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Biomedical subjects

F J Miller

Publications and source records attributed to F J Miller.

At least 145 records · Page 8Linked to original sources

Dose response of elastase-induced emphysema in hamsters.

Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment.

Animals↗

Effect of portasystemic shunt operations on hepatic portal perfusion.

We recently developed a radiocolloid technique for quantifying the fraction of superior mesenteric venous blood that bypasses liver sinusoids through extra- and intrahepatic collateral vessels. In the present investigation we applied this method, which is performed in conjunction with visceral angiography, to the assessment of patients with portal hypertension before and after surgical construction of portasystemic shunts. The mean corrected shunt index was 0.89 in 27 preoperative patients, and 48 percent of the patients had no evidence of sinusoidal perfusion by superior mesenteric venous blood (shunt index greater than 0.95). Sinusoidal perfusion was absent in five patients with residual hepatic portal flow by angiography, indicating that they had a high degree of intrahepatic shunting. Hepatic portal perfusion was preserved in 80 percent of patients after distal splenorenal shunt, and the corrected shunt index was significantly smaller after this procedure than after portacaval and interposition shunts. . Three patients with no sinusoidal perfusion by superior mesenteric blood preoperatively had restoration of portal flow after distal splenorenal shunt. Five patients undergoing portacaval and interposition shunts had no evidence of portal sinusoidal perfusion by the radiocolloid technique either before or after the operative procedure.

Angiography↗

Correlation of effects of inhaled versus intratracheally injected males on susceptibility to respiratory infection in mice.

Effects of intratracheally administered air pollutant chemicals on susceptibility of mice to infection by aerosolized bacteria were compared with effects of the same chemical previously studied by the inhalation route. Out of 22 compounds previously studied by inhalation, the same 3 (CdSO4, CuSO4, and ZnSO4) that caused significantly increased mortality because of infection after a 3-h exposure to 1 to 2 mg/m3 showed large (greater than or equal to 40% over sham injected) mortality increases when administered by intratracheal injection at lung concentrations calculated to be equivalent to those achieved during inhalation exposures (0.6 to 1.2 microgram). Dose-effect curves of these compounds were similar by the 2 routes. Five of the compounds caused a moderate (20 to 30%) enhancement in the mean excess mortality at concentrations of 2 to 3 microgram/animal. The remaining compounds, which showed no significant effect by inhalation, also showed no effect when given by intratracheal injection. Thus, similar effects on susceptibility to lung bacterial infection were seen whether chemicals were deposited in te lung by inhalation or by intratracheal injection.

Aerosols↗

Balloon catheter dilatation in patients with failing arteriovenous fistulas.

Six patients on hemodialysis who had stenotic segments of failing arteriovenous fistulas underwent attempted dilatations with a Grüntzig balloon catheter. In three patients the dilatation was successful: two fistulas were still functioning at the time of this study (10 and 8 months), and one fistula functioned up to the patient's death (2 months). Dilatation was unsuccessful in two patients because the stenosis located adjacent to the arteriovenous anastomosis could not be approached with the balloon. There were no complications secondary to the technique, and the dilatation attempt did not preclude surgical revision when it failed. This technique, which can be performed in ambulatory patients, provides an alternative to surgical revision of the failing arteriovenous fistula.

Arteriovenous Shunt, Surgical↗

Extrapulmonary effects of NO2 as reflected by pentobarbital-induced sleeping time in mice.

The influence of nitrogen dioxide (NO2) on pentobarbital (PEN)-induced sleeping time (S.T.) was investigated in mice. Acute exposure to concentractions as low as 470 microgram NO2/m3 (0.25 ppm) caused a significant increase in PEN-induced S.T. No significant effects on PEN-induced S.T. were detected after 1 or 2 days (3 h/day) exposure to 235 microgram NO2/m3 (0.125 ppm). None of the exposure regimens affected the time required for the drug to induce sleep. When the effects of repeated daily exposures (3 h/day) to 9400 microgram NO2/m3 (5 ppm) were compared in male and female mice, the females had a significantly increased PEN-induced S.T. after 1 and 2 days of exposure. However, an increase in PEN-induced S.T. was not observed in males until the 3rd day of exposure. Since the duration of PEN-induced S.T. is primarily determined by hepatic mixed function oxidase activity, it is possible that NO2 may alter some aspects of xenobiotic metabolism.

Animals↗

Decreased resistance to infection in exercised mice exposed to NO2 and O3.

A mechanized wheel was constructed for use in evaluating the interaction of exercise and gaseous pollutants such as O3 and NO2. Immediately after the pollutant exposure, both exercised and nonexercised female mice (CD-1) were combined with controls, challenged with an aerosol of viable Streptococcus pyogenes (group C), and then observed over a 15-d period for incidence of mortality. Exposure to O3 at 196 micrograms/m3 (0.1 ppm) or 590 micrograms/m3 (0.3 ppm) while exercising yielded mortality rates that were significantly higher than those observed in the O3 groups that were not exercised. With exposure to NO2 at 5640 micrograms/m3 (3 ppm), exercise produced a significant enhancement in mortality over the other treatment groups. These studies show that exercise can affect the mortality observed in this model system and indicate the need for establishing safe exposure levels of pollutants as a function of the activity level of the exposed population.

Air Pollutants↗

Factors determining degree of inflation in intratracheally fixed rat lungs.

The total lung capacity (TLC) of rats was measured in vivo and was compared to the displacement volume of the lungs following intratracheal fixation with glutaraldehyde or formaldehyde solution. When glutaraldehyde was used the speed of infusion of the fixative was an important factor in the final degree of lung inflation achieved. With a low rate of fixative infusion and a final pressure of 20 cm of fixative the glutaraldehyde-fixed lungs inflated to 55% TLC. With a high initial flow of glutaraldehyde and a final pressure of 20 cm of fixative the lungs inflated to 84% TLC. Fixation of lungs inside the intact chest wall was found to result in a higher degree of inflation. With a reservoir height of 20 cm and a low rate of fixative infusion lungs fixed in situ reached 74% TLC, whereas lungs fixed in situ, but from animals that have been exsanguinated prior to fixation, inflated to only 58% TLC. This suggests that the volume of the blood in the lungs prior to infusion of glutaraldehyde influences the degree of inflation achieved. Formaldehyde-fixed lungs required 72 h to be completely fixed and they were inflated to 90% TLC when a reservoir height of 20 cm was used. Because of the slow rate of fixation using with formaldehyde solution the rate of infusion was found not to limit the degree of inflation that could be achieved.

Animals↗

Single-breath diffusing capacity and lung volumes in small laboratory mammals.

We measured the single-breath diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) in anesthetized male hamsters, rats, guinea pigs, and rabbits whose weights varied from 40 to 3,500 g. TLC (defined as an airway pressure of 25 cmH2O) was calculated by neon dilution. The DLCO was estimated by a modification of the single-breath method. There was a high correlation between body weight and our measurement of both the diffusing capacity and the lung volumes. No significant difference in DLCO was observed in rats when measured in different body positions, at airway pressures of 10 or 20 cmH2O, from FRC or RV, in male or female rats, or following hyperventilation.

Animals↗

Nasopharyngeal removal of ozone in rabbits and guinea pigs.

In estimating pollutant concentrations responsible for observed pulmonary effects, nasopharyngeal removal of the pollutant plays an important role. The nasopharyngeal removal of ozone (O3) in anesthetized male guinea pigs and male and female rabbits was determined by drawing O3 through the isolated upper airways at a constant flow rate which approximated the animal's respiratory minute volume. The tracheal O3 concentration in rabbits and guinea pigs was markedly similar and was linearly related to the chamber concentration of O3 over a range of 196--3920 micrograms/m3 (0.1--2.0 ppm O3). Regression analyses showed that O3 removal in the nasopharyngeal region is approximately 50% in both species. Both rabbit sexes responded similarly over the concentration range studied. Exposures of guinea pigs to O3 concentrations between 3920 and 5880 micrograms/m3 (2.0 and 3.0 ppm) showed that, at these higher concentrations, relatively more O3 is removed by the upper airways.

Animals↗

Hemodynamic studies using a CT scanner.

New CT software programs allow rapid-sequence images to be obtained. During a period of 12 sec, multiple CT images can be produced, so that the progression of contrast flow at intervals of 1 sec or less can be followed. In addition, as many as 16 consecutive 3-sec scans can be performed, or arbitrary time intervals inserted between scans. The rapidity with which the contrast medium enters and leaves a specific tissue may be a valuable, non-invasive diagnostic tool in differentiating enhancing lesions. Other potential applications are mentioned.

Hemodynamics↗