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Biomedical subjects

Itzhak Shapira

Publications and source records attributed to Itzhak Shapira.

At least 19 recordsLinked to original sources

The interval between prothrombin time tests and the quality of oral anticoagulants treatment in patients with chronic atrial fibrillation.

BACKGROUND: The incidence of stroke in patients with atrial fibrillation (AF) can be significantly reduced with warfarin therapy especially if optimally controlled. OBJECTIVES: To evaluate the effect of the interval between consecutive prothrombin time measurements on the time in therapeutic range (INR 2-3) in a cohort of patients with AF on chronic warfarin treatment in the community. METHODS: All INR measurements available from a relatively large cohort of patients with chronic AF were reviewed and the mean interval between consecutive INR tests of each patient was correlated with the time in therapeutic range (TTR). RESULTS: Altogether 251,916 INR measurements performed in 4408 patients over a period of seven years were reviewed. Sixty percent of patients had their INR measured on average every 2 to 3 weeks and most others were followed at intervals of 4 weeks or longer. A small proportion (3.6%) had their INR measured on average every week. A significant decline in the time in therapeutic range was observed as the intervals between tests increased. At one to three weeks interval the TTR was 48%, at 4 weeks interval 45% and at 5 weeks 41% (P<0.0005). A five percent increment in TTR was observed if more tests were performed at multiplications of exactly 7 days (43% vs 48% P<0.0001). CONCLUSIONS: A better control with an increase in the TTR was observed in patients with atrial fibrillation if prothrombin time tests are performed at regular intervals of no longer than 3 weeks.

Administration, Oral↗

Correlated expression of high-sensitivity C-reactive protein in relation to disease activity in inflammatory bowel disease: lack of differences between Crohn's disease and ulcerative colitis.

BACKGROUND/AIMS: As opposed to regular C-reactive protein (CRP) assays, the introduction of high-sensitivity ones has enabled us to detect low grade inflammation in patients with inflammatory bowel disease (IBD). We addressed the subject of the degree of correlation between the concentration of high-sensitivity CRP (hs-CRP) and the inflammatory IBD activity score. METHODS: Included were 90 patients with Crohn's disease (CD), 70 with ulcerative colitis (UC) and 160 controls. Disease activity was determined using CD activity index (CDAI) for CD and Mayo score for UC. The Dade Boering BNII Nephelometer was used to determine the hs-CRP concentrations. RESULTS: The coefficient of correlation between hs-CRP and the disease activity score was similar for both UC (0.26) and CD (0.36). CONCLUSIONS: These findings are relevant for therapeutic intervention in which a greater absolute reduction in the hs-CRP concentration in CD patients (who generally present higher CRP concentrations than those found in UC) might be interpreted as a better response compared to the same absolute reduction in UC patients. This information is needed for clinicians using the hs-CRP assay to estimate IBD disease activity in daily practice.

Adult↗

Burnout and risk of cardiovascular disease: evidence, possible causal paths, and promising research directions.

Burnout is characterized by emotional exhaustion, physical fatigue, and cognitive weariness, resulting from prolonged exposure to work-related stress. The authors review the accumulated evidence suggesting that burnout and the related concept of vital exhaustion are associated with increased risk of cardiovascular disease and cardiovascular-related events. The authors present evidence supporting several potential mechanisms linking burnout with ill health, including the metabolic syndrome, dysregulation of the hypothalamic-pituitary-adrenal axis along with sympathetic nervous system activation, sleep disturbances, systemic inflammation, impaired immunity functions, blood coagulation and fibrinolysis, and poor health behaviors. The association of burnout and vital exhaustion with these disease mediators suggests that their impact on health may be more extensive than currently indicated.

Burnout, Professional↗

Lack of significant effect of low doses of aspirin on the concentrations of C-reactive protein in a group of individuals with atherothrombotic risk factors and vascular events.

Atherothrombosis is associated with the presence of a microinflammatory response, usually monitored by the use of C-reactive protein (CRP) measurements. In the Physician Health Study it was suggested that individuals who benefit most from the treatment are those who have enhanced concentrations of this biomarker. The possibility was suggested that one of the mechanisms of action of aspirin in thrombotic prevention is through its anti-inflammatory properties in terms of reducing the concentration of CRP. We conducted a regression analysis in a cohort of 3888 apparently healthy individuals and those with atherothrombotic risk factors and vascular events, 370 of whom were under the treatment of low doses (<or= 325 mg/day) of aspirin. The significant determinants of CRP concentrations included body mass index, oral contraceptives, hormonal replacement therapy, gender, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, physical activity, age, smoking status and the presence of diabetes mellitus but not the use of low dose of aspirin. We conclude that the use of low doses (<or= 325 mg/day) of aspirin does not have a significant role in the modulation of CRP concentrations in apparently healthy individuals and those with atherothrombotic risk factors and vascular events. The anti-atherothrombotic activity of this drug is probably not mediated through a significant reduction of the concentration of this protein.

Adult↗

Attempted forced titration of blood pressure to <130/85 mm Hg in type 2 diabetic hypertensive patients in clinical practice: the diastolic cost.

The authors assessed the practicality and results of forced titrating of blood pressure to <130/85 mm Hg based on guidelines of the sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the setting of a clinical practice in 257 diabetic, hypertensive patients. Goal diastolic pressure was achieved in 90% of the patients, but goal systolic pressure was achieved in only 33%. In 57% of the patients, the attained diastolic pressure was < or =70 mm Hg, and in 20% of the cohort diastolic pressure was reduced to <70 mm Hg (mean, 60+/-1 mm Hg). Patients with final diastolic pressure <70 mm Hg were older, had a higher prevalence of coronary artery disease, and higher initial systolic and pulse pressures compared with patients with final diastolic pressure of 71-85 mm Hg. Thus, attempted lowering of blood pressure to <130/85 mm Hg is associated with excessive lowering of diastolic pressure in a significant number of patients. Whether the benefits of tight systolic control outweigh the risks of excessive diastolic reduction requires further prospective assessment.

Aged↗

Gender differences in the expression of erythrocyte aggregation in relation to B beta-fibrinogen gene polymorphisms in apparently healthy individuals.

An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the B beta-fibrinogen -455 G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease. The purpose of this study was to investigate the influence of the beta-fibrinogen -455 G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the B beta-fibrinogen -455 G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the -455 A allele compared to subjects with the -455 GG genotype. This association did not exist in women carrying the fibrinogen -455 A allele. The -455 GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the -455 GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the B beta-fibrinogen -455 A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia and a functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.

Aged↗

Increased red blood cell aggregation in patients with idiopathic intracranial hypertension. A hitherto unexplored pathophysiological pathway.

It was the objective of this study to explore the possibility that the aggregation of red blood cells is enhanced in individuals with increased intracranial hypertension (IIH). This is a prospective cross sectional examination in a cohort of patients with IIH and matched controls. The aggregation of red blood cells in the peripheral venous blood was determined by using a slide test and image analysis. We have presently included a group of 33 women with IIH and the same number of women matched for age, body mass index, vascular risk factors and medications. A significant (p = 0.038) increment in fibrinogen concentrations was noted in the patients (341 +/- 60.8 mg/dl) as opposed to the controls 307.9 +/- 64.8). The same stands for the aggregation of red blood cells (aggregation parameter of 8.7 +/- 4.9 in patients vs.5.9 +/- 3.2 in the controls, p = 0.001). We noted an increment in the aggregation of red blood cells in the peripheral blood of 33 women with IIH as opposed to matched controls. Being associated with capillary slow flow, these findings might be relevant to the ethiopathogenesis of this disease.

Adolescent↗

Erythrocyte aggregation is increased in preterm premature rupture of the membranes.

OBJECTIVE: To asses the degree of erythrocyte aggregation in the peripheral blood of women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: This was a prospective case control study. Twenty patients with preterm premature rupture of the membranes and matched controls were recruited at the Lis Maternity Hospital. A slide test and image analysis were used to quantitate the degree of erythrocyte aggregation. Hematological indices and markers of inflammation such as the erythrocyte sedimentation rate and C-reactive protein were also compared. RESULTS: The vacuum radius (VR) of the study group was significantly higher than in the control group at 14.8+/-1.6 microm versus 10.0+/-1.0 microm, respectively (P=0.03). Other hematological indices were not changed significantly between the groups. CONCLUSIONS: We found an increase in erythrocyte aggregation in the peripheral blood of patients with preterm premature rupture of the membranes. We used this sensitive marker of inflammation to further support the theory that PPROM is an inflammatory state.

Adult↗

Inflammation-sensitive proteins and erythrocyte aggregation in atherothrombosis.

OBJECTIVE: To find the relative contribution of various inflammation-sensitive proteins including fibrinogen, immunoglobulins (IgG, IgM and IgA), ceruloplasmin and high sensitivity C-reactive protein (hs-CRP) to the induction and/or maintenance of enhanced erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors. METHODS: The degree of erythrocyte adhesiveness/aggregation was determined by a simple slide test and image analysis. In addition, we measured various inflammation-sensitive protein levels including fibrinogen, ceruloplasmin, immunoglobulins and hs-CRP in a group of 234 individuals with atherothrombotic risk factors and healthy ones. Pearson partial correlations and multiple linear regression analysis were performed. RESULTS: Fibrinogen was found to be the major protein contributing to the enhanced erythrocyte adhesiveness/aggregation, explaining 30% of the model. Fibrinogen and IgG together explained 32.4% of the model. Other inflammation-sensitive proteins did not reach statistical significance and were excluded from the model. CONCLUSIONS: Among inflammation-sensitive proteins measured in our cohort, fibrinogen is the dominant contributor to erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors and healthy ones. These findings may pave the way for the development of therapeutic strategies directed at the attenuation of erythrocyte aggregability in individuals with atherothrombosis.

Aged↗

Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis.

OBJECTIVE: Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion. METHODS: Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion. RESULTS: Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s, P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03, P=0.2), while further increase was observed in the control group (from 1.0+/-0.1 to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart effluent in the control group was increased during reperfusion (79+/-30 and 200+/-22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked TNF-alpha immunostaining of left ventricular tissue was observed only in the control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A treated group at 40 min of reperfusion. CONCLUSION: Monophosphoryl lipid A-induced preconditioning renders the heart more tolerant to ischemia-reperfusion in terms of left ventricular diastolic and systolic function, and prevents tumor necrosis factor-alpha production during ischemia, through aborting the translation phase of tumor necrosis factor-alpha synthesis.

Animals↗

Inflammation-related erythrocyte aggregation in patients with inflammatory bowel disease.

Chronic inflammation is associated with increased erythrocyte adhesiveness/aggregation. This might have deleterious effects on the microcirculatory flow and tissue oxygenation. We aimed to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with inflammatory bowel disease (IBD). Fifty-two patients (24 women and 28 men) with ulcerative colitis (UC) at a mean age of 44.0+/-16.8 years and 96 patients (44 women and 52 men) with Crohn's disease (CD) at a mean age of 38.0+/-15.5 years, with various degrees of disease activity, were matched to normal controls. A simple slide test and image analysis were used to determine the degree of erythrocyte adhesiveness/aggregation. CD activity index (CDAI) was determined in patients with CD, while clinical colitis activity index was applied for patients with UC. A significant (P < 0.0005) increment in the degree of erythrocyte adhesiveness/aggregation was noted in both groups of IBD patients compared with matched control groups. This increment was evident even in individuals with a low index of disease activity and during remission. The highly significant correlation with the concentrations of fibrinogen suggests that the degree of erythrocyte adhesiveness/aggregation is an inflammation-related phenomenon. An enhanced state of erythrocyte adhesiveness/aggregation was noted in the peripheral blood of patients with IBD. This might have a deleterious effect on intestinal microcirculatory flow and tissue oxygenation.

Adult↗

Erythrocyte adhesiveness/aggregation: a novel biomarker for the detection of low-grade internal inflammation in individuals with atherothrombotic risk factors and proven vascular disease.

BACKGROUND: We have introduced a concept of using the erythrocyte as a sensor for the detection of enhanced inflammation-sensitive protein concentrations. We presently evaluated the capability of this new biomarker to detect the presence of inflammation in individuals with a history of a vascular disease as opposed to individuals with atherothrombotic risk factors but no clinically evident vascular disease. METHODS: The degree of erythrocyte adhesiveness/aggregation was determined in the peripheral venous blood by using a simple blood test. Blood was drawn into a syringe containing sodium citrate and trickled onto a slide at an angle of 30 degrees. The slides were than scanned by a blinded technician by using an image analyzer to determine the area that is covered by the erythrocytes. RESULTS: One hundred fifty-six subjects (61 women and 95 men) of 2586 (1238 women and 1348 men) met the criteria of a definite vascular disease (history of stroke, myocardial infarction, coronary artery bypass grafting, or peripheral vascular disease). The degree of erythrocyte aggregation was significantly (P = .008) higher in men, but not in women, with vascular disease as opposed to these without a vascular disease. The results of receiver operating characteristic curve analysis confirmed the diagnostic superiority of the erythrocyte aggregation biomarker over other commonly used markers of the acute phase in men. Similar results were obtained by using discriminant analysis. Finally, a significant correlation was found between the degree of erythrocyte aggregation and other markers of the acute phase suggesting its relevance for the detection and quantitation of low-grade inflammation in individuals with atherothrombosis. CONCLUSION: Erythrocyte adhesiveness/aggregation may be a useful biomarker to detect internal inflammation in individuals with atherothrombosis.

Adhesiveness↗

Revascularization of the right coronary artery in bilateral internal thoracic artery grafting.

BACKGROUND: Bilateral internal thoracic artery (BITA) grafting with a composite T-graft enables right coronary artery (RCA) system revascularization with the distal end of the free right internal thoracic artery (RITA). This study compares this grafting technique to left-sided BITA grafting and RCA revascularization with the right gastroepiploic artery (RGEA) and saphenous vein grafts (SVG). METHODS: From April 1996 to July 1999, 1000 consecutive patients underwent left-sided revascularization with BITA. In 231 patients RCA grafting was performed with free RITA, in 246 with RGEA, in 142 with SVG, and 381 did not receive any graft to the RCA (no-graft group). RESULTS: Female gender, old age (> 70), emergency, and congestive heart failure were less prevalent in the RGEA group, and prior percutaneous transluminal coronary angioplasty was more prevalent in the no-graft group. Thirty-day mortality (3.6%, 4.9%, 2%, and 3.4% in the RITA, SVG, RGEA, and no-graft groups, respectively) and occurrence of perioperative complications (sternal infection, myocardial infarction, cerebrovascular accident, and bleeding) were similar. Overall, however, the trend was toward a higher complication rate in the RITA group (10.3%, 4.9%, 5.6%, and 7.3% respectively, p = 0.06). Midterm follow-up (40 to 78 months) showed similar 6-year survival (Kaplan-Meier) (88%, 87%, 89.5%, and 85.5%, respectively) and similar return of angina (10.8%, 6.3%, 10.6%, and 9.5%, respectively) in the four groups. CONCLUSIONS: Early and midterm results in patients undergoing left-sided BITA grafting are not affected by the conduit used for RCA grafting.

Aged↗

Introducing the wide range C-reactive protein (wr-CRP) into clinical use for the detection of microinflammation.

BACKGROUND: The determination of low grade inflammation in apparently healthy individuals (microinflammation) has prognostic significance in terms of future vascular events and accelerated atherothrombotic disease. METHODS: We compared the Bayer wide range (wr)-C-reactive protein (CRP) immunoturbidometric assay on the ADVIA 1650 system to the Dade Behring high sensitivity (hs)-CRP on the BNII Nephelometer in 1446 apparently healthy individuals having a relatively low (<10 mg/l) concentration. The correlation between the 2 assays was also analyzed in relation to other commonly used microinflammatory biomarkers. RESULTS: A significant (p<0.0005) correlation was noted between the hs-CRP and the wr-CRP for the entire cohort (r=0.99) as well as for both women (r=0.99 n=483) and men (r=0.99 n=963). The mean difference between the measures (hs-CRP minus wr-CRP) was -0.039 (SD 0.317). The Deming regression results for the entire cohort showed a slope of 1.112+/-0.004 and an intercept of -0.263+/-0.01. CONCLUSIONS: The Bayer wr-CRP assay performed presents a reasonable alternative to the Behring Dade hs-CRP assay. The advantages of the wr-CRP assay are its online and real time availability as well as lower costs.

Adult↗

The association between burnout, depression, anxiety, and inflammation biomarkers: C-reactive protein and fibrinogen in men and women.

Following the demonstrated association of employee burnout or vital exhaustion with several risk factors for cardiovascular disease (CVD) and CVD risk, the authors investigated the possibility that one of the mechanisms linking burnout with CVD morbidity is microinflammation, gauged in this study by high-sensitivity C-reactive protein (hs-CRP) and fibrinogen concentrations. Their sample included 630 women and 933 men, all apparently healthy, who underwent periodic health examinations. The authors controlled for possible confounders including 2 other negative affective states: depression and anxiety. In women, burnout was positively associated with hs-CRP and fibrinogen concentrations, and anxiety was negatively associated with them. In men, depression was positively associated with hs-CRP and fibrinogen concentrations, but not with burnout or anxiety. Thus, burnout, depression, and anxiety are differentially associated with microinflammation biomarkers, dependent on gender.

Adaptation, Psychological↗

Acute phase response detection and quantitation at the point of care in older adults with acute bacterial infections.

BACKGROUND: We investigated the reliability of a slide test in determining the presence of acute bacterial infections in a group of older adults to determine the usefulness of this test at the point of care. METHODS: The study group included older adults with an acute bacterial infection and matched controls. We examined the white blood cell count (WBCC), the erythrocyte sedimentation, fibrinogen concentration, and high sensitivity C-reactive protein (hs-CRP), in addition to the slide test that reveals the number of leukocytes and degree of erythrocyte aggregation. RESULTS: There were 144 patients and 144 controls at a respective mean +/- standard deviation age of 71.3 +/- 20.7 and 70.6 +/- 20.2 years. A highly significant difference was noted between patients and controls in all laboratory markers, both conventional and those obtained by the slide test. By using hs-CRP, we correctly predicted the individual group as control or bacterial infection. When analyzed by means of a receiver-operated characteristic (ROC) curve, hs-CRP was again most reliable, with the slide leukocyte test being superior to the WBCC. CONCLUSION: The slide leukocyte count provided a similar diagnostic yield to that of the WBCC. The availability of this slide test at the point of care will provide the clinician with a useful biomarker when faced with clinical decisions in the care of older adults.

Acute-Phase Reaction↗