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Biomedical subjects

D Berry

Publications and source records attributed to D Berry.

At least 37 records · Page 2Linked to original sources

Effects of distention of the preterm fetal lamb lung on lung function with ventilation.

Constant distending pressure when applied to the immature fetal lamb lung was reported to improve compliance and prevent the subsequent development of the respiratory distress syndrome after delivery. These experiments were designed to repeat those observations and identify the mechanism(s) responsible for the effects of constant distending pressure on subsequent lung function. The compliance of the lungs of exteriorized fetal lambs at 130 to 133 days gestational age increased 2.5-fold after 1 h of 15 cm of distending pressure. However, subsequent ventilation of the lambs exposed to distending pressure and control lambs resulted in comparable sequential compliance and blood gas and pH measurements. Severity of lung disease as reflected by the peak inspiratory pressure needed to normalize Pco2 values decreased as surfactant-saturated phosphatidylcholine pool sizes increased (r values greater than 0.90) and minimum surface tensions of alveolar washes decreased, but the distention procedure did not change these relationships. Distention of the fetal lung did result in an apparent increase in pulmonary blood flow in the fetus and an increased leak of labeled albumin from the vascular space to the lung interstitium and airways during the 1-h period of ventilation after delivery. However, the leak of protein into the lungs exposed to the distending pressures was not increased during the period of exteriorization and distention, suggesting that distention sensitized the preterm lung to leak protein with subsequent mechanical ventilation. The leak of labeled albumin out of the airways was not changed by distention, and total lung water was not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Adrenal Cortex Hormones

Comparison of four surfactants: in vitro surface properties and responses of preterm lambs to treatment at birth.

Natural sheep surfactant, rabbit surfactant, human surfactant, and surfactant TA were compared for in vitro surface properties and for responses of preterm lambs to treatment. Equivalent amounts of sheep, rabbit, and human surfactants were needed to lower the surface tension to less than 10 dynes/cm, whereas four times less surfactant TA similarly lowered the surface tension. Surface-spreading rates were similar for the surfactants. The surface adsorption of the batch of human surfactant tested was much slower than was adsorption of the other surfactants. Ventilation was significantly improved in all surfactant-treated lambs relative to the control lambs, indicating the general efficacy of the surfactant treatments. Overall, surfactant TA had the best in vitro characteristics, yet the preterm lambs treated at birth with surfactant TA had lower PO2 values and higher ventilatory requirements than did the sheep surfactant-treated lambs. The in vivo responses to rabbit surfactant were intermediate between the responses to sheep surfactant and to surfactant TA. Human surfactant resulted in the least effective clinical response. More of the phosphatidylcholine associated with human surfactant and surfactant TA was lost from the alveoli and lung tissue after four hours of ventilation than was lost from sheep or rabbit surfactant-treated lambs. More intravascular radiolabeled albumin leaked into the alveoli of the surfactant TA-treated lambs than sheep or rabbit surfactant-treated lambs. The four surfactants also had different sensitivities to the effects on minimum surface tensions of the soluble proteins present in alveolar washes. The study demonstrates that the range of clinical responses was not predictable based on the in vitro surface properties that we measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pharmacodynamics and side effects of flecainide acetate.

We compared side effects with flecainide trough levels and ECG intervals among 43 patients who received flecainide for up to 34 months. Flecainide plasma levels were higher when associated with cardiovascular side effects (mean 1063 ng/ml; range 296 to 2050 ng/ml) than when no side effects occurred (mean 609 ng/ml; range 89 to 1508 ng/ml; P less than 0.001). The PR interval (P less than 0.001), QRS interval (P less than 0.001), and the rate-corrected QT interval (P less than 0.001) were greater at the time of cardiovascular side effects, but the rate-corrected JT interval was not. The therapeutic-toxic window for flecainide plasma level was 381 ng/ml (at least 50% probability of efficacy) to 710 ng/ml (less than 10% probability of cardiovascular side effects). The risk of cardiovascular side effects increases at higher plasma levels of flecainide and is associated with greater increases in the PR and QRS intervals from baseline than are routinely observed during flecainide dosing.

Aged

Thymus deficiency in an infant with a chromosome t(18;22)(q12.2;p11.2)pat rearrangement.

The finding of an unbalanced t(18;22)pat chromosome rearrangement in a boy with multiple anomalies including apparent absence of the thymus is described. The observation is of interest because of the reported association of chromosome 22 rearrangements with the DiGeorge sequence. In contrast to previous reports of this association, the deletion involving chromosome 22 is confined to the short arm.

Abnormalities, Multiple

IS222, a new insertion element associated with the genome of Pseudomonas aeruginosa.

A new insertion element, IS222, was identified to be associated with the DNA of a mutant strain of the converting Pseudomonas aeruginosa bacteriophage D3. The insertion sequence was 1,350 base pairs in size and possessed terminal inverted repeats. The nucleotide sequence contained single cleavage sites for EcoRI and PvuI but none for BamHI, PstI, HindIII, SmaI, or SalI. By Southern hybridization analysis, no homology was found with genomic DNA from P. aeruginosa PAT or Escherichia coli. Genomic DNA from the phage host, P. aeruginosa PAO, contained two sequences homologous to IS222.

DNA Restriction Enzymes

Effect of lipopolysaccharide mutations and temperature on plasmid transformation efficiency in Pseudomonas aeruginosa.

We have isolated, and characterized electrophoretically, two new lipopolysaccharide-defective (rough) mutants of Pseudomonas aeruginosa strain PAO. These strains, AK1401 and AK1414, together with two previously characterized isolates, AK1012 and AK1282, were used as recipients in transformation experiments with plasmid pR01614 DNA. The roughest mutant, AK1282, was not transformable, while the transformation efficiency of AK1012, and to a lesser extent the wild-type strain, was dependent upon the growth temperature. The two new isolates which are less rough than AK1012 were transformed at a frequency equivalent to that of the wild type-strain.

Electrophoresis, Polyacrylamide Gel

Respiratory distress and surfactant inhibition following vagotomy in rabbits.

We used the model of bilateral cervical vagotomy of adult rabbits to cause respiratory failure characterized by pulmonary edema, decreased lung compliance, and atelectasis. We documented an 18-fold increase in radiolabeled albumin leak from the vascular space into alveolar washes of vagotomy vs. sham-operated rabbits (P less than 0.01). Despite a twofold increase in percent of prelabeled saturated phosphatidylcholine secreted (P less than 0.01), the alveolar wash saturated phosphatidylcholine pool sizes were not different. The minimum surface tensions were 19.6 +/- 2.5 vs. 9.4 +/- 2.2 dyn/cm for alveolar washes from vagotomy and control rabbits, respectively (P less than 0.01). The soluble proteins from alveolar washes inhibited the surface tension lowering properties of natural surfactant, whereas those from the control rabbits did not (P less than 0.01). When vagotomy rabbits in respiratory failure were treated with 50 mg natural surfactant lipid per kilogram arterial blood gas values and compliances improved relative to control rabbits. Vagotomy results in alveolar pulmonary edema, and surfactant dysfunction despite normal surfactant pool sizes and respiratory failure. A surfactant treatment can improve the respiratory failure.

Animals

Hemodynamic effects of high frequency ventilation in surfactant-treated preterm lambs.

We compared the hemodynamic status and left ventricular (LV) performance in 7 twin pairs of preterm lambs delivered at 124 days gestational age (83% of term gestation) and ventilated by either conventional ventilation (CV) or high frequency ventilation (HFV) at 15 Hz. The lambs were treated with suspensions of natural sheep surfactant to permit ventilation and survival, and ventilatory settings were adjusted to maintain physiologic blood gas values. The ductus arteriosus was occluded with a balloon catheter at 40-45 min of age to eliminate the variable of a left to right ductal shunt. Cineangiocardiographic, pressure, and blood flow measurements were made 1 and 2 h after ductal occlusion. At the same mean airway pressures, the heart rates, LV end-diastolic volumes, and mean arterial pressures were similar in both groups. LV stroke volumes, ejection fractions, LV outputs, and organ blood flows also did not differ between the two groups. When compared with CV, HFV provides comparable ventilation with no apparent deleterious hemodynamic effects in preterm surfactant-treated lambs with occluded ductus arteriosus.

Acid-Base Equilibrium

A protein that inhibits surfactant in respiratory distress syndrome.

A protein that interferes with surfactant function is present in the airways and alveoli of infants with respiratory distress syndrome (RDS). This inhibitor is also found in serum and amniotic fluid and presumably appears in the alveoli because of the abnormal protein leak present in the lungs of infants with RDS. This protein has a molecular weight of about 110,000 and is resistant to boiling or lipid extraction. As measured by radioimmunoassay, the ratio of inhibitor to phosphatidylcholine decreased from 8.1 +/- 2.3 early in the course of RDS to 0.7 +/- 0.1 on the day of extubation. The value at extubation was the same as that measured for preterm infants without RDS. The inhibitor to phosphatidylcholine ratio in airway samples from infants with RDS correlated significantly with simultaneously recorded pO2/FiO2 ratios and the peak inspiratory pressures used to normalized pCO2 values. These results are consistent with the concept that the inhibitor contributes to surfactant dysfunction and thus the respiratory failure characteristic of RDS.

Amniotic Fluid

Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species.

Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 +/- 1.8% per 24 h (mean +/- SE) of the injected doses of surfactant that contained from 0.41 to 10.2 mumol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.

Animals

Leakage of protein in the immature rabbit lung; effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.

Albumins

Lung protein leaks in ventilated lambs: effects of gestational age.

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.

Albumins

Distribution of pulmonary blood flow in relation to atelectasis in premature ventilated lambs.

To investigate the ability of the preterm, ventilated lung to redirect blood flow away from atelectatic regions, we studied lambs with respiratory distress syndrome and spontaneous atelectasis or atelectasis caused by bronchial obstruction with a balloon catheter. Pulmonary blood flow distributions were measured by quantifying 15-mu, microsphere-associated radioactivity within multiple pieces of lung. Lambs with well aerated or very atelectatic lungs had relatively uniform blood flow/gram lung in all pieces of lung. Blood flow was much less uniform in lungs with both aerated and atelectatic regions. In 9 lambs with spontaneous atelectasis that included 25 +/- 5% (mean +/- SE) of the lungs by weight, blood flow was 29 +/- 4% less to atelectatic than to aerated lung volumes (p less than 0.01). In 5 lambs with well-aerated lungs, 18 +/- 3% of the lung by weight was made atelectatic by balloon occlusion of a major lower lobe bronchus. There was a 44 +/- 11% decrease in blood flow to the atelectatic lung segments. These studies document the ability of the lung of the premature, ventilated lamb to shunt pulmonary blood flow away from atelectatic lung volumes.

Animals

Brain syndrome and WAIS PIO VIO difference scores corrected for test artifact.

Found an artifactual discrepancy of six units between VIQ and PIQ in Ss (N = 62) of low and bright, but not of mid-range IQ. Despite the matching of psychiatric cases for dominant and nondominant cognitive function, the discrepancy took the form of a lowered PIQ. The application of an equivalent correction to the PIQs of consecutive and unmatched psychiatric cases failed to improve the neurological predictive utility of the VIQ PIQ difference score. The latter failed statistically as an alerting device for abnormal CT and EEG results and whether a neurological event was recorded in the file. Despite the observation of a strong relationship between CT outcome and VIQ PIQ difference score evidence of cognitive intactness, it was concluded that difference score, whether corrected or not, should be used with extreme caution as a screening device for psychiatric cases who might be harboring an underlying brain syndrome.

Adult

A pharmacokinetic comparison of choline magnesium trisalicylate and soluble aspirin.

Claims that twice-daily dosage of choline magnesium trisalicylate (CMT) may alter salicylate disposal kinetics and result in sustained plasma levels were examined. Plasma levels, urine excretion and pharmacokinetics of salicylate were estimated in six men following the recommended twice-daily dose of CMT and a smaller dose of soluble aspirin. The plasma salicylate levels achieved with CMT were lower than those seen in previous studies but this probably reflected differences of methodology. Salicylate levels were not sustained between doses and elimination rates and half-life were similar for both preparations. No major alteration of disposal kinetics could be demonstrated for CMT with the dose used in the present study.

Administration, Oral