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Biomedical subjects

W R Rogers

Publications and source records attributed to W R Rogers.

At least 37 records · Page 2Linked to original sources

Thyroid hormone levels and cigarette smoking in baboons.

Using a primate animal model, two studies were undertaken to examine the effects of cigarette smoking on thyroid hormone levels. In study 1, mean total triiodothyronine (total T3) and mean total thyroxine (total T4) levels were measured in two groups of baboons (Papio cynocephalus) who were taught to smoke cigarettes using operant conditioning techniques. The smokers were divided into established and naive smokers according to pack-years of exposure. A control group of never-smoker baboons was included for comparison. Blood sampling was done after long-term cigarette consumption and again 1 week after cigarette deprivation. In the naive smoker group, mean total T3 concentrations were reduced below control group values (P less than 0.05). After cigarette deprivation for 1 week, mean total T3 values returned to normal. No significant differences in total T4 levels were observed in either group. In study 2, we assessed some other indices of thyroid function. The same groups of baboons were divided into good and poor smokers by plasma cotinine and blood carboxyhemoglobin (% COHb) levels during 28 weeks of cigarette smoking activity. Immediate fluctuations and reductions in total T3 levels were observed that were not accompanied by reductions in total T4. The animals were then cigarette deprived for 1 week and blood samples were obtained every other day during this period. Significant increases in total T3 concentrations were observed in poor smokers immediately after cessation. Both groups also exhibited significant reductions (P less than 0.05) in T3 uptake and free T4 index (FT4I) when compared to control group values. These data suggest that poor smokers are more susceptible to thyroid hormone level shifts than more established smokers, since the established smokers become habituated to the compounds contained in cigarette smoke through repeated exposure.

Animals↗

Effects of cigarette nicotine content on smoking behavior of baboons.

Human cigarette smokers modify the way in which they smoke cigarettes of differing nicotine content, apparently to maintain nicotine exposure at a preferred level. The effects of changing from moderate to high or low nicotine content cigarettes were examined in 11 baboons (superspecies Papio cynocephalus) trained to smoke cigarettes for water rewards. Relative to the moderate nicotine content cigarette, the animals took significantly (p less than .05) more puffs on the high nicotine content cigarette, and the puffs on the high nicotine cigarette were significantly larger in volume. The animals made the same number of puffs, relative to the moderate nicotine content cigarette, on the low nicotine content cigarette, but the volume of the puffs was significantly smaller. The cotinine output in urine varied significantly and was directly related to cigarette nicotine content; cotinine is the primary metabolite of nicotine. Baboons, like people, prefer high nicotine content cigarettes. Nonhuman primates also regulate nicotine exposure by modification of their puffing behavior. These results indicate that the nonhuman primate also can be used as a model for the investigation of the behavioral aspects of cigarette smoking.

Animals↗

Unstable angina.

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Angina Pectoris↗

Analysis of urinary mutagens produced by cigarette-smoking baboons.

Urine concentrates from 17 cigarette-smoking baboons and 12 sham puffers were analyzed for mutagenic activity in S. typhimurium tester strain TA1538. Both the proportion of animals exhibiting measurable mutagenic activity in urine and the mean level of mutagenic activity present were significantly greater in cigarette smoking baboons (P less than 0.05). Mutagenic activity in the urine of male and female cigarette-smoking baboons was not significantly different. Age and smoking history did not, but mean blood carboxyhemoglobin did, correlate with mutagenic activity of the urine concentrate from individual animals. Fractionation of the urine concentrates on silicic acid separated the concentrate into fractions that were more active in TA100 and others that were more active in TA1538. Further fractionation was accomplished by HPLC.

Animals↗

Coronary bypass for acute rest angina. 10 year follow-up.

We followed up for 6.5 to 10.3 years 100 consecutive patients who had had coronary bypasses (1.8 per person) for acute angina at rest. There was a mean of 2.1 coronary stenoses per person. Mortality rates were 1.4% per postoperative year, or 2.2 times that of normal subjects of the same age. Angina was usually satisfactorily relieved but severe recurrences, mainly from late graft closure, required reoperation in 20 patients. Life style has been preserved; and 91 resumed work, with 52 at an average age of 61 years continuing to work eight years later. Better results that these may be obtained from the improved diagnostic and therapeutic methods of the 1980's.

Actuarial Analysis↗

Effects of acute and chronic exposure to nicotine aerosol on bronchial reactivity to inhaled methacholine.

Normal baboons, like humans, demonstrate a wide range of bronchial reactivity to inhaled methacholine. Cigarette-smoking baboons demonstrate reduced bronchial reactivity to inhaled methacholine compared with sham-smoking controls after 6 pack-yr of smoking. To evaluate the role of nicotine in this blunting of airway reactivity, we studied the effects of both acute and chronic nicotine inhalation on reactivity to methacholine in baboons. Inhalation of 2 mg of nicotine had no acute effect on lung function but blunted bronchial reactivity in highly reactive animals. This effect was not diminished after daily inhalation of nicotine for 90 days. Marked interindividual differences in bronchial reactivity to methacholine were not abolished by propranolol, suggesting that factors other than beta-adrenergic tone account for this intersubject variability.

Aerosols↗

Cigarette smoking by baboons: in vivo assessment of particulate inhalation using bronchoalveolar lavage to recover [14C]dotriacontane.

In order to demonstrate quantitatively that cigarette-smoking baboons inhale particulate matter into the lung, a bronchoalveolar lavage method for recovery of [14C]dotriacontane was developed. First, 9 baboons were exposed to a known dose of [14C]dotriacontane labeled particulate matter delivered in a manner providing extensive deposition of particulates in the lung. The lungs of these passively exposed animals then were lavaged so that the efficiency of recovery of the standardized lavage procedure could be determined. Second, 9 baboons actively smoked labeled cigarettes, and the lungs of these animals were lavaged to recover labeled [14C]dotriacontane. The total amount of particulate matter present in the lungs was estimated using the efficiency factor previously determined. The smoking baboons retained an average of 9% of he total cigarette particulate matter. Differences among animals in retention of particulate matter were considerable, and the inter-animal variability was related to differences in number, volume, duration, and pressure of puffs. The retention of particulate matter by baboons is similar to particulate retention by other animal smoke inhalation models.

Alkanes↗

Bronchial reactivity to inhaled methacholine in cigarette-smoking baboons.

We expected that cigarette smoking would increase airway reactivity to inhaled methacholine. To remove the self-selection bias inherent among humans, we randomly assigned young male baboons (Papio cynocephalus) to cigarette-smoking or sham-smoking groups. The animals were taught to puff on lit cigarettes (smokers) or on a similar resistance (shams). After 6 pack-yr of smoking (40 cigarettes/day for 3 yr), we studied airway reactivity. The animals were anesthetized and intubated for measurement of lung volumes, compliance, and expiratory flow with air and with 80% helium-20% oxygen using both partial expiratory flow-volume and maximal expiratory flow-volume maneuvers. Baseline lung function was similar in smokers and shams. Following methacholine, residual volume increased significantly (P less than 0.05) in shams but not in smokers. Smokers showed significantly (P less than 0.04) greater postchallenge flow rates than did shams, and the dose of methacholine required to produce a 20% decrement in flow was significantly (P less than 0.05) greater in smokers. Chronic cigarette smoking in a nonhuman primate model decreases airway reactivity to inhaled methacholine even when base-line lung function is normal.

Animals↗

Effects of C5a on baboon alveolar macrophage migration.

The effect of C5a, a fragment of the fifth complement component, on alveolar macrophage migration was studied using a micropore method. Cells were obtained by broncho-pulmonary lavage, in vivo or in vitro, from control baboons and baboons taught to smoke cigarettes. Macrophage migration directly depended on the C5a concentration cells encountered. The highest C5a concentrations studied enhanced migration more than 20-fold. Cells from smokers exhibited greater migration than those from nonsmokers, and cells recovered in vivo exhibited greater migration than in vitro cells, but these differences were not significant. A gradient analysis suggested that C5a-induced migration was chemotactic, i.e., oriented; C5a enhanced migration more than N-formyl-methionyl-phenylalanine, and C5a without the C-terminal arginine lost over two thirds of its capacity to enhance migration. The observation that C5a induces alveolar macrophage chemotaxis established that alveolar macrophages are similar to other mononuclear phagocytes with respect to C5a-enhanced migratory responses, and demonstrated that complement components may participate in lung inflammatory reactions through effects on cells other than neutrophils.

Animals↗

Quantitation and stability of the fifth component of complement (C5) in bronchoalveolar lavage fluids obtained from non-human primates.

The functional activity and antigenic expression of the fifth component of complement (C5) in concentrated bronchoalveolar lavage fluids (BALF) and serum samples obtained from 13 nonsmoking and 13 smoking baboons was quantified by specific hemolytic titration and radioimmunoassays. The number of C5H505 units per milligram of albumin in BALF obtained from nonsmoking and smoking baboons indicated a nearly 2-fold increase in C5 hemolytic activity in lavage fluids as compared to matched serum samples. No significant differences (p greater than 0.05) in C5 hemolytic or antigenic (radioimmunoassay) expression were evident between BALF samples obtained from nonsmoking and smoking baboons. C5 stability in BALF was indicated by the highly significant correlation (p less than 0.005) between C5 hemolytic activity and antigenic expression. The absence of C5-cleaving enzymes in BALF was verified by incubation of 125I-C5 with these fluids, followed by SDS5 polyacrylamide slab gel and autoradiographic analyses. These results demonstrated the presence and stability of substantial quantities of functionally active C5 in the secretions of primate lungs, which represents a readily available source of phlogistic fragments for the initiation of pulmonary inflammation.

Animals↗

Atherosclerosis-related responses to cigarette smoking in the baboon.

Thirty-six young adult male baboons (Papio cynocephalus) were fed an atherogenic diet (40% calories from lard, 1.5 mg cholesterol/kcal) and taught to puff by operant conditioning with water rewards. Eighteen baboons (smokers) were assigned randomly to smoke 43 cigarettes a day, and 18 baboons (shams) were assigned randomly to puff air under conditions equivalent to those of the experimental group. During months 14-19 of smoking, cigarette-smoking baboons had significantly higher carbon monoxide and thiocyanate concentrations in blood and cotinine concentrations in urine. There were no significant differences in serum total cholesterol, VLDL + LDL cholesterol, HDL cholesterol or triglyceride concentrations of smokers and shams. Smoking baboons had significantly higher fasting blood glucose concentrations and lymphocyte counts. Platelet count, platelet aggregation, food and water intake, and body weight were not significantly different in the two groups.

Animals↗

Coronary bypass surgery for unstable angina: a five-year follow-up.

A total of 125 consecutive patients who were hospitalized for unstable angina underwent early coronary arteriography. One hundred of them were suitable for operation and were operated on promptly. There were no early deaths. The patients who had surgery have been followed up to 87 months (means, 57 months). Eighty-eight percent of the patients who had surgery returned to work. The actuarial five-year survival rate of those patients was 92%. At an average of five years, conditions of 62% of those who survived surgery were classified as functional class I, and 23% were class II. These data indicate that patients with unstable angina can safely undergo early arteriography and operation with late results that appear to be superior to the results of medical management of similar patients.

Adult↗

Q fever endocarditis in the United States.

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.

Animals↗