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Biomedical subjects

F J Miller

Publications and source records attributed to F J Miller.

At least 109 records · Page 6Linked to original sources

Intraarterial fibrinolytic therapy for popliteal and tibial artery obstruction: comparison of streptokinase and urokinase.

Experience with using intraarterial fibrinolysis in the treatment of occlusive disease of the popliteal artery and runoff vessels is limited. We describe the techniques and results in 25 patients with 30 fibrinolytic infusions of the popliteal and tibial arteries and compare them with the initial and long-term results of treatment using streptokinase and urokinase. The roles of catheter delivery systems and systemic heparin in the prevention of pericatheter thrombus were also studied. Urokinase was initially successful in 18 (90%) of 20 intraarterial infusions, whereas streptokinase was effective in 8 (80%) of 10 intraarterial infusions. Urokinase had the advantages of a shorter effective infusion time and fewer complications. Long-term follow-up was available in 20 of the successfully treated patients. Sixteen of these patients were doing well with an average follow-up of 27 months. The duration of the initial occlusion may be useful in identifying patients at risk for early reocclusion. No limbs were lost because of complications of therapy. The coaxial catheter system with a divided fibrinolytic dose provided protection against pericatheter thrombus, while systemic heparin was ineffective. Our results suggest that urokinase is more effective than streptokinase for intraarterial infusion in the treatment of occlusion of the popliteal and tibial arteries; this procedure is an important alternative to surgery or an adjuvant to surgery in selected patients.

Arterial Occlusive Diseases↗

Effects of subchronic inhalation of low concentrations of nitrogen dioxide. I. The proximal alveolar region of juvenile and adult rats.

Inhalation of nitrogen dioxide (NO2) produces injury to the epithelium of terminal airways and the alveoli proximal to the airways. Techniques were devised to isolate alveolar tissue from this region for morphometric studies to define the extent of alveolar septal injury caused by NO2. One-day-old and six-week-old rats were exposed to either room air or 0.5 ppm NO2 for 23 hr per day 7 days per week for 6 weeks. An additional group of 6-week-old rats were exposed to 2.0 ppm NO2 for the same duration. Two daily hour spikes to three times the background concentrations (0.5 to 1.5 ppm and 2.0 to 6.0 ppm) were applied Monday through Friday. At the end of the exposure, rat lungs were fixed by intratracheally infusing buffered 2% glutaraldehyde. Pieces of lung tissue were embedded in large plastic blocks which were softened with heat and thin (0.3 mm) sliced. Terminal bronchioles and their corresponding proximal alveolar regions were identified from the thin plastic slices, removed, and glued to cylindrical EM blocks for thin sectioning. Morphometric analysis revealed that epithelial injury occurred in all exposed animals. The juvenile rats which had been exposed to 0.5 ppm NO2 since 1 day of age exhibited changes in the characteristics of type II epithelial cells. These cells spread to cover more alveolar surface and became thinner. Adult animals exposed to 0.5 and 2.0 ppm NO2 showed changes in alveolar macrophages and in the alveolar interstitium in addition to changes in the epithelium. Animals exposed to 0.5 ppm NO2 showed spreading and hypertrophy of type II epithelial cells. Those animals exposed to the higher concentration of NO2 had similar changes in type II epithelial cells and in addition showed an increase in type I cell number. The type I epithelial cells were smaller and covered less alveolar surface area than normal type I cells, suggesting a regenerating population of type I cells. These results suggest that prolonged exposure to low concentrations of NO2 can cause injury to the alveolar epithelium indicated initially by spreading and hypertrophy of type II cells followed by differentiation into type I cells to compensate and repair the injury. Adult rats were as sensitive or more sensitive to NO2 injury than were juvenile rats.

Aging↗

The role of spindle microtubules in the timing of the cell cycle in echinoderm eggs.

Spindle microtubules play an important role in the mechanisms that control the timing of cell cycle events in the eggs of the sea urchins L. variegatus and L. pictus. However, recent work which used colchicine to block microtubule assembly in the eggs of two other echinoderms, S. purpuratus and D. excentricus, has raised serious questions about the generality of this role for spindle microtubules. Thus, we have systematically examined the role of spindle microtubules in the timing of the cell cycle in the fertilized eggs of these latter species. We treated eggs of both species with 5-10 microM Colcemid for several minutes starting 30 min after fertilization to completely prevent spindle microtubule assembly for several h. We used Colcemid, instead of colchicine, because it is effective at lower doses and, at these doses, shows no detectable toxic side effects. We compared for control and treated eggs the time course of nuclear envelope breakdown/reformation and DNA synthesis. We found for both species that the eggs continue to cycle without spindle microtubules; mitosis is up to twice the normal duration while interphase remains essentially unaffected. To test for the possible toxic side effects of the 1-2 mM colchicine used earlier on S. purpuratus and D. excentricus, we treated eggs of these two species, and also those of L. variegatus, with 1 mM lumi-colchicine. This photo-inactivated form of colchicine, which does not bind to tubulin, substantially prolongs mitosis and, to a lesser extent, interphase. Thus, the results of the earlier work are most easily explained by the combination of specific and nonspecific effects of the 1-2 mM colchicine used. Our present results indicate that the importance of spindle microtubules in the mechanisms that control the timing of the mitosis portion of the cell cycle is a general phenomenon.

Animals↗

Radiographic and clinical findings in unusual abdominal aortic aneurysms.

Atherosclerotic abdominal aortic aneurysms typically present either asymptomatically or with abdominal or back pain. Inflammatory, mycotic, and traumatic aortic aneurysms and aneurysms complicated by venous fistula are less common. The different clinical presentations of these latter aneurysms should raise a suspicion to their diagnosis and appropriate preoperative evaluation. The radiographic and clinical features of inflammatory, mycotic, traumatic, and complicated atherosclerotic aneurysms are presented and discussed.

Adult↗

The effects of inhalation of organic chemical air contaminants on murine lung host defenses.

The potential health hazards of exposure to threshold limit value (TLV) concentrations of acetaldehyde, acrolein, propylene oxide, chloroform, methyl chloroform, carbon tetrachloride, allyl chloride, methylene chloride, ethylene trichloride, perchloroethylene, benzene, phenol, monochlorobenzene, and benzyl chloride, compounds which may be present in the ambient or work room atmosphere were investigated. The effects of single and multiple 3-hr inhalation exposures were evaluated in mice by monitoring changes in their susceptibility to experimentally induced streptococcus aerosol infection and pulmonary bactericidal activity to inhaled Klebsiella pneumoniae. When significant changes in these parameters were found, further exposures were performed at reduced vapor concentrations until the no-measurable-effect level was reached. Multiple exposures on 5 consecutive days were then performed at this concentration. Significant increases in susceptibility to respiratory streptococcus infection were observed after single 3-hr exposure to TLV concentrations of methylene chloride, perchloroethylene, and ethylene trichloride. For methylene chloride and perchloroethylene, these exposure conditions also resulted in significantly decreased pulmonary bactericidal activity.

Air Pollutants↗

Effects of ammonium nitrate aerosol exposure on lung structure of normal and elastase-impaired rats and guinea pigs.

Groups of rats and guinea pigs with normal lungs and others with elastase-induced emphysema were exposed to NH4NO3 aerosols of 0.60 mass median aerodynamic diameter at 1 mg/m3 for 6 hr/day, 5 days/week, for 4 weeks. Morphologic and morphometric studies were performed on lungs perfused with cacodylate-buffered 2% glutaraldehyde under 20 cm H2O pressure at necropsy. The tissues were studied for pathologic change by light and electron microscopy; emphysema was evaluated by subgross and microscopic methods, including changes in mean alveolar chord length using scanning electron microscopy techniques. Elastase produced emphysema to a degree quantifiable by all criteria studied; however, it apparently obscured the effects of nitrate inhalation. The NH4NO3 exposure (compared to air alone) tended to increase values for pulmonary parameters in normal animals of both species and to decrease them in elastase-treated animals. The NH4NO3 exposure increased values for lung volume in rats, percentage area affected in elastase-treated rats, and chord length beta in normal animals of both species. The responses to NH4NO3 were slight (P less than 0.10) and were not accompanied by any detectable changes in alveolar structure. Therefore, the effects of NH4NO3 at this exposure level and duration, are regarded as biologically insignificant for rats and guinea pigs.

Aerosols↗

The reproduction of centrosomes: nuclear versus cytoplasmic controls.

The tight coordination normally found between nuclear events and the doubling of centrosomes at each cell cycle suggests that nuclear activities may be part of the mechanism that controls the reproduction of centrosomes. To determine if this is the case, we used a micropipette to completely remove the nucleus from eggs of the sea urchin Lytechinus variegatus at prophase of the first mitosis, leaving only one centrosome in the cell. The subsequent behavior of this centrosome was then followed in vivo with the polarization microscope. In all cases the centrosome reproduced in a precise 1:2:4:8 fashion with a periodicity that was slightly slower than the centrosome cycle of control eggs. The cell cycle-related changes in centrosome morphology were identical to those of control eggs in that: (a) the astral birefringence varied cyclically to a normal extent, (b) the astral focus enlarged and then flattened during the telophase equivalent, (c) cleavage furrows were initiated as the astral birefringence faded, and (d) daughter centrosomes separated before the increase in astral birefringence at the onset of each mitosis. To determine if centrioles also reproduced normally, enucleate eggs were followed in vivo until they contained eight centrosomes. They were then individually removed from the preparations, fixed, and embedded. Each egg was serially 0.25-micron sectioned for observation with the high voltage electron microscope. We completely reconstructed 23 centrosomes in four eggs; all centrosomes contained two centrioles apiece. These results demonstrate that the subunits for complete centrosome assembly can be stockpiled ahead of time and that the properly controlled use of these subunits for centrosome reproduction does not require nuclear transcription or nuclear DNA synthesis at each cell cycle.

Animals↗

Effect of ozone on serum lipids and lipoproteins in the rat.

Exposure of male rats to 0 (air), 1, 1.75, and 3 ppm ozone (O3) 5 hr/day for a total of 10 days resulted in a positive linear relationship between ozone concentration and the concentrations of serum total lipoprotein free cholesterol (FCh) and high-density lipoprotein total cholesterol (HDL-Ch). The latter response was reflected in both its free (HDL-FCh) and esterified (HDL-ChE) components. On the other hand, serum triglycerides (TG) showed a marked decreasing linear trend with increasing ozone concentration. As judged by decreased body weights with no accompanying differences in feed consumption, apparent metabolic rate increased as ozone concentration increased. In another experiment, male rats were exposed 5 hr/day to either air or 1 ppm O3 for a total of 15 days. Groups of animals from each exposure were sampled at times ranging from immediately after to 44 hr postexposure. In agreement with the concentration response study, effects of O3 included increases in serum total cholesterol (Ch), HDL-Ch and HDL-FCh, and a decrease in TG. In addition, the degree of effects appeared to be maintained over the 44-hr period and to be greater than that observed at 1 ppm O3 in the concentration-response study.

Animals↗

A model of the regional uptake of gaseous pollutants in the lung. I. The sensitivity of the uptake of ozone in the human lung to lower respiratory tract secretions and exercise.

An ozone (O3) dosimetry model is presented that takes into account convection and diffusion of O3 in the lumen and airspaces of the lower respiratory tract and transport and chemical reactions in the mucous and surfactant layers and in the underlying tissue and capillaries. The model was applied to human airway morphometric data. Values for the chemical and physical parameters that define the liquid tissue and blood compartments were based on reported experimental data. Simulation results illustrate the variability of results due to an uncertainty in the knowledge of transport parameters, liquid, tissue, and blood compartment thicknesses, and chemical reaction rates. Results were most sensitive to mucous compartment thickness and reaction rate constant and least sensitive to transport and blood parameters. Exercise was simulated, showing little effect on tracheobronchial uptake but a pronounced effect on pulmonary uptake.

Air Pollutants↗

Inhalation studies of Mt. St. Helens volcanic ash in animals. I. Introduction and exposure system.

Due to the lack of information on the effects of inhaled Mt. St. Helens volcanic ash and its potential interaction with sulfur dioxide (SO2), animal studies were performed to determine the acute and chronic health effects of a short-term exposure. This paper describes the inhalation exposure system designed for these studies and theoretically compares the pulmonary deposition in the rats to that in humans. Considering the similarities and differences in regional pulmonary deposition in humans and animals, inhalation studies were performed with fine-mode (less than 2.5 micron aerodynamic diameter, Dae) ash. Comparisons to coarse-mode (greater than 2.5 micron Dae) ash were made using intratracheal instillation. A whole-body exposure system was designed to provide inhalation exposures of animals to Mt. St. Helens volcanic ash, SO2, or a combination of both. All exposures were conducted using fine-mode ash samples generated by a Wright dust feed mechanism at a mean concentration of 9.4 mg/m3 +/- 1.0 SD. Sulfur dioxide was maintained at 2.5 mg/m3 +/- 0.13 SD. Scanning electron microscopy, X-ray diffraction, and X-ray fluorescence were used to characterize the ash.

Air Pollutants↗

Gastrointestinal hemorrhage associated with chronic mesenteric venous occlusion.

Chronic mesenteric venous thrombosis without involvement of the splenic or portal veins may lead to gastrointestinal hemorrhage from mesenteric varices. Three cases are presented in this report; 1 patient died secondary to blood loss and 2 patients have experienced a benign clinical course. The presentation, methods of diagnosis, and therapeutic options for this disorder are described.

Adult↗

Effects of toluene inhalation on pulmonary host defenses of mice.

The potential hazards of exposure to vapor-phase toluene on pulmonary host defenses were evaluated. Mice exposed to concentrations ranging from 2.5-500 ppm, including the threshold limit value level of 100 ppm, exhibited increased susceptibility to respiratory infection with Streptococcus zooepidemicus. The no-measurable-effect level for single, as well as for 5 exposures was 1 ppm. Significantly decreased pulmonary bactericidal activity was observed after single exposures to 500, 250, 100 and 2.5 ppm toluene, and after 5 daily 3-h exposures to 1.0 ppm of toluene. A 20-exposure study with toluene at 1 ppm produced no changes in either of the 2 assays.

Animals↗

Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice.

The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0.4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to 35S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

Aerosols↗

Digital angiography: matched filtration versus mask-mode subtraction.

Matched filtration was compared to mask-mode subtraction in patients undergoing routine intravenous digital subtraction angiography. Images were analyzed for noise and edge sharpness, and the two techniques were compared subjectively by three radiologists. The quantitative results indicated that matched filtration increased the signal-to-noise ratio by an average of 2.23 but did not significantly increase vessel blurring. Subjectively, the observers favored matched filtration over mask-mode subtraction for overall image quality in 26 out of 30 cases (p less than 0.005) in terms of both sharpness and freedom from motion artifacts.

Angiography↗

Tomographic digital subtraction angiography: initial clinical studies using tomosynthesis. Work in progress.

We have developed a method for acquiring multiple tomographic subtraction images using a rapid, repetitive, circular tomographic motion. The method combines the principles of digital subtraction angiography (DSA) and electronic tomosynthesis. Fifteen patients were examined with the technique using single intravenous bolus injections of contrast material. The image sequence obtained during each injection was first processed with a nontomographic mask subtraction, and the result was then compared with the tomographic DSA scans synthesized from the same sequence. The effective section thickness was approximately 0.5 cm, with each section being 0.5-1.0 cm apart. Twelve of the intravenous DSA scans provided the necessary diagnostic or clinically useful information. Two of the three nondiagnostic scans were caused by avoidable technical reasons. In eight cases, the tomographic DSA scans were superior in quality to the nontomographic scans, exhibited significantly less artifact from patient motion and overlying bowel gas, and were effective in separating overlapping vessels. Tomosynthesis permits multiple electronic imaging of the area of interest without reinjection of contrast material and appears to be more informative than nontomographic intravenous DSA imaging.

Angiography↗

Ambient sulfate aerosol deposition in man: modeling the influence of hygroscopicity.

Atmospheric sulfate aerosols [H2SO4, (NH4)2SO4, and NH4HSO4] are of international concern because of their global prevalence and potential irritant or toxic effects on humans. To assess hazards following inhalation exposure, the total dose delivered to the human respiratory tract and its regional distribution must be determined. The mass median aerodynamic diameter of the inhaled aerosol will influence the sites of deposition in the respiratory tract. Atmospheric sulfate aerosols are hygroscopic and will have changing particle sizes and densities as they absorb water vapor in the humid environment of the human respiratory tract. Experimental and theoretical data that describe particle size as a function of temperature and relative humidity were used in computer subroutines of an aerosol deposition model in order to calculate the dose dispersion of H2SO4, (NH4)2SO4, and NH4HSO4 aerosols in man. Different temperature and relative humidity environments that approximately correspond to nasal and oral breathing were studied. The predicted deposition patterns are very different from those of nonhygroscopic aerosols with identical inhaled mass median aerodynamic diameter values.

Aerosols↗

Effects of inhalation of 0.12 and 0.25 parts per million ozone on the proximal alveolar region of juvenile and adult rats.

The degree of lung injury caused by prolonged inhalation of low levels of ozone (O3) is of interest since urban environmental levels periodically reach 0.2 to 0.3 ppm. Since the area of the junction of the conductive and respiratory regions of the lung has been reported as the major site of injury due to O3 inhalation, techniques were devised to specifically study alveolar tissue from this region. One-day-old or 6-week-old male rats were exposed to either 0.25 ppm O3 12 hours/day or to continuous room air for 6 weeks. An additional group of 6-week-old rats were exposed to 0.12 ppm O3 for the same time period. All lungs were fixed at the end of the exposure by intratracheal installation of buffered 2% glutaraldehyde. Cylinders of tissue containing a cross-section of a terminal bronchiole were punched out of lung tissue slices using a sharpened cannula. These tissue cylinders were oriented, embedded in Epon, serial sectioned until the first alveolar duct bifurcation was reached, and then thin sectioned for electron microscopy. Qualitative examination of the tissue revealed little observable damage to the proximal alveolar tissues. However, by ultrastructure morphometric analysis, significant changes occurred in the alveolar epithelium of the proximal alveolar region of all exposed animals. In the animals exposed to 0.25 ppm O3 from 1 day of age (juvenile animals), the number of type 1 epithelial cells doubled, their mean surface area decreased 38%, and their mean thickness increased 24%. The number of alveolar type 2 epithelial cells increased, and the number of alveolar macrophages doubled. Adult animals exposed to 0.25 ppm O3 showed similar patterns of changes in the epithelium of the proximal alveolar region and in addition had a doubling of interstitial macrophages, indicating a mild inflammatory stimulus in the interstitium. Adult animals exposed to 0.12 ppm O3 showed smaller, but statistically significant changes in the alveolar type 1 epithelium, suggesting a relatively linear concentration-response relationship. The change in number and size of type 1 cells in all exposed animals is consistent with an increased cell turnover rate due to prolonged O3 inhalation. These results suggest that low concentrations of O3 cause a chronic epithelial injury in the proximal alveolar region and that the extent of these changes occurs in a concentration-dependent manner, even at concentrations as low as 0.12 ppm. No statistically significant age-dependent effects were found.

Aging↗