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T E Albertson

Publications and source records attributed to T E Albertson.

At least 37 records · Page 2Linked to original sources
PubMed1998

An unusual exposure to methyl bromide leading to fatality.

INTRODUCTION: Methyl bromide has been responsible for deaths that usually occur from its accidental inhalation during fumigation. CASE REPORT: We report an accidental fatality that occurred after methyl bromide seeped through underground conduits from a fumigated building to an adjacent guest house on the same property. The patient developed refractory seizures, intermittent fever, and multiorgan system failure before dying 19 days after exposure. The initial serum bromide was 27 mg/dL. Postmortem analysis detected methyl bromide concentrations of 2.9 mg/dL in the blood, 1.7 mg/dL in the bile, 24 micrograms/g in the liver, and 28 micrograms/g in the adipose tissue. CONCLUSION: Methyl bromide, although applied under acceptable safety standards, led to the inadvertent death of a young woman. Extreme care must be used when fumigating to insure no unsuspected seepage routes exist.

Adult↗
PubMed1997

Ortho-substituted 2,2',3,5',6-pentachlorobiphenyl (PCB 95) alters rat hippocampal ryanodine receptors and neuroplasticity in vitro: evidence for altered hippocampal function.

The effects of PCBs on hippocampal function were studied in vitro, by radioligand-receptor binding analysis and electrophysiological measurements of the hippocampal slice preparation. [3H]Ryanodine, a conformation-sensitive probe for ryanodine receptors, was employed to determine how PCBs influence specific high-affinity occupancy to receptors found in microsomes isolated from rat hippocampus. PCB 95 (2,2',3,5'6-pentachlorobiphenyl) exhibited a dose-dependent enhancement of [3H]ryanodine receptor occupancy with an EC50 of 12 microM. In contrast, PCB 66 (2,3'4,4'-tetrachlorobiphenyl) showed no activity toward ryanodine receptors, up to its solubility limit (> or = 200 microM. Population spike (PS) and excitatory postsynaptic potential (EPSP) responses were recorded from striatum pyramidale of the CA1 region, which were generated from single pulse orthodromic stimulation of Schaffer collateral/commissural (SC/C) fibers at striatum radiatum of the hippocampal slice preparation. After the introduction of PCB 95 to the perfusion medium, PCB 95 depressed PS amplitude, especially at high stimulus intensities. Significant reductions in PS and EPSP maxima were seen, even after induction of long term potentiation, a model of neuroplasticity. However, these actions were not observed with PCB 66 which lacks ryanodine receptor activity, implicating a ryanodine receptor-mediated mechanism in the general depression of pyramidal cell excitability seen with PCB 95. Taken together, these results reveal a novel, arylhydrocarbon (Ah) receptor-independent, mechanism by which PCB 95 alters neuronal Ca2+ signaling and neuroplasticity in adult brain.

Animals↗
PubMed1997

The effects of lindane and long-term potentiation (LTP) on pyramidal cell excitability in the rat hippocampal slice.

An in vitro orthodromic stimulation technique was used to examine the effects of lindane and long-term potentiation (LTP) inducing stimuli, alone or in combination, on the excitatory afferent terminal of CA1 pyramidal cells and on recurrent collateral evoked inhibition using the rat hippocampal slice model. Hippocampal slices of 400 microns thickness were perfused with oxygenated artificial cerebrospinal fluid. Stimulation of Schaffer collateral/commissural fibers produced extracellular excitatory postsynaptic potential (EPSP) and/or populations spike (PS) responses recorded from electrodes in the CA1 region. A paired-pulse technique was used to measure gamma-aminobutyric acid (GABAA)-mediated recurrent inhibition before and after treatments. After both lindane and LTP, larger PS amplitudes for a given stimulus intensity were seen. The resulting leftward shift in the curve of the PS amplitude versus stimulus intensity was larger after LTP than after 25 microM lindane. Both lindane and LTP treatments reduced PS thresholds and reduced or eliminated recurrent inhibition as measured by paired-pulse stimulation at the 15 msec interval. The reduction of recurrent inhibition after both treatments was more pronounced at lower stimulus intensities. When LTP stimuli were applied after lindane exposure a further large shift to the left was seen in the PS amplitude versus stimulus intensity curve. A smaller shift to the left was seen in the PS amplitude versus stimulus intensity curve only at the higher stimuli when lindane exposure occurred after LTP. Only at low stimulus intensities were further argumentations seen in PS amplitudes when the LTP stimuli was followed by a second LTP stimuli. Previous exposure to 25 microM lindane stimuli does not block the development of a further robust LTP in this in vitro model.

Animals↗
PubMed1996

The effect of propofol on CA1 pyramidal cell excitability and GABAA-mediated inhibition in the rat hippocampal slice.

An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of propofol on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid, and electrodes were placed in the CA1 region to record extracellular field population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. The major effect of propofol (7-28 microM) was a dose and time dependent increase in the intensity and duration of GABA-mediated inhibition. This propofol effect could be rapidly and completely reversed by exposure to known GABAA antagonists, including picrotoxin, bicuculline and pentylenetetrazol. It was also reversed by the chloride channel antagonist, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was not antagonized by central (flumazenil) or peripheral (PK11195) benzodiazepine antagonists. Reversal of endogenous inhibition was also noted with the antagonists picrotoxin and pentylenetetrazol. Input/output curves constructed using stimulus propofol caused only a small enhancement of EPSPs at higher stimulus intensities but had no effect on PS amplitudes. These studies are consistent with propofol having a GABAA-chloride channel mechanism causing its effect on recurrent collateral evoked inhibition in the rat hippocampal slice.

Action Potentials↗
PubMed1995

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Deoxyribonuclease I↗
PubMed1995

Developing guidelines for biotechnology drug use: experience with antithrombin III.

Development of institutional guidelines for use of high-cost biotechnology drugs, such as antithrombin III, is a valuable tool in formulary management. This article describes the process by which the University of California Davis Medical Center used an ad hoc committee to the P & T Committee to develop guidelines for antithrombin III use. Performing an objective analysis of available literature to address the appropriate role of a biotechnology agent is necessary to develop consensus guidelines. Approval of use guidelines by the P & T Committee provides the necessary structure for optimal use of biotechnology agents, such as antithrombin III.

Antithrombin III↗
PubMed1995

Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell excitability in the rat hippocampal slice.

An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed analyses of the effects of lindane. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. Perfusion with lindane produced both time and dose dependent changes in a number of the responses measured. The most striking effect produced by lindane was the loss of GABAA-mediated recurrent collateral inhibition. This tended to occur rapidly, often before changes in EPSP or PS responses could be detected. With longer exposures to lindane, repetitive discharge of pyramidal cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM) also completely reversed the effects of the injectable anesthetic, propofol, a compound known to potentiate GABAA-mediated inhibition via a direct action on the GABAA receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed that lindane increased EPSP and PS response amplitudes at any given stimulus intensity resulting in a leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low intensity stimuli and became progressively less so as stimulus intensities approached those yielding maximal responses. In addition lindane significantly increased paired pulse facilitation of EPSPs during paired stimulus presentation.

Anesthetics, Intravenous↗
PubMed1994

Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications.

STUDY HYPOTHESIS: Administration of the benzodiazepine antagonist flumazenil may unmask seizures in mixed cocaine-benzodiazepine intoxication. DESIGN: Male Sprague-Dawley rats received 100 mg/kg cocaine IP alone, 5 mg/kg diazepam alone, or a combination of diazepam and cocaine. Three minutes later, groups were challenged with vehicle or flumazenil 5 or 10 mg/kg IP. Animal behavior, seizures (time to and incidence), death (time to and incidence), and cortical EEG tracings were recorded. INTERVENTIONS: Administration of flumazenil to animals after they had received a combination dose of cocaine and diazepam. RESULTS: In group 1, animals received cocaine followed by vehicle. This resulted in 100% developing seizures and death. Group 2 received diazepam alone followed by vehicle. Animals became somnolent and none died. Group 3 received diazepam followed by 5 mg/kg flumazenil. Animals became somnolent after diazepam and then active after flumazenil administration. In group 4, a combination of cocaine and diazepam was administered simultaneously. This resulted in no overt or EEG-detectable seizures and a 50% incidence of death. Group 5 received a similar combination of cocaine and diazepam, followed later by 5 mg/kg flumazenil. This resulted in an increased incidence of seizures, 90% (P < .01), and death, 100% (P < or = .01), compared with group 4. Group 6 received cocaine and diazepam followed by 10 mg/kg flumazenil. This also resulted in an increased incidence of seizures, 90% (P < or = .01), and death, 90% (P < or = .05), compared with group 4. CONCLUSION: Flumazenil can unmask seizures and increase the incidence of death in a model of combined cocaine-diazepam intoxications.

Animals↗
PubMed1994

An evaluation of the hemodynamic effects of HA-1A human monoclonal antibody.

OBJECTIVES: We sought to determine whether there might be acute changes in hemodynamics attributable to HA-1A, a monoclonal antibody to endotoxin, in patients with presumed Gram-negative sepsis. DESIGN: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled study. PATIENTS: A total of 543 patients with severe sepsis presumed to be caused by Gram-negative bacteria who were enrolled in a clinical trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody. INTERVENTIONS: Patients were randomly assigned to receive either 100 mg of HA-1A or placebo. MEASUREMENT AND MAIN RESULTS: Patients were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were monitored from before, until 72 hrs after infusion of the study drug. For the entire study population (n = 543), no changes over time attributable to study drug were noted in the mean arterial pressure (p > .19), heart rate (p > .53) or the need for vasopressor administration (p > .62). One hundred ninety-seven patients underwent pulmonary artery catheterization and had hemodynamic data available from before the infusion of HA-1A or placebo until at least 12 hrs after infusion. Evaluating all 197 patients on an intent to treat basis demonstrated no significant differences over time in cardiac index (p > .15), oxygen delivery index (p > .43), or left ventricular stroke work index (p > .48) between patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and study drug received also failed to demonstrate any significant difference attributable to HA-1A in mean arterial pressure (p > .54), heart rate (p > .84), cardiac index (p > .13), oxygen delivery index (p > .05), or left ventricular stroke work index (p > .48) between populations. CONCLUSION: There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic profiles over the 72-hr study period.

Antibodies, Monoclonal↗
PubMed1993

NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats.

Paired-pulse facilitation was studied at the perforant path-granule cell synapses in the dentate gyrus of urethane-anesthetized rats. Extracellular field potentials comprising excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) were used to compare facilitation of both responses at interpulse intervals between 10 and 1000 ms. In this model system EPSPs, produced at stimulus intensities well below the PS threshold, exhibited paired-pulse facilitation (PPF) at intervals less than 40 ms. Between 40 and 100 ms both responses were of equal size and from 200 to 1000 ms the second response exhibited paired-pulse depression (PPD). With higher stimulus intensities, PSs exhibited early (10-30 ms) and late (400-1000 ms) PPD and intermediate interval (40-200 ms) PPF. The enhanced PS amplitude during facilitation was accompanied by a modest decrease in EPSP slope and increase in PS latencies to onset and to peak. If PS amplitude was increased to the same extent by simply increasing stimulus intensity, an increase in EPSP slope and decrease in PS latencies to onset and peak were observed. Current source-density analysis revealed that the current sink generated by synaptic activation of granule cell dendrites was indistinguishable between control and facilitated responses up to the onset of the PS. However, the facilitated response exhibited a marked increase in the duration and amplitude of current flowing into the dendrites during the late phase of the EPSP. PPF of the PS was attenuated or blocked by the administration of the known NMDA receptor-ion channel blockers, MK-801, dextromethorphan and ketamine. The depressant effects of these pharmacological agents on facilitation shared the same time course as facilitation itself, peaking at 60 ms and lasting approximately 200 ms. These data suggest that facilitation in this situation is due to postsynaptic rather than presynaptic modulations, and is based upon an increase in the NMDA-mediated component of the evoked response. No increase in transmitter release, per se, could be demonstrated.

Analysis of Variance↗
PubMed1993

Acute cocaine toxicity: the effect of agents in non-seizure-induced death.

Death from cocaine intoxication results from one or more of the multiple mechanisms including seizures, cardiovascular collapse, or apnea. In the free-moving rat model, continuous seizures are a major cause of death. To study other mechanisms of death unrelated to seizures in this model, we suppressed lethal seizures with diazepam (DZP) and investigated the effect of several pharmacological agents. Rats were pretreated with vehicle alone, diazepam 5 mg/kg alone, or a combination of DZP plus either nifedipine (NIFD) 2 mg/kg, propranolol (PROP) 10 mg/kg, or prazosin (PRAZ) 5 mg/kg. Five minutes after pretreatment, all animals received cocaine 100 mg/kg. Each test group consisted of 15 animals and all agents were given IP. Two animals in each group had cortical electrodes implanted. Animals that received vehicle followed by cocaine had 100% incidence of seizures and death. Those rats that received DZP alone followed by cocaine had no seizures and 53% death. Rats that received DZP plus NIFD or DZP plus PROP had suppression of seizures but no significant change in the incidence of death. The group that received DZP and PRAZ followed by cocaine had no seizures and 13% incidence of death (p < 0.001). Electroencephalogram recordings showed cortical electrical spike activity or spike-and-wave afterdischarges in all animals clinically observed to have seizures. In the absence of clinical seizure activity, no significant cortical spike activity was noted. It is concluded that animals protected from seizures with diazepam can still have nonseizure deaths after high-dose cocaine. The incidence of death in these animals is not reduced with nifedipine or propranolol pretreatment but is reduced with prazosin pretreatment.

Animals↗