Clinical nurse specialist and staff nurse colleagues in integrating nursing research with clinical practice.

To advocate for cost-effective patient care and to strengthen the registered nurse's professional practice, the CNS must support nursing research in acute care facilities. This support for research includes sparking the staff nurse's interest and involvement in all segments of the research process. We must recognize our clinical nurses' efforts on behalf of research through greater financial reward; the CNS is challenged to use his or her influence to persuade administrators to grant this support. How the CNS and staff nurse, working together, can disseminate the findings of nursing research, thus promoting cost-effective care and solidifying the nurse's professional practice, is discussed in this article.

A dose-response trial of once-daily diltiazem.

This trial was performed to determine the safe and effective dosage range of once daily diltiazem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent.

Marijuana and tobacco smoke gas-phase cytotoxins.

To evaluate the in vivo versus in vitro paradoxical effects of marijuana and tobacco smoke on pulmonary defenses, the responses to smoke constituents were assessed with an alveolar macrophage tissue culture bioassay. A dose-response impairment of macrophage bactericidal activity was associated with water-soluble, gas-phase constituents. A model airway surface was constructed to examine the behavior of specific gas-phase constituents removed as they passed over wetted surfaces simulating the characteristics of the human respiratory system. Chemical analyses in the bioassay flask and in the model airway were compared. Gas-phase cytotoxins were measured after passage over wetted surface areas analogous to the trachea between the larynx and second-order bronchus. A wetted surface comparable to only 5% of the human airway, or less than 0.05% of the gas-exchanging surface of the entire lung, was capable of complete detoxification of the highly water-soluble gas-phase cytotoxins. In conclusion, gas-phase cytotoxins demonstrable by in vitro bioassays may have no cytotoxic potential when inhaled by humans.

Theoretical and experimentally quantifiable determinants of tobacco smoking behavior for the development of successful smoking cessation strategies.

Death rates from a number of diseases linked epidemiologically to tobacco use continue to rise despite major reductions in per capita tobacco consumption, despite reductions in the total number of smokers, and despite very significant reductions in "tar", in other tumorigens and in essentially all classes of potential toxins in smoke delivered to the consumer. One concern is that smokers consume low delivery cigarettes differently and in a potentially more hazardous way than higher delivery cigarettes. The effect of nicotine reduction in cigarettes on human smoking behavior was studied in 102 human subjects by quantifiable determinants of tobacco-smoking behavior. This study indicates that reduction in nicotine delivery results in some accommodation in smoking behavior to titrate nicotine needs. In addition, smokers appear to adjust their smoking behavior as a function of taste preference, and this adjustment is as strong as the accommodation for nicotine. The theoretical application of these observations to the development of successful smoking cessation strategies is reviewed.

A method for measuring respiratory deposition of cigarette smoke during smoking.

An understanding of the factors influencing respiratory deposition of cigarette smoke in smokers is needed to accurately control this important source of respiratory exposure in epidemiological studies of workers. Only a few studies have characterized the deposition of cigarette smoke in smokers and these involve methods that interfere with normal smoking. A technique for measuring puff volume, inhaled amount, and respiratory deposition of cigarette smoke particulate phase has been developed. It provides satisfactory accuracy (+/- 10%) and causes minimal disruption of normal smoking pattern. The technique captures exhaled smoke with an exhaust hood and establishes the amount of inhaled smoke by monitoring puff volume, puff duration, and puff timing and replaying the exact smoking sequence with matched cigarettes. Mass of captured cigarette smoke is evaluated by fluorophotometry. Preliminary trials with 11 paid volunteers gave an average puff volume of 53 mL and smoke deposition ranged from 22% to 75% with an average of 47%. Measured depositions are lower than previously published values and higher than would be predicted for submicrometer sized particles during normal breathing.

Characterization of a postlavage, in situ pulmonary macrophage population.

A postlavage in situ subpopulation of pulmonary macrophages (PM), biochemically distinct from the lavaged population, has recently been isolated from rats. After exhaustive bronchopulmonary lavage to extract the free lung cells, the lungs were excised, homogenized, and filtered, and the resultant cell suspension was allowed to form a monolayer on plastic Petri dishes. Electron microscopic morphometry failed to indicate any morphologic differences in the two populations. The postlavage in situ PM were more active metabolically during phagocytosis of zymosan particles or stimulation by phorbol myristate acetate (PMA) than the corresponding lavage population, as evidenced by greater superoxide generation. Macrophages prepared by either method became more avidly phagocytic when incubated with cell-free medium isolated in the preparation of the situ population. Peroxidase, an enzyme absent from the granules of PM separated by lavage techniques, was found in a granule-rich fraction of the in situ macrophage. Catalase activity was found in similar amounts in both supernatants and granule-rich fractions of both populations. The results support the concept of subpopulations of PM and suggest that these subpopulations are distinguished by their biochemical properties and their functional abilities.

Contractile performance of rat myocardium after chronic tobacco smoke inhalation.

The mechanical performance of isolated left ventricular muscle preparations from rats exposed to smoke from Kentucky Reference cigarettes was examined for possible chronic effects. Eight rats were subjected to smoke for periods of 10 min/hr for 5 hr/day for 180 days. Nineteen additional rats served as either sham-smoked controls or weight-matched, food-deprived controls. Rats exposed to tobacco smoke had a significant diminution in body and left ventricular weight compared to sham-smoked controls. When compared to food-deprived rats, no differences in weights were observed. Contraction mechanics were measured for each muscle at the peak of its length tension curve. No significant difference in cardiac muscle performance was found in rats exposed to tobacco smoke when compared to control animals with respect to contractile performance under oxygenated conditions, muscle performance during 60 min of hypoxia or subsequent reoxygenation, or sensitivity of mechanical performance to isoproterenol. Thus, chronic cigarette smoke exposure did not alter the intrinsic mechanical performance of isolated rat ventricular muscle.

Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke.

Effect of cigarette smoke and dietary cholesterol on plasma lipoprotein composition.

The effect of acute inhalation of cigarette smoke and consumption of dietary cholesterol on plasma lipoprotein composition in atherosclerosis-susceptible White Carneau pigeons was examined. Pigeons were assigned to four treatment groups: 1) Controls fed a chow diet ad libitum and retained in their cages throughout the study; 2) Sham pigeons fed a cholesterol-saturated fat diet and exposed to fresh air by the Lorillard smoking machine; 3) Low nicotine-low carbon monoxide (LoLo) animals also fed the cholesterol diet and exposed to low concentrations of these cigarette smoke products; and 4) High nicotine-high carbon monoxide (HiHi) birds fed the cholesterol diet and subjected to high concentrations of these inhalants. Plasma very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins were isolated by density gradient ultracentrifugation. Smoke-related differences appeared in HiHi HDL which contained relatively more free and esterified cholesterol and total lipid, but relatively and absolutely less total protein than HDL from Sham-smoked pigeons. Similarly, VLDL from birds exposed to cigarette smoke (LoLo and HiHi) contained relatively more total lipid, but less total protein than VLDL from Sham pigeons. Inhalation of tobacco smoke also produced a marked depression in the HDL2/HDL3 ratio resulting from an increased proportion of the HDL3 subfraction relative to HDL2. Pigeons (Sham, LoLo, HiHi) fed the cholesterol-saturated fat diet circulated HDL with greater free and esterified cholesterol mass than Controls. VLDL particles from these three treatment groups were relatively enriched with cholesterol and cholesteryl ester at the expense of triglyceride. Diet also altered the type of cholesteryl ester present in HDL with cholesteryl linoleate representing the predominant form in Control pigeons and cholesteryl oleate in cholesterol-fed birds. These results demonstrate that cigarette smoking can mediate alterations in lipoprotein composition independent of changes induced by dietary cholesterol and saturated fat.

Marijuana, tetrahydrocannabinol, and pulmonary antibacterial defenses.

Although marijuana is now consumed extensively, little is known of its biologic effects on the lung. To study this problem, the intrapulmonary inactivation of an aerosolized challenge of Staphylococcus aureus was quantified in rats exposed to graded amounts of fresh marijuana smoke. Controls inactivated 85.1 percent +/- 0.3 percent of the bacteria six hours after inoculation. Following an in vivo accumulative exposure to smoke from progressively increasing numbers of marijuana cigarettes for periods of ten minutes each hour for five consecutive hours, intrapulmonary bacterial inactivation was impaired in a dose-dependent manner. Evaluation of the effects of parenterally administered delta-9-tetrahydrocannabinol (THC) or of exposure to fresh smoke from THC-extracted marijuana placebo cigarettes indicated that the cytotoxin in marijuana was not related to the primary psychomimetic component. Thus, marijuana smoke is toxic to the lung and impairs the pulmonary antibacterial defense system in a dose-dependent manner.

A morphometric analysis of the male and female tracheal epithelium after experimental exposure to marijuana smoke.

Male and female rats were exposed to marijuana smoke that was generated from nonfiltered marijuana research cigarettes three times each day for 31 +/- 1 consecutive days. Morphometric analyses of the tracheal epithelium were made for the volume density of secretory cells in the trachal epithelium, volume density of glycoprotein in the secretory cells, and number of secretory cells per unit length of the tracheal epithelium. Glycol methacrylate sections of the trachea stained with a combined Alcian Blue and periodic acid-Schiff technique and hematoxylin permitted analysis of not only stained secretory cells and their glycoprotein composition but also unstained secretory cells, providing a complete profile of the total secretory cell population in the tracheal epithelium. Exposure to marijuana smoke resulted in an increase in the volume density of glycoprotein in the secretory cells in association with an increase in the number of stained secretory cells per unit length of epithelium and a shift in the secretory cell mucin production from periodic acid-Schiff-positive to the production of mixtures of periodic acid-Schiff-positive and Alcian Blue-positive glycoproteins. Exposure to marijuana smoke, however, decreased the volume density of total secretory cells and the number of unstained secretory cells. It appears that the increased number of stained secretory cells in marijuana smoke-exposed rats was the result of a conversion from unstained to stained secretory cells. Female rats demonstrated larger relative increases than male rats in the total glycoprotein in secretory cells, in the number of stained secretory cells, and a larger shift in glycoprotein composition after exposure to smoke.