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P D Lew

Publications and source records attributed to P D Lew.

64 records · Page 4Linked to original sources
PubMed1982

Loculated pleural empyema: identification of complement breakdown products in contiguous sterile pleural fluid.

In view of the recent demonstration of complement consumption in human empyema, we searched for evidence of complement activation in 4 patients presenting initially with sterile postpneumonic effusions, but who were later shown to have contiguous loculated pleural empyemas. These results were compared with those obtained on 13 patients with postpneumonic uncomplicated effusions, and on 13 patients with primary empyema. C3d and Ba, respectively, breakdown products of complement components C3 and Factor B were both significantly elevated in the postpneumonic effusions of the 4 patients with loculated empyemas, when compared with those obtained in postpneumonic uncomplicated effusions (p less than 0.005). Total hemolytic complement activity (CH50) was similar in these 2 groups of pleural effusions. Plasma levels of C3d and Ba were undetectable, and CH50 values were within the same range in all groups of patients. These results suggest that the low molecular weight breakdown products of C3 and Factor B had diffused from the adjacent empyema, where active complement breakdown was occurring, into the sterile postpneumonic effusion. This study provides information about complement catabolism in extravascular sites during infection. The potential usefulness of this approach for the detection of loculated purulent collections is discussed.

Aged↗
PubMed1981

Effect of calcium on superoxide production by phagocytic vesicles from rabbit alveolar macrophages.

Phagocytic vesicles from rabbit lung macrophages produced superoxide in the presence of NADH or NADPH. At 37 degrees C, these vesicles generated 51+/-7.8 nmol O(2) (-)/min per mg protein in the presence of 0.5 mM NADPH. The apparent K(m) for NADPH and NADH (66 and 266 muM, respectively), the pH optimum for the reaction (6.9), and the cyanide insensitivity were similar to properties of plasma membrane-rich fractions of stimulated polymorphonuclear leukocytes studied by others. The activity of the phagocytic vesicles was trypsin sensitive. The specific superoxide-generating activity of macrophage phagocytic vesicles isolated from cells incubated up to 90 min with phagocytic particles remained constant. Calcium in micromolar concentrations inhibited the NADPH-dependent O(2) (-)-generating activity of phagocytic vesicles. In a physiological ionic medium (100 mM KCl, 2.5 mM MgCl(2), 30 mM imidazole-HCl, pH 6.9), a maximal inhibition of O(2) (-) generation by phagocytic vesicles of 80% was observed at 40 muM free Ca(2+). The half maximum inhibitory effect was at 0.7 muM Ca(2+). Variations of the calcium concentration resulted in rapid and reversible alterations in O(2) (-)-forming activity. Preincubation of phagocytic vesicles in the presence of EGTA rendered their O(2) (-) generation rate in the presence of NADPH insensitive to alterations in the free calcium concentration. This desensitization by low EGTA concentrations (</=100 muM) was reversible by the addition of excess calcium, but desensitization by high EGTA concentrations (>1 mM) was not reversible by the addition of calcium either in the presence or absence of purified rabbit lung macrophage or bovine brain calmodulins. Furthermore, trifluoperazine, a drug that inhibits calmodulin-stimulated reactions, did not alter the activity or the calcium sensitivity of the superoxide-generating system of sensitive phagocytic vesicles. Peripheral plasma membrane vesicles (podosomes) prepared by gentle sonication of macrophages possessed on O(2) (-)-generating system with similar properties to those of phagocytic vesicles. We conclude that the activated O(2) (-)-generating system of rabbit lung macrophages has its initial localization in the plasmalemma and undergoes subsequent internalization into phagocytic vesicles, where it can function for prolonged periods of time. Calcium at concentrations likely to exist in macrophage cytoplasm exerts a regulatory effect on the activated system.

Animals↗
PubMed1979

Decreased heat-labile opsonic activity and complement levels associated with evidence of C3 breakdown products in infected pleural effusions.

Heat-labile opsonic activity was measured simultaneously in serum and pleural fluid of patients with transudates, infectious exudates (with positive or negative bacterial culture) and neoplastic exudates, using two different complement-dependent phagocytic tests: the killing of Staphylococcus aureus Wood 46 variant strain (K50 opsonic titers) and the assessment of ingestion rate of endotoxin-coated paraffin particles (Oil Red 0 uptake test). K50 opsonic titers were lower in culture-positive pleural effusions as compared to culture-negative (P < 0.002) or neoplastic effusions (P < 0.002). These results were corroborated by the Oil Red 0 uptake test. The data obtained with the two assays showed a significant correlation (P < 0.001). The hemolytic activity of complement (CH50) as well as the levels of C3 breakdown product, C3d, were measured in the same sera and pleural fluid samples and in an additional group of patients with pleural effusions of the same etiology. Effusions with positive cultures showed lower CH50 values (P < 0.01) and higher C3d values (P < 0.05) when compared to culture-negative pleural fluids. Finally, evidence for immune complexes in pleural effusions and sera was looked for by determination of Clq binding activity. Levels were higher in culture-positive effusions when compared to culture-negative fluids (P = 0.005).K50 opsonic titers showed a positive correlation with CH50 values (P < 0.001) for all fluids tested. Similarly Clq binding activity correlated with C3d levels in effusions of infectious origin (P = 0.05). Recovery experiments using the various bacterial species isolated from culture-positive pleural effusions showed evidence of complement inactivation upon incubation with pooled sera at concentrations of 10(7)-10(8) microorganisms/ml. These results indicate that one important reason for bacterial persistence in empyema may be decreased opsonization secondary to local consumption of complement.

Adult↗
PubMedDate not supplied

Perioperative antibiotic prophylaxis of wound and foreign body infections: microbial factors affecting efficacy.

Numerous microbial factors are responsible for perioperative infections and influence the efficacy of antibiotic prophylaxis. These factors include the staphylococcal carrier state, bacterial adherence to a number of host proteins, the production of glycocalyx by sessile bacteria, and shifts in antibiotic resistance. A full understanding of the mechanisms involved will lead to further reductions in the number of postoperative infections. Unfortunately, the microbial factors affecting prophylaxis cannot be evaluated separately under clinical conditions; they are easier to study under circumstances whose bacteriologic features are well defined and in which the presence of foreign materials (e.g., sutures) greatly potentiates pathogenic mechanisms. Such circumstances exist, for example, in infections developing after "clean" surgery and in experimental models. Since even clean wounds are found to be contaminated when sampled carefully, the control of infection is more a quantitative than a qualitative problem. The critical period for the development of infection is short: an antibiotic course not exceeding 24 hours seems effective in preventing infection.

Animals↗
PubMedDate not supplied

Complement activation in the adult respiratory distress syndrome following cardiopulmonary bypass.

We investigated complement fractions in patients after extracorporeal circulation for coronary bypass operations or cardiac valve replacement, and in two cases developing an adult respiratory distress syndrome (ARDS) after this type of intervention. The patients presenting an ARDS had significantly increased levels of C3d (p less than 0.001), the small molecular breakdown product of C3, associated with decreased levels of total classic haemolytic activity (p less than 0.05) and of the complement component C1q (p less than 0.001) when compared to a group of 10 patients who had uneventful evolution after bypass. However, all patients undergoing cardiopulmonary bypass had significantly increased levels of C3d (p less than 0.005 or less) associated with significant decrease of various complement components within 24 h after bypass, when compared to a control group of 5 patients investigated after aorto-iliac bypass graft surgery. We conclude that significant complement activation can persist in patients 24 h after bypass and--at higher levels--be a pathogenic and biological marker of ARDS after extracorporeal circulation.

Adult↗
PubMedDate not supplied

Prekallikrein activation in the adult respiratory distress syndrome.

Prekallikrein is the zymogen form of plasma kallikrein, a proteolytic enzyme of the contact system of blood coagulation, fibrinolysis and kinin formation. To assess whether prekallikrein was activated in the adult respiratory distress syndrome (ARDS), we examined plasma samples from 12 critically ill patients including five individuals with ARDS. Using the ratio between functional prekallikrein and prekallikrein-kallikrein antigen as an index for prekallikrein activation, we found that prekallikrein was extensively activated in patients with ARDS, while this was significantly less in the case of critically ill patients without ARDS. Following activation of prekallikrein in plasma, kallikrein reacts with its substrates and with protease inhibitors, among which the alpha 2-glycoprotein C1-inhibitor. Thus, we examined whether C1-inhibitor of critically ill individuals was modified in a way suggesting that it had reacted with kallikrein. Such a modification was found in the five patients with ARDS, while it was not detectable in the seven patients without ARDS. This observation further confirmed the activation of prekallikrein in patients with ARDS. We suggest that plasma kallikrein-mediated reactions, which include bradykinin release and neutrophil activation, may contribute to the pathogenesis of ARDS.

Adolescent↗