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Biomedical subjects

Moshe Y Flugelman

Publications and source records attributed to Moshe Y Flugelman.

At least 19 recordsLinked to original sources
PubMed2006

Pulmonary venous drainage through a highly vascularized left atrial tumor.

We present a patient with symptomatic congestive heart failure due to a left atrial sarcoma infiltrating and apparently occluding the left pulmonary veins. The tumor was highly vascularized and enabled attenuated blood drainage from the left upper and lower pulmonary veins despite intra-operative appearance as completely obliterative, thus avoiding persistent left lung pulmonary edema. The tumor was partially removed and the pathologic findings showed advanced angiogenesis. Malignant tumors may occlude large blood vessels and thus may result in the development of a collateral flow. However, we suggest that highly vascularized tumors (macroscopic totally occlusive) may serve as a sponge and enable attenuated blood flow through the tumor and hence may avoid a complete cut off in blood supply or drainage.

Aged, 80 and over↗
PubMed2006

Brachial reactivity and extent of coronary artery disease in patients with first ST-elevation acute myocardial infarction.

We examined peripheral endothelial function, as measured by brachial artery reactivity, in 49 stable patients with a first episode of acute ST-segment elevation myocardial infarction to examine the relation between extent of coronary disease and peripheral vascular reactivity. Brachial artery reactivity was assessed by ultrasound and flow-mediated dilation (FMD) was calculated as the change in brachial artery diameter after release of suprasystolic blood pressure cuff inflation. FMD was classified as abnormal in (< or =6%) 19 patients (group 1) and as normal in 30 patients (group 2). Average FMDs were 2 +/- 2% in group 1 and 11 +/- 4% in group 2. Patients in group 1 were older (62 +/- 5 vs 54 +/- 11 years, p = 0.02) and more often had a history of hypertension (n = 10, 52%, vs 6, 20%, p = 0.017). Patients with abnormal endothelial function (group 1) had a larger number of coronary obstructive (>or =50%) lesions (3.6 +/- 2.4 vs 2.0 +/- 1.7, p = 0.01) and more extensive coronary disease (1.9 +/- 0.8 vs 1.4 +/- 0.8 vessel disease, p = 0.05). In patients with 3-vessel disease, FMD was lower (4.0 +/- 1.8% vs 8.2 +/- 0.8%, p = 0.04) than in those with lesser coronary involvement. In conclusion, in patients with a first episode of ST-segment elevation myocardial infarction, there was a strong correlation between extent of coronary artery disease and brachial artery reactivity. Patients with localized coronary disease had relatively normal brachial reactivity, whereas those with diffuse coronary disease had more severe abnormal brachial artery reactivity.

Adult↗
PubMed2006

Reevaluation of routine invasive strategy versus noninvasive testing following uncomplicated ST-elevation myocardial infarction.

BACKGROUND AND AIMS: While current guidelines recommend a selective invasive approach after low-risk ST-elevation myocardial infarction (STEMI) treated by thrombolysis, based on noninvasive identification of patients with residual or inducible myocardial ischemia, in many instances physicians employ a strategy of routine angiography. The present study was undertaken to reexamine the correlation between noninvasive testing and coronary angiography in patients recovering from uncomplicated STEMI with regard to detection and management of residual infarct artery stenosis and to identify patients with multivessel (MVD) or high-risk coronary disease. METHODS: We prospectively performed predischarge exercise testing (ETT) and myocardial perfusion scintigraphy (MPS) prior to routine predischarge coronary angiography in 83/276 consecutive STEMI patients, who after treatment with initial and early thrombolysis, were defined as low risk by ACC/AHA risk classification. RESULTS: ETT was positive for myocardial ischemia in 11/43 (26%) patients with single-vessel disease (SVD) and 11/22 (50%) patients with MVD, but normal or nondiagnostic in the remainder. MPS revealed significant reversible perfusion defects in 13/40 (32%) patients with SVD and 13/22 (59%) patients with MVD. A selective strategy of ETT followed by MPS for nondiagnostic ETT missed residual infarct-related artery stenosis and/or MVD in 31/81 (38%) of the cohort. Among patients who may not otherwise have been referred for angiography, severe (> or =70%) residual stenosis of the infarct-related artery was present in 56% and MVD in 16%. CONCLUSIONS: Early predischarge ETT and/or MPS had limited sensitivity for the detection of coronary disease in low-risk post-STEMI patients. The study supports a simpler strategy of routine coronary angiography in most patients after low-risk STEMI.

Coronary Angiography↗
PubMed2006

Cell and gene therapies in cardiovascular disease with special focus on the no option patient.

Morbidity and mortality attributed to diseases of the heart and blood vessels are growing steadily around the globe, as a result of changing lifestyles and increased longevity. Even in affluent countries many patients with cardiovascular syndromes do not benefit from current conventional therapies. Failure of drugs, catheter-based, and surgical interventions leaves millions of patients in a great need for new therapies. Cell and gene therapy hold great promise for cardiovascular therapies. As most cardiovascular pathologies are confined to a specific organ and are associated with arterial occlusion or muscle damage, both may be amenable to local cell and gene therapies. Local delivery of genes or cells that can promote the formation of new blood vessels (angiogenesis) or lead to tissue regeneration should be achievable with current knowledge and molecular technologies. So far, however, the promise of gene and cell therapy has not fulfilled the expectations. Nevertheless, careful review of the work and of current thinking in the field leaves room for optimism that gene and cell therapy may reach the clinical setting in the near future, providing a new option for many patients. In this paper, we review clinical studies of gene and cell therapy and discuss their impact on future research.

Cardiovascular Diseases↗
PubMed2006

Initial experience with a cardiologist-based chest pain unit in an emergency department in Israel.

BACKGROUND: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over-diagnosis may be costly. OBJECTIVES: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel. METHODS: During a 5 week pilot study, we examined resource utilization and ER diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS, exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded. RESULTS: All patients had at least two cardiac troponin T measurements, 19 underwent EST, 9 echocardiography and 29 cardiac MDCT. Fourteen patients were referred for early cardiac catheterization (same/next day). A specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 patients (56%) who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 +/- 8.6 hours vs. 12.9 +/- 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after reassessment. CONCLUSIONS: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to a decision regarding admission/discharge from the ER.

Adult↗
PubMed2006

[Fat emboli syndrome mimicking acute coronary syndrome and pulmonary congestion].

Fat emboli syndrome (FES) is associated with major trauma, orthopedic surgery and various atraumatic conditions. Clinically, FES presents with the triad of respiratory symptoms, mental changes and petechiae. This is a case history of a woman who presented with acute respiratory distress and ECG changes after knee surgery initially diagnosed as pulmonary congestion secondary to acute coronary syndrome. The diagnostic workup and review of literature are presented. FES should be considered in the differential diagnosis of dyspnea after orthopedic surgery.

Aged↗
PubMed2005

Cellular and molecular therapeutic modalities for arterial obstructive syndromes.

Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), peripheral arterial disease (PAD), and cerebral vascular disease (CVD) is a major goal for modern medicine. Molecular and cell-based therapies for arterial obstructive syndromes have the potential to become clinically useful in the near future. Molecular therapy employs angiogenic proteins and genes in order to initiate the development of new blood vessels that by-pass an arterial occlusion. The induction of a collateral artery system is termed therapeutic angiogenesis or neovascularization. Proteins have been delivered either directly into the ischemic area or via a vector encoding an angiogenic gene. Both protein and gene therapies have been associated with promising preclinical and early phase human trial results in patients with PAD as well as CAD. However, to date, efficacy has not been demonstrated in placebo-controlled, large trails. Today's cell-based therapy is focused on stem cells (SCs) for the treatment of patients after acute myocardial infarction (AMI) or for patients with severe left ventricular dysfunction. Stem cells have shown to increase cardiac performance in uncontrolled, early phase human studies. This improvement is believed to have its origin in myogenesis and neovascularization. In the following review, we will cover current state of molecular- and cellular-based treatments for PAD and CAD that have reached the clinical arena.

Animals↗
PubMed2005

Diagnosis of coronary in-stent restenosis with multidetector row spiral computed tomography.

OBJECTIVES: The purpose of this study was to assess the accuracy of a new generation spiral multidetector computed tomography (MDCT) scanner (Brilliance 40, Philips Medical Systems, Cleveland, Ohio) in the diagnosis of coronary in-stent restenosis (ISR). BACKGROUND: Noninvasive imaging of ISR would be clinically useful, but artifacts caused by metallic stent struts have limited the role of early generation MDCT scanners. METHODS: We examined 65 patients (age 63 +/- 12 years, 48 [73.8%] men) with 111 implanted coronary stents who were referred for repeat invasive coronary angiography (ICA). Patients underwent 40-slice MDCT one to three days before scheduled ICA, using intravenous contrast enhancement. Images were reconstructed in multiple formats using retrospective electrocardiographic gating. Stents were viewed in their long and short axes and luminal contrast attenuation graded from MDCT grade 1 (minimal restenosis) to 4 (severe restenosis) by consensus of two observers. RESULTS: In-stent restenosis (>/=60% luminal narrowing by quantitative coronary angiography) was found on ICA in 18 (16.2%) of the stented segments and in 16 (24.6%) patients. The MDCT findings correlated with ICA restenosis, with restenosis in only 1 of 59 (1.6%) MDCT grade 1 segments, but in more than three-quarters (12 of 15, 80%) of MDCT grade 4 segments (sensitivity 72.2%, specificity 92.5%, positive predictive value [PPV] 65.0%, negative predictive value [NPV] 94.5% [five stents not assessable by MDCT considered as restenosis]). Using MDCT grades 3 or 4 combined for restenosis, sensitivity of MDCT was 88.9%, specificity 80.6%, PPV 47.1%, and NPV 97.4%. CONCLUSIONS: In-stent restenosis can be diagnosed with moderate sensitivity using a new generation 40-slice MDCT scanner. The high NPV implies a significant role for MDCT in excluding ISR.

Coronary Restenosis↗
PubMed2005

Anaemia and heart failure: statement of the problem.

While advances in treatment strategies and pharmacotherapy have produced a dramatic reduction in the mortality of patients with heart failure during the past 15 years, there is still a major challenge to improve patient well being, reduce hospitalizations and reduce mortality further. The prevalence of heart failure is not decreasing, and heart failure is currently a cause for hospitalization in >25% of admissions to internal medicine and cardiology departments. It has recently become apparent that anaemia is present in 20-30% of patients with heart failure, and the severity of anaemia has important implications regarding outcome and prognosis. Anaemia may be due to a number of causes, including iron and vitamin deficiency, insidious blood loss, haemodilution, renal impairment and bone marrow depression with resistance to erythropoietin. In the presence of a damaged heart and often coronary artery disease, anaemia may worsen contractile ability and systolic function, while the necessary volume load and ventricular hypertrophy which accompany anaemia contribute to diastolic dysfunction. Preliminary data show that appropriate treatment of anaemia, based on correction of the underlying cause, with, in most patients, the addition of exogenous erythropoietin and iron therapy, improves ventricular function and clinical status. Treatment of anaemia has opened a new frontier in the management of heart failure. We await the results of ongoing clinical trials for more detailed information regarding appropriate haemoglobin targets, choice of medication and dosing and the degree of improvement that may be expected when the issue of anaemia is properly addressed.

Adult↗
PubMed2004

Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate (HS) at specific intrachain sites, an activity that is strongly implicated in cell dissemination associated with metastasis and inflammation. In addition to its structural role in extracellular matrix assembly and integrity, HS sequesters a multitude of polypeptides that reside in the extracellular matrix as a reservoir. A variety of growth factors, cytokines, chemokines, and enzymes can be released by heparanase activity and profoundly affect cell and tissue function. Thus, heparanase bioavailability, accessibility, and activity should be kept tightly regulated. We provide evidence that HS is not only a substrate for, but also a regulator of, heparanase. Addition of heparin or xylosides to cell cultures resulted in a pronounced accumulation of, heparanase in the culture medium, whereas sodium chlorate had no such effect. Moreover, cellular uptake of heparanase was markedly reduced in HS-deficient CHO-745 mutant cells, heparan sulfate proteoglycan-deficient HT-29 colon cancer cells, and heparinase-treated cells. We also studied the heparanase biosynthetic route and found that the half-life of the active enzyme is approximately 30 h. This and previous localization studies suggest that heparanase resides in the endosomal/lysosomal compartment for a relatively long period of time and is likely to play a role in the normal turnover of HS. Co-localization studies and cell fractionation following heparanase addition have identified syndecan family members as candidate molecules responsible for heparanase uptake, providing an efficient mechanism that limits extracellular accumulation and function of heparanase.

Animals↗
PubMed2004

Evaluation of isoproterenol in patients undergoing resuscitation for out-of-hospital asystolic cardiac arrest (the Israel Resuscitation with Isoproterenol Study Prospective Randomized Clinical Trial).

The Israel Resuscitation with Isoproterenol Study included 79 consecutive patients with witnessed out-of-hospital asystolic cardiac arrest who were resuscitated with epinephrine and atropine and randomized to receive additional isoproterenol or no isoproterenol. The rate of return of spontaneous circulation and survival to hospital admission did not differ in patients receiving standard therapy and those receiving additional isoproterenol.

Adrenergic beta-Agonists↗
PubMed2004

Processing and activation of latent heparanase occurs in lysosomes.

Heparanase is a heparan sulfate degrading endoglycosidase participating in extracellular matrix degradation and remodeling. Heparanase is synthesized as a 65 kDa non-active precursor that subsequently undergoes proteolytic cleavage, yielding 8 kDa and 50 kDa protein subunits that heterodimerize to form an active enzyme. The protease responsible for heparanase processing is currently unknown, as is the sub-cellular processing site. In this study, we characterize an antibody (733) that preferentially recognizes the active 50 kDa heparanase form as compared to the non-active 65 kDa heparanase precursor. We have utilized this and other anti-heparanase antibodies to study the cellular localization of the latent 65 kDa and active 50 kDa heparanase forms during uptake and processing of exogenously added heparanase. Interestingly, not only the processed 50 kDa, but also the 65 kDa heparanase precursor was localized to perinuclear vesicles, suggesting that heparanase processing occurs in lysosomes. Indeed, heparanase processing was completely inhibited by chloroquine and bafilomycin A1, inhibitors of lysosome proteases. Similarly, processing of membrane-targeted heparanase was also chloroquine-sensitive, further ruling out the plasma membrane as the heparanase processing site. Finally, we provide evidence that antibody 733 partially neutralizes the enzymatic activity of heparanase, suggesting that the N-terminal region of the molecule is involved in assuming an active conformation. Monoclonal antibodies directed to this region are likely to provide specific heparanase inhibitors and hence assist in resolving heparanase functions under normal and pathological conditions.

Animals↗
PubMed2004

Brachial artery endothelial function in residents and fellows working night shifts.

Brachial artery endothelial function, which is measured as responsiveness to reactive hyperemia (flow-mediated dilation [FMD]) was abnormal in residents and house staff after a 24-hour shift, including night duty. The greatest decrease in FMD was observed in physicians with a longer history of night-shift duty and in those reporting fewer sleeping hours during the shift. The finding that FMD is decreased after night duty raises the issue of the effects of shift duty on cardiovascular function in healthcare personnel, particularly in those undertaking night duty for a prolonged period of time.

Adult↗
PubMed2004

Heparanase induces endothelial cell migration via protein kinase B/Akt activation.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate (HS) at specific intra-chain sites. Blood-borne neutrophils, macrophages, mast cells, and platelets exhibit heparanase activity that is thought to be stored in specific granules. The degranulated heparanase is implicated in extravasation of metastatic tumor cells and activated cells of the immune system. Degranulation and heparanase release in response to an inflammatory stimulus or platelet activation would facilitate cellular extravasation directly, by altering the composition and structural integrity of the extracellular matrix, or indirectly, by releasing HS-bound proinflammatory cytokines and chemokines. We hypothesized that in addition to such indirect effect, the released heparanase may also locally affect and activate neighboring cells such as endothelial cells. Here, we provide evidence that addition of the 65-kDa latent heparanase to endothelial cells enhances Akt signaling. Heparanase-mediated Akt phosphorylation was independent of its enzymatic activity or the presence of cell membrane HS proteoglycans and was augmented by heparin. Moreover, addition of heparanase stimulated phosphatidylinositol 3-kinase-dependent endothelial cell migration and invasion. These results suggest, for the first time, that heparanase activates endothelial cells and elicits angiogenic responses directly. This effect appears to be mediated by as yet unidentified heparanase receptor.

Cell Movement↗
PubMed2003

Perceived patient comprehension in acute and chronic cardiovascular clinical trials.

An anonymous patient perception comprehension and satisfaction questionnaire was sent to 438 patients 1-3 months after they had participated in a clinical cardiovascular trial to examine the level of patient comprehension as perceived by the patient. We compared perceived comprehension in acute (acute myocardial infarction) and chronic (outpatient heart failure) clinical trials. Partially or fully completed questionnaires were received from 220 patients (70 chronic, 150 acute). The findings were similar in the 2 patient groups. Perceived full comprehension (understood most or all) of the trial was reported by 18 (27%) of chronic and 40 (31%) of 129 acute patients, while almost 20% of both groups reported little or no understanding of the trial. The level of comprehension was related to the recollected duration of explanation (p = 0.003 chronic, p < 0.001 acute). Perceived comprehension was not related to the personnel explaining the study (physician or nurse) or to whether the explanation as recollected was oral or written. However, in both acute and chronic patients, the majority (51% chronic; 63% acute) preferentially recalled the oral rather than written explanation of the trial. The very similar findings in the acute and chronic situation suggest that perceived understanding reflects human nature and willingness to be involved in medical issues. Considerable effort should be directed to improve the duration of explanation (particularly oral), if we are to achieve our goal of true informed consent in clinical cardiovascular trials.

Cardiovascular Diseases↗