Background. The expression of neutrophil integrin CD11b is up-regulated after cardiopulmonary bypass (CPB) and is the neutrophil adhesive molecule of most importance in neutrophil–endothelial ...adherence. This neutrophil–endothelial adherence is responsible for post-CPB neutrophil-induced reperfusion injury. Low-dose aprotinin protocols inhibit the CPB-induced neutrophil CD11b up-regulation. This investigation was undertaken to evaluate the effects of pump prime only aprotinin (280 mg) on the CPB-induced up-regulation of this neutrophil integrin.
Methods. Twenty-two patients scheduled for elective myocardial revascularization were randomized into two groups: (1) control (n = 12), or (2) pump prime only aprotinin (280 mg) (n = 10). Neutrophils were isolated at baseline, 50 minutes of CPB, and 30 minutes after CPB and neutrophil CD11b expression was measured.
Results. The control group demonstrated a significant (
p < 0.05) increase in neutrophil CD11b immunofluorescent staining at 50 minutes of CPB and at 30 minutes after CPB when compared to same group baseline and to the pump prime only aprotinin group at similar time intervals.
Conclusions. These results indicate that pump prime only aprotinin modulates the CPB-induced up-regulation of neutrophil CD11b integrin, an important indicator of the systemic inflammatory response to CPB. In addition to blunting of the CPB-induced up-regulation of this neutrophil integrin expression, this pump prime only dose of aprotinin is also reported to be effective at reducing post-CPB bleeding and transfusion requirements. This salutary effect of pump prime only aprotinin suggests that such low-dose regimens can be both therapeutically effective and cost effective.
Cardiopulmonary bypass (CPB) is characterized by translocation of intestinal endotoxin and subsequent endogenous production of the pro-inflammatory cytokine interleukin-6 (IL-6). Plasma lipid ...fractions, especially high density lipoproteins, bind and neutralize endotoxin and, therefore, inhibit endotoxin-induced macrophage cytokine production, including IL-6. Increased IL-6 plasma levels have been implicated in adverse consequences associated with CPB. Previous studies demonstrated large interpatient variability in IL-6 plasma levels after CPB. The purpose of this study was to evaluate the relationship between plasma lipid concentrations and the concentrations of IL-6 following CPB in humans.
In a prospective study, a group of 15 patients selected to exclude variables known to influence post-CPB plasma levels of IL-6 (preoperative left ventricular ejection fraction > 45%, similar durations of aortic cross clamping and total CPB time, similar temperature control during CPB, and avoidance of platelet transfusion and shed mediastinal blood re-infusion), IL-6 was measured at baseline, one and 24 hr post-CPB.
Interleukin-6 plasma concentrations (mean +/- SD) increased at one (142 +/- 89 pg.ml-1, P < 0.05) and 24 (129 +/- 82 pg.ml-1, P < 0.05) hr post-CPB compared with baseline (1.5 +/- 1 pg.ml-1) concentrations. An inverse correlation was found between IL-6 plasma concentrations at one hour post-CPB and plasma cholesterol concentrations (r = -0.592, P = 0.02), high density lipoprotein (r = -0.595, P = 0.02), and low density lipoprotein (r = -0.656, P = 0.01).
These results suggest that plasma lipids attenuate the production of IL-6 during CPB and may partly explain the variability of interpatient levels of IL-6 reported post-CPB by others.
Objective: This investigation examines the hypothesis that the antiplatelet effect of abciximab and its reversal can be monitored using the Hemodyne (Hemodyne, Inc, Midlothian, VA) analyzer and ...modified Thrombelastograph (Haemoscope, Skokie, IL).
Design: In vitro dose-response and reversal study.
Setting: Anesthesia Research (Dallas, TX) and Special Studies Coagulation Laboratories (Washington, DC).
Participants: Nine healthy volunteers.
Interventions: The addition of increasing concentrations of abciximab, 0 to 10 μg/mL, and purified fibrinogen, 50 to 400 mg/dL. The reversal of abciximab, 4 μg/mL, with the addition of fresh platelet-rich plasma (PRP) sufficient to increase the platelet concentration by approximately 10%.
Measurements and Main Results: Platelet aggregation and platelet contractile force using the Hemodyne analyzer were used as platelet-specific measurements. The Thrombelastograph maximum amplitude (MA) for platelets (MAPLT) was calculated by subtracting the MA from a platelet-poor plasma (PPP) sample (MAppp) determined in one thromboelastography well from that of whole-blood MA (MAWB) run simultaneously in the second thromboelastography well. The addition of abciximab, 0 to 10 μg/mL, resulted in significant concentration-dependent reductions in platelet aggregation (p < 0.001), platelet contractile force (p < 0.001), and MAPLT (p < 0.001). Platelet contractile force (p < 0.03) and MAPLT (p < 0.05) were significantly more responsive than MAWB to the effect of abciximab, 4 μg/mL, and its reversal with the addition of fresh PRP. Purified fibrinogen concentration directly correlated with thromboelastography MA (rs = 0.97; p < 0.001), yet had no effect on platelet contractile force. The addition of abciximab had no measurable influence on the MAPPP.
Conclusion: This in vitro study suggests that the Hemodyne analyzer and modified Thrombelastograph might be clinically useful methods to monitor the platelet inhibitory effects of agents such as abciximab.
We have previously shown that IFN-β inhibits hepatitis B virus (HBV) replication by noncytolytic mechanisms that either destabilize pregenomic (pg)RNA-containing capsids or prevent their assembly. ...Using immortalized murine hepatocyte cell lines stably transfected with a doxycycline (dox)-inducible HBV replication system, we now show that replication-competent pgRNA-containing capsids are not produced when the cells are pretreated with IFN-β before HBV expression is induced with dox. Furthermore, the turnover rate of preformed HBV RNA-containing capsids is not changed in the presence of IFN-β or IFN-γ under conditions in which further pgRNA synthesis is inhibited by dox removal. In summary, these results demonstrate that types 1 and 2 IFN activate hepatocellular mechanism(s) that prevent the formation of replication-competent HBV capsids and, thereby, inhibit HBV replication.
To determine the prevalence of osteonecrosis (ON) of the femoral head in renal transplant recipients and determine the natural history of previously undetected lesions.
The hips of 132 renal ...transplant recipients were examined with magnetic resonance (MR) imaging, with radiographs obtained only in the patients with positive MR images.
Ten patients (15 hips) were considered to have ON (prevalence, 7.6%). Eleven of the hips had Ficat stage 0 disease (asymptomatic, preradiographic) and were followed up with serial radiography and MR imaging. Over an average follow-up of 22 months, only one of these lesions showed progression. The other 10 hips did not show progression at MR imaging or radiography.
Previously undetected ON may have a benign course in many cases. Although a substantial number of patients have previously unsuspected disease, further study is necessary to assess the need for "prophylactic" surgery in such cases.
Occasionally, vertebral body lesions are encountered that are ill suited to the standard posterolateral approach to biopsy. The authors used a transpedicular approach to spine biopsy in six such ...cases. The authors suggest that this approach be used when the location of the lesion does not allow easy access by means of the posterolateral approach.
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