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Biomedical subjects

M Dolovich

Publications and source records attributed to M Dolovich.

At least 19 recordsLinked to original sources
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↗
PubMed1986

Aerosol therapy of asthma: principles and applications.

Aerosols are the mainstay of therapy of reversible airflow obstruction. Currently available aerosols include bronchodilators such as beta-adrenoceptor agonists and anticholinergic agents which may be used alone or together with prophylactic, anti-inflammatory medications such as sodium cromoglycate and steroids. These agents are characterized by primarily topical activity and thus result in minimal systemic effects. By combining these medications in optimum doses, most patients can be readily managed. In patients with severe airway hyperreactivity, aerosols may need to be combined with oral sustained-release theophylline compounds and/or systemic steroids, the latter being used in minimum doses and if possible on alternate days to minimize adrenal suppression and steroid-related systemic complications. In recent years, an improved understanding of aerosol physics, pharmacology and airway physiology has led to greatly improved aerosol therapy with increasing emphasis on metered dose inhalers as the delivery system of choice while nebulizers are used less frequently except in hospital and pediatric applications. The use of intermittent positive-pressure devices for aerosol delivery has decreased considerably as physicians recognize that simpler delivery methods work equally well at much lower cost. While aerosol therapy techniques are now well worked out, research is continuing on methods of improving the efficiency of aerosol delivery and in the development of newer pharmacological agents such as longer-acting adrenoceptor agonists, calcium channel blockers, antagonists of mediators derived from arachidonic acid as well as higher dose aerosolized steroids.

Aerosols↗
PubMed1986

Optimal use of MDIs.

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Administration, Intranasal↗
PubMed1985

Ventilation scanning with technetium labeled aerosols. DTPA or sulfur colloid?

We have compared the distribution in the lungs of submicronic aerosols of either Tc-99m sulfur colloid or Tc-99m DTPA immediately after inhalation with the distribution 20 minutes later in 83 patients. Thirty-two of the 83 patients were active smokers. Of the 28 smokers who received Tc-99m DTPA aerosol, the total lung count fell by a mean of 27 +/- 14% between the 0 and 20 minute image. Eleven of these patients also had a major change in distribution of isotope during this time. In the nonsmoking patients total lung counts from Tc-99m DTPA fell by only 16 +/- 8% and none had a major change in distribution pattern. None of the smoking or non-smoking patients who received Tc-99m sulfur colloid had a significant change in count rate or distribution pattern over 20 minutes. The effects on the ventilation images of these rapid changes in count rate and distribution pattern after Tc-99m DTPA aerosol can be minimized by completing the ventilation study as quickly as possible after inhaling Tc-99m DTPA or by using a nondiffusible agent such as Tc-99m sulfur colloid.

Aerosols↗
PubMed1975

Sulfur dioxide and tracheobronchial clearance in man.

Tracheobronchial clearance was measured in nine healthy, nonsmoking adults. Technetium Tc 99m albumin aerosol (mass median diameter, 3 mu; geometric standard deviation, 1.6) was inhaled as a bolus under controlled conditions to achieve reproducible deposition in large airways. Each subject was studied in three seperate three-hour experiments: twice under control conditions and once exposed to 5 ppm sulfur dioxide (pollutant exposure after aerosol inhalation). Lung retention of activity was measured using a gamma camera interfaced to a data storage and retrieval system. The study showed that (1) Both deposition and clearance were highly reproducible in individuals in repeat control studies. (2) Acute exposure to 5 ppm sulfur dioxide had no significant effect (P greater than .05) on mucocillary clearance in resting healthy subjects, except perhaps for a small transient change (P=.05) after one hour. (3) Pulmonary function tests showed a decrease in maximal midexpiratory flow (P less than .01) but no other significant changes.

Adult↗