33 research outputs found
The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome
BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO(2)/FiO(2) (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome
Circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells and arterial function in patients with beta-thalassaemia major
Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells
Vascular Endothelial Dysfunction in β-Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO
The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside) produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO). While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS) in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression
Pleural effusions in Hematologic malignancies
Nearly all hematologic malignancies can occasionally present with or
develop pleural effusions during the clinical course of disease. Among
the most common disorders are Hodgkin and non-Hodgkin lymphomas, with a
frequency of 20 to 30%, especially if mediastinal involvement is
present. Acute and chronic leukemias, myelodysplastic syndromes, are
rarely accompanied by pleural involvement. Furthermore, 10 to 30% of
patients receiving bone marrow transplantation develop pleural
effusions. In cases of hematologic pleural effusions, drug toxicity,
underlying infectious, secondary malignant or rarely autoimmune causes
should be carefully sought. In most cases, the pleural fluid responds to
treatment of the primary disease, whereas resistant or relapsing cases
may necessitate pleurodesis
A randomized comparison of danazol and leuprolide acetate suppression of serum-soluble CD23 levels in endometriosis
Objective: To determine the effects of treatment with danazol and
leuprolide acetate depot on serum-soluble CD23 concentrations in women
with endometriosis.
Methods: This randomized trial involved 20 women 18-42 years old with
regular menses and known pelvic endometriosis who were recruited from a
university hospital between 1993 and 1998. Ten women took 200 mg of
danazol three times daily for 6 months, and the remaining ten were given
3.75 mg of leuprolide acetate depot every 28 days for 6 months.
Blood-soluble CD23 levels were measured before treatment, during the
last 15 days of the 6-month treatment course, and 3 months after
treatment. Only one blood sample was taken from ten women without
endometriosis, between the 5th and 7th days of their menstrual cycles.
For statistical analysis, we used independent and paired t tests with
the Pearson correlation coefficient.
Results: Soluble CD23 levels were significantly higher in women with
endometriosis before treatment than in ten normal controls. Levels
decreased significantly during treatment with either danazol or
leuprolide acetate. Three months after treatment, soluble CD23 values
remained lower than before treatment. There was no correlation between
soluble CD23 concentrations and severity of endometriosis.
Conclusion: Our findings suggest that endometriosis increases soluble
CD23 levels, which can be suppressed with either danazol or leuprolide
acetate injection. (Obstet Gynecol 2000;95:810-3. (C) 2000 by The
American College of Obstetricians and Gynecologists)
Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis
Essential thrombocytosis (ET) is a myeloproliferative disorder resulting
in an increased production of abnormal platelets. Reactive
thrombocytosis (RT) is occasionally observed in clinical situations
including chronic inflammation and malignancy. The aim of the present
study was to evaluate the discriminatory efficiency of various
laboratory tests in patients with ET and cancer-related RT. Forty-five
patients with ET, 52 patients with RT, and 25 age-matched normal
individuals comprised the study population. Plasma interleukin-1 alpha
(IL-1a), IL-2, IL-6, tumor necrosis factor alpha (TNF-a), platelets,
hematocrit, hemoglobin, erythrocyte sedimentation rate (ESR), C-reactive
protein (CRP), lactate dehydrogenase (LDH) and ferritin were determined.
We found increased levels of territin, LDH, CRP, ESR, IL-1a, and IL-6 in
RT compared with ET (p < 0.01 to p < 0.0005). Hemoglobin, hematocrit,
and platelets were significantly lower in RT than in ET (p < 0.0005).
Furthermore, ferritin and ESR were negatively correlated with Hct,
hemoglobin, and TNF-a, whereas ferritin was positively correlated with
ESR, IL-1a, IL-6, and CRP, and IL-1a was positively correlated with
IL-6. We consider that the aforementioned parameters should be included
in the investigation of unexplained thrombocytosis for the
differentiation of essential from cancer related thrombocytosis
Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for determination of GHB, precursors and metabolites in different specimens: Application to clinical and forensic cases
Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma
Angiogenesis plays an important role in multiple myeloma (MM)
progression. Various mitogens such as vascular endothelial growth factor
(VEGF) and basic fibroblast growth factor (FGF-2) have been implicated
in the angiogenic process of various malignancies. Interleukin-6 (IL-6)
is a growth factor of myeloma cells and its signaling is mediated via a
cell surface receptor complex (IL-6r). IL-6 and tumor necrosis
factor-alpha (TNF-alpha) are involved in the secretion of VEGF by IL-6r
expressing myeloma cells. In this study, serum FGF-2, VEGF, IL-6r, and
TNF-alpha were measured in 46 untreated MM patients and were studied in
relation to disease stage (by Salmon-Durie criteria) and severity
[assessed by serum beta(2)-microglobulin (beta(2)M), C-reactive
protein (CRP), alpha(1)-antitrypsin (alpha(1)AT), and lactic
dehydrogenase (LDH) levels]. The results showed that FGF-2, VEGF, IL-6r,
and TNF-alpha were significantly elevated in MM patients in comparison
to controls (p<0.008) and were significantly higher in stage III disease
in comparison to stages I and II (p<0.03). The mean concentrations of
IL-6r were 877 374, 1220+/-308, 1431+/-878, and 453+/-180 pg/ml for
stages I, II, and III and controls, respectively. Levels of beta(2)M,
alpha(1)AT, CRP, and LDH were all significantly higher in MM patients
than controls and increased with advancing stage of disease. There were
positive correlations of both VEGF and FGF-2 with IL-6r, TNF-alpha,
beta(2)M, alpha(1)AT, CRP, and LDH. We conclude that IL-6r and TNF-alpha
increase in parallel to VEGF and FGF-2 with increasing stage of MM
disease. These molecules correlate with biochemical markers of disease
activity and may play a role in the progression of multiple myeloma
Clinical significance of circulating endothelial adhesion molecules (sE-selectin and sICAM) in untreated multiple myeloma patients
Background: The expression of adhesion molecules is important for the
interaction of myeloma cells with the bone marrow microenvironment. In
the current study, serum soluble adhesion molecules (sICAM-1 and
sE-selectin) were measured in untreated multiple myeloma (MM) patients
in relation with other markers of disease activity. Materials and
methods: The study group consisted of 67 patients with MM (classified
according to the Durie-Salmon classification) and 15 controls.
Interleukin-6 (IL-6), sICAM-1 and sE-selectin concentrations were
determined by enzyme-linked immunosorbent assay (ELISA). In addition,
the monoclonal protein, erythrocyte sedimentation rate (ESR) and
hemoglobin (Hb) concentration were also determined. Results: Serum
sICAM-1 level increased significantly at advanced stages of MM and was
higher in comparison to controls (p<0.01). sE-selectin increased
significantly with advancing stage of the disease, but did not differ
from controls. IL-6, ESR and M-component were significantly higher and
Hb concentrations lower with advancing stage of disease. There was a
positive correlation of IL-6 with sICAM-1 and sE-selectin. Conclusions:
We conclude that serum sICAM-1 differs in multiple myeloma patients from
normals and together with sE-selectin increase in parallel to increasing
stage of disease, which may reflect a dysregulation and possible
involvement of these adhesion molecules in myeloma progression. (C) 2004
Elsevier B.V. All rights reserved
Relation between bone marrow angiogenesis and serum levels of angiogenin in patients with myelodysplastic syndromes
Angiogenesis is implicated in the progression of myelodysplastic
syndromes (MDS). Bone marrow microvascular density (MVD), serum
angiogenin (ANG) and interleukin 6 (IL-6) were measured in 67 patients
with untreated MDS. MVD, ANG and IL-6 were significantly higher in the
patient group as a whole when compared to controls (P < 0.01). MVD and
ANG were significantly higher in subtypes with a high-risk for leukemic
transformation (RAEB, RAEB-t and CMML) than in low-risk subtypes (RA and
RARS) (P < 0.01). In the MDS group, a positive correlation was found
between ANG and IL-6 (P < 0.001) and also between MVD and IL-6 (P <
0.05). Using multivariate analysis, only IL-6 displayed independent
prognostic value and was inversely related to MDS survival. (C) 2004
Elsevier Ltd. All rights reserved