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Biomedical subjects

R J Lemen

Publications and source records attributed to R J Lemen.

At least 19 recordsLinked to original sources
PubMed1993

Fractal and morphometric analysis of lung structures after canine adenovirus-induced bronchiolitis in beagle puppies.

Acute viral respiratory infections are commonly associated with alteration in lung growth and with chronic obstructive disease. However, it is difficult to quantify these changes in lung function. We determined that the recently described techniques of fractal analysis gave additional information about the changes in lung function after viral illness compared to standard morphometric techniques. Fractal and morphometric parameters change with lung growth after acute infection with canine adenovirus type 2 (CAV2, n = 5) or no infection (controls, n = 6) in beagle puppies. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation but no emphysema in the CAV2-infected puppies. Morphometric studies at approximately 236 days of age demonstrated accelerated lung growth in the CAV2-infected dogs as evidenced by significant increases in lung volume (VL) and internal surface area (ISA). Fractal analysis showed an increased fractal dimension (Df) of the alveolar perimeter length in the CAV2 group associated with increased growth that was similar to the percentage change in VL and ISA. These data suggest that a single infection with CAV2 in beagle puppies accelerates lung growth and increases the complexity (Df) of the alveolar structure.

Adenoviridae Infections↗
PubMed1992

Bronchoalveolar lavage fluid cytology reflects airway inflammation in beagle puppies with acute bronchiolitis.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.

Acute Disease↗
PubMed1992

Aerosolized lipopolysaccharide increases pulmonary clearance of 99mTc-DTPA in rabbits.

Bacterial endotoxins alter the permeability of endothelium, but little is known of their effect on epithelium. We exposed specific pathogen-free rabbits to aerosolized Pseudomonas aeruginosa LPS or saline and performed serial measurements of RL, Cdyn, BP, WBC count and differential, and platelet counts. Pulmonary 99mTc-DTPA half-life was measured 4, 6, or 8 h after exposure. The animals were sacrificed and BAL performed. Background and PMA-stimulated superoxide production was measured from individual AM using electrooptical determination of reduction of NBT. Lung tissue was processed for light microscopy and ratio of wet to dry weight. 99mTc-DTPA half-life was significantly shorter in LPS-exposed animals at 6 h (p < 0.05) and 8 h (p < 0.001). There were no differences in Cdyn, RL, BP, WBC, differential, platelet, or BAL cell count at any time between groups. No histologic changes or differences in lung wet to dry weight ratios were found. PMA-stimulated AM superoxide production was significantly increased (p < 0.01) in LPS-exposed animals. This effect was time dependent and could be duplicated in AM from control animals following a 4-h incubation with LPS, lavage fluid from LPS-exposed animals, or recombinant murine TNF. These results demonstrate that aerosolized Pseudomonas LPS increases pulmonary epithelial permeability and primes AM superoxide production.

Aerosols↗
PubMed1991

Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.

Adenoviridae Infections↗
PubMed1991

Canine parainfluenza type 2 and Bordetella bronchiseptica infection produces increased bronchoalveolar lavage thromboxane concentrations in beagle puppies.

Acute infections in beagle puppies with canine parainfluenza virus type 2 (CP12), and CP12 in combination with Bordetella bronchiseptica (Bb) produce bronchiolitis and increased airways responsiveness to aerosolized histamine during the acute infection. In order to determine whether these observations were associated with increased levels of eicosanoids, the stable metabolites of thromboxane A2 and prostacylin, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) respectively, and leukotriene B4 were measured in the bronchoalveolar lavage (BAL) fluid of 25 beagle puppies (age = 76 +/- 1 days, mean +/- SEM) 3-4 days after no infection (control, n = 6), inoculation with both CP12 and Bb (CP12-Bb, n = 11), inoculation with CP12 alone (CP12, n = 4), and inoculation with Bb alone (Bb, n = 4). In addition, plasma levels of TXB2 and 6-keto-PGF1 alpha were measured before and after infection in the CP12-Bb and control groups. The BAL concentration of thromboxane B2 was increased in the CP12-Bb group (520 +/- 120 pg/ml), but not in the CP12 (88 +/- 40 pg/ml), Bb (235 +/- 100 pg/ml), or control groups (120 +/- 60 pg/ml, p less than 0.01). There also was a borderline increase in BAL concentration of LTB4 in the CP12-Bb group. No differences were observed in the BAL concentration of 6-keto PGF1 alpha. Furthermore, neither TXB2 nor PGF1 alpha was elevated in the plasma of control or CP12-Bb puppies. These data suggest that increased thromboxane concentrations in BAL fluid are associated with histamine hyperresponsiveness during acute infection in the CP12-Bb group.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effect of smoke inhalation on immediate changes in lung chemical mediators.

We studied the effects of acute smoke exposure on lung and alveolar macrophage (AM) function in New Zealand white rabbits. Six rabbits were exposed to smoke (SE, N = 6) and a control group of rabbits (SS, N = 6) were exposed to sham smoke. The smoke exposure consisted of 60 tidal volume breaths of air and smoke which were aspirated by syringe from a sampling port of a smoke chamber. The smoke was generated by the combustion of 20 ml diesel fuel and 0.2 g polycarbonate plastic shavings. The smoke was administered in 8-9 min. The rabbits were then killed and the lungs were removed for lavage. Acute smoke exposure caused a significant (p = 0.037) increase in bronchoalveolar lavage fluid levels of leukotriene B4 in the SE rabbits; 643 (+/- 30, SEM) pg/ml compared to 539 (+/- 43, SEM) pg/ml for SS rabbits at 3-4 min post-exposure. Lung surfactant, measured as mumoles/kg phosphatidylcholine, was decreased (p = 0.039) in SE rabbits' bronchoalveolar lavage fluid, 1.07 (+/- 0.12, SEM) -vs- 1.45 (+/- 0.15, SEM) for SS. Furthermore, cultured SE alveolar macrophage superoxide secretion after stimulation with phorbol myristate acetate was significantly decreased versus SS alveolar macrophage superoxide values at 40 min in culture. We conclude that acute smoke exposure causes immediate increases in bronchoalveolar lavage fluid levels of LTB4, and decreases in alveolar macrophage superoxide production and lung surfactant. These changes in chemical mediators may contribute to the lung injury caused by the smoke insult.

Animals↗
PubMed1991

Effects of intravenous and aerosolized arachidonic acid on alveolar epithelial permeability in rabbits.

To determine whether arachidonic acid (AA) alters alveolar epithelial permeability, we studied the effect of both continuous intravenous and aerosolized AA on clearance of [99m]Tc-DTPA from lung to blood in rabbits. Although intravenous AA increased prostacyclin production and aerosolized AA decreased systemic blood pressure, neither continuous intravenous nor aerosolized AA augmented alveolar epithelial permeability.

Aerosols↗
PubMed1990

Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema.

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Aerosols↗
PubMed1990

Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Adenoviridae Infections↗
PubMed1990

Canine parainfluenza type 2 bronchiolitis increases histamine responsiveness in beagle puppies.

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1990

Acute canine adenovirus 2 infection increases histamine airway reactivity in beagle puppies.

Acute infection with canine adenovirus was studied in 23 specific pathogen-free outbred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsiveness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [RL(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p greater than 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsiveness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Localization of inflammation and virions in canine adenovirus type 2 bronchiolitis.

Beagle puppies develop bronchiolar inflammation and histamine hyperresponsiveness with canine adenovirus type 2 (CAV2) infections. We determined the distribution of bronchiolar lesions and correlated inflammation with virions and bronchoalveolar lavage fluid (BALF) cytology. Nineteen beagle puppies were inoculated with tissue culture fluid (control puppies, n = 8), or CAV2 (CAV2, n = 11). The puppies had clinical assessments and measurements of lung resistance (RL), and dynamic compliance (Cdyn) immediately before inoculation (Day zero) and 3 days later (Day 3). The puppies were killed on Day 3, the lungs were removed, and the right intermediate lobe was lavaged. The BALF was assessed for total and differential cell counts. Bronchiolar inflammation was quantitated by bronchiolar inflammation scores (BIS). CAV2 was localized by immunofluorescent antibody staining and electron microscopy. The control puppies remained healthy. The CAV2 puppies had positive cultures for CAV2, respiratory symptoms, and generalized necrotizing bronchiolitis. Alveolar inflammation was quantitatively less prominent than bronchiolar inflammation, and RL and Cdyn were unchanged. The BALF neutrophilia correlated with the BIS. CAV2 was present within bronchiolar epithelium, alveolar epithelial type 2 cells, neutrophils, and macrophages. CAV2 was not found in airways smooth muscles or nerves, nor in any noninflamed tissues of CAV2 puppies or in control animals. Our data suggest that acute CAV2 in beagle puppies produces an inflammation of most bronchioles. Intracellular CAV2 was found in bronchiolar epithelium, macrophages, neutrophils, and alveolar epithelial type 2 cells. Bronchiolar inflammation was reflected in BALF cytology. We conclude that bronchiolar inflammation as indicated by BIS and BALF cytology is related temporarily to histamine hyperresponsiveness in our beagle puppies.

Adenoviridae↗
PubMed1990

Bronchoconstriction induced by inhaled sodium metabisulfite in the guinea pig. Effect of capsaicin pretreatment and of neutral endopeptidase inhibition.

Sodium metabisulfite (MBS), a commonly used preservative, induces bronchoconstriction in asthmatics, probably through the release of sulfur dioxide (SO2). The mechanisms involved in MBS- and SO2-induced bronchoconstriction are not yet certain. We aerosolized MBS or acid control solution (pH, 2.7) to anesthetized, tracheostomized guinea pigs pretreated intravenously with propranolol (1 mg/kg). MBS was given at increasing doubling concentrations (0.01, 0.02, 0.04, and 0.08 M) every 5 min. Steep concentration-response curves were observed, and most animals responded at 0.02 or 0.04 M. Tachyphylaxis was seen at high concentrations and during a subsequent MBS challenge 15 min later. For pharmacologic studies, we stopped the challenge when lung resistance (RL) had increased by at least 350%; a second challenge was found to be reproducible. MBS response was measured as the concentration needed to increase RL by 350% (PC350). Atropine (1 mg/kg given intravenously) did not affect PC350 or the peak RL response. Inhibition of neutral endopeptidase by inhaled phosphoramidon (7.5 nmol) administered before the repeated challenge did not alter PC350 value to MBS or peak RL responses (phosphoramidon, 201 +/- 49% of first peak; vehicle, 164 +/- 35%). In addition, the increase in RL was not prolonged in the phosphoramidon-treated group. Animals treated subcutaneously with capsaicin (50 mg/kg) 1 wk before the experiment, so as to deplete neuropeptides from airway sensory nerves, had PC350 values similar to those of the control animals. Our data demonstrate that inhaled MBS causes bronchoconstriction in guinea pigs by mechanisms that are due neither to a cholinergic reflex nor to the release of tachykinins from airway sensory nerves.

Aerosols↗
PubMed1989

Assessment of lactose absorption by measurement of urinary galactose.

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.

Adolescent↗