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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 α[sub 1]-antitrypsin (α[sub 1]AT), antichymotrypsin (ACT) and secretory leucocyte protease inhibitor (SLPI) levels were analysed. Free proteolytic and elastolytic activities were also determined. CLD correlated with low α[sub 1]AT (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, elastaseand NP4–α[sub 1]AT complexes during the first week of life, with one exception: RDS X-ray severity and the elastase-α[sub 1]AT complex concentration were correlated at 3–4 d 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–α[sub 1]AT complex or neutrophil lipocalin levels were not correlated with the development of CLD. The correlation between CLD and low α[sub 1]AT 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–α[sub 1]AT 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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).

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.

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.

Comparative studies on the isothiocyanate content of rape-seeds and rape-seed oil show that, apart from nearly 300 mg/100 g of vinyl thio-oxazolidone, rape-seeds contain almost 200--300 mg/100 g of isothiocyanates of which 3-butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are the main components as evidenced thin-layer and gaschromatographically. Only about 1 mg/100 g of isothiocyanates are found in pressed rape-seed oil; and but circa 10 mg/100 g, in extracted rape-seed oil. 3-Butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are once more the main components. Thioglycerides are not detected in the oil. Vinyl thio-oxazolidone is found only in extracted rape-seed oil (about 2 mg/100 g).

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.

Ten newborn babies with severe respiratory distress syndrome, all dependent on artificial ventilation, were treated via the airways with the isolated phospholipid fraction of bovine or porcine surfactant. After treatment with surfactant at a median age of 10.5 h, there was in all patients a striking improvement of lung aeration in chest films, with a decrease in parenchymal fluid retention and in distension of bronchioli. These radiologic findings were associated with a dramatic improvement of oxygenation and a significant reduction of the right-to-left shunt. In spite of the rapid therapeutic response, four patients died from cerebral hemorrhage. One of the surviving patients developed bronchopulmonary dysplasia. Our findings document efficacy of this new surfactant preparation in the neonatal respiratory distress syndrome, but the long-term effects need to be further tested in randomized clinical trials.