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Biomedical subjects

Dan Gilon

Publications and source records attributed to Dan Gilon.

16 recordsLinked to original sources
PubMed2006

Transcription factor MITF regulates cardiac growth and hypertrophy.

High levels of microphthalmia transcription factor (MITF) expression have been described in several cell types, including melanocytes, mast cells, and osteoclasts. MITF plays a pivotal role in the regulation of specific genes in these cells. Although its mRNA has been found to be present in relatively high levels in the heart, its cardiac role has never been explored. Here we show that a specific heart isoform of MITF is expressed in cardiomyocytes and can be induced by beta-adrenergic stimulation but not by paired box gene 3 (PAX3), the regulator of the melanocyte MITF isoform. In 2 mouse strains with different MITF mutations, heart weight/body weight ratio was decreased as was the hypertrophic response to beta-adrenergic stimulation. These mice also demonstrated a tendency to sudden death following beta-adrenergic stimulation. Most impressively, 15-month-old MITF-mutated mice had greatly decreased heart weight/body weight ratio, systolic function, and cardiac output. In contrast with normal mice, in the MITF-mutated mice, beta-adrenergic stimulation failed to induce B-type natriuretic peptide (BNP), an important modulator of cardiac hypertrophy, while atrial natriuretic peptide levels and phosphorylated Akt were increased, suggesting a cardiac stress response. In addition, cardiomyocytes cultured with siRNA against MITF showed a substantial decrease in BNP promoter activity. Thus, for what we believe is the first time, we have demonstrated that MITF plays an essential role in beta-adrenergic-induced cardiac hypertrophy.

Animals↗
PubMed2006

Impact of follow-up on the success rate of the cryosurgical maze procedure in patients with rheumatic heart disease and enlarged atria.

OBJECTIVES: The most important predictors for failure of the maze procedure are long standing atrial fibrillation (AF), rheumatic heart disease (RHD), and enlarged atria. It is well documented, however, that some patients have recurrence of atrial arrhythmia only late in follow-up. The aims of this study are to assess the effectiveness of the maze procedure and late cardioversion (pharmacologic or electrical) in patients wtih an increased risk for procedure failure. PATIENTS AND METHODS: Fifty-five patients with AF, enlarged left atrium (>5 cm), and/or RHD were enrolled in the study. Cryosurgery was performed on all patients and was combined with bipolar radiofrequency in the last four patients. The lesion pattern resembles the maze procedure. A follow-up was completed on all patients (24.5 +/- 9.6 months with a range of 3-39 months). RESULTS: The operative mortality was 3.7% (2 patients), both deaths unrelated to the maze procedure. Ninety-eight percent of patients were free of AF upon discharge, with an 11% incidence of early pacemaker implantation. In the first three months postoperatively, 53% of the patients experienced intermittent atrial arrhythmia. Four patients were recorded with permanent AF in late follow-up. The only predictor for late AF (>3 months of follow-up) was perioperative AF. Atrial size, RHD, and AF duration did not predict late failure. CONCLUSIONS: The maze procedure can be applied with high success rate in patients with RHD, enlarged atria, and long-standing AF. In our experience many of the late recurrences were recorded late in the follow-up and were treated successfully with antiarrhythmic drugs and/or cardioversion. Therefore a close follow-up is required to enhance the success rate of the procedure.

Adult↗
PubMed2006

Automatic endocardial-boundary detection in low mechanical-index contrast echocardiography.

This paper presents a novel algorithm, aimed at automatic endocardial boundary (inner boundary) detection in myocardial opacification scenarios. The data acquisition protocol uses (on purpose) low mechanical index imaging (i.e., weak ultrasound signal), so that the acquired images are characterized by low signal-to-noise ratios. The proposed algorithm is based on converting the frames, given in Cartesian coordinates, into polar coordinates, and applying a set of filters in order to compute the initial estimation of the endocardial boundary. The final estimation of the endocardial boundary is produced by an error correction process, which uses both spatial and temporal filtering. The estimated boundaries are converted into Cartesian coordinates, for display. Our algorithm has been tested on nine cine-loops. The resulting myocardial outlines have been separately assessed by two clinicians, scoring each segment in each cine-loop on a scale between 5 (excellent) and 1 (completely unacceptable). The mean overall score is 3.8 +/- 0.8, which seems adequate. The same clinicians have also manually drawn the contours of the endocardial boundary for the end-systolic and the end-diastolic frames of each cine-loop. The results show, that the mismatch between the automatically determined outlines and the manually drawn outlines is of the same order of magnitude as the interobserver variability. These results further support the validity of our method.

Algorithms↗
PubMed2005

Clinical experience did not reduce the variance in physicians' estimates of pretest probability in a cross-sectional survey.

BACKGROUND AND OBJECTIVES: In light of the increasing popularity of the threshold approach in clinical decision-making, this study assesses the role of expertise in physicians' agreement in estimating the probability of disease in patients. METHODS: A cross-sectional survey of physicians of different specialties, attending weekly staff meetings in four teaching hospitals in Jerusalem, Israel. An anonymous questionnaire describing three case scenarios of patients with chest pain was administered and participants were asked to estimate pretest probabilities of disease. RESULTS: Eighty-six physicians (practicing cardiology, internal medicine, and family medicine, as well as general practitioners and internists) out of 125 approached (response rate 69%). The mean estimated probabilities were very similar for residents and specialists; however, the standard deviation was higher for specialists in all three cases: 20.7, 21.0, and 19.1 among specialists and 16.4, 20.5, and 14.9 among residents, respectively. CONCLUSION: This study, based on case scenarios, did not find that medical expertise improved agreement among doctors when estimating the probability of disease in patients-despite the common belief that senior physicians should have smaller interobserver differences in probability estimates. The wide variation observed calls into question the applicability of the threshold approach.

Cardiology↗
PubMed2005

Does circadian and seasonal variation in occurrence of acute aortic dissection influence in-hospital outcomes?

The risk of acute aortic dissection (AAD) exhibits chronobiological variations with peak onset in the morning and in winter. However, it is not known whether the time of day or season of the year of the AAD affects clinical outcomes. We studied 1,032 patients enrolled in the International Registry of Acute Aortic Dissection from January 1997 to December 2001. For circadian and seasonal analysis, the time and date of symptom onset were available for 741 and 1,007 patients, respectively, and were grouped into four 6h periods (morning, afternoon, evening, and night) and four seasons (winter, spring, summer, and autumn). The chi2 test for goodness of fit was used to evaluate non-uniformity of the time of day and time of year for critical in-hospital clinical events, including death. While highest incidence of AAD occurred in the morning and winter, clinical events (including mortality) were similar during the four different periods of the 24 h (chi2 = 1.9, p = 0.60) and seasonal (chi2 = 1.2, p = 0.75) periods.

Aged↗
PubMed2005

Stuck bioprosthetic aortic valve--a new entity? A case report.

We describe herein a case of bioprosthetic valve malfunction, which closely imitates a stuck valve. Although the term "stuck" was used originally for the immovable mechanical valve leaflets, the echocardiographic manifestation of this malfunction is similar to those of a mechanical one. The clinical presentation of the stuck bioprosthesis is, however, far more benign than a stuck mechanical valve. Familiarity with this entity is important.

Aged↗
PubMed2004

Differences in clinical presentation, management, and outcomes of acute type a aortic dissection in patients with and without previous cardiac surgery.

BACKGROUND: There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). METHODS AND RESULTS: In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males (P=0.02), older (P=0.014), and to have a history of previous aortic dissection (P<0.001) or aneurysms (P<0.001). In contrast, PCS patients were less likely to have presenting chest pain (P<0.001). Cardiac tamponade was less common in PCS patients (P=0.007). Fewer AAD patients with PCS underwent surgical repair (P=0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age 70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. CONCLUSIONS: Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients.

Acute Kidney Injury↗
PubMed2004

Acute type B aortic dissection in elderly patients: clinical features, outcomes, and simple risk stratification rule.

BACKGROUND: The clinical features and outcomes of elderly patients with acute type B aortic dissection (ABAD) are less well known. Accordingly, we sought to evaluate the clinical features and outcomes and derive a simple risk stratification rule for elderly with ABAD. METHODS: We categorized 383 patients with ABAD enrolled in the International Registry of Acute Aortic Dissection into two strata (aged less than 70 years and aged 70 years or more) and compared their clinical features and in-hospital outcomes. Further, we developed a clinical decision rule to risk-stratify elderly with ABAD. RESULTS: Forty-two percent (161 of 383) of patients with ABAD were aged 70 years or more. Hypertension, diabetes, history of prior aortic aneurysm, and arteriosclerosis were more common in the elderly patients, whereas Marfan syndrome and cocaine abuse were less common. The in-hospital complication of hypotension/shock was more common among elderly, and malperfusion of a visceral organ less frequent among elderly patients. In-hospital mortality was higher in the elderly cohort compared with the younger patients (16% versus 10%, p = 0.07). A classification tree identified that elderly patients with hypotension/shock had the highest risk of death (56%). In absence of this, any branch vessel involvement was associated with the next highest mortality rate (28.6%) followed by presence of periaortic hematoma (10.5%). In contrast, elderly patients without any of these three risk factors had an extremely low mortality rate (1.3%). CONCLUSIONS: Our study highlights important differences between older and younger patients with ABAD in their clinical characteristics, management, and outcomes. We also propose a simple decision rule that allows stepwise risk-stratification in elderly patients with ABAD.

Aged↗
PubMed2004

Aspirin decreases vascular endothelial growth factor release during myocardial ischemia.

BACKGROUND: Vascular Endothelial Growth Factor (VEGF) is an important angiogenesis factor involved in pathophysiology of cardiovascular diseases. Controlling this factor's level in the serum might have significant prognostic outcomes. METHODS: Twenty-four patients undergoing coronary artery bypass grafting were prospectively categorized into two groups according to aspirin administration before surgery. Vascular Endothelial Growth Factor levels were compared and correlated and adjusted with platelets count between two groups in the serum, before and after the surgery. Serum creatine kinase (CK) levels were determined before and after the operation in parallel to other clinical data. RESULTS: Vascular Endothelial Growth Factor levels were significantly lower in patients of the aspirin group compared to those of the non-aspirin group; 94+/-61 vs. 241+/-118 pg/ml, p=0.0003, respectively, this-despite an absence of difference in the platelet count between the groups. These titers decreased postoperatively in both groups, 94+/-61 to 10+/-9 pg/ml, p=0.001 in aspirin group and from 241+/-118 to 84+/-54 pg/ml, p=0.001 in control group. Serum creatine kinase levels were higher in the non-aspirin group, 214+/-83 u/l compared to 70+/-32 u/l in the aspirin group. Creatine kinase levels increased significantly postoperatively in both groups; however, the aspirin group had a significantly lower creatine kinase levels compared to non-aspirin group, 107+/-51 vs. 401+/-127 u/l, respectively, p=<0.0001. A significant correlation was seen between VEGF levels and platelets count in both groups, r=0.5. CONCLUSIONS: Aspirin treated patients have lower Vascular Endothelial Growth Factor titer levels in the perioperative course. This difference between the aspirin and the non-aspirin group is not accounted for by the platelets count.

Aspirin↗
PubMed2004

Pericardial fluid and serum VEGF in response to different types of heparin treatment.

BACKGROUND: Heparin is an important medication in the treatment of patients with unstable angina pectoris. We designed an observational study to compare the effects of standard heparin (SH) with low molecular weight heparin (LMWH) on vascular endothelial growth factor (VEGF) levels in patients undergoing coronary artery bypass grafting (CABG). METHODS: Thirty-two patients with unstable angina pectoris undergoing CABG were prospectively categorized into two groups according to the type of heparin administration before surgery. VEGF levels determined by enzyme linked immunosorbent assay (ELISA) were compared between the two groups' blood samples obtained before the surgery and pericardial fluid after pericardial opening. RESULTS: There was no difference in preoperative characteristics between the two groups. Serum VEGF levels were similar (P=0.3) in patients treated by SH (85+/-55 pg/ml) compared to those treated with LMWH (105+/-64 pg/ml). VEGF levels in the pericardial fluid were significantly raised (P<0.0001) in patients of LMWH group (36+/-13 pg/ml) compared to SH group (13+/-6 pg/ml). A good correlation was observed between VEGF in the serum and platelet count in both SH group (r=0.8) and LMWH group (r=0.7). CONCLUSIONS: Local response of the ischemic myocardium, as expressed by VEGF levels, differs in patients treated with SH compared to patients treated with LMWH. VEGF levels in pericardial fluid of patients receiving LMWH were 2-3-folds higher than patients in SH group.

Adult↗
PubMed2002

Effect of three-dimensional valve shape on the hemodynamics of aortic stenosis: three-dimensional echocardiographic stereolithography and patient studies.

OBJECTIVES: This study tested the hypothesis that the impact of a stenotic aortic valve depends not only on the cross-sectional area of its limiting orifice but also on three-dimensional (3D) valve geometry. BACKGROUND: Valve shape can potentially affect the hemodynamic impact of aortic stenosis by altering the ratio of effective to anatomic orifice area (the coefficient of orifice contraction [Cc]). For a given flow rate and anatomic area, a lower Cc increases velocity and pressure gradient. This effect has been recognized in mitral stenosis but assumed to be absent in aortic stenosis (constant Cc of 1 in the Gorlin equation). METHODS: In order to study this effect with actual valve shapes in patients, 3D echocardiography was used to reconstruct a typical spectrum of stenotic aortic valve geometrics from doming to flat. Three different shapes were reproduced as actual models by stereolithography (computerized laser polymerization) with orifice areas of 0.5, 0.75, and 1.0 cm(2) (total of nine valves) and studied with physiologic flows. To determine whether valve shape actually influences hemodynamics in the clinical setting, we also related Cc (= continuity/planimeter areas) to stenotic aortic valve shape in 35 patients with high-quality echocardiograms. RESULTS: In the patient-derived 3D models, Cc varied prominently with valve shape, and was largest for long, tapered domes that allow more gradual flow convergence compared with more steeply converging flat valves (0.85 to 0.90 vs. 0.71 to 0.76). These variations translated into differences of up to 40% in pressure drop for the same anatomic area and flow rate, with corresponding variations in Gorlin (effective) area relative to anatomic values. In patients, Cc was significantly lower for flat versus doming bicuspid valves (0.73 +/- 0.14 vs. 0.94 +/- 0.14, p < 0.0001) with 40 +/- 5% higher gradients (p < 0.0001). CONCLUSIONS: Three-dimensional valve shape is an important determinant of pressure loss in patients with aortic stenosis, with smaller effective areas and higher pressure gradients for flatter valves. This effect can translate into clinically important differences between planimeter and effective valve areas (continuity or Gorlin). Therefore, valve shape provides additional information beyond the planimeter orifice area in determining the impact of valvular aortic stenosis on patient hemodynamics.

Adult↗
PubMed2002

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era.

OBJECTIVES: We sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection. BACKGROUND: Few data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort. METHODS: We categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and >or=70 years) and compared their clinical features, management, and in-hospital events. RESULTS: Thirty-two percent of patients with type A dissection were aged >or=70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03). CONCLUSIONS: Our study shows significant differences between older (age >or=70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort.

Acute Disease↗
PubMed2002

Predicting death in patients with acute type a aortic dissection.

BACKGROUND: Given the high mortality rates in patients with type A aortic dissection, predictive tools to identify patients at increased risk of death are needed to assist clinicians for optimal treatment. METHODS AND RESULTS: Accordingly, we evaluated 547 patients with this diagnosis enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 1999. Univariate testing followed by multivariate logistic regression analysis was performed to identify independent predictors of death. In-hospital mortality rate was 32.5% in type A dissection patients. In-hospital complications (neurological deficits, altered mental status, myocardial or mesenteric ischemia, kidney failure, hypotension, cardiac tamponade, and limb ischemia) were increased in patients who died compared with survivors (P<0.05 for all). Logistic regression identified the following presenting variables as predictors of death: age > or =70 years (OR, 1.70; 95% CI, 1.05 to 2.77; P=0.03), abrupt onset of chest pain (OR 2.60; 95% CI, 1.22 to 5.54; P=0.01), hypotension/shock/tamponade (OR, 2.97; 95% CI, 1.83 to 4.81; P<0.0001), kidney failure (OR, 4.77; 95% CI, 1.80 to 12.6; P=0.002), pulse deficit (OR, 2.03; 95% CI, 1.25 to 3.29, P=0.004), and abnormal ECG (OR, 1.77; 95% CI, 1.06 to 2.95; P=0.03) (area under receiver operating curve, 0.74; Hosmer-Lemeshow statistic, P=0.75). CONCLUSIONS: The in-hospital mortality rate in acute type A aortic dissection is high and can be predicted with the use of a clinical model incorporated in a simple risk prediction tool. This tool can be used to educate patients with dissection about their predicted risk and in clinical research for risk adjustment while comparing outcomes of different therapies.

Aged↗