Biomedical subjects

T Curstedt

Publications and source records attributed to T Curstedt.

At least 55 records · Page 3Linked to original sources

PubMed1995

Structural and functional importance of the C-terminal part of the pulmonary surfactant polypeptide SP-C.

A synthetic non-palmitoylated form of the pulmonary surfactant protein SP-C and three peptides of different lengths corresponding to its N-terminal and middle parts were reconstituted into dipalmitoylglycerophosphocholine/phosphatidylglycerol (7:3, by mass) lipid bilayers. The adsorption properties of each reconstituted system were determined by measurement of the surface pressure after injection of the samples underneath an air/water interface. Attenuated total reflection infrared spectroscopy provided information about the structure and orientation of peptides in lipid bilayers. The hydrophobic C-terminal helix is crucial for the rapid adsorption as shortening of the C-terminal part drastically restricted this activity. The C-terminal amino acid sequence can however be replaced with that of the second transmembrane helix of bacteriorhodopsin without significantly modifying the adsorption properties. The data suggest that the hydrophobic C-terminal part allows the anchorage of SP-C in the lipid bilayer in such a manner that the N-terminal domain adopts an optimal conformation and orientation for the rapid adsorption of phospholipids at the air/water interface, and/or that a membrane-spanning helix as such is needed for this activity.

Adsorption↗

PubMed1995

An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B.

The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary surfactant-associated polypeptide SP-B exhibit 24% residue identities (49% similarities), including six half-cystine residues in the same disulphide bonding pattern, and similar far-UV circular dichroism spectra corresponding to 45-55% alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the conformations of NK-lysin and SP-B are similar. In contrast, the functional properties of the two proteins are dissimilar: SP-B does not exhibit antibacterial activity and NK-lysin does not significantly effect phospholipid spreading at an air/water interface. Saposins, which solubilize lipids and activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities with NK-lysin (and SP-B), including the six conserved half-cystine residues. The inclusion of NK-lysin extends the family of saposin-like polypeptides, all members of which appear to interact with lipids. Strictly conserved structural features with implications for helix topology and lipid interactions are observed.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1995

Effect of surfactant on nitroblue tetrazolium reduction of polymorphonuclear leucocytes stimulated with type Ia group B streptococci.

Activation of polymorphonuclear leucocytes (PMN) was investigated after incubation of adult human PMN and group B streptococci (GBS) type Ia with a type-specific polyclonal antiserum and a modified porcine surfactant (Curosurf). The level of oxidative metabolism of PMN was studied using a micromethod modification of the nitroblue tetrazolium (NBT) reduction test. GBS alone did not stimulate significant oxygen metabolite release from PMN, and incubation of PMN with surfactant alone resulted in decreased NBT reduction. After opsonization of GBS with a specific antibody, PMN were activated and the increased oxygen metabolite release was not suppressed when surfactant was added to the system. We conclude that the encapsulated GBS strain investigated needs opsonization with specific antibody to increase oxidative metabolism of PMN, and that incubation of PMN and opsonized GBS with surfactant does not interfere with NBT reduction.

Adult↗

PubMed1995

Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits.

We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.

Animals↗

PubMed1995

A possible alteration of surfactant in broncho-alveolar lavage fluid from healthy smokers compared to non-smokers and patients with sarcoidosis.

In disorders affecting the alveoli and lung interstitium and altered composition of the epithelial lining fluid, i.e. the surfactant, may affect the outcome of the disease. The phospholipid composition in bronchoalveolar lavage (BAL) fluid was determined in healthy non-smoking (n = 8) and smoking (n = 12) volunteers, and in non-smoking patients with clinically active sarcoidosis (n = 7). The total amount of phosphatidylcholines (median +/- SD) were in the non-smoking control group (21.8 +/- 5.7 mumol/L) and in the non-smoking sarcoidosis group (26.1 +/- 9.1 mumol/L), while healthy smokers had significantly (p < 0.05 for both) lower amounts (14.6 +/- 5.6 mumol/L). The composition of phosphatidylcholines was similar in all three groups with one exception. Palmitoylmyristoyl-phosphatidylcholine constituted a significantly higher fraction among the smokers (12.7 +/- 2.1 mol%) compared to the non-smoking control group (10.6 +/- 1.4 mol%; p < 0.05) and the sarcoidosis group (10.6 +/- 0.6 mol%; p < 0.01). In conclusion, no quantitative or qualitative differences in phosphatidylcholines were observed between non-smoking healthy volunteers and non-smoking patients with clinically active sarcoidosis. However, in smoking healthy volunteers the total amount of phosphatidylcholines was reduced and their composition altered. Earlier reported conflicting results may be due to the fact that the smoking habits have not been considered.

Adolescent↗

PubMed1994

The NMR structure of the pulmonary surfactant-associated polypeptide SP-C in an apolar solvent contains a valyl-rich alpha-helix.

The nuclear magnetic resonance (NMR) structure of the pulmonary surfactant-associated lipoplypeptide C (SP-C) was determined in a mixed solvent of C2H3Cl/C2H3OH/ 1 M HCl 32:64:5 (v/v). Sequence-specific 1H NMR assignments and the collection of conformational constraints were achieved with two-dimensional 1H NMR, and the structure was calculated with the distance geometry program DIANA. The root mean square deviations for the well-defined polypeptide segment of residues 9-34 calculated for the 20 best energy-minimized DIANA conformers relative to their mean are 0.5 and 1.3 A for the polypeptide backbone atoms N, C alpha, and C', and for all heavy atoms, respectively. The 35-residue polypeptide chain of SP-C forms an alpha-helix between positions 9 and 34, which includes two segments of seven and four consecutive valyls that are separated by a single leucyl residue. The N-terminal hexapeptide segment, which includes two palmitoylcysteinyls, is flexibly disordered. The length of the alpha-helix is about 37 A, and the helical segment of residues 13-28, which contains exclusively aliphatic residues with branched side chains, is 23-A long and about 10 A in diameter. The alpha-helix is outstandingly regular, with virtually identical chi 1 angles for all valyl residues. The observation of a helical structure of SP-C was rather unexpected, considering that Val is generally underrepresented in alpha-helices, and it provides intriguing novel insights into the structural basis of SP-C functions as well as into general structural aspects of protein-lipid interactions in biological membranes.

Amides↗

PubMed1994

Intracerebral haemorrhages in surfactant treated neonates with severe respiratory distress syndrome: age at diagnosis, severity and risk factors.

UNLABELLED: Within a randomized European multicentre trial the time of onset, severity and progression of intracerebral haemorrhages (ICH) were investigated prospectively by serial cranial ultrasonography in 343 ventilated infants with severe respiratory distress syndrome (RDS) following instillation of single or multiple doses of a natural porcine surfactant (Curosurf). In 148/343 infants (43%) ICH was diagnosed (grade I or II: 22%, grade III or IV: 21%). In 26 cases (8%) ICH was present on the ultrasound scan prior to surfactant instillation at a median age of 6 h. Incidence and severity of ICH was similar after single- or multiple-dose surfactant treatment. Using a logistic regression model the following risk factors predictive of ICH were defined: low birth weight, allocation to certain hospitals, vaginal delivery, Apgar score < or = 6, rectal temperature on admission < or = 36 degrees C, primary anaemia, acidosis prior to treatment, RDS grade IV in pre-treatment chest films and poor response to surfactant treatment. CONCLUSION: Our study provides supportive evidence that multiple doses of Curosurf do not increase the risk for ICH as compared to single-dose administration.

Biological Products↗

PubMed1994

Effect of different surfactants on pulmonary group B streptococcal infection in premature rabbits.

OBJECTIVES: To evaluate the effects of different surfactants on pulmonary infection with group B streptococci in premature rabbits and to examine the effects of different surfactants on pulmonary alveolar macrophage function of newborn rabbits. MODEL: Preterm and term rabbit pups. METHODS: Rabbit pups were infected with GBS aerosols followed by intratracheal administration of either calf lung surfactant extract, minced porcine lung surfactant (Curosurf), synthetic surfactant (Exosurf Neonatal), minced bovine lung surfactant (Survanta), human amniotic fluid-derived surfactant, rabbit surfactant, saline vehicle, or no treatment. Intrapulmonary clearance of GBS was determined by comparing bacterial counts in left lungs cultured immediately after aerosol infection with similarly infected lungs analyzed 4 hours after surfactant therapy. Phagocytosis of streptococci was ascertained by microscopic examination of the right lungs fixed in situ at 4 hours. For comparison, an in vitro method was used to measure growth of GBS in the different surfactants. RESULTS: Preterm animals had a sixfold increase in pulmonary bacterial growth compared with a slight decrease in intrapulmonary GBS in term animals when all were delivered by cesarean section (p < 0.05). In premature rabbits, GBS proliferation was lowest in animals treated with Exosurf Neonatal and highest in animals receiving Curosurf and human amniotic fluid-derived surfactant (p < 0.05). None of the surfactants promoted accelerated growth of GBS in comparison with control animals. Similar growth of GBS was seen in in vitro cultures. Intrapulmonary phagocytosis of GBS in premature pups was not altered by any of the surfactants. In term rabbit pups, the following measures of macrophage population kinetics remained normal at 1 and 24 hours after surfactant administration: viability, cell numbers based on lung lavage, and in vivo incorporation of thymidine. CONCLUSIONS: Surfactants used in clinical practice do not accelerate the in vivo growth of group B streptococci in the lungs of preterm rabbits. Some surfactants inhibit streptococcal proliferation. The effects of different surfactants are not explained by changes in macrophage function.

Animals↗

PubMed1994

Comparison of surface properties and physiological effects of a synthetic and a natural surfactant in preterm rabbits.

AIMS: To compare the physical and physiological properties of a synthetic surfactant (Exosurf, Wellcome Foundation) and a natural surfactant (Curosurf, Chiesi Farmaceutici). METHODS: Surface properties of the surfactant suspensions (10 mg phospholipid/ml) were evaluated using the pulsating bubble surfactometer. Lung-thorax compliance was determined in 47 immature newborn rabbits with a gestational age of 27 days, treated with recommended clinical doses of either surfactant (Exosurf 67.5 mg/kg; Curosurf 200 mg/kg). The lungs were examined histologically. RESULTS: The mean (SD) contractile forces of the surface at maximum and minimum bubble size were significantly lower for Curosurf than for Exosurf: 31 (2) and 0 (0) mN/m v 53 (5) and 29 (4) mN/m, respectively. Mean (SD) lung-thorax compliance after one hour of ventilation was significantly higher in rabbits treated with Curosurf compared with animals receiving Exosurf or those serving as controls: 0.60 (0.15) ml/cm H2O.kg v 0.44 (0.03) and 0.34 (0.18) ml/cm H2O.kg, respectively. Both surfactants increased alveolar volume density compared with results for control animals, but only Curosurf significantly reduced the incidence of moderate or severe bronchiolar epithelial disruption. CONCLUSIONS: The natural surfactant, Curosurf, reduced the contractile force at an air-liquid interface to a greater extent than the synthetic surfactant, Exosurf, and led to a greater improvement in compliance and less airway epithelial damage when given in clinical treatment doses to immature rabbits.

Animals↗

PubMed1994

Surface activity of lipid extract surfactant in relation to film area compression and collapse.

The physical properties of modified porcine surfactant (Curosurf), isolated from minced lungs by extraction with chloroform-methanol and further purified by liquid-gel chromatography, were investigated with the captive bubble technique. Bubble size, and thus the surface tension of an insoluble film at the bubble surface, is altered by changing the pressure within the closed bubble chamber. The film surface tension and area are determined from the shape (height and diameter) of the bubble. Adsorption of fresh Curosurf is characterized by stepwise decreases in surface tension, which can easily be observed by sudden quick movements of the bubble apex. These "adsorption clicks" imply a cooperative movement of large collective units of molecules, approximately 10(14) (corresponding to approximately 120 ng of phospholipid) or approximately 10(18) molecules/m2, into the interface during adsorption. Films formed in this manner are already highly enriched in dipalmitoyl phosphatidylcholine, as seen by the extremely low compressibility, close to that of dipalmitoyl phosphatidylcholine. Near-zero minimum tensions are obtained, even at phospholipid concentrations as low as 50 micrograms/ml. During dynamic cycling (20-50 cycles/min), low minimum surface tensions, good film stability, low compressibility, and maximum surface tensions between 30 and 40 mN/m are possible only if the films are not overcompressed near zero surface tension; i.e., the overall film area compression should not substantially exceed 30%.

Adsorption↗

PubMed1994

Exogenous surfactant improves lung compliance and oxygenation in adult rats with meconium aspiration.

We studied the effects of exogenous surfactant on lung function and morphology in an adult rat model of severe meconium aspiration syndrome. Animals ventilated with 100% oxygen received 4-6 ml of human meconium (25 mg/ml) intratracheally. After 30 min, lung-thorax compliance had decreased by > 30% and arterial PO2 was < 10 kPa. Animals were then treated with no material (MECO group), 0.9% NaCl (MECO-saline group), natural porcine surfactant (NPS group) at a dose of 100 mg/kg, or modified porcine surfactant at a dose of either 100 (MPS100 group) or 200 mg/kg (MPS200 group) and were ventilated for another 180 min. Immediate and sustained improvement of arterial PO2 and compliance was observed in the MPS200 group, whereas the MPS100 and NPS groups showed less pronounced effects. There was a significant improvement of quasi-static lung volumes at maximum insufflation pressure and during deflation in the MPS200, MPS100, and NPS groups. Recordings with Wilhelmy balance showed that minimum surface tension of bronchoalveolar lavage fluid from animals receiving either type or dose of surfactant was significantly lower than in the MECO and MECO-saline groups. Meconium aspiration induced diffuse and prominent atelectasis, intra-alveolar edema, and hyaline membranes. These morphological abnormalities were reversed by exogenous surfactant, especially by the high-dose regimen.

Animals↗

PubMed1994

The proteins of the surfactant system.

The structural and functional integrity of pulmonary surfactant depends on several specific proteins. Two of these, SP-A and SP-D, are large and water-soluble, while SP-B and SP-C are small and very hydrophobic. SP-A is an 18-mer of 26 kDa polypeptide chains and contains N-linked oligosaccharides. Structurally, it can be characterized as a collagen/lectin hybrid. Together with SP-B, SP-A is required for conversion of secreted endogenous surfactant to tubular myelin in the alveolar lining. It also regulates surfactant secretion and reuptake of surfactant lipids by type II cells; these functions are probably receptor mediated. SP-D, a 12-mer of 39 kDa polypeptide chains, is a collagenous glycoprotein with structural similarities to C-type lectins. Both SP-A and SP-D stimulate alveolar macrophages. SP-B is a 79-residue polypeptide that contains three intrachain disulphide bridges. It exists mainly as a homodimer, which is strongly positively charged and may selectively remove anionic and unsaturated lipid species from the alveolar surface film, thereby increasing surface pressure. SP-C is a mainly alpha-helical, extraordinarily hydrophobic polypeptide containing 35 amino acid residues and covalently linked palmitoyl groups. Its alpha-helical portion is inserted into surfactant lipid bilayers. SP-C accelerates the adsorption of lipid bilayers to an interfacial monolayer. In babies with respiratory distress syndrome, the clinical response to treatment with surfactant containing SP-B and SP-C is much faster than in babies treated with protein-free synthetic surfactant. We speculate that, in the near future, surfactant preparations based on recombinant hydrophobic proteins will be available for clinical use.

Glycoproteins↗

PubMed1994

Experimental neonatal group B streptococcal pneumonia: effect of a modified porcine surfactant on bacterial proliferation in ventilated near-term rabbits.

We studied bacterial proliferation in relation to surfactant treatment in a model of neonatal group B streptococcal (GBS) pneumonia. Surfactant (Curosurf) was isolated from pig lungs with a method preserving only polar lipids and hydrophobic proteins. Near-term rabbit fetuses were ventilated in a body plethysmograph system. At 15 min, a suspension of GBS strain 090 Ia LD (5 mL/kg, concentration approximately 10(9)/mL) was instilled intratracheally. At 30 min, surfactant (n = 12) or sterile saline (n = 13) was administered via the airways (2.5 mL/kg). A control group (n = 12) received the same volumes of saline. After 5 h the animals were killed, and samples for blood cultures and blood gases were taken from the heart. The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates. The results were expressed as mean log10 colony forming units/g lung +/- SD. Compared with animals (n = 12) killed immediately after GBS instillation (8.13 +/- 0.54), there was a significant increase in bacterial numbers in both groups ventilated for 5 h, but values for surfactant-treated animals (8.96 +/- 0.38) were lower than those for animals receiving saline (9.46 +/- 0.50; p < 0.05). After 5 h, 96% of GBS-infected animals had positive blood cultures. Light microscopic examination of the right lung of GBS-infected animals revealed inflammatory changes that tended to be less prominent in surfactant-treated rabbits. We conclude that intratracheal inoculation of near-term rabbits with GBS resulted in a significant bacterial proliferation during 5 h of ventilation and that bacterial growth was mitigated by treatment with surfactant.

Animals↗

PubMed1994

Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome.

In an attempt to restore functional surfactant to the lungs of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the onset of ARDS with a single dose of hydrophobic components of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a modest transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were detected. Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, alpha-1-proteinase inhibitor specific activity, or cell count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration levels and fell by 24 h. In addition, in two patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations suggest a role for surfactant replacement in the treatment of patients with ARDS and support the need for continuing investigation.

Adult↗

PubMed1993

Surfactant inhibition in experimental meconium aspiration.

Human meconium components were separated into a water-methanol soluble phase containing mainly proteins and bilirubin and a chloroform soluble phase containing free fatty acids, triglycerides and cholesterol. Various amounts of original meconium, the water-methanol soluble fraction or the chloroform soluble fraction were added to standard suspensions of porcine surfactant (Curosurf). In a pulsating-bubble or Wilhelmy-balance system, meconium and its subfractions inhibited surfactant activity, but the chloroform soluble fraction had the highest specific inhibitory activity. Original meconium in saline (130 or 65 mg/ml) was instilled into the airways of ventilated near-term newborn rabbits (dose 6 ml/kg). Lung-thorax compliance was reduced by 38% in animals aspirating the higher dose and by 27% in the low-dose group. Histological sections showed intra-alveolar accumulation of fine meconium particles in experimental animals, but no plugging of larger airways. We conclude that respiratory failure from meconium aspiration may be mediated, in part, by inactivation of surfactant.

Adsorption↗

PubMed1993

Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration.

Nearly mature newborn rabbits (gestational age 29.5 days) were tracheotomized at birth and received, via the tracheal cannula, 6 ml/kg body weight of a filtered saline suspension of human meconium, 65 or 130 mg/ml. Animals were kept in body plethysmographs and ventilated for 60 min with standardized tidal volume (8-10 ml/kg). Aspiration of meconium caused, in both groups, a statistically significant reduction in lung-thorax compliance, elevated PCO2 in heart blood and reduced alveolar volume density (VV) in histological sections. Both groups responded to treatment with exogenous surfactant (Curosurf, 200 mg/kg) with a moderate, statistically significant improvement in lung-thorax compliance, PCO2 and alveolar VV. Our data indicate that respiratory failure after neonatal meconium aspiration may be influenced favorably by treatment with exogenous surfactant.

Animals↗

PubMed1993

Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique.

Surfactant bolus instillation has been reported to cause changes in arterial blood pressure (BP) and cerebral blood flow velocities which may increase the risk of intraventricular haemorrhage. To avoid these effects, slow tracheal infusion was evaluated as a possible alternative method of surfactant administration. Saline lung lavages were performed in 13 anesthetized and artificially ventilated adult rabbits to produce respiratory distress syndrome. Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC) and/or red microspheres (RMS) was instilled into the trachea either as a single bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood gases and BP. To determine surfactant distribution, the lungs were cut into 60-70 pieces and radioactivity and/or the number of RMS were measured in each piece. The distribution of RMS was closely related to the distribution of 14C-DPPC (r = 0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2 (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS changed neither BP nor PaO2 during the observation period of 60 min. The pulmonary distribution of CS was extremely uneven after infusion. The distribution of exogenous surfactant and its effects on gas exchange are influenced by the instillation method. An inadequate instillation technique may add to the causes of "poor response" after surfactant replacement.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1993

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Biological Products↗