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H Repo

Publications and source records attributed to H Repo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Neutrophil free oxygen radical production and blood total antioxidant capacity in patients with coronary heart disease using various medications.

Despite convincing results of studies in vitro, less is known about the effects of antioxidants on in vivo redox balance in humans. We developed a novel parameter of in vivo redox balance, and studied it and its relation to dental infections in 51 patients on medication for coronary heart disease (CHD) and 39 random controls matched for age group, sex, social class and locality. In vivo redox balance was the ratio of plasma antioxidant capacity, as measured with radical-trapping assay, to neutrophil respiratory burst capacity, as measured with whole blood chemiluminescence assay. Dental infections were quantitated with four rating scales. CHD patients had higher values than controls. Patients on acetosalicylic acid (ASA), diuretics or beta blockers, but not the ones on calcium channel blocker, had significantly higher redox balance than non-users. Combination of calcium channel blockers and ASA was associated with redox balance similar to taking beta blockers or diuretics. Diuretics and ASA were independent determinants of redox balance in multivariate analyses. Redox balance did not correlate with severity of dental infections (Spearman's r 0.06 to 0.11). The results contrast experimental data indicating that calcium channel blockers are as antioxidants superior to other cardiovascular drugs. Total antioxidant capacity in parallel with oxygen species production capacity should be considered in attempts to solve the antioxidant paradox.

Adrenergic beta-Antagonists↗
PubMed2001

Procalcitonin strip test in the early detection of severe acute pancreatitis.

BACKGROUND: Early identification of patients who subsequently develop severe acute pancreatitis would enable the selection of patients who may benefit from early intensive management. Because severe acute pancreatitis is characterized by the development of systemic inflammation the authors studied whether procalcitonin, a marker of systemic inflammation, differentiated between patients with mild and severe acute pancreatitis. METHODS: On admission and 24 h thereafter, serum procalcitonin level was measured by a rapid, semiquantitative PCT-Q test and serum C-reactive protein (CRP) by an immunoturbidimetric method in a consecutive series of 162 patients with acute pancreatitis. There were 38 severe and 124 mild cases. The accuracy of procalcitonin and CRP in predicting severe acute pancreatitis was compared with that of Ranson and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. RESULTS: The PCT-Q test was more accurate in predicting severe acute pancreatitis (sensitivity 92 per cent and specificity 84 per cent at 24 h) than CRP, APACHE II score and Ranson score. Its negative predictive value was high (97 per cent at 24 h), and it detected each patient who developed subsequent organ failure (n = 22). CONCLUSION: The PCT-Q test was a useful screening method for detecting severe acute pancreatitis. It is simple and quick to perform and, unlike currently available multiple factor scoring systems, can easily be adopted into routine clinical practice.

Acute Disease↗
PubMed2001

Cellular markers of systemic inflammation and immune suppression in patients with organ failure due to severe acute pancreatitis.

BACKGROUND: Few data are available on cellular markers of systemic inflammation and immune suppression in early acute pancreatitis. The aim of this study was to describe the cellular immune inflammatory status of patients with acute pancreatitis in relation to development of organ failure. METHODS: Prospective study including 89 patients who presented within 72 h of onset of pain. Fifty-eight of them had mild disease (Grade I group), 19 had severe disease with no organ dysfunction (Grade II group) and 12 had severe disease with organ dysfunction (Grade III group). Serial blood samples were collected on admission and following 2 days. Phagocyte surface markers were analysed using flow cytometry. RESULTS: The proportion of HLA-DR-positive monocytes, a marker of immune suppression, and CD11b expression level on neutrophils and monocytes, a marker of systemic inflammation, were related to Grades I-III (P for trend <0.001). In Grade III patients, the proportion of HLA-DR-positive monocytes was low on presentation, or decreased rapidly during follow-up, whereas CD11b expression levels were persistently high. L-selectin and monocyte CD14 expression levels were not related to disease severity. CONCLUSIONS: Immune suppression develops early, rapidly and unexpectedly in patients with acute pancreatitis. Monitoring immune inflammatory status may provide the means by which to identify patients who benefit from biological response modifier therapy.

Acute Disease↗
PubMed2001

Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin in predicting the severity of acute pancreatitis.

OBJECTIVE: To investigate whether marker(s) of systemic inflammation detect, at an early stage of acute pancreatitis, patients who may ultimately develop severe disease. DESIGN: Prospective study. SETTING: University hospital emergency unit. PATIENTS: Thirty patients with mild acute pancreatitis (SEV0 group) and 27 with severe acute pancreatitis. Of the latter, 11 did not develop organ failure (SEV1 group), whereas the other 16 patients developed acute respiratory failure and 9 of them also developed renal failure (SEV2 group). INTERVENTIONS: Blood samples were collected at admission to the hospital (T0), and at 12 hrs (T12) and 24 hrs (T24 after admission. MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of procalcitonin (PCT), soluble E-selectin (sE-selectin), soluble interleukin-2 receptor (sIL-2R), and the serum concentration of C-reactive protein (CRP) were monitored. PCT levels at T0 were significantly higher in the SEV1 group (median 0.4 ng/mL, range 0.2-2.3) and the SEV2 group (0.8 ng/mL, 0.2-73.5) than in the SEV0 group (0.3 ng/mL, 0.1-3, p < .05 and p < .001, respectively). At T12, PCT level in the SEV2 group was significantly higher than that in the SEV1 group (2.2 ng/mL, 0.2-86.6 vs. 0.4 ng/mL, 0.3-2.8, p = .05), as it also was at T24 (2.2 ng/mL, 0.4-73.3 vs. 0.5 ng/mL, 0.3-4, p < .01). Among SEV2 patients, PCT concentration correlated negatively with the time elapsed between admission and the diagnosis of organ failure. At T12, sIL-2R levels of the SEV1 group (1,011 U/mL, range 334-2,211) and the SEV2 group (1,495 U/ml, range 514-4,526) both differed significantly from the SEV0 group (636 U/ml, range 356-1,678, p < .05 and p < .001, respectively) as they also did at T24. Although CRP level in the SEV1 group at T12 did not differ from the SEV0 group, the difference between SEV2 (272 microg/mL, range 46-462) and SEV0 was significant (53 microg/mL, range 5-243, p < 0.01). sE-selectin levels did not differ between groups. CONCLUSIONS: At admission to hospital, concentrations of PCT, but not those of CRP, sE-selectin, or sIL-2R, are higher in patients with severe acute pancreatitis than in patients with mild pancreatitis. PCT test had sensitivity of 94% and specificity of 73% for development of organ failure. PCT may be useful to identify the patients who benefit from novel therapies aimed at modifying the course of systemic inflammation.

Adult↗
PubMed2001

Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis.

OBJECTIVE: To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of early-onset infection in neonates. METHODS: The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life. Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay. Both data were available from 35 of 39 neonates. Serum C-reactive protein was determined at initial evaluation and, later, on the basis of the clinical picture. Neonates were allocated retrospectively into 2 groups. In the sepsis group (N = 22), 4 had culture-proven sepsis, and 14 had an antenatal risk factor for infection. In the possible-infection group (N = 13), each neonate had a noninfective disorder, but co-occurring infection remained a possibility. Twelve healthy term infants served as controls. RESULTS: CD11b expression and IL-8 levels both increased in order of sepsis > possible infection > healthy. Sensitivity and specificity by the CD11b test for sepsis were equal, at 1.00, and those by the IL-8 test 0.91 and 1.00, respectively; 6 (17.1%) of the 35 neonates had CD11b and IL-8 below cutoff levels. CONCLUSIONS: Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis. The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates.

Biomarkers↗
PubMed2000

Systemic inflammation in hemorrhagic fever with renal syndrome correlates with hypotension and thrombocytopenia but not with renal injury.

Systemic inflammation is common in patients with nephropathia epidemica (NE), a European form of hemorrhagic fever. Markers of inflammation were studied in a patient with NE with respiratory insufficiency (patient 1), 18 other patients with NE, and 13 patients with a viral infectious disease other than NE. Neutrophil and monocyte CD11b expression levels, determined by flow cytometry; soluble interleukin (IL)-2 receptor (sIL-2R), IL-6, and IL-8 concentrations, determined by means of Immulite; and soluble E-selectin, determined by ELISA, were higher in patients with NE than in healthy subjects. The findings were not specific for NE and did not correlate with serum creatinine levels, but the findings correlated inversely with mean arterial pressure (sIL-2R and monocyte CD11b expression) and minimum platelet count (sIL-2R, IL-6, neutrophil, and monocyte CD11b expression). Monocyte CD11b expression in patient 1 was extremely high, suggesting that monocytes may contribute to development of lung injury. Severity of inflammation in patients with NE is related to hypotension and platelet consumption but not to renal injury.

Adolescent↗
PubMed2000

Transhepatic neutrophil and monocyte activation during clinical liver transplantation.

BACKGROUND: During experimental liver transplantation, neutrophil sequestration results in increased oxygen free radical production and correlates inversely with graft viability. Neutrophil activation in clinical liver transplantation is poorly understood. METHODS: We assessed leukocyte sequestration and transhepatic differences of neutrophil and monocyte CD11b expression, neutrophil free radical production, and plasma concentrations of interleukin 6 and interleukin 8 in nine patients during liver transplantation. RESULTS: Significant hepatic neutrophil sequestration occurred during initial graft rewarming with portal blood, after inferior vena cava declamping, and after hepatic artery declamping (all P<0.05). A positive transhepatic difference (i.e., outcoming - ingoing) in CD11b expression of neutrophils was observed after portal vein declamping (51+/-32 relative fluorescence unit [RFU]) and in CD11b expression of monocytes during initial graft rewarming (67+/-86 RFU, both P<0.05). A transcoronary increase in both unstimulated (74+/-80 RFU) and N-formyl-methionyl-leucylphenylalanine-stimulated (112+/-168 RFU) neutrophil free radical production took place after hepatic artery declamping (both P<0.05). A negative transcoronary difference of interleukin 6 occurred during initial graft rewarming (-192+/-176 pg/ml) and a positive difference of interleukin 8 occurred after hepatic artery declamping (17+/-23 pg/ml, both P<0.05). CONCLUSIONS: Hepatic sequestration and transhepatic activation of neutrophils, and hepatic production of interleukin 8 occur during clinical liver transplantation. A splanchnic influx of interleukin 6 occurs to the graft, possibly modulating neutrophil-mediated graft reperfusion injury.

Adult↗
PubMed1999

Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood.

R6.5 (BIRR-1, Enlimomab), a murine IgG2a mAb to the human ICAM-1, inhibits leukocyte adhesion to the vascular endothelium, thereby decreasing leukocyte extravasation and inflammatory tissue injury. In initial clinical trials, R6.5 proved to be beneficial in reducing both disease activity in refractory rheumatoid arthritis and the incidence of acute rejection after kidney and liver allograft transplantations. However, adverse effects such as fever, leukopenia, or cutaneous reactions were not infrequent. We studied the effects of R6.5 on neutrophil function in whole blood samples ex vivo. Surprisingly, at the concentrations achieved in clinical trials, R6. 5 activated neutrophilic granulocytes, as indicated by a significant increase in expression of the adhesion molecule beta2-integrin CD11b, a concurrent decrease in L-selectin expression, and an enhancement of the oxidative burst activity. Neutrophil activation was not exerted by an anti-ICAM-1 mAb of the IgG1 isotype, by isotype-matched, irrelevant anti-2-phenyloxazolone mAb, or by F(ab')2 fragments of R6.5. Neutrophil activation was completely inhibited by soluble complement receptor type 1. We conclude that in whole blood, R6.5 activates resting neutrophils in a complement-dependent manner. This finding can explain, at least in part, the side effects associated with R6.5 therapy.

Animals↗
PubMed1999

Nitecapone reduces cardiac neutrophil accumulation in clinical open heart surgery.

BACKGROUND: To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients. METHODS: In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping. RESULTS: Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range]. CONCLUSION: Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.

Adult↗
PubMed1999

Mechanisms and consequences of phagocyte adhesion to endothelium.

Leukocyte adhesion to endothelium is essential for the development of an appropriate immune-inflammatory response. The vital importance of leukocyte-endothelial adhesive interactions in host defense and homeostasis is illustrated by the clinical manifestations of patients with congenital defects of leukocyte adhesion functions. However, under some circumstances leukocyte adhesion to endothelium may instead lead to vascular and tissue damage. In recent years, there has been remarkable progress in the understanding of the molecular basis of leukocyte adhesion to endothelium, and this knowledge has led to a new approach to immunomodulation in human disease, ie 'antiadhesion' therapy. This review focuses on cell adhesion molecules mediating adhesion of circulating phagocytes to vascular endothelium, on congenital defects of phagocyte adhesion in man, and on the current status of antiadhesion therapy directed towards phagocyte and endothelial adhesion molecules. We will also consider markers of phagocyte activation, which may provide a means to identify those patients who would benefit most from antiadhesion therapy.

Biomarkers↗
PubMed1999

Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency.

Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C-reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation.

Acute Disease↗
PubMed1999

Markers of systemic inflammation predicting organ failure in community-acquired septic shock.

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.

APACHE↗
PubMed1997

Binding of human peripheral blood polymorphonuclear leukocytes to E-selectin (CD62E) does not promote their activation.

E-selectin (CD62E) is a cytokine-inducible endothelial cell adhesion molecule that tethers polymorphonuclear leukocytes (PMNs) and supports PMN rolling under conditions of flow. We examined whether interaction of PMNs with E-selectin also leads to activation of CD11b/CD18 (Mac-1, alphaMbeta2), an event that can promote firm adhesion. PMNs were added to monolayers of IL-1beta-activated HUVECs and Chinese hamster ovary (CHO) cells transfected with E-selectin cDNA. PMN activation was assessed by 1) increased CD11b/CD18 surface expression, 2) appearance of activation epitope on CD11b/CD18 (CD11b*) detected by mAb CBRM1/5, and 3) decreased L-selectin (CD62L) expression, as determined by flow cytometry. Both adherent and nonadherent supernatant PMNs became activated on IL-1beta-pretreated HUVECs. This activation was not affected by CD62E-blocking mAb P6E2. The activation state of PMNs adhered to CHO cells transfected with E-selectin cDNA was not increased over background and was similar to that of PMNs exposed to parent CHO cells. The findings were confirmed using confocal microscopy, which allowed staining of the cells for CD11b* in situ. In concert, the results suggest that PMN binding to E-selectin does not elicit inter-receptor signaling that could result in strengthening of PMN adhesion to endothelium.

Animals↗
PubMed1996

Heterogeneity of rearranged T cell receptor V alpha and V beta gene transcripts in synovial fluid T cells of HLA-B27 positive reactive arthritis patients.

To analyze the T cell receptor (TCR) V-alpha/beta gene usage by synovial fluid (SF) and peripheral blood (PB) T cells of HLA-B27+ reactive arthritis (ReA) patients. The TCR V-alpha/beta gene usage was determined by the polymerase chain reaction on freshly isolated SF and PB mononuclear cells (MNC) of five HLA-B27+ ReA patients. A total of 30 TCR V alpha and 23 V beta (sub)family specific primers in combination with a C alpha or C beta specific primer, respectively, were used. In five patients most of the TCR V alpha and V beta gene segments expressed by PB T cells were also detected in the paired SF samples. Although one patient showed an increased expression of TCR V alpha2 in SF when compared to PB, the SF samples showed a heterogeneous TCR V-gene repertoire similar to PB. Although this study was limited to a small group of patients, the apparent lack of a restricted TCR V-gene repertoire in SF does not support the involvement of a single or limited number of T cell subsets in the disease process of HLA-B27+ ReA patients.

Adult↗
PubMed1996

Standardization of a flow cytometric assay for phagocyte respiratory burst activity.

The authors optimized the flow cytometric dichlorofluorescin (DCFH)-oxidation assay for buffy coat neutrophil and monocyte respiratory burst activity. Sample handlings were minimized, monocytes identified with a CD14 antibody, and viability evaluated with propidium iodide. Sodium citrate was a better anticoagulant than heparin, with a more intense Yersinia enterocolitica (YER)-induced dichlorofluorescein (DCF)-fluorescence intensity and a higher proportion of DCF-positive cells. EDTA was unsuitable as an anticoagulant with reduced cell viability and poor DCF response. Exposure of cells to YER, phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) elicited two neutrophil subpopulations, one with low and the other with high forward light scattering properties. FMLP induced only a marginal DCF response, but after YER or PMA, virtually all neutrophils responded with an increased DCF production. During optimal conditions, the resulting DCF- fluorescence histogram was two-peaked, and the subset of cells with increased forward light scattering properties corresponded to the cells with intense DCF-fluorescence. A similar heterogeneity was frequently but not always observed amongst monocytes. The results indicate that in the peripheral blood there are at least two neutrophil and monocyte populations. One is an effective responder to stimuli, the other exhibiting a moderate response only. Properly optimized, the DCFH-oxidation assay may be used for evaluating neutrophil and monocyte subsets in a clinical setting.

Adult↗