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D H Taylor

Publications and source records attributed to D H Taylor.

At least 19 recordsLinked to original sources

Daily rhythmicity of the rat acoustic startle response.

We have measured the acoustic startle response (ASR) amplitude and latency in rats housed in a 12:12 light:dark (LD) cycle. The response amplitudes to eliciting stimuli (ES) of 110 dB or 120 dB (white noise) were significantly higher (nearly two-fold) during D than during L. Similar, but nonsignificant, trends were also observed at ES intensities of 90 dB or 100 dB. While some significant LD ASR latency differences were observed, we cannot ascribe them to the photoperiodic phase at this time. These findings conclusively demonstrate that the mammalian ASR amplitude exhibits daily rhythmicity.

Acoustic Stimulation

The incidence of pacemaker dysfunction during helicopter air medical transport.

A number of recent publications have raised concern regarding in-flight pacemaker dysfunction during air medical transport. Unfortunately the clinical importance of this problem is unknown. The authors' purpose was to examine the incidence of pacemaker use and malfunction during helicopter air medical transport, using an incidence (cohort) study of an air medical service of a tertiary-care teaching hospital. During the study period, April 1, 1987 through December 31, 1991 2,388 patients were air-transported. Cardiac patients constituted 72% of the total population. Pacemakers were used in 44 patients, temporary transvenous pacemakers in 35, permanent transvenous in five, and transcutaneous pacers in four patients. No rate-responsive pacemakers were transported. No episodes of pacemaker malfunction were observed (95% confidence interval 0 to .002 for the population as a whole). The authors conclude that pacemaker dysfunction during air medical transport is a very rare occurrence, in part due to the infrequent transport of patients requiring these devices.

Aged

Circadian modulation of the rat acoustic startle response.

The acoustic startle response (ASR) of male rats was measured during several sessions over a 24-hr period in both a light-dark cycle and a constant-dark condition. Each session consisted of 10 trials each at 80, 90, 100, 110, and 120 dB white noise. The results indicate robust daily and circadian modulation of ASR amplitude that consist of an approximately twofold nocturnal increase at eliciting-stimuli intensities above 80 dB. Similar results were observed in female rats in constant-dark conditions. To determine whether daily changes in auditory thresholds were responsible for the observed modulation, ASR reflex modification procedures were used. These procedures were designed to measure auditory thresholds at frequencies of 10 and 40 kHz at several times of day. The results suggest a lack of significant circadian differences in auditory thresholds at these frequencies. This study demonstrates a novel role of the rat circadian system in the modulation of ASR amplitude.

Acoustic Stimulation

Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the lactating rat and nursing pup. The lactating dam was exposed to TCE either by inhalation or by ingestion in drinking water. The nursing pup's exposure to TCE was by ingestion of maternal milk containing TCE. The kinetics of trichloroacetic acid (TCA), a metabolite of TCE, were described in the lactating dam and developing pup by a hybrid one-compartment model. The lactating dam's exposure to TCA was from metabolism of TCE to TCA. The pup's exposure to TCA was from metabolism of TCE ingested in suckled milk and from direct ingestion of TCA in maternal milk. For the PB-PK model, partition coefficients (PCs) were determined by vial equilibration, and metabolic constants for TCE oxidation, by gas uptake methods. The blood/air and the fat/blood PCs for the dam were 13.1 and 34.2, and for the pup, 10.6 and 42.3, respectively. The milk/blood PC for the dam was 7.1. In lactating rats and rat pups (19-21 days old) the maximum velocities of oxidative metabolism were 9.26 +/- 0.073 and 12.94 +/- 0.107 mg/kg/hr. The plasma elimination rate constant (K = 0.063 +/- 0.004 hr-1) and apparent volume of distribution (Vd = 0.568 liter/kg) for TCA in the lactating dam were estimated from both intravenous dosing studies and an inhalation study with TCE. For the pup, K (0.014 +/- hr-1) and Vd (0.511 liter/kg) were estimated from a single 4-hr inhalation exposure with TCE. The dose-rate-dependent stoichiometric yield of TCA from oxidative metabolism of TCE in the lactating rat is 0.17 for a low-concentration inhalation exposure (27 ppm TCE) and 0.27 for an exposure above metabolic saturation (about 600 ppm TCE). For the pup, the stoichiometric yield of TCA is 0.12. With changing physiological values during lactation for compartmental volumes, blood flows, and milk yields obtained from the published literature and kinetic parameters and PCs determined by experimentation, a PB-PK model was constructed to predict maternal and pup concentrations of TCE and TCA. To test the fidelity of the PB-PK lactation model, a multiday inhalation exposure study was conducted from Days 3 to 14 of lactation and a drinking water study, from Days 3 to 21 of lactation. The inhalation exposure was 4 hr/day, 5 days/week, at 610 ppm. The TCE concentration in the drinking water was 333 micrograms/ml. Prediction compared favorably with limited data obtained at restricted time points during the period of lactation.

Animals

Comparison of Albendazole and Praziquantel therapy of Echinococcus granulosus in naturally infected sheep.

The effects of albendazole (10 mg kg-1 day-1) and praziquantel (50 mg kg-1 day-1) for 6 weeks on naturally infected sheep with pulmonary cysts of Echinococcus granulosus of proven viability were studied. Immediately following therapy, one of three sheep treated with praziquantel had viable cysts and 7 months later one of two sheep had viable cysts. One sheep died during albendazole therapy, but 7 months following therapy only one of five sheep had viable cysts. Electron microscopy demonstrated necrotic germinal layer tissue in most albendazole-treated cysts and praziquantel also had an effect on cyst ultrastructure. These data suggest that recurrence in humans treated with albendazole may be small. Whilst praziquantel was not particularly effective in this animal model, its clear effect on the ultrastructure suggests that an increased dose and combination therapy with albendazole may be more effective.

Albendazole

Echinococcus granulosus: development of resistance to albendazole in an animal model.

Gerbils with well developed peritoneal cysts of Echinococcus granulosus were randomized to albendazole 50 mg/kg/day or untreated control. Treated animals had less disease at post mortem after 3 months of treatment. Cysts were then taken from both albendazole-treated and control animals and cultured in vitro either with or without albendazole sulphoxide (Alb Sx) 500 micrograms/L for 14 days. Viability of cysts was then established by implantation of whole cysts into gerbils. Whilst naive cysts were affected by Alb Sx (only 2 cysts developed/gerbil) cysts from animals treated with albendazole were not sensitive to further therapy (6.4 cysts/gerbil).

Albendazole

Perioperative prophylactic chemotherapy of Echinococcus granulosus: determination of minimum effective length of albendazole therapy in in vitro protoscolex culture.

Protoscoleces of Echinococcus granulosus were cultured in vitro in 500, 250 or 100 micrograms/l albendazole sulphoxide for 1,3,7,10,14d and then 'rescued' (R) into drug-free medium for the remainder of the culture period. Successful minimum lengths of therapy were much longer than for praziquantel, and only at 500 micrograms/l was the 10dR treatment as effective as continuous therapy for 28d. Treatment with 100 micrograms/l both in continuous culture and in the 'R' experiments was ineffective over a 35d period. The results are compared with those from similar experiments using praziquantel.

Albendazole

Maternal exposure to 1,1,2-trichloroethylene affects myelin in the hippocampal formation of the developing rat.

The effect of 1,1,2-trichloroethylene (TCE), an industrial solvent, on myelin in the dorsal hippocampus of the developing rat was investigated. Rat pups were exposed to TCE via their dams' drinking water while in utero and until they were sacrificed at 21 days of age. Frozen coronal sections through the dorsal hippocampus were stained for the presence of myelin using a modification of the Heidenhain procedure developed for frozen sections. A significant decrease in myelinated fibers was found in the stratum lacunosum-moleculare, an area comprised of distal dendritic profiles of CA1 pyramidal neurons which receive input from the entorhinal cortex. These findings suggest that the reduction in myelin in the hippocampus may be responsible, in part, for behavioral effects observed following TCE exposure.

Animals

Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 +/- 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0.045 +/- 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from TCE was estimated to be 0.12 in pregnant rats. To develop a data base for testing the fidelity of the PB-PK model, inhalation and bolus gavage exposures were conducted from Day 3 to Day 21 of pregnancy and a drinking water exposure from Day 3 to Day 22 of pregnancy. Inhalation exposures with TCE vapor were 4 hr/day at 618 ppm. The TCE concentration in drinking water was 350 micrograms/ml and the gavaged rats received single daily doses of 2.3 mg TCE/kg. Time varying physiological parameters for compartment volumes and blood flows during pregnancy were obtained from the published literature. Using the kinetic parameters determined by experimentation, TCE concentrations in maternal and fetal blood and TCA concentrations in maternal and fetal plasma were predicted from the PB-PK model by computer simulation and compared favorably with limited data obtained at restricted time points during pregnancy for all three routes of exposure. On the basis of the PB-PK model, fetal exposure to TCE, as area-under-the-curve, ranged from 67 to 76% of maternal exposure. For TCA the fetal exposure was 63 to 64% of the maternal exposure. The fetus is clearly at risk both to parent TCE and its TCA metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation

Echinococcus multilocularis: ultrastructural effect of in vivo albendazole and praziquantel therapy, singly and in combination.

Cotton rats with Echinococcus multilocularis infections of one month's standing were treated for six months with albendazole (50 mg kg-1 day-1), or praziquantel (500 mg kg-1 day-1), or both drugs simultaneously. The germinal layer of albendazole-treated cysts differed little from control tissue apart from marginal increase in cyton vesiculation and the presence of small lamellated residual bodies. Protoscolex tissue appeared unaffected. The germinal layer of praziquantel-treated cysts differed markedly from control tissue, with increased vesiculation and mitochondrial number in those with intact germinal layers, and disintegration and detachment of the layer in other cysts. Protoscoleces were necrotic. After combined therapy, the germinal layer was either intact but with increased vesiculation and residual bodies present, or was disintegrating and detaching from the laminated layer.

Albendazole

Albendazole is effective against established Echinococcus granulosus in gerbils: comparison of serum concentrations achieved by gavage and feed administration.

Serum levels of albendazole sulphoxide in gerbils infected with Echinococcus granulosus and treated with albendazole (20 or 50 mg kg-1 day-1) by gavage were dose dependent, whereas albendazole administered in feed at a rate equivalent to 80 mg kg-1 day-1 achieved serum levels calculated to be equivalent to those produced by administration of 40 mg kg-1 day-1 by gavage. This regimen, over a three-month period, was effective and reduced parasite weight to 4.6% of that in control gerbils, and the treated parasite tissue showed ultrastructural changes ranging from severe accumulation of residual bodies to total disintegration of the germinal layer.

Administration, Oral

Comparison of albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model.

The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01).

Albendazole

In vitro culture of Echinococcus multilocularis: protoscolicidal action of praziquantel and albendazole sulphoxide.

The metacestode stage of Echinococcus multilocularis was cultured in vitro. Sensitivity of protoscoleces to the presence of albendazole sulphoxide, praziquantel and methanol was assessed. 10 micrograms/litre of praziquantel or 500 micrograms/litre of albendazole sulphoxide significantly reduced protoscolex viability. The presence of methanol (at 0.25%) had no significant effect. In vitro culture of E. multilocularis can be used to assess possible chemotherapeutic agents.

Albendazole

Echinococcus multilocularis: in vivo results of therapy with albendazole and praziquantel.

The effects of albendazole and praziquantel on the growth of Echinococcus multilocularis were studied in cotton rats. Albendazole (20 and 50 mg/kg) reduced parasite weight and increased the length of survival of infected animals but viable infection was present after treatment. In an in vitro system albendazole sulphoxide entered cysts of E. multilocularis passively. Praziquantel 100 mg/kg was ineffective but 500 mg/kg significantly inhibited growth. A combination of albendazole and praziquantel was no more effective than either agent alone.

Albendazole