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Biomedical subjects

G Noack

Publications and source records attributed to G Noack.

At least 19 recordsLinked to original sources

Tracheobronchial aspirate fluid neutrophil lipocalin, elastase- and neutrophil protease-4-alpha1-antitrypsin complexes, protease inhibitors and free proteolytic activity in respiratory distress syndrome.

UNLABELLED: This study aimed to determine whether the protease/protease inhibitor balance and neutrophil activity is of pathophysiological importance in the severity and resolution of respiratory distress syndrome (RDS) and the eventual development of neonatal chronic lung disease (CLD). Ventilated preterm infants with RDS (n = 43) were studied during their first week of life. Tracheobronchial aspirate fluid (TAF) concentrations of neutrophil lipocalin, the elastase- and neutrophil protease-4 (NP4) complex concentrations, and alpha1-antitrypsin (alpha1AT), antichymotrypsin (ACT) and secretory leucocyte protease inhibitor (SLPI) levels were analysed. Free proteolytic and elastolytic activities were also determined. CLD correlated with low alpha1AT (p = 0.02) and ACT (p = 0.02) levels at 3-4 d of age and low SLPI (p = 0.03) at 7-8 d of age. No correlations were found between CLD or severity of RDS (as judged from radiological examination) and neutrophil lipocalin, elastase- and NP4-alpha1AT complexes during the first week of life, with one exception: RDS X-ray severity and the elastase-alpha1AT complex concentration were correlated at 3-4d of age (p = 0.02). Free proteolytic activity occurred in the TAF of 7/30 infants tested on day 3-4 and free elastolytic activity in 1 patient. During the rest of the first week of life no free elastolytic or proteolytic activities were observed. Caesarean section was correlated with low levels of SLPI on day 3-4 (p = 0.01), NP4 (p = 0.03) and ACT (p = 0.05) on day 5-6. Gestational age was positively correlated with protease inhibitors and their complexes at 3-4 d of age. CONCLUSION: Free proteolytic or elastolytic activity in the TAF of RDS infants in the first week of life occurred by way of exception. Elastase-/NP4-alpha1AT complex or neutrophil lipocalin levels were not correlated with the development of CLD. The correlation between CLD and low alpha1AT or ACT at 3-4 d and SLPI at 7-8 d of age may be due to either immaturity or complex formation. The severity of RDS as judged from radiological examination was correlated with elastase-alpha1AT complex on day 3-4. The main hypothesis, that TAF protease/protease inhibitor levels or imbalance and leucocyte activity are important factors indicating a high risk of severe RDS and subsequent CLD development, was principally not confirmed.

Bronchoalveolar Lavage Fluid↗

Downregulatory cytokines in tracheobronchial aspirate fluid from infants with chronic lung disease of prematurity.

UNLABELLED: Chronic lung disease of prematurity (CLD) is associated with an inflammatory response in the preterm lung and increased levels of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF). We investigated TAF levels of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-12 (IL-12) cytokines possibly important in downregulating the proinflammatory response and/or inducing lung fibrosis in infants with developing and established CLD. Infants with CLD (n = 24) were compared with preterm infants with RDS that resolved (n = 22) and postoperative infants without lung disease (n = 23). TAF levels of TGF-beta1, IL-10, IL-4 and IL-12 were studied by quantitative enzyme immunoassay. Levels of TGF-beta1 were significantly higher during the first week of life in infants who developed CLD, remained high at 2 wk and past 4 wk of age. TAF levels of TGF-beta1 did not decrease significantly in six infants with CLD after treatment with steroids. TAF IL-10 was detected in 12/46 (26%) preterm infants. Infants with CLD or RDS were more likely to have measurable TAF levels of IL-10, compared with the postoperative infants without lung disease (p < 0.02 and 0.04, respectively). TAF levels of IL-4 or IL-12 were below the detection limits in all samples. CONCLUSIONS: We have demonstrated a sustained increase of TGF-beta1 levels in TAF from preterm infants who develop CLD, suggesting an important role for TGF-beta1 in the fibrotic response in the CLD lung. The elevated TGF-beta1 levels, combined with an absent or irregular secretion of IL-4, IL-10 and IL-12, can have importance for the increased tendency for the development of CLD in preterm infants.

Age Factors↗

Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants.

AIM: To investigate if early changes in concentrations of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF) from preterm infants could be used to detect infants at risk of chronic lung disease (CLD) and help in the selection of patients for early steroid treatment. METHODS: Twenty eight preterm infants less than 34 weeks of gestation (median 26 weeks) were intubated and daily measurements of TAF concentrations of tumour necrosis factor alpha (TNF alpha) and the interleukins IL-1 beta, IL-6, and IL-8 were made, using enzyme immunoassay techniques. RESULTS: Seventeen of the infants developed CLD. The infants who developed CLD had significantly increased concentrations of TNF alpha, IL-1 beta, IL-6 on days 2 and 3. TNF alpha, IL-6, and IL-8 concentrations were significantly related to gestational age and duration of supplemental oxygen; TNF alpha, IL-6, and IL-8 concentrations also correlated with length of time on the ventilator. CONCLUSION: These data indicate that tracheobronchial aspirate fluid cytokine concentrations may be used as a predictor of subsequent CLD and may help select a group of preterm infants at high risk of developing CLD for early treatment.

Biomarkers↗

Inhibition of gamma-aminobutyric acid aminotransferase from rat brain mitochondria by chloride and acetate.

10-100 mmol/l of acetate inhibits gamma-aminobutyric acid aminotransferase from rat brain mitochondria by 35-90%. Similarly, 50-100 mmol/l of chloride inhibits this enzyme by 10-30%. In either case, the inhibition is competitive with GABA and noncompetitive with alpha-ketoglutarate. The effect of sodium and potassium is negligible. gamma-Aminobutyric acid aminotransferase from rat liver mitochondria is also inhibited by acetate and chloride. The degree of inhibition of both hepatic and cerebral enzyme is nearly the same.

4-Aminobutyrate Transaminase↗

Ontogeny of a human polychlorinated biphenyl-binding protein. Level of expression in tracheal aspirates in bronchopulmonary dysplasia.

A human lung polychlorinated biphenyl binding protein (PCB-BP,M(r) 13 kd) has recently been purified from lavage fluid. Polyclonal monospecific antibodies against PCB-BP were produced and used for immunohistochemical staining in sections of human lung tissue. PCB-BP was found to localize preferentially to the nonciliated (Clara) cells of the lung, whereas the alveolar cells and ciliated cells of the larger airways were devoid of staining. Tracheal aspirates from infants receiving mechanical ventilation were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation and Western immunoblotting. The antibodies to human PCB-BP detected a single band of the expected molecular weight, and a quantitative analysis of the ontogeny of PCB-BP in tracheal aspirates was performed by construction of Western immunoblot standard curves. A significant increase in the levels of PCB-BP in late gestation (gestational weeks 39 to 41) was demonstrated. In similar experiments, levels of PCB-BP in tracheal aspirates obtained from infants with bronchopulmonary dysplasia (BPD) at the postconceptional age of less than 38 weeks were found to be significantly elevated as compared with a normal study group of similar gestational age (21.8 +/- 4.8 vs 3.1 +/- 0.8 ng of PCB-BP per microgram of total protein, p < 0.005). It is suggested that the high levels of PCB-BP at the postconceptional age of less than 38 weeks observed in infants with BPD may reflect inflammatory injury and regeneration of airway epithelium, associated with proliferation of Clara cells.

Blotting, Western↗

Correlations between radiological and cytological findings in early development of bronchopulmonary dysplasia.

Sequential chest radiographs from 40 newborn infants requiring assisted ventilation for respiratory distress syndrome or other conditions were evaluated with a new scoring system aiming at identifying abnormal expansion patterns and interstitial infiltrates representing an early stage of bronchopulmonary dysplasia (BPD). Age at examination ranged from 3 to 23 days. Tracheal effluent samples obtained from the babies during the same period of observation were examined cytologically for evidence of regenerating airway epithelium with squamous metaplasia, indicating BPD. According to the radiological scoring system 24 babies (60%) developed BPD, first diagnosed at a median age of 9 days. By cytological criteria 20 babies (50%) developed BPD, first diagnosed at a median age of 10.5 days. The results from radiological and cytological diagnosis of BPD were concordant in 16 babies (P < 0.05 by chi-square test). Using oxygen dependency at the age of 28 days as evidence of established BPD, the radiological scoring system alone had a sensitivity of 93% and a specificity of 53%. The corresponding figures for cytological assessment alone were 73% and 58%, respectively. By combining radiological and cytological findings, values for sensitivity and specificity were 67% and 68%, respectively.

Bronchopulmonary Dysplasia↗

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide.

The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises.

Acidosis↗

Passive expiratory flow-volume recordings in immature newborn rabbits. Effect of surfactant replacement on the time constant of the respiratory system.

Immature newborn rabbits with a gestational age of 27 days were paralyzed and kept in body plethysmographs. They were ventilated for 10 min with a tidal volume of approximately 10 ml/kg, with or without previous surfactant treatment via the airways. Tidal volumes and flow were recorded with a pneumotachograph connected to the body plethysmograph, and the expiratory time constant of the respiratory system (trs) was determined from flow-volume diagrams. The values of trs after 10 min were significantly higher in surfactant-treated animals than in controls (50 +/- 7 vs. 23 +/- 4 ms; p less than 0.002), indicating stabilization of the alveoli. There was also a close correlation between trs and the compliance values calculated from tidal volumes and ventilator pressure (r = 0.80; p less than 0.001), as well as between trs and the alveolar volume density in histological lung sections, determined by automated image analysis (r = 0.71; p less than 0.001).

Animals↗

Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.

Ten newborn infants (795-1680 g) with severe respiratory distress syndrome (RDS) were treated with the isolated phospholipid fraction of bovine or porcine surfactant, which was administered via the airways (dose 200 mg/kg), at a median age of 10.5 h. Before receiving surfactant, all the infants were on artificial ventilation (FiO2 0.6-1.0). Within 2 h after surfactant replacement, the arterial-to-alveolar PO2 ratio increased from 0.1 to 0.35. There was a concomitant improvement in lung aeration on the chest roentgenograms and a significant reduction in the right-to-left shunt. Four patients died of cerebral hemorrhage; two of them also had a patent ductus arteriosus. One surviving infant developed bronchopulmonary dysplasia, and another succumbed 8 months later to the sudden infant death syndrome. No antibodies against surfactant were detected in the sera of the survivors. Since our results show a significant improvement in lung function after replacement therapy, the efficacy of this new surfactant preparation should be further tested in randomized clinical trials.

Chromatography, Gel↗

[Surgical treatment of the saddle joint arthrosis].

In addition to the usual methods of arthroplasty of the carpometacarpal joint of the thumb an alternative technique of transosseus suspension for the first metacarpal is described. The basic idea is to reconstruct the intermetacarpal ligaments I-II with a distally pedicled slip of the flexor carpi radialis tendon to prevent proximal migration of the first ray after removal of the trapezium. This technique is considered simple, avoiding implantation of silastic or other material with their well known problems. Follow-up results of 97 patients out of a series of 151 operations between 1976 and 1982 are shown and discussed.

Arthritis↗

Circulatory adaptation in newborn infants of strictly controlled diabetic mothers.

Possible relations between neonatal circulatory function and maternal diabetic control were investigated in 22 infants of strictly controlled diabetic mothers during the first 2 days after birth. Eleven infants were delivered vaginally (V) and 11 infants by elective cesarean section (S). Maternal diabetes was more severe in the latter group. Half of the infants had one or more episodes of neonatal morbidity although none presented symptomatic hypoglycemia. Plasma glucose FFA and C-peptide were measured at birth and 3-6 hours later together with skinfold thickness; heart size was determined by X-ray at 24-28 hours; stroke volume and cardiac output were repeatedly determined by transthoracic impedance and ECG. C-peptide at birth was higher in group S than in V. C-peptide in both groups were neither related to glucose or FFA nor to birthweight or skinfold thickness. Infants with neonatal complications including cardiomegaly had the highest C-peptide values. Skinfold was positively correlated to maternal pregnancy glucose level, birthweight percentile and infant heart volume. Mean values for stroke volume and cardiac output were similar in both groups and not different from normal controls when related to body weight. Heart volume and stroke volume were significantly related. ECG abnormalities were seen in 6 infants who showed cardiomegaly on X-ray. We suggest that the present finding of an association between elevated C-peptide concentration at birth and the occurrence of neonatal complications including cardiomegaly and ECG abnormalities could be the consequence of functional hyperinsulinism and that the cardiomegaly is of adaptive type.

Blood Glucose↗

Robertsonian karyotype variation in wild house mice from Rhaeto-Lombardia.

The European longtailed house mouse (M. m. brevirostris and domesticus) in the Rhaetian Alps and Lombardia presents a complex system of Robertsonian (Rb) variation and karyotype diversity, several adjoining populations homozygous for multiple Rb metacentric chromosomes, sites of coexistence of different Rb types, and zones of hybridization with non-Rb populations. The original "tobacco mouse" is just one of many local Rb variants, such as those from other Alpine areas (e.g., Orobian Alps) or from Central Lombardia, where a relatively large region within which the population is homogeneous for multi-Rb metacentrics is found. The present study is based strictly on material in which the chromosome arms were identified by G-banding, so that karyotypes within the areas under investigation could be compared. Altogether 111 mice were studied.

Animals↗

Steric factors in the pharmacokinetics of lindane and alpha-hexachlorocyclohexane in rats.

1. The elimination of alpha-1,2,3,4,5,6-hexachlorocyclohexane (alpha-HCH) by rats, as assessed by g.l.c. determination of the chemical's disappearance from depot fat, exhibited a sex difference (males:females = 4:1) and a sizeable deuterium isotope effect (6.3 in males). 2. Lindane (gamma-HCH), by contrast, disappeared from depot fat, skeletal muscle, brain and blood at nearly the same rates in both sexes. Perdeuteration, though effective in reducing hepatic removal, did not significantly retard the overall elimination of this isomer (isotope effect in males less than 2). Partial explanation of this finding is that lindane and lindane-d6 are equally subject to dechlorination in the gut. 3. alpha-HCH distributed into cerebral white matter in preference to grey matter to a much higher degree than did lindane and the beta-isomer of HCH, and elimination from that tissue was slow. The finding is considered to indicate a stereoselective affinity of alpha-HCH to some component(s) of myelin.

Animals↗

Morphine kinetics in children.

The kinetics of morphine in the plasma of children (0 to 15 yr) can in most cases be adequately described by a triexponential function. When the dosage in children receiving morphine as premedication before surgery is based on kilograms of body weight, there are only minor differences in the kinetic patterns of morphine at different ages (0 to 1, 1 to 7, and 7 to 15 yr). No significant difference in the morphine kinetics was observed between patients (7 to 15 yr) receiving the drug only as premedication and those who also received doses during surgery. The minimum morphine concentration in plasma necessary to suppress the clinical signs of pain during surgery was found to be 65 ng/ml (95% confidence limits of 46 to 83 ng/ml). Based on these minimum effective plasma levels of morphine, there does not seem to be any difference between children of different ages in their sensitivity to morphine. No difference was found in the minimum effective level of morphine when clinical signs of pain were observed by different anesthesiologists.

Adolescent↗

Serial measurements of thoracic impedance and cardiac output in healthy neonates after normal delivery and caesarean section.

Thoracic electrical impedance measurements were serially performed during the 1st, 2nd, 8th and up to the 32nd hour of life in two groups (V and S) of healthy infants. In group V, all 24 infants were delivered vaginally, in group S, all 24 infants were delivered by caesarean section for obstetrical reasons. Basal thoracic impedance (Zo), heart rate (HR), stroke volume (SV) and cardiac output (Q) were determined on each examination. In group V, Zo increased from 31.9 to 34.0 ohm between 2 hours and the last recording between 8 and 32 hours. SV decreased from 4.1 to 3.4 ml between 2 and 4 hours and was accompanied by a decrease of Q from 560 to 450 ml/min. Heart rate slowed from 129 to 115 beats/min between 2 hours and the last recording at greater than or equal to 8 hours. In group S, Zo increased from 32.2 to 35.9 ohm between 2 and 8 hours. Mean SV increased from 3.6 to 4.4 ml between 8 and 32 hours and heart rate slowed from 131 to 113 beats/min between 1 and 8 hours. No significant differences were observed between the groups. The accuracy of the impedance--SV and Q data cannot be validated. For the most part they compare favourably with values previously obtained by soluble gas methods. Serial changes may reflect not only decreasing shunts and/or increasing aeration but also changes in total fluid volume of the lungs, intra- or extravascular. The precision of the measurements is good since reproducibility of single SV and Q determinations is higher than with standard dilution techniques. The data obtained may serve as baseline values for comparison with data in infants of the same age with various anomalies.

Cardiac Output↗