Prediction of outcome from critical illness. A comparison of clinical judgment with a prediction rule.

Quantitative methods to enhance clinical judgment would be of tremendous benefit to physicians caring for the critically ill. The ability of physicians to predict outcome is a logical standard on which to base the prospective evaluation of a prediction rule intended for this clinical use. The APACHE (acute physiology and chronic health evaluation)-II score was compared with critical care physicians' prediction of outcome for a group of patients in a medical intensive care unit. Physicians were significantly better in predicting outcome in the critically ill. However, the APACHE-II score was still a good predictor of outcome in the intensive care unit and, according to analysis using Bayes' theorem, might still be a useful test to support physicians' judgment, especially in patients with a predicted mortality risk of less than 30%.

Neutrophils in reexpansion pulmonary edema.

This study investigated the possible contribution of neutrophils to development of reexpansion pulmonary edema (RPE) in rabbits. Rabbits' right lungs were collapsed for 7 days and then reexpanded with negative intrathoracic pressure for 2 h before study, a model that creates unilateral edema in the reexpanded lungs but not in contralateral left lungs. Two hours after lung reexpansion, significant increases in lavage albumin concentration (17-fold), percent neutrophils (14-fold), and total number of neutrophils (7-fold) recovered occurred in the reexpanded lung but not in the left. After 2 h of reexpansion increased leukotriene B4 was detected in lavage supernatant from right lungs (335 +/- 33 pg/ml) compared with the left (110 +/- 12 pg/mg, P less than 0.01), and right lung lavage acid phosphatase activity similarly increased (6.67 +/- 0.35 U/l) compared with left (4.73 +/- 0.60 U/l, P less than 0.05). Neutropenia induced by nitrogen mustard (17 +/- 14 greater than neutrophils/microliters) did not prevent RPE, because reexpanded lungs from six neutropenic rabbits were edematous (wet-to-dry lung weight ratio 6.34 +/- 0.43) compared with their contralateral lungs (4.97 +/- 0.04, P less than 0.01). An elevated albumin concentration in reexpanded lung lavage from neutropenic rabbits (8-fold) confirmed an increase in permeability. Neutrophil depletion before reexpansion did not prevent unilateral edema, although neutrophils were absent from lung sections and alveolar lavage fluid from neutropenic rabbits.

Superoxide dismutase and cytochrome oxidase in collapsed lungs: possible role in reexpansion edema.

This study examined the effects of lung collapse, a condition that causes relative hypoxia in lung tissues, on superoxide dismutase (SOD), cytochrome oxidase (cyt ox), and pyruvate kinase (py ki) activities in rabbits. Cyanide-insensitive respiration measurements were done in collapsed and contralateral lungs, as an index of intracellular free radical production. Rabbits' right lungs were collapsed for 7 days after which the animals were killed. We found that control rabbit lungs contained approximately 25 SOD units/mg DNA measured with 10(-5) M KCN (total SOD) and approximately 11 SOD units/mg DNA measured with 10(-3) M KCN (mitochondrial or MnSOD). Right lung collapse caused a 25% decrease in mitochondrial SOD activity after 7 days (P less than 0.05), whereas no significant changes occurred in right or left lungs' total SOD activity. In control rabbits cyt ox activity averaged approximately 0.009 mumol ferrocytochrome c.min-1.mg DNA-1. Right lung collapse caused a greater than 40% decrease in cyt ox activity after 7 days of collapse (P less than 0.05), whereas cyt ox activity in contralateral left lungs did not change. Pyruvate kinase activity, a marker for anaerobic glycolysis resulting from tissue hypoxia, increased 49% in collapsed right lungs (P less than 0.01). Cyanide-insensitive respiration was 83% higher in 7 day-collapsed lungs (2.28 +/- 0.66 microliters O2.min-1.g-1) compared with contralateral lungs (1.24 +/- 0.34, P less than 0.05), indicating increased O2-. and H2O2 production in this tissue after homogenization at normoxic PO2 (approximately 150 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)

Polyethylene glycol-conjugated superoxide dismutase in unilateral lung injury due to re-expansion (re-oxygenation).

This study evaluated the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) in re-expansion pulmonary edema, a unilateral lung injury due in part to re-oxygenation of hypoxic, collapsed lung tissue. The hypothesis underlying this investigation was that extracellular superoxide contributed to the lung inflammation in this model, and that PEG-SOD could be used to test for extra-cellular superoxide involvement. The right lungs of 2-3 kg rabbits were collapsed for seven days by intrapleural air injections. Immediately prior to lung re-expansion, rabbits received intravenously 10,000 units/kg PEG-SOD (n = 6) or an equal volume of H2O2-inactivated PEG-SOD (n = 6). Inactive PEG-SOD pretreated rabbits had a marked increase in re-expanded lungs' lavage albumin concentration (right 1653 +/- 230 micrograms/ml, left 404 +/- 160 micrograms/ml; p less than .01). Active PEG-SOD did not inhibit this permeability increase (right 1744 +/- 242 micrograms/ml, left 180 +/- 53 micrograms/ml; p less than .01). However, active PEG-SOD significantly decreased both total number and percent neutrophils in alveolar lavage (right 24.8 +/- 9.4%, left 4.2 +/- 0.8%; p less than .05) compared to inactive PEG-SOD pretreated rabbits (right 52.8 +/- 5.8%, left 8.7 +/- 2.4%; p less than .01). Pretreatment with active PEG-SOD significantly increased lung tissue (20.4 +/- 1.5 units/mg DNA), blood (400 +/- 8 units/ml) and right lung lavage (30.0 +/- 3.1 units/ml) SOD activities compared to those from inactive PEG-SOD pretreated rabbits (respectively: 16.0 +/- 1.0 units/mg DNA, 335 +/- 14 units/ml and 10.8 +/- 1.3 units/ml; p less than .05 for each comparison).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized prospective trial of hyperbaric oxygen in a referral burn center population.

Various studies of the effect of hyperbaric oxygen (HBO) in a wide variety of disease entities have been carried out. In the treatment of burns, animal and human studies have yielded somewhat contradictory results. Controlled studies in humans are limited. A randomized study on the effect of HBO was conducted involving 125 burn patients admitted within 24 hours of injury who were matched by age, burn size, and presence or absence of inhalation injury. Patients in the treatment arm received oxygen at two atmospheres of pressure for 90 minutes twice a day for a minimum of 10 treatments and a maximum of one treatment per total body surface per cent burn. The control group was treated in a similar fashion, except for the absence of HBO. There were no statistically significant differences between the two groups for the outcome measures of mortality, number of operations, and length of stay for the survivors. In this large clinical trial, we were unable to demonstrate any significant benefit to burn patients from the use of HBO.

Interstitial macrophage subpopulations: responsiveness to chemotactic stimuli.

Recent data suggest that interstitial macrophages are a heterogeneous group of cells with several subpopulations. This study was undertaken to determine if there is heterogeneity among rat interstitial macrophage subpopulations ability to respond to chemotactic stimuli. Alveolar macrophages were harvested and separated into density-defined fractions by centrifugation through a continuous iso-osmotic gradient of colloidal silica. Unfractionated and density-defined interstitial macrophages were then characterized as to their ability to migrate towards F-Met-Leu Phen and zymosan activated serum. Interstitial macrophages of density 1.053 and 1.083-1.097 gm/ml were found to have the greatest migrational movement towards F-Met-Leu-Phen which was lower than the unfractionated population. Interstitial macrophage subpopulations migrational movement towards zymosan activated serum exhibited a major peak by macrophages of density 1.053 gm/ml and a minor peak by macrophages of density 1.083-1.097 gm/ml which was lower than the unfractionated population. These results demonstrated that interstitial macrophages are heterogeneous in their migrational ability towards the chemotactic stimuli F-Met-Leu-Phen and zymosan activated serum and that there may be a cooperative interaction between the subpopulations which affects macrophages migrational ability.

Hyperbaric oxygen therapy for beta-radiation-induced scleral necrosis.

BACKGROUND: Beta-radiation has been used since 1950 as a postoperative measure to reduce the recurrence of pterygia. Scleral necrosis has been a major complication after radiotherapy that has led to perforation of the globe, endophthalmitis, and visual loss in some cases. METHOD: A patient is presented in whom scleral necrosis developed 25 days after a pterygiectomy with bare sclera technique followed by 3000 cGy in 3 weekly, divided doses of strontium 90. After a conjunctival graft failure, the patient was treated with hyperbaric oxygen therapy. RESULTS: The sclera revascularized and returned to nearly normal thickness after 14 sessions of hyperbaric oxygen therapy. CONCLUSION: Hyperbaric oxygen therapy may be an effective treatment for acute scleral necrosis after postoperative beta-radiation.

Alveolar macrophage subpopulations' responsiveness to chemotactic stimuli.

Recent data suggest that alveolar macrophages are a heterogeneous group of cells with several subpopulations. This study was undertaken to determine if there is heterogeneity among rat alveolar macrophage subpopulations ability to respond to chemotactic stimuli. Alveolar macrophages were harvested by bronchoalveolar lavage and fractionated into density-defined fractions by centrifugation through a continuous isoosmotic gradient of colloidal silica. Unfractionated and density-defined alveolar macrophages were then characterized as to their ability to migrate towards F-Met-Leu-Phen and zymosan-activated serum. Alveolar macrophages of density 1.083-1.097 gm/ml were found to have the greatest migrational movement toward F-Met-Leu-Phen, which was higher than the unfractionated population. In contrast, 2 peaks in alveolar macrophage subpopulations migrational movement towards zymosan-activated serum were noted that were lower than the unfractionated population. These results demonstrated that alveolar macrophages are heterogeneous in their migrational ability towards the chemotactic stimuli F-Met-Leu-Phen and zymosan-activated serum and that there may be a cooperative interaction between the subpopulations that affects macrophage migrational ability.

Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema.

Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 +/- 165 micrograms/ml in right lung and 29 +/- 15 micrograms/ml in left lung (p less than 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 +/- 319 micrograms/ml (p less than 0.02 vs. lodoxamide-treated animals). PMN percentages in right BAL (3.8 +/- 3.1) and left BAL (2.9 +/- 2.2) did not differ in lodoxamide-treated animals (p greater than 0.65); PMN percentage in right BAL of untreated animals was 18.7 +/- 2.9 (p less than 0.001 vs. lodoxamide-treated animals).(ABSTRACT TRUNCATED AT 250 WORDS)

Re-expansion pulmonary edema. A potential role for free radicals in its pathogenesis.

Re-expansion pulmonary edema (RPE) has been attributed to decreased lung interstitial pressures from a variety of mechanisms. Because some recent studies have implicated mechanisms that increase microvascular permeability in RPE, we tested whether the edema were due to free radical generation during re-expansion and reoxygenation of the collapsed lung. We used a rabbit model of RPE to test the effects of intracellular (dimethylthiourea) or extracellular (catalase) oxygen metabolite scavengers. Allopurinol was administered separately to determine whether xanthine oxidase was an important source of superoxide in this model. Edema was quantitated both gravimetrically and histologically, and lung xanthine oxidase activity was measured using a sensitive fluorometric assay with pterin as substrate. The results suggest indirectly that OH. or H2O2 (derived from O2-) contribute to the well-documented increase in lung permeability in RPE because dimethylthiourea, dimethylthiourea plus catalase, or catalase alone inhibited the edema to various degrees. Further, we observed histologically that increased numbers of neutrophils were present in re-expanded lungs and that neutrophil infiltration appeared to be diminished by antioxidant administration. Allopurinol did not decrease the edema, because xanthine oxidase activity in rabbit lung tissue is extremely low. We speculate that free radical generation in lung tissue contributes to the pathogenesis of RPE, although reinitiation of lung perfusion and ventilation requires a rapid change in intrathoracic pressure.

Features of asthma in older adults.

A study compared clinical and functional features of elderly patients with asthma to younger patients at a university medical center. Older patients had a larger than predicted reduction in pulmonary function parameters even though physician-assessed severity, duration of diagnosed asthma, and smoking status were no different between groups. A significant increase in the comorbid diagnosis of chronic obstructive pulmonary disease was noted in older patients with asthma. These two points support the hypothesis that long-standing asthma may lead to irreversible airflow obstruction. Older patients reported better medication compliance and decreases in some respiratory symptoms and demonstrated lower health care utilization.