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Biomedical subjects

M A Matthay

Publications and source records attributed to M A Matthay.

At least 181 records · Page 10Linked to original sources
PubMed1990

Comparison of transesophageal echocardiographic and scintigraphic estimates of left ventricular end-diastolic volume index and ejection fraction in patients following coronary artery bypass grafting.

Transesophageal echocardiography (TEE) has become a commonly used monitor of left ventricular (LV) function and filling during cardiac surgery. Its use is based on the assumption that changes in LV short-axis ID reflect changes in LV volume. To study the ability of TEE to estimate LV volume and ejection immediately following CABG, 10 patients were studied using blood pool scintigraphy, TEE, and thermodilution cardiac output (CO). A single TEE short-axis cross-sectional image of the LV at the midpapillary muscle level was used for area analysis. Between 1 and 5 h postoperatively, simultaneous data sets (scintigraphy, TEE, and CO) were obtained three to five times in each patient. End-diastolic (EDa) and end-systolic (ESa) areas were measured by light pen. Ejection fraction area (EFa) was calculated (EFa = (EDa - ESa)/EDa). When EFa was compared with EF by scintigraphy, correlation was good (r = 0.82 SEE = 0.07). EDa was taken as an indicator of LV volume and compared with LVEDVI which was derived from EF by scintigraphy and CO. Correlation between EDa and LVEDVI was fair (r = 0.74 SEE = 3.75). The authors conclude that immediately following CABG, a single cross-sectional TEE image provides a reasonable estimate of EF but not LVEDVI.

Adult↗
PubMed1990

Intact epithelial barrier function is critical for the resolution of alveolar edema in humans.

Within 15 min of endotracheal intubation, the resolution of pulmonary edema was studied over the next 12 h in 34 mechanically ventilated patients by (1) serial measurements of the alveolar-arterial oxygen difference, (2) the extent of edema on the initial and follow-up chest radiograph, and (3) by an initial and final measurement of total protein and albumin concentration in sequential samples of pulmonary edema fluid. Based on the oxygenation and chest radiographic data, 24 patients clinically improved and 10 patients did not improve. In the 10 patients who did not clinically improve (3, hydrostatic edema; 7, permeability edema), there was no change in the final edema fluid protein concentration (4.1 +/- 1.1 g/100 ml) compared with the initial edema fluid protein concentration (4.2 +/- 1.0 g/100 ml) (p = ns). However, in the 24 patients who clinically improved (15, hydrostatic edema; 9, permeability edema), there was an increase in every patient's final edema protein concentration (5.6 +/- 2.3 g/100 ml) compared with their initial edema protein concentration (3.8 +/- 1.2 g/100 ml) (p less than 0.01). In 13 of these 24 patients, the final edema fluid concentration (7.3 +/- 1.6 g/100 ml) exceeded the final plasma protein concentration (5.6 +/- 0.8 g/100 ml) by a mean value of 1.7 g/100 ml protein. The data provide the first evidence in humans to support the hypothesis that active ion transport across the alveolar epithelial barrier is the primary mechanism for clearance of edema fluid from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗
PubMed1990

Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome.

In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome. Acute lung injury was quantified on a four-point scoring system. At the time of entry into the study, none of the 45 patients had evidence of lung injury. Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury. The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588 +/- 204 vs. 338 +/- 196, percentage of control, P less than 0.01). Furthermore, a plasma vWf-Ag level greater than or equal to 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis. In addition, the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury. Also, a plasma vWf-Ag level greater than 450 had a positive predictive value of 80% for identifying nonsurvivors. Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value.

Acute Disease↗
PubMed1990

The adult respiratory distress syndrome. Definition and prognosis.

This article provides an expanded definition of acute lung injury and the adult respiratory distress syndrome and describes the value of using this definition for establishing prognosis by discussing the basis for the acute lung injury scoring system, the various clinical disorders that may be associated with acute lung injury and how they affect outcome, and the influence of nonpulmonary organ failure on the outcome of patients with acute lung injury.

Acute Disease↗
PubMed1990

Pulmonary endothelial cell injury and altered lung metabolic function. Early detection of the adult respiratory distress syndrome and possible functional significance.

Markers of endothelial cell damage or dysfunction may be sensitive probes for the detection of the earliest phases of acute lung injury and may be a guide to the severity of injury or response to therapy as well. Depressed lung metabolic function may contribute to the intrapulmonary or systemic pathophysiology of ARDS.

Animals↗
PubMed1989

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

To evaluate the possibility of administering therapeutic proteins via the respiratory route, we administered an aerosol of recombinant DNA-produced human alpha 1-antitrypsin (rAAT) to anesthetized sheep and measured levels of the protein in epithelial lining fluid (ELF), lung lymph, blood, and urine. Using a nebulizer that generated aerosol droplets with a mass median aerodynamic diameter of 2.7 micron (55% of droplets were less than 3 micron, a particle size optimal for deposition on the alveolar epithelium), in vitro studies demonstrated that the aerosolized rAAT remained intact and fully functional as an inhibitor of neutrophil elastase. When aerosolized to sheep, the 45-kDa rAAT molecule diffused across the alveolar epithelium, as evidenced by its presence in lung lymph and in blood. Comparison of ELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with approximately 10-fold concentration differences in each consecutive compartment, respectively. Importantly, evaluation with aerosolized 125I-labeled rAAT demonstrated that the rAAT molecules that reached the lung lymph and the systemic circulation remained intact as a 45-kDa protein. These results demonstrate the feasibility of using aerosolization to the pulmonary epithelial surface to administer sizeable proteins of therapeutic interest, thus circumventing the necessity of the traditional parenteral modes of administration of such molecules.

Absorption↗
PubMed1989

Protein clearance from the air spaces and lungs of unanesthetized sheep over 144 h.

We studied the rate, the routes, and the mechanisms for protein clearance from the air spaces and lungs of 20 unanesthetized sheep over 144 h. We instilled 100 ml of autologous serum labeled with 125I-albumin into one lung. At the end of 24, 48, 96, or 144 h, the lungs were removed and the residual native protein and 125I-albumin in the air spaces were determined by bronchoalveolar lavage. Also the fraction of the instilled 125I-albumin remaining in the rest of the lung was measured in the lung homogenate. Clearance of the 125I-albumin from the lung into the plasma, lymph, thyroid, urine, and feces was also determined. The removal of both the 125I-albumin and the native protein from the air spaces was slow, following a monoexponential decline. The removal rate of the 125I-albumin from the air spaces was slightly but significantly faster (1.6%/h) than the clearance rate of the native protein (0.9%/h). Clearance of the 125I-albumin from the lung also followed a slow monoexponential decline at a rate of 1.4%/h. At all time periods, 75% of the 125I-albumin remaining in the lung was located in the air spaces, thus indicating that the pulmonary epithelium is the principal barrier to protein clearance from the normal lung. Macrophages appeared to play a minor role in alveolar protein clearance because the quantity of 125I-albumin present in the phagocytic cells in the air spaces was less than 1% of the instilled 125I-albumin at all time periods. However, macrophages may play some role in protein clearance after 48 h because we visualized phagolysosomes in macrophages, and there was an increase in free iodine in lung lavage, urine, thyroid, and feces after 48 h. However, gel electrophoretic studies showed that most of the 125I-albumin was cleared from the lung as an intact molecule, although only 24.7 +/- 4.7% of the 125I-albumin was cleared by the lymphatics.

Animals↗
PubMed1989

Effects of leukotriene B4 in the human lung. Recruitment of neutrophils into the alveolar spaces without a change in protein permeability.

Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 X 10(-7)M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCl (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar lavage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCl = 6.8 +/- 1.0 X 10(6) vs. LTB4 = 26.4 +/- 5.0 X 10(6), P less than 0.01), most of which were PMN (NaCl = 12.2 +/- 4.6% vs. LTB4 = 55.7 +/- 6.0%, P less than 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.

Adult↗
PubMed1989

The adult respiratory distress syndrome. New insights into diagnosis, pathophysiology, and treatment.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, and John G. Fitz, MD, Assistant Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Humans↗
PubMed1989

Pulmonary manifestations of endocrine and metabolic disorders.

In summary, there are a number of important respiratory manifestations of endocrine diseases. Hypothyroidism may be associated with respiratory failure that can be caused by a reduction in central respiratory drive, upper airway obstruction, and associated restrictive pulmonary function from pleural effusions or an intrinsic decrease in lung volumes. Hyperthyroidism can present with dyspnea as a major clinical manifestation because of the increase in central respiratory drive associated with thyrotoxicosis. Cardiac dysfunction associated with hyperthyroidism may lead to pulmonary edema in some patients. Hypoparathyroidism may occur acutely, especially after thyroid surgery and be associated with hypocalcemia and acute tetany, laryngeal stridor, and muscle weakness. Ovarian tumors, both benign and malignant, may present with unilateral or bilateral effusions. Finally, patients with diabetes mellitus are at increased risk of developing a variety of pulmonary disorders. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes, although cardiogenic and noncardiogenic pulmonary edema can also be a complication of their disease.

Diabetes Complications↗
PubMed1988

Bedside catheterization of the pulmonary artery: risks compared with benefits.

The decision to use bedside pulmonary artery catheterization for managing patients must involve a careful assessment of the risks compared to the benefits. Complications can be minimized by following specific guidelines for catheter insertion and maintenance. Pulmonary artery catheterization has been shown to be more accurate than clinical assessment alone in critically ill patients for determining the cause of shock (hypovolemic, cardiogenic, or septic) or for assessing the cause of severe pulmonary edema (cardiogenic or noncardiogenic). The diagnosis of cardiac failure in medical or surgical patients with invasive hemodynamic monitoring provides physiologic data that guide pharmacologic treatment that may favorably influence preload and afterload in the failing or ischemic heart. Managing hemodynamics with the aid of pulmonary artery catheterization in patients with the adult respiratory distress syndrome has received considerable attention, but a contribution to better patient outcome has not been established. Similarly, although clinical management of hemodynamic instability in septic shock is facilitated by pulmonary artery catheterization, the mortality remains very high because of the lack of specific therapy to reverse the sepsis syndrome. Adequate volume resuscitation and improved tissue oxygenation are universally accepted goals, but specific hemodynamic endpoints are controversial and direct measurements of tissue oxygenation are not possible. Prospective studies to define the clinical value of pulmonary artery catheterization are needed, but must be designed very carefully in order to identify unequivocally the effect of pulmonary artery catheterization on outcome in critically ill patients.

Catheterization, Swan-Ganz↗
PubMed1988

Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome.

The human pulmonary edema fluid concentrations of LTC4 and of LTD4 and LTE4, derived peptidolytically from LTC4, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (+/- SD) of LTD4 of 19.2 +/- 25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE4 of 192 +/- 309 nM for 10 of the patients were significantly higher (P less than 0.005 and P less than 0.05) than those of 2.2 +/- 2.4 and 11.0 +/- 18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC4 were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC4 and LTD4 peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [3]LTC4 and [3]LTD4 by 100 microliter of pulmonary edema fluid attained respective mean maximum levels of 74.5 +/- 2.9% (N = 5) and 37.7 +/- 10.2% (N = 4) after 30 min at 37 degrees C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD4 and LTE4 over LTC4 in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.

Adolescent↗
PubMed1988

Hydrostatic versus increased permeability pulmonary edema: diagnosis based on radiographic criteria in critically ill patients.

To evaluate radiographic criteria recently proposed for determining causes of pulmonary edema, the authors studied 45 patients with severe pulmonary edema. Hydrostatic and increased permeability edemas were distinguished by means of the ratio of pulmonary edema fluid protein to plasma protein concentration and clinical and hemodynamic data. Chest radiographs were classified as showing hydrostatic, increased permeability, or mixed edema by three independent readers without knowledge of the clinical diagnosis. Overall, 87% of patients with hydrostatic edema but only 60% of patients with increased permeability edema were correctly identified. A patchy, peripheral distribution of edema was the single most discriminating criterion and was relatively specific for increased permeability edema, occurring in 13% of patients with hydrostatic and 50% with increased permeability edema (P less than .05). Some features considered more typical of hydrostatic edema were commonly found in patients with increased permeability, including a widened vascular pedicle (56%), pleural effusions (36%), peribronchial cuffs (72%), and septal lines (40%). The authors conclude that chest radiography is limited in the differentiation of type of pulmonary edema in severe cases.

Capillary Permeability↗
PubMed1988

Alveolar liquid and protein clearance from normal dog lungs.

To determine whether liquid and protein clearance from the air spaces and lungs of anesthetized and unanesthetized dogs is the same as in sheep, we quantified these variables at three different time periods (4, 8, and 12 h) by instilling heparinized plasma (3 ml/kg) labeled with 125I-albumin into one lower lobe. Protein clearance, measured from the residual 125I-albumin in the lung homogenate, was slow and monoexponential (approximately 1%/h), similar to our previous data for protein clearance from the lungs in sheep. Lung liquid clearance in dogs, however, was 50% less than in previous experiments in sheep. Residual lung liquid (as percent of instilled) was 88.7 +/- 7.0 at 4 h, 70.5 +/- 9.1 at 8 h, and 64.0 +/- 5.8 at 12 h. At each time period, alveolar protein concentration increased by 0.6 +/- 0.4 g/dl at 4 h, 1.3 +/- 1.2 g/dl at 8 h, and 2.1 +/- 0.8 g/dl at 12 h. This increase in alveolar protein concentration was proportional to the volume of liquid removed from the lungs. beta-Adrenergic agonist therapy with terbutaline (10(-5) M mixed with the instilled plasma) doubled the volume of liquid cleared from the lungs over 4 h, and the alveolar protein concentration increased proportionally. However, lung liquid clearance in dogs that were treated with beta-agonists was proportionally (50%) less than in sheep treated with beta-agonists. The slower liquid clearance in dogs compared with sheep cannot be explained by differences in hemodynamics, pulmonary blood flow, anesthesia, mode of ventilation, or alveolar surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗