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Biomedical subjects

M Svartengren

Publications and source records attributed to M Svartengren.

At least 73 records · Page 4Linked to original sources

Distribution and concentration of cadmium in human kidney.

The left kidneys from twenty males, aged 30 to 59, were examined. On an average, the cortex, medulla, and the remainder (renal pelvis and adjacent fatty tissue) constituted 65, 27, and 8 percent of the whole kidney weight, respectively. The mean cadmium concentrations were 18.4, 6.9, and 3.2 micrograms Cd/g wet wt, respectively. The mean whole kidney cadmium concentration was 14.4 micrograms Cd/g wet wt. The kidney cortex concentration of cadmium can be approximated by multiplying the whole kidney concentration by a factor of 1.25, which is somewhat lower than the factor of 1.5 previously used. It may be necessary to recalculate previously reported estimates of critical concentrations for cadmium in kidney cortex based on neutron activation analyses in vivo of whole kidney.

Adipose Tissue↗

Spirometric data and penetration of particles to the alveoli.

The percentage retention at 24 hours of 4 micron Teflon particles, aerodynamic diameter about 6 micron, was studied in 29 healthy male volunteers. The particles were inhaled at 0.5l/s with maximally deep breaths. The 24 hour retention correlated significantly with FEV1 and FVC and persisted when the subjects were divided into different categories according to profession and smoking habits. The results suggest that for exposure to metal particles at a size where impaction is an important deposition mechanism--that is, particles larger than a few microns--workers with large FEV1 values may run a greater risk of receiving systemic toxic effects than those with small FEV1 values.

Adult↗

Regional deposition of particles in human lung after induced bronchoconstriction.

The percentage 24-hr lung retention (Ret24), a measure of penetration to the aveoli, of 4 micron monodispersed Teflon particles, aerodynamic diameter 6 micron, was studied in 8 healthy nonsmokers. The particles were inhaled at 0.2 1/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholinebromide aerosol for one exposure before and for one exposure after inhalation of the Teflon particles. Airway resistance (Raw) was measured using a whole body pletysmograph before and after the induction of bronchoconstriction and increased on an average by a factor 2-3. Ret24 was significantly lower when the Teflon particles were inhaled during bronchoconstriction than when bronchoconstriction was induced after inhalation of the Teflon particles, 26 +/- 12% and 48 +/- 6% (mean +/- SD), respectively. These experimental data agree fairly well with data on deposition due to impaction and sedimentation using a lung model where the diameters of the airways were varied so that an increase in airway resistance occurs similar to that produced in our experimental subjects. However, the experimental data tended to be lower than the theoretical ones when the particles were inhaled during the induced bronchoconstriction. In this study, where the mucociliary transport system was stimulated by methacholinebromide, the percentage 3-hr retention (Ret3) was highly correlated with Ret24, r = 0.97, i.e., Ret3 can be used instead of the Ret24. This implies that radionuclides with shorter half-lives which give lower radiation doses, can be used, and that subjects can be studied within shorter periods of time.

Adult↗

Decreased blood lead levels in residents of Stockholm for the period 1980-1984.

A number of measures have been taken to decrease the spread of lead to ambient air and food. In a study of the effect of these and other preventive measures, blood samples from approximately 100 persons living in the inner city area of Stockholm were collected and analyzed for lead content on three different occasions, in 1980, 1983, and 1984. The same subjects were examined on at least two occasions and the analytical method, atomic absorption spectrophotometry, was carefully controlled by means of reference samples on each occasion. The blood lead levels decreased during the observation period. The average blood lead concentrations for all the examined persons were 0.37, 0.26, and 0.25 mumol/l for 1980, 1983, and 1984, respectively. The mean of the differences in individual blood lead levels for 1980 and 1984 was 0.12 mumol/l. This figure corresponds to an average decrease in blood lead of 34% for all the subjects examined in 1980. The decrease occurred mainly during the period 1980-1983 (mean 0.11 mumol/l) and, thereafter, was only slight for the period 1983-1984 (mean 0.01 mumol/l). Factors such as age, sex, and change of residence during the observation period did not influence the final results.

Adult↗

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis collected from a register covering all hospital stays within the county of Stockholm were asked to participate in a study of lung mucociliary clearance. Twenty-one patients inhaled 6 um Teflon particles labelled with 99mTc and radioactivity was measured externally. The patients were also clinically classified. Clearance varied from normal to extremely slow. The average retention at 2 hours was significantly higher in the patients, 65+27%, (mean +/- SD) than in healthy nonsmokers, 36+22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started, all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in two lungs in 18 patients and was similar in both lungs with one exception. A full presentation of this investigation is submitted to Eur. J. Respir. Dis.

Adult↗

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis were collected from a register covering all hospital stays within the county of Stockholm. They were asked to come for an interview, a clinical examination and to participate in a study of lung mucociliary clearance. The subjects inhaled 6 microns Teflon particles labelled with 99mTc and radioactivity was measured externally. Clearance varied from normal to extremely slow. The average retention of the Teflon particles at 2 h was significantly higher in the 21 patients, 65 +/- 27% (mean +/- SD), than in healthy nonsmokers, 36 +/- 22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started; all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in the two lungs in 18 patients and was similar in both lungs, with one exception.

Adult↗

Airway resistance and deposition of particles in the lung.

The percentage 24-h lung retention of 4-micrometers monodispersed Teflon particles, aerodynamic diameter about 6 micrometers, was studied twice in 8 healthy nonsmokers. The particles were inhaled at 0.5 liter/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine-bromide aerosol for one exposure before and for the other 20-30 min after the inhalation of the Teflon particles. For both exposures, airway resistance (Raw) was measured with a whole body plethysmograph before and after the induction of the bronchoconstriction and was found on an average to increase with a factor of 2-3. For the exposure when bronchoconstriction was induced after the inhalation of the Teflon particles, Raw and 24-h lung retention correlated significantly. Retention at 24 h was markedly lower when bronchoconstriction was induced before inhalation of the Teflon particles than when bronchoconstriction was induced after, the ranges being 13-24% and 38-68%, respectively. The experimental data agreed well with theoretical data from a lung model wherein the diameters of the airways were varied. The results indicate that the magnitude of bronchoconstriction occurring in real life can protect the alveolar part of the lung by reducing the amount of inhaled particles that deposit there.

Adult↗

Human tracheobronchial deposition and effect of two cholinergic aerosols.

The effects of two methacholine aerosols with mass median diameters congruent to 7 and 3 microns were measured in 10 healthy subjects. The concentrations of the two aerosols were increased until forced expiratory volume in 1 s (FEV1) decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%, R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns radiolabeled Teflon particles were studied before and after bronchial challenge with the two aerosols. Output from the nebulizers and size distribution were measured and from these data and from data on deposition of Teflon particles from this and seven earlier studies the doses of the two methacholine aerosols to the tracheobronchial region were calculated. The changes in all pulmonary function parameters and deposition of 3.6-microns particles were similar for the two aerosols. The calculated dose for the aerosol with the large particles was 3-4 times higher than that with the smaller particles. The results indicate greater effect of a certain dose to the tracheobronchial part of the lung if the mass is spread on many small particles than on fewer large ones.

Adult↗

Human deposition and clearance of 6-micron particles inhaled with an extremely low flow rate.

In human experimental data, tracheobronchial deposition reaches its maximum for particles of about 6 microns inhaled at 0.5 L/s. The purpose of the present study was to investigate if tracheobronchial deposition of 6-microns particles could be increased, especially in the smaller bronchi, using an extremely slow inhalation rate. Six healthy nonsmokers inhaled monodisperse 6-microns (aerodynamic diameter) Teflon particles labeled with 111In at 0.04 L/s. Radioactivity in mouth and throat, lung, and stomach was measured immediately after inhalation by profile scanning and in the lung also after 24, 48, 72, and 96 h. There was a substantial clearance between 24 and 72 h; around 20% of the total clearance occurred between 24 and 72 h. This is in contrast to earlier studies in which only around 1% of 6-microns particles inhaled at 0.5 L/s cleared between 24 and 72 h. This indicates a markedly higher deposition in the smaller bronchi at 0.04 L/s than at 0.5 L/s. The total tracheobronchial deposition was 50%, compared to about 30% when particles were inhaled at 0.5 L/s. These findings could be therapeutic use. They also implicate the possibility of developing a diagnostic model that can separate between bronchial reactivity in large and small bronchi.

Adult↗

Retention of particles inhaled in boli with and without induced bronchoconstriction.

Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.

Administration, Inhalation↗

Clearance in smaller airways of inhaled 6-microm particles in subjects with immotile-cilia syndrome.

In subjects with an inherited lack of mucociliary transport, so called immotile-cilia syndrome (ICS), coughing effectively clears particles deposited in larger airways of the tracheobronchial region. The present study investigated clearance in smaller airways of 111In-labeled 6-microm (aerodynamic diameter) monodisperse Teflon particles in six subjects with ICS. The particles were inhaled at an extremely slow flow, 0.05 L/s. Theoretical calculations and experimental data in healthy subjects using this slow flow support particle deposition mainly in smaller ciliated airways, i.e., in bronchioli (generations 12-16). This contrasts with the more centrally deposited pattern obtained using a normal inhalation flow, 0.5 L/s. Lung retention was measured at 0, 24, 48,72 and 96 h. Clearance was significant every 24 h measured over the first 72 h, whereupon it slowed down. The fractions of retained particles were significantly (p < .01) larger than those found for healthy subjects using the slow inhalation flow and those found for ICS subjects using a normal inhalation flow. The results indicate that clearance of particles in smaller airways is incomplete and that cough cannot fully compensate for the lack of mucociliary transport in this region.

Adult↗

Deposition and clearance in large and small airways in chronic bronchitis.

Tracheobronchial clearance was studied twice in 16 patients with chronic obstructive bronchitis after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure the particles were inhaled at an extremely slow flow, 0.05 L/s; at the other they were inhaled at a normal flow, 0.5 L/s. Theoretical calculations and experimental data in healthy subjects indicate particle deposition mainly in the smallest ciliated airways using 0.05 L/s, i.e., in the bronchiolar region, and an enhanced deposition in larger airways using 0.5 L/s. Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significantly every 24 h for both exposures (p < .05). The fractions of retained particles were significantly larger for particles inhaled at 0.05 L/s compared to 0.5 L/s at all points of time (p < .001). Compared to healthy subjects, the retained fractions of deposited particles were larger in patients with bronchitis breathing at 0.05 L/s, but smaller with breathing at 0.5 L/s (p < .01). Significant relationships were found between lung retentions and airway resistance (Raw) at 0.5 L/s, r = -.68 (p < .01), but not at 0.05 L/s, and between lung retention at 24 h and weight of expectorated sputum at 0.05 L/s, r = -.50 (p < .05). There was, furthermore, an almost significant relationship between sputum volume and rate of tracheobronchial clearance between 0 and 24 h (in percentage of the total amount cleared during 72 h) at 0.05 L/s, r = .42 (p = .05). The results indicate that in patients with chronic bronchitis overall clearance of particles in small airways is incomplete, as compared to larger airways. An increased amount of mucus, however, seemed to improve clearance of peripherally deposited particles, possibly by making cough more effective in small airways.

Adult↗

Clearance of particles from small ciliated airways.

In recent years, there has been a debate on whether a considerable fraction of particles is retained after 24 h in the tracheobronchial region. In the present study, 8 healthy subjects inhaled 6.2-microns monodisperse Teflon particles labeled with 111 In twice, at flow rates of 0.45 and 0.045 L/s. According to theoretical calculations, the particles inhaled at 0.45 L/s should deposit mainly in large bronchi and in the alveolar region, whereas the particles inhaled at 0.045 L/s should be deposited mainly in small ciliated airways. Twenty-four hours after inhalation, about half of the particles inhaled with both modes of inhalation had cleared. Clearance during the period from 1 to about 30 days after inhalation, could, for both modes of inhalation, be described by the sum of two exponential functions. For the inhalation rate of 0.45 L/s, 15% cleared with a half-time of 3.4 days and 85% with a half-time of 190 days. For the inhalation of 0.045 L/s, 20% cleared with a half-time of 2.0 days and 80% with a half-time of 50 days. The results strongly indicate (1) that a considerable fraction of particles deposited in small ciliated airways had not cleared within 24 h, and (2) that these particles cleared differently from particles deposited in the alveolar region. The experimental data agree quite well with the IRTM predictions made using its default slow clearance fractions.

Administration, Inhalation↗

Human bronchiolar deposition and retention of 6-, 8- and 10-micrograms particles.

Three groups, each consisting of 6 healthy subjects, inhaled, respectively, 6-micrograms (aerodynamic diameter), 8-micrograms, and 10-micrograms Teflon particles, labeled with indium-111. The particles were inhaled at an extremely low flow rate, 0.05 L/s. Lung retention was measured after 0, 24, 48, and 72 h. Two models were used to calculate particle deposition in the lungs in the various generations: the Karolinska Institute model (KI model) and the University of Southampton model (US model). From the experimental clearance data and the theoretical deposition data, it was calculated that the average retention after 24 h was around 100% for particles deposited in generations 13-16 (ciliated bronchioles) and around 20% in generations 0-12 (both large and small ciliated airways). In these calculations, it was assumed that the retained fractions were independent of particle size. The depositions in the bronchial region (generations 0-8), bronchiolar region (generations 9-15 or 9-16), and the alveolar region were calculated using the two models and compared with the recent ICRP model. On the whole, the three models agreed fairly well.

Administration, Inhalation↗

Effect of adrenergic stimulation on clearance from small ciliated airways in healthy subjects.

Mucociliary transport is an important clearance mechanism of larger airways, but in the smallest ciliated airways (bronchioles) it may be less effective. The present study aimed at investigating whether clearance from the bronchioles in subjects with healthy airways was stimulated by an adrenergic agonist (terbutaline sulphate). Tracheobronchial clearance was studied twice in 10 healthy subjects after inhalation of 6-micron (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure, oral treatment with terbutaline sulphate, known to stimulate clearance in large airways, began immediately after inhalation of the particles. The other exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 L/s, which gave deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48, and 72 h. Clearance was significant every 24 h for both exposures (p < .05, two-tailed paired t-test), with similar fractions of retained particles at all time points. During treatment with terbutaline sulphate, the subjects' pulse rates tended to be higher, but clearance rates did not increase. We found, as expected, no significant correlation between lung retention and lung function in either exposure. This study shows that an adrenergic agonist does not significantly influence overall clearance from the bronchiolar region in healthy subjects. This suggests that mucociliary transport does not significantly contribute to clearance from the smallest ciliated airways. Other mechanisms may be more important for the transportation of mucus from these airways.

Administration, Inhalation↗

Regional deposition of inhaled Evans blue dye in mechanically ventilated rabbits with air or helium oxygen mixture.

An animal model has been used and further developed to examine and evaluate differences in regional deposition patterns of an Evans Blue dye (EB) tracer aerosol. This was done by using different carrier gas composition of either He-O2 (80% helium, 20% oxygen) or air (79% nitrogen, 21% oxygen) in histamine-provoked and nonprovoked rabbits. The ratio of peripheral deposition to total deposition (central + peripheral), in relation to percentage increase in intratracheal pressure (ITP delta %), was used as an evaluation tool. The animals were tracheostomized, cannulated, and ventilated in a volume-controlled mode until they were stable. Saline or histamine was then administrated for 2 min before the tracer aerosol EB was given. The percentage increase in intratracheal pressure before and after provocation was calculated (ITP delta %) and was, on average, 51 +/- 20% for air and 51 +/- 20% for He-O2. EB was extracted from lung tissues and measured with a spectrophotometer. The absorbance in different lung regions was used as a measure of the distribution of aerosol. Bronchial provocation gave a central deposition 0.55 +/- 0.11 (mean +/- SD, ratio = peripheral deposition/central + peripheral deposition) compared to 0.80 +/- 0.09 in the control group. He-O2-ventilated rabbits showed significantly higher peripheral deposition ratio (0.67 +/- 0.12) compared with air-ventilated rabbits (0.55 +/- 0.11). The latter finding may be due to the difference in the degree of turbulent flow. There were significant correlations between intratracheal peak pressure and peripheral deposition, r = -.60 and r = -.71 for air and He-O2, respectively. This study demonstrates the possibility of using a rabbit model and different carrier gases for evaluation of effects of bronchial provocation.

Administration, Inhalation↗

Influence of bethanechol on retained particles deposited on the first bifurcation of rabbits.

Retention of 4 micron 51Cr labelled Teflon particles administered to nine male rabbits via trachea was measured externally. About 5 microliter of a suspension with a particle concentration of 40 mg X ml-1 was deposited on the first bifurcation through a fiberoptic bronchoscope under urethane anesthesia. Over a period of two weeks, the rabbits were exposed twice, under the influence of the cholinergic drug bethanechol chloride and in a control examination. The time period during which 90% of deposited particles had cleared was significantly shorter in the presence of bethanechol (16 h) than in the control experiment (70 h). The magnitude of the fraction which cleared within the first hour did not differ significantly for drug administration and control, being 39.0% and 36.8%, respectively. The fraction which did not clear within the first hour tended (p = 0.1) to clear faster, half-time 10.4 h, when bethanechol chloride was given than it did in the controls, half-time 31.3 h. A reasonable interpretation of the results is that the cholinergic compound, bethanechol, increases bronchial secretion, which results in a reversed movement of the particles that previously penetrated the mucous layer, back to the mucous layer.

Animals↗