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Biomedical subjects

W G Johanson

Publications and source records attributed to W G Johanson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

Acute Disease↗
PubMed1989

O2- and pneumonia-induced lung injury. I. Pathological and morphometric studies.

The physiological, morphological, and morphometric findings of several lung injury models in baboons have been compared in the following six study groups: 1) initial injury with oleic acid followed by ventilation with 100% O2, 2) ventilation with 100% O2, 3) ventilation with 80% O2, 4) ventilation with 80% O2 followed by inoculation of Pseudomonas aeruginosa, 5) ventilation with 40% O2, and 6) normal nonventilated room-air-breathing animals. The animals were maintained for 11 days in an intensive care unit. Light microscopically, animals ventilated with 40 and 80% O2 showed mild lung injury, consisting mostly of an increase in alveolar macrophages in peribronchiolar sites and focal alveolar wall widening. The 100% O2-oleic acid, 100% O2, and 80% O2-Pseudomonas-treated baboons showed mixed exudative-reparative diffuse alveolar lesions. Ultrastructurally, the type II cells of these three groups had significantly altered morphology with aberrations of lamellar body configurations. Morphometric findings showed increases in type II and interstitial cells and decreases in type I and endothelial cells in these injured animals. A striking finding was that the physiological, morphological, and morphometric changes of an 80% O2-Pseudomonas insult was as injurious as 100% O2. This synergistic effect of hyperoxia and infection very likely reflects the most frequent evolution of adult respiratory distress syndrome in patients in intensive care units.

Animals↗
PubMed1989

Clinical determinants of abnormalities in pulmonary functions in survivors of the adult respiratory distress syndrome.

Pulmonary function tests (PFTs) were performed in 39 survivors of the adult respiratory distress syndrome (ARDS) in whom clinical data had been prospectively collected during the acute episode. PFTs stabilized within 6 months of the episode and had returned to normal in most survivors. Persistent abnormalities were found after 6 months in diffusing capacity (14 of 23 patients, 61%), vital capacity (10 of 23 patients, 43%), and total lung capacity (five of 24 patients, 21%). To clarify the mechanisms underlying these persistent abnormalities, we attempted to correlate long-term PFT outcomes with estimates of the severity of initial lung injury as assessed from clinical data and with other features of the patient's course. The severity of lung function impairment during the first 3 days of ARDS was not related to long-term PFT values. However, a lower DLCO was related to a higher AaDO2, higher pulmonary artery pressure, and worse radiographic appearance on Days 4 through 7 and to the occurrence of sepsis. A lower FVC was related to higher pulmonary vascular resistance in Days 4 through 7 of ARDS. Long-term values for FVC and TLC were directly related to increasing levels of PEEP applied from Days 4 through 7 of ARDS in patients with peak airway pressures less than 50 cm H2O. Long-term abnormalities of pulmonary function of survivors of ARDS were not related to initial lung impairment but were directly related to persistence of impaired lung function during the acute episode. Recovery of lung function may also have been directly related to therapeutic modalities such as PEEP and impaired by the occurrence of sepsis.

Adolescent↗
PubMed1988

Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation.

Cultures of tracheal secretions, bronchoalveolar lavage (BAL), protected specimen brushes (PSB), and direct lung aspirates were compared with cultures of lung homogenates and histologic findings in 35 baboons after 7 to 10 days of intubation and mechanical ventilation. Six animals received no antibiotics, while the remainder were treated with a variety of prophylactic regimens of intravenous and topical agents. Bacterial contamination at each culture site was expressed as a "bacterial index" (BI), obtained as the sum of the logarithmic concentrations of individual species. In the absence of antibiotics, pneumonias occurred in all animals and were polymicrobial; 56% of organisms in lung tissue were members of the normal upper respiratory tract flora, while 44% were gram-negative bacilli with a mean total bacterial index of 13.94/g. Lobar tissue BI values greater than 6.0/g were found in 77% of lobes containing pneumonias judged by histologic criteria to be moderate or severe in extent, whereas only 7% of lobes with lesser inflammatory changes had similar BI values. The BI values of BAL were linearly related to tissue values, whether the BAL was performed of the same lobe cultured or a different lobe. BAL recovered 74% of all species present in lung tissue compared to 41% by PSB and 56% for needle aspirates. False positive specimens were found with similar frequency with these 3 procedures. Tracheal aspirates revealed 78% of organisms found in lung tissue, but 14 of 35 (40%) of species isolated were not present in lung tissue. BAL provides the best reflection of the lung's bacterial burden, both quantitatively and qualitatively, in the setting of prolonged intubation and ventilation.

Animals↗
PubMed1988

Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents.

The efficacy of antimicrobial agents applied topically in the oropharynx and trachea with and without intravenous antibiotics in preventing bacterial pneumonias during prolonged (7 to 10 days) mechanical ventilation was studied in 35 baboons, 30 of which had acute lung injury induced by either oleic acid or hyperoxia. In 12 animals receiving no antibiotics, only topical application of polymyxin B (PB), or only intravenous penicillin and gentamicin (IV PCN/GM), moderate or severe pneumonia was found in 81% of lobes examined at necropsy; no lobes were sterile. Pneumonias were polymicrobial in the absence of antibiotics, due to PCN-sensitive organisms in the topical PB group, and due to gram-negative bacilli in the IV PCN/GM group. Combinations of topical PB or GM or both plus IV PCN were highly efficacious in preventing pneumonia in 23 animals as only 15% of the lobes contained moderate to severe pneumonia and 52% of lobes were sterile. In these groups, histologically evident pneumonias were associated with low concentrations of bacteria in lung tissue, principally gram-negative bacilli resistant to the topical agent being used. Resistance to PB appeared to be solely due to selection of intrinsically resistant species, whereas resistance to GM may have developed through additional mechanisms as well. Although this approach to pneumonia prevention is clearly efficacious in this animal model, clinical studies are needed to define the frequency and significance of microbial resistance in human subjects.

Administration, Topical↗
PubMed1987

Nutritional changes in nonhuman primates during mechanical ventilation.

To characterize the baseline nutritional changes occurring in healthy baboons receiving an acute lung injury, we prospectively evaluated serial nutritional changes in eight adult baboons that received oleic acid (0.08 mL/kg) and then required mechanical ventilation for a period of 8 d. The animals were given hypocaloric feeding. Nutritional assessment included the measurement of changes in muscle mass and changes in visceral protein concentration and plasma lipids. Both serum protein and albumin concentrations decreased for 3 d after mechanical ventilation began but then remained stable. The animals exhibited a marked increase in bronchoalveolar lavage fluid (BALF) protein concentrations after receiving oleic acid. We conclude that previously healthy baboons receiving only dextrose infusion during mechanical ventilation have marked decreases in serum albumin occurring after the lung injury. Decreases in albumin occur very early and may represent pooling of albumin in the lung after the oleic acid injury.

Animals↗
PubMed1987

One hundred percent oxygen lung injury in adult baboons.

Healthy adult baboons exposed to 100% oxygen for 5 to 7 days maintained on continuous mechanical ventilation develop severe bilateral noncardiogenic pulmonary edema that resembles in many aspects the human adult respiratory distress syndrome (ARDS). In the present study, we evaluated the effects of hyperoxia for 5 to 6 days in 8 baboons to compare changes in abnormalities in bronchoalveolar lavage fluid (BALF) biochemical markers, hemodynamic measurements, and pulmonary function tests in order to find early predictors of lung injury. All animals had bilateral alveolar infiltrates, severe hypoxemia, and progressive deterioration of pulmonary function tests. Diffuse alveolar damage and mild-moderate pneumonias were found and were associated with low-grade bacterial infection. Total lung capacity, diffusing capacity for carbon monoxide, pulmonary static compliance, and oxygenation were significantly impaired after Day 5; BALF proteins, elastase, and total polymorphonuclear leukocytes increased significantly at least 24 h before (Day 4) any abnormalities in chest radiographs, pulmonary function tests, and hemodynamic measurements were detected. We conclude that exposure to 100% oxygen in this model causes marked gas exchange, hemodynamic, biochemical, cytologic, radiographic, and pathologic changes similar to those noted in patients with ARDS. Bronchoalveolar lavage abnormalities precede hemodynamic and gas exchange abnormalities.

Animals↗
PubMed1987

Fluid balance and the adult respiratory distress syndrome.

This study examined the effect of fluid balance on survival in ARDS. Of the 213 patients entered into a prospective data collection study, we evaluated 113 patients who met strict criteria for ARDS. Multiple variables were analyzed for as long as 14 days after intubation including cardiac output, pulmonary capillary wedge pressure, mean blood pressure, intake minus output (I-O), cumulative intake minus output (cum I-O), and change in weight (delta wt). We found significant differences in cum I-O and delta wt between survivors and nonsurvivors on almost every day. Survivors lost weight and had a significantly lower cum I-O compared with nonsurvivors. Logistic regression was used to determine if delta wt and cum I-O could predict survival. Patients who lost 3 kg or more weight had a much higher survival than did those who gained 3 kg or more weight (67 and 0%, respectively, on Day 14). Similar results were obtained using comparably low and high values for cum I-O. The logistic regression equations demonstrated that weight loss and low cumulative I-O correlated with improved survival. Although cause and effect relationships are difficult to determine from these types of analyses, they can be used to formulate prospective studies and predict survival in patients.

Body Weight↗
PubMed1986

Morphologic and microbiologic features of Pseudomonas aeruginosa pneumonia in normal hamsters.

A model of pneumonia due to Pseudomonas aeruginosa was produced in hamsters by an intratracheal bolus instillation of microorganisms. Sequential lung changes from 4 hr through 11 days were studied by morphologic and microbiologic methods. Hamsters inoculated with greater than 10(6) pseudomonads survived but consistently had histologic evidence of mild bronchopneumonia 24 hr postinoculation, whereas a severe bronchopneumonia and a 100% mortality were elicited with a 10(8) inoculum of organisms in 0.5 ml phosphate-buffered saline (PBS). An inoculum of 10(7) pseudomonads/0.5 ml PBS was then used to define the changes in the bacterial population in Pseudomonas pneumonia and to obtain serial histopathologic observations. Quantitative lung cultures obtained within 1 hr postinoculation demonstrated a mean of 10(6) colony forming units per lung, and none of the hamsters were bacteremic. However, by 24 hr bacterial counts had increased and all animals were bacteremic. Bacterial proliferation continued through 48 hr; however, the number of bacteremic animals had decreased. By 72 hr, bacterial counts had decreased with total Pseudomonas clearance noted by 120 hr. A striking polymorphonuclear leukocyte-rich alveolar exudate was present by 12 hr. Pseudomonas "vasculitis" was evident by 24 hr. The evolution of this vascular lesion correlated with the bacteremic state of the hamsters. By 11 days, resolution of the pneumonic process was seen. The macroscopic and microscopic features of this hamster model of Pseudomonas pneumonia are very similar to those reported in infected patients.

Animals↗
PubMed1986

Pathophysiology of soman intoxication in primates.

Adult baboons were monitored during intravenous infusion of Soman (1,2,2-trimethylpropyl ester, phosphonofluoridate). Three groups of animals were studied. Two groups were anesthetized with sodium pentobarbital (initial dose, 20 mg/kg), instrumented for measurement of systemic blood pressure (BP), pulmonary artery pressure, cardiac output (CO), ECG, ventilatory flow, translaryngeal pressure (PTL), transdiaphragmatic pressure (Pdi), transpulmonary pressure (PTP), diaphragm EMG, and efferent phrenic nerve traffic (Eph). One group received no Soman and served as controls. In the other group, Soman was infused over 10 min at doses of 13.1, 8.21, 4.92, or 3.3 micrograms/kg. The onset of intoxication occurred within 7-8 min (before the end of the 10-min infusion), manifested by muscular fasciculations, stridorous breathing, copious secretions, and atrioventricular arrhythmias. Mean BP decreased to 30 mm Hg by the combination of decreased CO and decreased vascular resistance. There was a dose-related response in the onset and duration of these effects. Apnea occurred in most animals and coincided with cessation of the Eph signal. Stimulation of the diaphragm via the phrenic nerve following apnea yielded Pdi values unchanged from baseline, indicating an intact neuromuscular apparatus. All animals required ventilatory support. Some surviving animals exhibited severe behavior changes. The third group of animals was studied without anesthesia. Instrumentation was performed 3 days before using a tether system for the measurement of BP, CO, and ECG, and an arterial line for blood withdrawal. Soman was infused over 10 min at a dose of 13.1 micrograms/kg. The onset of intoxication occurred within 2-3 min, manifested by hyperactivity, severe muscle fasciculations which simulated grand-mal convulsions, stridorous respiratory sounds, copious secretions, and cardiac arrhythmias. Apnea and severe lactic acid acidosis developed in all animals and all required ventilatory assistance. None recovered spontaneous ventilation at the end of 4 hr.

Animals↗
PubMed1986

Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome.

Bacterial infection in the adult respiratory distress syndrome (ARDS) is associated with the occurrence of multiple organ failures and death. We studied 108 infections in 129 patients with ARDS and evaluated the organisms responsible, the body sites involved, and the outcomes of therapy. Gram-negative bacilli represented 57% of the microbial pathogens and gram-positive cocci 36%. Only 7% of infections were caused by other organisms (fungi, viruses, Pneumocystis, Legionella). Gram-negative organisms were more common in the lung, abdomen, and pleura. Bacteremia was more common in abdominal infections (11 of 17, 67%) than in infections at other sites (18 of 65, 28%), (p less than 0.01); ;9 patients were bacteremic from clinically undetected sites. Ten of 17 (59%) patients with abdominal infections survived compared with 7 of 56 (13%) patients with lung infections (p less than 0.001). A retrospective review of in vitro organism susceptibility and the antibiotics administered revealed that the patients who received adequate antibiotic therapy did not have a higher survival rate (20 of 69, 29%) than those who received inadequate antibiotic therapy (3 of 13, 23%). These data suggest that further investigation of infections in patients with ARDS is required and that emphasis should be placed on pathogenesis, prevention, and host responses.

Adult↗
PubMed1986

Bacterial infection and acute lung injury in hamsters.

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

Animals↗
PubMed1986

The effect of almitrine bismesylate on hypoxemia in chronic obstructive pulmonary disease.

Almitrine bismesylate was studied for its effects on hypoxemia in 67 patients with chronic obstructive lung disease in a placebo-controlled, double-blind study. Arterial Po2 rose by 11.2 mm Hg (p less than 0.05) in 21 patients receiving 100 mg twice daily and by 6.0 mm Hg (p less than 0.05) in 22 patients receiving 50 mg twice daily. Arterial Pco2 decreased by 3.8 mm Hg (p less than 0.05) in the group receiving 100 mg twice daily but was unchanged in patients receiving 50 mg twice daily. Lung function was unaltered except for a slight increase in forced mid-expiratory flow in both dosage groups (p less than 0.05). The major side effect was the unexplained worsening of dyspnea, which occurred in 4 patients (19%) receiving 100 mg twice daily, 2 (9%) receiving 50 mg twice daily group, and 1 (4%) receiving placebo. Almitrine bismesylate improves arterial blood gas values in patients with chronic obstructive lung disease, apparently by reducing intrapulmonary ventilation-perfusion mismatching, and appears to be useful in the long-term management of these patients.

Adult↗