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Biomedical subjects

L Gortner

Publications and source records attributed to L Gortner.

At least 19 recordsLinked to original sources
PubMed1992

Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.

OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).

Bacteria↗
PubMed1992

Immunogenicity and immunomodulatory activity of bovine surfactant (SF-RI 1).

Respiratory distress syndrome in preterm infants can be treated successfully by endotracheal administration of a bovine surfactant preparation (SF-RI 1). Before the routine use of xenogenic surfactant preparations can be recommended, their immunogenicity as well as their in-vivo and in-vitro immunomodulatory activity have to be investigated. High titers of anti-surfactant antibodies were detected by a sensitive ELISA after immunizing rats, rabbits and mice with SF-RI 1. Repeated endotracheal administration of SF-RI 1 resulted in a humoral antibody response in three out of eight rabbits. After treatment of 34 preterm infants with SF-RI 1 (50-200 mg/kg), a humoral immune response to SF-RI 1 could not be detected. In-vitro restimulation of peripheral blood lymphocytes with SF-RI 1 after primary in-vivo administration did not result in cell proliferation as measured by 3H-thymidine incorporation. SF-RI 1 did not stimulate peripheral blood lymphocytes of neonates in vitro. The mitogenic response of these cells to stimulation with PHA, ConA or PWM was heavily impaired in the presence of SF-RI 1 concentrations increasing from 0.04 to 4 mg/ml. These data indicate that SF-RI 1 is immunogenic and that it may have an influence on lymphocyte proliferation in vivo.

Animals↗
PubMed1992

Prophylactic low-dose vancomycin treatment in very-low-birth-weight infants.

For the prophylaxis of septicemia with coagulase-negative staphylococci in a high-risk very-low-birth-weight population, we administered 5 mg/kg of vancomycin every 12 h. Distribution volume and half-life of vancomycin were determined. Serum peak and trough levels were obtained on day 3 of treatment. With this low-dose regimen, serum concentrations in the therapeutic range were achieved in 35 of the 45 patients. Distribution volume and half-life were 0.692 liters/kg and 7.4 h, respectively. The distribution volume was not related to the gestational age; the half-life in the group of patients with a gestational age < 30 weeks was considerably higher. The 10 small-for-gestational-age children had a significantly smaller distribution volume. The vancomycin trough levels correlated with the serum creatinine concentrations and, therefore, with the gestational age. Our study indicates that this low vancomycin dose is sufficient in very-low-birth-weight infants to achieve therapeutic serum levels, being suitable for both prophylaxis and sepsis therapy.

Creatinine↗
PubMed1992

Short-term outcome in infants with birth weights less than 1750 g born to mothers with HELLP syndrome.

Premature infants born to mothers with HELLP syndrome were reported to have a less favourable outcome compared to infants with uncomplicated maternal history. We investigated the short term outcome in 21 premature infants with birth weights less than 1750 g born to mothers with HELLP syndrome. Median birth weight was 1050 g (range 420 g-1750 g), corresponding gestational age 29 weeks (range 26-35 weeks). Mechanical ventilation for RDS was necessary in 15 infants. Intracranial hemorrhage was diagnosed in 2 infants, 1 of the surviving infants developed bronchopulmonary dysplasia. Acute renal failure was observed in 3 infants immediately after birth. Mortality was attributed to progressive respiratory failure in 2 patients (b.w. 420 g and 490 g) and persisting acute renal failure in 1 patient (b.w. 520 g) Leucocytopenia (less than 9000/mm3) was observed in 13 infants and thrombocytopenia (less than 115000/mm3) was noted in 4 infants during the first day. Eighteen infants survived. We conclude, that the short term outcome in infants born to mothers with HELLP syndrome is not as poor, as previously reported.

Birth Weight↗
PubMed1992

In vitro lymphocyte functions in the presence of bovine surfactant and its phospholipid fractions.

Endotracheal administration of human or xenogenic surfactant preparations is an effective treatment of the respiratory distress syndrome of preterm infants. The application of large amounts of phospholipids to the lung may result in a significant alteration of the local immune response. We studied the influence of the bovine surfactant preparation SF-RI 1 (Alveofact) on lymphocyte functions in vitro. PHA-induced cell proliferation and immunoglobulin synthesis in the presence of whole surfactant as well as six different defined phospholipids were investigated. A marked concentration-dependent suppression of immunoglobulin production independent of the immunoglobulin isotype and cell proliferation was observed in the range of 5 ng/ml-3 mg/ml of a single phospholipid (or SF-RI 1 respectively). It could be demonstrated that suppression of lymphocyte functions was only due to the phospholipid content of the surfactant preparation. These data indicate that in vivo immune functions may be significantly altered by the administration of exogenous surfactant. This may be particularly important in the presence of primary or secondary pulmonary infections.

Chromatography, Thin Layer↗
PubMed1992

Natural surfactant for neonatal respiratory distress syndrome in very premature infants: a 1992 update.

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)

Combined Modality Therapy↗
PubMed1991

Gonadal agenesis in a 46,XY female with multiple malformations and positive testing for the sex-determining region of the Y chromosome.

A full-term 46,XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.

Abnormalities, Multiple↗
PubMed1991

Drug utilization in very premature infants in neonatal intensive care units.

Neonatal drug utilization in very premature infants (gestational age (GA) 24-29 weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 +/- 1.2 (SD) weeks, b.w. 970 +/- 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and analgesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.

Dose-Response Relationship, Drug↗
PubMed1991

Does prophylactic use of bovine surfactant change drug utilization in very premature infants during neonatal period?

The efficacy of a bovine surfactant preparation (SF-RI 1) to increase survival without bronchopulmonary dysplasia (BPD) was studied in very premature infants in a multicenter, randomized sequential trial. Thirty-four infants were randomized to surfactant treatment, whereas 35 infants served as controls. As part of the study, pharmacotherapy with antibiotics, sedatives, catecholamines, diuretics, methylxanthines, mucolytics, muscle relaxants, digoxin, and indomethacin was registered during week 1 and weeks 2-4. As to the endpoint of the study a significantly increased survival rate without BPD was observed in surfactant-treated infants (76%) compared to controls (40%). Significant differences concerning drug utilization were found through week 1 with increased use of methylxanthines in surfactant-treated infants, which persisted during weeks 2-4 as well as a reduced incidence of diuretic therapy in surfactant-treated infants during weeks 2-4. These differences may be attributed to the shorter interval of mechanical ventilation in surfactant-treated infants (11 days) compared to controls (27 days), and to the above mentioned increased survival rate without BPD.

Animals↗
PubMed1990

Effects of bovine surfactant in premature lambs after intra-tracheal application.

Twenty-two premature lambs (gestational age 124-125 days, term 144-160 days) were intubated and supported by infant ventilators immediately after delivery. Respiratory rate was 60/min, inspiratory time 0.4 s, peak inspiratory pressure (PIP) 35 cm H2O, positive endexpiratory pressure (PEEP) 2 cm H2O, FiO2 1.0. 15 min after delivery 10 lambs (group 1) were treated with 35 mg/kg body weight bovine surfactant (SF-RI 1), whereas 1 ml/kg body weight saline was instilled in 12 lambs as controls (group 2). Sequential measurements of blood gases and acid base status (every 30 min) as well as continuous registration of PIP, PEEP, respiratory rate and tidal volume (TV) were performed in all lambs for 300 min. PIP was varied between 20 and 40 cm H2O in order to attain paCO2 values between 35 and 50 mm Hg. Significantly improved oxygenation was observed in group 1 lambs with maximum differences 30 min after delivery for 2 h. Ventilation was likewise affected: paCO2 and PIP values were significantly lower in the surfactant-treated animals (group 1). Total lung-thorax compliances (calculated from TV and delta P, i.e. PIP-PEEP) per kg body weight also significantly reflected the improvement of pulmonary function in group 1 compared to group 2 lambs. Intratracheal instillation of SF-RI 1 improved gas exchange in premature lambs, whereas control animals exhibited severe respiratory failure characteristic of respiratory distress syndrome (RDS).

Animals↗
PubMed1990

[Treatment of respiratory distress syndrome in very small premature infants with bovine surfactant].

In a clinical, uncontrolled study, bovine surfactant was administered intratracheally to 32 very low birth weight infants. In the first 18 patients, the dose was 20-40 mg/kg body weight (group 1, median birth weight 750 g) in the other 14 infants 40-50 mg/kg (group 2, median birth weight 840 g). The bovine surfactant was given, if the peak inspiratory pressures (PIP) were above 22-27 cm H2O depending on the infant's birth weight or whether the fraction of inspired oxygen (FiO2) was greater than 0.5. The FiO2 decreased from the pretreatment value of 0.7 to 0.46 after 1 hour, whereas PIP could not be lowered as rapidly as FiO2 (PIP from 29 to 26 cm H2O after 1 h). Surfactant treatment was more effective in group 2 comparing the reduction in FiO2 (delta FiO2 0.34 versus 0.16 in group 1 after 1 h), survival in group 2 was higher (71%) than in group 1 (56%). Our data are consistent with those of other groups using other natural surfactant preparations.

Birth Weight↗
PubMed1990

[Effect of a bovine surfactant in very low birth weight premature infants with congenital pneumonia].

15 VLBW-infants, who were classified to suffer from congenital pneumonia, were treated with a bovine surfactant. Mean gestational age was 25.5 weeks (range 23-27 weeks), mean birth weight was 700 g (range 530-930 g). Surfactant was instilled intratracheally at a mean dose of 41 mg/kg body weight (b.w.) (range 30-50 mg) 8 h after birth (range 6-12 h), if the fraction of inspired oxygen (FiO2) was greater than 0.5 or the peak inspiratory pressure (PIP) was greater than 22 cm H2O (b.w. less than 750 g) or greater than 25 cm H2O (b.w. 751-1000 g). Retreatment up to a total maximum of 4 doses of surfactant was permitted. Surfactant treatment reduced FiO2 from a pretreatment value of 0.79 to 0.50 one hour after application, however, 12 h later FiO2 had increased again to 0.75. Ventilation pressures showed a slight decrease during 12 h after surfactant treatment. 6 infants received 1 dose, multiple doses were given to 9 infants. 5 infants survived, 4 infants died from respiratory failure, 4 from sepsis and 2 from severe intracranial haemorrhage.

Bacterial Infections↗
PubMed1989

Acute and protracted effects of intratracheal surfactant application on internal carotid blood flow velocity, blood pressure and carbondioxide tension in very low birth weight infants.

As a part of a multicentre clinical trial of prophylactic treatment with bovine surfactant (SF-RI 1) given to immature infants below 31 gestational weeks, short term and protracted effects on cerebral haemodynamics were assessed by Dopplersonographic measurements of the right internal carotid artery. Measurements were performed every 10 min for 1 h after intratracheal application of the surfactant in ten treated infants. The results of additional measurements every 12 h up to the age of 100 h were compared with a control group. In single cases there were changes of time averaged mean maximum velocity (Vmax) of as much as 100% immediately after intratracheal surfactant application, although the mean short term and protracted variability of Vmax was the same as the protracted variability in the control group. Variability of mean arterial blood pressure and transcutaneous carbondioxide tension (tcpCO2) was even less. With proper adjustment of ventilatory settings intratracheal treatment with surfactant does not affect variability or absolute values of internal carotid Vmax, mean arterial blood pressure and transcutaneous pCO2 in low birth weight infants within 100 h after application.

Blood Flow Velocity↗
PubMed1989

Peritoneal dialysis in the treatment of metabolic crises caused by inherited disorders of organic and amino acid metabolism.

Four neonates who presented with coma secondary to hyperammonaemia resulting in central respiratory failure were treated with peritoneal dialysis for between 16 and 120 hours. Underlying diseases were maple-syrup-urine disease, propionic acidaemia and citrullinaemia in two patients. Clinical improvement was observed in three patients within 16 to 72 hours after institution of peritoneal dialysis. Biochemical analysis revealed a rapid reduction in plasma concentration of leucine, isoleucine and valine as well as their alpha-keto-analogues in the infant suffering from maple-syrup-urine disease. Correction of ammonia, glycine, alanine and propionic acid concentrations was observed in the infant with propionic acidaemia 24-72 hours after institution of peritoneal dialysis. Severe hyperammonaemia (1,000-2,500mumol/l) in two infants with citrullinaemia before peritoneal dialysis was treated successfully in one infant; whereas the second infant showed no clinical improvement despite amelioration of biochemical parameters. Glucose-absorption from peritoneal dialysis solution was in the range of 216-441 mg/kg/h.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Quantitative structure-activity studies of beta-adrenoceptor blocking drugs to decrease ventricular arrhythmias in guinea pigs.

The correlations between the physicochemical properties (n-octanol-buffer partition coefficients, P) of two series of N-alkylated and ring alkylated beta-adrenoceptor blocking phenoxypropanolamines and their antiarrhythmic activities were studied. For this purpose dose-response curves of the influence on the ventricular arrhythmia threshold (VAT) and on heart rate (HR) were determined in the anaesthetized guinea pig. The degree of N-alkylation correlated with the potency of the drugs to raise VAT and to lower HR. Intraventricular conduction was likewise depressed. Increasing ring alkylation did not consistently further increase biological activity. The combined data from series of drugs showed statistically significant parabolic correlations between hydrophobicity (log P' for pH 7.4) and the biological responses. It is concluded that the nonspecific antiarrhythmic and negative chronotropic activity of the investigated beta-adrenoceptor blocking drugs largely depend on their lipophilic properties. In addition steric and pharmacokinetic factors may be operative.

Adrenergic beta-Antagonists↗
PubMed1988

[Treatment of unilateral space-occupying pulmonary interstitial emphysema with positioning measures and high-frequency ventilation].

Five very low birthweight infants manifested unilateral tension pulmonary interstitial emphysema (PIE). All infants required intermittent positive pressure ventilation for respiratory distress syndrome. PIE was managed by positioning the infant on his (or her) side with PIE and by shortening the inspiratory time, in four patients also by shortening exspiratory time resulting in a higher frequency ventilation. PIE resolved within 3-6 days after institution of this treatment. This was paralleled by a reduction of FiO2 as well as peak inspiratory pressures. All infants could successfully be extubated 2-6 weeks after birth.

Combined Modality Therapy↗