubMed1989

Flow and volume dependence of respiratory mechanical properties studied by forced oscillation.

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.

Adult↗
PubMed1989

Regulation of delayed-type hypersensitivity-like responses in the mouse lung, determined with histological procedures: serotonin, T-cell suppressor-inducer factor and high antigen dose tolerance regulate the magnitude of T-cell dependent inflammatory reactions.

We have studied delayed-type hypersensitivity (DTH) responses to picryl chloride (PCl) in the lungs of mice. Intranasal challenge with 0.6% picryl sulphonic acid (PSA), a water soluble form of PCl, of BALB/c mice, sensitized with PCl epicutaneously 1 week earlier, induced an accumulation of mononuclear inflammatory cells around bronchioli and blood vessels. Maximal inflammatory responses were seen 48 hr after challenge. These responses were antigen-specific, and also T-cell dependent, since athymic nude mice failed to show this reaction. A role for mast cells in the responses was studied using two strains of mast cell-deficient mice. In one of these (W/Wv) lung DTH responses to PCl were reduced severely. In the other strain (S1/S1d) the responses around vessels were decreased slightly, whereas the responses in the interstitial tissue and around bronchioli were similar to those in +/+ littermate controls. Involvement of serotonin was investigated using two serotonin receptor antagonists, i.e. methysergide and ketanserin. Treatment of mice with either of the antagonists prevented occurrence of the DTH-like reaction in the lung after intranasal antigen challenge. In the lungs of sensitized mice, significantly increased permeability was established 2 hr after antigen challenge. It was concluded that release of serotonin in the lung may provide an environment that comprises local vascular permeability and that facilitates the local recruitment and possibly the activation of DTH effector T cells, leading to subsequent attraction of mononuclear leucocytes into the lung. Immunological regulation of the DTH-like reactions in the lung was similar to that of contact sensitivity in the skin, since intravenous injection of an antigen-specific T-cell suppressor inducer factor prior to sensitization or pretreatment with a high dose of picryl sulphonic acid intravenously both resulted in reduction of the DTH-like lung histological response to picryl sulphonic acid. From these findings it was concluded that DTH-like lung responses are similar to DTH responses in the skin.

Animals↗
PubMed1988

One-year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa.

To study the effect of bilateral intranasal electrocoagulation damage on the susceptibility of rats to formaldehyde vapour, male Wistar rats with a damaged or undamaged nasal mucosa were exposed to atmospheres containing 0, 0.1, 1 or 10 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 or 52 weeks. Electrocoagulation damage was induced in the anterior third part of the nose. The repair process followed the pattern of wound healing. Loss of turbinates and perforation of the septum were common irreversible findings. After 13 weeks basal cell hyperplasia and squamous metaplasia of the respiratory epithelium, and rhinitis were still visible. After 52 weeks effects attributable to electrocoagulation were slight basal cell hyperplasia and some rhinitis. Major formaldehyde-related adverse effects in the 10 ppm group not subjected to electrocoagulation included growth retardation, reduced urine production, and rhinitis accompanied by squamous metaplasia of the nasal respiratory epithelium. No adverse effects were seen at 0.1 or 1 ppm in rats with an intact nasal mucosa. The principal untoward effects of formaldehyde in electrocoagulation-treated rats seen after 13 and/or 52 weeks comprised increase in basal cell hyperplasia, squamous metaplasia of the nasal respiratory epithelium, damage to the olfactory epithelium at 10 ppm, and focal squamous metaplasia of nasal respiratory epithelium at 0.1 and 1 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1988

Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour.

To study in detail possible effects of low concentrations of formaldehyde on the nasal epithelium, Wistar rats were exposed to 0, 0.3, 1 and 3 ppm formaldehyde vapour for 6 h/day, 5 days/week during 3 days or 13 weeks, using in vivo [3H]thymidine labeling for cell proliferation studies, and light and electron microscopy for detecting morphological effects. Compound related histopathological nasal changes varying from epithelial disarrangement to epithelial hyperplasia and squamous metaplasia were found in the 3 ppm group, and were restricted to a small area of the anterior part of the nose which is normally covered with respiratory epithelium. These changes were confirmed by electron microscopy and were not observed in the other groups. Increased cell turnover in the same anterior location confirmed high mitotic activity in the 3 ppm group after 3 days and 13 weeks of exposure. At a slightly more posterior level in the nose a transient response in cell turnover was observed. After 3 days of exposure a nearly log-linear relationship was found between cell turnover and exposure concentration reaching a 10-fold increase in the 3 ppm group, and suggesting challenge of the mucociliary and/or regenerative defence systems not only at 3 ppm but also at 0.3 and 1 ppm. After 13 weeks of exposure mean turnover rates in all exposed groups were markedly lower than after 3 days, and the mean rates of the formaldehyde-exposed groups tended to be below that of the controls. The variation in turnover rate after 13 weeks had increased in a concentration related way, suggesting individual variation in adaptation. The most likely adaptive mechanism at this more posterior level of the nose seemed to be the mucociliary defence apparatus.

Adaptation, Physiological↗
PubMed1988

Human whole-blood O2 affinity: effect of CO2.

The proton Bohr factor (phi H = alpha log PO2/alpha pH), the carbamate Bohr factor (phi C = alpha log PO2/alpha log PCO2), the total Bohr factor (phi HC = d log PO2/dpH[base excess) and the CO2 buffer factor (d log PCO2/dpH) were determined in the blood of 12 healthy donors over the whole O2 saturation (SO2) range. All three Bohr factors proved to be dependent on SO2, although to a lesser extent than reported in some of the recent literature. At SO2 = 50% and 37 degrees C, we found phi H = -0.428 +/- 0.010 (SE), phi C = 0.054 +/- 0.006, and phi HC = -0.488 +/- 0.007. The values obtained for phi H, phi C, and d log PCO2/dpH were used to calculate phi HC. Calculated and measured values of phi HC proved to be in good agreement. In an additional series of 12 specimens of human blood we determined the influence of PCO2 on phi H and the influence of pH on phi C. At SO2 = 50%, phi H varied from -0.49 +/- 0.009 at PCO2 = 15 Torr to -0.31 +/- 0.010 at PCO2 = 105 Torr and phi C from 0.157 +/- 0.015 at pH = 7.80 to 0.006 +/- 0.009 at pH = 7.00. When on the basis of these data a second-order term is taken into account, a still slightly better agreement between measured and calculated values of phi HC can be attained.

Carbon Dioxide↗
PubMed1988

Performance of an automated six-wavelength photometer (Radiometer OSM3) for routine measurement of hemoglobin derivatives.

A new instrument for spectrophotometric determination of oxygen saturation (SO2) and the fractions of carboxyhemoglobin (FHbCO) and methemoglobin (FHi), the Hemoximeter OSM3 (Radiometer), was tested by comparative measurements with a multiwavelength method. We found that it gave reliable results for freshly drawn samples from patients. When samples with artificially induced high proportions of HbCO or Hi, or both, were introduced, results were still sufficiently accurate. The presence of sulfhemoglobin (SHb) seriously interfered with the measurement of SO2, FHbCO, and FHi, but the instrument reliably indicated its presence. Because SHb is rarely encountered, a reliable warning for its presence is adequate for clinical practice. Using the instrument in its fetal mode, we obtained accurate results for blood samples from newborns.

Adult↗
PubMed1987

Calibration of a practical haemoglobinometer.

A practical instrument for routine haemoglobinometry (HemoCue) was compared with the reference haemiglobincyanide (methaemoglobincyanide (HiCN] method. The precision of the routine method was adequate, but a systematic error of about -3.5% was found. As this resulted from errors in the procedure for coupling the haemoglobinometer read-out to the reference HiCN method, we drew up an improved calibration procedure for practical haemoglobinometers to ensure comparability of results with the reference method. After recalibration according to these rules, the HemoCue system proved to be accurate to within +/- 1.5%.

Calibration↗
PubMed1987

A new trend in blood gas chemistry: the measurement of clinically relevant hemoglobin derivatives. Performance of the OSM3 hemoximeter.

Supplementing the determination of total hemoglobin (CHb*) and oxygen saturation (SO2) with measuring the fractions (F) of inactive hemoglobins (dyshemoglobins: carboxyhemoglobin, HbCO; methemoglobin, Hi; sulfhemoglobin, SHb) in human blood is becoming common practice in many hospitals. We tested the performance of a new instrument for this purpose, the hemoximeter OSM3 (Radiometer, Copenhagen, Denmark) by comparing the results with those of an established multiwavelength method (MWM). For 100 fresh blood samples from patients with SO2 ranging between 20 and 100%, the difference between the two methods (OSM3-MWM) was 0.90% SO2 +/- 1.14% (SD). A series of 214 consecutive blood samples from patients with FHbCO ranging from 0 to 12% showed for HbCO a difference (OSM3-MWM) of 0.03% FHbCO +/- 0.47% (SD). In the same blood samples FHi was between 0 and 1.4%. The OSM3 gave a mean value of 0.81%, the MWM 0.47%. In order to put the OSM3 to a more severe test we made from normal human blood several series of specimens with high concentrations of dyshemoglobins. The difference between OSM3 and MWM was for 37 specimens of blood with 1-60% HbCO 0.29% FHbCO +/- 0.96% (SD), and for 34 specimens of blood with 0-70% Hi -0.29% FHi +/- 2.29%. For specimens with high fractions of HbCO and Hi the agreement between the SO2 measurement made with the two methods remained good, even when the dyshemoglobins were present in combination. Hi fractions of up to 70% did not interfere with the measurement of HbCO; the same holds good for the measurement of Hi in the presence of HbCO.

Blood Gas Analysis↗
PubMed1987

Analysis for carboxyhemoglobin by gas chromatography and multicomponent spectrophotometry compared.

Measurements of carboxyhemoglobin (HbCO) by gas chromatography (GC) were compared with those obtained by multicomponent spectrophotometric analysis (MCA). Correlation was good for HbCO ranges (proportion of total hemoglobin) of 1.5 to less than or equal to 5% (GC = 0.94 MCA + 0.37%, n = 25, r = 0.98); 5.0 to less than or equal to 10.0% (GC = 0.89 MCA + 0.63%, n = 19, r = 0.93); greater than 10% (GC = 1.01 MCA - 0.02%, n = 22, r = 0.99); and greater than 0% (GC = 1.01 MCA - 0.10%, n = 95, r = 1.00). The correlation is lower for the clinically normal range of 0 to less than or equal to 1.5% (GC = 0.65 MCA + 0.24%, n = 29, r = 0.87). The gas-chromatographic method is linear for HbCO proportions of 30% to as little as 0.15%. Re-analysis of blood samples after two-month storage at 4 degrees C showed that samples remained stable under these conditions.

Carboxyhemoglobin↗
PubMed1986

Excretion-retention data of steady state gas exchange in tidal breathing. I. Dependency on the blood-gas partition coefficient.

The aim of this study is to investigate the steady state gas transfer properties of the lungs. These properties can be derived from excretion-retention (E-R) data of inert tracer gases that are infused intravenously. E = PE/Pv and R = Pa/Pv, where PE, Pa and Pv represent the partial pressures of the tracer gases in mixed expired gas, arterial blood and mixed venous blood, respectively. In this paper, special attention is paid to the effects of tidal breathing on E-R data sets of tracer gases with different blood-gas partition coefficients. To that end, E-R data sets have been simulated with a lung model that takes into account tidal breathing, the morphometric geometry of the airways, diffusion limited gas mixing and gas dissolved in superficial lung tissue. The simulated E-R data sets are compared with E-R data sets obtained from anaesthetized dogs. Both the simulated E-R data sets and most of the in vivo determined E-R data sets are incompatible with a model description of pulmonary gas transfer with parallel placed compartments with different ventilation-perfusion ratios. Concerning the simulated E-R data sets, this incompatibility is due to the large buffering capacity of lung tissue for highly soluble gases in combination with the within-breath partial pressure oscillations in the airways.

Animals↗
PubMed1986

Excretion-retention data of steady state gas exchange in tidal breathing. II. Dependency on the diffusion coefficient.

The steady state gas transfer properties of the lung can be derived from excretion-retention (E-R) data of inert tracer gases that are infused intravenously. E = PE/Pv and R = Pa/Pv, where PE, Pa and Pv represent the partial pressures of the tracer gases in mixed expired gas, arterial blood and mixed venous blood, respectively. In this paper, we investigate the influence of diffusive gas mixing in the lung on E and R. To that end, E-R data sets were simulated with a lung model that takes into account tidal breathing, the morphometric geometry of the airways, diffusion limited gas mixing in the alveolar space and gas dissolved in superficial lung tissue. The results show a linear relationship between R/E and D-0.5, where D represents the diffusion coefficient of the tracer gases in the alveolar gas mixture. This is in contrast to the results of simulations with a lung model that describes the different gas transport mechanisms, including diffusion, as a constant rate process, where a linear relationship between R/E and D-1 is predicted. It is further shown that E-R data of helium and sulphur hexafluoride cannot be used to demonstrate diffusion limited gas mixing in the lung, in particular, in the presence of a real shunt fraction. For that purpose, excretion data of pairs of tracer gases with different D but equal, medium blood-gas partition coefficients (1 less than lambda less than 30) should be used. For such pairs of tracer gases, the E values may differ by more than 10% when the D values for the two gases are 0.22 and 0.1 cm2s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗