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F J Miller

Publications and source records attributed to F J Miller.

At least 19 recordsLinked to original sources
PubMed1992

Effect of methyl bromide on regional brain glutathione, glutathione-S-transferases, monoamines, and amino acids in F344 rats.

Both metabolic and neurotransmitter changes have been implicated in the pathogenesis of monohalomethane neurotoxicity in rodents. This study in male and female F344 rats examined the effects of methyl bromide (MeBr) on regional brain glutathione-S-transferase (GST) activities and concentrations of glutathione (GSH), monoamines, and amino acid. Inhalation exposure to 150 ppm MeBr (6 hr/day x 5 days) yielded no histologic evidence of brain lesions but resulted in a number of biochemical changes. GSH depletion and GST inhibition were detected in the frontal cortex, caudate nucleus, hippocampus (examined for GSH only), brain stem, and cerebellum from animals of both sexes. Differences between sexes were detected for GSH depletion. Simultaneous treatment of rats with the inhibitor of monohalomethane toxicity, BW 755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline; 10 mg/kg bw ip, 1 hr pre- and 1 hr postexposure) completely protected against GST inhibition in all brain regions of both sexes. Partial protection by BW 755C against GSH depletion was observed in the cerebral cortex and in the cerebellum only. In males, MeBr exposure had no effect on the regional concentrations of the monoamines dopamine and serotonin and the amino acids glutamate, glutamine, taurine, and gamma-aminobutyric acid. Regional increases of brain aspartate and glycine levels were observed after exposure of males to MeBr but BW 755C had no effect on these changes induced by MeBr. Thus, of all the parameters studied, only GST, and in some brain areas GSH, correlated with inhibition of toxicity. It is concluded that, in contrast to the monoamines and the amino acids, GST and GSH are sensitive and potentially relevant indicators of MeBr neurotoxicity which could explain sex and regional differences in response to the monohalomethanes.

Amino Acids↗
PubMed1992

Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone.

Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery period, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers. Interstitial matrix accumulation underwent partial recovery during follow-up periods in air; however, the thickening of the basement membrane did not resolve. Analysis of terminal bronchioles showed that short-term exposure to O3 caused a loss of ciliated cells and differentiation of preciliated and Clara cells. The bronchiolar cell population stabilized on continued exposure; however, chronic exposure resulted in structural changes, suggesting injury to both ciliated and Clara cells. We conclude that chronic exposure to low levels of O3 causes epithelial inflammation and interstitial fibrosis in the proximal alveolar region and bronchiolar epithelial cell injury.

Administration, Inhalation↗
PubMed1992

Approaches to evaluating the toxicity and carcinogenicity of man-made fibers: summary of a workshop held November 11-13, 1991, Durham, North Carolina.

The Workshop on Approaches to Evaluating the Toxicity and Carcinogenicity of Man-Made Fibers (MMF) was held in Durham, North Carolina, on November 11-13, 1991. The goal of the workshop was to reach a consensus, or to determine the extent to which a consensus existed, in two areas. Participants were asked to identify scientifically sound approaches for evaluating the toxicity and carcinogenicity of man-made fibers based on today's science and to determine research appropriate for study during the next 5 years that can provide an improved scientific basis for future revisions of approaches used to evaluate man-made fiber toxicity and carcinogenicity. During the first day, a series of "state of knowledge" presentations were made to provide all participants with a common data base from which to interact and discuss scientific issues. The workshop participants were assigned to one of four discussion groups, which met separately in three half-day sessions following the first day of presentations. All groups discussed the same topics: exposure assessment, hazard identification, and dose-response information needed to integrate to characterize risk in the first session; approaches to obtaining the needed information in the second session; and recommended approaches and guidelines for evaluating the toxicity and carcinogenicity of MMF and research needs in the third session. The workshop participants reconvened as a whole after each discussion session, and one member from each group reported the group's conclusions. A closure period was also included at the end of the workshop for review and discussion of items that had been considered during the workshop. The primary conclusions reached were the following: -All fiber types capable of depositing in the thorax are not alike in their pathogenic potential. -Only fiber samples with dimensions similar to those to which humans can inhale should be tested. -A complete characterization (i.e., dimensions, fiber number, mass, and aerodynamic diameter) of the fiber aerosol and retained dose is essential. -Appropriate aerosol generation methods must be used for inhalation studies in order to preserve fiber lengths. -A tiered approach to toxicity evaluation is recommended that includes: 1. In vitro screening for durability, surface properties, cytotoxicity, and similar properties, etc; 2. Short-term inhalation or other in vivo studies; 3. That chronic inhalation studies are the "gold standard" (i.e., provide most appropriate data for risk characterization). -The rat is the most appropriate species for inhalation studies. -In chronic inhalation studies, animals should be retained to at least 20% survival after 2-year exposure. -Serial lung burden analyses are an essential component of inhalation studies and are essential for understanding exposure-dose-response relationships. -Studies oriented to understanding mechanisms of toxicity and carcinogenicity are important adjuncts to traditional toxicity studies. -Histopathological analyses of tissues of the respiratory tract represent primary endpoints for evaluating effects of inhaled fibers. Major effects include pulmonary fibrosis, lung tumors, and mesotheliomas. Experimental tissues should be archived for future studies; wherever possible, handling and preservation of tissues should be done in a way that maximizes their future use in mechanistic studies. -Potential human exposures throughout the entire life-cycle of the fiber must be considered and fibrous material for toxicologic studies prepared accordingly. -Intracavity studies are inappropriate for risk characterization but can play a useful screening role in assessing fiber toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of brief myocardial ischemia on sympathetic coronary vasoconstriction.

The purpose of the present study was to determine whether sympathetic coronary vasoconstrictor responses are altered after brief ischemia and reperfusion. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate, arterial pressure, left ventricular pressure, left ventricular dP/dt, anterior myocardial wall thickening, and left circumflex coronary artery (LCX) and left anterior descending coronary artery (LAD) blood flow velocities. Changes in coronary vascular resistance were recorded during intravenous bolus doses of norepinephrine and bilateral electrical stimulation of the stellate ganglia. After beta-adrenergic blockade and bilateral vagotomy, electrical stimulation of the stellate ganglia increased coronary vascular resistance in the LAD and LCX beds by 38 +/- 5% and 39 +/- 5%, respectively. After a 15-minute LAD occlusion, repeat electrical stimulation produced increases in coronary resistance of 16 +/- 3% and 45 +/- 8%, respectively (p less than 0.05 for the LAD before versus after the occlusion). The peak increase in coronary vascular resistance to two doses of norepinephrine was unchanged. After a shorter period of myocardial ischemia (7 minutes), similar increase in coronary resistance to stellate stimulation were observed before (27 +/- 4%) and after (26 +/- 6%) myocardial ischemia. The mechanism of this impaired sympathetic coronary vasoconstriction was further tested by examining the responses to bretylium and tyramine. Brief ischemia did not alter the coronary constrictor responses to either bretylium or tyramine, suggesting that mechanisms governing prejunctional release of norepinephrine are intact in the postischemic coronary arterial bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Embolization of hepatic arteriovenous malformations using radiolabeled and nonradiolabeled polyvinyl alcohol sponge in a patient with hereditary hemorrhagic telangiectasia: case report.

Polyvinyl alcohol sponge (PVA) radiolabeled with 99mTc-sulfur colloid was used to evaluate a large hepatic arteriovenous malformation (AVM) in a 71-yr-old white female prior to embolization. The patient had hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) with severe left-to-right shunting through the hepatic AVM which resulted in high-output congestive heart failure. The patient also had severe pulmonary hypertension. Scintigraphic imaging of the embolized radiolabeled PVA particles allowed us to be certain that the particles did not flow through the liver and inadvertently embolize the lungs; with the patient's already poor pulmonary status, embolization could have been fatal.

Aged↗
PubMed1991

Protection against 2-methoxyethanol-induced teratogenesis by serine enantiomers: studies of potential alteration of 2-methoxyethanol pharmacokinetics.

Several simple physiological compounds attenuate the teratogenic effects of 2-methoxyethanol (2-ME) when coadministered with 2-ME to mice. The mechanism of this protective action, however, has not been elucidated. Alteration of the kinetics of 2-ME and its oxidation product 2-methoxyacetic acid (2-MAA), the putative ultimate toxicant, was considered. D-Serine, the most efficacious attenuator, and L-serine (both 16.5 mmol/kg po) were examined for their abilities to mitigate 2-ME teratogenicity and to alter the disposition of an oral or sc bolus dose of 2-ME (3.3 mmol/kg containing 6 microCi 2-[methoxy-14C]ethanol) given to CD-1 mice on Gestation Day 11. L-Serine reduced the incidence of malformed fetuses from greater than or equal to 72% to 26-28%, while only 18 and 9% of fetuses were affected after coadministration of D-serine with sc and po 2-ME, respectively. Changes in the metabolism of orally administered 2-[14C]ME were specific to each enantiomer. D-Serine reduced the amount of 2-methoxy-N-acetylglycine eliminated in the urine to 70-75% of values observed with 2-ME alone, and concurrently increased the amount of urinary 2-MAA. L-Serine induced an initially higher rate of 14CO2 exhalation. Both enantiomers delayed gastrointestinal absorption of 2-ME, and significantly reduced 2-MAA levels in maternal plasma during the first hour after dosing. This resulted in a nonsignificant decrease (10-17%) in total embryonic exposure to 2-MAA. However, when 2-ME was injected sc, maternal plasma 2-ME/2-MAA pharmacokinetics were not affected by serine. In addition, dosing with 2.3 and 1.3 mmol 2-ME/kg sc alone showed that the embryo 2-MAA exposure levels which cause malformations in less than or equal to 35% fetuses were considerably lower than those measured following serine plus 3.3 mmol 2-ME/kg (po or sc). These data infer that serine does not protect against 2-ME-induced teratogenicity by altering 2-ME pharmacokinetics and reducing 2-MAA levels in the embryo.

Animals↗
PubMed1991

Alveolar epithelial cell injuries by subchronic exposure to low concentrations of ozone correlate with cumulative exposure.

Electron microscopy morphometry has been used to study the effects of cumulative exposure of low levels of inhaled O3 on lung proximal alveolar tissue. Six-week-old Fisher 344 rats were exposed to O3 in two different subchronic low-level exposure patterns. The first was a 12 hr/day exposure for 6 weeks and included two O3 concentrations, 0.12 and 0.25 ppm. The second consisted of an exposure profile having a background level of 0.06 ppm with an exposure peak 5 days each week that went from 0.12 to 0.25 ppm and back to 0.12 ppm over a 9-hr period. Rats given the second exposure pattern were exposed for either 3 or 13 weeks. Changes in the volumes of alveolar epithelium were found to be consistent and reproducible markers for cell injury and/or response. Results from the first study indicated that the relative volume of the type I epithelium increased 13 and 23% over the control value (p less than 0.05) following exposures for 6 weeks to 0.12 and 0.25 ppm, respectively. The magnitude of the increases were clearly concentration related. Similarly, when a fixed exposure concentration was employed the relative volume of type I epithelium was found to increase in proportion to the exposure time. In the second exposure, increases of 9 and 33% in relative volume of type I epithelium were found respectively after 3 and 13 weeks of exposure. If the total exposure determined by the product of O3 concentration (including background) and exposure time is plotted against the relative volume of type I epithelium from both the 0.12 ppm (60.5 ppm-hr) and 0.25 ppm (126 ppm-hr) exposures and the 3-week (45.3 ppm-hrs) and 13-week (196.2 ppm-hr) exposures, a linear relationship between increases in type I cell volume and the concentration X time product is observed. The coefficient of correlation (r2) for the linear regression of the animal means is 0.72. Changes in the volume of Type II epithelial cell also correlate with the concentration X time product (r2 = 0.66). This suggests that epithelial cell reactions to low-level subchronic exposure of O3 are directly related to the cumulative oxidant concentration. The pattern of exposure did not appear to affect the resulting degree of injury. Furthermore, a low level of background exposure may contribute to the epithelial cell injuries.

Animals↗
PubMed1991

Routine fluoroscopic cholangiography during laparoscopic cholecystectomy: an argument.

We evaluated the impact of routine fluoroscopic cholangiography on our first 100 laparoscopic cholecystectomies. Catheterization of the cystic duct was successfully performed in 89 of 99 attempts. The cholangiogram altered the course of the procedure in 9 (10%) of these cases. In three subjects, the information obtained revealed unsuspected choledocholithiasis. In the remaining six patients, unusual and potentially hazardous anatomic relationships were discovered that were not visible via laparoscopic exposure alone. Arguments for the selective use of cholangiography during open cholecystectomy are based only on the identification of unsuspected stones. The strongest argument for routine cholangiography during laparoscopic cholecystectomy is the additional anatomic information obtained. Based on our experience, we advocate that routine cholangiography be a part of all laparoscopic cholecystectomies.

Adult↗
PubMed1991

Regional increases in rat nasal epithelial cell proliferation following acute and subchronic inhalation of formaldehyde.

Short-term studies (9 days) in the rat have demonstrated that formaldehyde-induced nasal epithelial lesions are associated with increases in surface epithelial cell proliferation rates. The present studies were designed, in part, to investigate cell proliferation rates in the nasal epithelium of rats exposed to formaldehyde for a longer duration in order to determine if correlations exist between (1) the concentration-response in cell proliferation rate with the previously published formaldehyde bioassay tumor response; (2) sites of increased cell proliferation and the regions of the nasal passages that exhibit formaldehyde-induced cytotoxicity; and (3) sites of increased cell proliferation and the regions of the rat nasal passages previously determined to be most susceptible to neoplasia (i.e., the lateral meatus and nasal septum of the anterior nasal passages). Another important endpoint of this study was to provide data for a comparison of formaldehyde-induced responses in rats with previous findings in rhesus monkeys. Fischer-344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 6 weeks and pulse labeled with tritiated thymidine prior to each scheduled termination. Exposure to formaldehyde at 6 ppm or higher induced site-specific lesions in the nasal respiratory epithelium and was associated with increases in cell proliferation rate which remained statistically elevated throughout the 6 weeks. While a direct correlation between sites susceptible to formaldehyde-induced nasal cancer and increased cell proliferation was not evident, results from the present studies did demonstrate a clear correlation between sites of cellular injury and increases in cell proliferation and a concentration-dependent response which correlated with the previously published formaldehyde bioassay tumor response. Furthermore, this work demonstrated that formaldehyde-induced responses in rats exposed to 6 ppm were morphologically similar to those reported in the rhesus monkey; however, the distribution of lesions between the two species differed significantly.

Administration, Inhalation↗
PubMed1991

Airway structure variability in the Long-Evans rat lung.

Mathematical models used to study deposition of inhaled toxicants require morphometric data to represent the tracheobronchial airways of laboratory animals. Because of the difficulty and cost of obtaining detailed measurements, morphometric models are generally based on measurements from a small number of specimens. To determine the degree of interanimal variability among laboratory animals of the same strain and size, lengths and diameters of the same 200 airways were measured in solid casts in each of 10 male Long-Evans rats. Intraanimal variability was substantially greater than interanimal variability for airway lengths and diameters. Intraanimal variability was reduced when the airways were grouped so that airway generations were adjusted for lobar position. The study results suggest that detailed measurements of the conducting airways in a small number of casts with summarization techniques that retain lobar information will provide a less variable estimate of lung geometry than a smaller number of measurements made in several casts.

Animals↗
PubMed1991

Percutaneous rotational contact biliary lithotripsy: initial clinical results with the Kensey Nash lithotrite.

The percutaneous rotary lithotrite introduces a new concept to fragmentation and percutaneous removal of gallstones. A fluid vortex is generated, pulling calculi into a high-speed blade that fragments stones to predominantly under 500 microns. The results of treating the first 10 patients with this instrument reveal that large stone burdens as well as small stones (2-3 mm) of any composition can be removed if the gallbladder is of sufficient size to accommodate the six-pronged basket. Rotation times of 7-39 minutes were required. Nine of 10 procedures were completed; access was lost in one case. One major complication occurred. At repeat oral cholecystography, the gallbladder was visualized after 3-6 weeks in eight of the nine patients. Ursodeoxycholic acid was administered from 3 to 12 months to five patients with either residual stones or aggregates. The hospital stay ranged from 48 to 72 hours. All patients (except the patient who underwent surgery) resumed light activity in 3-4 days and strenuous activity and full diet within 3 weeks.

Cholelithiasis↗
PubMed1991

Intraoperative cholangiography: use of portable fluoroscopy and transmitted images.

Intraoperative cholangiograms were obtained with portable fluoroscopy in 53 patients during laparoscopic cholecystectomy, and the images were transmitted to the radiology department. Each image was assessed for diagnostic quality and bile duct abnormalities (eg, retained stones and duct aberrancies). The aberrancy rate was 5.7% with the aberrant duct in the region of surgical dissection. The fluoroscopic technique provided diagnostic images with the advantage of real-time visualization, immediate communication with the surgeon, and the potential to decrease the risk of bile duct injury.

Cholangiography↗
PubMed1991

Activation in the region of parabrachial nucleus elicits neurogenically mediated coronary vasoconstriction.

A role for parabrachial nucleus in cardiovascular regulation is suggested by evidence that electrical stimulation in this region elicits increase in heart rate and arterial pressure. We hypothesized that parabrachial nucleus may also be involved in control of coronary vasomotor tone. After beta-adrenergic receptor blockade in anesthetized cats, electrical stimulation in the region of parabrachial nucleus produced no change in heart rate, an increase in arterial pressure (34 +/- 6 mmHg), and a transient reduction in coronary blood flow velocity (-21 +/- 2%). Coronary resistance (72 +/- 9%) and femoral resistance (189 +/- 31%) increased markedly. The decrease in coronary blood flow velocity was abolished by stellate ganglionectomy or alpha 1-adrenergic blockade without altering pressor or femoral responses. Injection of the neurotransmitter L-glutamate or kainic acid into parabrachial nucleus also elicited coronary vasoconstriction. We conclude that electrical or chemical activation in the region of parabrachial nucleus elicits coronary vasoconstriction as part of a generalized sympathetic activation. The fact that the coronary response is elicited by chemical activation suggests that cell bodies in the region of medial parabrachial nucleus and subceruleus, as opposed to fibers of passage, are involved in this central neural coronary vasoconstriction.

Animals↗
PubMed1991

Inhomogeneity of ventilatory unit volume and its effects on reactive gas uptake.

This study addressed the question of whether variations in the volume of alveoli and alveolar ducts forming single units of ventilation can significantly influence the distribution and uptake of inspired reactive gases. Quantitative serial section analyses of vascular perfusion-fixed rat lungs were used to determine the anatomic dead space proximal to specific ventilatory units as well as the gas volume of these ventilatory units. Three reconstructions, each consisting of ventilatory units distal to a specific bronchus, were carried out. The number of ventilatory units for each reconstruction varied from 26 to 71. The average ventilatory unit volume for the three reconstructions [0.53 +/- .03 (SE) mm3] was not significantly different from measurements based on random sampling. The distribution of ventilatory unit volume was diverse, with 15% of the population having a volume less than 0.3 mm3 and 9% of the population having a volume greater than 1.0 mm3. For a gas of relatively low reactivity (e.g., oxygen) the predicted oxygen uptake per unit surface area did not vary significantly between ventilatory units. The predicted oxygen uptake was approximately 92% of the uptake in the absence of gradients in oxygen concentration between ventilatory units. For a highly reactive gas (e.g., ozone), the predicted uptake per unit surface area in the proximal portions of larger ventilatory units was significantly greater than the average uptake. These results suggest that focal areas of injury likely result from exposure to inhaled reactive gases.

Animals↗
PubMed1991

Percutaneous gallstone lithotripsy. Results in acute and chronic swine models.

The authors describe here a rotary catheter for the percutaneous fragmentation of gallstones. Gallstones are drawn into the rotating impeller by a powerful vortex and mechanically fragmented. Fragments are aspirated from the gallbladder following use of the device. The safety and efficacy of the device was tested after placement of human gallstones in the pig's gallbladder in 19 acute, 15 chronic, and two control experiments. In 27 completed experiments, 206 human gallstones (6-20 mm) were implanted. Most residual fragments were less than 2 mm; 24 fragments were 2 to 4 mm and seven were 5 to 8 mm. Acute histologic changes included focal loss of mucosa, mucosal and submucosal hemorrhage, and deposition of biliary material in the mucosa and submucosa. At 30 and 90 days, gallbladder histology revealed regeneration of the mucosa with isolated granuloma formation.

Acute Disease↗
PubMed1990

2,5-Hexanedione-treated tubulin microinjected into sea urchin zygotes induces mitotic abnormalities.

Zygotes of Lytechinus pictus and Lytechinus variegatus were microinjected with 2,5-hexanedione (2,5-HD)-treated tubulin prior to the first mitotic cycle. Mitotic spindles were small with a well-defined metaphase plate, but poor birefringence and poor astral development. Abnormalities were observed in chromosome movement at anaphase and cytokinesis. Neither microinjections of untreated tubulin or 3-acetyl-2,5-hexanedione-treated tubulin, nor incubation of zygotes in 2,5-HD-containing sea water produced abnormalities. The results can be explained in terms of the nondissociating properties of 2,5-HD-treated tubulin. 2,5-HD-treated tubulin dissociates slowly from microtubules, a property which, besides favoring the formation of stable microtubules, allows this tubulin to induce microtubule assembly when present in substoichiometric amounts. These characteristics have been implicated as a cause of 2,5-HD-induced Sertoli cell dysfunction. The effect of 2,5-HD-treated tubulin on microtubule dynamics in sea urchin zygotes may bear similarities to the effects of 2,5-HD treatment in vivo on Sertoli cell microtubules.

Animals↗