Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Variation of B-type natriuretic peptide concentrations and intrauterine growth restriction: mother, fetus and newborn.

To evaluate maternal, fetal, neonatal B-type natriuretic peptide (BNP) concentrations related to Intra Uterine Growth Restriction (IUGR). BNP concentrations in 43 IUGR and 35 healthy, Appropriate for Gestational Age (AGA) infants/paired mothers have been compared, from delivery/birth to first month of life. Maternal and IUGR cord BNP concentrations were coupled to fetal ultrasonography. Neonatal echocardiography was performed too. On delivery BNP was higher in all IUGR mothers, suffering or not from gestational hypertension, than in AGA (median 37.14 vs 11.1 pg/ml p=0.002). Maternal BNP was not associated to cord/neonatal BNP or fetal ultrasonographic parameters. Cord BNP was higher in IUGR than AGA newborns (median 23.9 vs 11.4 pg/ml p=0.0007) independently of gestational age, while varied with amniotic fluid (p=0.0044) and umbilical artery flowmetry (p=0.0121). Earlier drop of BNP on day 3 was reported in IUGR neonates (p=0.0001).Ventricular mass change/body weight varied positively in AGA newborns (p<0.001), while declined in IUGR ones (p=0.003). Carrying IUGR fetus is a stress factor resulting in high maternal BNP concentration. Altered fetal ultrasonographic parameters in IUGR newborns lead to higher BNP cord levels. A rapid BNP drop and probable ventricular mass adjustment of IUGR newborns may indicate earlier post-natal cardiovascular adaptation than AGA infants.

Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.

Preterm newborns are provided with triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble fraction (sTREM-1) are useful markers of infection in adults. Neonates, especially preterm infants, are exposed to high risk of sepsis due to the immature immune system and few data are available regarding TREM-1, mainly focused on the soluble form. We therefore decided to investigate the baseline assessment of TREM-1, membrane and soluble receptors, in preterm newborns without clinical or microbiological evidence of infection, in order to precociously measure the possible changes due to sepsis and compare them to the obtained reference values. Fifty-nine newborns were enrolled in the study. Median and Interquartile range of TREM-1 were: in monocytes 96 percent with 71 Mean Fluorescence Intensity (50-94); in PMNs: 80 percent (68-87); soluble TREM-1: 29.1 pg/ml (14.55-103.93). Monocyte expression and soluble TREM-1 concentrations appeared comparable to healthy adults, while not all PMNs expressed this receptor, possibly due to their immaturity. Birth weight negatively correlated with sTREM-1, while there were no statistical significances with gestational age, maternal age, gender, mode of delivery, patent ductus arteriosus, intrauterine growth restriction, premature rupture of membranes and TREM-1 or sTREM-1. We also reported a statistical relationship between monocyte TREM-1 and surfactant administration and between sTREM-1 and antenatal steroid prophylaxis. Even if untrained, the neonatal immune system of preterm newborns is equipped with TREM-1 system, but further studies are needed to evaluate the functionality in newborns.

Human colostrum T lymphocytes and their effector cytokines actively aid the development of the newborn immune system.

Colostrum contains soluble and cellular components, the latter mainly T lymphocytes. We expanded in vitro colostrum T lymphocytes (CoTL) to evaluate phenotype and capability of cytokine production. We also considered paired cord blood T-lymphocytes (CBTL) representing the newborn "virgin" immune system. CoTL showed memory phenotype while CBTL expressed mainly naïve phenotype. CoTL included a balanced percentage of helper and cytotoxic subsets. We observed higher percentages of IL-2 (p=0.003) and IL-4 (p=0.027) producing cells by helper rather than by cytotoxic T lymphocytes. The greatest percentage of IFN-gamma producing cells was in cytotoxic cells (p=0.0048), while no difference was found for IL-10. Cord blood samples consisted of a statistically significant greater percentage of helper than cytotoxic cells (p<0.001), with a low percentage of cytokine producing cells, confirming the immaturity of the newborns immune system. CBTL percentage of IL-2 producing cells was higher for helper than cytotoxic subset (p<0.001). We observed a greater percentage of IFN-gamma (p=0.001), IL-4 (p=0.003) and IL-10 (p<0.001) producing cells by cytotoxic than helper T lymphocytes. CoTL demonstrated to protect the newborn through the mothers previous immune experience and to supply active cytokines, which can help the postnatal development of both T type 1/T type 2 response.

The -374T/A variant of the rage gene promoter is associated with clinical restenosis after coronary stent placement.

Upregulation of the receptor for advanced glycation end products (RAGE) may play a crucial role in neointimal formation upon vessel injury. The -374T/A variant of the RAGE gene promoter, which has been associated with an altered expression of the cell-surface receptor, could exert a protective effect toward the development of vascular disease. The aim of this study is to determine the impact of this common genetic variant in the occurrence of clinical in-stent restenosis after coronary stent implantation. The -374T/A polymorphism of the RAGE gene promoter was evaluated by PCR-RFLPs in 267 patients with coronary artery disease who underwent coronary stent implantation and a subsequent coronary angiography 6-9 months later for suspected restenosis. In-stent restenosis was assessed by means of quantitative angiography. Carriers of the -374AA genotype showed a significantly reduced risk of developing restenosis after percutaneous transluminal intervention than non-carriers. To determine whether the protective effect of the homozygous AA genotype toward clinical restenosis was independent of potential confounders, we performed multivariable logistic regression analysis. After allowance for clinical and biochemical risk factors and stent length, the AA genotype remained significantly associated with a reduced prevalence of in-stent restenosis. No relation was evident between the RAGE genotype and established cardiovascular risk factors. In conclusion, the -374AA genotype of the RAGE gene promoter could be associated with a reduced risk of in-stent restenosis after coronary stent implantation.

Increased production of inflammatory cytokines in patients with silent myocardial ischemia.

OBJECTIVES: The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exhibit any particular cytokine pattern. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient's perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors. METHODS: Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at -80 degrees C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-beta) and the proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta and -6). RESULTS: In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups. CONCLUSIONS: The data suggest that an "anti-inflammatory pattern" of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

Cigarette smoking and hypertension influence nitric oxide release and plasma levels of adhesion molecules.

Progression of atherosclerosis is currently believed to involve interactions between leukocytes and vascular endothelium. Epidemiological risk factors for atherosclerosis such as hypertension and smoking are known to cause endothelial dysfunction, which is an early event in the atherosclerotic process; they also may be considered in the light of their effects on adhesion molecule expression and release. Little is known about the additive effect between these two risk factors on endothelial adhesion molecule expression and nitric oxide release. Soluble adhesion molecules and the nitric oxide were quantified in smoking hypertensive patients in comparison to those from patients with hypertension alone. Cotinine, a stable metabolite of nicotine, has been used to identify smokers. One hundred and three hypertensive patients were selected: 51 smokers (plasma cotinine levels >25 ng/ml) and 52 non-smokers. Plasma concentrations of soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-I) were quantified with ELISA methods. Plasma concentration of nitric oxide metabolites was measured by HPLC, whilst plasma concentration of cotinine was measured by RIA. Significant increases of sICAM-1 and sVCAM-1 were demonstrated in smokers (p<0.001 and p<0.05, respectively). In the same patients, a positive significant correlation between sVCAM-1 and plasma cotinine levels was observed (p<0.002). Nitric oxide metabolites were reduced significantly (p<0.04) in smokers. In conclusion, our data show that the two risk factors, smoking and hypertension, are additive risk factors in generating endothelial dysfunction and vascular damage, which plays a key role in atherogenesis.

Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T.

OBJECTIVE: To measure plasma interferon gamma, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina. DESIGN: Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease. PATIENTS: 76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3). MAIN OUTCOME MEASURES: Plasma interleukin 6, interferon gamma, MCP-1, and troponin T in the three groups of patients. RESULTS: Interleukin 6 was increased in group 1 (median 2.19 (range 0.53-50.84) pg/ml) compared with the control group (1.62 (0.79-3.98) pg/ml) (p < 0.005), whereas interferon gamma was higher in group 1 (range 0-5.51 pg/ml) than in the other two groups (range 0-0.74 pg/ml and 0-0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon gamma than those with negative troponin T (0-5.51 pg/ml v 0-0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6-8670) pg/ml) than in the other two groups (134 (19-890) pg/ml and 84.5 (5-325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5-8670) pg/ml v 69 (6-3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T. CONCLUSIONS: The inflammatory cytokines interferon gamma and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.

Increased expression of peripheral benzodiazepine receptors on leukocytes in silent myocardial ischemia.

OBJECTIVES: The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms. Benzodiazepines and their receptors play key roles in pain, in interactions with peptide opioids, in inflammation and in the response to stress. METHODS: The study group consisted of 57 patients with reproducible exercise-induced myocardial ischemia. The presence of a constant behavior in the anginal pain perception during both exercise-induced ischemia and daily life was the most important inclusion criterion. Venous blood samples were taken from all patients to evaluate the expression of peripheral benzodiazepine receptors by flow cytometry. The study cohort was classified into two groups: 24 patients who had anginal pain both at home and during the exercise stress test and 33 patients who were asymptomatic during both daily life and exercise-induced ischemia. RESULTS: Flow cytometry analysis showed increased expression of peripheral benzodiazepine receptors on all types of leukocytes in the asymptomatic patients. The difference was statistically significant for lymphocytes (p < 0.005), monocytes (p < 0.001) and granulocytes (p < 0.001). CONCLUSIONS: These data show that expression of peripheral benzodiazepine receptors was higher in patients with silent myocardial ischemia than in symptomatic patients.

Cyclosporine induces different responses in human epithelial, endothelial and fibroblast cell cultures.

BACKGROUND: Nephrotoxicity, accelerated atherosclerosis, and graft vascular disease are common complications of cyclosporine long-term treatment characterized by a wide disruption of organ architecture with increased interstitial areas and accumulation of extracellular matrix (ECM). How cyclosporine induces these changes is not clear, but it is conceivable that they are the sum of changes induced at the cell level. METHODS: We studied the effects of cyclosporine on human endothelial (HEC), epithelial (HK-2), and fibroblast (MRC5) cells. Cell proliferation was evaluated by cell counting, apoptosis and collagen production by enzyme-linked immunosorbent assay, and nitric oxide by measuring the concentration of nitrite/nitrate in the cell supernatant. (alpha1)I and (alpha2)IV collagen, matrix metalloprotease-9 (MMP9), and tissue inhibitors of metalloprotease-1 (TIMP-1) mRNA levels were measured by reverse transcription-polymerase chain reaction. Proteolytic activity was evaluated by zymography. RESULTS: Cyclosporine showed a marked antiproliferative and proapoptotic effect on endothelial and epithelial cells. Fibroblast growth was not affected by cyclosporine. Nitric oxide was up-regulated by cyclosporine in epithelial cells and fibroblasts but not in endothelial cells. (alpha1)I and (alpha2)IV collagen synthesis was increased in cyclosporine-treated endothelial and epithelial cells, respectively. Proteolytic activity was increased in endothelial and epithelial cells. TIMP-1 mRNA was up-regulated by cyclosporine in fibroblasts. CONCLUSIONS: Our results demonstrate that cyclosporine exhibits an antiproliferative effect on endothelial and epithelial cells. This effect is associated with induction of apoptosis probably via nitric oxide up-regulation in epithelial cell cultures. Cyclosporine treatment induces ECM accumulation by increasing collagen synthesis in endothelial and epithelial cells and reducing its degradation by up-regulating TIMP-1 expression in fibroblasts. We conclude that cyclosporine affects cell types differently and that the disruption of organ architecture is the result of multiple effects at the cell level.

Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease.

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.

The effects of iloprost infusion on microcirculation is independent of nitric oxide metabolites and endothelin-1 in chronic peripheral ischaemia.

BACKGROUND: Endothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators. METHODS: Fourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2-/NO3-) and endothelin-1 (ET-1) plasma concentrations were detected; moreover, the endothelium-dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo-Doppler device. RESULTS: The echo-Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 +/- 17.49 vs. 310.71 +/- 36.32 s; P > 0.04). NO2-/NO3- and ET-1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected. CONCLUSION: This study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2-/NO3- or ET-1.

In vitro effects of GM-CSF on mature peripheral blood neutrophils.

GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.

[beta-Interferon therapy of chronic hepatitis HCV+, 1b genotype]. / La terapia con beta-interferone dell'epatite cronica HCV+, genotipo 1b.

Various papers reported that chronic viral hepatitis is the principal cause of chronic liver disease, as cirrhosis and hepatocarcinoma. Interferon is the only agent known to have a beneficial effect in chronic hepatitis. The response rate has been less than 10 percent in patients with genotype 1b, but in patients with genotype 2 or 3 it has been greater than 40 percent. Aim of our investigation was to study 10 patients suffering from chronic viral hepatitis HCV related, genotype 1b, non responder to interferon-alpha therapy. In these patients we administered beta-interferon at the dose of 6 million units, 3 times a week, for 3 months. A significant reduction of aminotransferase level was reported after 3 months of the start of the therapy. An higher level of beta-interferon plasma rate was found in 3 non responder patients. The interaction of beta-interferon with the immune system was demonstrated with an increase of CD8+ lymphocytes that correlated with decrease of HCVRNA. The treatment with beta-interferon have a beneficial effect in patients with chronic hepatitis HCV related, genotype 1b, no responder to interferon-alpha therapy.

CD44 isoforms, including the CD44 V3 variant, are expressed on endothelium, suggesting a role for CD44 in the immobilization of growth factors and the regulation of the local immune response.

Endothelium plays a central role in the regulation of site and inflammation specific leukocyte migration. Some of the mediators involved in leukocyte migration, such as chemokines, can bind to heparan sulfate on the endothelium resulting in immobilization near their sites of production. Because CD44 variants expressing V3 have been shown to carry heparan sulfate side chains and to interact through these side chains with heparan sulfate binding growth factors, we investigated the expression of CD44 variants on endothelium. We found a strong expression of V5, V7-8 and V10 CD44 variants and a weaker expression of V3 and V6 CD44 variants on endothelium by using immuno-histochemistry and by FACS analysis. Expression of CD44 V3 variants was confirmed at both the protein and mRNA levels by Western blotting and by reverse transcriptase-PCR respectively. Expression of CD44 variants was unaffected by IL-1beta, IL-8, TNFalpha, IFNgamma or IL-4 treatment, indicating either constitutive expression of these variants or involvement of other cytokines in their regulation.

Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation.

The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.

Solitary extramedullary plasmacytoma.

A rare case of abdominal plasmacytoma is described. A computed guided biopsy of abdominal mass permitted an accurate diagnosis. Blood findings revealed an increased gamma-globulin level and serum immunoelectrophoresis revealed high IgG-kappa spike. Bone marrow biopsy resulted negative for neoplastic infiltration. Plasmacytoma is a malignant proliferation of differentiated B lymphocytes which produce immunoglobulin. In our case, microscopically, biopsy of abdominal mass revealed the presence of plasmablasts with bizarre multiforme nuclei, spindled contours and positive immunoenzymatic reaction for CD38, suggestive for plasma cell proliferation.