Anti-Lipopolysaccharide Immunotherapy in Management of Septic Shock of Obstetric and Gynaecological Origin

Lachman, E; Pitsoe, S. B.; Gaffin, S L

doi:10.1016/s0140-6736(84)92324-9

Cited by 118 publications

(24 citation statements)

References 12 publications

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“…Moreover, antilipopolysaccharide did reduce the recovery period of survivors in the treated group compared with the placebo group, as has been seen in other similar studies. 6 These results indicate the need for further similar studies in neonatal septicaemia, using antilipopolysaccharide antibodies given intravenously. These are currently being prepared at the Natal Institute of Immunology.…”

Section: Discussionmentioning

confidence: 93%

Septicaemic low birthweight neonates treated with human antibodies to endotoxin.

Adhikari¹,

Coovadia²,

Gaffin³

et al. 1985

Archives of Disease in Childhood

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positive mouth cultures (31 C albicans, five C parapsilosis) and in 25 of these dummy cultures also grew candida (20 C albicans, five C parapsilosis). Only eight children without dummies had candida positive mouth cultures (using Yates' correction: x2=7.5 P<0*01). Only four of the children using dummies who had negative mouth swabs had positive dummy cultures.Ten children who used dummies had mouth swabs which were positive for candida on more than two occasions (repeatedly positive) and dummy cultures were also repeatedly positive for all except one of these children. No child who did not suck a dummy had repeatedly positive mouth swabs. DiscussionOur study suggests that dummy sucking in early childhood is associated with greater prevalence of thrush and with more frequent and more persistent mouth colonisation by candida. Where candida is present in the mouth, it is usually cultured from the dummy also. Objects placed in the mouth are likely to reflect oral flora but we were surprised that dummy sucking predisposed to oral colonisation and infection with candida.Candida is a common mouth commensal and its prevalence in our study is no more than that found in other studies.2 3 Positive cultures may reflect the density as well as the prevalence of candida colonisation. Thus our finding of a greater prevalence of Candida in the mouths of children with dummies may indicate either an absolute increase in prevalence of colonisation or, possibly, denser colonisation. Low density colonisation may explain why the correlation between dummy and mouth cultures in children who used dummies was not total. The finding of clinical thrush in only a minority of infants with positive mouth swabs suggests that gastrointestinal contamination from dummies should be considered in infants with candida napkin rash when there is no clinical evidence for oral thrush.Foreign bodies in the mouth such as dummies and false teeth4 predispose to candidal infection.Abramovits5 described a child in whom oral thrush did not respond to treatment until the child's dummy was confiscated. Our study also suggests that persistent oral and dummy infection go together. The dummy's role as pacifier may be more important to mothers than its aesthetic and health disadvantages. If this is the case, mothers need advice on effective treatment for infected dummies as well as for their children's thrush.

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Section: Discussionmentioning

confidence: 93%

Septicaemic low birthweight neonates treated with human antibodies to endotoxin.

Adhikari¹,

Coovadia²,

Gaffin³

et al. 1985

Archives of Disease in Childhood

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“…For a blood bank collecting 200 units/day this yield provides 7% x 200/day x 5 days/week x 50 weeks = 3,500 anti-LPS-rich plasma units/ year. Our experience is that the antibodies in approximately 6 units of such plasma are therapeutic for severe gram-negative septic shock in humans [11]. Therefore 580 adult doses can be prepared per year.…”

Section: Mouse Protectionmentioning

confidence: 99%

“…We partially solved this problem by recognising that significant numbers of blood units donated to a blood bank contain raised levels of anti-LPS antibodies [6], de veloping an ELISA procedure to rapidly screen donated blood, retaining and pooling those units with high concentrations of anti-LPS [9]. Such human anti-LPS was protec tive in animals against septic abortion [10] and in humans against septic shock [7,11], We report here on the properties of a gamma globulin (lot LG-1) prepared from such high titre human plasma.…”

Section: Introductionmentioning

confidence: 99%

Properties of Human Anti-Lipopolysaccharide Gamma Globulin: Specificity and Protective Effects

Gaffin¹,

Badsha²,

Vorster³

1985

Vox Sanguinis

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Blood donated to the Natal Blood Transfusion Service was screened by an enzyme-linked immunosorbent assay (ELISA) for anti-lipopolysaccharide (anti-LPS) antibodies. Plasma units with high concentrations (>40µg/ml) of anti-LPS IgG were pooled and fractionated to obtain a gamma globulin (lot LG-1). The binding of LG-1 antibodies to LPS prepared from 14 bacterial species and strains was found to be the highest to LPS from Shigella flexneri, Salmonella abortus equi and Salmonella typhimurium and intermediate with Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enteritidis and Escherichia coli 026 :B6. Differential absorption experiments showed that LG-1 contained a mixture of specific and cross-reacting antibodies. A large proportion of antibodies binding to Sh. flexneri LPS were mainly specific, while those binding to S. typhimurium and the other Salmonella species tested were largely cross-reactive. There was little correlation between the spectrum of activity of the LG-1 antibodies and the incidence of gram-negative bacteria in blood cultures taken from hospital patients in an area covered by the Transfusion Service. Mice treated with LG-1 prior to inoculation with P. aeruginosa were significantly protected against morbidity and mortality compared to controls.

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“…There have been three approaches to the development of passive immunization to endotoxin: (i) use of pooled blood bank plasma rich in anti-LPS (6,13,14), (ii) use of pooled immunoglobulin from volunteers immunized with an E. coli J5 boiled cell vaccine (2,19), and (iii) use of mouse (8,9) or human (5,12,18) monoclonal antibodies to E. coli J5.…”

mentioning

confidence: 99%

Phase I study of antilipopolysaccharide human monoclonal antibody MAB-T88

Daifuku¹,

Haenftling²,

Young³

et al. 1992

Antimicrob Agents Chemother

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Monoclonal antibody MAB-T88 is a human monoclonal immunoglobulin M antibody directed at the lipopolysaccharide of gram-negative bacteria. In this study, nine patients who were expected to become neutropenic from antineoplastic chemotherapy received an infusion of MAB-T88, three patients at each of three doses: 1, 4, and 8 mg/kg of body weight. MAB-T88 was shown to be safe, with an effective half-life in plasma of 25.4 h, and no patient developed immunoglobulin G antibody to MAB-T88.Bacterial endotoxins play a key role in septic shock by increasing the levels of interleukin-1 and tumor necrosis factor and by the humoral activation of at least four systems involved in the physiologic alterations that occur in patients with septic shock, i.e., complement, coagulation, fibrinolysis, and bradykinin (4,17 2,4,6, 24, 48, and 96 h after the start of the infusion; and on study day 7. Sera were obtained for analysis of the immune response to MAB-T88 before treatment and on study days 3, 7, 14, and 28.Human MAB-T88 was developed from a mouse-human heteromyeloma, as described previously (15). Briefly, human lymphocytes from a blood bank donor expressing 6-thioguanine resistance were fused with a mouse myeloma cell. The human-mouse nonsecreting hybrid (F3B6) was selected for with 6-thioguanine and ouabain, and B cells from a human spleen were fused with the human-mouse hybrid partner. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of MAB-T88 for pharmacokinetic analysis. A microdilution plate was coated with a mouse anti-MAB-T88 idiotype monoclonal antibody (2H6) at 5 ,ug/ml, incubated overnight, and washed in the morning. Monoclonal antibody 2H6 is highly specific for MAB-T88. Two hundred microliters of blocking buffer was added to each well, the plate was incubated for 2 h at ambient temperature, and the plate was washed and used immediately. The serum sample was diluted in phosphate-buffered saline to fall between 0.25 and 5.0 ng/ml for the assay. One hundred microliters of standards, controls, and samples was added to the appropriate wells of a microtiter plate. The

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Anti-Lipopolysaccharide Immunotherapy in Management of Septic Shock of Obstetric and Gynaecological Origin

Cited by 118 publications

References 12 publications

Septicaemic low birthweight neonates treated with human antibodies to endotoxin.

Septicaemic low birthweight neonates treated with human antibodies to endotoxin.

Properties of Human Anti-Lipopolysaccharide Gamma Globulin: Specificity and Protective Effects

Phase I study of antilipopolysaccharide human monoclonal antibody MAB-T88

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