Evolving radon diffusion through earthen barriers at uranium waste disposal sites.

Field measurements of Rn-222 fluxes from the tops and bottoms of compacted clay radon barriers were used to calculate effective Rn diffusion coefficients (DRn) at four uranium waste disposal sites in the western United States to assess cover performance after more than 20 years of service. Values of DRn ranged from 7.4 × 10-7 to 6.0 × 10-9 m2/s, averaging 1.42 × 10-7. Water saturation (SW) from soil cores indicated that there was relatively little control of DRn by SW, especially at higher moisture levels, in contrast to estimates from most steady-state diffusion models. This is attributed to preferential pathways intrinsic to construction of the barriers or to natural process that have developed over time including desiccation cracks, root channels, and insect burrows in the engineered earthen barriers. A modification to some models in which fast and slow pathway DRn values are partitioned appears to give a good representation of the data; 4% of the fast pathway was needed to fit the data regression. For locations with high Sw and highest DRn (and fluxes) at each site, the proportion of fast pathway ranged from 1.7% to 34%, but for many locations with lower fluxes, little if any fast pathway was needed.

Radon fluxes at four uranium mill tailings disposal sites after about 20 years of service.

To evaluate the properties of earthen covers over uranium mill tailings disposal cells after about 20 years of service, we measured Rn-222 fluxes and radon barrier properties at the Falls City, TX, Bluewater, NM, Shirley Basin South, WY, and Lakeview, OR disposal sites in western USA. A total of 115 in-service Rn fluxes were obtained at 26 test pit locations from the top surface of the exposed Rn barrier (i.e., after protective layers were removed by excavation) and 24 measurements were obtained from the surface of the underlying waste after excavation through the Rn barrier layer. Rn-222 concentrations were determined in accumulation chambers using a continuously monitoring electronic radon monitor (ERM) equipped with a solid-state alpha particle detector. Effects of surface features on Rn flux including vegetation, seasonal ponding, and animal burrowing were quantified. Comparison of measured fluxes with values that were measured shortly after the Rn barriers were completed (as-built) show that most measurements fell within the range of the as-built fluxes, generally at very low fluxes. At two sites fluxes were measured that were greater than the highest as-built flux. High fluxes are typically caused by a combination of enhanced moisture removal and preferential pathways for Rn transport, often caused by deep-rooted plants. Such localized features result in a spatially heterogeneous distribution of fluxes that can vary substantially over only a meter or two.

Evaluation of Soil Manipulation to Prepare Engineered Earthen Waste Covers for Revegetation.

Seven ripping treatments designed to improve soil physical conditions for revegetation were compared on a test pad simulating an earthen cover for a waste disposal cell. The field test was part of study of methods to convert compacted-soil waste covers into evapotranspiration covers. The test pad consisted of a compacted layer of fine-textured soil simulating a barrier protection layer overlain by a gravelly sand bedding layer and a cobble armor layer. Treatments included combinations of soil-ripping implements (conventional shank [CS], wing-tipped shank [WTS], and parabolic oscillating shank with wings [POS]), ripping depths, and number of passes. Dimensions, dry density, moisture content, and particle size distribution of disturbance zones were determined in two trenches excavated across rip rows. The goal was to create a root-zone dry density between 1.2 and 1.6 Mg m and a seedbed soil texture ranging from clay loam to sandy loam with low rock content. All treatments created V-shaped disturbance zones as measured on trench faces. Disturbance zone size was most influenced by ripping depth. Winged implements created larger disturbance zones. All treatments lifted fines into the bedding layer, moved gravel and cobble down into the fine-textured protection layer, and thereby disrupted the capillary barrier at the interface. Changes in dry density within disturbance zones were comparable for the CS and WTS treatments but were highly variable among POS treatments. Water content increased in the bedding layer and decreased in the protection layer after ripping. The POS at 1.2-m depth and two passes created the largest zone with a low dry density (1.24 Mg m) and the most favorable seedbed soil texture (gravely silt loam). However, ripping also created large soil aggregates and voids in the protection layer that may produce preferential flow paths and reduce water storage capacity.

Sound level exposure of high-risk infants in different environmental conditions.

PURPOSES: To provide descriptive information about the sound levels to which high-risk infants are exposed in various actual environmental conditions in the NICU, including the impact of physical renovation on sound levels, and to assess the contributions of various types of equipment, alarms, and activities to sound levels in simulated conditions in the NICU. DESIGN: Descriptive and comparative design. SAMPLE: Convenience sample of 134 infants at a southeastern quarternary children's hospital. MAIN OUTCOME VARIABLE: A-weighted decibel (dBA) sound levels under various actual and simulated environmental conditions. RESULTS: The renovated NICU was, on average, 4-6 dBA quieter across all environmental conditions than a comparable nonrenovated room, representing a significant sound level reduction. Sound levels remained above consensus recommendations despite physical redesign and staff training. Respiratory therapy equipment, alarms, staff talking, and infant fussiness contributed to higher sound levels. CONCLUSION: Evidence-based sound-reducing strategies are proposed. Findings were used to plan environment management as part of a developmental, family-centered care, performance improvement program and in new NICU planning.

Engineered containment and control systems: nurturing nature.

The development of engineered containment and control systems for contaminated sites must consider the environmental setting of each site. The behaviors of both contaminated materials and engineered systems are affected by environmental conditions that will continue to evolve over time as a result of such natural processes as climate change, ecological succession, pedogenesis, and landform changes. Understanding these processes is crucial to designing, implementing, and maintaining effective systems for sustained health and environmental protection. Traditional engineered systems such as landfill liners and caps are designed to resist natural processes rather than working with them. These systems cannot be expected to provide long-term isolation without continued maintenance. In some cases, full-scale replacement and remediation may be required within 50 years, at an effort and cost much higher than for the original cleanup. Approaches are being developed to define smarter containment and control systems for stewardship sites, considering lessons learned from implementing prescriptive waste disposal regulations enacted since the 1970s. These approaches more effectively involve integrating natural and engineered systems; enhancing sensors and predictive tools for evaluating performance; and incorporating information on failure events, including precursors and consequences, into system design and maintenance. An important feature is using natural analogs to predict environmental conditions and system responses over the long term, to accommodate environmental change in the design process, and, as possible, to engineer containment systems that mimic favorable natural systems. The key emphasis is harmony with the environment, so systems will work with and rely on natural processes rather than resisting them. Implementing these new integrated systems will reduce current requirements for active management, which are resource-intensive and expensive.

Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated.

Revegetation of an abandoned uranium millsite on the Colorado Plateau, Arizona.

We attempted to restore native plants on disturbed sites at a former uranium mill on the Colorado Plateau near Tuba City, AZ. Four-wing saltbush [Atriplex canescens (Pursh) Nutt.] was successfully established in compacted caliche soil and in unconsolidated dune soil when transplants were irrigated through the first summer with 20 L/plant/wk. The caliche soil was ripped before planting to improve water-holding capacity. The diploid saltbush variety, angustifolia, had higher survival and growth than the common tetraploid variety, occidentalis, especially on dune soil. The angustifolia variety grew to 0.3 to 0.4 m3 per plant over 3 yr even though irrigation was provided only during the establishment year. By contrast, direct seeding of a variety of native forbs, grasses, and shrubs yielded poor results, despite supplemental irrigation throughout the first summer. In this arid environment (precipitation = 100 to 200 mm/yr), the most effective revegetation strategy is to establish keystone native shrubs, such as four-wing saltbush, using transplants and irrigation during the establishment year, rather than attempting to establish a diverse plant community all at once.

Factors to consider in selecting an angiotensin-converting-enzyme inhibitor.

The results of clinical studies of the use of angiotensin-converting-enzyme (ACE) inhibitors in a variety of cardiovascular and renal disorders are reviewed, with emphasis on evidence-based formulary decision-making. In evaluating agents for formulary inclusion, efficacy, safety, dosing, and cost are considered. ACE inhibitors have been investigated in thousands of patients in clinical trials, so an evidence-based approach to their use is appropriate. All ACE inhibitors are effective antihypertensive agents and are generally well tolerated. Thus, in formulary decisions, once-daily dosing and good 24-hour blood pressure control are important considerations to ensure efficacy and patient compliance. ACE inhibitors are key in the prevention and management of heart failure but are underused for these indications. The rationale for use of ACE inhibitors after myocardial infarction is discussed, as is evidence of separate antihypertensive and renoprotective effects of ACE inhibitors. Evidence for the use of ramipril in patients at high risk for cardiovascular events, from the Heart Outcomes Prevention Evaluation Study (HOPE), is reviewed. Clinical trial results provide evidence that some ACE inhibitors have renoprotective and vasculoprotective effects and improve outcomes of patients with a variety of cardiovascular disorders; differences among the ACE inhibitors should be considered in formulary decision-making.

Degradation pathways of a peptide boronic acid derivative, 2-Pyz-(CO)-Phe-Leu-B(OH)(2).

The peptide boronic acid derivative 2-Pyz-(CO)-Phe-Leu-B(OH)(2) is a potent inhibitor of 20S proteasome and a proposed anticancer agent. During preformulation studies, the compound presented erratic stability behavior. Efforts were made to isolate and identify the degradation products, thereby helping to identify possible mechanisms for the degradation. The reaction of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) with hydrogen peroxide not only provided a convenient way to isolate the initial degradation products seen from hydrolysis in aqueous buffers but also showed that the major, initial degradation pathway was probably oxidative in nature. The isolated degradation products were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and optical rotation dispersion. In the presence of hydrogen peroxide, the boronic acid group was cleaved from 2-Pyz-(CO)-Phe-Leu-B(OH)(2) to give an alcohol with an apparent retention of the original stereochemistry. Subsequent isomerization and further hydrolysis were then seen. Surprisingly, added ascorbate and EDTA accelerated rather than inhibited degradation. Degradation of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) under acidic and basic conditions seemed to be mediated by an initial oxidative degradation pathway similar to that seen with the peroxide.

The management of depression: the implications for managed care--roundtable discussion: Part 3.

From the standpoint of managed care, the rising cost of depression can be addressed in multiple ways. In the final portion of the roundtable discussion, the faculty discuss not only disease management programs for depression, but other initiatives health plans (including at the pharmacy level) are undertaking to address the rising costs associated with depression. They also discuss the effect of mental health coverage "parity" laws, which can be expected to drive costs even higher.

The management of depression: the implications for managed care--roundtable discussion: Part 2.

One of the most commonly utilized drug classes today is antidepressant therapy, which accounts for billions of dollars in spending. Pharmacoeconomic tools may play an influential role in formulary decision making, particularly in this drug class. In part 2 of the roundtable discussion, a pharmacoeconomic model is presented that may clarify the health economic effects of placing serotonin-norepinephrine reuptake inhibitors on the drug formulary, particularly in the context of other antidepressant medications.

Halohydrin analogues of cryptophycin 1: synthesis and biological activity.

The chloro-, bromo-, and iodo-derivatives 2-4 of the antimitotic drug cryptophycin 1 were synthesized by opening the epoxide ring. The biological activities of the compounds were tested in an in vitro microtubule assembly and a cell proliferation assay. The chloro-derivative 2 showed lower activity in the tubulin assay compared to 3 and 4, but they all showed similar inhibition in the proliferation assay.

Adjuvant use of warm butyl alcohol vapor in experimental pulmonary edema.

Studies were done to determine if warm n-butyl alcohol vapor might be effective for the destruction of respiratory tract foam bubbles and for alleviation of the arterial hypoxemia accompanying severe acute pulmonary edema. In vitro studies showed that warm butyl alcohol vapors made from 5% and 7% butyl alcohol solutions at 39 degrees C were much more effective in antifoam activity against synthetic foam bubbles than ethyl alcohol vapors, made from 20% and 30% ethyl alcohol at 22 degrees C. Warm butyl alcohol vapor also slowly destroyed in vitro the fine foam bubbles of alveolar lining origin made in rabbit lung post mortem. Evolving lung edema was induced in anesthetized rabbits by aspiration of 1.1 ml/kg of 1.2 molal sorbitol/0.14 molal sodium chloride/0.01 molal hydrochloric acid solution of pH 2.0. After established severe arterial hypoxemia and in the absence of overt foam, inhalation of warm butyl alcohol/H2O vapor-air mixture, made by air humidification from 7% butyl alcohol at 39 degrees C, alleviated promptly the hypoxemia. The improvement was progressive over the first 45 minutes of continued vapor therapy. The lessened hypoxemia occurred without concurrent improvement in the amount of formed lung edema fluid. Control inhalations of warm 100% H2O vapor-air mixture did not improve the hypoxemia. The only noted side effects of warm butyl alcohol vapor treatments were slight hypotension and slight metabolic acidosis which developed very slowly. The results suggest that warm butyl alcohol vapor might prove to be an effective adjuvant agent to lessen critically severe hypoxemia in selective cases of acute pulmonary edema in man.

Potential use of warm butyl alcohol vapor as adjunct agent in the emergency treatment of sea water wet near-drowning.

The short-term course of sea water wet near-drowning was studied in anesthetized rabbits breathing spontaneously. Therapeutic trials were incorporated using warm n-butyl alcohol vapor both in inspired air and in inspired oxygen. The purpose was to determine if butyl alcohol vapor might alleviate the hypoxemia of sea water aspiration, possibly by a defoaming action on the fine foam bubbles of alveolar origin in the lung edema even without tracheal foam being present. The findings from 20 rabbits without overt tracheal foam, that had aspirated 2.05 mL/kg of sea water and were placed 10-minutes postaspirationally into four different inhalational treatment groups, showed remarkable differences. Warm butyl alcohol vapor made by humidification of 7.5% solution at 31 degrees C alleviated the hypoxemia. With vapor treatment for 15 minutes, mean arterial oxygen tension (PaO2) was not significantly changed in the water vapor-air group, but increased significantly to 50.5 +/- 4.6, 70.0 +/- 8.9, and 146.7 +/- 40.7 mm Hg in the butanol/water vapor-air, water vapor-oxygen, and butanol/water vapor-oxygen groups, respectively. With treatment for 30 minutes, mean PaO2 increased to 248.3 +/- 38.0 mm Hg with butanol/water vapor-oxygen inhalations, but only to 91.2 +/- 9.8 mm Hg with 100% water vapor-oxygen inhalations. Thus, the inspired vapor of butanol was much more effective in elevation of arterial blood oxygen pressures when combined with oxygen therapy over the values found when 100% water vapor-oxygen treatments were given. Respiratory and cardiac depressant effects from inspired butanol were not evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers.

The stability of taxol (NSC-125973) in various diluents and containers was determined, and the extent of leaching of di(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) bags caused by the taxol formulation was measured. A taxol formulation consisting of a 6-mg/mL solution of taxol in 50% polyoxyethylated castor oil and 50% dehydrated ethanol was added to 50- and 100-mL glass bottles, PVC infusion bags, and polyolefin containers containing 5% dextrose injection or 0.9% sodium chloride injection to give initial nominal taxol concentrations of 0.3, 0.6, 0.9, and 1.2 mg/mL. The containers were maintained at 20-23 degrees C for 12-24 hours. Samples were assayed by stability-indicating high-performance liquid chromatography, and clarity was determined visually. An experiment was run to ascertain whether DEHP would leach from a PVC administration set during a simulated infusion. There was no substantial loss of taxol over 24 hours. Filtration through a membrane resulted in no loss of taxol. All the solutions initially appeared hazy. Solutions stored in PVC bags became more hazy with time than solutions stored in glass or polyolefin containers. The haze seen in PVC bags was traced to leaching of DEHP. Agitation had no effect on the extent of leaching. Leaching was also seen during simulated delivery through PVC administration sets. No DEHP was detected when solutions were stored in glass or polyolefin containers and infused through polyethylene-lined sets. At the dilutions studied, taxol was visually and chemically stable for up to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Modest pressure natriuresis and autoregulation during water diuresis in dogs.

The effects of renal arterial pressure change on renal output of sodium and volume were measured during water diuresis in 25 chloralose-anesthetized dogs. Conditions included a minimal invasive stress, limited sodium administration, and mean renal arterial pressures varied suprarenally, by aortic balloon inflation to lowermost levels of 82-106 mm Hg. Group A dogs received no aldosterone; group B, C and D dogs were given aldosterone. Dogs of group C also received (1-Sar, 8-Ile)-angiotensin II. Group D dogs received phenylephrine which elevated arterial and right atrial pressures moderately without decrease in renal blood flow. In groups A, B and C, mean changes in sodium output, volume output, fractional excretions and free water clearances were not detectable with mean renal arterial pressure reductions, which averaged 29 +/- 2.9, 22 +/- 2.8 and 27 +/- 5.2 mm Hg, respectively. Right atrial pressures, effective renal blood flows and glomerular filtration rates did not change with the renal arterial pressure changes in these groups. In the group D dogs, during the larger pressure reductions of 54 +/- 6.6 mm Hg from higher values of 158 +/- 7.0 mm Hg, mean urine flow and effective renal blood flow remained constant while glomerular filtration rate and sodium output decreased only slightly. Output efficiency ratios related to perfusion pressure were calculated. With no more than modest pressure-induced excretory changes, it is concluded that excretory sodium and urinary volume autoregulation in concert with nearly perfect circulatory autoregulation were demonstrated with regionally varied mean renal arterial pressure. The same preglomerular myogenic responses to transvascular pressure, which restrict glomerular and transcapillary pressures, are viewed dominantly responsible for both circulatory and excretory autoregulation under normal conditions of minimal stress and low fractional sodium excretions. Homeostatic implications are discussed concerning likely relevance to the Guyton-Coleman theory for the long-term control of arterial blood pressure.