Biomedical subjects

Roland R Wauer

Publications and source records attributed to Roland R Wauer.

25 records · Page 2Linked to original sources

PubMed2003

Chlamydia pneumoniae affect surfactant trafficking and secretion due to changes of type II cell cytoskeleton.

Understanding the surfactant dysfunction by gram-negative bacteria pulmonary infection, the intracellular fate of Chlamydia pneumoniae (Cpn), its interaction with uptake, recycling, and secretion of surfactant and with the cytoskeleton of type II pneumocytes was investigated. Bacteria colocalized with surfactant protein (SP)-A-mediated endocytosed lipid and early endosomes (EEA1- and Rab5-positive) after 3 and 6 h of infection. No specific contact with late endosomes (Rab7- and M6PR-positive), lysosomal, or lamellar body markers (CD63, 3C9) was found after 12 h of infection. In Cpn-infected cells, SP-A-mediated lipid uptake was significantly increased. After SP-A-mediated lipid uptake followed by "re-secretion," 90% of the internalized lipid remained intracellularly. SP-A and lipid did strongly colocalize with early endosomes. Internalized SP-A cannot be resecreted rapidly to plasma membrane, and lipid is not transported toward late endosomes (Rab7- and M6PR-positive) or lamellar bodies (CD63- and 3C9-positive). These results indicate that increased surfactant internalization is caused by an inhibition in intracellular surfactant transport. Accumulation of SP-A-mediated lipid was associated with changes in beta-tubulin. Increases in surfactant secretion were associated with changes in F-actin. We postulate that Cpn infection of type II cells causes changes of the cytoskeleton, and that these effects are associated with alterations in intracellular transport and secretion of surfactant.

Actin Cytoskeleton↗

PubMed2003

In vitro validation of an ultrasonic flowmeter in order to measure the functional residual capacity in newborns.

Ultrasonic transit-time airflow meters (UFM) allow simultaneous measurements of volume flow V'(t) and molar mass MM(t) of the breathing gas in the mainstream. Consequently, by using a suitable tracer gas the functional residual capacity (FRC) of the lungs can be measured by a gas wash-in/wash-out technique. The aim of this study was to investigate the in vitro accuracy of a multiple-breath wash-in/wash-out technique for FRC measurements using 4% sulphur hexafluoride (SF6) in air. V'(t) and MM(t) were measured with a Spiroson SCIENTIFIC flowmeter (ECO Medics, CH) with 1.3 ml dead space. Linearity of airflow and MM were tested using different tidal volumes (V(T)) and breathing gases with different O2 and SF6 concentrations. To determine the accuracy of FRC measurements SF6 wash-in and wash-out curves from four mechanical lung models (FRC of 22, 53, 102 and 153 ml) were evaluated by the Spiroson. For each model five measurements were performed with a physiological V(T)/FRC ratio of 0.3 and constant respiratory rate of 30 min(-1). The error of measured V(T) (range 4-60 ml) was <2.5%. There was a strong correlation between the measured and calculated MM of different breathing gases (r = 0.989), and the measuring accuracy was better than 1%. The measured FRC of the four models were 20.3, 49.7, 104.3 and 153.4 ml with a coefficient of variation of 16.5%, 4.5%, 4.9% and 3%. Accordingly, for FRC <100 ml the in vitro accuracy was better than 8% and for FRC >100 ml better than 2.5%. The determination of FRC by MM measurements using the UFM is a simple and cost-effective alternative to conventionally used gas analysers with an acceptable accuracy for many clinical purposes.

Functional Residual Capacity↗

PubMed2003

Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion.

OBJECTIVE: Because alveoli fill with perfluorocarbons during liquid ventilation, an uptake of perfluorocarbons by type II pneumocytes can be postulated that might affect synthesis and secretion of pulmonary surfactant. The study was performed to answer the following questions: Do isolated type II pneumocytes take up perfluorocarbons? Do perfluorocarbons affect lipid synthesis of type II cells? Do perfluorocarbons change surfactant secretion of type II pneumocytes? DESIGN: Controlled experiments that used isolated type II pneumocytes. SETTING: Experimental laboratory of a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: To study perfluorocarbon uptake, isolated type II cells were incubated with fluorescence-labeled perfluorocarbons and examined with a laser scanning microscope. The effect of perfluorocarbons on biosynthesis of phospholipids and triglycerides was measured by incubating cells that were pulse-labeled with [H]-palmitic acid for 30 secs, with two different perfluorocarbons (PF 5080 or RM 101) for 10 mins. The effect of perfluorocarbon incubation on lipid secretion was studied by transmission electron microscopy. To quantify secretion, adherent type II pneumocytes (containing radioactively labeled phospholipids) were incubated with perfluorocarbons, and extra- and intracellular radioactivity was measured. MEASUREMENTS AND MAIN RESULTS: We found a significant uptake of labeled perfluorocarbons into lamellar bodies within 10 mins. Both perfluorocarbon species significantly (p <.05) reduced the biosynthesis of phospholipids when compared with control. Perfluorocarbon incubation did not affect mitochondrial activity, tested by MitoTracker staining. Transmission electron microscopy revealed changes that suggest an increased secretion of surfactant by type II cells. Studies with radioactively labeled surfactant revealed a significantly (p <.01) higher amount of extracellular lipids after RM 101 and PF 5080 treatment (RM 101, 17 +/- 7.9%; PF 5080, 9 +/- 1.9%) compared with control (5.3 +/- 1.9%). CONCLUSIONS: Our results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

Animals↗

PubMed2003

Measurement of changes in respiratory mechanics during partial liquid ventilation using jet pulses.

OBJECTIVE: To compare the changes in respiratory mechanics within the breathing cycle in healthy lungs between gas ventilation and partial liquid ventilation using a special forced-oscillation technique. DESIGN: Prospective animal trial. SETTINGS: Animal laboratory in a university setting. SUBJECTS: A total of 12 newborn piglets (age, <12 hrs; mean weight, 725 g). INTERVENTIONS: After intubation and instrumentation, lung mechanics of the anesthetized piglets were measured by forced-oscillation technique at the end of inspiration and the end of expiration. The measurements were performed during gas ventilation and 80 mins after instillation of 30 mL/kg perfluorocarbon PF 5080. MEASUREMENTS AND MAIN RESULTS: Brief flow pulses (width, 10 msec; peak flow, 16 L/min) were generated by a jet generator to measure the end-inspiratory and the end-expiratory respiratory input impedance in the frequency range of 4-32 Hz. The mechanical variables resistance, inertance, and compliance were determined by model fitting, using the method of least squares. At least in the lower frequency range, respiratory mechanics could be described adequately by an RIC single-compartment model in all piglets. During gas ventilation, the respiratory variables resistance and inertance did not differ significantly between end-inspiratory and end-expiratory measurements (mean [sd]: 4.2 [0.7] vs. 4.1 [0.6] kPa x L(-1) x sec, 30.0 [3.2] vs. 30.7 [3.1] Pa x L(-1) x sec2, respectively), whereas compliance decreased during inspiration from 14.8 (2.0) to 10.2 (2.4) mL x kPa(-1) x kg(-1) due to a slight lung overdistension. During partial liquid ventilation, the end-inspiratory respiratory mechanics was not different from the end-inspiratory respiratory mechanics measured during gas ventilation. However, in contrast to gas ventilation during partial liquid ventilation, compliance rose from 8.2 (1.0) to 13.0 (3.0) mL x kPa(-1) x kg(-1) during inspiration. During expiration, when perfluorocarbon came into the upper airways, both resistance and inertance increased considerably (mean with 95% confidence interval) by 34.3% (23.1%-45.8%) and 104.1% (96.0%-112.1%), respectively. CONCLUSIONS: The changes in the respiratory mechanics within the breathing cycle are considerably higher during partial liquid ventilation compared with gas ventilation. This dependence of lung mechanics from the pulmonary gas volume hampers the comparability of dynamic measurements during partial liquid ventilation, and the magnitude of these changes cannot be detected by conventional respiratory-mechanical analysis using time-averaged variables.

Airway Resistance↗

PubMed2002

Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels.

Interstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels. The female neonate was born at 37 weeks of gestation as the second child to a 31-year-old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double-outlet right-ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium. Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long-term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery.

Abnormalities, Multiple↗

PubMed2002

Cerebral oxygenation is affected by filling mode and perfluorochemical volume in partial liquid ventilation of healthy piglets.

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO(2)) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO(2), PaO(2) and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO(2), HbO(2) and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO(2)). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.

Animals↗

PubMed2002

Human adenovirus and human cytomegalovirus infections in preterm newborns: no association with bronchopulmonary dysplasia.

Connatal infection with human adenovirus (HAdV) has been recently proposed as a cofactor for the development of bronchopulmonary dysplasia (BPD) in preterm infants [Couroucli et al. 2000 Pediatr Res 47:225-232]. In another study, BPD was associated with an increased incidence of human cytomegalovirus (HCMV) infection [Sawyer et al. 1987 Am J Dis Child 141:303-305]. During a 18-mo study period, we investigated tracheal aspirates or pharyngeal aspirates and urine samples collected during the first month of life from 66 preterm newborns with very low birth weight (< or =1.500 g) for replication-potent HAdV as well as for adenoviral and HCMV DNA by virus culture and qualitative DNA PCR. Thus, our study included not only prenatal but also peri- and postnatal infections. Thirty-seven percent (24/66) of infants developed BPD(1), as defined by persistent oxygen dependency at day 28 of life. Replication-potent HAdV and/or adenoviral DNA could be detected repeatedly in tracheal aspirates/pharyngeal aspirates and/or urine from 20% (13/66) of preterm infants. Seventeen percent (4/24) of infants in the BPD(1) group and 21% (9/42) of infants in the non-BPD group had an HAdV infection, indicating that in our study the very recently proposed association between HAdV infection of the lung and BPD could not be confirmed. For comparison, active HCMV infection was diagnosed in 18% (12/66) of infants, 3 of which developed HCMV disease. 29% (7/24) in the BPD(1) group and 12% (5/42) in the non-BPD group were positive for HCMV. Again, there was no statistically significant association between HCMV infection and BPD. In summary, our findings indicate that HAdV and HCMV infection are frequent in preterm newborns with very low birth weight; however, a causal association with the development of BPD seems unlikely.

Adenoviridae↗