Sorption of estrogens estrone, 17ß-estradiol, estriol, 17α-ethinylestradiol, and diethylstilbestrol on sediment affected by different origins.

The sorption coefficients of estrone (E1), 17ß-estradiol (E2), and estriol (E3), 17α-ethinylestradiol (EE2), and diethylstilbestrol (DES) on four sediments (BS1-4) collected downstream of agricultural, domestic, and industrial discharges were determined. The objective was to investigate the effect of sediment origin on the sorption affinity of natural and synthetic estrogens on sediments. Experimental results indicate that the sediment samples from different origins had differing estrogen sorption affinities. Organic materials in sediment samples collected from downstream of agricultural and domestic discharge, i.e., BS1 and BS2, respectively, were readily biodegraded and biotransformed during sediment diagenesis, which enhanced the sorption capacity for estrogens. Sediment samples BS3 and BS4, which were obtained downstream of domestic and industrial discharges, respectively, may contain complex compositions, including hydrophilic substances that resulted in lower log K(oc) values. The estrogen sorption on sediments was reasonably regressive with linear models. The log K(oc) values for individual estrogens in individual sediments showed variation: 2.82-4.21 for E1; 2.73-4.14 for E2; 2.19-3.76 for E3; 3.24-3.94 for EE2; and, 4.07-5.25 for DES. Nevertheless, the relationship between log K(ow) and log K(oc) of individual estrogens in individual sediments was linear. The mean log K(oc) values for target estrogens followed the trend of DES (4.68) > EE2 (3.71) > E2 (3.52) > E1 (3.44) > E3 (2.99), corresponding to the trend of log K(ow) values. These analytical results suggest that sorption of estrogens on sediments varied with sample origin. Therefore, evaluations of the fate and transport of estrogens in river environments must consider surrounding agricultural, domestic, and industrial sources.

Contribution of emphysema and small airways in COPD.

BACKGROUND: The contribution and role of emphysema and small airways disease in causing expiratory airflow limitation in COPD is controversial. METHODS: We obtained high-resolution thin-section 2-mm CT scans of the lung for emphysema grading and lung function in 116 consecutively seen COPD outpatients with fixed expiratory airflow limitation. In this group, inflated whole lung(s) were subsequently obtained in 24 patients (23 autopsy, 1 surgery) for morphologic studies and results compared with lung CT. Airway histologic condition was studied in 17 of the 24 patients. RESULTS: There was fair to weak negative correlation between CT emphysema score and either FEV1/FVC percent (r = -0.51, p = 0.001) or FEV1 percent predicted (r = -0.31, p = 0.001). In only 24 of the 81 patients (30%) with FEV1 less than 50% predicted, the CT emphysema score was 60 or more, indicating severe emphysema. In the 24 patients studied, there was a good correlation (r = 0.86, p = 0.001) between CT and pathologic grade of emphysema. While respiratory bronchioles (RBs) and membranous bronchioles (MBs) demonstrated marked morphologic abnormalities, there was a weak correlation with emphysema grade (for RB, r = 0.36, p = 0.16; for MB, r = 0.41, p = 0.10) or with FEV1 percent predicted (for RB, r = -0.21, p = 0.42; for MB, r = -0.28, p = 0.28). There was no correlation between emphysema and FEV1 percent predicted (r = -0.13, p = 0.54). CONCLUSIONS: High-resolution CT lung scans are an in vivo surrogate to quantitate moderate to severe morphologic emphysema. Emphysema does not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. There was no correlation between severity of small airway histologic condition and emphysema or FEV1 percent predicted. The causes of the lesions responsible for small airways obstruction need to be identified.

Limited contribution of emphysema in advanced chronic obstructive pulmonary disease.

Previous studies on autopsy specimens or surgically resected lobes or lungs have reached varying conclusions regarding the importance of small airways disease and emphysema in causing fixed expiratory airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We obtained high resolution CT scans of the lung and lung function in 56 consecutive patients with fixed expiratory airflow limitation. There was poor correlation between CT emphysema score and either FEV1/FVC% (r = -0.36) or FEV1 % predicted (r = -0.20). In only 10 of the 35 patients with FEV1 < 50% predicted, the CT emphysema score was > 40, indicating significant emphysema. A strong negative correlation between diffusing capacity % predicted and diffusing capacity per alveolar volume and CT emphysema score was found only in patients with FEV1 > or = 1 L (r = -0.75, p < 0.0001). Thus, emphysema does not appear to be primarily responsible for expiratory airflow limitation in COPD. A low diffusing capacity may be spuriously misleading in patients with FEV1 < 1 L and no or trivial emphysema.

Inspiratory muscle work of breathing during flow-by, demand-flow, and continuous-flow systems in patients with chronic obstructive pulmonary disease.

The effect of flow-by continuous positive airway pressure (CPAP) in comparison with continuous-flow (CF) CPAP on inspiratory muscle work of breathing (WI) in intubated patients is not known. We hypothesized that WI during flow-by CPAP would be comparable with that during CF CPAP. In nine intubated male patients recovering from acute respiratory failure related to chronic obstructive pulmonary disease, we compared the effects of flow-by, demand-flow, and CF CPAP on WI. We also evaluated the extent to which the addition of 5 cm H2O of pressure support to demand-flow CPAP (DF-PS5) decreases WI. At CPAP levels of zero and 8 cm H2O, flow-by, demand-flow, DF-PS5 were applied in random order followed by CF CPAP for 15 min each. WI (expressed as Joules per liter and Joules per minute), maximal airway pressure drop during inspiration (delta Paw), total lung resistance (RL), lung compliance (CL), and ventilatory variables were measured. At CPAP of zero cm H2O, WI with flow-by was comparable with CF CPAP, and significantly less than with demand-flow CPAP. At both CPAP of zero and 8 cm H2O, the addition of 5 cm H2O PS to demand-flow CPAP reduced WI significantly to a level comparable with that of flow-by CPAP. At both CPAP levels, delta Paw was the largest, with demand-flow CPAP. RL and CL were not significantly different between the different CPAP systems. We conclude that WI with flow-by CPAP is comparable with that with CF CPAP, and significantly less than with demand-flow CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic aminophylline administration. Effect on diaphragm contractility and fatigue resistance in vitro.

The effects of acute and chronic administrations of aminophylline (AM) on diaphragm contractility and fatigue resistance were examined in 42 rats. In acute experiments (n = 22), the animals received an intravenous bolus of either AM (14 mg/kg; n = 11) or saline (n = 11). Serum AM level was determined 30 min after the bolus (17.8 +/- 0.8 mg/L, SD). In chronic experiments (n = 20), either AM (n = 10) or saline (n = 10) was infused subcutaneously via an osmotic minipump at a constant pumping rate of 2.5 microliters/h. Serum AM level was measured after 2 wk of pump infusion (12.3 +/- 2.0 mg/L, SD). For each animal in both acute and chronic experiments, a muscle strip from the right midcostal diaphragm was placed in an in vitro chamber containing Krebs solution and 12 microM/L curare. For the AM-treated group, AM was added to the tissue bath in a concentration similar to that in the serum. No AM was added to the bath for the control group. Forces were measured isometrically during direct muscle stimulation at different frequencies and standardized to muscle weight. Muscle fatigue was induced by repetitive stimulation at 40 pps, delivered in 330-ms trains, with one train presented each second. With either acute or chronic AM administration, a significant increase in diaphragm contractility was observed (p less than 0.01). In contrast, AM did not affect the rate of force decline during fatigue run.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of positive vs negative pressure ventilation in unloading the respiratory muscles.

We compared the efficacy of positive pressure ventilation (PPV) vs negative pressure ventilation (NPV) in providing ventilatory muscle rest for five normal subjects and six patients with chronic obstructive pulmonary disease (COPD). All participants underwent measurement of transdiaphragmatic pressure (Pdi), pressure time integral of the diaphragm (PTI), integrated diaphragmatic electromyogram (iEMG), minute ventilation (Ve), tidal volume (Vt), and end-tidal CO2 (etCO2) during 15 minutes of PPV and NPV. For each subject, ventilator adjustments were made to obtain Ve similar to levels measured during quiet breathing (QB). We found that the iEMG, Pdi, PTI, and average coefficient of variation of the tidal volume (CV-Vt) were consistently lower during PPV as compared with NPV (p = 0.01). The iEMG normalized for Ve and Vt was also significantly lower during PPV (p = 0.01). During PPV, subjects were mildly hyperventilated (lower etCO2 and higher Ve) compared with QB and NPV, but no significant correlation was noted between the change in etCO2 and the change in iEMG. The change in PTI was significantly correlated with the change in iEMG (p less than 0.01). We conclude that in the short term, PPV is more effective than NPV in reducing diaphragmatic activity. Positive pressure ventilation may be the preferred method of assisted ventilation in future studies of ventilatory muscle rest therapy.

Relative contribution of neurotransmission failure to diaphragm fatigue.

Two procedures were used to estimate the relative contribution of neurotransmission failure (NF) to fatigue of the rat diaphragm at different rates of phrenic nerve stimulation. In one, direct muscle stimulation was intermittently superimposed on neural stimulation of the diaphragm, and the relative contribution of NF was estimated by the difference in generated tension. In a second procedure, diaphragm fatigue was induced by using either direct muscle stimulation (with complete blockade of the neuromuscular junction by d-tubocurare) or phrenic nerve stimulation. The relative contribution of NF to diaphragm fatigue was then estimated by comparing the force loss during these two modes of stimulation. With both procedures, it was observed that 1) the relative contribution of NF to diaphragm fatigue was less than 45% at each frequency of phrenic nerve stimulation; 2) the relative contribution of NF to diaphragm fatigue increased at higher rates of phrenic stimulation, reaching a maximum at 75 pulses/s; and 3) the relative contribution of NF to diaphragm fatigue reached a plateau after 2 min of repetitive stimulation.

Pulmonary toxicity of recombinant human tumor necrosis factor.

Tumor necrosis factor is a cytokine produced by activated macrophages that causes hemorrhagic necrosis in various tumours. In preliminary clinical trials, patients have developed various degrees of respiratory insufficiency following administration of rTNF. Twenty-seven patients were studied prospectively to evaluate the effect of administration of rTNF on pulmonary function. Sixteen of the 27 patients completed the eight-week course of daily IM injection of rTNF. Spirometric data and Dsb were measured at baseline and on days 8, 15, and 56 of treatment. Both patients with and without progressive pulmonary metastases demonstrated a comparable mean decline in Dsb (-10.7 +/- 9.6 percent [+/- SD] and 14.7 +/- 10.0 percent, respectively; p less than 0.01) not accounted for by either a decline in the hemoglobin content of the blood or a reduction in alveolar volume. Marked interindividual variability in the response of Dsb to rTNF therapy was noted. The reduction in Dsb reached a plateau by day 15. In contrast, alveolar volume and FVC remained essentially unchanged throughout the course of treatment. Measurements of Dsb performed two weeks after cessation of rTNF therapy in seven of the 27 patients showed only a modest trend toward recovery, which was not statistically significant. We conclude that the administration of rTNF for the treatment of malignant neoplasms in this dosage and schedule can cause significant pulmonary injury reflected by a reduction in Dsb which reaches a plateau by two weeks after initiation of therapy.

Supercritical fluid chromatography of glycosphingolipids.

Glucose polymers and three classes of glycosphingolipids were permethylated and studied by supercritical fluid chromatography using a DB-5 coated capillary columns and carbon dioxide as the mobile phase. Column restrictors were fabricated at each column tip as described by E.J. Guthrie and H.E. Schwartz (1986, J. Chromatogr. Sci. 24, 236). Sample elution was facilitated by a programmed increase in density and detection was by flame ionization. Compounds up to 3000 Da showed excellent resolution for structural variations in carbohydrate moieties and in alkane chain heterogeneity caused by the sphingoid or N-acyl alkane chain residues.