Udi Nussinovitch

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel

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Publications (53)137.1 Total impact

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    ABSTRACT: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. To evaluate ANS function in colchicine non-responders by using the HRV tool. The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.
    No preview · Article · May 2015 · The Israel Medical Association journal: IMAJ
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    ABSTRACT: Vitamin D immune-modulating effects were extensively studied, and low levels have been linked with autoimmune diseases. The associations of vitamin D with autoimmune diseases of the liver, and particularly primary biliary cirrhosis (PBC), are yet to be defined. Hence, in this study, serum levels of vitamin D were determined in 79 patients with PBC and 70 age- and sex-matched controls by the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). Clinical and serological parameters of patients were analyzed with respect to vitamin D status. Mean levels of vitamin D were significantly lower among patients with PBC compared with controls (16.8 ± 9 vs. 22.1 ± 9 ng/ml; p = 0.029), and vitamin D deficiency (≤10 ng/ml) was documented in 33 % of patients with PBC versus 7 % of controls (p < 0.0001). Vitamin D levels inversely correlated with advanced liver damage and the presence of concomitant autoimmune diseases. In contrast, higher levels of vitamin D were observed among patients with PBC treated with ursodeoxycholic acid (UDCA). In conclusion, low vitamin D levels are common among patients with PBC and correlate with advanced disease, lack of UDCA therapy and autoimmune comorbidity. This alludes to the plausible roles of vitamin D as a prognostic marker of PBC severity, and as a potential player in this disease pathogenesis. While further studies are awaited, monitoring vitamin D in patients with PBC and use of supplements may be advisable.
    No preview · Article · Nov 2014 · Immunologic Research
  • Udi Nussinovitch · Bar Ronen · Evgeny Farber · Yoav Yanir

    No preview · Article · Dec 2012 · Transfusion
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    ABSTRACT: Eating disorders, in particular anorexia nervosa (AN), are associated with cardiovascular complications and risk of arrhythmias. In a recent published study, it was found that patients with eating disorders, especially those affected by bulimia nervosa (BN) and a history of AN have abnormal late ventricular potentials (LPs). LPs are electrocardiographic markers used in detecting abnormal depolarization and increased risk of arrhythmias. Given the paucity of knowledge regarding the affects of eating disorders on cardiac depolarization, our aim was to further explore LPs in patients with eating disorders. The study group included 30 hospitalized patients with eating disorders (14 with AN, 10 with BN with no history of AN, and 6 with BN and history of AN). Signal averaged electrocardiography was conducted on all patients usingthe Frank corrected orthogonal lead system. No patient with either eating disorder tested positive for LPs. Hospitalized patients with eating disorders, medically monitored and treated for several weeks, had normal serum electrolytes, started to normalize their weight, and did not appear to be prone to arrhythmias associated with abnormal depolarization. The prognostic significance of LPs in risk stratification of patients with eating disorders should be further evaluated by large cohort studies and longer follow-up studies. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2011;45:900-904).
    Full-text · Article · Nov 2012 · International Journal of Eating Disorders
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    ABSTRACT: Our aim was to investigate the reliability of ultra-short HRV in patients with DM. A good correlation was found between the 1 minute and 5 minute parameters for maximal-RR, minimal-RR, average-RR, SDNN, RMSSD, pNN50, and total power. Also, a good correlation between 10 second and 5 minute parameters was found for maximal-RR, minimal-RR, average-RR, and RMSSD. We suggest that certain ultra-short HRV parameters can be used efficiently in DM patients for autonomic evaluation.
    No preview · Article · Jun 2012 · Journal of diabetes and its complications
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    ABSTRACT: The association between familial Mediterranean fever (FMF) and subclinical cardiac disease remains controversial. The aim of the current study was to evaluate whether FMF patients, who do not respond to colchicine treatment, and thereby endure persistent inflammation, have increased QT dispersion (QTd) values. Twenty-two FMF patients and 22 age- and sex-matched control subjects were included in the study. Repolarization and QT dispersion parameters were computed from 12-lead ECG recording using designated computer software, and results of five beats were subsequently averaged. Both FMF patients and controls had similar comorbidities, similar values of average QT, average corrected QT interval length, average QTd interval, average QT corrected dispersion, QT dispersion ratio, JT dispersion (JTd), and JT corrected dispersion. In conclusion, FMF patients who were unresponsive to colchicine treatment and did not develop amyloidosis had normal QTd and JTd parameters, indicating a non-increased risk for repolarization-associated ventricular arrhythmias.
    No preview · Article · Apr 2012 · Clinical Rheumatology
  • Udi Nussinovitch · Ilan Ben-Zvi · Avi Livneh
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    ABSTRACT: The association between familial Mediterranean fever (FMF) and increased risk for ventricular arrhythmias is controversial, and data on this subject are meager. To evaluate QT variability index (QTVI) and other repolarization markers associated with arrhythmogenity in patients with amyloidosis of FMF. The study group comprised 12 FMF patients with amyloidosis, and 14 age and gender-matched healthy subjects served as the control group. QT measurements were conducted according to accepted procedure, using computerized software for recording and analysis. No differences were found in clinical and demographic parameters in the study and control groups, except for hypertension which was more common in the FMF amyloidosis group. QTc and power spectral analysis of QT variability parameters were similar in both groups. Nevertheless, QTVI values in FMF amyloidosis patients were significantly higher than in healthy individuals (-1.02 +/- 0.38, vs. -1.36 +/- 0.32 respectively, P = 0.02). Compared with healthy controls, amyloidosis of FMF is associated with increased QTVI. It remains unknown whether this finding is solely amyloidosis related and whether it has any prognostic significance.
    No preview · Article · Apr 2012 · The Israel Medical Association journal: IMAJ
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    ABSTRACT: Anorexia nervosa (AN) is an increasingly common medical condition. Some studies have demonstrated an increased prevalence of atrial premature contractions and anatomical changes in AN patients. Our aim was to investigate P wave parameters and P wave dispersion, an electrocardiographic marker for supraventricular arrhythmias, and its effect on AN. The study group included 48 patients with AN, most hospitalized for a few weeks, and a matched control group. All participants underwent 12-lead electrocardiography under strict standards. P wave length and P wave dispersion in each patient were computed from a randomly selected beat and an averaged beat constructed from 7 to 12beats, included in a 10 second ECG. There were no statistically significant differences found between the groups for minimal, maximal, average P wave duration and P wave dispersion, calculated either from a random beat or averaged beats. In conclusion, medically treated AN patients who have gained weight, have normal P wave parameters, and therefore do not appear to have an increased electrocardiographic risk for atrial fibrillation compared with healthy controls. Further studies are required to evaluate influence of different disease stages, electrolyte imbalance and other medical complications on P wave parameters and risk for supraventricular arrhythmias in AN patients.
    No preview · Article · Mar 2012 · Psychiatry Research
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    ABSTRACT: The association between familial Mediterranean fever (FMF), early atherosclerosis, and electrocardiographic markers for arrhythmias remains controversial. There are conflicting results as to the occurrence of high QT dispersion in FMF. The aim of the present study was to further investigate repolarization dynamics and other repolarization-associated pro-arrhythmogenic markers in FMF patients. To explore repolarization in FMF, patients who responded well to colchicine and patients who had not responded to colchicine, yet were amyloidosis-free, were included. We aimed to evaluate whether increased inflammatory burden, a characteristic of non-responsive patients, was specifically associated with abnormal repolarization. Included in the study were 53 FMF patients (27 colchicine non-responders) and 53 age- and sex-matched control subjects. Electrocardiograms were performed under strict standards. QT variability parameters were computed with custom-made computer software. No significant difference in any of the QT dynamic parameters was found in either FMF group compared with the healthy controls. Mean values of QT variability index, regardless of colchicine response, were similar to previously published results for healthy persons. In conclusion, patients with FMF who are continuously treated with colchicine and have not developed amyloidosis, regardless of their clinical response, have normal QT variability parameters, indicating normal repolarization dynamics and suggesting no increased risk of repolarization-associated cardiac arrhythmias.
    No preview · Article · Jan 2012 · Clinical Rheumatology
  • Udi Nussinovitch
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    ABSTRACT: P-wave dispersion (Pd) is an appealing marker for predicting the risk of developing atrial fibrillation. At present, no definitive cutoff value has been determined as to the diagnosis of high-risk patients. Our aims were to evaluate P-wave parameters of healthy subjects published in the literature, determine normal range and weighted means of Pd and P-wave parameters, and investigate the influences of gender, age, and BMI on the weighted results. A systematic search of studies published in PubMed was conducted. Only studies which included control groups of healthy individuals were included. Of the 657 studies initially identified, 80 were eligible for inclusion. The total number of participants was 6,827. The highest reported Pd values were 58.56 ± 16.24 ms; the lowest were 7 ± 2.7 ms. The weighted mean was 33.46 ± 9.65 ms; weighted median was 32.2 ms. Gender and age were not found to be associated with significant influences on P-wave parameter values. High-normal BMI was not found to be associated with increased P-wave parameter values. Pd, Pmax, and Pmin span a wide range of values in healthy individuals. Seemingly, abnormal values were often reported in healthy adults. The high variability of P-wave parameters in healthy individuals, and overlapping of the results with those reported for patients with increased risk for atrial fibrillation, might suggest that this technique has limited sensitivity and specificity. The variability between studies may stem from methodological issues and, therefore, there is a definite need for methodological standardization of Pd measurements.
    No preview · Article · Jan 2012 · Annals of Noninvasive Electrocardiology
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    ABSTRACT: A scarcity of data exists relating to the effect of amyloidosis of Familial Mediterranean fever (FMF) on the autonomic nervous system. Our aim was to further investigate the presence of dysautonomia in FMF-AA amyloidosis, using a comparative case series design. The study group consisted of 40 patients with FMF: 20 without co-morbidities or amyloidosis and 20 in various stages of renal amyloidosis. Time domain and power spectral analyses of heart rate dynamics were performed according to accepted procedures. Findings were compared with 20 healthy control subjects. No statistically significant differences were found in any of the studied heart rate variability (HRV) parameters between patients with uncomplicated FMF and controls. In contrast, patients with progressive amyloidosis (post renal transplantation or on dialysis) had significantly lower HRV parameters compared to control subjects (i.e. mean low frequency power spectral components 104.30 ms² vs. 172.09 ms², p <0.05, mean standard deviation of all normal RR intervals 32.27 ms vs. 51.51 ms, p <0.05, mean HRV triangular index 9.08 vs. 15.82, p <0.05). The adjusted odds ratio was 14.5 (95%CI 1.21-165.03, p = 0.04) for HRV triangular index lower than 12.2 in the progressive amyloidosis group, 41.24 (95%CI 1.81-938.68, p = 0.02) for low frequency power spectral components values lower than 142.35 ms², and 12.67 (95%CI 1.04-153.96, p = 0.04) for standard deviation of all normal RR intervals values lower than 40.15?ms. Amyloidosis of FMF, particularly at a progressive stage, is associated with HRV abnormalities suggestive of the presence of autonomic nervous system dysfunction.
    No preview · Article · Dec 2011 · Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis
  • Udi Nussinovitch · Yehuda Shoenfeld
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    ABSTRACT: Autoimmunity is influenced by multiple factors including gender and sex hormones. A definite female predominance is found in many autoimmune diseases. Gender is also associated with differences in clinical presentation, onset, progression and outcome of autoimmune diseases. Sex hormones might influence the target organ's vulnerability to an autoimmune response. Gender differences also exist in organ specific autoimmune diseases such as multiple sclerosis, Guillain-Barré syndrome, Crohn's disease and celiac disease. Nevertheless, other organ specific autoimmune diseases (i.e. ulcerative colitis) are seemingly characterized with similar prevalence in both males and females. The reason for gender differences in certain autoimmune diseases remains unknown, but may be attributed to sex hormone influence, fetal microchimerism, X chromosome inactivation, and X chromosome abnormalities. Sex hormones have been found to have immune modulating properties, as well as providing cellular protection following tissue damage in certain circumstances. Sex hormones also influence innate and adaptive immune cells, number of B and T cells, antigen presentation and cytokine secretion. Herein, we review the influence of gender on organ-specific autoimmune diseases affecting the heart, blood vessels, central nervous system and gastrointestinal tract. It appears that sex hormones may have a therapeutic potential in several autoimmune conditions, although further research is required before therapeutic recommendations can be made.
    No preview · Article · Nov 2011 · Autoimmunity reviews
  • Arie Altman · Udi Nussinovitch · Orly Goitein · Yehuda Shoenfeld

    No preview · Article · Oct 2011 · The Israel Medical Association journal: IMAJ
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    ABSTRACT: Anorexia nervosa (AN) may be complicated by cardiac arrhythmias and sudden death. A single study reported an increased QT variability index (QTVI), a marker for cardiac arrhythmogenicity, in AN patients. The aim of the current study was to further evaluate repolarization dynamics in a large cohort of patients with AN without electrolyte abnormalities and to evaluate previously unreported repolarization dynamics parameters. Forty-three AN patients and 45 age- and sex-matched controls were included in the study. Twenty-nine AN patients were hospitalized for a mean time of 1.5±1.1 months. The rest were ambulatory AN patients. Electrocardiograms were conducted under strict standards. QT variability index, normalized QT variability (QTVN) and power spectral analysis of QT dynamics were conducted with designated computer software. None of the patients had an electrolyte imbalance. Although mean QT was higher in AN patients compared with controls, QTc results were similar following corrections for RR interval. There was no significant difference in QTVI, QTVN and power spectral analysis parameters among groups. The results of QTVI and QTVN were comparable to those previously published for healthy individuals. During 3 years of follow-up, no patient developed arrhythmias or suddenly died. Medically treated AN patients who gained weight and had normal serum electrolytes appeared to have normal QTc and QT variability indexes, reflecting a nonincreased risk for cardiac arrhythmias. We suggest that weight normalization, medical treatment and lack of electrolyte abnormalities are responsible in part for these results. Further evaluation of the prognostic significance of QTVI and QTVN in AN is warranted.
    Full-text · Article · Aug 2011 · General hospital psychiatry
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    ABSTRACT: High values of resting heart rate were found to be correlated with adverse outcomes in various patient groups. Heart rate variability (HRV) is a reliable technique in determining autonomic nervous system function. Our aim was to evaluate whether a 10-second resting heart rate obtained from a resting electrocardiogram (ECG), could be used as a reliable evaluation of short-term HRV. Seventy-nine healthy volunteers were included in the study. All participants underwent a 10-second ECG, and 5-minute HRV measurement under strict criteria. A significantly negative correlation was found between resting heart rate and 5-minute max-RR, min-RR, standard deviation of normal RR intervals (SDNN), root mean square of successive differences of RR intervals (RMSSD), HRV triangular index, number of intervals differing by 50 milliseconds from the preceding interval (NN50), pNN50, standard deviation of the points perpendicular to the line of identity (SD1), standard deviation along the line of identity (SD2), and high frequency spectral component (HF). A significant positive correlation was found between resting heart rate and a 5-minute low frequency spectral component (LF) and LF/HF ratio. Specifically, max-RR and min-RR were found to have the best correlation with resting heart rate. Resting heart rate obtained from a 10-second ECG can be used for crude estimation of all HRV results in healthy individuals who do not take medications, with variable efficacy depending on the measured parameter. Resting heart rate was especially efficient in predicting max-RR and min-RR. Further research should focus on assessing the reliability of a resting heart rate for HRV evaluation, in patients with autonomic dysfunction and high-risk cardiac patients.
    No preview · Article · Jul 2011 · Pacing and Clinical Electrophysiology
  • Udi Nussinovitch · Yehuda Shoenfeld
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    ABSTRACT: The role of autoimmunity in cardiovascular diseases has become one of the focal points of research studies. Autoimmune response and autoreactive autoantibodies have been found in dilated cardiomyopathy, heart failure, rheumatic fever, myocarditis, atherosclerosis, and other diseases. Autoantibodies may appear due to tissue injury and exposure of autoantigens, in addition to molecular mimicry and cross-reactivity with antigens found in infectious agents in predisposed individuals. In the early 1990s, autoantibodies reacting with the M2 muscarinic receptor were found in patients with dilated cardiomyopathy and subsequently, in patients with Chagas heart disease and arrhythmic disorders. Immunization of animals with the corresponding antigen triggered cardiac abnormalities also appearing in dilated cardiomyopathy of humans. It has been suggested that antibodies against M2 muscarinic receptors play a role in the pathogenesis of cardiac diseases and may also alter the electrophysiological properties of cardiac tissue. Herein, we review the current knowledge of antibodies against M2 muscarinic receptors and the possible use of a targeted therapy against these autoantibodies.
    No preview · Article · Jun 2011 · Clinical Reviews in Allergy & Immunology
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    ABSTRACT: There is a paucity of knowledge regarding the autonomic nervous system function in patients with familial Mediterranean fever (FMF). Therefore, our aim was to evaluate autonomic responses in patients with FMF using complementary tests. The study groups included 33 patients with uncomplicated FMF and 39 control subjects. Autonomic function was evaluated by measuring responses to metronomic breathing, the Valsalva maneuver, and the Ewing maneuver. Autonomic parameters were computed from electrocardiograms with designated computer software. There were no statistically significant differences in any of the measured parameters of autonomic function between the patient and control group. The measured autonomic parameters of both groups were similar to those previously reported in healthy individuals. In conclusion, patients with FMF who did not develop amyloidosis due to continuous colchicine treatment appeared to have normal autonomic function, as reflected by the normal response to physiological autonomic stimuli.
    No preview · Article · May 2011 · Clinical Rheumatology
  • Udi Nussinovitch · Amos Nussinovitch

    No preview · Chapter · May 2011
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    ABSTRACT: Familial Mediterranean fever (FMF) is a hereditary disease characterized by attacks of fever and polyserositis. Recent studies differ as to whether FMF is associated with an abnormally high P-wave duration and P-wave dispersion, markers for supraventricular arrhythmogenicity. The aim of our study was to further evaluate atrial dispersion in FMF patients with amyloidosis. The study groups consisted of 16 patients with FMF and amyloidosis, and 16 age- and sex-matched control subjects. All participants underwent 12-lead electrocardiography under strict standards. P-wave length and P-wave dispersion in each individual patient were computed from a randomly selected beat and an averaged beat constructed from 7 to 12 beats, included in a 10-s electrocardiogram. No statistically significant differences were found between the groups for minimal, maximal, and average P-wave duration and P-wave dispersion, calculated either from a random beat or averaged beats. In conclusion, although a small difference cannot be excluded because of the small study groups, FMF patients with amyloidosis appear to have atrial conduction parameters similar to those of healthy controls, and therefore apparently do not have an increased electrocardiographic risk for developing supraventricular arrhythmias.
    No preview · Article · Apr 2011 · Clinical Rheumatology
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    ABSTRACT: Heart rate variability (HRV) is an accepted and reliable means for assessing autonomic nervous system dysfunction. A 5-minute measurement of HRV is considered methodologically adequate. Several studies have attempted to use shorter recordings of 1-2 minutes or 10 seconds. The aim of this study was to determine the reliability of HRV parameters calculated from ultra-short electrocardiogram recordings. Seventy healthy volunteers were recruited for the study. HRV was evaluated for 5 minutes according to accepted procedures. Thereafter, HRV parameters were recalculated from randomly selected 1-minute and 10-second intervals. The standard and ultra-short measurements were correlated using intraclass correlation coefficients. Good correlations between the 5-minute electrocardiograms (ECGs) and both the 1-minute and 10-second ECGs were noted for average RR interval, and root mean square of successive differences in RR intervals (RMSSD). No correlation was noted for standard deviation of the RR interval (SDNN) and several other HRV parameters. RMSSD, but not SDNN, seem a reliable parameter for assessing HRV from ultra-short (1 minute or 10 seconds) resting electrocardiographic recordings. Power spectral analysis and evaluation of other HRV parameters require longer recording periods. Further research is required to evaluate the importance of ultra-short RMSSD for cardiovascular risk stratification.
    No preview · Article · Apr 2011 · Annals of Noninvasive Electrocardiology

Publication Stats

501 Citations
137.10 Total Impact Points


  • 2014
    • Technion - Israel Institute of Technology
      H̱efa, Haifa, Israel
  • 2009-2011
    • Sheba Medical Center
      • • Department of Pathology
      • • Department of Medicine B
      Gan, Tel Aviv, Israel
  • 2008-2011
    • Tel Aviv University
      • • Department of Internal Medicine
      • • Department of Pediatrics
      • • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel