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Biomedical subjects

F C Pearson

Publications and source records attributed to F C Pearson.

At least 37 records · Page 2Linked to original sources

Detection of endotoxin in the plasma of patients with gram-negative bacterial sepsis by the Limulus amoebocyte lysate assay.

A total of 120 Limulus amoebocyte lysate (LAL) determinations were made on plasma obtained from normal, healthy human blood donors. Results demonstrated a mean endotoxin level in blood of 0.02 to 1.57 pg/ml. The amount of Escherichia coli endotoxin added to human plasma samples can be quantitated by both nephelometry and turbidimetry. Endotoxin-spiked samples were shown to be significantly different from unspiked samples. When plasma samples were collected from 45 patients hospitalized at three centers, a strong association was demonstrated between a positive Limulus amoebocyte lysate assay and a septic condition. Sensitivity, specificity, and false-positive and false-negative rates for the Limulus amoebocyte lysate assay as a diagnostic test for gram-negative bacteremia were estimated.

Endotoxins↗

Dialyzer hypersensitivity syndrome: possible role of allergy to ethylene oxide. Report of 4 cases and review of the literature.

The occurrence of hypersensitivity reactions in patients dialyzed on artificial kidneys is well recognized in the dialysis community, but has received little attention in the medical literature. We report 4 cases of dialyzer hypersensitivity reactions and review the previously reported cases. Dialyzer hypersensitivity syndrome presents as an acute anaphylactoid reaction, the symptoms of which may range from mild to life threatening in severity. The cause of this syndrome is unknown, but affected patients appear to have a high incidence of positive radioallergosorbent tests to a conjugate of human serum albumin and ethylene oxide, suggesting that ethylene oxide, a substance used to dry sterilize artificial kidneys, may be an offending allergen.

Adult↗

Comparison of chemical analyses of hollow-fiber dialyzer extracts.

Hollow-fiber hemodialyzers containing cellulose-based membranes have been shown to produce positive results with the Limulus amebocyte lysate (LAL) test. This study was undertaken to determine whether endotoxin was causing the reaction. Rinses from 45 parallel-plate and hollow-fiber dialyzers from eight different manufacturers were tested using three lysates and four LAL methods. In addition, four in vitro cellular methods--human leukocytic pyrogen, lymphocytic activating factor, peritoneal macrophage, and arginase release--were used to evaluate endotoxin activity. The substance causing the reaction was identified using chromatographic methods. Results indicate that the LAL-reactive material is cellulose derived and is not pyrogenic.

Arginase↗

Immunologic studies of hollow-fiber dialyzer extracts.

Testing failed to detect free isocyanates in dialyzer rinses or significant levels of immunoglobulin E antibodies to isocyanate-protein conjugates in the serum of individuals reacting during hemodialysis with dialyzers containing Cuprophan membranes. Extended immunization of rabbits with Limulus lysate-reactive material from dialyzer rinses demonstrated antigenic activity of the rinse that appears to originate from cotton linters used in hollow-fiber membranes. The possibility that an immunologic response to these antigens may be a mechanism in adverse reactions to hemodialysis is discussed.

Antigens↗

Allergy to ethylene oxide in chronic hemodialysis patients.

Almost a decade ago, a single chronic hemodialysis patient in Hamilton, Ontario, Canada, who was experiencing recurrent acute reactions during hemodialysis was found to have become allergic to ethylene oxide gas (EO). This observation recently provided a stimulus to examine the possibility that others exhibiting acute allergic-type reactions during hemodialysis might be similarly sensitized. Serum was obtained from 27 reacting patients and tested in a radioallergosorbent test (RAST) for antibodies to EO. The test was positive for 22 of these sera. EO-related specificity of the antibodies was confirmed. However, EO sensitization was not found in other hemodialysis patients with isolated eosinophilia. In a survey of the current Hamilton chronic hemodialysis population for EO-related antibodies, 9% had a positive allergy skin test and 12% had a positive RAST. The sensitized individuals had no distinctive symptoms. The lesser sensitivity of the skin test contrasts with usual findings in allergic individuals; however, the use of histamine and codeine in chronic hemodialysis and peritoneal dialysis patients might well explain a reduced sensitivity of the EO-related allergy skin test. Chronic peritoneal dialysis could not be invoked as a source of sensitization. None of these patients had a positive skin test or RAST for EO-related antibodies that could be attributed to peritoneal dialysis.

Antibodies↗

Characterization of Limulus amoebocyte lysate-reactive material from hollow-fiber dialyzers.

Hollow-fiber hemodialyzers containing cellulose-based membranes have been shown to produce positive results with the Limulus amoebocyte lysate test. This study was undertaken to determine whether endotoxin was causing the reaction. Rinses from 45 parallel-plate and hollow-fiber dialyzers from eight different manufacturers were tested before and after treatment with cellulase, using three lysates and four Limulus amoebocyte lysate methods. In addition, four in vitro cellular methods--human leukocytic pyrogen, lymphocytic activating factor, peritoneal macrophage, and arginase release--were used to evaluate endotoxin activity. The substance causing the reaction was identified by chromatographic methods. Results indicate that the Limulus amoebocyte lysate reactive material is cellulose derived and not pyrogenic.

Cellulose↗

Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities.

We examined the relationship between the fine structure of lipid A and the toxicity of endotoxin or lipopolysaccharides as measured by the Limulus amebocyte lysate (LAL), rabbit pyrogenicity, chicken embryo lethal dose, and dermal Shwartzman reaction tests. Lipid A and lipid A-like compounds obtained from deep-rough mutants of Salmonella spp. and Escherichia coli had a wide range of structural variations. These compounds included native lipopolysaccharides, diphosphoryl and monophosphoryl lipid A's, and lipid X (a monosaccharide). The LAL test was positive for all lipids tested with lysates from Travenol Laboratories and from Associates of Cape Cod (2.9 X 10(3) to 2.6 X 10(7) endotoxin units per mg), except for O-deacylated and dephosphorylated lipid X, which were negative. The Mallinckrodt lysate gave negative tests for lipid X. In the rabbit pyrogenicity and chicken embryo lethal dose tests, only native lipopolysaccharide and diphosphoryl lipid A's were judged toxic. The Shwartzman reaction was positive for a specific purified diphosphoryl lipid A (thin-layer chromatography-3 fraction) but negative for the purified monophosphoryl lipid A (also a thin-layer chromatography-3 fraction). These results show that the LAL test is not a valid measure of all parameters of toxicity of a lipid A or lipid A-like compound and can yield false-positive results. However, these findings are not in conflict with the widespread use of the LAL assay for pyrogens in the pharmaceutical industry since a good correlation exists between LAL results and pyrogenicity when undegraded endotoxin is evaluated in parallel assays.

Animals↗

Relative potencies of four reference endotoxin standards as measured by the Limulus amoebocyte lysate and USP rabbit pyrogen tests.

Four commonly used reference endotoxin standards, Escherichia coli O113:H10:K0, E. coli O55:B5, Salmonella abortusequi, and Shigella dysenteriae were compared by the USP rabbit pyrogen and the Limulus amoebocyte lysate tests. By the rabbit pyrogen test, S. abortus equi was identified as the most potent endotoxin, followed closely by E. coli O113:H10:K0 and E. coli O55:B5.

Animals↗

The Limulus amebocyte lysate endotoxin assay: current status.

Research conducted during this decade has clearly established the Limulus amebocyte lysate (LAL) test as the most sensitive assay for bacterial endotoxin. In addition, the assay is easily performed, relatively inexpensive, specific for endotoxin, and can be used to test materials that are toxic to rabbits employed in the rabbit pyrogen test. The LAL test has been used in the diagnosis of meningitis, urinary infection, mastitis, and endotoxemia. Other broad applications of the test include quality assurance of parenteral solutions and medical devices as well as the microbial quality of food and water. A review of recent developments in LAL testing is presented and experimental applications of the assay are discussed.

Animals↗