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L E Moore

Publications and source records attributed to L E Moore.

At least 19 recordsLinked to original sources
PubMed1999

NMDA-induced dendritic oscillations during a soma voltage clamp of chick spinal neurons.

An investigation of dendritic membrane properties was performed by whole-cell patch measurements of the biophysical properties of intact chick spinal neurons that are involved in rhythmogenesis. A whole-cell voltage clamp of the somatic membrane was used to block NMDA-induced voltage oscillations from the cell body, thus partially isolating the intrinsic oscillatory properties of dendritic membranes from those of the soma. An experimental approach was developed that takes into account the complexity of the dendritic tree in an environment as normal as possible, without the need for cell isolation or slice preparations. A computational study of the experimentally determined model showed that excitatory amino acid receptors on dendrites can dynamically control the electrotonic length of the dendrites through the activation of negative slope conductances. These experiments demonstrate the presence of NMDA receptors on the dendrites and that they induce intrinsic oscillations when the synaptic input from other cells is significantly reduced.

Animals↗
PubMed1999

N-Methyl-D-aspartate-induced oscillations in whole cell clamped neurons from the isolated spinal cord of Xenopus laevis embryos.

The patch-clamp technique was used to measure the effect of N-methyl-D-aspartate (NMDA) on Xenopus embryonic neurons in an isolated, but intact spinal cord. Whole cell recordings were done at external calcium concentrations of 1 mM. NMDA alone (50-200 microM) or in association with 10 microM serotonin or glycine induced oscillatory activity in most presumed motoneurons, which were therefore considered part of rhythm generating networks. In the presence of TTX, one-half of these neurons maintained this activity. The oscillations fell into two main categories: voltage-dependent, low-frequency (0.3-0.5 Hz) and voltage-independent, high-frequency (3-8 Hz) oscillations. NMDA alone induced TTX-insensitive oscillations in one-third of the neurons; however, the percentage of neurons showing oscillations was greater in the presence of exogenous 5-hydroxytryptamine (5-HT) or glycine. Because these observations were made at embryonic stages where little or no serotonergic innervation exists, it is likely that NMDA-induced intrinsic oscillatory activity in Xenopus embryonic neurons does not require 5-HT.

Animals↗
PubMed1998

Fluid therapy in the hypoproteinemic patient.

Hypoproteinemia can result in many adverse consequences, including hypovolemia and the formation of edema. An understanding of the normal forces governing plasma will help the clinician tailor appropriate fluid therapy in these patients. Various fluids that can be used including crystalloids, colloids, and blood products will be discussed.

Animals↗
PubMed1998

Simulation and parameter estimation study of a simple neuronal model of rhythm generation: role of NMDA and non-NMDA receptors.

Simple neural network models of the Xenopus embryo swimming CPG, based on the one originally developed by Roberts and Tunstall (1990), were used to investigate the role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in conjunction with faster non-NMDA components of synaptic excitation, in rhythm generation. The voltage-dependent NMDA current "follows" the membrane potential, leading to a postinhibitory rebound that is more efficient than one without voltage dependency and allows neurons to fire more than one action potential per cycle. Furthermore, the model demonstrated limited rhythmic activity in the absence of synaptic inhibition, supporting the hypothesis that the NMDA channels provide a basic mechanism for rhythmicity. However, the rhythmic properties induced by the NMDA current were observed only when there was moderate activation of the non-NMDA synaptic channels, suggesting a modulatory role for this component. The simulations also show that the voltage dependency of the NMDA conductance, as well as the fast non-NMDA current, stabilizes the alternation pattern versus synchrony. To verify that these effects and their implications on the mechanism of swimming and transition to other types of activity take place in the real preparation, constraints on parameter values have to be specified. A method to estimate synaptic parameters was tested with generated data. It is shown that a global analysis, based on multiple iterations of the optimization process (Foster et al., 1993), gives a better understanding of the parameter subspace describing network activity than a standard fit with a sensitivity analysis for an individual solution.

Animals↗
PubMed1997

Preclinical pharmacokinetics of beta-L-dioxolane-cytidine, a novel anticancer agent, in rats.

PURPOSE: beta-L-Dioxolane-cytidine (OddC), a novel L-nucleoside analog with potent cytotoxicity in vitro, appears to be a promising candidate for anticancer therapy. In this study, a high performance liquid chromatography (HPLC) analytical method was developed and the preclinical pharmacokinetics of OddC were characterized in rats. METHODS: Adult male Sprague Dawley rats were given 10, 25, or 50 mg/kg of OddC both intravenously and orally with a 6-day washout period between doses. Each rat received one dosage level of OddC and the route of administration was assessed by a randomized crossover design. Plasma and urine concentrations were determined by HPLC. Pharmacokinetic parameters were generated by area-moment analysis. RESULTS: Following intravenous administration, the plasma concentrations of OddC declined rapidly in a biexponential manner with a terminal phase half-life of 1.65 +/- 1.12 h (mean +/- SD). Mean total, renal, and nonrenal clearances were 1.38 +/- 0.62, 0.30 +/- 0.14, and 1.08 +/- 0.59 1/h per kg. Approximately 22% of the administered dose was excreted unchanged in the urine. Thus, nonrenal clearance was the predominant route of elimination of OddC. The steady-state volume of distribution averaged 1.42 +/- 0.66 1/kg, indicating intracellular distribution of OddC. The nucleoside analog was slowly absorbed after oral administration and bioavailability varied greatly between individual rats, averaging 41 +/- 27% when calculated from urinary excretion data and 37 +/- 25% when calculated from plasma OddC concentration data. CONCLUSION: The pharmacokinetics of OddC in rats were linear over the dose range studied.

Animals↗
PubMed1997

Venous air embolism: a review.

Venous air embolism (VAE) can be a lethal complication of surgical procedures, during which (1) venous pressure at the site of surgery is subatmospheric or (2) gas is forced under pressure into a body cavity. Though classically associated with neurosurgery, VAE is also a potential complication of laparoscopic, pelvic, and orthopedic procedures. It is, therefore, essential for the practicing anesthesiologist to recognize and treat venous air entrainment. An in-depth review of the pathophysiology, clinical presentation, detection, prevention, and treatment of VAE is presented.

Embolism, Air↗
PubMed1997

Relationship of urinary arsenic to intake estimates and a biomarker of effect, bladder cell micronuclei.

The purpose of this study was to investigate methods for ascertaining arsenic exposure for use in biomarker studies. Urinary arsenic concentration is considered a good measure of recent arsenic exposure and is commonly used to monitor exposure in environmental and occupational settings. However, measurements reflect exposure only in the last few days. To cover longer time periods exposure can be estimated using arsenic intake data, calculated by combining measures of environmental arsenic and inhalation/ingestion rates. We compared these different exposure assessment approaches in a population chronically exposed to arsenic in drinking water in northern Chile. The study group consisted of 232 people, some drinking water low in arsenic (15 micrograms/l) and others drinking water with high arsenic concentrations (up to 670 micrograms/l). First morning urine samples and questionnaire data, including fluid intake information, were collected from all participants. Exfoliated bladder cells were collected from male participants for the bladder cell micronuclei assay. Eight different indices of exposure were generated, six based on urinary arsenic (microgram As/l urine; microgram As/g creatinine; microgram InAs/l urine; microgram MMA/l urine; microgram DMA/l urine; microgram As/h, excreted), and two on fluid intake data (microgram As/day, ingested; microgram As/l fluid ingested-day). The relationship between the different exposure indices was explored using correlation analysis. In men, exposure indices were also related to a biomarker of effect, bladder cell micronuclei. While creatinine-adjusted urinary arsenic concentrations had the strongest correlations with the two intake estimates (r = 0.76, r = 0.81), unadjusted urinary arsenic showed the strongest relationship with bladder cell micronuclei. These data suggest that, in the case of the bladder, unadjusted urinary arsenic concentrations better reflect the effective target organ dose compared to other exposure measures for biomarker studies.

Adolescent↗
PubMed1997

Development of a nested PCR assay for detection of feline infectious peritonitis virus in clinical specimens.

A diagnostic test for feline infectious peritonitis virus (FIPV) infection based on a nested PCR (nPCR) assay was developed and tested with FIPV, feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV) and clinical fluid samples from cats with effusive feline infectious peritonitis (FIP). The target sequence for the assay is in the S1 region of the peplomer protein E2 gene. A vaccine strain of FIPV and two wild-type FIPV strains tested positive, but FECV, TGEV, and CCV tested negative. Preliminary tests with 12 cats with clinical evidence of effusive FIP and 11 cats with an illness associated with effusions, but attributed to other causes, were performed. Eleven of the 12 cats with effusive FIP tested positive, while 1 was negative. Ten of the 11 cats ill from other causes tested negative, while 1 was positive. On the basis of clinical laboratory and histopathologic criteria, the preliminary sensitivity and specificity of the assay were 91.6 and 94%, respectively.

Animals↗
PubMed1997

Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking water.

Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic.

Adult↗
PubMed1997

Decrease in bladder cell micronucleus prevalence after intervention to lower the concentration of arsenic in drinking water.

Epidemiological studies performed in Taiwan, Argentina, and Chile suggest that ingestion of arsenic (As) may cause bladder cancer. Because of these findings, we previously investigated the relationship between As ingestion and genetic damage to the urothelium in two cross-sectional biomarker studies, one in Nevada and one in Chile. In both studies, we found that increased levels of micronucleated cells (MNCs) in exfoliated bladder cells were associated with elevated concentrations of As in drinking water, suggesting that As induces genetic damage to bladder cells. To further investigate this relationship, we conducted an intervention study in a subset of highly exposed men (n = 34) from the cross-sectional study in Chile. Subjects whose usual source of water contained about 600 micrograms/liter As were supplied with water lower in As (45 micrograms/liter) for 8 weeks, allowing ample opportunity for renewal and exfoliation of bladder epithelial cells. Mean urinary As levels decreased during the intervention from 742 to 225 micrograms/liter. Bladder MNC prevalence also decreased from 2.63 MNCs/1000 cells preintervention to 1.79 MNCs/1000 cells postintervention (P < 0.05). When the analysis was limited to individuals previously having subcytotoxic urinary As levels (< 700 micrograms/liter), the change between pre- and postintervention MNC was more pronounced: the level decreased from 3.54 to 1.47 MNCs/1000 cells, respectively (P = 0.002). Among smokers, MNC prevalences decreased from 4.45 MNCs/1000 cells preintervention to 1.44 MNCs/1000 cells postintervention (P = 0.002). Among nonsmokers, the decrease was much smaller: 2.04 MNCs/1000 cells preintervention to 1.90 MNCs/1000 cells postintervention (P = 0.25), suggesting that smoker's bladder cells could be more susceptible to genotoxic damage caused by As. The reduction in bladder MNC prevalence with reduction in As intake provides further evidence that As is genotoxic to bladder cells.

Adult↗
PubMed1996

Use of the fluorescent micronucleus assay to detect the genotoxic effects of radiation and arsenic exposure in exfoliated human epithelial cells.

The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN-) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. We also applied the assay to exfoliated bladder cells of 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 micrograms As/L) and 18 matched controls (average level, 16 micrograms As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN-) and those containing whole chromosomes (MN+) both increased (1.65-fold, P = 0.07, and 1.37-fold, P = 0.15, respectively), suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN- frequency increased 2.06-fold (P = 0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN- and MN+ were positively associated with urinary arsenic and its metabolites. However, the association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can now be determined in epithelial tissues.

Adult↗
PubMed1996

Hypnotically-induced vasodilation in the treatment of repetitive strain injuries.

The study examined the effectiveness of behaviorally-induced vasodilation (hypnosis with biofeedback and autogenics) in the treatment of upper extremity repetitive strain injuries (RSI). Thirty patients with recent onset of upper extremity RSI symptoms were randomly assigned to 1 of 2 treatment conditions, i.e., hypnotically-induced vasodilation or a waiting-list control. Treatments were given on an individual basis, once a week for 6 weeks. Patients in the treatment condition showed highly significant increases in hand temperature between pre- and post-treatment. Patients in the treatment condition also showed highly significant reductions in pain in comparison to the waiting list condition.

Adult↗
PubMed1996

Capnography facilitates tight control of ventilation during transport.

OBJECTIVE: We tested the hypothesis that Paco2 would be more tightly controlled if end-tidal CO2 monitoring was used during hand ventilation for transport of intubated patients. DESIGN: Randomized, prospective analysis of the no-monitor and monitor-blind groups (the monitor was on the bed during transport but only the investigator was aware of the end-tidal CO2 values). Nonrandomized, prospective analysis of the monitor group (ventilation controlled using end-tidal CO2 value from monitor). SETTING: University hospital operating room and intensive care unit (ICU). PATIENTS: Fifty intubated patients who were transported from the operating room to the ICU or from the ICU to the neuroradiology suite were assigned randomly to one of two groups: a) no-monitor group (n = 25); and b) monitor-blind group (n = 25). An additional group (monitor group, n = 10) was subsequently added to the study. INTERVENTIONS: Capnography was instituted in all patients in a blocked fashion. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and end-tidal CO2 values were measured before and after transport. When comparing overall group data, pre- and post-Paco2 values were similar: monitor 39 +/- 2 vs. 41 +/- 2 torr (5.2 +/- 0.3 vs. 5.5 +/- 0.3 no-monitor 39 +/- 1 vs. 37 +/- torr (5.2 +/- 0.1 vs. 5.0 +/- 0.1 kPa). However, when comparing Paco2 values for individual patients, we found that there was significantly greater variability for Paco2 after transport when end-tidal CO2 was not used for control of ventilation during transport. CONCLUSIONS: These data do not support routine monitoring of end-tidal CO2 during short transport times in adult patients requiring mechanical ventilation. However, the monitor may prevent morbidity in patients requiring tight control of Paco2.

Adolescent↗
PubMed1996

Arsenic methylation patterns before and after changing from high to lower concentrations of arsenic in drinking water.

Inorganic arsenic (In-As), an occupational and environmental human carcinogen, undergoes biomethylation to monomethylarsonate (MMA) and dimethylarsinate (DMA). It has been proposed that saturation of methylation capacity at high exposure levels may lead to a threshold for the carcinogenicity of In-As. The relative distribution of urinary In-As, MMA, and DMA is used as a measure of human methylation capacity. The most common pathway for elevated environmental exposure to In-As worldwide is through drinking water. We conducted a biomarker study in northern Chile of a population chronically exposed to water naturally contaminated with high arsenic content (600 micrograms/l). In this paper we present the results of a prospective follow-up of 73 exposed individuals, who were provided with water of lower arsenic content (45 micrograms/l) for 2 months. The proportions of In-As, MMA, and DMA in urine were compared before and after intervention, and the effect of other factors on the distribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associated with a small decrease in the percent In-As in urine (from 17.8% to 14.6%) and in the MMA/DMA ratio (from 0.23 to 0.18). Other factors such as smoking, gender, age, years of residence, and ethnicity were associated mainly with changes in the MMA/DMA ratio, with smoking having the strongest effect. Nevertheless, the factors investigated accounted for only about 20% of the large interindividual variability observed. Genetic polymorphisms in As-methylating enzymes and other co-factors are likely to contribute to some of the unexplained variation. The changes observed in the percent In-As and in the MMA/DMA ratio do not support an exposure-based threshold for arsenic methylation in humans.

Adult↗
PubMed1996

Methylation study of a population environmentally exposed to arsenic in drinking water.

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.

Adolescent↗
PubMed1995

Antibiotics prevent liver injury in rats following long-term exposure to ethanol.

BACKGROUND/AIMS: Kupffer's cells participate in alcohol-induced liver injury, and endotoxemia is observed in human alcoholics and in a rat model. This study evaluated the effect of reducing bacterial endotoxin production by intestinal sterilization on alcohol-induced liver injury. METHODS: Male Wistar rats were exposed to ethanol continuously for up to 3 weeks via intragastric feeding. The gut was sterilized with polymyxin B and neomycin. RESULTS: Fecal culture of stool samples from ethanol-fed rats treated with antibiotics showed virtually no growth of gram-negative bacteria. Endotoxin levels of 80-90 pg/mL in plasma of ethanol-fed rats were reduced to < 25 pg/mL by antibiotics. Antibiotic treatment also completely prevented elevated aspartate aminotransferase levels and significantly reduced the average hepatic pathological score in rats exposed to ethanol. Oxygen tension on the surface of the liver measured in vivo was decreased significantly from control values of 48 +/- 1 to 39 +/- 1 mumol/L in ethanol-treated rats. This hypoxia was prevented by treatment with antibiotics. Moreover, the increase in rates of ethanol elimination due to long-term ethanol treatment was prevented by antibiotic treatment. CONCLUSIONS: Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.

Animals↗
PubMed1995

Inhibition of crossed caudal interneurons by lateral interneurons in lamprey spinal chord during fictive locomotion.

Templates of the membrane potential profiles from lateral (LI) interneurons and motoneurons during glutamate- and N-methyl-D-aspartate (NMDA)-induced fictive locomotion showed pronounced plateau phases. In contrast, crossed caudal (CC) interneurons had a less obvious and steeper plateau region that was followed by a clear notch coinciding with the end of the lateral interneuron plateau phase. These results indicate a significant inhibitory input from LI to CC interneurons.

Animals↗