Optimization of Field and Laboratory Sample Processing for Characterization of Metallic Residues at Military Training Ranges.

Military ranges are unlike many waste sites because the contaminants, both energetics and metals, are heterogeneously distributed in soil during explosive detonation or ballistic impact and cannot be readily characterized using conventional grab sampling. The Incremental Sampling Methodology (ISM) has been successful for characterization of energetic contamination in soils, but no published ISM processing studies for soils with small arms range metals such as Pb, Cu, Sb, and Zn exists. This study evaluated several ISM sample-processing steps: (1) field splitting to reduce the sample mass shipped to the analytical laboratory, (2) necessity of milling, and (3) processing a larger subsample mass for digestion in lieu of milling. Cone-and-quartering and rotary sectorial splitting techniques yielded poor precision and positively skewed distributions. Hence, an increase in digestion mass from 2 to 10 g was evaluated with milled and unmilled samples. Unmilled samples yielded results with the largest variability regardless of aliquot mass.

Applying Incremental Sampling Methodology to Soils Containing Heterogeneously Distributed Metallic Residues to Improve Risk Analysis.

This study compares conventional grab sampling to incremental sampling methodology (ISM) to characterize metal contamination at a military small-arms-range. Grab sample results had large variances, positively skewed non-normal distributions, extreme outliers, and poor agreement between duplicate samples even when samples were co-located within tens of centimeters of each other. The extreme outliers strongly influenced the grab sample means for the primary contaminants lead (Pb) and antinomy (Sb). In contrast, median and mean metal concentrations were similar for the ISM samples. ISM significantly reduced measurement uncertainty of estimates of the mean, increasing data quality (e.g., for environmental risk assessments) with fewer samples (e.g., decreasing total project costs). Based on Monte Carlo resampling simulations, grab sampling resulted in highly variable means and upper confidence limits of the mean relative to ISM.

Inadequacy of Conventional Grab Sampling for Remediation Decision-Making for Metal Contamination at Small-Arms Ranges.

Research shows grab sampling is inadequate for evaluating military ranges contaminated with energetics because of their highly heterogeneous distribution. Similar studies assessing the heterogeneous distribution of metals at small-arms ranges (SAR) are lacking. To address this we evaluated whether grab sampling provides appropriate data for performing risk analysis at metal-contaminated SARs characterized with 30-48 grab samples. We evaluated the extractable metal content of Cu, Pb, Sb, and Zn of the field data using a Monte Carlo random resampling with replacement (bootstrapping) simulation approach. Results indicate the 95% confidence interval of the mean for Pb (432 mg/kg) at one site was 200-700 mg/kg with a data range of 5-4500 mg/kg. Considering the U.S. Environmental Protection Agency screening level for lead is 400 mg/kg, the necessity of cleanup at this site is unclear. Resampling based on populations of 7 and 15 samples, a sample size more realistic for the area yielded high false negative rates.

Ventilation-perfusion inequality in chronic obstructive pulmonary disease.

A multiple inert gas elimination method was used to study the mechanism of impaired gas exchange in 23 patients with advanced chronic obstructive pulmonary disease (COPD). Three patterns of ventilation-perfusion (Va/Q) inequality were found: (a) A pattern with considerable regions of high (greater than 3) VA/Q, none of low (less than 0.1) VA/Q, and essentially no shunt. Almost all patients with type A COPD showed this pattern, and it was also seen in some patients with type B. (b) A pattern with large amounts of low but almost none of high VA/Q, and essentially no shunt. This pattern was found in 4 of 12 type B patients and 1 of type A. (c) A pattern with both low and high VA/Q areas was found in the remaining 6 patients. Distributions with high VA/Q areas occurred mostly in patients with greatly increased compliance and may represent loss of blood-glow due to alveolar wall destruction. Similarly, well-defined modes of low VA/Q areas were seen mostly in patients with severe cough and sputum and may be due to reduced ventilation secondary to mechanical airways obstruction or distortion. There was little change in the VA/Q distributions on exercise or on breathing 100% O2. The observed patterns of VA/Q inequality and shunt accounted for all of the hypoxemia at rest and during exercise. There was therefore no evidence for hypoxemia caused by diffusion impairment. Patients with similar arterial blood gases often had dissimilar VA/Q patterns. As a consequence the pattern of VA/Q inequality could not necessarily be inferred from the arterial PO2 and PCO2.

Night-to-night arousal variability and interscorer reliability of arousal measurements.

STUDY OBJECTIVES: Measurement of arousals from sleep is clinically important, however, their definition is not well standardized, and little data exist on reliability. The purpose of this study is to determine factors that affect arousal scoring reliability and night-to-night arousal variability. DESIGN: The night-to-night arousal variability and interscorer reliability was assessed in 20 subjects with and without obstructive sleep apnea undergoing attended polysomnography during two consecutive nights. Five definitions of arousal were studied, assessing duration of electroencephalographic (EEG) frequency changes, increases in electromyographic (EMG) activity and leg movement, association with respiratory events, as well as the American Sleep Disorders Association (ASDA) definition of arousals. SETTING: NA. PATIENTS: NA. INTERVENTIONS: NA. RESULTS: Interscorer reliability varied with the definition of arousal and ranged from an Intraclass correlation (ICC) of 0.19 to 0.92. Arousals that included increases in EMG activity or leg movement had the greatest reliability, especially when associated with respiratory events (ICC 0.76 to 0.92). The ASDA arousal definition had high interscorer reliability (ICC 0.84). Reliability was lowest for arousals consisting of EEG changes lasting <3 seconds (ICC 0.19 to 0.37). The within subjects night-to-night arousal variability was low for all arousal definitions CONCLUSION: In a heterogeneous population, interscorer arousal reliability is enhanced by increases in EMG activity, leg movements, and respiratory events and decreased by short duration EEG arousals. The arousal index night-to-night variability was low for all definitions.

Beta 2-adrenergic receptor characteristics in sleep apnea patients.

This study examined the relationship between sleep apnea and beta 2-adrenergic receptor characteristics. Using standard polysomnography, individuals were classified as either apneic (n = 15) or mild to nonapneic (n = 15) according to their respiratory disturbance index (RDI). Subjects were similar in terms of sodium excretion and blood pressure. Apneic subjects showed a decrease in beta 2-adrenergic receptor sensitivity (p = 0.01) [as determined by isoproterenol-stimulated cyclic adenosine 5'-monophosphate (AMP) production in lymphocytes] and an increased binding affinity to the beta receptor antagonist [125I]iodopindolol (p < 0.001). beta receptor density was also diminished in apneics, but not significantly (p = 0.08). Forskolin-stimulated cyclic AMP was not significantly different between the groups, indicating a similarity in postreceptor Gs-adenylate cyclase activation. Across all subjects, RDI was negatively correlated with beta receptor sensitivity (r = -0.35, p = 0.05) and Kd (r = -0.54, p < 0.01) and positively correlated with systolic blood pressure (r = 0.37, p < 0.05). The findings indicate that sleep apnea is associated with a diminished beta 2-adrenergic receptor function but no change in postreceptor components and suggest a mechanism for the high comorbidity between sleep apnea and hypertension.

The effect of hypoxia on baroreflexes and pressor sensitivity in sleep apnea and hypertension.

Many persons with sleep apnea are hypertensive. Forty-two subjects of similar age and weight were divided into four groups of hypertensives and normotensives with and without sleep apnea. All subjects had heart rate, blood pressure (BP), baroreflex sensitivity and pressor sensitivity to phenylephrine measured while breathing room air or 15% oxygen. Hypoxia raised heart rate and lowered BP in all groups (p < 0.001), with the greatest hypotensive effect among hypertensives. Hypertensives had blunted baroreflex sensitivity, and breathing a hypoxic mixture lowered baroreflex sensitivity of all four groups (p = 0.008). The apneic subjects tended to lower their baroreflex sensitivity more in response to hypoxia and also had an enhanced pressor response to phenylephrine, whether breathing room air or 15% oxygen. Episodes of sleep apnea lead to hypoxia, an initial period of hypotension and a subsequent increase in sympathetic nervous activity. Our studies suggest that apneics could have an exaggerated pressor sensitivity to norepinephrine. They might also have difficulty returning BP to normal levels, because hypoxia impaired baroreflexes.

Altered cardiac contractility in sleep apnea.

Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is difficult to summarize with one measure. Furthermore, the role of the adrenergic system in sleep apnea is often confounded with hypertension, making interpretation difficult in hypertensive apneics. Sixty-six people with and without apnea and/or hypertension (all were off antihypertensive medication) participated in this study. Cardiac beta-adrenergic drive, as assessed by systolic time intervals, was examined at rest and in response to a mild laboratory stressor. These measures of cardiac contractility included the pre-ejection period, electrical systole (QT) interval and the cardiac acceleration index. At rest, apneics showed elevated myocardial contractility on all measures (p = 0.001). In response to the laboratory stressor, non-apneics showed an increase in cardiac beta-adrenergic drive (p = 0.001), whereas the contractility in apneics did not change or decreased relative to baseline. These findings suggest disrupted cardiac adrenergic regulation in people with sleep apnea. Apnea appears to increase resting sympathetic activity and down regulate beta2-adrenergic receptors. The downregulation of cardiac beta-adrenergic receptor activity may explain the inability of people with sleep apnea to respond with appropriate cardiac contractility to a mild perturbation.

The effects of exercise testing on the prescription of oxygen therapy.

This study reviews the effects of using oxygen saturation measurements during exercise and the effects of the method of exercise testing on the prescription of oxygen therapy. Using cutaneous oximetry (designated A and B models) and co-oximetry, 25 of 41 patients (model A), 30 of 39 patients (model B), and 28 of 42 patients (co-oximetry) had an oxygen saturation measurement greater than 85 percent at maximal incremental exercise despite an arterial oxygen tension less than 55 mm Hg. Also, in a group of patients who underwent incremental followed by constant work rate testing, 9 of 28 exhibited a fall in arterial oxygen tension to 55 mm Hg or below only during the constant work rate testing. Oxygen saturation measurements cannot reliably be used as a substitute for arterial oxygen tension measurements for the prescription of oxygen therapy. The type of exercise study performed may influence the outcome of such oxygen prescription.

Pulmonary function tests cannot predict exercise-induced hypoxemia in chronic obstructive pulmonary disease.

We studied 40 patients with chronic obstructive pulmonary disease (COPD) to determine whether measurements of pulmonary function could predict a fall in arterial oxygen pressure (PaO2) with exercise. The PaO2 fell more than 3 mm Hg in 21 patients (group 1), did not change (+/- 3 mm Hg) in nine patients (group 2), and increased more than 3 mm Hg in ten patients (group 3). Group 3 had significantly less severe expiratory obstruction than groups 1 and 2. The most significant variables in predicting a change in PaO2 with exercise were the ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) and the single-breath carbon monoxide diffusing capacity (Dsb). Measurements of FEV1/FVC of 0.50 or more and Dsb of 20 ml/min/mm Hg or more were 100 percent predictive in excluding a fall in PaO2 with exercise. Measurements below these thresholds could not be used reliably to predict which patients would develop worsening hypoxemia with exercise. Because of wide variability in reference values from eight different published studies for diffusing capacity, recommended criteria based on the percent predicted Dsb should be used with caution. We conclude that pulmonary function measurements cannot be used to predict exercise-induced hypoxemia in patients with COPD; however, the measurements may be useful in identifying patients whose condition is less severe who are unlikely to develop worsening hypoxemia with exercise.

The use of cutaneous oximetry in the prescription of long-term oxygen therapy.

Using current Medicare guidelines for the prescription of long-term oxygen therapy, we studied the impact on decision-making of substituting cutaneous oxyhemoglobin saturation measurements (SaO2) for direct arterial oxygen tension measurements (PaO2). Fifty-five patients with chronic lung disease and resting hypoxemia were studied. More than 80 percent of patients with a resting PaO2 of 7.33 kPa (55 mm Hg) or less had a cutaneous oximetry SaO2 greater than 85 percent. These patients would not have met the guidelines for long-term oxygen therapy if the cutaneous oximetry measurements were used instead of direct PaO2 measurements. Substituting a threshold criterion of 88 percent instead of 85 percent resulted in fewer patients being denied oxygen therapy but also included patients with PaO2 values greater than 7.33 kPa (55 mm Hg). We conclude that cutaneous oximetry cannot be substituted equivalently for PaO2 measurements in prescribing long-term oxygen therapy.

Rapid changes in arterial blood gas levels after exercise in pulmonary patients.

We evaluated arterial blood gas levels at rest, end-exercise, and 20, 40, 60, and 120 seconds after exercise in 24 pulmonary patients. Significant changes from end-exercise arterial PO2 (PaO2) were noted by 40 seconds postexercise. Changes in arterial PCO2 were less pronounced. Sampling delays as short as 20 seconds led to significant underestimation of the changes in PaO2 during exercise in a few patients. Longer delays led to a greater number of misleading studies. We conclude that, if blood gas analyses are used to detect abnormal changes in PaO2 or P(A-a)O2 during exercise, then blood must be sampled during exercise. The common practice of performing arterial punctures after exercise may provide misleading information in some patients.

Gas exchange in chronic thromboembolism after pulmonary thromboendarterectomy.

Thromboendarterectomy is the treatment of choice for chronic large vessel thromboembolic pulmonary hypertension. To identify the mechanisms responsible for the improvement in gas exchange following thromboendarterectomy, we studied nine patients with chronic thromboembolic pulmonary hypertension before and eight to 18 months after surgery using the multiple inert gas elimination technique. Preoperatively, all subjects had pulmonary hypertension and were hypoxemic or had an elevated P(A-a)O2. The VA/Q distribution was widened with an elevated VD/VT and a low cardiac index. After thromboendarterectomy, significant improvement had occurred. The VA/Q distribution had narrowed to near normal, and the cardiac index increased. It was concluded that thromboendarterectomy improved gas exchange both by improving VA/Q relationships and by increasing cardiac output.

Proficiency testing materials for pH and blood gases. The California Thoracic Society experience.

The California Thoracic Society Blood Gas Proficiency Testing Program distributed ampules from three separate lots of quality control products every three months as unknowns to participating clinical (survey) laboratories and ten selected reference laboratories. For eight quarters, aqueous buffers were distributed. For each lot, PCO2 and pH measurements varied within narrow ranges between laboratories. Concurrently, the PO2 measurements varied widely between reference laboratories as well as survey laboratories, but varied minimally when repeatedly assessed on each reference laboratory machine. Change to a fluorocarbon-containing emulsion as a testing medium resulted in a significant reduction in within model and overall variability for PO2. We attribute this reduction in variability to the higher O2 content and decreased temperature sensitivity for PO2 of the fluorocarbon-containing emulsion. Because we have no evidence that the magnitude of the interinstrument differences in PO2 found with these materials would be found with fresh human blood we recommend that regulatory agencies use the results of proficiency testing for PO2 cautiously.

Membrane diffusion and capillary blood volume in chronic thromboembolic pulmonary hypertension.

A reduced diffusing capacity for carbon monoxide (DCO) is common among patients with chronic thromboembolic pulmonary hypertension (CTEPH) and often persists for more than a year following successful pulmonary thromboendarterectomy (PTE). To determine the relative contribution the pulmonary membrane diffusing capacity (DM) and pulmonary capillary blood volume (VC) make to the reduction in DCO, we measured both in 29 patients with CTEPH before and approximately 3 weeks after PTE. Mean preoperative DM was reduced in patients with CTEPH (28 mL min-1 mm Hg-1 vs 43 mL min-1 mm Hg-1 in control subjects; p < 0.001) and dropped significantly following PTE (21 mL min-1 mm Hg-1; p < 0.001). Mean preoperative VC was mildly reduced in the CTEPH group compared with healthy control subjects (57 vs 67 mL; p = 0.044) and did not rise following PTE (57 mL pre-PTE vs 54 mL post-PTE; p > 0.05) despite substantial reduction in mean pulmonary artery pressure and increase in cardiac output after surgery. We conclude that the low DCO observed in patients with CTEPH before and after PTE is principally caused by a reduced DM and to a lesser extent by a low VC. The mechanisms responsible remain speculative but may reflect pathophysiologic changes in the pulmonary microcirculation caused by chronic pulmonary hypertension that did not improve in the postoperative period studied.

Relationship of arousals from sleep to sympathetic nervous system activity and BP in obstructive sleep apnea.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) patients have a high frequency of arousals. We hypothesized that arousals significantly influence tonic sympathetic nervous system function. DESIGN: We examined the association of 11 variables measuring sympathetic activity, including plasma norepinephrine (NE), urinary NE, and BP measurements, with movement and cortical arousals. PATIENTS: Sixty-seven subjects with various degrees of hypertension and OSA were evaluated. All patients were free from antihypertensive medications. RESULTS: The age (range, 35 to 60 years), weight (range, 100 to 150% of ideal body weight), and diet of the subjects were similar. The movement arousal index was correlated with daytime baseline plasma NE (BNE), daytime urine NE, mean daytime diastolic BP, and systolic BP during rapid eye movement sleep (r = 0.39 to 0.53; p < or = 0.002). Cortical arousals did not correlate with any of the variables. A multiple regression procedure was performed to examine how well movement arousals predicted those variables with significant correlations. The respiratory disturbance index (RDI) and nighttime pulse oxyhemoglobin saturation were included in the regression equation due to their close association with movement arousals. Movement arousals independently predicted BNE (t [48] = 2.06; p < 0.05). No other variable independently predicted any of the measurements of sympathetic activity. CONCLUSIONS: These findings suggest that movement arousals may influence daytime sympathetic tone independently of RDI and nighttime saturation.

The role of sleep-disordered breathing in essential hypertension.

In recent years there have been numerous reports addressing the relationship between sleep-disordered breathing (SDB) and hypertension (HTN). This study investigated the relationship between SDB and BP after controlling for age, gross obesity, and notably, antihypertensive medications. Sixty-seven men and women between 30 and 60 years of age and between 0.90 to 1.5 times ideal body weight were studied. SDB was assessed over two nights of polysomnographic monitoring, and BP was measured over repeated visits to the hospital. The results indicate that respiratory disturbance index (RDI) independently predicts diastolic BP (DBP), accounting for 15% of the variance in DBP (p=0.02). In subjects with severe levels of SDB (RDI >30), RDI uniquely accounted for 36% of the variance in DBP (p=0.003). Interestingly, SDB was not independently related to systolic BP. The physiologic mechanisms responsible for these findings are currently being explored.

Inter-instrument comparison of blood gas analyzers and assessment of tonometry using fresh heparinized whole human blood.

Because of limitations associated with commercial blood gas quality controls and tonometry of stored blood, fresh heparinized blood was used to compare PO2 and PCO2 performance of ten blood gas analyzers. Function of nine gas mixer/tonometer systems was evaluated. These were used to create blood samples with target values for PO2 and PCO2. All ten analyzers had high precision; this magnified small differences between observed results and target values. Grand mean results from all ten analyzers were within 0.8 mm Hg of the target for PO2 of 40.0 and 100.0 and for PCO2 of 20.0 and 70.0 mm Hg. Eight automated blood gas analyzers gave clinically indistinguishable results for PO2 and PCO2 that were sufficiently accurate for clinical purposes. Also reported is the practicality of using tonometry of fresh heparinized blood in a per shift quality control program for PO2 and PCO2.

Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients.

OBJECTIVES: We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. SUBJECTS AND INSTRUMENTATION: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. DESIGN AND RESULTS: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 Omega/s(2), 22 Omega/s(2), and 14 Omega/s(2) on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 Omega/s(2) at baseline, 32 Omega/s(2) during speech preparation, and 36 Omega/s(2) while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAP- treated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. CONCLUSIONS: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.

Prediction of normal values in pulmonary function testing.

Appropriate use of reference equations for predicting normal values is important for maximizing the clinical and research usefulness of pulmonary function testing. Because of the diversity of clinical and research uses of pulmonary function testing, predictive equations derived from different populations may be needed for specific applications. Similarly, different limits of normalcy other than the traditional 95 per cent confidence limits may be more appropriate for some applications. Unanswered questions remain about the effects of race and altitude on predicted values for many pulmonary function parameters. In order to establish confidence that the predictive equations, lower limits of normalcy, and testing methodology are appropriate for specific patient populations, it is suggested that each clinical laboratory obtain PFT measurements on 10 to 20 individuals considered free of disease and representative of their patient population and compare these results with the prediction equations selected for use. Although the testing of such a small sample of normal subjects will not assist in the selection of optimal equations if the differences between equations are minor, it will detect grossly inappropriate predictive values and limits of normalcy as well as identify problems with testing methodology.