Increased erythropoiesis and subclinical inflammation as part of the metabolic syndrome.

Recent studies have suggested the insulin resistance might be accompanied by enhanced erythropoiesis. We have examined this association in individuals with the metabolic syndrome (MS) who in addition to insulin resistance harbor a chronic low grade inflammation. This study is relevant because chronic inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non-smoking women and men with respective age of 46.4+/-9.3 (mean+/-S.D.) and 44.0+/-11.0 years are included. A significant correlation was noted between the numbers of the components of the MS and the inflammatory biomarkers including the white blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations and the erythrocyte sedimentation rate. In addition, a significant correlation (r=0.157, p=0.008) was noted between the number of components of the MS and the number of red blood cells in the peripheral blood in women. The same was true for men (r=0.192, p<0.0005). We conclude that enhanced erythropoiesis could be a new, hitherto unrecognized component of the MS. The enhanced erythropoiesis could give an erroneous impression of general "good" health in these individuals.

Circadian rhythm of acute pulmonary edema.

We found that the onset of acute pulmonary edema demonstrates circadian periodicity. Most episodes occur in the morning or at night. Pulmonary edema occurs more frequently during the colder months.

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.

Cutaneous involvement in a rare case of adult visceral leishmaniasis acquired in Israel.

Skin lesions are rare in visceral leishmaniasis, especially in Mediterranean countries. We describe an unusual case of visceral leishmaniasis in a 41-year-old man that began with a skin lesion. The parasites isolated from both the skin lesion and the bone marrow were typed as Leishmania donovani sensu stricto. This pathogen is not endemic in Israel or neighboring countries; its contribution to adult visceral leishmaniasis in Israel is summarized.

Fatal pulmonary artery thrombosis in a patient with Behçet's disease, activated protein C resistance and hyperhomocystinemia.

Behçet's disease (BD) is known for its tendency for thromboembolism, which is thought to be due to vascular injury. The important role of inherited thrombophilias is now becoming increasingly clear. However, conflicting data exist in terms of the contribution of these factors to the thrombotic risk in BD. In this case report, we describe a patient with BD who presented with severe cor pulmonale due to recurrent chronic venous thromboembolism and pulmonary artery thrombosis. The biochemical evaluation revealed that the patient was homozygotic for the factor V Leiden (R506Q) mutation and had increased levels of homocysteine. His condition deteriorated despite adequate anticoagulation treatment, and he died suddenly after 7 months of follow-up. We assume that the presence of thrombophilic risk factors augments and synergizes with the hypercoagulable state already existing in BD, leading to fatal thrombosis in this patient.

Retinal artery occlusion in a patient with factor V Leiden and prothrombin G20210A mutations.

Retinal artery occlusion is rare in young adults, and may be associated with hereditary thrombophilia. We present a 19-year-old male who was evaluated for central retinal artery occlusion and found to be homozygous for the factor V Leiden mutation and heterozygous for the prothrombin G20210A mutation. Anterior chamber paracenthesis resulted in dramatic improvement, but recurring loss of vision necessitated repeated paracenthesis and the addition of aspirin to standard anticoagulation treatment. The literature concerning hereditary thrombophilia and retinal artery occlusion is reviewed, and the synergistic effect of multiple risk factors is emphasized. Screening for hereditary thrombophilia should be considered for young people presenting with unexplained retinal artery occlusion.

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 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.

Comparative analysis between dextran sulfate adsorption and direct adsorption of lipoproteins in their capability to reduce erythrocyte adhesiveness/aggregation in the peripheral blood.

The purpose of this study was to compare the degree of erythrocyte adhesiveness/aggregation (EAA) reduction of two low-density lipoprotein (LDL) apheretic procedures, namely direct adsorption of lipoproteins (DALI) and dextran sulfate adsorption (DSA). A significant (P < 0.001) reduction of EAA was noted in six hypercholesterolemic patients who underwent a total of 40 apheretic sessions and no difference was noted in the degree of EAA reduction by the two techniques. Thus. being a real-time and point-of-care test, the erythrocyte adhesiveness/aggregation test can be applied in relevant situations of acute ischemia, where therapeutic LDL apheresis could improve the hemorheology of individuals with increased concentrations of cholesterol and inflammatory sensitive proteins.

The appearance of L-selectin(low) polymorphonuclear leukocytes in the circulating pool of peripheral blood during myocardial infarction correlates with neutrophilia and with the size of the infarct.

BACKGROUND: It is assumed that not only leukocytosis, but also the activation of white blood cells (WBC) may play a role in the pathogenesis and prognosis of patients with myocardial infarction (MI). Activation of WBC includes upregulation of CD11b/CD18 and downregulation of CD62L (L-selectin) antigens. HYPOTHESIS: The activation of WBC is associated with the appearance of a larger MI. METHODS: CD11b/CD18 and CD62L were measured on the surface of WBC on Day 1 and Day 3 from the onset of MI. The size of the infarct with estimated by calculating the area under the curve of the creatine kinase enzyme, which was measured every 6 h. RESULTS: A negative correlation was noted between the absolute polymorphonuclear count and the availability of the CD62L on these cells during Day 1 (r = -0.46, p = 0.003) and Day 3 (r = -0.35, p = 0.05). There was a positive correlation between the size of MI and the WBC count (r = 0.46, p = 0.004) and a negative correlation with CD62L on polymorphonuclears (r = -0.35, p = 0.03). During Day 3, the CD11b/CD18 on the polymorphonuclears increased despite a decrement in the absolute number of these cells. CONCLUSION: The neutrophilia during the early phases of acute MI correspond to the appearance of the L-selectin(low) population of polymorphonuclear leukocytes. There is a correlation between the appearance of this population and the size of the infarct.

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 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.

Correlated expression of adhesive properties for both white and red blood cells during inflammation.

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.

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.

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.

Serum lipids as minor determinants of the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with low grade inflammation and moderately increased serum lipids.

Both lipids and inflammation sensitive proteins have been reported to affect the aggregation of red blood cells yet their relative importance in this regard have not been determined. We have included high sensitive C-reactive protein, erythrocyte sedimentation, fibrinogen concentrations as well as various serum lipid concentrations and the degree of erythrocyte adhesiveness/aggregation in the peripheral blood in a linear regression analysis. Partial Pearson correlation coefficients were included as well. In a group of 674 individuals with various atherosclerotic risk factors, low grade inflammation and moderately increased serum lipids, a relatively low correlation was noted between red blood cell adhesiveness/aggregation and triglycerides concentrations. A negative correlation was noted for HDL cholesterol. None of the lipid variables turned significant in the regression analysis. In a group of individuals with atherosclerotic risk factors, low grade inflammation and moderately increased serum lipids, the degree of erythrocyte adhesiveness/aggregation in the peripheral blood correlates much better with the presence of inflammation sensitive proteins than with the presence of increased lipid concentrations.

[Hormonal replacement therapy and inflammatory response--update].

Recent studies have shown that the administration of hormonal replacement therapy (HRT) to postmenopausal women might be associated with the appearance of increased concentrations of C-reactive protein (CRP). This marker of inflammation might be associated with an unfavorable outcome regarding the appearance of ischemic vascular diseases and accelerated atherosclerosis in elderly women. In addition, the use of HRT might be associated with an enhanced thrombotic tendency. Therefore, the administration of HRT to individuals who have increased concentrations of inflammatory markers (CRP for example) and/or thrombophilic ones, might be associated with an eventual less favorable clinical outcome.

Torsade de pointes induced by psychotropic drugs and the prevalence of its risk factors.

OBJECTIVE: To investigate all published case reports of torsade de pointes (TdP) induced by psychotropic drugs (PDs) in order to examine the prevalence of risk factors for TdP prior to the drug initiation. METHOD: We found 45 reports on 70 patients with TdP induced by PDs. Each report was analyzed for the presence of risk factors for TdP: female gender, heart disease, hypokalemia, high doses of offending agent, concomitant use of a QT interval prolonging agent, and a history of long-QT syndrome. RESULTS: Female gender was the most common risk factor for TdP (71.4%). The other studied risk factors were also frequently present (34.2-14.2%). Nearly all patients had at least one and 51 (73%) patients had >2 risk factors for TdP prior to PD initiation. CONCLUSION: We wish to raise the level of awareness of risk factors for TdP in the psychiatric community.