Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural surfactant (Surfactant TA, Survanta, CLSE, SF-RI 1, Curosurf and human surfactant obtained from amniotic fluid) therapy for RDS in very premature infants has been evaluated in 17 controlled clinical trials. Uniformly intratracheal surfactant administration caused a decreased intensity of mechanical ventilation during the first hours (reduced inspiratory pressure, reduced oxygen requirements) as an immediate effect of surfactant administration. Metanalysis reveals barotraumatic pulmonary complications mainly, pneumothorax and pulmonary interstitial emphysema to occur less frequently in surfactant-treated infants in virtually all trials; an increased incidence of survival without bronchopulmonary dysplasia following surfactant treatment was observed in 10 controlled clinical trials. The incidence of other complications of prematurity (intracranial hemorrhage, patent ductus arteriosus and necrotizing enterocolitis) was unchanged following natural surfactant treatment. Dosing of natural surfactant is still under investigation, however recent data indicate that the initial dose should not be less than 100 mg/kg b.w. and retreatment should be given to infants with unsatisfactory response (i.e. fraction of inspired oxygen (FiO2) > 40%). Timing of surfactant treatment still remains controversial. Prophylactic treatment shortly following birth has been compared with rescue-treatment, i.e. surfactant administration to infants suffering from manifest RDS in most studies 4-8 h after birth. Conflicting data from 5 controlled trials may be interpreted as follows: prophylactic treatment seems to be favourable for extremely premature infants (GA < or = 26 weeks) and rescue treatment seems to be adequate for infants of 27-30 weeks of gestation. Intratracheal surfactant instillation in very premature infants did not result in an improved lung function for 24 h to 48 h in all patients. Ten--25% of study infants were reported to be "non-responders", i.e. infants without sustained decrease in oxygen requirements (i.e. FiO2 > 40%). Various factors may be operative including congenital bacterial infections (sepsis or pneumonia), lung hypoplasia and cardiac failure. Inactivation of surface properties of natural surfactant caused by a leakage of proteins across the alveolar-capillary membrane was observed in experimental and clinical studies. Current investigations focus on a combination of postnatal steroids and surfactant treatment to improve lung function and outcome in "non-responders". As long as any controlled clinical studies are being published, this approach remains experimental. Up to now, any controlled clinical trials have been performed to assess different modes of artificial ventilation (e.g. high frequency oscillating ventilation versus conventional ventilation) combined with surfactant therapy. Data obtained from premature animals given natural surfactant indicate any advantage with respect to gas exchange and lung histology to result from high frequency ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Natural surfactant for neonatal respiratory distress syndrome in very premature infants: a 1992 update. 129 66

Respiratory distress syndrome (RDS) is associated with prematurity-related deficiency of surfactant. Surfactant replacement therapy has been used in premature infants to prevent RDS or reduce its severity. In this study we describe the pathology of the lungs after surfactant replacement therapy. All the neonatal autopsies during the years 1989 and 1990 (n = 235) were examined. Infants > or = 31 weeks gestation, with congenital anomalies or who lived more than 2 weeks were excluded from the study. Infants who had received intratracheal Survanta, a modified surfactant extracted from cow lung (n = 14), were compared with infants who did not receive exogenous surfactant (n = 20). The two groups were statistically comparable in terms of weight, gestational and postnatal age, gender, and clinical management. H&E-stained lung sections were examined independently by two pathologists without knowledge of surfactant treatment status; any discrepancies in histological evaluation were resolved by joint review. Nine histological features were evaluated including hyaline membranes, necrosis of the epithelium, hemorrhage, edema, inflammation, metaplasia, arteriolar muscular hyperplasia, interstitial fibrosis, and pulmonary interstitial emphysema (PIE). Histological changes were graded from 0 to 3+. When it was present, cerebral periventricular-intraventricular hemorrhage (PVH-IVH) was graded 1-4. The presence or absence of sepsis and necrotizing enterocolitis (NEC) were also determined. Comparisons between patient groups were performed using the Mann-Whitney U, Student's t and chi 2 tests. The severity of hyaline membrane disease, PIE, and epithelial necrosis was less severe in the surfactant-treated group than in the untreated group. There were no differences between the two groups in the degree of pulmonary hemorrhage or in the incidence of PVH-IVH, sepsis, or NEC.
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PMID:Pathology of the lung in surfactant-treated neonates. 797 82

Time to successful extubation (VENT-DC) and time to discontinuation of oxygen therapy (OX-DC) for infants treated with Exosurf and Survanta surfactant preparations were compared in an observational study. Proportional-hazards (Cox) regression was used to adjust for confounding by differences in baseline risk factors between treatment groups. The Exosurf/Survanta hazard ratios, representing the relative instantaneous probabilities of the next event (VENT-DC or OX-DC) occurring in the Exosurf versus Survanta groups, were close to the null value of 1.0 and were not statistically significant. For VENT-DC the ratio was 1.08 (95% confidence interval 0.73 to 1.61, p = 0.60); for OX-DC the ratio was 0.87 (0.58 to 1.30, p = 0.83). By contrast, the hazard ratios for female versus male sex and black versus white race, presented as internal reference values, were further from the null value and were statistically significant. Survival curves showing the estimated proportion of patients in whom VENT-DC or OX-DC was achieved over time were generated from the proportional hazards models. Our findings suggest that any difference between Exosurf and Survanta surfactant for VENT-DC or OX-DC is likely considerably smaller than the differences associated with gender or race. The rationales for (1) using proportional-hazards regression when duration of therapy is an outcome of interest and (2) generating internal reference risk ratios when multivariate analysis is used are discussed in relation to future studies of hyaline membrane disease or other problems of prematurity.
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PMID:Exosurf versus Survanta surfactant preparations: proportional-hazards regression analysis of time to successful extubation and discontinuation of oxygen therapy. 886 33

Somatic gene therapy for pulmonary diseases must be accomplished in vivo, requiring the spread of a gene transfer vector across a vast expanse of respiratory epithelium. Surfactant, a naturally occurring protein and lipid mixture used to treat the respiratory distress syndrome of prematurity, disperses rapidly and evenly throughout the lung. We employed exogenous bovine surfactant (Survanta beractant) as a carrier vehicle for pulmonary delivery of a recombinant adenovirus expressing beta-galactosidase (beta-Gal). Rats treated with an adenovirus-beractant mixture demonstrated more uniform lobar distribution of transgene expression than rats treated with the same amount of virus in saline. Tissue homogenates were examined for quantitative beta-Gal expression by reaction with o-nitrophenol beta-n-galactopyranoside (ONPG). The degree of beta-Gal activity was affected by both the volume and type of carrier used to deliver the virus. At low volumes (0.5 ml, 1.3 ml/kg), beractant-treated animals demonstrated significantly greater pulmonary beta-Gal activity than saline-treated animals (p < 0.002) and untreated controls. At high volume (1.2 ml, 4 ml/kg), average beta-Gal activity was similar between groups treated with beractant or saline, but was more variable within the saline treated group. Higher volumes of delivery medium were associated with increased levels of beta-Gal expression regardless of the carrier used. Survanta was well tolerated by the animals and did not affect the duration of transgene expression. Exogenous beractant provides a useful medium for delivering recombinant adenoviruses to the lung when diffuse distribution of transgene expression is desired.
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PMID:Exogenous surfactant enhances the delivery of recombinant adenoviral vectors to the lung. 901 20

This study compares the effects of synthetic (Exosurf) and natural (Survanta) surfactants on infants with neonatal respiratory distress syndrome in Oman. Subjects included 89 patients, randomly allocated to receive one of the two surfactants. Results suggest that 43 and 46 of the total infants enrolled in the study were randomized to the Exosurf and Survanta groups, respectively. The oxygenation index in the Exosurf and Survanta groups at 24 hours were the same (10.1 and 7, respectively; P 0.05). The magnitude and rapidity of response, however, were greater for Survanta than for Exosurf. Moreover, when arterial/alveolar oxygen tension ratios (a/A) were compared, the Exosurf group had a significantly worse a/A ratio at 24 hours than the Survanta group. There were no statistically significant differences between the two groups when the complications of prematurity were compared. In conclusion, both preparations offer reasonable choices in the treatment of the respiratory distress syndrome. However, this should be weighed against the minor theoretical risks of transmission of infectious agents in a natural preparation, and the easier storage and transport of the synthetic surfactant.
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PMID:Comparative trial of artificial and natural surfactants in the treatment of respiratory distress syndrome of prematurity: experiences in a developing country. 1034 7