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Biomedical subjects

M A Matthay

Publications and source records attributed to M A Matthay.

At least 163 records · Page 9Linked to original sources
PubMed1993

Pseudomonas aeruginosa-induced lung and pleural injury in sheep. Differential protective effect of circulating versus alveolar immunoglobulin G antibody.

The overall objective of these studies was to determine whether IgG antibody to Pseudomonas aeruginosa would modify the acute lung and pleural injury that developed over 24 h after the instillation of 10(10) live P. aeruginosa into the distal airspaces of one lung in unanesthetized sheep. Using a quantitative experimental model to measure protein permeability across the alveolar epithelial, lung endothelial, and pleural mesothelial barriers, the effect of IgG antibody to P. aeruginosa was examined under four different experimental conditions. First, the effect of IgG antibody to P. aeruginosa in the circulation was examined by instilling 10(10) live P. aeruginosa in 5% ovine albumin in sheep that had been vaccinated. Under these conditions, the presence of circulating IgG antibody to P. aeruginosa reduced lung endothelial injury but did not modify the lung epithelial or pleural injury caused by intraalveolar P. aeruginosa. Therefore, the second experimental protocol determined the effect of instilling immune serum from a sheep that had been vaccinated so that IgG antibody to P. aeruginosa was present in both the circulation and in the airspaces along with instillation of live bacteria. Under these conditions, injury to the lung endothelium, alveolar epithelium, and pleural space was completely prevented. Therefore, the third protocol examined the protective effect of instillation of IgG antibody to P. aeruginosa in the airspaces concurrent with the live bacteria. Interestingly, intraalveolar IgG antibody to P. aeruginosa prevented all evidence of lung epithelial and pleural injury, and this effect was associated with a marked decrease in the number of viable bacteria in the lung after 24 h. Therefore, the fourth protocol examined the prophylactic effect of instillation of the specific IgG antibody to P. aeruginosa 24 h before instillation of the bacteria. With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. Thus, delivery of IgG antibody to P. aeruginosa the distal airspaces of the lung alone may provide a novel therapeutic approach to preventing acute pulmonary infection caused by P. aeruginosa.

Animals↗
PubMed1993

Transient effect of epidermal growth factor on the motility of an immortalized mammary epithelial cell line.

The effects of growth factors on epithelial cell motility and dispersion have been examined on an immortalized human mammary epithelial cell line, the 184A1 nontumorigenic cell line. Among all the molecules tested, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) were demonstrated to stimulate an increase in mammary epithelial cell motility and wound closure that was associated with a morphological transformation of the cells and was accompanied by modifications in cell-cell and cell-substrate adhesion systems. The EGF-induced increase in cell motility and monolayer wound closure occurred over a 24 hour period and was not dependent on an increase in cell number. The effect of EGF was abolished by inhibiting alpha 2 integrins with specific antibodies, indicating that part of the mechanism for the increase in cell motility and accelerated wound closure depends on alpha 2 integrin functional expression. After 72 hours of exposure to EGF, the EGF-induced alterations in cell morphology, motility and cell adhesion systems underwent a spontaneous reversion that was correlated with a 10-fold reduction in the number of EGF receptors. The ability to regulate the scattering response induced by growth factors might be an important feature distinguishing normal epithelial cells from their tumoral counterparts.

Breast↗
PubMed1993

Preoperative and intraoperative factors associated with prolonged mechanical ventilation. A study in patients following major abdominal vascular surgery.

A study of 51 patients undergoing elective major abdominal surgery was carried out to determine the incidence of postoperative respiratory failure requiring mechanical ventilation for more than 24 h and which preoperative and intraoperative factors are associated with this respiratory complication. Mechanical ventilation for more than 24 h was required in 12 of the 51 patients. These 12 patients had a significantly longer stay in the intensive care unit and in the hospital than the patients who were successfully extubated in the postoperative period. Also, there was a trend for a higher mortality in the ventilated group compared to the group of patients who did not require postoperative ventilation. Preoperative abnormalities in FEV1 did not identify which patients were destined to require postoperative ventilation. Significant differences for the ventilated versus the nonventilated patients included a longer history of cigarette smoking, a lower preoperative PaO2, and a large intraoperative blood loss.

Abdomen↗
PubMed1993

Prevalence and severity of neurologic dysfunction in critically ill patients. Influence on need for continued mechanical ventilation.

OBJECTIVE: The relative importance of neurologic dysfunction in critically ill mechanically ventilated patients has not been well studied. This study investigates the prevalence of neurologic dysfunction in critically ill mechanically ventilated patients and its influence on preventing the discontinuation of mechanical ventilation and patient outcome. DESIGN: Prospective study. SETTING: University-based, tertiary care center. PATIENTS: All eligible adult patients mechanically ventilated for more than 48 h were included. A total of 66 patients were evaluated. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Two independent questionnaires, one completed by the critical care attending physician documenting the major clinical factors necessitating continued mechanical ventilation, and a second questionnaire, completed by a critical-care trained neurologist documenting neurologic status and objective cardiopulmonary status formed the basis for outcome measurements. Respiratory and physiologic data, the patient's clinical conditions, and outcome (mortality) were also included in the database. RESULTS: Pulmonary factors were the major reason for prolonged ventilation in only 51 percent of the patient evaluations. Neurologic status was the major factor necessitating continued mechanical ventilation in 32 percent of the patient evaluations and a significant contributing factor in an additional 41 percent. Of the neurologic factors, diminished level of consciousness was the major cause of continued ventilatory support. This was usually due to a systemic illness, rather than a primary central nervous system disorder. Mortality was significantly lower in patients who continued to require mechanical ventilation after 48 h because of neurologic factors as opposed to pulmonary factors (15 percent vs 72 percent, p = 0.002). CONCLUSIONS: There is a high prevalence of neurologic dysfunction in critically ill patients and this problem plays a significant role in preventing the discontinuation of mechanical ventilation. Altered mental status is a major factor necessitating continued mechanical ventilation in combined medical-surgical intensive care units.

Central Nervous System Diseases↗
PubMed1993

Alveolar epithelial barrier and acute lung injury.

The central importance of the alveolar epithelial barrier in the pathogenesis and recovery from acute lung injury has only recently been appreciated. Both in vivo and in vitro studies have provided a new understanding of the mechanisms that regulate transport of sodium, water, and protein across the alveolar epithelial barrier. This new information regarding the normal function of the alveolar epithelial barrier in regulating lung fluid and protein balance has made it possible to study the function of the alveolar barrier both experimentally and clinically in the setting of acute lung injury. The alveolar epithelial barrier is much more resistant to injury than the nearby lung endothelium. The mechanisms that cause injury to the alveolar barrier are just beginning to be explored in different experimental models of acute lung injury. Some progress has been made in understanding how alveolar barrier injury occurs, especially in bacterial pneumonia. Finally, while it is recognized that alveolar epithelial type II cells play an important role in both ion transport and surfactant production, it is now possible to study in vitro the contribution of alveolar epithelial type II cells in repair of the denuded alveolar barrier.

Animals↗
PubMed1992

Persistent paralysis in critically ill patients after long-term administration of vecuronium.

BACKGROUND: The muscle relaxant vecuronium is sometimes administered to facilitate mechanical ventilation. Neuromuscular paralysis lasting up to seven days may occur after the termination of long-term administration (i.e., more than two days) of vecuronium in critically ill patients. We investigated the role of clinical factors and plasma concentrations of vecuronium and its metabolite in causing this prolonged neuromuscular blockade. METHODS: We studied 16 critically ill adult patients (8 women and 8 men) who had received vecuronium to facilitate mechanical ventilation for at least two consecutive days. Clinical factors and plasma concentrations of vecuronium and 3-desacetylvecuronium, the active metabolite of vecuronium, were compared in patients with and without prolonged neuromuscular blockade. In addition, we performed detailed pharmacokinetic studies in the patients without prolonged neuromuscular blockade. RESULTS: Seven of the 16 patients had prolonged neuromuscular blockade, lasting from six hours to more than seven days, after the termination of vecuronium therapy. These seven patients, six of whom were women, had higher plasma magnesium concentrations and lower arterial blood pH values than the nine patients without prolonged neuromuscular blockade. They also had higher plasma concentrations of 3-desacetylvecuronium and a higher frequency of renal failure (seven of seven patients vs. four of nine patients, P less than 0.03). In the patients without prolonged neuromuscular blockade, the mean (+/- SD) plasma clearance, elimination half-life, and volume of distribution of vecuronium were 2.5 +/- 1.0 ml per kilogram of body weight per minute, 299 +/- 154 minutes, and 1.1 +/- 0.6 liters per kilogram, respectively. CONCLUSIONS: Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure and high plasma concentrations of 3-desacetylvecuronium.

Critical Illness↗
PubMed1992

Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome.

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.

Adult↗
PubMed1992

Clearance of different-sized proteins from the alveolar space in humans and rabbits.

Investigation of the clearance of proteins from the air spaces is important for an understanding of the resolution of pulmonary edema and also because of current interest in delivery of therapeutic peptides via the distal air spaces. Few experimental studies have examined the size dependence for alveolar clearance of large macromolecules; there have been no human studies. In anesthetized rabbits, we measured clearance of cyanocobalamin and different-sized human proteins instilled into the air spaces. After 8 h, the amounts of instilled tracer recovered in the lungs were [57Co]cyanocobalamin, 19.4 +/- 3.0% (Stokes radius 0.65 nm); 125I-labeled insulin, 64.6 +/- 3.9% (1.2 nm); 131I-labeled albumin, 87.0 +/- 4.0% (3.5 nm); and 125I-labeled immunoglobulin G, 91.8 +/- 3.3% (5.5 nm) (P < 0.05). Sieving of different-sized proteins occurred across the alveolar epithelial barrier because tracer concentrations in air space lavage fluid after 8 h were decreased more for the smaller tracers than the larger ones. Size selectivity for alveolar protein clearance in humans with resolving alveolar edema was investigated by measuring the changes in albumin and total protein concentration. The fraction of total protein concentration made up of albumin was greater in the edema fluid than in the plasma initially. The albumin fraction decreased with time in 9 of 10 patients with resolving edema, from 0.62 +/- 0.2 to 0.58 +/- 0.10 (P < 0.05) after 10 +/- 5 h. Thus both rabbit studies and human studies provide evidence for size-dependent clearance of protein from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils within the airspaces of the lungs. In order to determine if neutrophil activating protein (NAP)-1/interleukin-8 (NAP-1/IL-8) could be an important cause of neutrophil influx and activation in ARDS, we examined fluid, which was either directly aspirated or lavaged with saline from the lungs of patients with ARDS. NAP-1/IL-8 was present in significantly higher concentrations in the fluids of patients with ARDS compared with control subjects. There was a significant correlation between the percentage of neutrophils in the lavage fluids and the NAP-1/IL-8 concentration (r2 = 0.74). Furthermore, the NAP-1/IL-8 concentration of the pulmonary edema fluid was equivalent to the optimal concentration required to induce neutrophil chemotaxis in vitro. Although not all of the chemotactic activity of the edema fluid was removed by an anti-NAP-1/IL-8 affinity column, the data established that NAP-1/IL-8 is an important neutrophil chemotaxin in the airspaces of patients with ARDS. In addition, those patients with very high concentrations of NAP-1/IL-8 in their bronchoalveolar lavage fluids had a higher mortality rate than those patients with lower concentrations of NAP-1/IL-8. The correlation between NAP-1/IL-8 concentration and mortality is not paralleled by total protein concentration and mortality.

Adolescent↗
PubMed1992

Pulmonary edema associated with salt water near-drowning: new insights.

In this case report we describe the clinical and laboratory findings of a man who nearly drowned after aspirating a large quantity of seawater. The aspiration of salt water, which is strongly hypertonic with respect to plasma, resulted in severe pulmonary edema, both from the quantity of aspirated seawater and the osmotically driven ultrafiltrate of plasma that accumulated in the air spaces. The initial concentration of protein in the edema fluid sample was very low, 0.7 g/dl, consistent with only a minimal increase in epithelial permeability. Approximately 4 h later, there was a marked increase in the concentration of protein in the residual alveolar fluid associated with improvement in several clinical indices, indicating that the excess alveolar fluid was reabsorbed very rapidly. In addition, the magnesium concentration was markedly elevated because of the aspiration of magnesium-containing seawater, which may have diagnostic importance for near-drowning in salt water. The data from this case provide evidence for well-preserved alveolar epithelial barrier function after aspiration of large quantities of hypertonic salt water.

Animals↗
PubMed1992

Obstetric patients requiring critical care. A five-year review.

Only one study has examined the clinical issues presented by critically ill obstetric patients with respect to medical indications for intensive care unit (ICU) admission and fetal and maternal morbidity and mortality. Therefore, a review of all obstetric patients admitted to a medical-surgical ICU in a large tertiary referral center over a five-year period was conducted. Obstetric, ICU-related, and diagnostic data were recorded for each patient. The diagnosis of the disease responsible for the patient's critical illness was categorized as obstetric or nonobstetric. The diagnosis that prompted ICU admission was determined for each patient and was categorized as respiratory failure, hemodynamic instability, or neurologic dysfunction. There were 32 obstetric admissions representing 0.4 percent of all deliveries during this time period. There was a predominance of postpartum admissions and obstetric diagnoses responsible for the patient's critical illness. Preeclampsia was the single most common diagnosis representing 22 percent of all patients. Hemodynamic instability was never the cause of antepartum ICU admission in patients with a viable fetus. In contrast, hemodynamic instability accounted for 52 percent of postpartum ICU admissions. Of the eight women admitted with viable pregnancies to the ICU, seven were delivered during the ICU stay and all fetuses survived. There was a high incidence of acute lung injury (25 percent) that was associated with nonpulmonary or pulmonary infection in all eight cases. However, the mortality was only 25 percent.

Adolescent↗
PubMed1991

Alveolar and lung liquid clearance in anesthetized rabbits.

Alveolar and lung liquid clearance were studied over 8 h in intact anesthetized ventilated rabbits by instillation of either isosmolar Ringer lactate (2 ml/kg) or autologous plasma (2 or 3 ml/kg) into one lower lobe. The half time for lung liquid clearance of the isosmolar Ringer lactate was 3.3 h and that for plasma clearance was 6 h. In the plasma experiments, the alveolar protein concentration after 1 h was 5.2 +/- 0.8 g/dl, which was significantly greater than the initial instilled protein concentration of 4.3 +/- 0.7 g/dl (P less than 0.05). Thus alveolar protein concentration increased by 21 +/- 12% over 1 h, which matched clearance from the entire lung of 19 +/- 11% of the instilled volume. Overall the rate of alveolar and lung liquid clearance in rabbits was significantly faster than in prior studies in dogs and sheep. The fast alveolar liquid clearance rate in rabbits was not due to higher endogenous catecholamine release, because intravenous and alveolar (5 x 10(-5) M) propranolol did not slow the clearance. Also, beta-adrenergic therapy with alveolar terbutaline (10(-5) or 10(-4) M) did not increase the alveolar or lung liquid clearance rates. Phloridzin (10(-3) M) did not slow alveolar liquid clearance. However, amiloride (10(-4) M) inhibited 75% of the basal alveolar liquid clearance in rabbits, thus providing evidence that alveolar liquid clearance in rabbits depends primarily on sodium-dependent transport. This rabbit study provides further evidence for important species differences in the basal rates of alveolar liquid and solute clearance as well as the response to beta-adrenergic agonists and ion transport inhibitors.

Amiloride↗
PubMed1991

Alveolar and lung liquid clearance in the absence of pulmonary blood flow in sheep.

The effect of removing pulmonary blood flow on the clearance of excess liquid and protein from the air spaces and interstitium of the normal lung was studied in anesthetized ventilated sheep. To eliminate pulmonary blood flow to one lung, the left pulmonary artery was occluded. Autologous serum (3 ml/kg) with 125I-labeled albumin was then instilled into the left lower lobe. Hemodynamics and lung lymph were measured, and the lungs were removed after 4 h. Alveolar protein concentration over 4 h was used as the index of alveolar liquid clearance. Total lung liquid clearance was measured by the gravimetric method. The percent increase in alveolar protein concentration over baseline was similar between sheep without pulmonary blood flow (33.8 +/- 17.4) and with pulmonary blood flow (31.1 +/- 14.6); thus, alveolar liquid clearance was not changed by the absence of pulmonary blood flow. Also, in the absence of pulmonary blood flow, lung liquid clearance (as percent of instilled) over 4 h was 27.1 +/- 3.8 (n = 7), which was not significantly different from control experiments with pulmonary blood flow (26.4 +/- 7.1, n = 7). In the sheep without pulmonary blood flow, bronchopulmonary anastomotic flow was 41.5 +/- 21.3 ml/min. To further reduce blood flow to the lung, both the left pulmonary artery and the bronchoesophageal artery were occluded, which reduced bronchopulmonary anastomotic flow to the left lung to 12.0 +/- 9.3 ml/min. This further reduction in blood flow did not, however, change alveolar or lung liquid clearance. Even with this low blood flow to the left lung, the removal of 125I-albumin from the lung was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Although intravenous Escherichia coli endotoxin has been used extensively in experimental studies to increase lung endothelial permeability, the effect of E. coli endotoxin on lung epithelial permeability has not been well studied. To examine this issue in sheep, bidirectional movement of protein across the lung epithelial barrier was studied by labeling the vascular space with 131I-albumin and by instilling 3 ml/kg of an isosmolar protein solution with 125I-albumin into the alveoli. E. coli endotoxin was administered according to one of three protocols: intravenous alone (5-500 micrograms/kg), intravenous (5 micrograms/kg) plus low-dose alveolar endotoxin (10 micrograms/kg), and high-dose alveolar endotoxin alone (50-100 micrograms/kg). Alveolar liquid clearance was estimated based on the concentration of the instilled native protein. Sheep were studied for either 4 or 24 h. Although intravenous E. coli endotoxin produced a marked increase in transvascular protein flux and interstitial pulmonary edema, there was no effect on the clearance of either the vascular (131I-albumin) or the alveolar (125I-albumin) protein tracer across the epithelial barrier. High-dose alveolar E. coli endotoxin caused a 10-fold increase in the number of leukocytes, particularly neutrophils, that accumulated in the air spaces. In spite of the marked chemotactic effect of alveolar endotoxin, there was no change in the permeability of the epithelial barrier to the vascular or alveolar protein tracers. Also, alveolar epithelial liquid clearance was normal. Morphologic studies confirmed that the alveolar epithelial barrier was not injured by either intravenous or alveolar E. coli endotoxin. Thus, the alveolar epithelium in sheep is significantly more resistant than the lung endothelium to the injurious effects of E. coli endotoxin.

Albumins↗
PubMed1991

Resolution of pulmonary edema. New insights.

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine.

Animals↗