Prognostic implications of admission inflammatory profile in acute ischemic neurological events.

OBJECTIVE: To reveal the potential prognostic implications of admission inflammatory markers in patients with acute ischemic neurological events. PATIENTS AND METHODS: Sixty patients with an acute ischemic neurological event who were examined within 24 h from the appearance of symptomatology. We determined the high-sensitive C-reactive protein (hs-CRP) concentrations, erythrocyte sedimentation rate (ESR), fibrinogen concentrations and degree of erythrocyte adhesiveness/aggregation. RESULTS: A significant correlation was noted between baseline hs-CRP concentrations, ESR as well as adhesiveness/aggregation and the outcome of the ischemic neurological event as determined by the modified Rankin scale 8-12 months following the insult. CONCLUSION: Admission inflammatory markers have long-term prognostic implications in patients with acute ischemic neurological events. These findings are relevant in view of the new therapeutic interventions now available for reducing the inflammatory response.

Rheological determinants of red blood cell aggregation in diabetic patients in relation to their metabolic control.

AIMS: To determine whether increased red blood cell adhesiveness/aggregation in diabetic patients is related to the extent of their metabolic control. METHODS: We measured erythrocyte adhesiveness/aggregation in a group of 85 adult patients with diabetes mellitus by using citrated venous whole blood and a simple slide test. The erythrocyte adhesiveness/aggregation was determined by measuring the size of the spaces that are formed between the aggregated erythrocytes. We divided the patients into those with either low or high erythrocyte adhesiveness/aggregation values. RESULTS: The erythrocyte adhesiveness/aggregation values of the two groups differed significantly in terms of their fibrinogen concentration, erythrocyte sedimentation rate, high sensitive C-reactive protein (CRP), total cholesterol and triglyceride concentrations. There was no difference between the two groups regarding the concentrations of HbA(1c). Logistic regression was applied to construct a model to predict the belonging of a patient in the low or high erythrocyte adhesiveness/aggregation group. A linear regression was applied to construct a model to predict the erythrocyte adhesiveness/aggregation values. Both models turned out to include gender, age, fibrinogen, triglyceride, retinopathy, coronary artery disease and age and gender interaction. Neither HbA(1c) nor CRP entered the models. CONCLUSIONS: The degree of erythrocyte adhesiveness/aggregation and several variables of the acute-phase response in patients with diabetes mellitus are not directly related to the degree of metabolic control as evaluated by means of HbA(1c) concentration. Diabetic patients might benefit from rheological or anti-inflammatory interventions regardless of their metabolic control.

Clinical and epidemiologic significance of coagulase-negative staphylococci bacteremia in a tertiary care university Israeli hospital.

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.

The picture of inflammation: a new concept that combines the white blood cell count and erythrocyte sedimentation rate into a new hematologic diagnostic modality.

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.

Increased erythrocyte adhesiveness and aggregation in peripheral venous blood of women with pregnancy-induced hypertension.

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.

The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with type 2 diabetes and ischemic vascular disease.

White blood cells have a potential role in the pathogenesis of vasculopathy in diabetic patients. We studied the circulating peripheral blood in a cohort of patients with documented ischemic heart or brain disease with and without type 2 diabetes by means of image analysis and flow cytometry. Our study showed that the state of leukocyte adhesiveness/aggregation is slightly increased in those who had concomitant diabetes but that there was no difference regarding the expression of CD11b/CD18 and CD62L antigens on the surface of the peripheral blood white blood cells. The finding of a significantly increased number of white blood cells in the peripheral blood of patients with ischemic vascular diseases is important insofar as it is associated with a poorer prognosis.

A leukocyte and erythrocyte adhesiveness/aggregation test to reveal the presence of smoldering inflammation and risk factors for atherosclerosis.

The number of white blood cells in the peripheral blood, the presence of inflammation, increased fibrinogen concentrations and hyperlipidemia are established risk factors for atherosclerosis. It is known that hyperfibrinogenemia and hyperlipidemia cause increased erythrocyte aggregation, that inflammation will confer increased adhesive properties upon white blood cells and that the increased number of white blood cells can be detected in the peripheral blood. Therefore, we adopted a simple slide test and image analysis to determine the number of peripheral blood leukocytes and their state of adhesiveness/aggregation together with an erythrocyte adhesiveness/aggregation test to reveal the presence of these risk factors. The significant correlation between the fibrinogen and cholesterol concentration and the erythrocyte aggregation, between the white blood count and the number of leukocytes on the slides, and between the concentration of C-reactive protein and leukocyte adhesiveness indicate that we have succeeded in designing a simple one-step screening test that will identify patients at risk for atherosclerosis.

The feasibility of estimating the erythrocyte sedimentation rate within a few minutes by using a simple slide test.

The acute phase response is accompanied by the appearance of aggregated red blood cells in the peripheral blood. The Westergren erythrocyte sedimentation rate (ESR) is an indirect measurement of this enhanced aggregability. We adopted a simple slide test and image analysis to reveal the adhesiveness/aggregation of red blood cells. A significant correlation was found between the erythrocyte adhesiveness/aggregation test (EAAT) and the ESR. A predictive model for ESR based on EAAT and the age of the patients was created. This new approach will enable us to obtain within a few minutes a good estimate of whether a given individual has a mild moderate or significant acute phase response. With further development, we will be able to use a bedside small cartridge that will deliver the extrapolated ESR at low costs and within a couple of minutes.

Increased erythrocyte adhesiveness/aggregation in the peripheral venous blood of patients with ischaemic heart disease and an eventful course.

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.

Combined leukocyte and erythrocyte aggregation in patients with acute myocardial infarction.

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.

Image analysis for the detection of increased erythrocyte, leukocyte and platelet adhesiveness/aggregation in the peripheral blood of patients with diabetes mellitus.

Increased erythrocyte, leukocyte, and platelet adhesiveness and aggregation may contribute to the development of ischemic vascular conditions in diabetic patients. They have been described by using different diagnostic systems and following various ex vivo manipulations. We have adopted a simple slide test and image analysis to reveal the adhesiveness and aggregation of the three cellular elements in a picture that is obtained from one single citrated venous blood sample presented on a glass slide. A significant increment in the degree of adhesiveness/aggregation of erythrocytes, leukocytes and platelets was noted in 29 patients with diabetes mellitus as opposed to age- and gender-matched healthy controls. It is feasible to look at the increased state of adhesiveness/aggregation of erythrocytes, leukocytes and platelets present in their native milieu and following minimal manipulation by using an almost real time and low cost procedure.

The usefulness of telemedicine for the detection of infection/inflammation at the point of care.

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.

The multiplicity of atherosclerotic risk factors corresponds to the appearance of increased leukocyte count in the peripheral blood: relevance to the pathogenesis of the disease.

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.

The concomitant appearance of aggregated erythrocytes, leukocytes and platelets in the peripheral blood of patients with risk factors for atherothrombosis.

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.

Activated polymorphonuclear leukocytes and monocytes in the peripheral blood of patients with ischemic heart and brain conditions correspond to the presence of multiple risk factors for atherothrombosis.

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.

INFLAMET: an image analyzer to display erythrocyte adhesiveness/aggregation.

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.

Increased leukocyte aggregation induced by gamma-globulin: a clue to the presence of pseudoleukopenia.

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.

Combined leukocyte and erythrocyte aggregation in the peripheral venous blood during sepsis. An indication of commonly shared adhesive protein(s).

We have used a simple slide test and image analysis to reveal the state of leukocyte and erythrocyte adhesiveness/aggregation in the peripheral blood of 28 patients with sepsis and 28 controls. A significant (P<0.00001) increment in both leukocyte and erythrocyte adhesiveness/aggregation was noted in patients compared with controls. Moreover, a significant (r=0.73, n=56, P<0.001) correlation was noted between the two adhesiveness/aggregation variables themselves, suggesting a common mechanism responsible for these adhesive phenomena. The significant correlation with fibrinogen suggests that this protein might be such a "non-specific glue." Our results indicate that a simple slide technique and image analysis can assess the aggregability of both white and red blood cells in septic patients. This might have clinical application when interventions to reduce cell aggregability are planned in order to improve blood flow in the microcirculation.