Nitrogen deprivation in Fusarium oxysporum promotes mycotoxin production via intermediates in the Krebs cycle and unreported methylmalonyl-CoA mutase activity.

INTRODUCTION: Fusarium oxysporum has a high affinity for lignin and cellulose-based substrates and is known to grow in a wide range of environments. It is these properties and its ability to produce mycotoxins that have contributed to its pathogenicity in cereal crops that can affect human and animal health when ingested. OBJECTIVES: Identify the mechanisms of mycotoxin production and map the functional output of F. oxysporum under varying growth conditions. METHODS: Liquid and gas-based chromatography coupled with mass spectrometry was used to identify and map the untargeted metabolic pathway of F. oxysporum grown using nitrogen limited and organic/inorganic nitrogen supplemented media. RESULTS: Over 1300 metabolites were identified, relating to 42 metabolic pathways. Of these, 520 metabolites merged at pyruvate (glycolysis), succinate (Krebs cycle) and aspartate-glutamate metabolic pathways. CoA depletion at the growth stage triggered the initiation of fatty acid and branched amino acid degradation. This in turn activated propionyl CoA carnitine acetyltransferase enzymes, resulting in nitrogen preservation (urea, putrescine and organic acids end-products). CoA then transferred into the TCA cycle via previously unreported ß-alanine and propionyl CoA metabolic pathways, the latter likely being a novel methylmalonyl-CoA mutase activity for F. oxysporum. CONCLUSIONS: The lower supplementation of inorganic nitrogen compounds (≤ 50 mM) and the elimination of nitrates/organic nitrogen sources resulted in TCA autophagy events that boosted mycotoxin-based metabolism and decreased overall F. oxysporum growth. Such knowledge of functional mycotoxin production can be used to supplement agricultural crops and reduce the risk of mycotoxin contamination in human and animal food supplies.

Application of metabolomics to understanding biofilms in water distribution systems: a pilot study.

Biofilms formed in pipes are known to contribute to waterborne diseases, accelerate corrosion and cause aesthetic taste and odour issues within the potable water supply network. This paper describes a pilot study, undertaken to assess the potential of using metabolomics to monitor bacterial activity in biofilms of an urban water network. Using samples from a water mains flushing programme, it was found that a profile of intracellular and extracellular metabolites associated with microbial activity could be obtained by analysing samples using gas chromatography mass spectrometry. Chemometric analysis of the chromatograms in conjunction with data from the mass spectrometer showed that it is possible to differentiate between biofilms from different pipe materials and planktonic bacteria. This research demonstrates that metabolomics has the potential for investigating biofilms and other microbial activity within water networks, and could provide a means for enhancing monitoring programmes, understanding the source of water quality complaints, and optimising water network management strategies.

The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.

OBJECTIVE: To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. DESIGN: An unblinded multicentred randomised controlled trial. SETTING: A total of 1543 women were randomised from 68 centres in 21 countries. POPULATION: Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. METHODS: Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. RESULTS: Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. CONCLUSION: External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates.

BACKGROUND: Chronic lung disease remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease (CLD). SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), CINAHL (1982 - July 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 - April 2007). SELECTION CRITERIA: Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight <1500 grams were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks PMA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using RevMan 4.2.10. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: Three additional trials were identified for inclusion in this update. Eleven trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. Four trials were excluded. The present review includes data analyses based on seven qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days [typical RR 1.05 (95% CI 0.84, 1.32); typical RD 0.02 (95% CO -0.07, 0.11)] or at 36 weeks PMA [typical RR 0.97 (95% CI 0.62, 1.52); typical RD 0.00 (95% CI -0.07, 0.06)], when analyzed either for all randomized infants or among survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks PMA. There were no statistically significant differences in adverse events between groups. AUTHORS' CONCLUSIONS: Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Cytomegalovirus transmission to extremely low-birthweight infants through breast milk.

AIM: To determine the incidence, timing and clinical significance of acquired postnatal cytomegalovirus (CMV) in extremely low-birthweight (ELBW) infants. METHODS: Prospective, longitudinal surveillance study. ELBW infants were recruited in the first week of life. Maternal blood was tested for CMV-specific IgG antibodies. Weekly urine samples were obtained from infants for CMV culture and rapid antigen testing. Data were collected regarding clinical course and breast milk intake. RESULTS: Of 181 eligible infants, 119 infants, born to 101 mothers, were enrolled. Eighty of the 101 mothers had their serum checked for CMV status. Seventy percent of those tested were seropositive for CMV. Of the 65 infants born to seropositive mothers, 94% received breast milk during their hospital stay. Complete urine collection was obtained in 92 infants. CMV was cultured from the urine of only four infants, all of whom were born to seropositive mothers. Only one of these four infants was symptomatic. The range at which CMV was first detected was between 48 and 72 postnatal days of age. CONCLUSIONS: Despite a very high CMV seropositivity rate in mothers of ELBW infants, and the previously reported high rate of CMV excretion into breast milk, the incidence of postnatal CMV transmission was extremely low in our study.

The activity of the von Willebrand factor cleaving protease ADAMTS-13 in newborn infants.

BACKGROUND: Unusually large von Willebrand factor (VWF) multimers have been observed in patients with thrombotic microangiopathies (TMA), and absence of the VWF cleaving protease ADAMTS-13 activity is considered to be involved in the etiology of TMA. Increased amounts of large multimers of VWF have also been identified in neonates. OBJECTIVE: We assessed ADAMTS-13 activity in healthy neonates, children and adults to establish baseline levels. PATIENTS AND METHODS: Cord blood was collected from 38 full-term newborns; venous samples were taken from 15 neonates on day 2-3 of life. Seventeen children, 24 healthy adults and seven patients with TMA were studied as well. ADAMTS-13 activity was quantified by the binding of the subjects' plasma VWF to collagen before and after enzyme activation. The multimer distribution of VWF was also determined. RESULTS: Neonates and children had percentage ADAMTS-13 activity similar to adults. However, two groups were apparent in the cord blood samples: while 28/38 newborns had percentage activity within the normal range of healthy adults (102 +/- 3.0%), 10 had significantly lower percentage activity (53 +/- 1.1%; P < 0.0001) that normalized by day 2-3. The VWF multimer distribution was the same in all cord blood samples and was not different compared with children and adults. High-molecular-weight VWF multimers were significantly increased in the 2-3-day-old neonates and in TMA patients. CONCLUSIONS: Although ADAMTS-13 activity was similar in neonates compared with adults, 26% of neonates had mildly reduced activity. Further studies are needed to investigate the complex interaction of VWF production and secretion with its size control by ADAMTS-13 in different age groups.

Oesophageal perforation in preterm neonates: not an innocent bystander.

OBJECTIVE: To compare the clinical course and neonatal outcomes of preterm infants with oesophageal perforation (OP). METHODS: Retrospective case control study of infants admitted between 1994 and 2001 and diagnosed with OP was performed at two tertiary care centres in Toronto, Canada. One control per case was matched by the gestational age and the month of birth. Occurrence of air leak syndrome/pleural effusion requiring drainage, the duration of supplemental oxygen and the time to attain full feeds were compared. RESULTS: Ten cases of OP were identified. The commonest clinical presentation was air leak syndrome/pleural effusion. There was a statistically significant increase in the time to attain full enteral feeds in OP group (P = 0.02). The duration of supplemental oxygen was prolonged in infants with OP, however, this was statistically insignificant (P = 0.20). The infants were managed conservatively and perforation healed in all. CONCLUSION: Oesophageal perforation is a rare but important complication of modern neonatal intensive care setting. The diagnosis of OP should be considered in infants who present with sudden/acute deterioration in their respiratory status following procedures involving pharyngeal region. Conservative management in an otherwise uncomplicated case leads to complete recovery in neonates.

The influence of significant others on attitudes, subjective norms and intentions regarding dietary supplement use among adolescent athletes.

Dietary supplement use has increased significantly over the past decade. The use of supplements among adolescents seems to be influenced by their beliefs and attitudes. The influence of coaches, parents, and athletic trainers also may be important. The purpose of this study was (1) to determine whether attitudes are a better predictor of adolescents' intentions to use dietary supplements than are subjective norms, and (2) to assess the influence of significant others (coaches, parents, and trainers) on attitudes, subjective norms, and intentions among adolescent athletes. Adolescents (N = 1,626) who were enrolled in grades six through twelve in nine public schools completed a self-report questionnaire that measured attitudes, subjective norms, and intentions regarding dietary supplement use. Results indicated that attitudes were a better predictor of intentions to use dietary supplements than were subjective norms. It was also found that trainers had more influence on the attitudes, subjective norms, and intentions of adolescents regarding supplement use than did parents and coaches. Implications for prevention are addressed.

Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates.

BACKGROUND: Chronic lung disease remains a common complication amongst preterm infants. There is increasing evidence that inflammation play an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties corticosteroids is an attractive intervention strategy. However, there are growing concerns regarding short and long term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease(CLD). SEARCH STRATEGY: Systematic search in accordance with Cochrane Neonatal Review Group. Randomized and quasi-randomized trials were identified by searching MEDLINE, Embase, CINAHL, the Cochrane Library, reference lists of published trials and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight 1500 grams or less were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks corrected gestational age (CGA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks CGA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using Revman 3.1. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, number needed to treat (NNT) was calculated. MAIN RESULTS: Eight trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. The study by Kovacs 1998 was excluded as investigators evaluated the impact of a combination of systemic and inhaled corticosteroid for prevention of CLD. Seven trials qualified for inclusion in this review but data from two of these studies are awaiting assessment. Thus, the present review includes data analyses based on five qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days or at 36 weeks CGA, when analyzed either for all randomized infants or amongst survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks CGA. The meta-analysis supports a reduction in the need for systemic steroids, RR 0.78 (95% CI 0.62, 0.99), RD -0. 097 (95% CI -0.187, -0.008); however statistical heterogeneity was noted. The number needed to treat (NNT) to reduce the need for systemic steroid was 10 (95% CI 5.3, 125). There were no statistically significant differences in adverse events between groups. REVIEWER'S CONCLUSIONS: There is no evidence from the trials reviewed that early administration (in the first 2 weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. There was a reduction in the need for systemic steroids. Although this difference was statistically significant, there was significant heterogeneity between studies and the upper limit of the 95% CI for this outcome was very close to no effect. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Functional and antigenic concentrations of alpha-1-proteinase inhibitor after administration for the prevention of chronic lung disease of prematurity.

OBJECTIVE AND METHODS: Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficiency to impede the development of emphysema. A1PI supplementation may also be useful for protecting premature neonates who receive mechanical ventilation from the development of chronic lung disease (CLD). However, the pharmacokinetics of exogenous A1PI in this population are unknown. We attempted to determine the disposition of A1PI in premature infants with birth weight 600-1,250 g who received 60 mg/kg on days 0, 4, 7 and 14 in a randomized, placebo-controlled, double-blind trial. Functional and antigenic plasma concentrations of A1PI were measured at specified time points. RESULTS: On both functional and antigenic assays, concentrations began in the normal adult range and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the treatment and placebo groups. CONCLUSIONS: The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the adult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maintain A1PI plasma concentrations above baseline.

Outcome following pulmonary haemorrhage in very low birthweight neonates treated with surfactant.

AIM: To determine if pulmonary haemorrhage after surfactant treatment increases short and long term morbidity and mortality in neonates weighing <1500 g at birth. METHODS: Neonates weighing <1500 g at birth who developed pulmonary haemorrhage after surfactant treatment were identified from a database. Based on the change in FIO2, pulmonary haemorrhage was classified as mild, moderate, or severe. Controls were matched for birthweight, gestational age, Apgar scores and hospital. Chronic lung disease (CLD) was defined as the need for supplemental oxygen at 36 weeks of corrected gestational age. RESULTS: From January 1990 to May 1994, 94 of 787 (11.9%) neonates treated with surfactant developed pulmonary haemorrhage. Ten were excluded because of incomplete data or lack of controls. Eighty four were included for further analysis; two acceptable matches were found in 75, while only one match was possible in nine. For the pulmonary haemorrhage group, the mean (SD) birthweight was 917 (238) g, gestational age 27 (1.9) weeks. Pulmonary haemorrhage was severe in 39 (46%), moderate in 22 (26%), and mild in 23 (27%). Moderate and severe pulmonary haemorrhage were associated with chronic lung disease or death, OR 4.4 (confidence interval 1.3-15.7) and OR 7.8 (CI 2.6-28), respectively, while mild pulmonary haemorrhage was not, OR 1.8 (CI 0.55-5.8). pulmonary haemorrhage was associated with major intraventricular haemorrhage (IVH), OR 3.1 (CI 1.5-6.4), but not with minor IVH, OR 1.3 (CI 0.6-2. 6). In the survivors who could be assessed at >/=2 years, the differences in neurodevelopmental outcome among the two groups were not significant. CONCLUSIONS: In neonates treated with surfactant moderate and severe pulmonary haemorrhage is associated with an increased risk of death and short term morbidity. Pulmonary haemorrhage does not seem to be associated with increased long term morbidity.

Reducing neutrophil elastase-induced lung injury.

The first trial of alpha1-proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity was recently completed. Receipt of four intravenous doses of the medication was associated with a trend towards a reduction in respiratory morbidity. A dose-ranging trial is in progress.

A comparison of underwater bubble continuous positive airway pressure with ventilator-derived continuous positive airway pressure in premature neonates ready for extubation.

OBJECTIVE AND METHODS: As the result of vigorous bubbling, infants receiving continuous positive airway pressure (CPAP) by an underwater seal (bubble CPAP) were observed to have vibrations of their chests at frequencies similar to high-frequency ventilation (HFV). We performed a randomized crossover study in 10 premature infants ready for extubation to test whether bubble CPAP contributes to gas exchange compared to conventional ventilator-derived CPAP. Measurements of tidal volume and minute volume were made using the Bear Cub neonatal volume monitor, and gas exchange was measured using an oxygen saturation monitor and a transcutaneous carbon dioxide (tcpCO2) monitor. RESULTS: There was a 39% reduction in minute volume (p < 0.001) and a 7% reduction in respiratory rate (p = 0.004) with no change in tcpCO2 or O2 saturation for infants supported with bubble versus ventilator-derived CPAP. CONCLUSIONS: The lack of difference in blood gas parameters associated with a decrease in the infant's minute volume and respiratory rate with bubble CPAP compared with ventilator-derived CPAP suggests that the chest vibrations produced with bubble CPAP may have contributed to gas exchange. Bubble CPAP may offer an effective and inexpensive option for providing respiratory support to premature infants.

alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial.

BACKGROUND: An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD. DESIGN: A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28. RESULTS: A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups. CONCLUSIONS: In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely.

Point-of-care glucose testing in the neonatal intensive care unit is facilitated by the use of the Ames Glucometer Elite electrochemical glucose meter.

OBJECTIVE: To evaluate the Ames Glucometer Elite glucose meter for use in point-of-care glucose testing in the neonatal intensive care unit. METHODS: An important part of our quality control program involves a weekly comparison of glucose values obtained with each of the seven Elite analyzers and the Beckman CX7 analyzer located in the central laboratory. Each "split" sample involves measurement of the glucose by using the Elite analyzer in a sample of blood obtained from a heel stick at the bedside, followed by bleeding ("milking") 150 to 200 microl (4 to 5 drops) of blood into a heparinized microcontainer. This process should take no longer than 1 to 2 minutes, whereupon the microcontainer is placed on ice and sent to the laboratory. The values obtained were compared by regression analysis. Imprecision of the Elite meter was estimated at four levels of blood glucose concentration and on a normal-level quality control sample used for a period of 4 months. RESULTS: Regression analysis between the glucose values obtained on the Elite meter and the CX7 meter revealed r = 0.93, p less than 0.0001, n = 188, Sy/x = 0.59 mmol/L, intercept = 0.47 +/- 0.14 mmol/L (1 SEM), and slope = 0.91 +/- 0.028 (1 SEM). When we switched to on-ice delivery of split samples to reduce metabolic activity during transport of the specimens to the laboratory, scatter about the regression line was decreased and the Sy/x was reduced to 0.45 mmol/L. Before the on-ice delivery of split samples, 24% of the Elite analyzer's results differed from those of the CX7 analyzer by more than 15%, whereas only 8% differed from those of the CX7 meter by more than 15% after on-ice delivery of split samples. Of 30 samples read as "Lo" by the Elite meter, 29 were less than 2.2 mmol/L on the CX7 meter, whereas only 1 was 2.2 mmol/L. The coefficients of variation taken as a measure of imprecision were less than 5% for the normal-level aqueous control and less than 5% for four heel-stick blood glucose levels. CONCLUSIONS: The Ames Glucometer Elite analyzer can be used with confidence in measuring heel-stick blood glucose concentrations at the bedside in the neonatal intensive care unit. Hypoglycemic blood samples are reliably detected. As with adults, meticulous technique should be followed to prevent filling defects, and all split samples should be analyzed promptly on the CX7 analyzer, with delivery to the laboratory on ice. Unlike previous generations of glucometers, the Elite meter has been well accepted by the neonatal nursing staff.

Surfactant replacement in neonates with early chronic lung disease.

OBJECTIVE: To study the effect of a single dose of exogenous bovine surfactant on oxygen and ventilatory requirements of neonates with early chronic lung disease. STUDY DESIGN: Prospective pilot study. SETTING: Three regional neonatal intensive care units. METHODS: Infants 7 to 30 days old with birth weights less than 1500 g were eligible if they required a fraction of inspired oxygen (FIO2) of more than 0.4, had stable ventilatory requirements for 24 hours before study entry, and showed diffuse haziness on chest radiographs. Those with patent ductus arteriosus or active infection or those receiving steroid therapy were excluded. After treatment with the surfactant, differences in FIO2 and the ventilator efficiency index were analyzed using the Wilcoxon signed rank test. RESULTS: Ten patients were recruited. Median values (range): birth weight, 693 g (530 to 1100 g); gestation, 25 weeks (24 to 27 weeks); and postnatal age at study entry, 13 days (9 to 30 days). The FIO2 decreased significantly between 0 and 1 hour after surfactant administration, from a median (range) of 0.67 (0.47 to 0.88) to 0.39 (0.28 to 0.63). This effect was sustained for 24 hours (median FIO2, 0.36). Although the FIO2 subsequently increased to 0.49 (range, 0.35 to 0.88) at 72 hours, it was significantly lower than that entry before the study. There was a trend toward an increase in the ventilator efficiency index at 24 and 48 hours. CONCLUSIONS: A single dose of surfactant is effective in reducing oxygen requirements in neonates with early chronic lung disease. Surfactant replacement may be useful adjunctive therapy in these neonates.

Surfactant therapy in neonates with respiratory deterioration due to pulmonary hemorrhage.

OBJECTIVE: To study the effect of exogenous bovine surfactant on oxygen and ventilatory requirements in neonates with respiratory deterioration due to pulmonary hemorrhage. DESIGN: Retrospective case series. SETTING: Three regional neonatal intensive care units. METHODS: Infants who received surfactant following a clinically significant pulmonary hemorrhage during the time period July 1991 to December 1993 were identified from a database. Infants were excluded if any other cause was found to explain their deterioration. The primary outcome was change in respiratory status following surfactant therapy, as reflected by oxygenation index (OI) and arterial/Alveolar oxygen ratio. Data points were taken as averages of 3 through 6 hours and 0 through 3 hours for the 6 hours before and after surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. RESULTS: Fifteen patients fulfilled inclusion criteria. Median values (range): birth weight, 960 g (595 to 4045); age at pulmonary hemorrhage, 24.4 hours (0.3 to 62); and interval between pulmonary hemorrhage and surfactant therapy, 10 hours (3.7 to 46.5). Mean OI improved from 24.6, at 0 to 3 hours presurfactant, to 8.6 at 3 to 6 hours postsurfactant (P < .001). No patient deteriorated following surfactant therapy. The primary respiratory diagnosis was respiratory distress syndrome (RDS) in 8, meconium aspiration syndrome in 3, and isolated pulmonary hemorrhage in 4. All those with RDS had also received surfactant before their pulmonary hemorrhage. CONCLUSIONS: Exogenous surfactant appears to be useful adjunctive therapy in neonates with a clinically significant pulmonary hemorrhage. Its use for this indication should be further investigated by a randomized controlled trial.

Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis.

We investigated the presence of nitric oxide (NO) synthase in ovarian follicular cells obtained from women undergoing in vitro fertilization procedures. Endothelial NO synthase messenger RNA was demonstrated by polymerase chain reaction amplification of reverse transcribed RNA. NO synthase was localized to granulosa-luteal cells by immunocytochemistry, using a monoclonal antibody. Ovarian follicular cell NO synthase enzyme activity was confirmed by measuring the conversion of L-arginine to citrulline. To investigate the effect of NO on granulosa-luteal cell steroidogenesis, NO synthase inhibitors and NO donors were added to cell cultures. NG-Monomethyl-L-arginine and N-nitro-arginase methyl ester, selective inhibitors of NO synthase, significantly increased estradiol secretion by granulosa-luteal cells. S-Nitroso-L-acetyl penicillamine (S-NAP) and S-nitroso glutathione, NO donors, caused a dose-dependent decrease in both estradiol and progesterone secretion. The decrease by S-NAP was reversed by hemoglobin, which binds free NO. Although S-NAP increased the concentration of cGMP in granulosa-luteal cells, cGMP analogs had no effect on steroidogenesis in cell cultures. S-NAP and native NO in solution decreased cellular and microsomal aromatase activities. We conclude that NO synthase is present in human granulosa-luteal cells and that NO inhibits estradiol secretion independent of cGMP by directly inhibiting aromatase.

Bovine surfactant therapy and retinopathy of prematurity.

We reviewed the results of three randomized clinical trials of prophylactic bovine surfactant therapy on babies under 30 weeks gestational age to assess the effects of this treatment on the frequency and severity of retinopathy of prematurity (ROP). Of the 119 babies who received surfactant treatment, 54 (45.4%) had ROP compared to 33 (47.1%) of the 70 babies in the control group. Stage 2 ROP or greater was noted in 10 (8.4%) babies in the treatment group and in 10 (14.3%) of the untreated group. Prophylactic bovine surfactant replacement therapy does not have a significant effect on the frequency of ROP in preterm babies. The severity of ROP also appears to be unaffected by surfactant.

Selection of neighborhood controls for a study of factors related to the diagnosis of cervical cancer.

The level of effort required to generate neighborhood controls for a statewide matched case-control study of cervical cancer was investigated, with the aim of identifying hard-to-reach demographic subgroups. Cross reference telephone directories were used to identify households on the same street as the case. Letters were then sent to the households, followed by 'phone calls. A total of 2920 households were contacted to obtain 147 controls. Overall, 63.6% of age-eligible contacts participated in the study. In 49.3% of all households the major reason for not obtaining a control was "no age-eligible women". Level of effort required to obtain a matched control was greater for black women than for white women--on average 24 letters and 40 'phone calls for black women vs 12 letters and 20 calls for white women. Fewer eligible younger women refused to be interviewed than older. No marked differences were noted when the data were stratified by urban-rural area of residence.