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Biomedical subjects

M Griese

Publications and source records attributed to M Griese.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center.

In children, pulmonary sequelae contribute to early and late morbidity after bone marrow transplantation (BMT). Between 1975-1999, we performed 152 BMTs in 138 pediatric patients with malignant and nonmalignant diseases. Allogenic bone marrow was used from 99 HLA identical siblings and from 23 other related or unrelated donors. Autologous marrow was used in 30 transplantations. Median age was 8. 6 years (range, 1.1-22.4) at time of BMT. The median survival was 42%, the survival time was 6.5 years (range, 0.8-23.1), and the median follow-up time was 6.8 years (range, 0.8-23.2). Seventeen patients had severe respiratory complications. Early severe respiratory complications leading to death within the first 4 months after BMT were due to pulmonary edema (n = 1), or fungal (n = 3), bacterial (n = 1), or viral (n = 2) pneumonia. Late severe respiratory sequelae were defined as persistent respiratory symptoms for more than 4 months despite treatment, and these occurred in 10 patients, of whom 5 died. Underlying diagnoses covered a wide spectrum, including bronchiolitis obliterans (n = 3), severe restrictive lung disease (n = 2), idiopathic pneumonia syndrome (n = 3), chronic bronchitis (n = 1), and hepatopulmonary syndrome (n = 1). The overall probability for death was 0.58, and for death from severe respiratory complications, 0.16. With improved HLA matching, fewer BMTs after relapsed or primary progressive disease, and improved supportive care, including the usage of CMV negative blood products, after 1990 the probability of death from severe respiratory complications was only 0.04, whereas before 1990 it was 0.23 (P = 0.029; in each time period, n = 69). The disease spectrum has changed from initially more infectious complications to bronchiolitis obliterans and idiopathic pneumonia syndrome. Lung function measurements performed in 85 of 138 patients usually showed a mild restrictive pattern. To identify those children as early as possible who are at risk for severe respiratory complications, a close longitudinal follow-up after BMT by pediatric pulmonologists is necessary.

Adolescent↗
PubMed2000

Fractional analysis of bronchoalveolar lavage fluid cytology in cystic fibrosis patients with normal lung function. Bronchoalveolar lavage for the evaluation of anti-inflammatory treatment (BEAT) study group.

Cystic fibrosis (CF) is associated with a neutrophil dominated airway inflammation. So far bronchoalveolar lavage (BAL) studies in CF have used pooled BAL samples which may be more representative of the alveolar compartment rather than the airways. To assess whether the first sample of a BAL is more sensitive in the evaluation of airway inflammation, the authors have studied 105 stable CF patients aged 5-37 yrs with a mean forced expiratory volume in one second (FEV1) of 96+/-15% (mean+/-SD). BAL cytology of the first and pooled samples were compared to reference values obtained in children without respiratory disease. Absolute cell counts and the percentage of neutrophils were significantly increased in CF patients. If the 95% confidence interval was used as a cut-off point, 17/105 CF patients had a normal percentage of neutrophils in pooled BAL samples, but only three also had a normal percentage of neutrophils in the first BAL aliquot. Therefore, neutrophil dominated airway inflammation is more pronounced in the first, mainly bronchial, bronchoalveolar lavage sample suggesting that sequential analysis of bronchoalveolar lavage fluid may have a higher sensitivity to detect early inflammatory changes in CF patients.

Adolescent↗
PubMed1999

Characteristics of flow dependency of nitric oxide in exhaled air in children with cystic fibrosis and asthma.

Nitric oxide (NO) is a free radical produced by the lungs which can easily be measured in exhaled air. NO may serve as a non-invasive marker for airway inflammation in chronic inflammatory diseases like asthma. However in patients with cystic fibrosis (CF) and severe airway involvemen normal or low levels of NO have been reported. To investigate this further we measured NO levels in exhaled air at 5 different flow rates in 14 asthmatics, 15 CF-patients and 13 healthy children. A dependency of exhaled NO on expiratory flow was demonstrated in all three groups. At slow flows lower NO levels in CF-patients and significantly higher levels in asthmatics compared to healthy individuals were found. When the data were fitted to a one compartment model of the lung described by NO(MOUTH) = NO(LUNG) - NO(LUNG) x e(-T/Vex) (T = transfer factor; Vex = expiratory flow), NO(LUNG) was increased in asthmatics (191.9 +/- 53.8 ppb) and low in CF (26.7 +/- 5.7 ppb) compared to healthy individuals (76.9 +/- 50.9 ppb; p(anova) = 0.0213). NO produced in the central compartment of the lung behaved similarly and was distinguished from a peripheral compartment with the two compartment model NO(MOUTH) = NO(central) - (NO(central) - NO(peripher) ) x e(-T/Vex). We conclude that NO in exhaled air is flow dependent and at slow expiratory flows elevated in asthmatics and reduced in CF-patients compared to healthy children. Concentrations extrapolated for the whole lung and for the central airways changed proportionally.

Adolescent↗
PubMed1999

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

Asthma↗
PubMed1999

Compound SFTPB 1549C-->GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency.

Several human respiratory disorders have been linked to an abnormality of pulmonary surfactant synthesis or turnover. Among those conditions, hereditary deficiency in the hydrophobic surfactant protein B (SP-B) has been recognized as a rare cause of respiratory failure in term newborn infants. Homozygosity for a common mutation (1549C-->GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B. However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency.

Base Sequence↗
PubMed1999

Cardiopulmonary bypass reduces pulmonary surfactant activity in infants.

OBJECTIVE: Infants younger than 1 year of age undergoing cardiopulmonary bypass surgery often have severe lung injury necessitating increased postoperative respiratory mechanical support. Inasmuch as the mechanisms may involve an impairment of the pulmonary surfactant system, our aim was to determine whether changes of surfactant occur in such infants. METHODS: From the day of the operation to day 7 after the operation, serial tracheobronchial small-volume lavages of 19 infants (aged 166 +/- 29 days) were fractionated into a small and a large surfactant aggregate fraction and compared with those of 13 infants without lung disease (aged 203 +/- 33 days). RESULTS: After cardiac operations with cardiopulmonary bypass surgery, total protein in lavages was increased 3-fold to 4-fold and decreased linearly with time. Surfactant protein A was increased on day 1 and day 2 and then decreased, whereas surfactant protein B and total phospholipids were increased on day 1. The ratio of phospholipids in small and large surfactant fractions was unchanged, but the surface activity of the large-aggregate surfactant was impaired on days 1 to 3. CONCLUSIONS: Lung injury in infants after cardiopulmonary bypass surgery involves significant biochemical and functional disturbances of the pulmonary surfactant system. Inasmuch as substitution with natural surfactant might correct these deficiencies, the potential of this approach to reduce postoperative morbidity needs to be investigated.

Biomarkers↗
PubMed1999

Hepatopulmonary syndrome after allogeneic bone marrow transplantation.

A 10-year-old girl with aplastic anemia received an allogeneic bone marrow transplantation (BMT). Three years after an uneventful course apart from chronic graft-versus-host disease (GVHD) she presented with chronic hypoxemia, reduced diffusion capacity of the lungs, normal spirometric lung function and increased bilirubin and liver enzymes. Intrapulmonary vascular dilatations were demonstrated. Pulmonary complications after BMT may include a hepatopulmonary syndrome (liver disease, hypoxemia, intrapulmonary vascular dilatations).

Anemia, Aplastic↗
PubMed1999

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1999

Health effects of sulfur-related environmental air pollution: the pulmonary surfactant system is not disturbed by exposure to acidic sulfate and neutral sulfite aerosols.

The goal of this study was to assess the impact of long-term exposure to environmental sulfur-related aerosols on the biochemical and biophysical properties of lung surfactant. Eight Beagle dogs were housed under clean air conditions for 450 days, followed by an exposure period of 400 days to 0.36 mg/m3 of sulfite (16.5 h/d) and to 5.66 mg/m3 of sulfate (6 h/d) equivalent to a pulmonary hydrogen burden of 15 mumol/m3. Other dogs kept in clean air for the whole study period were additional controls. Serial bronchoalveolar lavages (BALs) were analyzed for total phospholipid concentration, content and ratio of a surfactant-rich large aggregate (LA) fraction and a small aggregate (SA) fraction, in vitro surface area cycling of LAs into SAs as a measure of alveolar extracellular pulmonary surfactant aggregate metabolism, and surface activity of native and lipid-extracted LA. No significant changes over time and no differences between the clean air period and the exposure period were observed. Thus, long-term environmental exposure of dogs to the sulfur-related air pollution tested does not lead to alterations in the amount, extracellular metabolism, or surface-active properties of pulmonary surfactant.

Aerosols↗
PubMed1999

Surfactant lipid uptake and metabolism by neonatal and adult type II pneumocytes.

Animal experiments suggest developmental changes in surfactant homeostasis. The uptake and metabolism of [(3)H]dipalmitoylphosphatidylcholine-labeled liposomes with a surfactant-like composition were evaluated in type II cells isolated from rats of different postnatal ages. The early part of the uptake process (0-60 min) was more rapid and reached higher levels in cells from 2-day-old rats than in those from 7-day-old, 14-day-old, or adult rats. Temperature independence of this initial phase, differences in response to trypsin-EDTA or neuraminidase treatment, and the dependency of increased neonatal uptake on the presence of phosphatidylglycerol in liposomes suggested binding as a major mechanism of cell-lipid interaction. Although a two to three times larger amount of lipid was associated with neonatal cells, the metabolism of phosphatidylcholine, indicated by a decrease in label in phosphatidylcholine and an accompanying increase in sphingomyelin, was significantly smaller in 2-day-old than in adult cells. These studies support the hypothesis that neonatal and adult cells may have differences in the interaction with alveolar phospholipids and in the metabolism of phosphatidylcholine.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Pulmonary surfactant in health and human lung diseases: state of the art.

Pulmonary surfactant is a complex and highly surface active material composed of lipids and proteins which is found in the fluid lining the alveolar surface of the lungs. Surfactant prevents alveolar collapse at low lung volume, and preserves bronchiolar patency during normal and forced respiration (biophysical functions). In addition, it is involved in the protection of the lungs from injuries and infections caused by inhaled particles and micro-organisms (immunological, non-biophysical functions). Pulmonary surfactant can only be harvested by lavage procedures, which may disrupt its pre-existing biophysical and biochemical micro-organization. These limitations must always be considered when interpreting ex vivo studies of pulmonary surfactant. A pathophysiological role for surfactant was first appreciated in premature infants with respiratory distress syndrome and hyaline membrane disease, a condition which is nowadays routinely treated with exogenous surfactant replacement. Biochemical surfactant abnormalities of varying degrees have been described in obstructive lung diseases (asthma, bronchiolitis, chronic obstructive pulmonary disease, and following lung transplantation), infectious and suppurative lung diseases (cystic fibrosis, pneumonia, and human immunodeficiency virus), adult respiratory distress syndrome, pulmonary oedema, other diseases specific to infants (chronic lung disease of prematurity, and surfactant protein-B deficiency), interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis), pulmonary alveolar proteinosis, following cardiopulmonary bypass, and in smokers. For some pulmonary conditions surfactant replacement therapy is on the horizon, but for the majority much more needs to be learnt about the pathophysiological role the observed surfactant abnormalities may have.

Humans↗
PubMed1998

Amphotericin B and pulmonary surfactant.

Targeted intrapulmonary delivery of drugs may reduce systemic toxicity, improve treatment efficacy, but inhaled drugs may also interfere with pulmonary surfactant function. We hypothesized that the lipophilic drug amphotericin B used to treat or prevent pulmonary infections with aspergillus species, might destroy surface activity of lung surfactant, as assessed in a pulsating bubble surfactometer. Pure amphotericin B had no effect on a natural surfactant preparation or on the lipid extracted surfactant SurvantaTM. However, amphotericin BTM (containing deoxycholic acid) or deoxycholic acid alone inhibited surfactant surface activity dose dependently and perturbed lipid organization. AmbisomeTM containing amphotericin B associated with liposomes, only marginally affected surfactant function. Intrapulmonary delivery of large amounts of amphotericin BTM has to consider the potential of interferences with lung surfactant function.

Administration, Inhalation↗
PubMed1998

Surfactant function in neonates with respiratory distress syndrome.

The function of pulmonary surfactant of a group of 14 preterm neonates (birth weight 907 +/- 60 g) who suffered from severe respiratory distress syndrome (RDS) and who had received exogenous bovine lipid extracted surfactant on the first day of life was compared to that in a second group of 8 neonates (birth weight 940 +/- 110 g) with mild RDS who had not received surfactant treatment. Mechanical respiratory support from day 2 on was the same in both groups. The minimal surface tension (gamma(min)) improved steadily, falling from about 30 mN/m initially to less than 20 mN/m before extubation. A consistent but loose correlation was found between gamma(min) and mechanical respiratory support necessary, as quantitated by the oxygenation index. Total protein was about 0.8 +/- 0.2 mg/mg of phospholipids and did not change during the first week of life. There were no correlations between total protein and gamma(min) or the oxygenation index. The data suggest that inhibition of surfactant function by proteins leaked into the airspaces does not play a major role during recovery from RDS. Instead, endogenous remodelling of surfactant might be of greater relevance.

Animals↗
PubMed1998

Inhibitors of elastase in airway lavage samples from ventilated preterm human neonates.

Surplus elastase released from neutrophils during lung injury is balanced mainly by alpha1-protease inhibitor (alpha1-PI) and by two acid-resistant inhibitors. The latter include mucus protease inhibitor (MPI, also named SLPI, BSI, ALP) and elastase-specific inhibitor (ESI or Elafin), but their functional role during the neonatal period has not yet been characterized precisely. The saline airway lavage samples from neonates intubated for respiratory distress were separated by centrifugation into a cellular and a soluble, supernatant fraction and then analyzed. During the first 36 h of life (42 neonates, gestational age 24-40 wk), elastase activity was confined to the cellular fraction. Thirty percent of the acid-resistant inhibitors but almost no alpha1-PI, was cell-associated. In the soluble fraction, about 20-30% of the acid-resistant inhibitors was functionally active, but only about 10% of alpha1-PI was. In seven infants with a nosocomial infection and deterioration during mechanical ventilation, only a very modest increase in elastase activity was observed. However, the functional activity of the acid-resistant inhibitors was reduced in the soluble fraction, whereas total mass remained unchanged. A full assessment of protease and protease inhibitors should include the cellular and the soluble lavage compartments.

Blotting, Western↗
PubMed1998

Smaller sized particles are preferentially taken up by alveolar type II pneumocytes.

The uptake of both lung surfactant and other particles from the alveolar space plays an essential role in surfactant metabolism, host defense and may be of relevance for targeting drugs into alveolar cells. To better understand the effect of particle size on the uptake by type II pneumocytes, rat type II cells in primary culture were investigated. We observed that inert latex particles of 15 nm were taken up to a much greater extent than bigger particles. No strong size dependency was observed in the range from about 200 to 1000 nm. A similar observation was made with a natural lipid extracted lung surfactant which was taken up to a greater extent when prepared at particles of about 100 nm than a preparation with a particle size range from about 200-2000 nm. Alveolar type II cells take up smaller particles better than larger ones, but the size selectivity is rather limited. These type II cell properties may contribute to a preferential elimination of the smaller particle fractions from the alveolar space.

Animals↗
PubMed1997

Binding of dipalmitoyl-phosphatidylcholine liposomes to lung epithelial type II cells and other surfaces.

To better understand the interaction of phosphatidylcholine liposomes with lung type II cells, their association with rat type II pneumocytes in primary culture was investigated. With a filtration assay technique free and cellularly bound liposomes were separated and an apparent binding site with a Bmax of 171 nmol/mg protein and a Kd of 470 nmol/l was detected. Bound liposomes were displacable by an excess of unlabelled liposomes, were sensitive to EDTA and trypsin treatment and were not significantly competed with by dioleyl-phosphatidylcholine liposomes. However, a site with identical characteristics was demonstrated in experiments performed with blanc dishes in the absence of cells. This site was generated by liposomes bound to the blanc culture dish, which could not be removed by extensive washing, but which were released by EDTA and trypsin and were trapped during filtration. These problems were overcome by a centrifugation assay technique. Then non-specific binding was less than 1% and cellular binding was inhibited dose-dependently by liposomes made from various phospholipids. These studies may facilitate attempts to direct liposomes as carriers to specific cellular targets in the lungs.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Tracheobronchial surface active material in cystic fibrosis.

Surface active material potentially present in the airway is difficult to analyse due to the tight binding of surfactant components to mucins. A surface active sol-fraction was obtained from sputum of patients with cystic fibrosis (CF), analysed and compared with the sol-fraction from sputum of tracheomized, non-CF patients. The release of phospholipids from CF sputum was relatively fast being completed within minutes, temperature dependent and averaged 5.6 +/- 2.2% of total phospholipid mass. In comparison to sputum, the phospholipid composition of the sol fraction was the same except for a lower percentage of phosphatidylethanolamine, which is usually found primarily cell membrane associated. The sol-fraction from the CF patient group had a lower percentage of phosphatidylcholine and about 3 times more surfactant protein A than that from the non-CF patients. Surface activity did not differ between CF and non-CF samples. Of interest, the adsorption rate (gamma ads, about 30-35 mN/m) and the minimal surface tension (gamma min, about 20-25 mN/m) were relatively low. These data support the hypothesis that surface active material can be released from sputum and that it might support its transport by reducing mucus adhesiveness to the airways.

Adolescent↗