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Biomedical subjects

W J Powers

Publications and source records attributed to W J Powers.

At least 19 recordsLinked to original sources

Keeping science in environmental regulations: the role of the animal scientist.

Environmental issues continue to be one of the biggest challenges faced by livestock producers. Whereas issues of the past have focused on manure nutrient impacts on water quality with some regulatory activity addressing odors, emerging issues are more diverse. To address emerging air quality issues, such as ammonia emissions, antibiotic transfer, human health impacts of emissions from animal agriculture, and estrogens in the environment, scientists with expertise in physiology, genetics, animal management, and nutrition will need to be enlisted. The objectives of this review are to highlight some of the prominent environmental regulatory activity that has occurred nationally in the past few years, to outline some of the emerging environmental issues, and to move members of the animal science profession toward thinking about what they can contribute toward addressing these issues. Animal scientists are uniquely qualified to engage in environmental research, education, and policymaking because of our comprehensive understanding of the complexity of whole-farm management and the interactions between animal management and manure management. Animal science departments have the opportunity to train students to be leaders in addressing environmental issues related to animal production, provided departments incorporate environmental education into curricula. Animal scientists can contribute greatly to the many areas of research that address emerging and current environmental issues, helping to ensure that policy is science-based and mitigation strategies are feasible.

Agriculture↗

An improved resazurin-based cytotoxicity assay for hepatic cells.

A simple resazurin-based cytotoxicity assay is presented for screening of cytotoxicity in hepatocytes and liver cell lines. Human hepatoma (HepG2) cells in 96-well culture plates were exposed to known toxic (cisplatin, 5-fluorouracil, ethionine, flufenamic acid, and diflunisal) and control (transplatin, 5-chlorouracil, methionine, and acetylsalicylic acid) compounds for 1-3 days, and resazurin (5 micromol/L) was added. A conventional short-term (1 h) assay was first performed, where cytotoxicity is indicated by decreased reduction of resazurin to its fluorescent product resorufin. Our improved assay consists of additionally measuring fluorescence 2-4 days later, when cytotoxicity is indicated by a striking increase in the concentration of resorufin, resulting from two distinct processes. First, viable liver-derived cells slowly convert resorufin to nonfluorescent metabolites. Fluorescence of control cell wells decreased to background during a 2- to 4-day exposure to resazurin. This metabolism of resorufin was largely blocked by dicumarol and to lesser extents by disulfiram and SKF525a. Second, dead or dying cells slowly convert resazurin to resorufin but do not further metabolize resorufin; thus this fluorescent metabolite accumulates to high levels in wells with dead cells by 2 to 4 days. A similar increase in fluorescence associated with cytotoxicity was observed in primary cultures of rat hepatocytes using the long-term resazurin-based assay. In addition to an improved signal relative to the short-term assay, the inversion of the fluorescent signal from high = alive short-term to high = dead long-term allows determination of two independent cytotoxicity endpoints after addition of one innocuous vital dye.

Animals↗

Effects of dietary ingredients on manure characteristics and odorous emissions from swine.

Two feeding studies were conducted to examine the impact of dietary inclusion of specific feed ingredients on manure characteristics and manure odor. In one study, 72 finishing pigs were used to evaluate the effects of distillers dried grains with solubles (DDGS) on pig performance, manure characteristics, and odorous emissions. Three diets containing 0, 5, and 10% DDGS were fed during six 4-wk feeding periods. Week 1 served as a dietary adjustment period. Animals were housed in two feeding rooms (six pigs/room) with one treatment/room. A new group of animals (average initial BW = 85.8 kg) was used for each feeding period. Diets were replicated four times. Rooms were equipped with individual shallow manure storage pits that were cleaned once weekly (d 7). On d 4 and 7 of each week, manure pit samples, for chemical analyses, and air samples, for olfactometry analysis, were collected from each room. Odor dilution threshold was greater on d 7 than on d 4 of manure storage across all treatments (P < 0.01). No treatment differences in manure composition were noted. In the second study, weaned pigs (approximately 5 wk old) were fed isonitrogenous diets containing 0, 1.5, or 3% bloodmeal. Pigs were housed by diet (three pigs/diet) in one of four individual feeding rooms. A new group of pigs was used for each of the two, 4-wk feeding periods. During period 1, the 3% bloodmeal diet was fed in two of the four rooms; the 0% bloodmeal diet was fed in two rooms during period 2. Manure samples, for chemical analyses, and air samples, for olfactometry analysis, were collected 2 d per week (d 4 and d 6) from each room during wk 2 through 4. No significant treatment differences were observed for odor dilution threshold (P = 0.30). Longer manure storage time, 6 d vs 4 d, resulted in a larger odor dilution ratio (P < 0.01). Manure composition was unaltered by storage time. Results suggest that odor intensifies during storage.

Air Pollutants↗

Technical note: fourier transform infrared (FTIR) spectroscopy as an optical nose for predicting odor sensation.

Quantifying odor is important for objectively assessing the impact of animal production systems on surrounding areas. A possible method that has received little attention is Fourier transform (mid) infrared spectroscopy (FTIR). Gases that contribute to odor have unique infrared spectra, and the advantage of FTIR over electronic nose technology or gas chromatography is that theoretically all these gases can be analyzed instantaneously. To determine the feasibility of FTIR for predicting odor, 71 air samples analyzed by olfactometry were scanned in a spectrometer using an 84-m path-length gas cell. Scans were obtained over a period of about 1 min and from 4,000 to 740 cm(-1) with a resolution of 0.5 cm(-1). Calibrations for predicting odor were developed using partial least squares regression with full cross-validation. Air samples were obtained from experiments with pigs fed diets formulated to alter odor emission or from stored manure. Odor threshold dilution ratios averaged 676+/-491 units, with a range from 120 to 2,161. Using these samples, a prediction error for odor sensation of 344 units (R2 = 0.51) was obtained. Log transformation of the odor data improved the R2 to 0.61. Based on the olfactometry data, it is estimated that the measurement error of olfactometry is 250 units, which limits the R2 of any method to approximately 0.74. Thus, this calibration is very encouraging. In conclusion, FTIR shows promise as a practical means for objectively assessing swine odor.

Air Pollutants↗

Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke.

Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05).

Adult↗

Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.

BACKGROUND: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and (15)O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.

Acute Disease↗

A default mode of brain function.

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

Adult↗

Quantitative measurements of cerebral blood flow in patients with unilateral carotid artery occlusion: a PET and MR study.

Although it has been demonstrated that quantitative measures of cerebral blood flow (CBF) can be obtained with the singular value decomposition (SVD) algorithm, the extent to which quantitative CBF measurements can be utilized under pathophysiological conditions has not been systematically studied. A total of five healthy volunteers and five patients with unilateral carotid artery occlusion were studied. Only magnetic resonance (MR) images were acquired for the volunteer group while both MR and positron emission tomography (PET) images were acquired for the patient group. Assessments of CBF from normal volunteers compared favorably with values reported in the literature. However, while a linear relationship was observed for each patient when MR measured CBF was compared to that obtained from PET, this linear relationship diminished when all patients were analyzed as a group (r = 0.41). A correction factor (CF) was proposed that was equal to the ratio of the area of the venous output function (VOF) in each patient to the mean VOF obtained from the volunteer group. After globally scaling the CBF of each patient based on the experimentally derived CF, a substantial improvement was observed (a slope of 1.02 and r = 0.8 for the linear regression line) in the relationship between MR estimated CBF and those obtained from PET.

Analysis of Variance↗

Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage.

A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 +/- 7.6 vs. 37.0 +/- 13.9 mL 100 g(-1) min(-1), P = 0.0004; CMRO2: 1.4 +/- 0.5 vs. 2.9 +/- 0.9 mL 100 g(-1) min(-1), P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 +/- 0.15 vs. 0.47 +/- 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 +/- 0.16 vs. 0.51 +/- 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset.

Adult↗

Severe hemodynamic impairment and border zone--region infarction.

PURPOSE: To investigate the relationship between the patterns of cerebral infarction that have been associated with hemodynamic impairment and the presence of severe chronic hemodynamic compromise (increased oxygen extraction fraction) in a large prospectively enrolled group of patients with carotid artery occlusion. MATERIALS AND METHODS: At enrollment in a prospective study of cerebral hemodynamics, 110 patients with carotid occlusion underwent (a) positron emission tomography for the measurement of cerebral oxygen extraction fraction and (b) computed tomographic (CT) or magnetic resonance (MR) examinations of the brain. Infarcts were categorized retrospectively by vascular territory, location, and pattern. The association of these findings with hemodynamic impairment (increased oxygen extraction fraction) was investigated. RESULTS: No border zone-region infarctions were found in 35 asymptomatic patients. In 75 symptomatic patients, cortical border zone-region infarction was found in seven of 36 patients with increased oxygen extraction fraction, and in two of 39 with normal oxygen extraction fraction (P =.08, difference not significant). The pattern of multiple white matter lesions arranged parallel to the lateral ventricle was observed only in symptomatic patients with increased oxygen extraction fraction (eight of 36 patients; P =.002; sensitivity, 22%; specificity, 100%). This finding was more frequent with MR imaging (seven of 14 patients) than with CT (one of 22 patients). CONCLUSION: Multiple white matter infarctions, arranged parallel to the lateral ventricle, are associated with severe hemodynamic impairment. This pattern of infarction is likely due to a hemodynamic mechanism.

Adult↗

Blood-to-brain glucose transport, cerebral glucose metabolism, and cerebral blood flow are not increased after hypoglycemia.

Recent antecedent hypoglycemia has been found to shift glycemic thresholds for autonomic (including adrenomedullary epinephrine), symptomatic, and other responses to subsequent hypoglycemia to lower plasma glucose concentrations. This change in threshold is the basis of the clinical syndromes of hypoglycemia unawareness and, in part, defective glucose counterregulation and the unifying concept of hypoglycemia-associated autonomic failure in type 1 diabetes. We tested in healthy young adults the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport, a plausible mechanism of this phenomenon. Eight subjects were studied after euglycemia, and nine were studied after approximately 24 h of interprandial hypoglycemia ( approximately 55 mg/dl, approximately 3.0 mmol/l). The latter were shown to have reduced plasma epinephrine (P = 0.009), neurogenic symptoms (P = 0.009), and other responses to subsequent hypoglycemia. Global bihemispheric blood-to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves-the latter determined by positron emission tomography (PET)-after intravenous injection of [1-(11)C]glucose at clamped plasma glucose concentrations of 65 mg/dl (3.6 mmol/l). For these calculations, a model was used that includes a fourth rate constant to account for egress of [(11)C] metabolites. Cerebral blood flow was measured with intravenous [(15)O]water using PET. After euglycemia and after hypoglycemia, rates of blood-to-brain glucose transport (24.6 +/- 2.3 and 22.4 +/- 2.4 micromol. 100 g(-1). min(-1), respectively), cerebral glucose metabolism (16.8 +/- 0.9 and 15.9 +/- 0.9 micromol. 100 g(-1). min(-1), respectively) and cerebral blood flow (56.8 +/- 3.9 and 53.3 +/- 4.4 ml. 100 g(-1). min(-1), respectively) were virtually identical. These data do not support the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport during subsequent hypoglycemia. They do not exclude regional increments in blood-to-brain glucose transport. Alternatively, the fundamental alteration might lie beyond the blood-brain barrier.

Adult↗

Risks of stroke and current indications for cerebral revascularization in patients with carotid occlusion.

Preventing further stroke in patients with complete carotid artery occlusion remains a difficult challenge because there is no therapy proven effective for this prevention. These patients comprise approximately 15% of patients with carotid artery territory transient ischemic attacks or infarction. Patients with symptomatic carotid artery occlusion have an overall risk of subsequent stroke of 7% per year and a risk of stroke ipsilateral to the occluded carotid artery of 5.9% per year. The presence of severe hemodynamic failure demonstrated by increased oxygen extraction fraction (OEF) of the brain, in a cerebral hemisphere distal to a symptomatic occluded carotid artery, is an independent predictor of subsequent ischemic stroke with a risk comparable to that seen in medically treated patients with symptomatic severe carotid artery stenosis.

Brain↗

Preview of a new trial of extracranial-to-intracranial arterial anastomosis: the carotid occlusion surgery study.

In 1985, the International Study of Extracranial-to-Intracranial Arterial Anastomosis demonstrated no benefit from extracranial-to-intracranial arterial bypass operations in treatment of patients with extensive cerebrovascular disease including those with occlusions of the internal carotid artery. Interest in the potential use of extracranial-to-intracranial arterial bypass operations, however, has been rekindled by evidence that some patients with occlusion of the internal carotid artery have a poor collateral circulation and a high risk for recurrent ischemic events. Other patients with adequate perfusion after occlusion have a low likelihood for recurrent stroke. Restricting surgical treatment to only those patients judged to have a high risk for recurrent stroke might improve the usefulness of the bypass operation. A new clinical trial is proposed, testing the potential usefulness of extracranial-to-intracranial arterial bypass operations for treatment of carefully selected patients with occlusion of the internal carotid artery. Several issues that are being addressed in this new trial are described in this article.

Arteriovenous Anastomosis↗

Comparison of PET oxygen extraction fraction methods for the prediction of stroke risk.

UNLABELLED: PET measurement of increased oxygen extraction fraction (OEF) identifies patients at high risk for subsequent stroke. OEF methodology remains controversial. In this study we compare the sensitivity and specificity of absolute OEF measurements with ipsilateral-to-contralateral ratios of absolute OEF and count-based OEF estimates. METHODS: Multivariate analyses of OEF methods were performed using data from patients with symptomatic carotid artery occlusion (n = 68). Outcome and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: All 3 methods were predictive of stroke risk in univariate analysis. Only the count-based method remained significant in multivariate analysis. The area under the ROC curve was greatest for the count-based ratio: 0.815 versus 0.769 (absolute) and 0.737 (ratios of absolute). CONCLUSION: All 3 methods are predictive of stroke risk in patients with unilateral carotid artery occlusion. ROC curve analysis is useful for selecting optimal thresholds for maximal sensitivity and specificity.

Arteriosclerosis↗

Benign prognosis of never-symptomatic carotid occlusion.

OBJECTIVE: To determine the prognosis of asymptomatic carotid artery occlusion. BACKGROUND: As opposed to symptomatic carotid occlusion, little information is available on the prognosis of asymptomatic carotid occlusion. METHOD: Thirty never-symptomatic and 81 symptomatic patients with carotid occlusion underwent baseline assessment of 15 risk factors together with PET measurements of oxygen extraction fraction (OEF). Every 6-month telephone contact recorded interval medical treatment and subsequent stroke occurrence during an average follow-up of 32 months. Patients, treating physicians, and an end point adjudicator were blinded to PET results. RESULTS: Ischemic stroke occurred in 1 of 30 of never-symptomatic patients (3.3%) and 15 of 81 of symptomatic patients (18.5%; p = 0.03). No strokes in the carotid territory distal to the occluded vessel occurred in the never-symptomatic patients. Multivariate analysis of baseline risk factors for all 111 patients revealed that age, plasma fibrinogen level, and PET findings of high OEF distal to the occluded carotid artery were the only independent predictors of subsequent stroke (p < 0.05). Previous ipsilateral hemispheric or retinal symptoms was not a significant predictive variable. The lower risk of stroke in never-symptomatic patients was associated with a lower incidence of high OEF (4 of 30) as opposed to symptomatic patients (39 of 81; p = 0.002), but there was no significant difference in age or fibrinogen level. CONCLUSIONS: Never-symptomatic carotid occlusion carries a very low risk of subsequent ischemic stroke. This benign prognosis is associated with a low incidence of cerebral hemodynamic compromise in these patients. These data support further the importance of hemodynamic factors in the pathogenesis of ischemic stroke in patients with carotid occlusion.

Aged↗