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Biomedical subjects

S Berliner

Publications and source records attributed to S Berliner.

At least 19 recordsLinked to original sources

Inherited factor XI deficiency confers no protection against acute myocardial infarction.

BACKGROUND AND PURPOSE: Factor XI (FXI) contributes to thrombin generation thereby affecting fibrin formation and to down regulation of fibrinolysis by activation of thrombin-activatable fibrinolysis inhibitor (TAFI). The purpose of this study was to evaluate whether patients with severe FXI deficiency are protected against acute myocardial infarction (AMI). METHODS: The incidence of AMI in patients with severe FXI deficiency (FXI activity less than 15 U dL(-1)) whose age was 35 years or more was compared to the incidence of AMI in age and gender matched persons of the general population. Atherosclerotic risk factors were assessed in FXI deficient patients and blood was tested for prothrombotic parameters such as FV Leiden, prothrombin G20210A, lupus anticoagulant, and platelet membrane polymorphisms. The common mutations causing FXI deficiency in Jews were also examined. RESULTS: Of 96 patients with severe FXI deficiency (55 women and 41 men) 16 had a history of AMI (6 women and 10 men). The median age at the time of AMI was 64.5 for women and 58 for men. The calculated annual rate of AMI in men was similar to the expected in the general Israeli population, whereas in women it was almost 2-fold higher, but this difference did not reach statistical significance. One or more atherosclerotic risk factors were observed in 13 of 16 patients (81.3%) with AMI compared to 44 of 79 patients (55.7%) without AMI (P < 0.001). The frequency distributions of platelet polymorphisms and of prothrombotic polymorphisms were not different between patients with severe FXI deficiency who experienced or not an AMI. None of the patients had lupus anticoagulant. The common genotypes which cause FXI deficiency in Jews were similarly distributed in patients with and without AMI. CONCLUSIONS: Severe FXI deficiency does not confer protection against AMI.

Adult↗

Capillary and venous leukocyte adhesiveness/aggregation to differentiate between viral and bacterial infection.

BACKGROUND: A simple capillary leukocyte adhesiveness/aggregation test (CAPLAAT) might be helpful in determining the intensity of inflammation in acute viral and bacterial infections. PATIENTS AND METHODS: We included 30 patients with acute bacterial infections, 14 with viral infections as well as 48 healthy controls. The leukocyte adhesiveness/aggregation test (LAAT) test was performed using a simple slide test and image analysis. RESULTS: The CAPLAAT had a similar discrimination power between bacterial and viral infections as both the white blood cell count (WBC) and the erythrocyte sedimentation rate (ESR). It was more sensitive than the WBC and the ESR (77%, 68% and 66%, respectively) for the detection of bacterial infections and had a comparable negative predictive value. By analyzing the size distribution of the aggregated leukocytes, we found that a venous leukocyte adhesiveness/aggregation test (VLAAT) of four cells and more had the best positive predictive value (94%) and specificity (95%) for diagnosis of an acute bacterial infection (from all the acute phase response variables examined). CONCLUSION: The CAPLAAT might be attractive for the detection of inflammation and for the assessment of its severity at points of care where the services of a clinical laboratory are not available around the clock.

Acute Disease↗

The leukocyte adhesiveness/aggregation test (LAAT) conveys information of biological relevance and is not a result of chance collision. Something more than another hypothesis.

The leukocyte adhesiveness/aggregation test is a sensitive marker for the detection of inflammation and for the assessment of its intensity. This has been convincingly shown by several independent groups as well as in various models of infection/inflammation. However, it has not been settled whether the concomitant appearance of leukocytosis and aggregation is a result of chance collision or not. We recently examined a group of individuals with proven acute infection/inflammation who had absolutely the same number of white blood cells in the peripheral blood and found significantly enhanced leukocyte adhesiveness/aggregation in patients as opposed to control. These findings clearly demonstrate that the phenomenon of leukocyte adhesiveness/aggregation does not result from a simple chance collision. It probably conveys a message of biological relevance reflecting both the appearance of cell adhesive molecules during activation as well as the contribution of plasmatic sticky proteins.

Acute Disease↗

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.

Acute Disease↗

The erythrocyte adhesiveness/aggregation test for the detection of an acute phase response and for the assessment of its intensity.

We have developed a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation in the peripheral blood of patients with various degrees of the humoral acute phase response. The significant correlation between the results of the erythrocyte adhesiveness/aggregation test (EAAT), the erythrocyte sedimentation rate and fibrinogen concentration support the notion that it is possible to use the EAAT as a marker for the intensity of the acute phase response. Within a group of 860 individuals, we were able to differentiate effectively between groups of patients with a different intensity of humoral acute phase response. The present study confirms previous observations that support the applicability of the EAAT to routine clinical practice.

Acute-Phase Reaction↗

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.

Acute-Phase Proteins↗

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.

Adult↗

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.

Aged↗

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.

Analysis of Variance↗

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.

Acute-Phase Reaction↗

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.

Arteriosclerosis↗

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.

Case-Control Studies↗

Idiopathic osteonecrosis in an adult with familial protein S deficiency and hyperhomocysteinemia.

We describe a 36-year-old man with familial protein S deficiency and homozygosity to the methylene tetrahydrofolate reductase (MTHFR) thermolabile variant who had a stroke followed by an episode of idiopathic osteonecrosis that was successfully managed by surgical core decompression. The patient's symptomatic thrombophilia, as well as that of several of his first-degree relatives who also had thrombotic events, raises the possibility that the thrombophilia was a contributing factor to the development of his osteonecrosis.

Adult↗

Parameters of red blood cell aggregation as correlates of the inflammatory state.

To identify clinically relevant parameters of red blood cell (RBC) aggregation, we examined correlations of aggregation parameters with C-reactive protein and fibrinogen in unstable angina (UA), acute myocardial infarction (AMI), and bacterial infection (BI). Aggregation parameters were derived from the distribution of RBC population into aggregate sizes (cells per aggregate) and changing of the distribution by flow-derived shear stress. Increased aggregation was observed in the following order: UA, AMI, and BI. The best correlation was obtained by integration of large aggregate fraction as a function of shear stress. To differentiate plasmatic from cellular factors in RBC aggregation, we determined the aggregation in the presence and absence of plasma and formulated a "plasma factor" (PF) ranging from 0 to 1. In AMI the enhanced aggregation was entirely due to PF (PF = 1), whereas in UA and BI it was due to both plasmatic and cellular factors (0 < or = PF < or = 1). It is proposed that clinically relevant parameters of RBC aggregation should express both RBC aggregate size distribution and aggregate resistance to disaggregation and distinguish between plasmatic and cellular factors.

Acute-Phase Reaction↗

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.

Acute-Phase Reaction↗

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.

Analysis of Variance↗

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.

Aged↗