Repellent and Attractive Effects of α-, ß-, and Dihydro-ß- Ionone to Generalist and Specialist Herbivores.

In plants, the oxidative cleavage of carotenoid substrates produces volatile apocarotenoids, including α-ionone, ß-ionone, and dihydro-ß-ionone, compounds that are important in herbivore-plant communication. For example, ß-ionone is part of an induced defense in canola, Brassica napus, and is released following wounding by herbivores. The objectives of the research were to evaluate whether these volatile compounds would: 1) be released in higher quantities from plants through the over-expression of the carotenoid cleavage dioxygenase1 (CCD1) gene and 2) cause herbivores to be repelled or attracted to over-expressing plants relative to the wild-type. In vivo dynamic headspace collection of volatiles coupled with gas chromatography-mass spectrometry was used to determine volatile organic compounds (VOC) in the headspace of the Arabidopsis thaliana ecotype Columbia-0 (L.) over-expressing the AtCCD1 gene. The analytical method allowed the detection of ß-ionone in the Arabidopsis headspace where emission rates ranged between 2 and 5-fold higher compared to the wild type, thus corroborating the in vivo enhancement of gene expression. A two chamber choice test between wild type and AtCCD1 plants revealed that crucifer flea beetle Phyllotreta cruciferae (Goeze) adults were repelled by the AtCCD1 plants with the highest transcription and ß-ionone levels. α-Ionone and dihydro-ß-ionone were not found in the headspace analysis, but solutions of the three compounds were tested in the concentration range of ß-ionone found in the Arabidopsis headspace (0.05 to 0.5 ng/µl) in order to assess their biological activity with crucifer flea beetle, two spotted spider mite Tetranychus urticae (Koch), and silverleaf whiteflies Bemisia tabaci (Gennadius). Choice bioassays demonstrated that ß-ionone has a strong repellent effect toward both the flea beetle and the spider mite, and significant oviposition deterrence to whiteflies. In contrast, dihydro-ß-ionone had attractant properties, especially to the crucifer flea beetle, while α-ionone did not show any significant activity. These findings demonstrate how regulating genes of the carotenoid pathway can increase herbivore deterrent volatiles, a novel tool for insect pest management.

How much do Indians pay for tuberculosis treatment? A cost analysis.

SETTING: India's National Tuberculosis Elimination Programme (NTEP) covers diagnostic and therapeutic costs of TB treatment. However, persons living with TB (PLWTB) continue to experience financial distress due to direct costs (payment for testing, treatment, travel, hospitalization, and nutritional supplements) and indirect costs (lost wages, loan interest, and cost of domestic helpers). OBJECTIVE: To analyze the magnitude and pattern of TB-related costs from the perspective of Indian PLWTB. DESIGN: We identified relevant articles using key search terms ('tuberculosis,' 'India,' 'cost,' 'expenditures,' 'financing,' 'catastrophic' and 'out of pocket') and calculated variance-weighted mean costs. RESULTS: Indian patients incur substantial direct costs (mean: US$46.8). Mean indirect costs (US$666.6) constitute 93.4% of the net costs. Mean direct costs before diagnosis can be up to four-fold that of costs during treatment. Treatment in the private sector can result in costs up to six-fold higher than in government facilities. As many as one in three PLWTB in India experience catastrophic costs. CONCLUSION: PLWTB in India face high direct and indirect costs. Priority interventions to realize India's goal of eliminating catastrophic costs from TB include decreasing diagnostic delays through active case finding, reducing the need for travel, improving awareness and perception of NTEP services, and ensuring sufficient reimbursement for inpatient TB care.

Increased surface tension favors pulmonary edema formation in anesthetized dogs' lungs.

The possibility that surface tension may affect the hydrostatic transmural pressure of pulmonary vessels and the development of pulmonary edema was studied in anesthetized, open-chested dogs. Isogravimetric pressure (the static intravascular pressure at which transmural osmotic and hydrostatic pressures are balanced such that net fluid flux is zero and lung weight is constant) was measured in nine animals under three conditions: (a) control, normal surface tension, at an alveolar pressure of 30 cm H2O with the apenic lung at room temperature; (b) after increasing surface tension by cooling and ventilating at a low functional residual capacity, at an alveolar pressure sufficient to produce the same lung volume present during control measurements; and (c) after restoring surface tension by rewarming while holding the lung at a high inflation volume, again at the control lung volume. Lung volumes were established from external dimensions and confirmed +/- 10% by deflation spirometry. The isogravimetric pressure (relative to alveolar pressure) was significantly less with increased surface tension than during either the initial control condition (P less than 0.01), or when the surface tension has been restored (P less than 0.01). Similar changes occurred in each of three additional studies performed with control alveolar pressures of 10 cm H2O. Thus, increased surface tension favors fluid leakage presumably because it increases the microvascular transmural pressure.

Structure and size of bronchopulmonary anastomoses in sheep lung.

The distribution and drainage of bronchial arterial blood flow are complex. We used two different methods to study the bronchial-pulmonary anastomoses in sheep lung. Initially, we injected two different sizes of fluorescent microspheres (15 and 100 microm diameter) into the bronchial artery and histologically determined where the different-size microspheres were entrapped in the lung. In a second series of animals, we injected Microfil into the bronchial artery to observe the anastomotic vessels. The microsphere data confirmed the existence of bronchial-to-pulmonary anastomoses. No microspheres were found in the systemic organs (heart and kidney), confirming the absence of large bronchial artery-to-pulmonary vein anastomoses. Unexpectedly, proportionately more large microspheres (100 microm) lodged in the alveolar parenchyma when compared to 15 microm microspheres. This suggests that there are many more small bronchial (< 100 microm) arterioles feeding the airway mucosa than the larger anastomotic vessels feeding into the parenchyma. In the Microfil cast lungs, we observed four types of anastomotic vessels: bronchial arteries/arterioles that anastomose with pulmonary arteries/arterioles that accompany airways; bronchial arterioles that anastomose directly with parenchymal (and eventually alveolar) vessels; bronchial arterioles that anastomose with blood vessels that do not accompany airways; and bronchial arterioles that anastomose with bronchial veins. Based on our in vivo microsphere data, the vessels that do not accompany the airways are most likely bronchial venules, not pulmonary venules.

Venous air embolism.

Venous air embolism causes injury primarily by obstruction of blood flow from the right side of the heart to the left. This is due to mechanical obstruction of the right ventricular pulmonary outflow tract and pulmonary vasculature and to poorly understood pulmonary vasoconstrictive mechanisms. Venous air embolism can result in considerable hypoxemia from ventilation-perfusion maldistribution and shunt. With large emboli, systemic hypotension, myocardial ischemia, and arrhythmias can occur and result in death. One should be familiar with the clinical setting where embolism occurs, as prevention is the best treatment. When air embolism is suspected, placement of the patient in the left lateral decubitus position, initiating closed chest massage or, if possible, aspiration of air through a right atrial or Swan-Ganz catheter are all acceptable forms of treatment. The patient should also be given 100% oxygen.

Pulmonary effects of topical timolol.

Timolol, a beta-adrenergic blocking agent, recently became available for the treatment of glaucoma. We report the occurrence of acute bronchospasm in a previously asymptomatic asthmatic patient following topical use of timolol. Therapy with the drug was discontinued, and four weeks later the patient was challenged with two drops of 0.5% timolol. A 25% decrease in forced expiratory volume at one second (FEV1) was demonstrated at one hour. The fall in FEV1 was even greater (47%) when the patient was rechallenged with four drops. We emphasize the need to avoid topical beta-adrenergic blocking agents in asthmatic patients.

Comparison of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs.

STUDY OBJECTIVE: The aim was to measure cardiac output while rebreathing tidal volumes, by correction of soluble gas uptake for gaseous mixing. DESIGN: Simultaneous measurements of cardiac output by indocyanin green and freon 22 uptake during rebreathing were made. Mixing for a hypothetical gas of identical gaseous diffusivity to freon 22 was calculated by interpolation between concentrations of two insoluble gases, helium and sulphur hexafluoride. Mixing efficiency was estimated by the number of breaths for helium to become 99% equilibrated with lung gas (n99-He). EXPERIMENTAL MATERIAL: Five anaesthetised dogs rebreathed at intervals with 300 ml of test gas. MEASUREMENTS AND MAIN RESULTS: 63 comparisons of cardiac output using indocyanin green and freon 22 uptake (over breaths 7-13 using the mean mixed volume of distribution), gave a mean (95% confidence interval) underestimation of 0.345 (0.093-0.597) litre.min-1 (14%). Exclusion of 12 points in which n99-He was greater than 15 resulted in a mean underestimation of 0.052(-0.163-0.267) litre.min-1 (2%). Without correction for gaseous mixing, freon 22 uptake for these data overestimated blood flow by a mean of 1.31 litre.min-1 (overestimation = 2.7 over breaths 5-11). Use of the equilibrium volume of distribution resulted in an overestimation of blood flow relative to green dye of 1.2 litre.min-1 (breaths 5-11) and 0.76 litre.min-1 (breaths 7-13). CONCLUSIONS: Estimates of cardiac output by soluble gas uptake are optimal when correction is made for mixing of gas of identical diffusivity. The mean mixed gas volume gives the best correlation with the reference method, implying a selective distribution of blood flow to the better ventilated areas.

Effect of diazepam on ventilatory responses.

To investigate the effects of diazepam on ventilatroy control, hypoxic and hypercapnic ventilatory responses were studied in 8 normal subjects before and after 10 mg of intramuscular diazepam. There was no significant change in either resting minute ventilation or resting end-tidal CO2 tension, but depression of hypoxic ventilatory response was observed 15 (60% of control) and 30 min (53% of control) after diazepam (p less than 0.05). No significant depression of hypercapnic ventilatory response was noted 70 to 130 min after diazepam. In view of the depression of hypoxic ventilatory response by diazepam in normal subjects, adverse responses along these lines should be considered in patients with impaired ventilatory function, such as chronic airways obstruction, and in those encountering acute hypoxemia.

Pleural mesotheliomas--an analysis of 18 cases and review of the literature.

Eighteen cases of mesothelioma, 7 benign and 11 malignant, were analyzed retrospectively. There were 5 females with benign tumors and 10 males with the malignant variety. The mean age was 59 years in the benign group and 55 years in those with malignant tumors. Exposure to asbestos was documented in one benign and five malignant mesotheliomas. Three patients with benign lesions were asymptomatic on presentation while all 11 with malignant tumors had symptoms, chest pain and dyspnea being the most frequent. Abnormal physical findings were rarely noted in the benign group while all the malignant tumors had abnormal findings on presentation. Signs of a pleural effusion were the most common abnormal physical findings, occurring in 8 of 11 patients. Pleural effusion was the most common roentgenologic finding in malignant mesotheliomas, while a mass lesion was the presenting finding in six of seven of the benign group. Pleural effusion was a usual accompaniment of malignant tumors and was an exudate, usually hemorrhagic with leukocyte counts up to 20,000/mm3. Thoracotomy established the diagnosis in each of the five benign and seven malignant cases in which it was attempted. Pleural biopsy was diagnostic in three of six with malignant and one of two with benign tumors. Pleural fluid cytology did not yield a diagnosis in the seven instances in which it was studied. Excisional surgery was performed in five of the benign cases and all have survived one to six years. No treatment was curative of malignant mesotheliomas. Ten of the 11 with malignant tumors died from 3 to 24 months after onset of symptoms (mean 9.9 months). The clinical features of 82 benign and 160 malignant mesotheliomas from selected series in the literature are reviewed and compared with the present series. The roentgenographic features of 51 benign and 87 malignant tumors are also presented. The clinical and diagnostic features which help differentiate mesotheliomas from bronchogenic carcinomas are discussed. A careful approach to the diagnosis of malignant mesotheliomas may help avoid an unnecessary thoracotomy.

Ipratropium bromide in chronic bronchitis/emphysema. A review of the literature.

Many studies have evaluated the efficacy of ipratropium bromide in chronic obstructive pulmonary disease (COPD). Single-agent studies have shown ipratropium to be both safe and effective in COPD. Several studies have compared ipratropium with sympathomimetic agents or methylxanthines in patients with chronic bronchitis or emphysema; all of these studies have shown at least an equal, and in most instances a superior, bronchodilator action with ipratropium in terms of duration of action as well as peak bronchodilator effect in patients with COPD. In some patients with COPD, beta agonists, theophylline, or corticosteroids may have some additive, but not synergistic, bronchodilator effects when given with ipratropium.

The effect of fiberoptic bronchoscopy on cardiac rhythm.

Cardiac rhythm was monitored in 70 patients prior to, during, and following fiberoptic bronchoscopic procedures. Minor abnormalities in rhythm were frequent. Major cardiac arrhythmias occurred in 11% (8/70) of the patients during the bronchoscopic procedure. All arrhythmias were self-limited and had no hemodynamic consequence. Patients with evidence of coronary arterial disease, chronic obstructive pulmonary disease, or previously known premature ventricular contractions were at no higher risk for developing major arrhythmias. Hypoxemia (arterial oxygen pressure less than 60 mm Hg) at the end of the procedure correlated significantly with the development of new major arrhythmias.

The effect of atropine inhalation in "irreversible" chronic bronchitis.

Fifteen patients with chronic bronchitis and airflow obstruction which was not improved by inhalation of isoproterenol (increase in forced expiratory volume in one second [FEV1] less than 15 percent) received an aerosol of atropine sulfate (0.05 mg/kg of body weight), in order to determine their response to an anticholinergic bronchodilator drug. The improvement over initial values for FEV1 at 15 minutes following inhalation of isoproterenol and at 90 minutres following inhalation of atropine averaged 5.9 percent and 19.2 percent, respectively (P less than 0.01). Eleven of 15 patients demonstrated a 15 percent or greater increase in FEV1 following inhalation of atropine, and six subjects demonstrated more than 25 percent improvement. The maximum effect of atropine was observed at or later than 90 minutes following inhalation in nine of 11 patients who were responsive to atropine. Minimal systemic toxic effects resulted from inhalation of atropine, although dryness of the mouth was frequent. In patients with chronic bronchitis, airflow obstruction resistant to isoproterenol may respond to inhalation of an aerosol of atropine sulfate.

Efficiency of air compressor-driven nebulizers.

Five different volumes of test solutions (1 to 3 ml) containing 15 mg of metaproterenol were placed in each of five different nebulizers. The time to complete nebulization and the amount of drug delivered varied considerably, depending upon the initial volume of solution placed in the nebulizer. Small volumes (1 ml) were almost totally retained in the nebulizer, whereas larger volumes (3 ml) took an unacceptably long time for nebulization. With vigorous agitation, a maximum of 53 to 72 percent of the dose left the nebulizer, but even less (34 to 59 percent) was delivered under simulated clinical conditions. When nebulization was synchronized with breathing, only 0.33 to 0.54 ml of solution (2 to 3.2 mg of metaproterenol) was delivered with 90 deep inhalations. If nebulization was continuous instead of intermittent during the time to take 90 breaths, the majority of the drug was nebulized to the atmosphere.

Unsuspected pulmonary alveolar proteinosis complicating acute myelogenous leukemia.

A patient with acute myelogenous leukemia developed pulmonary alveolar proteinosis in the terminal phase of the leukemia. The diagnosis of pulmonary alveolar proteinosis was unsuspected during life and was established only at autopsy. Other reported cases of the same association are reviewed. This report serves to stress the importance of considering the diagnosis of pulmonary alveolar proteinosis in malignant hematologic diseases and the need for hematologic evaluations in pulmonary alveolar proteinosis.

Atropine and terbutaline aerosols in chronic bronchitis: efficacy and sites of action.

To examine the additive properties and the sites of action of inhaled atropine sulfate (0.05 mg/kg of body weight) and terbutaline sulfate (0.005 mg/kg) in patients with chronic airflow obstruction, we tested these aerosols separately and together in a double-blind random sequence. Twelve patients with chronic bronchitis and perennial obstruction of airflow were studied by measuring three indices of efficacy (specific airway conductance [Gaw/VL], the forced expiratory volume in one second [FEV1] and the forced vital capacity [FVC]) and three indices of the site of action within the airway (delta [(Gaw/VL)/FEV1], the difference between the change in forced expiratory flow at 75 percent of vital capacity and the change in forced expiratory flow at 25 percent of vital capacity, and the change in density dependence of maximal airflow at 50 percent of vital capacity). Both atropine and the combination of atropine and terbutaline improved all indices of efficacy significantly more than did terbutaline. With individual exceptions, the addition of terbutaline to atropine improved Gaw/VL but not forced airflow. All measures of site of action suggested an advantage for atropine in relatively proximal airways. These results indicate that combined therapy with beta-adrenergic and anticholinergic bronchodilator drugs is marginally more effective than therapy with atropine alone in these patients and suggest that anticholinergic aerosols dilate larger airways more effectively than the beta-agonists.

The pulmonary sequelae associated with accidental inhalation of chlorine gas.

Twenty previously healthy individuals were accidentally exposed to high concentrations of chlorine gas in 1975. Pulmonary function tests were performed on these individuals on several occasions over the next 12 years. On average, each subject was followed up for 8.5 years and 13 of the 20 exposed persons were tested 12 years following the exposure. Pulmonary function tests obtained one day following the accident were most notable for the high prevalence of airflow obstruction and air trapping. Over the ensuing years, the airflow obstruction persisted; however, the high prevalence of air trapping resolved. Of note, the prevalence of a low residual volume consistently increased during the follow-up period (p less than 0.001) and at year 12, 67 percent of those tested had residual volumes below 80 percent of their predicted value. We also found that five of 13 subjects tested at year 12 had an increase in airway reactivity (greater than 15 percent decline in FEV1) to inhaled methacholine. Those individuals with reactive airways were older (p = 0.004) and had more marked airflow obstruction (p = 0.03) and air trapping (p = 0.03) immediately following the exposure. These data suggest that exposure to high concentrations of chlorine gas may result in long-term pulmonary complications that are characterized by a reduced residual volume. Unfortunately, these data preclude us from determining whether the chlorine exposure led to the development of airway reactivity or the presence of reactive airways accounted for the air trapping that was observed following the exposure to chlorine gas.

Influence of lung volume and left atrial pressure on reverse pulmonary venous blood flow.

Infarction of the lung is uncommon even when both the pulmonary and the bronchial blood supplies are interrupted. We studied the possibility that a tidal reverse pulmonary venous flow is driven by the alternating distension and compression of alveolar and extra-alveolar vessels with the lung volume changes of breathing and also that a pulsatile reverse flow is caused by left atrial pressure transients. We infused SF6, a relatively insoluble inert gas, into the left atrium of anesthetized goats in which we had interrupted the left pulmonary artery and the bronchial circulation. SF6 was measured in the left lung exhalate as a reflection of the reverse pulmonary venous flow. No SF6 was exhaled when the pulmonary veins were occluded. SF6 was exhaled in increasing amounts as left atrial pressure, tidal volume, and ventilatory rates rose during mechanical ventilation. SF6 was not excreted when we increased left atrial pressure transients by causing mitral insufficiency in the absence of lung volume changes (continuous flow ventilation). Markers injected into the left atrial blood reached the alveolar capillaries. We conclude that reverse pulmonary venous flow is driven by tidal ventilation but not by left atrial pressure transients. It reaches the alveoli and could nourish the alveolar tissues when there is no inflow of arterial blood.

Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow.

We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end-expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries.

Bronchial circulation and cyclooxygenase products in acute lung injury.

The role of cyclooxygenase products in the response of the bronchial circulation to acute lung injury was examined in 30 dogs. By use of an open-chest preparation the left lower lobe (LLL) pulmonary circulation was isolated, continuously weighed, and perfused in situ. The anastomotic bronchial blood flow [Qbr(s-p)] was measured as the rate of increase in the volume of the LLL-perfusion circuit. Four groups of dogs were studied. In group A, six dogs received cyclooxygenase inhibition (COI) with either indomethacin (2 mg/kg) or ibuprofen (10 mg/kg). In group B (n = 10) lung injury caused by airway instillation of glucose (15 mg) with glucose oxidase (500 micrograms/kg) (G/GO) or LLL pulmonary arterial infusion of alpha-napthyl thiourea (ANTU, 2 mg/kg). Group C (n = 10) received COI, and 30 min later injury was induced as above with either ANTU or G/GO. Group D (n = 4) received COI immediately after anesthesia; then, 30 min after completion of the surgical preparation, injury was induced with ANTU or G/GO. After COI, Qbr(s-p) decreased to 35 +/- 9% of the basal values (P less than 0.05). After administration of ANTU or G/GO, Qbr(s-p) increased irrespective of whether COI was present. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) were measured by radioimmunoassay in the LLL pulmonary artery and systemic venous blood, demonstrating an increase in 6-keto-PGF1 alpha due to surgical preparation and confirming complete COI in those animals receiving COI immediately after anesthesia. These findings demonstrate that 1) the bronchial circulation is capable of a sevenfold increase in flow in response to acute lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute increases in anastomotic bronchial systemic to pulmonary blood flow due to generalized lung injury.

Since pulmonary blood flow to regions involved in adult respiratory disease syndrome (ARDS) is reduced by hypoxic vasoconstriction, compression by cuffs of edema, and local thromboses, we postulated that the bronchial circulation must enlarge to provide for the inflammatory response. We measured anastomotic bronchial systemic to pulmonary blood flow [QBr(s-p)] serially in a lung lobe in 31 open-chest dogs following a generalized lobar injury simulating ARDS. The pulmonary circulation of the weighed left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in anesthetized dogs. QBr(s-p) was measured from the amount of blood which overflowed from this closed vascular circuit corrected by any changes in the lobe weight. The LLL was ventilated with 5% CO2 in air. The systemic blood pressure (volume infusion), gases, and acid-base status (right lung ventilation) were kept constant. We injured the LLL via the airway by instilling either 0.1 N HCl or a mixture of glucose and glucose oxidase or via the pulmonary vessels by injecting either alpha-naphthylthiourea or oleic acid into the LLL pulmonary artery. In both types of injury, there was a prompt rise in QBr(s-p) (mean rise = 247% compared with control), which was sustained for the 2 h of observation. The cause of this increase in flow was studied. Control instillation of normal saline into the airways or into the pulmonary vessels did not change QBr(s-p) nor did a similar increase in lobar fluid (weight) due to hydrostatic edema. Neither cardiac output nor systemic blood pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)