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Biomedical subjects

W D Welch

Publications and source records attributed to W D Welch.

31 records · Page 2Linked to original sources

Vulnerability and immune response. An overview.

A summary of the scope and mechanisms of the immune response is given and the hypothesis is put forth that, from the immunologic point of view, infections and neoplasms are the result of deficient recognition or arousal of effective defense systems against a foreign invader. An overview is provided of animal and human natural history, epidemiological, or experimental studies relating psychosocial variables to host defenses against infectious and neoplastic disorders; these studies implicate the involvement and competency of the immune system. An exploratory study is reported examining the relationship of a depressive reaction in 7 human subjects to the immune function of polymorphonuclear neutrophils. The 3 most depressed and/or hostile subjects showed significant inhibition of normal (chemiluminescence) immune response of polymorphonuclear neutrophils as compared to nondepressed healthy subjects. This inhibition of the immune response could not be attributed to the effects of pharmacologic agents, plasma cortisol levels, or differences in circadian rhythm.

Adjustment Disorders↗

Effect of halothane and N2O on the oxidative activity of human neutrophils.

The effect of clinically used concentrations of halothane and N2O on the microbicidal oxidative function of human neutrophils was investigated. Neutrophil oxidative activity was assessed utilizing the method of luminol dependent chemiluminescence (LDCL) by particulate (opsonized zymosn) and nonparticulate (phorbol myristate acetate, [PMA]) stimulated cells. In vivo exposure of neutrophils to 2 and 3% halothane resulted in a 13 and 40% inhibition, respectively of the air-exposed LDCL response with zymosan-activated neutrophils; 1% halothane had no effect. Similar results were seen with PMA-stimulated neutrophils. N2O 80% did not inhibit the LDCL response, and also did not show an additive inhibition when combined with halothane. Although th halothane inhibition of LDCL was reversible (equal to control, no anesthetic, LDCL responses following exposure to air), neutrophils treated with N2O plus halothane and then exposed to air for 30 min showed a significantly higher LDCL response over the control experiments. The inhibition of zymosan- or PMA-stimulated neutrophil LDCL by halothane suggests either a membrane perturbation or a direct inactivation of oxidative enzyme(s) by the anesthetic. This impairment of oxidative activity may partly explain the reduced bacterial killing by neutrophils seen after exposure to halothane.

Adult↗

Reduced hemoglobin as an inhibitor of human polymorphonuclear leukocyte bacterial killing. Role of hemoglobin--oxygen tension in polymorphonuclear function.

The effect of reduced hemoglobin (Hb) on in vitro human polymorphonuclear leukocyte (PMNL) bactericidal activity was investigated. Addition of Hb at physiologic concentrations and oxygen partial pressures (150 mg/ml, 35 torr) to PMNL bactericidal assays significantly inhibited the killing of blood culture isolates of Escherichia and Staphylococcus aureus. Raising the oxygen partial pressure above 35 torr greatly decreased this inhibition. Carboxy hemoglobin, produced by equilibrium of Hg with carbon monoxide, is unable to bind oxygen and did not inhibit PMNL bactericidal killing. We postulate that reduced Hb may scavenge oxygen near the surface of the PMNL therapy preventing utilization of oxygen by PMNL for maximal bactericidal activity.

Bacterial Physiological Phenomena↗

Antacid aspiration in rabbits: a comparison of Mylanta and Bicitra.

The effects of aspiration of (a) 2 ml of Mylanta (a particulate antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (b) 2 ml of half-strength Bicitra (a soluble antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (c) 4 ml of hydrochloric acid (pH 1.5), and (d) 4 ml of normal saline (pH 6.5) on arterial blood gas tensions and lung pathology were compared in anesthetized rabbits. PaO2 decreased similarly in all animals 15 minutes after aspiration, but recovered to normal levels 4 hours after aspiration of saline and 48 hours after aspiration of Bicitra. PaO2 remained depressed after aspiration of Mylanta and HCl. Gross and microscopic evidence of lung injury was most severe in animals that aspirated Mylanta. One animal died 8 hours after aspiration of Mylanta.

Aluminum Hydroxide↗

Halothane reversibly inhibits human neutrophil bacterial killing.

The effect of halothane, at clinically relevant concentrations on the ability of human polymorphonuclear leukocytes (PMNL) to kill the most frequently isolated gram-negative organisms responsible for human bacteremias, Escherichia coli and Klebsiella pneumoniae, was studied. Exposure of PMNL to 0.75 per cent halothane is air significantly inhibited the killing of E. coli (from 81 per cent to 65 per cent) but not K. pneumoniae. At 1.0 per cent halothane there was no killing of E. coli and the killing of K. Pneumoniae was reduced from 98 per cent to 82 per cent. With 1.5 per cent halothane, the killing of K. pneumoniae by PMNL was further reduced to 65 per cent. This inhibition of bacterial killing could be reversed after exposure of halothane-treated PMNL to air. The mechanism of inhibition may be due in part to a deleterious effect of halothane on the oxidative microbicidal activity of human PMNL. Although halothane reversibly inhibits the ability of PMNL to kill bacteremic culture isolates, the degree of susceptibility of bacteria to halothane-treated PMNL may vary.

Bacteriological Techniques↗

Effect of antimicrobial agents on human polymorphonuclear leukocyte microbicidal function.

The effect of 19 antimicrobial agents on human polymorphonuclear leukocyte function was evaluated by chemiluminescence assays, yeast phagocytosis and killing, and lactate dehydrogenase release. Tetracycline and trimethoprim inhibited chemiluminescence and reduced killing at therapeutic concentrations of 2 microgram/ml. Cephalothin inhibited yeast killing at a concentration of 20 microgram/ml, but a significant depression of polymorphonuclear leukocyte chemiluminescence was encountered only at higher levels of 200 microgram/ml. The inhibition shown by these drugs was reversible. None of the other antimicrobial agents tested demonstrated inhibition of chemiluminescence, phagocytosis, or killing at usual clinical serum levels. No antimicrobial agent tested caused release of lactate dehydrogenase from polymorphonuclear leukocytes. The results suggest that therapeutic concentrations of tetracycline, trimethoprim, and cephalothin may inhibit optimal polymorphonuclear leukocyte microbicidal function.

Anti-Infective Agents↗

Unique temperature-sensitive nutritional requirements of bacteremic Escherichia coli isolates.

Of 50 strains of Escherichia coli isolated from blood cultures of bacteremic patients, 14 (28%) were unable to grow on minimal medium at 42 degrees C, compared to only 2 of 50 nonbacteremic strains. In 7 of the 14 bacteremic strains, growth at 42 degrees C was restored by adding nicotinic acid. These unique temperature-sensitive auxotrophic patterns warrant evaluation as a marker correlating with clinical pathogenicity in E. coli.

Culture Media↗

Correlation between measurements of the luminol-dependent chemiluminescence response and bacterial susceptibility to phagocytosis.

The generation of chemiluminescence by phagocytosing leukocytes has been suggested to reflect concomitant microbicidal activity. Correlation between measurements of the chemiluminescence response and susceptibility of bacteria to phagocytosis, however, has not been studied. To examine and compare a range of responses in the two assays, four Escherichia coli serotypes were chosen as test organisms with degrees of susceptibilities to phagocytosis ranging from 0 to 100% bacteria killed. No complete correlation between peak, slope, or curve area integral measurements of the chemiluminescence response and bacterial susceptibility to phagocytosis were found, although a correlation between the two assays could be made after using specific opsonization procedures like the addition of antiserum to selected serotypes. Intrinsic differences present among the bacterial serotypes may be responsible for the observed lack of correlation between the two assays.

Antibodies, Bacterial↗

Relative opsonic and protective activities of antibodies against K1, O and lipid A antigens of Escherichia coli.

The K1 Escherichia coli capsular antigen has been implicated as a virulence factor because of the frequency of isolation of K1 containing strains from certain invasive human infections. In the study of the interaction between K1 strains, normal human polymorphonuclear cells (PMNs) and fresh human serum, we have found varying susceptibility to phagocytosis and killing; thus, the in vitro opsonophagocytic and in vivo protective role of K1, somatic O and core glycolipid antibodies remain unclear. We have therefore examined strains of E. coli with defined susceptibility to phagocytosis by normal PMNs and sera and compared the effect of K1, somatic O and lipid A antibodies in opsonophagocytic tests and mouse protection experiments. K1 E. coli strains demonstrating relative resistance to phagocytosis and killing were effectively opsonized only with specific K1 capsular antisera. Similarly, K1 capsular antisera, but not anti-O or lipid A antisera, also provided protection in mice challenged with a LD100 of K1 E. coli that were "resistant" to phagocytosis. The ability of purified capsular antigens from Neisseria meningitidis group B and K1 "resistant" E. coli to inhibit the phagocytosis of a "sensitive" non-K1 and a K1 E. coli strain of "intermediate" susceptibility to opsonophagocytosis was also investigated. Purified K1 and group B capsular antigens were able to block specific capsular-antibody mediated opsonophagocytosis, yet these capsular antigens failed to inhibit the phagocytosis of non-K1 "sensitive" or K1 "intermediate" E. coli. These studies suggest that K1 antibodies are obligatory for the in vitro and in vivo opsonophagocytosis of "resistant" K1 E. coli and that the K1 antigen must remain in situ on the bacterial surface to exert an anti-phagocytic effect.

Animals↗

Quantitative bacteriology of intraoperative wound tissue in contaminated surgery.

This study was designed to evaluate the predictive value of quantitative bacteriology of intraoperative wound tissue in identifying the patient likely to develop wound infection, as well as its subsequent flora. Forty-one patients undergoing contaminated cancer surgery of the head and neck were studied. Intraoperatively, a sample of wound tissue was cultured and anaerobic and aerobic bacterial isolates quantitated. The wound infection rate was 22% (9 of 41). There was no significant correlation between intraoperative tissue bacterial density and subsequent wound infection, or contaminating and infecting bacteria.

Bacteria↗