Ibrahim Marai

Rambam Medical Center, H̱efa, Haifa District, Israel

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Publications (24)45.09 Total impact

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    ABSTRACT: Recent research in systemic lupus erythematosus (SLE) yielded new antigens and antibodies in SLE patients. We describe the various autoantibodies that can be detected in patients with SLE.A literature review, using the terms “autoantibody” and “systemic lupus erythematosus”, was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity and other clinical manifestations.One hundred and eighty autoantibodies were so far described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of an autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 180 autoantibodies.SLE is so far the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of a polyclonal B cell activation, impaired apoptotic pathways, or the outcome of an idiotypic network dysregulation.
    Autoimmunity Reviews 10/2014; · 7.10 Impact Factor
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    ABSTRACT: The aim of this study was to characterize the abnormalities in glucose homeostasis in intensive care unit patients following an acute coronary event. The study population included all non-diabetic patients ages 20-80 years that were admitted to a coronary intensive unit. Glucose, insulin and C-peptide levels during an oral glucose tolerance test (OGTT) were measured during the acute admission. From January to September 2003, 277 patients were admitted to the coronary unit. Of these, 127 patients underwent an OGTT. Of these, only 29 patients (23%) exhibited normal glucose metabolism. The remainder had type 2 diabetes (32%), impaired glucose tolerance (37%) or isolated impaired fasting glucose (8%, 100-125 mg/dl). Based on homeostasis model assessment (HOMA) calculations, diabetic patients had impaired beta-cell function and patients with elevated fasting glucose levels were insulin resistant. Beta-cell dysfunction during the acute stress seems to contribute to the glucose abnormalities. Most patients who experience an acute coronary event demonstrate abnormal glucose metabolism. Post glucose-load abnormalities are more common than abnormal fasting glucose level in this situation. It is postulated that the acute stress of a coronary event may contribute to the dysglycemia.
    Acta Diabetologica 12/2008; 46(3):209-16. · 4.63 Impact Factor
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    ABSTRACT: The main limitation of primary PCI in acute MI is lack of tissue reperfusion due to distal embolization. We sought to examine the safety and feasibility of a manual thrombus aspiration device in patients undergoing primary PCI. Seventy-eight consecutive patients with ST-elevation MI eligible for primary PCI were included. The device was used immediately after guidewire crossing only if a total occlusion (thrombolysis in myocardial infarction [TIMI] flow 0) existed or if a large filling defect was observed. End points were TIMI flow immediately after thrombus aspiration and at the end of procedure and ST resolution of more than 70%. Mean age was 59+/-12 years, and 79% of patients were males. Risk factor profile included smoking in 62%, diabetes in 21%, hypertension in 46%, and hyperlipidemia in 45%. The infarct-related artery was LAD in 42%, RCA in 36%, and LCX in 22%. Initial TIMI flow was 0 in 71%, I in 10%, and II/III in 19%. Immediately after aspiration, TIMI flow was II/III in 89% of patients and I in 9%. Direct stenting was performed in 73%. Final TIMI flow was III in 90%, II in 9%, and 0 in 1%. ST-segment resolution of more than 70% was observed in 76% of patients. No major device-related complications occurred. Based on this preliminary data, manual thrombus aspiration using the Export device during primary PCI appears to be feasible and safe. The advantages over routine primary PCI should be further evaluated in randomized trials.
    Cardiovascular Revascularization Medicine 07/2008; 9(3):140-3.
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    ABSTRACT: Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. The aim of this study was to detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects without apparent coronary artery disease (CAD). We prospectively assessed brachial flow-mediated dilation (FMD) in 435 consecutive healthy subjects: 281 (65%) men, mean age 54+/-12 years and body mass index 28+/-4 kg/m(2). After overnight fasting and discontinuation of all medications for > or =12 h, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high resolution linear array ultrasound. Subjects were divided into 2 groups: below (n=221) and above (n=214) the median FMD of 10.7%, and were comparable regarding CAD risk factors, lipoproteins, fasting glucose, C-reactive protein, and concomitant medications, with a mean clinical follow-up of 32+/-2 months. Composite cardiovascular endpoints (all-cause mortality, non-fatal myocardial infarction, heart failure or angina pectoris hospitalization, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with below median FMD of 10.7%, than above (11.8% vs 4.7%, p=0.007, respectively). Univariate analysis demonstrated that median FMD significantly predicted cardiovascular events [odds ratio (OR) of 2.78 and 95% CI 1.35 to 5.71 (p=0.003)]. After multivariate analysis including conventional CAD risk factors, median FMD was the best independent predictor of long-term cardiovascular adverse events [OR of 2.70 and 95% CI 1.16 to 6.32 (p=0.011)]. Brachial artery median FMD independently predicts long-term adverse cardiovascular events in healthy subjects in addition to traditional risk factor assessment.
    International journal of cardiology 05/2008; 134(1):52-8. · 6.18 Impact Factor
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    ABSTRACT: Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.
    The American Journal of Cardiology 05/2008; 101(8):1094-7. · 3.43 Impact Factor
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    ABSTRACT: Intravenous immunoglobulin (IVIG) preparations are increasingly being used in the treatment of autoimmune disorders. This treatment is regarded as generally safe, and most of the adverse effects associated with IVIG administration are mild and transient. This paper reports a 72-year-old patient with known ischemic heart disease admitted for a Guillain-Barré syndrome variant, who developed acute ST elevation myocardial infarction (MI) during the first hours of IVIG infusion. The literature on acute MI during IVIG treatment is reviewed. Evaluation of each patient for cardiovascular risk prior to IVIG treatment is recommended as is the assessment of risk versus benefit. If IVIG is prescribed, we propose close monitoring and slow infusion rate.
    Annals of the New York Academy of Sciences 10/2007; 1110:315-8. · 4.31 Impact Factor
  • Ibrahim Marai, Yehuda Shoenfeld
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    ABSTRACT: Statins, HMG-CoA reductase inhibitors, are widely used for the treatment of hypercholesterolemia and the prevention of cardiovascular diseases. Recent experimental and clinical studies evaluated the effect of statins on immune and inflammatory cells, and the efficacy of statins in treatment of immune diseases. This review discusses the roles of statins in the treatment of immune and inflammatory diseases.
    Drug News & Perspectives 05/2007; 20(3):165-9. · 3.13 Impact Factor
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    ABSTRACT: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value. To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease. We prospectively assessed brachial artery flow-mediated dilatation in 110 consecutive subjects (46 CVD patients and 64 healthy controls), mean age 57 +/- 11 years; 68 were men. After an overnight fast and discontinuation of all medications for > or = 12 hours, percent improvement in FMD and nitroglycerin-mediated vasodilatation were assessed using high resolution ultrasound. %FMD but not %NTG was significantly lower in CVD patients (9.5 +/- 8.0% vs. 13.5 +/- 8.0%, P = 0.012) compared to healthy controls (13.4 +/- 8.0% vs. 16.7 +/- 11.0%, P = 0.084; respectively). In addition, an inverse correlation between %FMD and the number of traditional CVD risk factors was found among all study participants (r = -0.23, P = 0.015) and healthy controls (r = -0.23, P = 0.036). In a mean follow-up of 15 +/- 2 months, the composite CVD endpoints (all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with FMD < 6% compared to subjects with FMD > 6% (33.3% vs. 12.1%, P < 0.03, respectively). Thus, brachial artery %FMD provides important prognostic information in addition to that derived from traditional risk factor assessment.
    The Israel Medical Association journal: IMAJ 04/2007; 9(4):271-6. · 0.90 Impact Factor
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    ABSTRACT: To compare the clinical response of patients with right ventricular apical pacing (RVAP) upgraded to cardiac resynchronization therapy (CRT) to that of previously nonpaced heart failure (HF) patients who had de novo CRT implantation. The role of CRT in patients with wide QRS and HF due to RVAP is less well established than in other CRT candidates. Ninety-eight consecutive patients with CRT were studied (mean age 70, mean ejection fraction 0.23). Group A: patients having RVAP prior to CRT implantation (n = 25), group B: patients without prior RVAP (n = 73). Clinical and echocardiographic parameters were recorded prior to, and 3 months after, CRT implantation. Group A patients had a wider QRS at baseline compared to group B (203 +/- 32 ms vs 163 +/- 30 ms respectively, P < 0.001), and a shorter 6-minute walking distance (222 +/- 118 m vs 362 +/- 119 m, respectively, P < 0.005). Otherwise, clinical and echocardiographic parameters were not different. At follow up, group A patients had an average 0.7 +/- 0.5 decrease in their NYHA functional class, compared to 0.3 +/- 0.7 in group B patients (P < 0.05). Six-minute walking distance increased by 93 +/- 113 m in group A, versus 36 +/- 120 m in group B (P = 0.22). There was no difference in echocardiographic response to CRT between the groups. HF patients with prior RVAP demonstrate clinical improvement after upgrading to CRT that is comparable, and in some aspects, even better than that observed in HF patients with native conduction delay who undergo de novo CRT implantation.
    Pacing and Clinical Electrophysiology 08/2006; 29(8):880-4. · 1.25 Impact Factor
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    ABSTRACT: Benign prostatic hypertrophy is the most common benign tumor in males, resulting in prostatectomy in 20-30% of men who live to the age of 80. There are no data on the association of prostatectomy with autoimmune phenomena in the English-language medical literature. To report our experience with three patients who developed autoimmune disease following prostatectomy. Three patients presented awith autoimmune phenomenon soon after a prostectomy for BPH or prostatic carcinoma: one had clinically diagnosed temporal arteritis, one had leukocytoclastic vasculitis, and the third patient developed sensory Guillian-Barré syndrome following prostatectomy. In view of the temporal association between the removal of the prostate gland andthe autoimmune process, combined with previously known immunohistologic features of BPH, a cause-effect relationship probably exists.
    The Israel Medical Association journal: IMAJ 10/2005; 7(9):575-7. · 0.90 Impact Factor
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    ABSTRACT: Autoimmunity encompasses a wide spectrum of diseases from organ-specific diseases like Hashimoto thyroiditis, to systemic diseases such as systemic lupus erythematosus. These diseases are characterized by inflammation and the production of a wide range of autoantibodies directed against multiple autoantigens. Although their etiology is still poorly understood, genetic, immunological, hormonal, and environmental factors are major predisposing and triggering factors. These multiple factors, like pieces in a mosaic, may interplay in different forms, leading to the expression of various autoimmune manifestations and diseases. This phenomenon, which has been referred by us as the "mosaic of autoimmunity", illuminates the diversity of autoimmune manifestations among susceptible individuals. From this theoretical framework we conducted a wide search of the literature, on the prevalence of thyroid autoimmunity, the commonest of the autoimmune conditions, among other autoimmune diseases, and discuss the possible clinical significance of this association.
    Autoimmunity 06/2005; 38(3):247-55. · 2.75 Impact Factor
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    ABSTRACT: The anticardiolipin (aCL) antibody test was first established in 1983, using cardiolipin (negatively charged phospholipid) as an antigen in a solid-phase immunoassAy. It was first applied to the study of systemic lupus erythematosus patients, and was found associated with thromboses and recurrent pregnancy losses. The wide use of this test was determinant in the definition of the "aCL or antiphospholipid syndrome" (APS).Later, it was demonstrated that aCL antibodies do not recognize anionic phospholipids but are directed against plasma proteins bound to anionic phospholipids, mainly beta-2-glycoprotein I, which is now considered as the autoantigen in APS. Anti-beta-2-glycoprotein I (anti-beta2GPI) is not yet accepted as a serological criterion for APS, but most investigators would consider a patient with anti-beta2GPI antibodies and clinical features of APS to have the syndrome. aCL and anti-beta2GPI are a heterogeneous group of antibodies with different clinical significances and can be present in different autoimmune diseases as well as in infectious diseases.
    Autoimmunity 03/2005; 38(1):33-8. · 2.75 Impact Factor
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    ABSTRACT: Antiphospholipid autoantibodies (aPL), antithyroid antibodies and anti-extractable nuclear antigens (anti-ENA) have all been reported to be associated with recurrent miscarriages (RM) and infertility. However, this association remained controversial. Fifty-eight women with impaired fertility (38 women with RM and 20 women with infertility, but no miscarriages) and 28 control parous women were screened for seven autoantibodies [antithyroglobulin (aTG), antithyroid peroxidase (aTPO), anticardiolipin (aCL), antiphosphatidyl-serine (aPS), antiprothrombin antibodies (aPT), anti-beta 2 glycoprotein 1 (abeta2GP1), and anti-ENA]. There was no evidence for autoimmune diseases in the patients or the control. The analysis was also performed with several panels of autoantibodies, each of which contained two or more autoantibodies. Anti-TPO was the only antibody to be associated with RM (P = 0.01). A significant association was found between RM, and autoantibodies in the 'aTG + aTPO + anti-ENA' or 'aTG + aTPO' panels. The 'aTG + aTPO + anti-ENA' panel was also associated with RM when the analysis was performed only on 17 women who had secondary infertility: 10 from the 38 women with RM, and seven from the 20 women with infertility and no miscarriages. A significant association (P < 0.001) was also apparent between anti-CL and anti-PS and infertility compared with the 28 control women. RM was associated with autoantibodies to aTPO and the combined panel of aTPO, aTG and anti-ENA, but not with aPL. aPL were associated with infertility.
    American journal of reproductive immunology (New York, N.Y.: 1989) 03/2004; 51(3):235-40. · 2.67 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) and coeliac disease (CD) are diseases of an autoimmune origin that share the human leukocyte HLA-B8 and HLA-DR3 histocompatibility antigens, yet the co-association of CD with SLE is mainly based on case reports. Thus, the real prevalence of CD in SLE is unclear. The aim of this study was to determine the prevalence of antitissue transglutaminase (anti-tTG) in SLE and the relation between SLE and CD. In this case-control study, 100 patients with SLE, and 120 healthy subjects were studied. Sera from all participants were analysed for the presence of IgA and IgG anti-tTG antibodies using a human recombinant tissue transglutaminase (tTG) immuno-enzymatic assay. Anti-tTG positive patients and controls were further tested for antiendomysial (EMA) antibodies by an indirect immunofluorescence and HLA typing (DQalpha1*0501-DQbeta1*0201 allele determination). Subjects who had EMA or the mentioned allele, underwent duodenal biopsy to confirm a possible diagnosis of CD. Anti-tTG antibodies (IgA or IgG isotypes) were found in three of the 100 SLE patients (overall prevalence of 3%): one had the IgA and two the IgG isotypes. Only 1 of 120 healthy subjects (0.8%) had a low positive reaction for IgA anti-tTG. Only the IgA anti-tTG positive SLE patient was diagnosed as having CD based on a positive IgA-EMA and small bowel biopsy findings. The two IgG anti-tTG positive SLE patients and the IgA anti-tTG positive healthy subject were classified as false positives (EMA negative and HLA DQalpha1*0501-DQbeta1*0201 allele negative). In conclusion, anti-tTG antibodies were found at a low rate in SLE patients and mostly did not indicate the presence of CD. Thus, serological screening for CD is not recommended in SLE, unless a clinical suspicion of CD is present.
    Lupus 02/2004; 13(4):241-4. · 2.48 Impact Factor
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    ABSTRACT: Antiphospholipid syndrome (APS, Hughes' syndrome) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis and recurrent foetal loss, accompanied by mild to moderate thrombocytopaenia and elevated titres of antiphospholipid antibodies (aPLs): lupus anticoagulant (LAC) and/or anticardiolipin (aCL) antibodies. APS was defined originally in 1983 in systemic lupus erythematosus (SLE) patients, but later it was found that APS can be primary or secondary to other autoimmune diseases or malignancy. During the past 20 years many organs have been reported to be involved in this syndrome and the clinical manifestations are seen in every medical field. Moreover, many aPLs have been found in APS besides aCLs and LACs, which bind to the autoantigen beta-2-glycoprotein I (beta2GPI). Treatment for APS, based on antiplatelet and anticoagulation drugs, is dependent on various parameters, including whether SLE is also present, classical vs non-classical manifestations of the diseases, women with APS based on pregnancy morbidity, the presence of elevated aCL antibody titres in the absence of clinical manifestations, and catastrophic APS.
    Scandinavian Journal of Rheumatology 02/2004; 33(6):365-72. · 2.61 Impact Factor
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    ABSTRACT: In autoimmune diseases including systemic lupus erythematosus (SLE), the immune system attacks various autoantigens and causes damage in target organs. Recently, it was found that dead cells serve as a repertoire for autoantigens which can stimulate an autoimmune response in sensitive persons. The mechanisms which lead to induction and progress of apoptosis include extra-cellular stimuli, intra-cellular signals, and cleavage of proteins. During apoptosis, several events occur including migration of intra-cellular components to the cell membrane, removal of apoptotic cells by specific proteins and complement systems, and phagocytosis of apoptotic cells by macrophages. In recent years, evidence has accumulated that the autoimmune response can be initiated as a result of defects in apoptosis and/or removal of apoptotic material. In this article, the association of apoptosis to the pathogenesis of systemic lupus erythematosus is discussed.
    Harefuah 01/2004; 142(12):844-7, 877, 876.
  • Ibrahim Marai, Yair Levi
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    ABSTRACT: Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. Hiccups serve no known physiologic function. Mostly, it is a benign symptom which terminates without treatment. Persistent and intractable hiccups may indicate an organic disorder, thereby requiring evaluation based on history, physical examination, and selected laboratory tests. The treatment is based on the organic disorder, if it is found. The combination therapy with cisapride, omeprazole and baclofen is the most effective empiric treatment. We describe a number of case reports of patients with hiccups due to digitalis intoxication, ischemia of the inferior wall of the heart, peptic disease and gastroesophageal reflux disease.
    Harefuah 02/2003; 142(1):10-3, 79.
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    ABSTRACT: Antiphospholipid antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combinations of phospholipids, phospholipid binding proteins or both. To evaluate the frequency of anticardiolipin (aCL) or anti-beta-2 glycoprotein I (anti-beta2GPI) antibodies in a cohort of patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome and other rheumatic and infectious conditions. Sera were drawn from 226 patients with PAPS (n= 66), SAPS (n= 60), rheumatoid arthritis (RA) (n= 30), scleroderma (SSc) (n= 30) or syphilis (n= 30). IgG, IgM, IgA aCL and anti-beta2GPI antibodies were determined for all patients. We employed Varelisa diagnostic kits (Pharmacia Diagnostics GmbH & Co.KG, Germany). In APS patients: aCL and anti-betaGP1 antibodies were detected in 81.8% and 70% in PAPS and SAPS patients, respectively. In PAPS, aCL were detected in 71.2%, and anti-beta2GP1 in 50% of patients. In SAPS, aCL were detected in 63.3%, and anti-beta2GP1 in 53.3% of patients. In syphilis, aCL and anti-beta2GP1 antibodies were detected in 46.7% of patients in low levels: aCL in 36.7% and anti-beta2GP1 in 20% of patients. aCL antibodies were detected in 10%, 13.3%, and 0% of RA patients, SSc patients, and healthy persons, respectively. Anti-beta2GP1 antibodies were not detected in RA patients, SSc patients, and healthy persons. aCL and anti-beta2GP1 antibodies are more frequently found in sera of APS patients, and can be found in low levels in syphilis. Anti-beta2GP1 assay found to be more specific than aCL in antiphospholipid antibodies determination.
    Human antibodies 01/2003; 12(3):57-62.
  • Harefuah 07/2002; 141(6):527-9.
  • Ibrahim Marai, Yehuda Shoenfeld
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    ABSTRACT: Minocycline in another drug that can induce drug-induced lupus. Minocycline is frequently used for acne as a prolonged treatment, so it is important to be aware of the risks in this treatment. The risk ratio for the development of lupus due to minocycline is not known, but it seems to be low. We described a 26 year old female who was treated with minocycline due to acne. The treatment was complicated by rash and serological signs of lupus (antinuclear antibodies and anti-DNA antibodies). The aim of this article is to raise the level of awareness of this complication due to minocycline.
    Harefuah 03/2002; 141(2):151-2, 223, 222.

Publication Stats

285 Citations
45.09 Total Impact Points


  • 2014
    • Rambam Medical Center
      • Department of Cardiology
      H̱efa, Haifa District, Israel
  • 2001–2008
    • Sheba Medical Center
      • Department of Medicine B
      Gan, Tel Aviv, Israel
  • 2005–2007
    • Tel Aviv University
      • Department of Internal Medicine
      Tell Afif, Tel Aviv, Israel