Reduced tumor necrosis factor alpha production in lipopolysaccharide-treated whole blood from patients in the intensive care unit.

OBJECTIVE: To determine the cytokine response to lipopolysaccharide in patients in the intensive care unit. PATIENTS: Patients in a mixed medical/surgical intensive care unit with fever and a de novo clinical dysfunction of at least one organ system. METHODS: Whole blood from patients and from laboratory controls was stimulated with 8 ng/mL of lipopolysaccharide (Escherichia coli 0111:B4) at 37 degrees C, and tumor necrosis factor alpha (TNF-alpha) was measured using enzyme linked immunosorbent assay at 4, 8, and 24 hours. The same subjects' purified monocytes were cultured with 8 ng/mL of lipopolysaccharide in the presence of autologous or pooled control plasma or cocultured with purified autologous polymorphonuclear leukocytes at a polymorphonuclear leukocyte-monocyte ratio of 10:1, and TNF-alpha was measured at 24 hours using the enzyme linked immunosorbent assay. RESULTS: We detected high (n = 5) and low (n = 5) TNF-alpha responders in whole blood producing a mean (+/- SEM) of 27.2 +/- 6.3 pg/mL per 1000 monocytes vs 0.0 +/- 2.4 pg/mL per 1000 monocytes, respectively (controls, 58.0 +/- 13.0 pg/mL per 1000 monocytes). The kinetics of TNF-alpha production in both groups were comparable. Purified monocytes from both groups of patients cultured with lipopolysaccharide alone produced equivalent TNF-alpha values (42.4 +/- 10.5 vs 40.8 +/- 12.5 pg/mL per 1000 monocytes). Assayable TNF-alpha was not different with autologous vs control serum but was markedly diminished by the presence of polymorphonuclear leukocytes in patients as well as in controls; the two groups of patients did not differ in this polymorphonuclear leukocyte effect. CONCLUSION: Lipopolysaccharide stimulation of monocytes in the whole blood results in marked variation of TNF-alpha production. This phenomenon may account for the variable septic response to infection in patients in the intensive care unit.

A donor-derived asialo-GM1+ cell induces depression of B-cell genesis during systemic graft-versus-host disease.

The nature of the effector cell(s) responsible for the depression of B-cell genesis in the bone marrow of mice undergoing systemic graft-versus-host disease (GVHD) has been examined. Donor C57BL/6 (B6) mice were treated in vivo with either a single injection of anti-asialo GM1 antibody (anti-ASGM1) to eliminate naturally occurring (endogenous) ASGM1+ cells or B6xAF1 (B6AF1) lymphoid cells followed by anti-ASGM1 to eliminate both endogenous and "induced" ASGM1+ cells. Lymphoid cells from donor mice after the elimination of endogenous ASGM1+ cells produced severe GVHD and concomitant depression of B-cell genesis when injected into B6AF1 recipients. In contrast, cells from donors depleted of both the endogenous and inducible ASGM1+ populations did not cause GVHD or depletion of B lineage cells in B6AF1 recipients but did depress B-cell genesis in B6C3F1 mice. The "induced" ASGM1+ cells were Thy 1+, but their elimination did not significantly alter either overall T-cell function or specific cytotoxic T-cell (CTL) reactivity against the sensitizing (B6AF1) strain. The results suggest that the effector cell responsible for the depression of B-cell genesis during systemic GVHD can be induced to express ASGM1, is strain-specific and Thy 1+; but is not a conventional CTL.

A physician-centred intervention to shorten hospital stay: a pilot study.

BACKGROUND: Studies of length of stay (LOS) in hospital usually focus on physician-independent factors. In this study, the authors identified physician-dependent factors and tested an intervention aimed at them to determine its effect on LOS. METHODS: A prospective comparison of LOS on 2 general medical wards in a tertiary care teaching hospital before and after the intervention. The pre-intervention (control) period and the intervention period were each 4 weeks. The intervention consisted of a checklist for planning management and discharge. RESULTS: Overall, the mean LOS was shorter during the intervention period than during the control period, but the difference was not statistically significant (12.0 and 14.4 days respectively, p = 0.13). The difference was significant on ward A (11.0 v. 14.7 days respectively, p = 0.02) but not on ward B (13.0 and 14.0 days respectively, p = 0.90). INTERPRETATION: An intervention at the level of the admitting physician may help to shorten LOS on a general medical ward.