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Biomedical subjects

I Shapira

Publications and source records attributed to I Shapira.

At least 55 records · Page 3Linked to original sources

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.

Aged↗

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↗

Retrograde embolism and atherosclerosis development in the human thoracic aorta: are the fluid dynamics explanations valid?

The mechanisms of atherosclerosis development in the thoracic aorta is miscellaneous and still only partially understood. The marked variability of the sites of deposition of atherosclerotic plaques in the aorta could not be clarified based solely on the risk-factors theory of atherosclerosis. The sites of deposition of atherosclerotic plaques are considered to be affected by blood-flow patterns that cause areas of altered shear stress on the aortic wall. Close relations between protruding aortic plaques (PAP), stroke and peripheral emboli were established. The analysis of PAP distribution and motion to characterize atherogenesis in the human thoracic aorta and the pathogeneses of embolic events was performed. We concluded that protruding aortic plaques and markers of relative aortic flow instability (occurrences of vortices) are predominantly noticed in the human arch and in the descending aorta, whereas the ascending aorta showed lesser prevalence of atheromatosis. Reversal and rotational blood-flow in the thoracic aorta most likely exist in all patients with systemic emboli and mobile protruding aortic atheromas. Therefore, retrograde cerebral embolism from distal aortic plaques is conceivable.

Adolescent↗

Bilateral skeletonized internal thoracic artery grafts in patients with diabetes mellitus.

OBJECTIVE: Increased risk of deep sternal infections has prohibited routine bilateral internal thoracic artery grafting in diabetic patients. The technique for harvesting the skeletonized internal thoracic artery provides the potential to minimize this risk. The purpose of this study was to compare the outcome of bypass grafting with bilateral skeletonized internal thoracic arteries in diabetic and nondiabetic patients. METHODS: From May 1996 to April 1998, 231 consecutive diabetic and 534 nondiabetic patients underwent bilateral skeletonized internal thoracic artery grafting. Mean age was 66 years. Compared with the nondiabetic group, the diabetic group comprised more women (29% vs 18%, P =.001), had a greater prevalence of hypertension (53% vs 44%, P =.019) and congestive heart failure (20% vs 14%, P =.016), but a lower prevalence of preoperative acute myocardial infarction (26% vs 34%, P =.027). RESULTS: Operative mortality of diabetic patients was comparable with that of nondiabetic patients (3% vs 2.6%). The two groups also had similar occurrences of deep sternal infection (2.6% vs 1.7%, respectively, P =.40). Deep sternal infection was significantly more prevalent in obese, diabetic women (3/20 = 15%) than in diabetic patients without this combination of risk factors (3/211 = 1.4%, P <.0001) (odds ratio 11.1, confidence interval 2.1-59.4). Diabetic patients also had a higher incidence of stroke (3.5% vs 0.9%, P =.014). Three-year actuarial survival of diabetic patients was lower (91.3% vs 94.7%, P =.083). CONCLUSIONS: Bilateral skeletonized internal thoracic artery grafting is a good surgical revascularization option in diabetic patients. Operative mortality and prevalence of sternal infection are comparable with those of nondiabetic patients. However, the risk of sternal infection in obese diabetic women is high, and for them we advocate the use of a single artery instead of bilateral internal thoracic arteries.

Aged↗

Identification of new mutations in Israeli patients with X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by impaired peroxisomal betaoxidation of very-long-chain fatty acids (VLCFAs). This is probably due to reduced activation of the VLCFAs and results in demyelination of the nervous system and adrenocortical insufficiency. The ALD gene is localized on Xq28, has 10 exons and encodes a protein of 745 amino acids with significant homology to the membrane peroxisomal protein PMP70. Characterizing the disease causing mutations is of importance in prenatal diagnosis because 12-20% of women who are obligatory carriers show false-negative results when tested for VLCFA in plasma. We have analyzed DNA from blood samples of 7 Jewish (5 Sephardi and 2 Ashkenazi) and 3 Arab Israeli families suffering from ALD. Five missense-type mutations were identified: R104H, Y174C, L229P, R401Q, and G512C. A single mutation, R464X, was nonsense, and two, Y171 frameshift and E471 frameshift, were frameshift. Interestingly, a single mutation was identified in three families of Moroccan Jewish descent, probably due to a founder effect.

Adrenoleukodystrophy↗

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↗

Protamine-induced cardiotoxicity is prevented by anti-TNF-alpha antibodies and heparin.

BACKGROUND: We investigated the role of tumor necrosis factor alpha (TNF-alpha) in protamine-induced cardiotoxicity and the possibility of preventing or decreasing this effect by anti TNF-alpha antibodies and heparin. METHODS: Isolated rat hearts were perfused for 60 min with Krebs-Henseleit solution (KH). The control group was perfused with KH alone, the KH > protamine > KH group was treated from the 20th to the 40th minute with protamine, and the KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF group was treated the same as the KH > protamine > KH group but with anti-TNF-alpha antibodies added throughout perfusion. The KH + heparin > protamine + heparin > KH + heparin group was treated the same as the KH > protamine > KH group but with heparin added to KH throughout perfusion. The KH > protamine > KH + heparin was perfused the same as the KH> protamine > KH group but with heparin added to KH for the last 20 min. Left ventricular (LV) function and coronary flow were measured every 10 min. TNF-alpha was measured in the coronary sinus effluent. Left ventricular TNF messenger RNA was determined in the control and KH > protamine > KH groups at baseline and after the 40-min perfusion. RESULTS: Protamine caused a significant decrease of peak systolic pressure and dP/dt (to 25% of baseline). Significant amounts of TNF-alpha in the effluent in the KH > protamine > KH group (102.3 +/- 15.5 pg/min) and TNF messenger RNA expression in left ventricular samples were detected. TNF-alpha was below detectable concentrations in the control, KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF, and KH + heparin > protamine + heparin > KH + heparin groups. TNF-alpha concentrations correlated with depression of LV peak systolic pressure (r = 0.984; P = 0.01) and first derivate of the increase of LV pressure (r = 0.976; P = 0.001). Heparin improved LV recovery and decreased protamine-induced TNF-alpha release (KH > protamine > KH + heparin group). CONCLUSIONS: Anti-TNF-alpha antibodies and heparin prevent protamine-induced TNF-alpha release and depression of LV function. Heparin improves protamine-induced depression of cardiac function.

Animals↗

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↗

Methylene blue abolishes aortal tone impairment induced by liver ischemia-reperfusion in a dose response manner: an isolated-perfused double-organ rat model study.

Liver ischemia-reperfusion (IR) generates remote organ reperfusion injury attributable to oxidative mediators. We tested the protective properties of methylene blue (MB) on aortal dysfunction. An ex vivo rat liver-aortal ring model was used to study the results of aortal exposure to post-ischemia (IR) hepatic effluent and its response to phenylephrine and isosorbide dinitrate in the absence or presence of increasing concentrations of MB in the effluent. Aortal incubation with IR effluents resulted in abnormal contraction. Ring's response to the vasoactive drugs was abnormally weak both during and following this exposure. Return to stabilization tone was irregular. MB (1.28 mM) best avoided overall dysfunction; 0.86 mM was partially effective, and 0.42 mM was ineffective. Nitrite/nitrate levels were similar to controls in the only IR 1.28 mM perfusate. Liver IR interferes with aortal tone and its response to vasoactive drugs, probably via oxidative interaction with nitric oxide. MB reverses these effects in a dose-dependent fashion.

Acetylcholine↗

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 effect of agmatine administration on ischemic-reperfused isolated rat heart.

BACKGROUND: The natural polyamine Agmatine (Ag) plays a significant role in protection of nerve cell ischemic injury. A previous report indicated that Ag given intraperitoneally to rats enhanced the recovery of the heart from ischemic injury. Based on this initial observation, a larger investigation was undertaken to explore a dose-response effect and possible mechanisms underlying the protective effects. METHODS: Using the modified Langendorff model, 36 isolated hearts were divided into five groups: group 1, hearts receiving 100 microM/L Ag pre-ischemia (n=7); group 2, hearts receiving 100 microM/L Ag pre- and post-ischemia, (n=7); group 3, hearts receiving 250 microM/L Ag pre-ischemia (n=7); group 4, hearts receiving 250 microM/L Ag pre- and postischemia (n=7); and group 5, hearts receiving Krebs-Hensleit solution served as control (n=8). The study design included 20 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion. RESULTS: After ischemia, group 2 developed higher left ventricular pressure P(max) (P<0.01), improved first-derivative of the rise (dP/dt max; P<0.02), and fall (dP/dt min; P<0.04) in left ventricular pressure, and the area calculated under the left-ventricle developed pressure curve (pressure-time integral; P<0.015), but coronary flow was not significantly increased (P=0.06) compared to the control group. Group 1 had improved diastolic recovery: dP/dt min (P<0.05) and coronary flow (P<0.03), compared with the control group. Group 3 had improved P(max) (P<0.01), dP/dt min (P<0.01), and coronary flow (P<0.02); group 4 had no improvement in all hemodynamic parameters. CONCLUSION: Low doses of Ag given pre- and post-ischemia, and high doses given only pre-ischemia have favorable, protective effects on the hemodynamic recovery of isolated rat heart undergoing global ischemia and reperfusion.

Agmatine↗

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↗

TB or not TB: cavitary bronchiolitis obliterans organizing pneumonia mimicking pulmonary tuberculosis.

Two patients with subacute symptoms and signs compatible with pulmonary tuberculosis (TB) had right upper lobe cavitary infiltrates shown on chest radiography. In both patients, purified protein derivative and microbiologic testing excluded TB, and tissue examination yielded typical histologic changes of bronchiolitis obliterans organizing pneumonia (BOOP). Glucocorticoid therapy led to clinical and radiologic resolution. Though probably rare in this situation, BOOP should be considered in the differential diagnosis of patients presenting with clinical and radiologic features of pulmonary TB.

Aged↗

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↗