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Previous studies have documented the presence of increased red blood cell aggregability in patients with ischemic heart and brain diseases. We adapted a simple slide technique and image analysis to reveal the state of erythrocyte adhesiveness/aggregation (EAA) in the peripheral blood of 206 such patients and in 174 controls. A significant (P

This study tests the hypothesis that mitral annular calcium (MAC) detected by transthoracic echocardiography (TTE) is a marker for high prevalence and severity of coronary artery disease (CAD) in patients undergoing coronary angiography. Pathological studies have suggested that there is an association between MAC and calcific deposits in coronary arteries; however, there are no clinical data to support this association. One hundred sixty-five patients with MAC (101 women and 64 men; mean age 71 +/- 8 years) who underwent cardiac catheterization with coronary angiography for various reasons were compared with 147 age-matched controls without MAC who underwent coronary angiography for the same indications during the same period. MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet detected by TTE. Obstructive CAD was defined as either > or = 50% reduction of the internal diameter of the left main coronary artery or > or = 70% reduction of the internal diameter of the left anterior descending, right coronary, or left circumflex artery distribution. Compared with controls, the MAC group had a significantly higher prevalence of CAD (89% vs 75%, p = 0.001) and higher rates of 3-vessel disease (45% vs 24%, p = 0.001) and left main CAD (13% vs 5%, p = 0.009). Nonsignificant CAD was more common in the control group (25% vs 11%, p = 0.001). Multivariate analysis identified MAC (p = 0.0002), indications for cardiac angiography (p = 0.02), sex (p = 0.03), and diabetes mellitus (p = 0.03) as independent predictors for the presence and severity of obstructive CAD. MAC detected by TTE may be a marker for high prevalence and severity of CAD in patients undergoing coronary angiography. [ABSTRACT FROM AUTHOR]

The objective of this study was to document the reduced acute phase response that appears in children with viral as opposed to bacterial infections. The white blood cell count (WBCC), the erythrocyte sedimentation rate (ESR), and leukocyte and erythrocyte adhesiveness/aggregation were determined in 36 children with acute bacterial infection, 29 children with viral infection, and 19 controls. A significant reduced WBCC, ESR, and leukocyte and erythrocyte adhesiveness/aggregation was noted in the children with acute viral infection as opposed to those with bacterial infection: 10,800 +/- 3600 and 20,000 +/- 10,000 cells/cm2, 29 +/- 21 and 53 +/- 35 mm Hg, 23 +/- 9 and 41 +/- 15%, and 3.4 +/- 5.1 and 9.8 +/- 13.6 microns, respectively. The results indicate that a reduced acute phase response can be observed in children with an acute viral infection. This can have diagnostic implications and pathophysiological consequences in terms of less flow impairment in the microcirculation due to less red and white blood cell aggregation.

We applied an erythrocyte adhesiveness/aggregation test (EAAT) to a model of plasma exchange in individuals with familial and primary hypercholesterolemia. The significant (p < 0.0001) reduction in the concentration of fibrinogen by 56%, globulins by 48%, and cholesterol by 53% corresponded to the expected significant (p < 0.0001) reduction in the degree of erythrocyte adhesiveness/aggregation in the peripheral venous blood. By virtue of its being a real-time, simple, very-low-cost, and essentially bedside technique, the EAAT might have the potential of disclosing information of rheological relevance immediately before, during, as well as following apheretical procedures administered to patients with an impaired rheological profile.

Objectives: To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia., Design: Prospective cohort study., Setting: A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997., Results: Of 137 episodes of positive blood cultures for CNS, 41 (30%) were considered as true infection. Twenty-seven of 119 episodes associated with only 1 blood culture positive for CNS (23%) met the definition of infection as compared with 14 of 18 episodes (78%) associated with 2 or more blood cultures positive for CNS (P <.001). Methicillin resistance was significantly more frequent among Staphylococcus epidermidis isolates of episodes of true bacteremia than of episodes of contamination (15 of 22 [68%] vs. 11 of 33 [33%], respectively; P =.02). S hominis was isolated only in episodes considered as contamination (P =.01). It was estimated that CNS represents 24% of all nosocomial bloodstream pathogens. When CNS were isolated in the first 48 hours of hospitalization, an intravascular device was more frequently associated with episodes of true bacteremia than in those considered as contamination (7 of 7 [100%] vs. 10 of 57 [18%], respectively; P <.001). The mortality rate among patients with true CNS bacteremia was 16%., Conclusion: Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

Background: Medical personnel who work in small geriatric institutions most frequently do not have access to realtime laboratory facilities., Methods: In order to present a new method to determine the presence of an inflammatory response and for the assessment of its intensity, 118 patients aged 77 +/- 6 years with various bacterial infections were evaluated as well as 129 elderly individuals with various stressful conditions but no acute infections who served as controls. The leukocyte and erythrocyte adhesiveness/aggregation tests were performed by using a simple slide test and image analysis. The availability of the CD11b/CD18 and CD62L antigen on the leukocytes' surface was measured by whole blood flow cytometry, and the quantitative C-reactive protein by using laser nephelometry and specific antihuman C-reactive protein antibodies., Results: A significant difference was noted between patients and controls for all variables obtained by the slide test and image analysis. In addition, a highly significant correlation was noted between the number of leukocytes counted on the slides and white blood cell count, between the leukocyte adhesiveness/aggregation test and quantitative C-reactive protein, and between the degree of erythrocyte adhesiveness/aggregation and either the Westergren sedimentation or fibrinogen concentration., Conclusions: By using our low-cost and real-time slide test, any medical or paramedical personnel can get relevant information regarding the presence of an acute phase response at the point of care.

Increased red cell aggregability might have unfavorable rheological effects in the microcirculation. It has been suggested that thrombolysis-related hypofibrinogenemia might be associated with a reduced erythrocyte adhesiveness/aggregation. We followed the reduction in erythrocyte adhesiveness/aggregation using a simple slide test and image analysis that measures the spaces that are formed between the aggregated erythrocytes. A significant (p = 0.01) reduction in the degree of erythrocyte adhesiveness/aggregation was noted in patients with acute myocardial infarction who received thrombolysis as opposed to individuals with Braunwald Class IIIB unstable angina who had normal fibrinogen concentrations. No change was found in the Westergren erythrocyte sedimentation rate, which is an indirect method to detect changes in aggregability of red blood cells. The present study shows the superiority of using a direct measurement of red blood cell adhesiveness/aggregation. This extremely rapid, cheap and almost bedside methodology to detect changes in erythrocyte adhesiveness/aggregation might be useful to detect changes of hemorheological relevance following thrombolysis., (Copyright 2002 S. Karger AG, Basel)

The objective of this study is to examine the possibility of using Telemedicine to diagnose the presence of the inflammatory response and to assess its intensity at the point of care. One drop of citrated peripheral venous blood from 15 patients with infection/inflammation and 15 controls were used to prepare the slides. Unstained pictures were analyzed using a microscope, video camera and image analyzer (INFLAMETTM, Biovision, Tel Aviv, Israel). The jpg-compressed images were transferred via telephone to a physician in a remote location. A significant correlation was noted between the white blood cell count and the number of leukocytes per square mm by image analysis (r = 0.67 p < 0.0001 n = 30), between the degree of leukocyte adhesiveness/aggregation and the concentration of C-reactive protein (r = 0.42 p = 0.02 n = 29) and between the degree of erythrocyte aggregation and either fibrinogen concentrations (r = 0.73 p < 0.0001) or erythrocyte sedimentation (r = 0.83, p < 0.0001). No problems occurred during file transmission and there were no transfer errors. Physicians can successfully estimate the presence of an inflammatory response and its intensity using a simple slide test, image analysis, and Telemedicine technology.

White blood cells may have a role in the aetiopathogenesis of atherosclerosis disease in patients with risk factors for this disease. We examined the white blood cell count in a group of 331 patients and controls of the same age group (139 women and 192 men), the numbers of individuals with no, one, two or more atherosclerotic risk factors being 29, 47, 35 and 28 for women and 50, 45, 68 and 29 for men, respectively. The risk factors included were hypertension, hyperlipidaemia, current smoking and diabetes mellitus. A stepwise increment in the white blood cell count was found in both women and men, the respective values for no, one, two or more risk factors being 6.3 +/- 1.5, 7.6 +/- 1.9, 7.5 +/- 1.8, 7.3 +/- 1.4 and 6.6 +/- 1.6, 6.9 +/- 1.9, 7.4 +/- 2.1, 8.1 +/- 2.6 (absolute number of cells per cm x 103). The one-way analysis variance was found to be significant for both women (P=0.01) and men (P=0.01), as well as the entire cohort (P=0.03). We conclude that the multiplicity of risk factors for atherosclerosis is associated with the appearance of an increased number of white blood cells in the peripheral blood. These findings might represent an enhanced inflammatory response in these individuals and at the same time reveal a potential harmful role of the cells in the aetiopathogenesis of the disease.

Objective: To study the state of erythrocyte adhesiveness/aggregation in the peripheral blood of women with pregnancy-induced hypertension as well as in matched controls using a simple slide test and image analysis., Methods: We recruited 25 women with pregnancy-induced hypertension. Twenty-five age- and gestational age-matched normotensive volunteers took part in the study and served as controls. Blood smears were evaluated by an image analysis system (INFLAMET). Quantitative measures of erythrocyte aggregation were used to describe the state of erythrocyte adhesiveness/aggregation such as vacuum radius, which measures the spaces between the aggregated erythrocytes. The number of participants was established by power analysis (given alpha of 0.05 and 80% power and considering a minimum difference to detect 4 microm in vacuum radius with a standard deviation of approximately 5)., Results: A significant (P =.002) increment in the state of erythrocyte aggregation was noted in the study group compared with the controls, the vacuum radius values being 16.1 +/- 1.3 and 10.3 +/- 1.2, respectively. Erythrocyte sedimentation rate but not fibrinogen concentration was significantly elevated in the study group. The increased aggregation correlated significantly with fibrinogen concentration, systolic, and diastolic blood pressures., Conclusion: We observed increased aggregability of red blood cells in hypertensive conditions of pregnancy. Our findings are significant in that they reveal blood pressure-related increment in red cell adhesiveness/aggregation despite there being no significant increment in clottable fibrinogen concentrations.

Objectives: To determine whether the increased aggregability of both white and red blood cells previously reported in acute myocardial infarction (aMI) correlates with each other., Design: Cross-sectional study comparing two groups of patients and a group of healthy controls., Setting: A tertiary university affiliated hospital (Intensive Cardiac Care Unit and Department of General Internal Medicine)., Patients: Consecutive patients with aMI, patients with chest pain and no infarction, and healthy controls., Measurements and Results: We adapted a simple slide test and image analysis to reveal the state of both leukocyte and erythrocyte adhesiveness/aggregation in the peripheral blood of patients with aMI. A significant (P=0.0001) increment in the aggregation of both cellular populations was noted in 48 patients with aMI as opposed to the 141 patients with ischemic heart disease and no infarction and in 45 matched controls. In addition, a significant correlation was noted between the various variables of the leukocyte and erythrocyte adhesiveness/aggregation tests., Conclusions: The significant correlation between the aggregability of white and red blood cells in patients with aMI is suggestive of there being a commonly shared adhesive protein(s). The prompt identification of patients with increased aggregation might have clinical and therapeutic implications.

Objective: To determine whether increased erythrocyte aggregability has prognostic implications in patients with established ischaemic heart disease., Methods and Results: We have adopted a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation (EAA) in the peripheral blood of patients with ischaemic heart disease and an eventful course (n=46) as opposed to those with an uneventful (n=43) course. A significant correlation was noted between the results of the erythrocyte adhesiveness/aggregation test (EAAT) and either erythrocyte sedimentation or fibrinogen concentration. When we sampled the results of fibrinogen in the group of eventful course they were not significantly different from the results obtained in the uneventful one. This was the case with the results of the erythrocyte sedimentation rate. However, the variables of the EAAT showed a significant difference, the values in the eventful group being higher than those observed in the uneventful one., Conclusions: The EAAT is a valuable tool to disclose the presence of increased red blood cell aggregability in patients with ischaemic heart disease. Increased EAA might have prognostic implications in patients with ischaemic heart disease.

Risk factors for atherothrombosis including increased leukocyte count, hyperlipidemia, diabetes mellitus, hypertension as well as smoldering inflammation and hyperfibrinogenemia might affect the aggregability of peripheral blood erythrocytes, leukocytes as well as platelets. We have used a simple slide test and image analysis to reveal the presence of these aggregabilities obtained in one single drop of peripheral venous citrated blood in 48 individuals with risk factors for atherothrombosis. A significant correlation was noted between the state of adhesiveness/aggregation of all the above mentioned three cellular elements and the concentrations of total and LDL cholesterol. The correlation with triglycerides concentrations was more modest. A significant reduction of adhesiveness/aggregation was noted in 18 individuals following an intervention to reduce the concentration of cholesterol and triglycerides. This reduction might have a favorable hemorheologic effect. Our results are significant in that they show that it is possible to detect the above mentioned changes in whole blood, following a single step and minimal manipulations, at real time and low cost.

Background: Physicians who work in small clinics, far away from medical centers, cannot obtain relevant information regarding the acute phase response at low cost and real time., Methods: We adopted a simple slide test and image analysis to determine the number of white blood cells in the peripheral blood, their degree of adhesiveness/aggregation as well as that of the red blood cells. Three independent observers scored the images into categories of no (1), mild (2), moderate (3) or severe (4) inflammation., Results: A substantial interobserver agreement was noted for all three observers. No patient classified as having no (1) inflammation was given a score of moderate (3) or severe (4) inflammation and vice versa. The one-way analysis of variance (age- and gender-adjusted) confirmed that the data obtained from the image analyzer are significantly different between the above-mentioned four categories., Conclusions: It is possible to use a simple slide test and image analysis to discriminate effectively between various degrees of inflammation intensity. Since it is possible to send the pictures via telephone, Inter- or Intranet to a physician somewhere else, it might be attractive for medical personnel who work in small clinics not equipped with sophisticated laboratory facilities. This technique is currently being evaluated for possible Telemedicine and E-Health uses., (Copyright 2001 S. Karger AG, Basel)

Background: Due to a lack of simple, inexpensive, and real-time methodology, the state of erythrocyte adhesiveness/aggregation is not measured in daily practice by most clinicians. Methods: We measured the state of erythrocyte adhesiveness/aggregation before and following the administration of intravenous high-dose gamma globulins in 18 patients with various autoimmune diseases using a simple slide test and image analysis system (INFLAMET). Results: A significant (P=0.01) increment in the state of erythrocyte adhesiveness/aggregation (from 2+/-3 to 8+/-9 arbitrary units) was noted in the entire study group despite a significant (P=0.008) decrement (from 350+/-97 to 323+/-127 mg%) in the concentration of fibrinogen and no significant change in the erythrocyte sedimentation rate (32+/-30 mm/h before and 35+/-29 mm/h following administration of gamma globulin). Conclusions: By using a simple slide test and image analysis, we were able to provide relevant rheological information that was not available from either of the routine indirect tests, i.e. the Westergren erythrocyte sedimentation rate and the concentration of fibrinogen.

Background: Previous articles have reported the appearance of leukopenia after the administration of high-dose intravenous gamma-globulins., Methods: A simple slide test was used to reveal the state of leukocyte aggregation (LA) in the peripheral blood as well as the absolute number of leukocytes in the slides., Results: A significant (P < 0.00001) increment was noted in the state of LA, from 9 +/- 6% before to 25 +/- 11% after gamma-globulin administration. This was accompanied by a significant (P < 0.0004) reduction in the number of white blood cells in the peripheral blood (from 8433 +/- 3905 to 6550 +/- 3252 cells/mm3) but no significant change in the absolute number of the cells as determined by the leukocyte count per high power field in the peripheral slides., Conclusions: We raise the possibility that the leukopenia reported in some patients after the intravenous administration of high dose gamma-globulin is explained in part by the agglutination effect of the drug.

The state of leukocyte and erythrocyte adhesiveness/aggregation was determined in the peripheral blood of 382 patients with infection/inflammation as well as in 72 controls by using a simple slide test and image analysis. A highly significant correlation (r = 0.4, n = 455, p < 0.001) was found between the state of leukocyte and erythrocyte adhesiveness/aggregation. The extent of both leukocyte and erythrocyte aggregation correlated with the concentration of fibrinogen. Significant aggregation of leukocytes with erythrocytes was noted as well. We conclude that both leukocyte and erythrocyte aggregation occur in the peripheral blood of patients with infection/inflammation. Such cell aggregation, which might have detrimental rheological consequences, can be detected by using our novel technique.

Objective: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation., Methods: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions., Results: There was a highly significant (p<0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) +/- SD, 210+/-102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159+/-73). Similar results were observed on the monocytes: 309+/-151 and 235+/-97, respectively (p<0. 00001)., Conclusion: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals.

Background and Purpose: It has been established that mitral annulus calcification (MAC) is an independent predictor of stroke, though a causative relationship was not proved, and that carotid artery atherosclerotic disease is also associated with stroke. The aim of this study was to determine whether there is an association between the presence of MAC and carotid artery atherosclerotic disease., Methods: Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 133 patients (60 men and 73 women; mean age, 74.3+/-8 years; range, 47 to 89 years) underwent carotid artery duplex ultrasound for various indications; the study group comprised these patients. They were compared with 129 age- and sex-matched patients without MAC (57 men and 72 women; mean age, 73.6+/-7 years; range, 61 to 96 years) who underwent carotid artery duplex ultrasound during the same period for the same indications. MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet. MAC was considered severe when the thickness of the localized, highly reflective area was > or =5 mm on 2-dimensional echocardiography in the 4-chamber view. Carotid artery stenosis was graded as follows: 0%, 20%, 40%, 60%, 80%, and 100%., Results: Compared with the control group, the MAC group showed a significantly higher prevalence of carotid stenosis of > or =40% (45% versus 29%, P=0.006), which was associated with > or =2-vessel disease (23% versus 10%, P=0.006) and bilateral carotid artery atherosclerotic disease (21% versus 10%, P=0.011). Severe MAC was found in 48 patients. More significant differences were found for the severe MAC subgroup (for carotid stenosis of > or =40%) in rates of carotid artery atherosclerotic disease (58% versus 29%, P=0.001), and > or =2-vessel disease (31% versus 10%, P=0.001), in addition to bilateral carotid artery stenosis (27% versus 10%, P=0.004) and even bilateral proximal internal carotid artery stenosis (21% versus 8%, P=0.015). Furthermore, significant carotid artery atherosclerotic disease (stenosis of > or =60%) was significantly more common in the severe MAC subgroup than in the controls (42% versus 26%, P<0.05) and was associated with higher rates of > or =2-vessel disease (19% versus 7%, P=0.02) and bilateral carotid artery stenosis (17% versus 7%, P=0.05). On multivariate analysis, MAC and age but not traditional risk factors were the only independent predictors of carotid atherosclerotic disease (P=0.007 and P=0.04, respectively)., Conclusions: There is a significant association between the presence of MAC and carotid artery atherosclerotic disease. MAC may be an important marker for atherosclerotic disease of the carotid arteries. This association may explain the high prevalence of stroke in patients with MAC.