Validation of metastasis-free survival as a surrogate endpoint for overall survival in localized prostate cancer in the era of docetaxel for castration-resistant prostate cancer.

BACKGROUND: Prior work from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium (ICECaP-1) demonstrated that metastasis-free survival (MFS) is a valid surrogate for overall survival (OS) in localized prostate cancer (PCa). This was based on data from patients treated predominantly before 2004, prior to docetaxel being available for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate surrogacy in a more contemporary era (ICECaP-2) with greater availability of docetaxel and other systemic therapies for mCRPC. PATIENTS AND METHODS: Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for localized PCa, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS was defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R2 ≥ 0.7 defined a priori as clinically relevant. RESULTS: A total of 15 164 IPD from 14 trials were included in ICECaP-2, with 70% of patients treated after 2004. The median follow-up was 8.3 years and the median postmetastasis survival was 3.1 years in ICECaP-2, compared with 1.9 years in ICECaP-1. For surrogacy condition 1, Kendall's tau was 0.92 for MFS with OS at the patient level, and R2 from weighted linear regression (WLR) of 8-year OS on 5-year MFS was 0.73 (95% confidence interval 0.53-0.82) at the trial level. For condition 2, R2 was 0.83 (95% confidence interval 0.64-0.89) from WLR of log[hazard ratio (HR)]-OS on log(HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. CONCLUSIONS: MFS remained a valid surrogate for OS in a more contemporary era, where patients had greater access to docetaxel and other systemic therapies for mCRPC. This supports the use of MFS as the primary outcome measure for ongoing adjuvant trials in localized PCa.

Handrubbing with sprayed alcohol-based hand rub: an alternative method for effective hand hygiene.

BACKGROUND: Hand hygiene is crucial in infection prevention and control. It is unclear whether sprayed alcohol-based hand rub (ABHR) is non-inferior to the World Health Organization (WHO)-recommended method of handrubbing with poured ABHR. AIM: To test whether sprayed ABHR can be an alternative (non-inferior) method for effective hand hygiene with/without handrubbing. METHODS: A laboratory experiment was conducted with ABHR (isopropanol 60% v/v) according to European Norm 1500. Hand hygiene was performed by: (1) handrubbing with ABHR poured on to the palm of the hand; (2) handrubbing with sprayed ABHR; and (3) applying sprayed ABHR to hands without handrubbing. Hands were contaminated with Escherichia coli ATCC 10536, followed by hand hygiene and microbiological sampling. A generalized linear mixed model with a random intercept per subject was used to analyse the reduction in bacterial count following hand hygiene. FINDINGS: In total, 19 healthcare workers participated in the study. Handrubbing with sprayed ABHR was non-inferior [margin log10 0.6 colony-forming units (cfu)/mL] to the WHO-recommended method of handrubbing with poured ABHR; bacterial count reductions were log10 3.66 cfu/mL [95% confidence interval (CI) 1.68-5.64] and log10 3.46 cfu/mL (95% CI 1.27-5.65), respectively. Conversely, non-inferiority was not found for sprayed ABHR without handrubbing [bacterial count reduction log10 2.76 cfu/mL (95% CI 1.65-3.87)]. CONCLUSION: Handrubbing with sprayed ABHR was non-inferior to handrubbing with ABHR poured on to the palm of the hand to reduce bacterial counts on hands under experimental conditions. Handrubbing with sprayed ABHR may be an acceptable alternative hand hygiene method pending assessment in other settings and for other pathogens.

Antibacterial efficacy of handrubbing for 15 versus 30 seconds: EN 1500-based randomized experimental study with different loads of Staphylococcus aureus and Escherichia coli.

OBJECTIVES: Compliance with the World Health Organization 'how to handrub' action is suboptimal. Simplifying the hand-hygiene action may improve practice. However, it is crucial to preserve antibacterial efficacy. We tested the non-inferiority of 15 versus 30 seconds handrubbing for Staphylococcus aureus and Escherichia coli contamination at different loads, using hand-size customized alcohol-based handrub (ABHR) volumes. METHODS: In an EN1500-based study, 18 health-care workers (HCWs) with extensive experience in hand hygiene rubbed hands with a hand-size customized volume of isopropanol 60% v/v. They repeated the following sequence: hand contamination (E. coli or S. aureus; broth containing 108 or 106 CFU/mL); baseline fingertips sampling; handrubbing (15 or 30 seconds); re-sampling. The main outcome was log10 CFU corrected reduction factor (cRF) on HCWs' hands, applying a generalized linear mixed model with a random intercept for subject. RESULTS: The median cRF was 2.1 log10 (interquartile range 1.50-3.10). After fitting the model, cRF was significantly higher for S. aureus compared with E. coli but there was no significant effect for duration of handrubbing or contamination fluid concentration. Fifteen seconds of handrubbing was non-inferior to 30 (-0.06 log10, 95% CI -0.34 to 0.22; EN1500 0.60 log10 non-inferiority margin). This was confirmed in all pre-specified subgroups. CONCLUSION: Among experienced HCWs using a hand-size customized volume of ABHR, handrubbing for 15 seconds was non-inferior to 30 seconds in reducing bacterial load, irrespective of type of bacteria or contamination fluid concentration. This provides further support for a shorter, 15-seconds, hand-hygiene action.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Vaccination with neutrophil inhibitory factor reduces the fecundity of the hookworm Ancylostoma ceylanicum.

Neutrophil inhibitory factor (NIF), a protein isolated from hookworms of the genus Ancylostoma, inhibits CD11b/18-dependent leucocyte function, binding to the I domain of CD11b. Historically, NIF was serendipitously isolated from whole worm extracts during a search for novel antihaemostatic agents, and little is known of its source or biological significance to the parasite. NIF has also been identified as a possible hookworm vaccine candidate. Ancylostoma ceylanicum recombinant NIF, expressed in its active form in Pichia pastoris, was purified and its functional activity confirmed using neutrophil adhesion assays and confirmatory immunoassay. Recombinant NIF was subsequently used in vaccination trials in the A. ceylanicum-hamster model system for human hookworm infection. Vaccinated and challenged animals were not protected in terms of worm burden or haematocrit values, despite the presence of high levels of specific antibody against NIF. However, adult worms resident in vaccinated animals showed a significant reduction in fecundity (85.8% by day 21 postinfection), indicating a degree of protection against subsequent transmission by vaccination. These data indicate that targeted vaccination with recombinant subunit material, derived from a known and effective immune suppressant secreted by the parasite, may offer partial protection against the transmission of hookworm infection. Furthermore, we can also report that a biological activity characteristic of NIF is detectable in the secretions of A. ceylanicum using two complementary bioassays. Complete neutralization of this secreted activity by vaccination in combination with other vaccine candidates may result in improved protection against A. ceylanicum infection.

Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells.

The MCF10 series of cell lines was derived from benign breast tissue from a woman with fibrocystic disease. The MCF10 human breast epithelial model system consists of mortal MCF10M and MCF10MS (mortal cells grown in serum-free and serum-containing media, respectively), immortalized but otherwise normal MCF10F and MCF10A lines (free-floating versus growth as attached cells), transformed MCF10AneoT cells transfected with T24 Ha-ras, and premalignant MCF10AT cells with potential for neoplastic progression. The MCF10AT, derived from xenograft-passaged MCF10-AneoT cells, generates carcinomas in approximately 25% of xenografts. We now report the derivation of fully malignant MCF10CA1 lines that complete the spectrum of progression from relatively normal breast epithelial cells to breast cancer cells capable of metastasis. MCF10CA1 lines display histologic variations ranging from undifferentiated carcinomas, sometimes with focal squamous differentiation, to well-differentiated adenocarcinomas. At least two metastasize to the lung following injection of cells into the tail vein; one line grows very rapidly in the lung, with animals moribund within 4 weeks, whereas the other requires 15 weeks to reach the same endpoint. In addition to variations in efficiency of tumor production, the MCF10CA1 lines show differences in morphology in culture, anchorage-independent growth, karyotype, and immunocytochemistry profiles. The MCF10 model provides a unique tool for the investigation of molecular changes during progression of human breast neoplasia and the generation of tumor heterogeneity on a common genetic background.

Detection of human and animal rotavirus sequences in drinking water.

Reverse transcription-PCR analysis of drinking water in the homes of 56 children suffering from rotaviral gastroenteritis has shown the presence of the rotavirus genome in four samples. These strains were different from human rotaviruses detected in the children's feces, as determined by sequencing of the VP7-amplified fragments-three of them of animal origin (porcine or bovine) and one of human origin.

Monitoring rotavirus environmental contamination in a pediatric unit using polymerase chain reaction.

Rotavirus environmental contamination in a pediatric unit was investigated. Surfaces were swabbed, then viruses eluted, ultracentrifuged, and detected by polymerase chain reaction (PCR) amplification. Of 55 samples, 25 (46%) tested positive. Rotavirus RNA was more prevalent on surfaces in direct contact with children (thermometers and play mats) than on other environmental surfaces (washbasins, door handles, etc). PCR has proved useful for monitoring rotavirus environmental contamination.

[Virus resistance in a hospital environment: overview of the virucide activity of disinfectants used in liquid form]. / Résistance des virus dans l'environnement hospitalier: le point sur l'activité virucide des désinfectants utilisés à l'état liquide.

Human pathogenic viruses can be detected in the hospital environment, on contaminated surfaces or medical instruments. Their transmission to patients or staff has already been reported. Lipophilic viruses (HIV, HBV, HCV,...) are susceptible to many liquid chemicals, but they can survive during short time on inadequately disinfected surfaces. Hydrophilic viruses, without envelope, are more resistant, but generally not associated with severe illnesses. Viruses survival in environment depends on many factors and is always improved with viral aggregation and low temperature, whereas organic matters and relative humidity effects are contrasted. The mechanism of virucide disinfectants is not yet well established, and their targets are not known with precision. Different disinfection procedures (disinfectant concentration, contact time, temperature, pH) can provide a similar virucidal activity on a given virus. The virucidal activity of a disinfectant is evaluated with a cell culture assay in Afnor guidelines. But, there are three major problems with this method, concerning need of high viruses titers, residual disinfectant cytotoxicity on cell culture, and non cultivable viruses. Non standardized tests are also described in papers, but their results can generally not be compared. Molecular biology improvements may lead to reproducible and sensitive tests. At present, no general disinfection procedure effective for most of the viruses, without risks for staff or materials, and with an acceptable economic cost can be recommended.

[Validation of a sampling method for the channels of a flexible endoscope which is experimentally contaminated]. / Validation d'une méthode de prélèvement des canaux d'un endoscope souple contaminé expérimentalement.

The increase of endoscopic actions and infectious risks explains of interest in endoscopic material maintenance processing. This purpose study was to set to the point and validate a microbiological flexibles endoscopes channels (suction, biopsy, air/water) sample method. An inoculum made of faeces contents material and microorganisms suspension (Pseudomonas aeruginosa or Candida albicans), at low or high concentration, was injected into digestive endoscope's channels. For each microorganism, five trials were carried out at both of the two concentrations. After incubation, a global channels sample was performed with a recovering solution, then a counting was made. A variance analysis (ANOVA) concerning restated measures was performed for the whole results. The mean difference between the number of microorganisms injected and those recovered's is 0.114 log (IC95% [+0.088; +0.140]). It does not vary significantly according to the micro-organisms (p = 0.69) and the inoculum (p = 0.70). The coefficient of variation which is 0.525 (min: 0.010; max: 0.260) shows this method can be reproduced. This technique are allowed to be recommended to evaluate and to validate manuals and automatics endoscopes maintenance processing.

Neoplastic progression of breast epithelial cells--a molecular analysis.

Molecular changes associated with breast cancer progression were characterized using the MCF-10F cell series. MCF-10F was established from fibrous mastectomy tissue of a patient without detectable cancer. In vitro treatment of MCF-10F cells with benzo(a)pyrene resulted in a transformed subclone MCF-10F-BP1 (BP1). Transfection of clone BP1 with T24-Hras resulted in the tumorigenic line MCF-10F-BP1-Tras (BP1-Tras). Using flow cytometry, the expression of HLA I, ERBB-2 and MUC-1 was found to be comparable in 'normal' MCF-10F, transformed BP1 and tumorigenic BP1-Tras cells. Glycosylated mucin is elevated in BP1 but reduced in BP1-Tras cells. Using mRNA differential display analysis, cDNA profiles of the 'normal', transformed and tumorigenic cell lines were strikingly similar, yet distinct and elevated expression of several common cDNA fragments was detected in BP1 and BP1-Tras when compared with MCF-10F cells. These fragments were cloned and sequenced. The sequences of clones T1-360 and C4-310 are homologous to two reported EST cDNA clones from human fetal tissue and were further characterized. Elevated expression of the genes corresponding to clones T1-360 and C4-310 was verified using Northern blotting. High-level expression of these genes was also detected in the breast cancer cell line MCF-7 that was derived from the pleural effusion of a patient with advanced breast cancer. Therefore, specific molecular changes associated with breast cancer development were identified and may be indicators of neoplastic progression.

Expression of transforming growth factor-beta receptor type II and tumorigenicity in human breast adenocarcinoma MCF-7 cells.

To analyze transforming growth factor-beta (TGF-beta) response during MCF-7 cell progression, early passage (MCF-7E, < 200 passage) and late passage (MCF-7L, > 500 passage) cells were compared. MCF-7E cells showed an IC50 of approximately 10 ng/ml of TGF-beta1, whereas MCF-7L cells were insensitive. MCF-7E cells contained approximately threefold higher levels of TGF-beta receptor type II (TbetaRII) mRNA than MCF-7L, but their TbetaRI levels were similar. MCF-7E parental cells showed higher TbetaRII promoter activity than MCF-7L cells, which could be attributed to changes in Sp1 nuclear protein levels. Receptor cross-linking studies indicated that the cell surface receptor levels parallel mRNA levels in both cell lines. Limiting dilution clones of MCF-7E cells were established to determine the heterogeneity of TbetaRII expression in this cell line, and they showed varying degrees of TbetaRII expression. Fibronectin was induced at higher levels in cells expressing higher TbetaRII levels. All three TGF-beta isoforms were detected in limiting dilution clones and parental cells, but TGF-beta1 was more abundant relative to TGF-beta2 or 3, and no correlation between TGF-beta isoform profile with TGF-beta sensitivity was found. MCF-7L cells were tumorigenic and formed xenografts rapidly and progressively, whereas MCF-7E parental and limiting dilution clonal cells showed transient tumor formation followed by regression. These results indicate that decreased TbetaRII transcription in breast cancer cells leads to a loss of TbetaRII expression, resulting in cellular resistance to TGF-beta which contributes to escape from negative growth regulation and tumor progression.

Transforming and oncogenic potential of activated c-Ha-ras in three immortalized human breast epithelial cell lines.

The ability of activated c-Ha-ras (codon 12 valine) to transform human breast epithelial cells varied for three different immortalized normal human breast epithelial cell lines established from two different women. Although activated c-Ha-ras may transform and induce a preneoplastic phenotype in MCF10A cells, activated c-Ha-ras was not sufficient to transform MCF10-2A cells. Only two of three MCF10-2A clones which expressed mutant p21 protein acquired the ability to form colonies in soft agar. When xenografted into nude beige mice, two MCF10-2A clones formed squamous carcinomas and one formed no lesions at all. The ability to form tumors did not correlate with growth in soft agar. All three activated c-Ha-ras-transfected clones of MCF-12A formed colonies in soft agar but only two produced squamous carcinomas in nude beige mice. Unlike activated c-Ha-ras-transfected MCF10A cells, none of the activated c-Ha-ras-transfected MCF10-2A or MCF-12A clones formed ducts in xenografts. Rather, initial xenograft lesions consisted of nests of cells with squamous differentiation. These observations illustrate that additional events are involved in the transformation and progression of human breast epithelial cells with activated c-Ha-ras.

Attenuation of the inflammatory response in an animal colitis model by neutrophil inhibitory factor, a novel beta 2-integrin antagonist.

BACKGROUND: Neutrophils are significant effector cells in acute inflammatory bowel disease. Recruitment of these cells is dependent on beta 2-integrin-mediated adhesion and transmigration. The efficacy of neutrophil inhibitory factor (NIF), an antagonist of the beta 2-integrin CD11b/CD18, in ameliorating inflammation was tested in an animal model of acute colitis. METHOD: Immune-complex colitis was induced in groups of rabbits by using various formalin concentrations (2%, 0.75%, and 0.5%). Animals were treated with rNIF, 10 mg/kg. After they had been killed the mucosal appearance was scored, and tissue saved for histology and quantitation of myeloperoxidase (MPO), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2). RESULTS: In the 2% formalin group therapy with rNIF resulted in lower LTB4 (p < 0.05) levels. For the 0.75% and 0.5% groups, MPO was lower with rNIF treatment (p < 0.03 and p < 0.05, respectively), as were LTB4 concentrations (both, p < 0.04). PGE2 and TXB2 levels remained unchanged. Histology showed polymorphonuclear cell infiltration to be reduced by rNIF in the 2% and 0.75% formalin-treatment groups (p < 0.05). CONCLUSION: These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.

Mechanisms underlying neutrophil adhesion to apical epithelial membranes.

Crypt abscesses allow prolonged apposition of activated neutrophils to the epithelial surface of the colon. Adhesion of neutrophils to both the vascular endothelium and basolateral epithelial membrane share common effector molecules but are distinct processes. This study aimed to define the mechanisms that effect adhesion, independent of transmigration, to the apical epithelium. HT29 (cl 19A) cells were grown to confluency and incubated with neutrophils under conditions of: (i) neutrophil stimulation with phorbol-myristate-acetate; (ii) monolayer stimulation with interferon gamma, tumour necrosis factor alpha (IFN gamma, TNF alpha); and (iii) recent epithelial cell trypsinisation. These experiments were carried out in the presence of neutralising antibodies to CD18, CD11b, LFA-1, E-selectin, P-selectin, intracellular adhesion molecule 1 (ICAM-1), and ICAM-2; a novel CD11b/CD18 antagonist, neutrophil inhibitory factor (rNIF); adenosine receptor agonists (5'N-ethycarboxamido adenosine/N6-cylopentyladenosine (NECA/CPA)) and a platelet activating factor (PAF) receptor antagonist lexipafant. Adhesion of stimulated neutrophils to resting monolayers was Mac-1, CD18 dependent and ICAM-1, ICAM-2, E-selectin, P-selectin, PAF independent. Cytokine activated monolayers exhibited higher binding of neutrophils which was inhibited by rNIF and aCD18. Recently trypsinised monolayers bound neutrophils in a CD11b/CD18 and CD18 independent manner. Adenosine agonists failed to influence neutrophil adhesion under any condition. This study shows neutrophil adhesion to apical epithelial membranes is similar to that at the epithelial basolateral membrane, though different to that seen at the vascular endothelium. These results highlight regional differences in neutrophil adhesion molecule usage.

Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats.

We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced by insertion of an intraluminal suture. Infusion of the drug was initiated at the onset of reperfusion. Infarct volume was determined 48 hours after reperfusion. Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO) staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with control animals. The number of neutrophils within the infarcted tissue correlated positively with the size of the area of infarction (p < 0.001, r = 0.6) within representative cerebral coronal sections. We demonstrated a significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduced number of neutrophils within the ischemic tissue. These results demonstrate potential therapeutic properties of rNIF in the management of stroke.

Neutrophil inhibitory factor prevents neutrophil-dependent lung injury.

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.

A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion in the liver after hemorrhagic shock.

This study was designed to assess the effect of neutrophil inhibitory factor (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40 mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or placebo control protein administered as a single intravenous bolus (10 mg/kg) at the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in vivo fluorescence microscopy. There were no significant differences observed in hemodynamic parameters between the shock groups throughout the study, however, NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results suggest that NIF may be beneficial in the attenuation of the pathological shock-induced leukocyte adhesion.