Coronary artery calcification, common carotid artery intima-media thickness and aortic pulse wave velocity in patients on peritoneal dialysis.

An increasing body of evidence suggests that atherosclerosis in patients with uremia differs from that found in general population in terms of advancement and localization of vascular lesions. It has also been suggested that different non-invasive techniques of vascular system evaluation are designed to show different types of lesions (i.e. vascular calcification, stiffness or 'classical' atherosclerosis). The aim of the study was to search for possible associations between results obtained with three different non-invasive methods of vascular system assessment in three different vascular sites in patients treated with peritoneal dialysis (PD). 61 patients (28 F, 33 M), mean age of 50.4+/-13.6 years, on maintenance PD for a median period of 10 months (range 1-96 months) were included. Coronary artery disease (CAD) was present in 21 subjects. In all subjects coronary artery calcification score (CaSc) using multi-row spiral computed tomography (MSCT), aortic pulse wave velocity (AoPWV) and ultrasound-based common carotid artery intima-media thickness (CCA-IMT) were performed as methods for assessing coronary calcium burden, arterial stiffness and atherosclerosis, respectively. Median value of CaSc equaled 11.5 Agatston units (range 0-5502.8 units). Median AoPWV was 10.4 m/s (range 7.56-18.1 m/s), and median CCA-IMT-0.6 mm (range 0.3-1.0 mm). In 16 patients (26.2%) at least one plaque in at least one common carotid artery was found on ultrasound. CaSc correlated with AoPWV (R=0.32, p<0.01) and with CCA-IMT (R=0.35, p<0.005), whereas no association was found between AoPWV and CCA-IMT. AoPWV, but not CaSc nor IMT correlated with blood pressure. The values of CCA-IMT and AoPWV increased together with consecutive Agatston categories (with p<0.001 for differences in AoPWV and p<0.05 for CCA-IMT). Patients with at least one plaque found in at least one CCA and patients with CAD were characterized with significantly higher values of CaSc, IMT and PWV, when compared to plaque-free and CAD- negative subjects, respectively. Association between CaSc and both IMT and PWV may suggest that the mechanism of three assessed vascular pathologies may be based, to some extent, on the process of pathologic calcium-phosphate deposition. Lack of correlation found between PWV and IMT may suggest that aortic stiffness and carotid atherosclerosis may partially differ in their pathologic background and/or are dissociated in time.

Mass changes and dissolution of platinum during electrical stimulation in artificial perilymph solution.

The electrochemistry of platinum electrodes in artificial perilymph solution subjected to cyclic and steady-state potentials was studied by a quartz crystal electrochemical microbalance and by analysis of electrolyte for dissolved platinum. The effect of amino acid adsorption appears to be one of blocking sites for platinum oxidation and oxide reduction, a process in which the amino acid competes with chloride from phosphate-buffered saline. For amino acids such as cysteine, which are known to interact strongly with platinum, the voltammograms became nearly featureless and only a small change in mass was observed during cycling of the potential. There were no mass changes of an electrode in solution containing human serum albumen, but its presence did inhibit dissolution of platinum. The overall magnitudes of dissolved platinum found in the buffered solutions were low, remaining below 5 ppb in most cases. Dissolution was greatest in solutions containing high concentrations of cysteine. Extrapolation of the results to implanted auditory prosthesis electrodes indicated that platinum dissolution would not lead to toxic concentrations in the body.

Aerosolized surfactant treatment of preterm lambs.

To evaluate the potential for aerosolized surfactant treatments of surfactant deficiency, twin lamb fetuses were delivered at 130-132 days gestational age and received nebulized natural surfactant (Neb NS), nebulized Survanta (Neb Surv), tracheally instilled natural surfactant (Inst NS), or nebulized saline (Neb Saline). Neb NS and Neb Surv groups had significant increases in ventilatory efficiency index and dynamic compliance values (P less than 0.05). Both groups also had pressure-volume curves that were comparable to the Inst NS group. The Neb Saline control group had deterioration of the ventilation efficiency index and dynamic compliance values over time as well as pressure-volume curves that demonstrated smaller lung volumes compared with all three surfactant-treated groups (P less than 0.01). Delivery of aerosolized surfactant to the lung was only approximately 2 mg lipid/kg for the nebulized groups, a dose one-twentieth of that previously noted to be effective in instillation protocols. Distribution histograms of the aerosolized surfactant-treated groups differed from the instilled animals as there was more deposition in the right upper lobes and tracheae in the nebulized groups compared with the instilled group (P less than 0.05). Pulmonary blood flow was not altered by aerosolized surfactant treatment. Administration of aerosolized surfactant to preterm lambs improved lung function at a very low surfactant dose.

Corticosteroid and thyrotropin-releasing hormone effects on preterm sheep lung function.

Four groups of twin sheep fetuses were catheterized at 121 days of gestational age and intravenously infused with saline, 0.75 mg.kg-1.h-1 cortisol for 60 h, five intermittent bolus injections of 5 micrograms/kg thyrotropin-releasing hormone (TRH) at 12-h intervals, or both hormones before delivery at 128 days. At birth, the lambs were randomized to receive surfactant or no treatment. Surfactant treatment improved lung function of all the groups. Corticosteroids alone and in combination with TRH improved compliance and gas exchange as well as pressure-volume curves. Corticosteroids alone dramatically decreased the recovery of intravenously administered radiolabeled albumin in the lung tissue and air space and improved the pulmonary response to surfactant treatment. There were no additional effects of TRH when given with corticosteroids on lung function or albumin leak. There were no changes in alveolar surfactant-saturated phosphatidylcholine pool sizes after any hormone treatment. The single significant effect of combined corticosteroid and TRH treatment was a fivefold increase in surfactant protein A in alveolar lavage fluid relative to all other groups.

Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant.

Adult sheep (35 +/- 3 kg) underwent saline lung lavage and 1.5 h of mechanical ventilation to induce acute lung injury. Animals received 100 mg lipid/kg body wt of tracheally instilled surfactant (Inst Surf) or either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) and were killed 3 h later. Inst Surf and Neb Surf groups had significant improvements in oxygenation (P < 0.01) and peak inspiratory pressures (PIP) (P < 0.05) compared with pretreatment values. Improvements in oxygenation and PIP for Inst Surf animals were significantly greater than for Neb Surf animals (P < 0.05). Volumes of maximal pressure of quasi-static pressure-volume curves measured at the time the animals were killed were significantly greater for Inst Surf and Neb Surf animals than for animals given Neb Saline (P < 0.05). Alveolar recovery of exogenous surfactant was 100 times greater for Inst Surf animals (1,732 +/- 70 mg) than for Neb Surf animals (15.3 +/- 2.9 mg) at the time they were killed. Although there were no differences in exogenous surfactant distribution patterns at the lobar level between the two surfactant-treated groups, distribution histograms calculated for 10-g lung pieces revealed the Neb Surf animals had significantly more pieces within 25% of the mean value of 1.0 (42.7 +/- 6.9%) than did Inst Surf animals (20.8 +/- 5.5%) (P < 0.01). Exogenous surfactant therapy improved lung function with significantly different quantities of surfactant deposited in lung tissue for the two delivery methods evaluated.

Chronic electrical stimulation of the auditory nerve using high surface area (HiQ) platinum electrodes.

High surface area cochlear implant electrodes with much smaller geometric surface areas than current designs might be used in the future to increase the number of stimulating electrodes along the carrier. Potential problems with an increase in charge density for a common stimulus resulting from decreasing the geometric surface area would be reduced by the enlarged real surface area of such electrodes. Electrochemically modified (HiQ) platinum (Pt) electrodes, with a real surface area approximately 75 times greater than the current standard Pt electrodes of the same geometric size, had shown in vitro a low polarization (Z(pol)) and electrode impedance (Z(e)), as well as a low residual direct current (DC). In this study we examined the chronic performance of HiQ electrodes in cats, which were bilaterally implanted with a two-channel HiQ or standard Pt scala tympani electrode array and unilaterally stimulated for periods of up to 2390 h. Stimuli consisted of 50 micros/phase charge-balanced biphasic current pulses presented at 2000 pulses/s/channel with a 50% duty cycle. Electrode impedance (Z(e)), access resistance (R(a)) and polarization impedance (Z(pol)) were calculated from current and voltage measurements obtained periodically throughout the implantation period. Immediately following implantation HiQ electrodes showed a significantly smaller Z(pol), resulting in a reduced Z(e) (P<0.0001) compared to standard electrodes, while there was no significant difference between R(a) of both electrode designs (P=0.91). Subsequently, Z(e) generally increased mainly due to a rise in R(a), which dominated Z(e) and obliterated the effect of a lower Z(pol) on Z(e) in HiQ electrodes. Peak R(a) levels correlated closely (r=0.85) with the amount of intracochlear fibrous tissue found adjacent to the array. Following explantation of the array, voltage waveforms for both electrode designs recorded in saline were again very similar to those recorded immediately after implantation. Mean DC levels were consistently lower for HiQ electrodes compared with standard electrodes (22.45 nA vs 134.7 nA). Histopathological examination of corresponding cochlear sections comparing the stimulated test side with the unstimulated control side showed no significant difference (P>0.05) for either animals implanted with HiQ electrodes (n=6) or standard electrodes (n=2). Nor were there any significant differences between the spiral ganglion cell density of the basal turn implanted with HiQ or standard electrodes for both the stimulated test (P=0.31) and the unstimulated control side (P=0.84). Although these findings are based on a small group of animals implanted with standard electrodes (n=2), and those negative statistical results could potentially be due to the small sample size, similar spiral ganglion cell survival was found in a previous study of a larger group of animals using standard electrodes stimulated with the same stimulus paradigm as in the present study [Xu et al. (1997) Hear. Res. 105, 1-29]. Our data indicate that while some initial advantages of HiQ electrodes are lost during chronic implantation due to intracochlear fibrous tissue growth, low DC levels and the high surface area appear to be maintained, suggesting that HiQ electrodes may have important clinical applications.

Electrical stimulation of the auditory nerve: direct current measurement in vivo.

Neural prostheses use charge recovery mechanisms to ensure the electrical stimulus is charge balanced. Nucleus cochlear implants short all stimulating electrodes between pulses in order to achieve charge balance, resulting in a small residual direct current (DC). In the present study we sought to characterize the variation of this residual DC with different charge recovery mechanisms, stimulation modes, and stimulation parameters, and by modeling, to gain insight into the underlying mechanisms. In an acute study with anaesthetised guinea pigs, DC was measured in four platinum intracochlear electrodes stimulated using a Nucleus C124M cochlear implant at moderate to high pulse rates (1200-14,500 pulses/s) and stimulus intensities (0.2-1.75 mA at 26-200 microseconds/phase). Both monopolar and bipolar stimulation modes were used, and the effects of shorting or combining a capacitor with shorting for charge recovery were investigated. Residual DC increased as a function of stimulus rate, stimulus intensity, and pulse width. DC was lower for monopolar than bipolar stimulation, and lower still with capacitively coupled monopolar stimulation. Our model suggests that residual DC is a consequence of Faradaic reactions which allow charge to leak through the electrode tissue interface. Such reactions and charge leakage are still present when capacitors are used to achieve charge recovery, but anodic and cathodic reactions are balanced in such a way that the net charge leakage is zero.

The use of congo red as a lyotropic liquid crystal to carry stains in a model immunotargeting system--microscopic studies.

The lyotropic liquid crystal dye-Congo Red was used as a carrier in a model immunotargeting system constructed from sheep red blood cells (SRBC) representing the antigen target and rabbit IgG anti-SRBC as the specific driving immunoglobulin. Rhodamine B and Hemin stains were chosen as example chemicals carried to the target. The carried stains were introduced to the micellar organization of Congo Red by intercalation. Preserving its supramolecular organization, Congo Red binds spontaneously and selectively to antibodies that have altered structure extorted by interaction with the antigen in the immune complex. The functionality of the studied immunotargeting model was verified by fluorescence and electron microscopy. The results indicate that the supramolecular nature of protein ligands offers new ligation capabilities possibly useful for carrying stains or drugs in immune-oriented systems.

An association between aortic pulse wave velocity, blood pressure and chronic inflammation in ESRD patients on peritoneal dialysis.

Increased aortic pulse wave velocity (AoPWV) has been identified as a risk factor for cardiovascular morbidity in the general population and in patients on dialysis. Most of the studies in ESRD patients refer to subjects on hemodialysis. Influence of the inflammatory process on aortic stiffening remains largely unknown. The aim of the present study was to evaluate potential relationships between AoPWV and blood pressure, basic anthropometric parameters, selected growth factors and markers of the inflammatory process in ESRD patients treated with peritoneal dialysis. The study population consisted of 43 patients (19 F, 24 M) with a mean age of 50.6 +/- 13.4 years on PD for a mean period of 21.9 +/- 20.7 months. AoPWV was measured using two pressure transducers placed on the carotid and femoral arteries and connected to an automatic processor (Complion Colson AS, Paris, France). Serum levels of Tumor Necrosis Factor alpha (TNFalpha), interleukin 6 (IL-6) and plasma basic Fibroblast Growth Factor (bFGF) were measured with ELISA; C-reactive protein and fibrinogen with nephelometry. Serum lipid profile was also assessed. Blood pressure was measured in an outpatient department under standardized conditions. Mean aortic pulse wave velocity in the study population was 10.7 +/- 2.1 m/s. No difference in AoPWV was found between men and women. AoPWV correlated significantly with age (R = 0.41; p < 0.01) but not with time on dialysis. Positive relationship between AoPWV and body weight and BMI was shown (R = 0.31; p < 0.05 and R = 0.35; p < 0.05, respectively). AoPWV correlated significantly with systolic blood pressure (SBP), mean arterial pressure (MAP) and pulse pressure (PP) (R = 0.46, p < 0.005, R = 0.46, p < 0.005 and R = 0.43, p < 0.01, respectively). AoPWV correlated with serum IL-6 and plasma bFGF (R = 0.32, p < 0.05 and R = 0.4, p < 0.01; respectively). The correlation with serum CRP was borderline significant (p < 0.53). In multiple regression analysis age (beta 0.38; p < 0.005), plasma bFGF level (beta 0.3; p < 0.05), and systolic blood pressure (beta 0.29; p < 0.05) were independently associated with pulse wave velocity. Our results suggest that AoPWV values in patients on PD are associated with factors similar to those encountered in the general population. We suggest that increased aortic stiffening may also be related to the chronic inflammatory process in PD patients.

[Nonsteroidal anti-inflammatory drugs--nephrotoxic mechanism of action]. / Niesteroidowe leki przeciwzapalne--mechanizm dzialania nefrotoksycznego.

Non-steroid anti-inflammatory drugs are easily available and commonly used. Mechanism of their action is based on inhibiting prostaglandin synthesis. Prostaglandins are arachidonic acid derivatives that are responsible, among others, for regulation of renal blood flow. In some kidney disorders as well as in hemodynamic disturbances, their increased release aims at balancing substances causing kidney ischemia. Blocking prostaglandin synthesis in such conditions may result in development of nephrotoxic effect, manifesting in water-electrolyte imbalance, acute tubulo-interstitial nephropathy, nephrotic syndrome, acute and chronic renal papillary necrosis as well as acute or chronic renal failure. Analgesic nephropathy with papillary necrosis is a particular form of the nephrotoxic effect of non-steroid anti-inflammatory drugs. Development of this complication has been described in patients abusing phenacetin or other analgesic drugs and especially their combination.

Serum concentrations of brain-derived neurotrophic factor (BDNF) are decreased in colorectal cancer patients.

OBJECTIVE: To determine the usefulness of brain-derived neurotrophic factor (BDNF) as a diagnostic biomarker for colorectal cancer (CRC). MATERIALS AND METHODS: ELISA immunoassay was used to examine BDNF concentrations in the sera of two different retrospective cohorts consisting of CRC patients and age/gender matched controls. Cohort 1 consisted of 99 controls and 97 CRC patients, whereas cohort 2 consisted of 47 controls and 91 CRC patients. RESULTS: In cohort 1, the median concentration of BDNF was significantly (p< 0.0001) lower in CRC patient samples (18.8 ng/mL, range 4.0-56.5 ng/mL) than control samples (23.4 ng/mL, range 3.0-43.1 ng/mL). This finding was validated in an independent patient cohort (CRC patients: 23.0 ng/mL, range 6.0-45.9 ng/mL; control patients: 32.3 ng/mL, range 14.2-62.4 ng/mL). BDNF concentrations did not differ significantly between Dukes' staging in the patient cohort, however patients with Stages A, B, C and D (p< 0.01 for each stage) tumours had significantly reduced BDNF levels compared to healthy controls. Receiver operating characteristic analysis was performed to determine the ability of BDNF to discriminate between healthy controls and those with CRC. At 95% specificity, BDNF concentrations distinguished CRC patients with 25% and 18% sensitivity, respectively, in cohorts 1 and 2 (cohort 1: AUC=0.79, 95% CI 0.70-0.87; cohort 2: AUC =0.69, 95% CI 0.61-0.76). CONCLUSION: The serum levels of BDNF were significantly lower in colorectal cancer patients when compared to a control population, and this did not differ between different Dukes' stages.

Polyhydramnios and elevated intrauterine pressure during amnioinfusion.

Amnioinfusion has been demonstrated to be useful in relieving and preventing repetitive variable decelerations. There have been no reported complications. This case illustrates the potential for iatrogenic polyhydramnios and elevated intrauterine pressure during amnioinfusion.

Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Perinatal outcome associated with PCP versus cocaine use.

Phencyclidine (PCP) remains a widely used illicit drug, especially among adolescents and young adults. The pharmacologic effects of PCP are similar to those of cocaine; therefore, in this retrospective study 37 PCP-intoxicated parturients were matched for ethnicity, tobacco use, age, gravidity, and degree of prenatal care with 37 cocaine-intoxicated parturients. Infants exposed to PCP in utero, like those exposed to cocaine, had a high incidence of intrauterine growth retardation (32 vs 19%, N.S.), precipitate labor (43 vs 27%, N.S.), symptoms of neonatal drug withdrawal/intoxication, and prolonged neonatal hospitalizations. Moreover, they were more likely to have meconium-stained amniotic fluid (30 vs 19%, p = .05) and less likely to be born prematurely as cocaine-exposed infants. The comparison between the long-term developmental outcome of these groups awaits further study.

Size selectivity of lung protein accumulation in preterm ventilated lambs.

The 1-hour net accumulation of four labeled proteins of different sizes (6.5, 29, 69 and 150 kD) from the vascular space into the lungs and airspaces was measured in preterm ventilated lambs at 132 days gestational age. Lambs treated with Survanta, a surfactant prepared from bovine lung, were studied at 1, 3, 5 and 8 h after birth, while lambs not treated with this surfactant were studied up to 5 h of age because of severe respiratory failure. The labeled proteins were lost from the vascular space more rapidly over the first 1 h of life than at later times (p less than 0.01). Labeled protein recoveries were similar at 1 and 3 h in surfactant and control lambs and decreased by 8 h in surfactant-treated lambs (p less than 0.05). In both the surfactant-treated and control animals, there was a sequential decrease in labeled protein recoveries based on protein size (p less than 0.01). There was no change with time in size selectivity for accumulation of the labeled proteins into the lungs for either the control or surfactant-treated lambs, although surfactant treatments decreased accumulation of the 6.5 and 29 kD proteins at 5 h when compared to the control group (p less than 0.05). Labeled protein recoveries in alveolar washes demonstrated less size selectivity. These studies documented that size selectivity of the vascular endothelium did not change over the first 8 h of life in preterm ventilated lambs, a pattern that was not indicative of progressive lung injury.

Effects of surfactant protein-A on surfactant function in preterm ventilated rabbits.

Surfactant protein-A (SP-A) isolated from cow surfactant was added to organic solvent extracts of natural bovine surfactant or of Survanta (Abbott Laboratories), and dynamic compliances and pressure-volume curves were measured in rabbits with a gestational age of 27 days. Organic solvent extracts of natural surfactant and Survanta significantly improved dynamic compliances and lung volumes compared with those in control rabbits, but the effects were less than for natural surfactant. Adding 1 to 10% by weight SP-A to organic solvent extracts of natural surfactant increased dynamic compliances and maximal lung volumes on pressure-volume curves to values comparable with natural surfactant. Lung volumes at 10 cm H2O on deflation curves increased in a dose-dependent fashion at concentrations of SP-A between 0.5 and 5% by weight with no further improvement at 10% SP-A, although the volumes were significantly lower than for natural surfactant. Five percent by weight SP-A did not improve any measurements for Survanta. These results indicated that SP-A favorably improved organic solvent extracted natural surfactant function in vivo. However, the responses could not be generalized to another surfactant.

Dose response of thyrotropin-releasing hormone on pulmonary maturation in corticosteroid-treated preterm rabbits.

The dose-response effect of thyrotropin-releasing hormone in enhancing pulmonary maturation was investigated with six dosing regimens. Pregnant does received thyrotropin-releasing hormone (5, 10, or 50 micrograms/kg every 12 hours for four doses or one dose of 20 micrograms/kg) in conjunction with betamethasone beginning on day 25 of gestation, with betamethasone alone or saline solution used as comparison treatment groups. Half of the newborn rabbits received supplemental surfactant therapy after delivery on day 27, and all were ventilated on a ventilator plethysmography system for 30 minutes. There were no differences among the four thyrotropin-releasing hormone doses in surfactant pool sizes, compliances, or proteins leak into or out of the air spaces. The groups that received multiple doses of thyrotropin-releasing hormone had significantly higher perinatal loss rates than the single-dose group. The lungs of the group treated with thyrotropin-releasing hormone plus steroid and the rabbits treated only with steroid were more compliant than the controls without surfactant therapy, and showed significant improvements in protein leak. The addition of thyrotropin-releasing hormone to betamethasone improved several of the protein leak measurements compared with use of betamethasone alone. These results question the necessity of multiple doses of thyrotropin-releasing hormone to induce pulmonary maturation, especially when the higher perinatal mortality and the theoretical long-term effects of fetal hyperthyroidism on thyroid axis function are considered.

Detection of human papillomavirus deoxyribonucleic acid from vulvar dystrophies and vulvar intraepithelial neoplastic lesions.

Vulvar biopsy specimens from 16 patients with gross lesions of the vulva consistent with vulvar dystrophy were examined histologically and for the presence of human papillomavirus deoxyribonucleic acid by southern blot hybridization. None of the nonatypical dystrophies probed positive for human papillomavirus; however, three of five atypical hyperplastic dystrophies (vulvar intraepithelial neoplasia) contained human papillomavirus deoxyribonucleic acid type 16. We conclude that human papillomavirus does not seem to be a causal factor in nonatypical chronic epithelial changes of the vulva.

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.