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Biomedical subjects

G Keren

Publications and source records attributed to G Keren.

At least 37 records · Page 2Linked to original sources
PubMed2001

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↗
PubMed2001

The probability-outcome correspondence principle: a dispositional view of the interpretation of probability statements.

This article presents a framework for lay people's internal representations of probabilities, which supposedly reflect the strength of underlying dispositions, or propensities, associated with the predicted event. From this framework, we derive the probability-outcome correspondence principle, which asserts that strong dispositions should lead to (1) strong (forceful) and (2) immediate outcomes and, hence, be characterized by high probabilities. In contrast, weak dispositions lead to (1) weak (fragile) and (2) delayed outcomes and are thus associated with low probabilities. We describe six experiments designed to test the correspondence principle. In the final discussion, we examine the implications of the proposed framework, from both a normative and a descriptive viewpoint.

Adult↗
PubMed2001

Why is p = .90 better than p = .70? Preference for definitive predictions by lay consumers of probability judgements.

What do people regard as an informative and valuable probability statement? This article reports four experiments that show participants to have a clear preference for more extreme and higher probabilities over less extreme and lower ones. This pattern emerged in Experiment 1, in which no context was provided, and was further explored in Experiment 2 within a positive and a negative context. The findings were further confirmed in Experiment 3, which employed a Bayesian framework with revisions of opinions. Finally, Experiment 4 showed how preference for high probabilities can lead people to prefer an overconfident to a more well-calibrated (accurate) forecaster. The results are interpreted as manifestations of a search for definitive predictions principle, which asserts that high probabilities are preferred to medium ones and often favored over the corresponding complementary low probabilities on the basis of their capacity to predict the occurrence of single outcomes.

Adult↗
PubMed2001

Selective renal vasodilation and active renal artery perfusion improve renal function in dogs with acute heart failure.

Renal failure is common in heart failure due to renovascular constriction and hypotension. We tested whether selective pharmacological renal artery vasodilation and active renal artery perfusion (ARP) could improve renal function without adverse effects on systemic blood pressure in a canine model of acute heart failure (AHF). AHF was induced by coronary microembolization in 16 adult mongrel dogs. In five dogs, selective intrarenal (IR) papaverine (1, 2, and 4 mg/min) was administered into the left renal artery. In six dogs, ARP was performed in the left renal artery to normalize mean renal arterial pressure followed by administration of IR papaverine (2 mg/min). In five dogs, ARP plus intravenous furosemide was tested. Urine output (UO) and cortical renal blood flow decreased during AHF and were restored by 2 mg/min IR papaverine (UO: baseline 4.2 +/- 0.6, AHF 1.6 +/- 1.3, IR papaverine 5.8 +/- 1.1 ml/15 min; cortical blood flow: baseline 4.3 +/- 0.2, AHF 2.4 +/- 0.6, IR papaverine 4.2 +/- 1.2 ml/min/g) with no significant change in aortic pressure. ARP also increased urine output and cortical renal blood flow (UO: baseline 5.0 +/- 1.1, AHF 0.5 +/- 0.4, ARP 3.8 +/- 3.1 ml/15 min; cortical blood flow: baseline 4.0 +/- 0.5, AHF 2.0 +/- 0.8, ARP 3.52 +/- 1.1 ml/min/g). A combination of these methods in AHF further increased urine output to twice the normal baseline (10.5 +/- 7.5 ml/15 min). Addition of furosemide synergistically increased UO above that achieved with ARP alone (5.5 +/- 2.6 versus 40.3 +/- 24.7 ml/15 min, p = 0.03). In conclusion, ARP and selective renal vasodilation may effectively promote salt and water excretion in the setting of heart failure, particularly when systemic blood pressure is low.

Acute Disease↗
PubMed2001

Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases.

The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.

Aged↗
PubMed2000

Protamine induces vasorelaxation of human internal thoracic artery by endothelial NO-synthase pathway.

BACKGROUND: Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect. METHODS: A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nomega-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained. RESULTS: Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin. CONCLUSIONS: Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine.

Coronary Artery Bypass↗
PubMed2000

Direct ultrasound application had no effect on cardiac hemodynamic performance in a baseline isolated rat heart model.

Therapeutic ultrasound (US) has been used for more than 3 decades to promote tissue healing in cases of tissue injury and muscle soreness. It was previously suggested that US may have vasorelaxatory and inotropic properties. However, the direct effect of therapeutic US in a whole heart model has not yet been investigated. Our hypothesis was that application of US might enhance cardiac function. The Langendorf model was modified in a special manner to allow application of US to the heart. Using this model, 20 male rats were equally divided into two groups. Group 1: the hearts were perfused for 15 min, to obtain baseline measurements, and then they were perfused for another 15 min in a special bath full of perfusate. Group 2: after 15 min of baseline measurements, continuous US of 1 MHz 2 W/cm(2) was applied for another 15 min. The parameters that were measured at 5-min intervals were: left ventricular pressure P(max), first derivative of the rise and fall in left ventricular pressure (dP/dt(max), dP/dt(min)), and pressure-time integral. There was no significant difference between the two groups in all parameters at baseline and during US application. P(max) and dP/dt(max) remained constant. After 15 min of US propagation, P(max) was 98% +/- 3 from baseline level vs. 98% +/- 7 in the control group, and dP/dt(max) was 98% +/- 3 vs. 99% +/- 9 in the control. In dP/dt(min), a gradual decline after 15 min of perfusion was measured. In the US- treated group, it declined to 80% +/- 10 vs. 83% +/- 5 in the controls. In conclusion, US radiation at the dose specified does not improve healthy isolated heart hemodynamic performance. We established a model that may be used for further investigation.

Animals↗
PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗
PubMed2000

Captopril and L-arginine have a synergistic cardioprotective effect in ischemic-reperfusion injury in the isolated rat heart.

OBJECTIVES: The present study was designed to evaluate the possible effect of the combined administration of both captopril (Cap) and L-arginine (L-a) in the isolated ischemic rat heart model. BACKGROUND: Recent studies suggest that L-arginine and angiotensin-converting enzyme (ACE) inhibitors possess independent cardioprotective effects in ischemic hearts. The pharmacological effect of the combination of both drugs has not yet been investigated in the ischemic myocardium. METHODS: Using the modified Langendorf model, rats were perfused with either Cap 360 micromol/L (n = 6) or (L-a) 3mmol/L (n = 6), both captopril and L-arginine (Cap+L-a) (n = 8), or saline control (Con) (n = 8). The study design included 30 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion thereafter. RESULTS: Hearts treated with both Cap+L-a demonstrated an improved performance in all parameters. After 10 minutes of reperfusion, the P(max) in the Cap+L-a group was 98 +/- 8 mmHg (P <.001), 59 +/- 14 mmHg in the Cap group (P <.02), and 44.3 +/- 10 mmHg in the L-a group (P = NS), compared with only 42 +/- 8 mmHg in the control. After 10 minutes of reperfusion the dP/dt(min) was: in the Cap+L-a group: -1,650 +/- 223 mmHg/s (P <. 006); in the Cap group: -1,051 +/- 302 mmHg/s (P <.03); in the L-a group: -870 +/- 131 mmHg/s (P = NS), compared with only -487 +/- 131 mmHg/s in the control. Coronary flow was significantly increased in all 3 groups: Cap+L-a group: 22.3 +/- 1.5 mL/min (P <.001); Cap group: 18 +/- 1.6 mL/min (P <.01); L-a group: 19.8 +/- 0.9 mL/min (P <.02), compared with 12.6 +/- 0.9 mL/min in the Con group. Total NO level was significantly increased in the Cap+L-a group: 13.4 +/- 2 micromol (P <.03) vs. 6.1 +/- 1 micromol for the L-a group. NO levels of both the Cap group and the Con group were beneath detectable values. CONCLUSION: Combined administration of captopril and L-arginine has a synergistic, protective effect on heart function and coronary flow that may be mediated by enhanced NO production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

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.

Acute Disease↗
PubMed2000

Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity.

Diabetes and atherosclerosis have been proposed to be influenced by immune and autoimmune mechanisms. A common incriminated antigen in both disorders is the heat shock protein (HSP)-60/65. In the current study, we established a model combining hyperglycemia with hyperlipidemia in LDL receptor-deficient (LDL-RD) mice and assessed its possible influences on lipid profile, HSP60/65, and atherogenesis. LDL-RD mice were injected either with streptozotocin to induce hyperglycemia or with citrate buffer (control). When hyperglycemia was induced, both study groups were challenged with a high-fat (Western) diet for 6 weeks. Plasma fasting glucose, lipid profile, and antibody levels to HSP65 and oxidized LDL were assessed. At death, the spleens from both groups were evaluated for their proliferative response to HSP65 and the consequent cytokine production. The extent of atherosclerosis was assessed at the aortic sinus. Plasma glucose, cholesterol, and triglyceride levels were elevated in mice injected with streptozotocin compared with control mice. Atherosclerotic lesions were significantly larger in the streptozotocin-injected hyperglycemic LDL-RD mice (132 +/- 23 x 10(5) microm2) in comparison to their normoglycemic litter-mates (20 +/- 6.6 x 10(5) microm2; P < 0.0001). Both humoral and cellular immune response to HSP65 was more pronounced in streptozotocin-injected mice. When challenged with HSP65 in vitro, splenocytes from streptozotocin-injected mice favored the production of the T-helper (TH)-1 cytokine gamma-interferon. In conclusion, we have established a mouse model that combines hyperglycemia with diet-induced hyperlipidemia in LDL-RD mice and studied its effect on atherosclerosis progression. The accelerated atherosclerotic process is associated with heightened immune response to HSP65 and a shift to a TH1 cytokine profile.

Animals↗
PubMed1999

Clinical and inflammatory effects of dietary L-arginine in patients with intractable angina pectoris.

We evaluated the effects of oral L-arginine on the clinical outcome and the inflammatory markers of patients with intractable angina pectoris. Our findings demonstrated a significant clinical improvement in 7 of 10 patients, which was associated with a significant decrease in cell adhesion molecule and proinflammatory cytokine levels. Dietary L-arginine may have clinical beneficial effects in patients with intractable angina pectoris, and may have anti-inflammatory properties.

Administration, Oral↗
PubMed1999

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.

Acute Disease↗
PubMed1999

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.

Aged↗
PubMed1999

Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: further evidence for smoldering inflammation in patients with atherosclerosis.

BACKGROUND: This study examined the availability of the CD11b/CD18 and CD62L antigens on the surface of peripheral blood leukocytes in patients with ischemic heart disease. METHODS AND RESULTS: The study population included 45 patients with angiographically documented ischemic heart disease admitted to our department of internal medicine and the cardiology department during 1 month (December 1997). Sixty-six healthy members of the hospital medical staff served as control subjects. Another 39 post-trauma patients who were admitted to the emergency room were also evaluated. Patients with ischemic heart disease had significantly (P <.002) higher concentrations of CD11b/CD18 antigen on the surface of their polymorphonuclear leukocytes and monocytes (mean fluorescence intensity of 203 +/- 81 and 261 +/- 75, respectively) compared with the control group (mean fluorescence intensity 158 +/- 68 and 211 +/- 74, respectively) and to the group of patients with acute stress (mean fluorescence intensity of 146 +/- 70 and 200 +/- 22, respectively). CONCLUSIONS: The presence of increased concentration of CD11b/CD18 suggests that circulating leukocytes are activated in patients with ischemic heart disease. This activation probably reflects the presence of an inflammatory response involving the atherosclerotic lesion and is not merely a result of acute stress.

Aged↗
PubMed1999

The susceptibility of Streptococcus pneumoniae to levofloxacin and other antibiotics.

The aim of this study was to determine the in-vitro susceptibility of Streptococcus pneumoniae to levofloxacin, ciprofloxacin, sparfloxacin, ofloxacin, amoxycillin, cefepime and cefuroxime. In total, 105 isolates (clinical blood and sputum isolates from 1995-96) were selected from the collection of the Department of Clinical Microbiology of the Chaim Sheba Medical Centre. MICs were determined with an agar dilution method according to NCCLS guidelines. The MIC ranges with the test antibiotics against the pneumococcal isolates were: 0.5 mg/L, levofloxacin; 0.12-0.5 mg/L, sparfloxacin; 0.5-2 mg/L, ciprofloxacin; 0.5-1 mg/L, ofloxacin; < 0.03-2 mg/L, amoxycillin; < 0.03-2 mg/L, cefepime; < 0.03-2 mg/L, cefuroxime. The results indicated that although all isolates were susceptible to all the fluoroquinolone agents except ciprofloxacin, some isolates had reduced susceptibility to amoxycillin, cefepime and cefuroxime. We conclude that all S. pneumoniae isolates tested were susceptible to levofloxacin, ofloxacin and sparfloxacin. However, about 85% were susceptible to amoxycillin and the other beta-lactam antibiotics tested.

Anti-Bacterial Agents↗
PubMed1999

The Effect of Agmatine on Ischemic and Nonischemic Isolated Rat Heart.

OBJECTIVE: the natural polyamines play a protective role during ischemic injury. We studied the effects of agmatine on ischemic and nonischemic isolated rat hearts. METHODS: Thirty-one rats were randomly assigned to one of four experimental groups. Sixteen rats were injected with saline (group 1, n = 9; group 3, n = 7), and 15 rats were injected with 100 mg/kg of agmatine (group 2, n = 8; group 4, n = 7). Injections were given twice: 24 hours and 1 hour before the experiment. Using the modified Langendorf model, rat hearts were perfused with Krebs-Henseleit solution for 105 minutes during phase 1 of the experiment (groups 1 and 2). During phase 2, hearts were exposed to 45 minutes of global ischemia (groups 3 and 4). RESULTS: During phase 1, no statistically significant differences were observed between the agmatine and the control groups. During phase 2, agmatine caused a significant increase in left ventricular pressure (P <.003). At the end of reperfusion, P(max) was 111% +/- 10% from the baseline levels versus only 82% +/- 5% in the control group. After 20 minutes of reperfusion, dP/dt (first-time derivative of the ventricular pressure) in the agmatine group reached full recovery of 106% +/- 12% versus only 64% +/- 14% in the saline group (P =.059). Agmatine also caused a significant increase in coronary flow rate (P <.004) throughout the reperfusion period. Quantitative immunohistochemical staining disclosed reduced cell damage in the agmatine-treated hearts (P <.02) versus the control group. CONCLUSION: Agmatine injection given before induced ischemia improves hemodynamic recovery by mechanisms that may be attributed to its vasodilatory properties.

Journal Article↗