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Biomedical subjects

A Anzueto

Publications and source records attributed to A Anzueto.

63 records · Page 4Linked to original sources

The technique of bronchoalveolar lavage. A guide to sampling the terminal airways and alveolar space.

Bronchoalveolar lavage (BAL) provides a means of recovering cells and biochemical substances directly from the alveoli in patients with numerous pulmonary diseases. It is also useful in diagnosing opportunistic infections in immunocompromised patients. Upper airway contamination of BAL specimens is the chief liability. In diffuse lung disease, the bronchoscope is usually positioned in the middle lobe; when focal lung disease is present, the bronchoscope is placed in the area of greatest roentgenographic involvement. Sterile saline is instilled and recovered for analysis. Most side effects are related to endoscopic technique, location and extent of lavaged lung area, and the volume and temperature of instilled fluid.

Bronchoalveolar Lavage Fluid↗

Acute inhalation toxicity of soman and sarin in baboons.

Adult baboons (Papio sp.; 8-12 kg) were anesthesized with sodium pentobarbital (20 mg/kg iv). The animals were instrumented for measurement of mean blood pressure (MBP), pulmonary artery pressure (PAP), ECG, arterial and mixed venous blood gases, lung volumes, lung pressures, and efferent phrenic nerve activity. Bronchoalveolar lavage (BAL) was performed. Studies were done prior to exposure, at intervals during the first 4 hr postexposure, and at 4 and 28 days after exposure. Control animals received a sham exposure to 2-propanol (N = 5). Soman (pinacolyl methylphosphonofluoridate) at 13.14 micrograms/kg (2 X LD50) was vaporized into the upper airway in a second group of animals (N = 5), and sarin (isopropyl methylphosphonofluoride) 30 micrograms/kg (2 X LD50) was vaporized into a third group of animals (N = 4). Controls showed no change in any parameter either immediately after diluent exposure or during the monitoring period. Soman and sarin produced a decline in MBP and bradyarrhythmias that were reversed with atropine. Apnea occurred in all soman- and sarin-exposed animals within 5 min postexposure, and was associated with absence of phrenic nerve signal. Ventilation was mechanically supported until the animal could maintain normal arterial blood gases during spontaneous breathing. BAL studies revealed an increase in total white cell population and neutrophils at 4 hr in all three groups. There were signs of impaired hemodynamics and persistent lung injury for 4 days that resolved by 28 days after exposure. In conclusion, inhalation of soman and sarin in the baboon is associated with cardiac arrhythmias, development of apnea, and a significant decrease in MBP. Inhalation exposure also resulted in a persistent influx of neutrophils and hypoxemia.

Administration, Inhalation↗

Effects of hydrogen chloride on respiratory response and pulmonary function of the baboon.

The effects of hydrogen chloride (HCI) inhalation on respiratory response during exposure and on pulmonary function during the 3 mo following exposure were studied in the baboon. Each of 4 groups of three anesthetized animals was exposed in a head-only mode for 15 min to air or one of three HCI concentrations (500, 5000, or 10,000 ppm). The acute respiratory response consisted of a concentration-related increase in frequency and minute volume, with a marked decrease in blood PaO2 at the two highest concentrations. The exposures did not cause significant alterations in any of the pulmonary function parameters measured at 3 d and 3 mo postexposure. Thus, nonhuman primates were able to survive short exposures to high concentrations of HCI without any significant effects on pulmonary function during the 3 mo after exposure. Furthermore, comparison of the response of primates and rodents suggests that the human is much less sensitive to the effects of HCI than the mouse.

Animals↗

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↗

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↗

Efficacy of ciprofloxacin and clarithromycin in acute bacterial exacerbations of complicated chronic bronchitis: interim analysis. Bronchitis Study Group.

In a multicenter, community-based study involving more than 300 primary care physicians in the United States, the efficacy and safety of ciprofloxacin and clarithromycin were compared in the treatment of patients with complicated or severe acute bacterial exacerbations of chronic bronchitis (i.e., those who had failed previous antibiotic treatment within the prior 2 to 4 weeks; those with susceptibility data suggestive of a resistant pathogen; those having three or more acute exacerbations of chronic bronchitis [AECB] within the past year; and those having three or more comorbid conditions). Patients were randomized to either ciprofloxacin (CIP) 750 mg BID or clarithromycin (CLR) 500 mg BID, both administered for 10 days; all patients were treated on an outpatient basis. Clinical response at the end of therapy was the primary efficacy variable. An interim analysis was performed on the results from 743 patients (369 CIP, 374 CLR) with clinical and bacteriologic evidence of a bronchopulmonary infection who had completed an ongoing study as of the end of May 1997. Three hundred nine pathogens were isolated before therapy, including Haemophilus spp (75 isolates), Moraxella catarrhalis (67 isolates), Staphylococcus aureus (55 isolates), and Streptococcus pneumoniae (23 isolates). Seven hundred eighteen patients (97%) were included in the efficacy-valid population. Clinical success at the end of therapy was observed in 90% (272 of 302) and 88% (274 of 313) of efficacy-valid patients treated with CIP and CLR, respectively (95% confidence interval [CI] = -2.4 to 7.6). Corresponding rates for the intent-to-treat population were also 90% (283 of 314) and 88% (281 of 321), respectively (95% CI = -2.3 to 7.5). The bacteriologic response for efficacy-valid patients at the end of therapy was 98% (119 of 122) for CIP-treated and 93% (103 of 111) for CLR-treated patients (95% CI = -0.8 to 10.2). The eradication rates for the three most commonly isolated gram-negative pathogens were 100% for CIP-treated and 95% for CLR-treated patients and 96% each for the two most commonly isolated gram-positive organisms. Superinfections due to respiratory tract pathogens were more common in the CLR group (10 organisms) than in the CIP group (4 organisms). Seventy-four (20%) CIP-treated and 62 (17%) CLR-treated patients reported 118 and 103 respective study-emergent adverse events. Headache, abdominal pain, diarrhea, nausea, and vomiting in CIP-treated patients and diarrhea, nausea, vomiting, and taste perversion in CLR-treated patients were the most commonly reported adverse events. Treatment of patients with complicated or severe AECB with CIP 750 mg BID was associated with rates of clinical success and bacteriologic eradication similar to those with CLR.

Anti-Bacterial Agents↗

Etiology, susceptibility, and treatment of acute bacterial exacerbations of complicated chronic bronchitis in the primary care setting: ciprofloxacin 750 mg b.i.d. versus clarithromycin 500 mg b.i.d. Bronchitis Study Group.

Although controversial, antimicrobial therapy for the treatment of acute exacerbations of chronic bronchitis (AECB) appears beneficial in patients with a history of repeated infections, those who have comorbid illnesses, and those with marked airway obstruction. In a community-based, open, randomized trial, the efficacy and safety of ciprofloxacin (CIP) 750 mg and clarithromycin (CLA) 500 mg, each given twice daily for 10 days, were compared in 2180 patients with AECB (1083 CIP, 1097 CLA). Patients were >40 years of age and had complicated/severe AECB episodes defined as at least three episodes within the past year, at least three comorbid conditions, previous failed antibiotic treatment for AECB within the previous 2 to 4 weeks, or community susceptibility data indicating a high number of resistant pathogens. Significant bacterial isolates (>10(5) colony-forming units per milliliter) from homogenized sputa were identified. Susceptibility to a range of antimicrobials was determined by the microbroth dilution technique. The majority of patients were white (83%) and were current or previous smokers (81%). Mean patient age was 62 years. A history of at least three AECB episodes in the previous year was reported by 54% of CIP-treated patients and 53% of CLA-treated patients. Of 777 primary isolates positively identified and cultured from 673 patients, the bacterial pathogens isolated and their incidence included Haemophilus species, 28%; Moraxella catarrhalis, 18%; Enterobacteriaceae, 18%; Staphylococcus aureus, 17%; Streptococcus pneumoniae, 7%; and Pseudomonas aeruginosa, 4%. Beta-lactamase production was found in 38% of Haemophilus influenzae, 10% of Haemophilus parainfluenzae, and 85% of M catarrhalis isolates. Thirty-four percent of S pneumoniae isolates were resistant to penicillin (minimum inhibitory concentration > or =0.12 mg/L). Among the 673 patients who were valid for clinical assessment and had a pretherapy pathogen isolated, clinical success and overall bacteriologic eradication rates at the end of therapy were 93% and 98% for CIP versus 90% and 96% for CLA. The differences between CIP and CLA did not reach statistical significance. Superinfections were reported significantly more frequently in CLA-treated (3%) versus CIP-treated patients (1%). Eradication rates for specific organisms for CIP and CLA, respectively, were Haemophilus species, 99% and 93%; M catarrhalis, 99% and 100%; S pneumoniae, 91% and 92%; and Enterobacteriaceae, 100% and 95%. Drug-related adverse events occurred in 12% of CIP-treated patients and 10% of CLA-treated patients. CIP 750 mg b.i.d. had a higher (but not statistically significant) clinical and bacteriologic cure rate than CLA 500 mg b.i.d. in the treatment of patients with bacteriologically proven complicated/severe AECB. The causative bacterial pathogens of AECB appear to be evolving, with a predominance of gram-negative and other resistant organisms observed. Thus antibiotic therapy for at-risk patients with AECB should include agents that have activity against gram-negative pathogens.

Acute Disease↗

Exercise performance after lung transplantation.

Heart-lung, double lung, and single lung transplantation have been shown to be effective in the treatment of patients with advanced cardiopulmonary disorders. An overlap in indications occurs for the different procedures, and in many situations the factors that are important in selecting the best operation for a given patient have not been clearly elucidated. To determine whether the anticipated exercise capacity should be an important consideration in the selection of the optimal procedure for a given patient, we compared exercise performance in patients who had undergone the different lung transplantation procedures in the preceding year and were otherwise well. Eleven heart-lung, six double lung, and 16 single lung recipients and 28 control subjects underwent maximal symptom-limited incremental exercise tests using a cycle ergometer. At peak exercise, transplant recipients reached maximum oxygen uptakes in the range of 40% to 60% of predicted values; no significant differences existed between the means of the different transplant groups. Ventilatory factors did not appear to limit exercise in any group. The exercise responses in the transplant subjects were characterized by reduced aerobic capacity and diminished oxygen pulse, factors indicating abnormal cardiovascular performance. Our data indicate that moderate levels of exercise can be anticipated early after heart-lung, double lung, and single lung transplantation. In the absence of substantial differences in exercise capacity, other considerations would appear to be more important in guiding the selection of the optimal lung replacement procedure for an individual patient.

Adult↗