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Biomedical subjects

E J Ziegler

Publications and source records attributed to E J Ziegler.

At least 19 recordsLinked to original sources
PubMed1997

Amebic meningoencephalitis caused by Balamuthia mandrillaris: case report and review.

Balamuthia mandrillaris, formerly referred to as a leptomyxid ameba, is a free-living ameba that has recently been identified as a cause of meningoencephalitis. Previously, only two genera, Naegleria and Acanthamoeba, were recognized as causes of central nervous system (CNS) infections in humans. In contrast to Naegleria, Balamuthia causes a subacute-to-chronic infection of the CNS. Distinct from Acanthamoeba, which appears to favor the immunocompromised host, Balamuthia is capable of infecting both healthy and immunosuppressed hosts. Retrospective analyses as well as an accumulation of newly identified cases have demonstrated that this ameba is an increasingly important pathogen to recognize. We report the isolation, histopathologic features, and confirmation by indirect immunofluorescence of B. mandrillaris in a case of fatal amebic meningoencephalitis.

Adult↗
PubMed1997

Influence of alterations in foregoing life-sustaining treatment practices on a clinical sepsis trial. The HA-1A Sepsis Study Group.

OBJECTIVES: To evaluate the timing of foregoing life-sustaining treatments in patients enrolled in a sepsis trial and to determine their influence on patient outcome and trial results. DESIGN: Subset of patients in a prospective, randomized, double-blind, placebo-controlled study. SETTING: Twenty-three academic medical centers. PATIENTS: Enrolled patients who had life-sustaining therapies withheld or withdrawn. MEASUREMENTS AND MAIN RESULTS: The number of patients, types of disorders and interventions, reasons, and timing of withholding and withdrawing life-sustaining treatments and their effect on mortality and trial results were assessed. Foregoing of life-sustaining therapies took place in 117 (22%) of 543 patients and occurred within 72 hrs of study drug administration in 38 (32%) patients. Withholding treatment (60%) was more common than withdrawing treatment (40%), but withdrawing treatment was more frequent (51%) than withholding treatment (20%) in the first 72 hrs of the trial (p < .01). Sixty-one (52%) patients had severe underlying disorders with a poor prognosis. The hospital mortality rate was 94% (of the 117 patients). The mean time (SEM) from withholding or withdrawing of treatment until death was 2.83 +/- 0.57 and 0.32 +/- 0.13 days, respectively (p < .001). Patients who had therapies foregone in the first 24, 48, and 72 hrs after receiving the study drug had higher mortality rates in the first 72 hrs (p < .01). CONCLUSIONS: A substantial number of patients enrolled in a sepsis trial had severe underlying diseases and had foregoing of therapies early in the course of the trial, which led to a higher early mortality rate. Enrollment of patients in clinical trials with severe underlying disorders with a high likelihood of having therapies foregone may bias the potential for showing the efficacy of new therapeutic modalities.

Antibodies, Monoclonal↗
PubMed1992

HA-1A. A human monoclonal antibody for the treatment of gram-negative sepsis.

HA-1A is a human monoclonal IgM antibody that binds to endotoxin. The results of the clinical trials of HA-1A demonstrate that HA-1A reduces mortality among patients with sepsis and gram-negative bacteremia. Secondary endpoints, including resolution of organ failure, discharge from intensive care unit, and discharge from the hospital, support the beneficial effects of the antibody. The antibody is well tolerated with rare side effects, including hypotension and urticarial rash. No anti-HA-1A antibodies have been detected.

Antibodies, Monoclonal↗
PubMed1991

Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group.

BACKGROUND: HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. METHODS: To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected. CONCLUSIONS: HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Antibodies, Monoclonal↗
PubMed1988

Inhibition of lipopolysaccharide activation of 7OZ/3 cells by anti-lipopolysaccharide antibodies.

We have investigated the ability of mAb against LPS to inhibit LPS-induced activation of 7OZ/3 pre-B cells. The fine specificity and relative affinity of these mAb for lipid A and LPS were also determined. We found that antibodies inhibited only the activity of glycolipids which they bound with relatively high affinity. However, two high affinity antibodies binding to non-lipid A epitopes did not block cellular activation. Some, but not all, relatively high affinity antibodies binding to the lipid A region of the LPS molecule inhibited biologic activity. The inhibitory antibodies bound to at least two distinct epitopes within the lipid A region. These data suggest that LPS interacts with 7OZ/3 cells in a highly specific fashion.

Animals↗
PubMed1988

Antiserum to endotoxin in hemorrhagic shock.

Antiserum to Escherichia coli J5, a mutant endotoxin (LPS) which contains only core determinants, has proven effective in reducing mortality from endotoxic shock due to a wide variety of gram-negative bacteria. Twenty New Zealand white rabbits with coliforms in the gut were subjected to hemorrhagic shock of 36 mm Hg for 3 hr. Treated rabbits were resuscitated with 15 cc of rabbit J5 antiserum (hemagglutinating antibody titer against J5 lipopolysaccharide of 1:1024), remaining shed blood, and lactated Ringer's to achieve a mean arterial blood pressure (MABP) within 20% of baseline. The control group was similarly resuscitated but received 15 cc normal rabbit serum (titer 1:2). Catheters were removed and rabbits were returned to their cages until death or 5 days of survival. Hemodynamic parameters (heart rate, MABP, cardiac output, and total peripheral resistance) did not differ significantly between groups. However, six treated rabbits survived 5 days (60%) and no control rabbit lived past the third postexperimental day (P less than 0.019). Our data suggest that systemic endotoxemia may contribute to morbidity and mortality in severe hemorrhagic shock.

Alanine Transaminase↗
PubMed1987

Demonstration of cross-reactive antibodies to smooth gram-negative bacteria in antiserum to Escherichia coli J5.

We investigated the discrepancy between the broad cross-protection against gram-negative infections afforded by antiserum to Escherichia coli J5 and its apparently narrow cross-reactivity in vitro. Rabbits immunized with J5 bacteria produced antibodies to both the J5 lipopolysaccharide (LPS; titer by ELISA, 1:60,000) and LPS from the Re mutant of Salmonella minnesota (i.e., to the ketodeoxyoctonate [KDO] and lipid A determinants; titer, 1:3,200). In highly diluted antiserum, titers of antibody to J5 LPS were reduced by 28%-41% after adsorption with seven strains of smooth gram-negative bacteria and by only 4% after adsorption with the Re mutant. Smooth gram-negative bacteria adsorbed virtually all antibody to Re LPS. Therefore, rabbit antiserum to J5 contains type-specific antibodies to core determinants distal to KDO that can obscure highly cross-reactive antibodies to lipid A-KDO in vitro. Cross-reactive antibodies are demonstrable by adsorption with whole bacteria at limiting concentrations of antibody.

Adsorption↗
PubMed1986

Analysis of the fine specificity and cross-reactivity of monoclonal anti-lipid A antibodies.

We have investigated the fine specificity of anti-lipid A antibodies to identify conserved lipid A antigens. Because lipid A derived from many different Gram-negative bacteria has similar biologic activities, the conserved regions may be of particular importance for the immunostimulatory and toxic properties of lipid A. We found that five of nine antibodies bound to a wide variety of Gram-negative bacteria. All these widely cross-reactive antibodies bound to the same antigenic site within lipid A. Polymyxin B, an inhibitor of lipid A activity, bound to this site as well. The widely cross-reactive antibodies bound to native and base-hydrolyzed lipid A equally well, and also bound to the monosaccharide precursor lipid X. The less cross-reactive antibodies recognized base-hydrolyzed lipid A poorly, and did not recognize lipid X at all. Other investigators have shown that lipid X has some of the activities of lipid A in vitro and can inhibit the lethal toxicity of LPS in vivo. On the basis of this study, we suggest that lipid X contains a conserved lipid A epitope as well.

Antibodies, Monoclonal↗
PubMed1985

Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid.

The prophylactic effect of antibody to endotoxin core glycolipid was studied in surgical patients at high risk of gram-negative infection. At randomisation (on admission to intensive care unit), every 5 days thereafter, and at onset of septic shock, patients received plasma taken from donors before (control) or after immunisation with Escherichia coli J5, a mutant with only core determinants in its endotoxin. Gram-negative shock occurred in 15 of 136 controls and 6 of 126 J5 antibody recipients and related deaths in 9 of 136 and 2 of 126, respectively. J5 antibody was most effective in abdominal surgery patients, in whom shock occurred in 13 of 83 controls and 2 of 71 antibody recipients. Although antibody prophylaxis did not lower the infection rate, it prevented the serious consequences of gram-negative infections and thus improved the overall prognosis.

Bacterial Infections↗
PubMed1984

An immunoprotective monoclonal antibody to lipopolysaccharide.

The ability of antisera against lipopolysaccharide (LPS) raised by immunization with gram-negative bacteria to prevent LPS toxicity and death from gram-negative bacteremia is well established. To demonstrate conclusively that the protective antibody is specific for LPS, we tested an anti-LPS monoclonal antibody (mAb) in three animal models. 7G is an IgG3 mAb directed against an oligosaccharide side chain determinant of LPS from E. coli 0111:B4. This anti-LPS mAb increased the LD50 of 0111:B4 LPS in mice and protected rabbits against the dermal Shwartzman reaction elicited by 0111:B4 LPS. 7G mAb also protected mice against lethal infection with mucin-enhanced E. coli 0111:B4. Pretreatment with 250 micrograms of 7G increased the LD50 by more than 1.5 logs. These studies prove that oligosaccharide side chain-specific antibody to LPS confers protection against LPS toxicity in vivo and against experimental gram-negative infection. In addition, these studies suggest the potential of anti-LPS monoclonal antibody as therapy for gram-negative infection.

Animals↗
PubMed1983

Ineffectiveness of single-dose human antiserum to core glycolipid (E. coli J5) for prophylaxis of bacteremic, gram-negative infections in patients with prolonged neutropenia.

It has been recently established that serum from human volunteers immunized with E. coli J5 vaccine prevents death of patients with gram-negative shock. The present study addressed the question whether the prophylactic administration of a similar amount of J5 antiserum could protect neutropenic patients from acquiring gram-negative infections. One hundred patients, the majority of which had acute non-lymphoblastic (63%) and lymphoblastic (29%) leukemia, presented 109 episodes of neutropenia. Sixty of the 100 patients underwent bone marrow transplantation. All patients were given one unit of either pre-immune (control) or J5 antiserum serum from volunteers at the onset of neutropenia. When compared to control serum, J5 antiserum given prophylactically did not reduce the number of febrile days, the number of gram-negative bacteremic episodes, or death from these infections. This inability to demonstrate a beneficial effect of prophylaxis with a single unit of J5 antiserum in prolonged neutropenia may have several explanations that are discussed.

Adolescent↗
PubMed1982

Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli.

In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.

Adolescent↗