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M Dolovich

Publications and source records attributed to M Dolovich.

At least 37 records · Page 2Linked to original sources
PubMed1997

Computer simulations of lung morphologies within planar gamma camera images.

A mathematical model and computer code have been developed to unambiguously interpret planar gamma camera images. Specifically, the algorithm permits airway composition of the central, intermediate and peripheral partitions of scans to be determined quantitatively. The algorithm unambigously identifies the spatial coordinates of each of the millions of airways within the adult human lung, and assigns every individual airway to a precise location within the gamma camera image format prescribed by the clinician. This is done on a patient-by-patient basis. The algorithm has evolved from clinical applications of the previous work of Martonen et al. [1]. The objective of the current work was to advance the original protocol and derive an algorithm that was: (1) from a medical perspective, more physiologically realistic; and (2) from a technical perspective, easier to apply in the medical arena. Regarding (1), the major elements of the algorithm are that the outer boundary of the lung is formulated directly from lung perfusion imaging data and that the lung is divided into distinct left and right components. Regarding (2), the algorithm has been written for use with common workstations. It is our hope that the improvements will facilitate applications of the new model-code into aerosol therapy regimens.

Adult↗
PubMed1997

Changing delivery methods for obstructive lung diseases.

There are three types of modalities for production of aerosolized medications, but numerous specific devices using these techniques are available. The recognition that children and adults need to use optimal methods to derive maximum therapeutic benefit with minimal side effects has resulted in recent developments such as spacers for pressurized metered-dose inhalers and breath-actuated dry powder inhalers and nebulizers. These methods provide finer aerosols that can be readily inhaled and deposited in the lung with improved efficiency. Delivery systems designed specifically for particular formulations have generally been well studied, but there is a paucity of information from manufactures characterizing the drug aerosols available from their devices. Clinicians are guided by data from drug trials, but must also be furnished with details of the delivery systems to allow them to compare devices and make intelligent choices for their patients. The material presented in this review provides an evaluation of some of the systems currently available for treating asthma and other lung diseases as well as a discussion of devices planned for the future.

Administration, Inhalation↗
PubMed1997

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

Administration, Inhalation↗
PubMed1996

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗
PubMed1995

Chest position and pulmonary deposition of surfactant in surfactant depleted rabbits.

AIMS: To investigate the correlation between chest position and the distribution of surfactant in the lungs of surfactant depleted rabbits, to corroborate current guidelines on the intratracheal instillation of exogenous surfactant in newborns. METHODS: Twelve tracheotomised rabbits, depleted of pulmonary surfactant by saline bronchoalveolar lavage, were given intratracheal 99m Technetium labelled Exosurf in three positions (prone, right side down, and left side down) (n = 4 in each group). They were monitored for 10 minutes using dynamic gamma scintigraphy monitoring. Instillation completed, the lateral lying animals were turned to the opposite side to determine whether redistribution of the surfactant had taken place. The amount of radiolabelled surfactant deposited at the peripheral, central, dorsal and ventral parts of the lungs was then estimated by gamma counting of the lung sections at necropsy. RESULTS: Both gamma scintigraphy and gamma counting showed similar rates and total amount of surfactant accumulation in both lungs of the prone animals. In the lateral lying animals surfactant accumulated at a significantly faster rate in the dependent lungs: the amount of surfactant deposition was three to 14-fold that in the raised lungs (p = 0.017; nested ANOVA). Changing the chest position immediately after instillation did not redistribute the surfactant. In all three groups of animals there was no significant difference in deposition between the peripheral, central, ventral and dorsal parts of the lungs. CONCLUSIONS: Pulmonary distribution of intratracheally instilled surfactant is largely determined by gravity, and changing the chest position after instillation does not result in any redistribution of the surfactant. During the instillation of exogenous surfactant to newborn infants, keeping the chest in the horizontal position may therefore result in the most even distribution of the surfactant in the two lungs. Further deposition studies are required to evaluate the validity of the current recommendations on surfactant administration.

Animals↗
PubMed1995

Metered-dose inhaler salbutamol-induced tracheal epithelial lesions in intubated rabbits. Effects of the site of administration and time.

STUDY OBJECTIVES: To determine (1) whether metered-dose inhaler (MDI) salbutamol administered at the elbow connector of the anesthetic circuit produced tracheal epithelial lesions in intubated rabbits, and (2) the time course for resolution of tracheal lesions produced by MDI salbutamol through an intratracheal catheter. DESIGN: Prospective, randomized, controlled trial. SETTING: University-affiliated animal research laboratory. PARTICIPANTS: Thirty-nine adult New Zealand white rabbits. INTERVENTIONS: (1) Twenty-one intubated rabbits received 0,5, or 20 puffs of MDI salbutamol delivered at the elbow connector of the anesthetic circuit. (2) Eighteen intubated rabbits received five puffs of MDI salbutamol through an intratracheal catheter and were killed 1 h, 24 h, or 1 week later. MEASUREMENTS: Samples of trachea, bronchi, and lungs were examined by light microscopy, and the degree of epithelial injury was assessed semiquantitatively. RESULTS: MDI salbutamol (5 or 20 puffs) administered at the elbow did not induce tracheal epithelial injury. When administered through an intratracheal catheter, MDI salbutamol (five puffs) produced moderate or severe tracheal epithelial injury in those killed 1 h after the study. Evidence of epithelial regeneration was observed 24 h after the injury and recovery was virtually complete by 1 week. CONCLUSION: Epithelial lesions do not occur when the MDI salbutamol (5 or 20 puffs) is administered at the elbow connector of the ventilation circuit. Tracheal epithelial lesions produced by MDI salbutamol (five puffs) administered through an intratracheal catheter resolve within 1 week of the injury.

Albuterol↗
PubMed1994

Definition of airway composition within gamma camera images.

The efficacies of inhaled pharmacologic drugs in the prophylaxis and treatment of airway diseases could be improved if particles were selectively directed to appropriate sites. In the medical arena, planar gamma scintillation cameras may be employed to study factors affecting such particle deposition patterns within the lung. The value and versatility of such instruments, however, are compromised by the limited resolution of their images. Specifically, it is not possible to determine the composition of their central (C) or large airway, intermediate (I), and peripheral (P) or small airway zones. We present an analytical model to assist the clinician in the systematic analysis and interpretation of gamma camera images. Using the Cray Y-MP supercomputer, a range of human lung morphologies has been mapped to function as templates that can be superimposed on scans. The model is intended to complement laboratory regimens by providing a previously unavailable method to define the C, I, and P zones of the human lung generation by generation. A quantitative value now can be assigned to the degree of overlapping that exists in the images. For example, for a "typical" lung morphology consisting of 16,777,215 airways (total), the C zone itself may contain 1,608,246 airways, of which 1,595,940, or 99.2%, are alveolated airways. By identifying composition, our intent is to integrate the model into future aerosol therapy protocols and thereby assist procedures that target delivery of airborne pharmaceuticals.

Administration, Inhalation↗
PubMed1994

Proximate delivery of a large experimental dose from salbutamol MDI induces epithelial airway lesions in intubated rabbits.

The delivery of aerosolized drugs by metered dose inhaler (MDI) to intubated patients can be substantially improved by actuating the MDI through a narrow catheter placed inside the tracheal tube. However, the deposition of increased quantities of drug, surfactant, in particular oleic acid, and chlorofluorocarbon propellants on the lung surface could result in adverse effects not observed after oral MDI administration. To investigate this hypothesis, 42 adult intubated rabbits (six groups, n = 6 to 9/group) received Ventolin MDI, Ventolin placebo, a placebo MDI containing lecithin as surfactant, instilled salbutamol sulfate, instilled oleic acid solution, or no treatment (control). Heart rate, invasive blood pressure, and hemoglobin oxygen saturation, recorded continuously for the 3-h experiment, were unchanged from baseline (awake) values. Sections of trachea and lungs were reviewed blindly and graded using a four-point, nine-variable Ophoven scale. Blood was obtained after either 1 puff or 20 puffs MDI salbutamol to determine the pharmacokinetic profile of salbutamol. Multiple doses of both Ventolin and Ventolin placebo aerosols produced significant lesions to the epithelium of the trachea and main bronchi (p < 0.05). The histologic injury after lecithin placebo or salbutamol solution did not differ significantly from control, and all were significantly less than that observed after Ventolin MDI administration. Instilled oleic acid caused gross airway lesions. Maximum serum concentrations of salbutamol were 4.4 +/- 1.8 ng/ml after 1 puff and 419 +/- 168 ng/ml after 20 puffs. After 20 puffs, the total body clearance of salbutamol was 108 +/- 27 ml/min/kg, volume of distribution was 3.6 +/- 1.8 L/kg, and the elimination half-life was 22 +/- 7 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1993

Dosing efficiency and particle-size characteristics of pressurized metered-dose inhaler aerosols in narrow catheters.

An experimental in vitro model was used to determine the effects of intraluminal catheter diameter and length on the delivered dose and particle-size characteristics of salbutamol (albuterol) aerosol delivered by metered dose inhaler (MDI) (Ventolin, 100 micrograms per puff). The dose of aerosolized drug that exited a 16-cm-long tracheal tube with an inner diameter (ID) of 6 mm was compared with that from 4 catheters of differing diameters and lengths that were inserted individually into the tracheal tube. The salbutamol MDI canister was actuated ten times into each delivery system, and the effluent aerosol was trapped onto a filter. The filtrate was dissolved in methanol, and the salbutamol concentration was determined using high-performance liquid chromatography. For the 3 22-cm-long catheters, the delivered dose (mean +/- SD) of salbutamol per actuation for the 22-standard wire gauge (SWG) catheter was 97.5 +/- 3.9 micrograms, which was similar to that for the 19-SWG catheter (102.3 +/- 2.5 micrograms) but was significantly less than that for the 14-SWG catheter (108.2 +/- 4.2 micrograms) (p < 0.05). These delivered doses exceeded those of the 6.0-mm-ID tracheal tube alone (2.33 +/- 0.76 micrograms) and the 13-cm-long 19-SWG catheter (2.17 +/- 0.29 micrograms) (p < 0.001). In a second experiment using a cascade impactor, the distribution of aerosol particle diameters that exited the 6-mm-ID tracheal tube was compared with that exiting a 13-cm-long 19-SWG catheter that extended halfway down the tracheal tube and with that exiting a 22-cm-long 19-SWG catheter inserted into the distal end of the 6-mm-ID tracheal tube. The mass median aerodynamic diameter (mean +/- SD) of the salbutamol aerosols delivered through both the 6.0-mm-ID tracheal tube (1.1 +/- 0.1 microns) and that of the 13-cm-long 19-SWG catheter (1.2 +/- 0.2 microns) were significantly less than that delivered through the 22-cm-long 19-SWG catheter (2.0 +/- 0.1 microns) (p < 0.05). The authors conclude that delivery of respirable aerosol can occur through narrow catheters that function as extended nozzles for MDIs. Optimal dosing will be obtained when the catheter extends the full length of the tracheal tube.

Aerosols↗
PubMed1991

Measurement of particle size characteristics of metered dose inhaler (MDI) aerosols.

Measurement of the aerodynamic size of an aerosol allows a prediction of its deposition efficiency and behaviour in the lung. The dynamics of volatile or pressurized (MDI) aerosols presents problems not encountered in the characterization of solid or liquid particles alone. For example, the data obtained in real-time sampling as opposed to measuring an aged aerosol provide a truer representation of circumstances during actual clinical use, yet this may be difficult to achieve due to propellent evaporation. A number of particle sizing systems have been developed based upon light scattering techniques and aerodynamic principles. Each method has its limitations; in general, they successfully measure the aerodynamic size distributions of MDI aerosols. Cascade impactors, the "gold standard" of the industry have the advantage that they allow analysis of drug mass as well as other tracers within the aerosol, but the process as a whole is labour intensive, with limited resolution. Highly automated laser-based systems developed over the past 10 years measure the surface characteristics of the aerosol rather than the direct measurement of mass. Because of different values obtained from various sizing systems, it is suggested that all MDI drugs be sized using cascade impactors but that parallel data be obtained using an alternative sizing system.

Administration, Inhalation↗
PubMed1989

Antigen-induced lung solute clearance in rats is dependent on capsaicin-sensitive nerves.

Chemosensitive sensory nerves have an important effector role in the control of vascular permeability in rat airways after neurogenic inflammation. To investigate whether they also have a role in antigen-induced lung inflammation, we have studied the changes in lung solute clearance (LSC) in sensitized rats after aerosol challenge with allergen and the effect of prior capsaicin-induced denervation on these changes. Sprague-Dawley rats were immunized with egg albumin (EA), using aluminum hydroxide and Bordetella pertussis as adjuvants. After 11 days, the animals were challenged for 5 min with aerosolized EA, and the clearance from the lungs of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) over 7.5 min (LSC 7.5) was subsequently measured at various times after challenge as an index of epithelial permeability or integrity. Sensitized animals responded to the challenge with immediate respiratory symptoms and with an increased 99mTc-DTPA clearance rate that was detectable at 20 min (mean +/- SE LSC 7.5: baseline, 6 +/- 1%; 20 min, 17 +/- 3%; p less than 0.05), persisted at 4 h (14 +/- 1%; p less than 0.05), and returned to normal values after 24 h. Unsensitized rats exposed to EA and sensitized rats exposed to PBS or to bovine serum albumin did not show any change. Bronchoalveolar lavage failed to show significant changes of cell populations until 24 h, when an increased presence of lymphocytes, PMN, and eosinophils was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1988

Lung clearance of 99mTc-DTPA in patients with acute lung injury and pulmonary edema.

Several acute and chronic conditions that alter the integrity of the pulmonary epithelium increased the rate of absorption or clearance into the circulation of small solutes deposited in the alveoli. Technetium 99m diethylenetriamine pentaacetic acid can be deposited in the lungs as a submicronic aerosol and its rate of clearance measured with a gamma camera or simple probe. This clearance technique is currently being used to evaluate patients who have developed pulmonary edema and also to detect those patients from a high risk group who are likely to develop adult respiratory distress syndrome (ARDS). Its role in the evaluation of patients with pulmonary edema is still under active investigation. It is clear that a single measurement in patients who smoke is not useful, but repeated measurements may provide important information. The lung clearance measurement is very sensitive to changes in epithelial integrity but is not specific for ARDS. It may be most useful in combination with other predictive tests or when the clearance rate is normal.

Capillary Permeability↗
PubMed1988

Solute movement across the alveolar-capillary membrane after intratracheally administered bleomycin in rats.

The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1987

Evaluation of lung epithelial permeability.

During the last few years a number of factors affecting the measurement of the rate of absorption of 99mTc-DTPA across the alveolar-capillary membrane have been identified. These have helped to provide insights into the significance of lung epithelial permeability (LEP) measurements and their potential limitations. Pulmonary absorption of 99mTc-DTPA has been studied in a variety of clinical conditions and the results are discussed.

Animals↗
PubMed1987

Lung epithelial permeability in sarcoidosis.

Sarcoidosis is a multisystem disease with a 90% prevalence of lung involvement. It is now accepted that lymphocytes play a major modulatory role in the pathogenesis of this disease. However it has become evident in recent years that a number of other inflammatory cells capable of releasing mediators which can cause lung injury are involved as well. Although sarcoidosis is a relatively benign disease, it is well recognized that about 25% of the patients, perhaps those with unresolved injury, experience a relentless course and ultimately die from the disease. The rate of absorption from the lung of 99m Tc-DTPA is influenced by the integrity of the pulmonary epithelium, which might be altered as a result of injury to the lung. Several groups have measured 99m Tc-DTPA absorption in patients with sarcoidosis and have shown that it was increased in more than 50% of the patients studied. This abnormality seemed to prevail in patients with more advanced disease and in those who did not show a benign course. Whether a persistent increase in the rate of absorption of 99m Tc-DTPA reflects current or unresolved lung injury is unclear. The possibility of this technique being useful in monitoring the course of sarcoidosis deserves attention and should be further explored.

Epithelium↗