Rivka Rotstein

Prognostic implications of admission inflammatory profile in acute ischemic neurological events

Anuk T, Assayag EB, Rotstein R, Fusman R, Zeltser D, Berliner S, Avitzour D, Shapira I, Arber N, Bornstein NM. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002: 106: 196–199.

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 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‐inducedhypertension. 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 αof 0.05 and 80% power and considering a minimum difference to detect 4 μm 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 clotable fibrinogen concentrations.

The erythrocyte adhesiveness/aggregation test (EAAT): A new biomarker to reveal the presence of low grade subclinical smoldering inflammation in individuals with atherosclerotic risk factors

BACKGROUND Multiple acute phase proteins and atherosclerotic risk factors increase the aggregability of erythrocytes. METHODS AND RESULTS We used a simple slide test and image analysis to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of 222 women and 221 men with no, one, two or more atherosclerotic risk factors. The degree of erythrocyte adhesiveness/aggregation correlated significantly with the concentration of commonly used variables of the acute phase response. We also showed that individuals with low erythrocyte adhesiveness/aggregation tend to be younger and to have fewer risk factors for atherosclerosis, including diabetes mellitus, hypertension, hyperlipidemia and smoking. CONCLUSIONS The association between increased erythrocyte adhesiveness/aggregation, higher concentrations of acute phase proteins, and increased atherosclerotic risk factors points to a possible clinical applicability of the erythrocyte adhesiveness/aggregation test (EAAT) to reveal the presence of both low-grade subclinical smoldering inflammation and morbid biology in individuals with risk factors for atherosclerosis.

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.

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.

AN INFLAMMATION METER TO REVEAL THE PRESENCE AND EXTENT OF INFLAMMATION IN OLDER PATIENTS

and no significant difference in muscle area (Table 1) . We found a strong linear correlation between bone and muscle area in both groups of women (Figure 1). Women with osteoporotic fractures had bone areas lower than expected given their muscle areas. In linear regression analyses fitted separately for the two groups (Figure l), we found similar slopes (2.98 vs 2.73) but significantly different intercepts (32.29 vs 113.84; P < .0001). These findings suggest that the reduction in bone mass often observed in women with osteoporotic fractures is attributable to a primary bone-related pathophysiologic process. The bone/muscle ratio may help to identify women with true osteoporosis from those in whom reduction in bone mass is merely the consequence of severe sarcopenia in the context of ageassociated frailty and not a primary disturbance of bone metabolism.

The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients with ischemic brain events.

We adopted a simple slide test and image analysis to determine the state of erythrocyte adhesiveness/aggregation in the peripheral blood of 45 patients with acute ischemic stroke, 30 with TIA and 27 matched controls. A highly significant (P=0.005) difference was noted between patients and controls regarding the degree of erythrocyte adhesiveness/aggregation while there was no significant difference for both erythrocyte sedimentation rate or fibrinogen concentrations. We suggest that our slide test might be a low cost and real time method to detect the increased erythrocyte aggregability in the peripheral blood of patients with acute ischemic neurological events. These findings might be relevant in view of recent studies that suggest a favorable effect of therapeutic interventions directed at the improvements of this hemorrheological aspect in individuals with ischemic vascular conditions.

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

Abstract 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.