Bnai Zion Medical Center

Haifa, Israel

Bnai Zion Medical Center

Haifa, Israel
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Kessel A.,Bnai Zion Medical Center | Toubi E.,Bnai Zion Medical Center
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010

Background: The treatment of severe chronic urticaria (CU) remains a difficult goal to achieve. Many patients do not respond to anti-histamine therapy, even when off-label doses are given. Thus, cyclosporine-A (CsA) becomes a good therapeutic option for severe patients and for some, long-term therapy is required. We evaluated the effectiveness and safety of low-dose CsA, when treatment cannot be discontinued and long-term CsA therapy is needed to maintain severe CU in remission. Methods: Among 2000 patients with CU who were referred to our outpatient clinic, 120 patients who suffered from a very severe CU began treatment with CsA 3 mg/kg. A clinical and laboratory followup was performed during this period of treatment. Results: In 20 patients, CsA was discontinued within 2-15 days after initiation because of side-effects. Among 62 of the remaining 100 patients (62%), CsA was administered for a period of 3 months with a highly beneficial outcome. In another 20 patients (20%), CsA was considered beneficial; however, it was required for a longer period of time, 5-10 years for some of the cases. In all cases, CsA was well tolerated and most important, it was safe. For 18 patients (18%), CsA therapy was reported as failed. Conclusion: A low dose of CsA is a good option for patients who suffer from especially severe CU. In most cases, this therapy regimen is considered effective and safe. For a small group of patients, long-term therapy is needed, and until now it is considered safe. © 2010 John Wiley & Sons A/S.


Kessel A.,Bnai Zion Medical Center
Pediatric Pulmonology | Year: 2014

Background Subjects with allergic rhinitis (AR) suffer from impaired lung function, especially decreased FEF25-75%. The purpose of this study was to examine lung function and the long-term response to INCS in AR patients with impaired lung function, and to characterize the phenotype of these children. Methods Two hundred two children with AR underwent an allergy evaluation including a skin prick test and spirometry. Children with impaired lung function were treated with daily nasal corticosteroids spray (INCS) and antihistamine as needed. Results Fifty-three children out of 202 (26.3%) had impaired lung function: 34 of them (64.2%) had FEF25-75% values under 80% of predicted and normal FEV1 values, and 19 individuals (35.8%), had both FEF25-75% and FEV1 values below 80% of predicted. A positive correlation between FEV1 and FEF 25-75% values (r = 0.369, P = 0.007) and a reverse correlation between duration of nasal symptoms and FEF25-75% values (r = -0.364, P = 0.012) were found. Post-ronchodilation FEV1 levels increased from 81.9 ± 8.0 to 87.7 ± 10.4 (P < 0.0001). Thirty-five of the 53 children complied with a continuous INCS treatment regimen over a period of 3-12 months, demonstrated increased FEF25-75% (84.4 ± 13.6 vs. 70.1 ± 7.1, P < 0.001) and FEV1 (92.3 ± 10.9 vs. 84.4 ± 7.8, P < 0.0001) after INCS treatment. However, FEF 25-75% values were still significantly lower compared to the group of AR children with normal lung function (84.4 ± 13.6 vs. 95.7 ± 8.8, P < 0.0001). Conclusions INCS improve FEF25-75% above 80% of predicted values in 2/3 of children with abnormal lung function. However, this improvement does not reach levels of AR children with normal lung function. © 2013 Wiley Periodicals, Inc.


Oliven A.,Bnai Zion Medical Center
Current Opinion in Pulmonary Medicine | Year: 2011

Purpose of Review: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent pharyngeal collapse secondary to sleep-induced hypotonia of peri-pharyngeal structures. Therapy for OSA is sometimes poorly tolerated and not always effective. The current study reviews a new treatment modality, hypoglossus stimulation, recently evaluated by multiple physiological studies and currently assessed by several clinical studies. Recent Findings: A phase-I, implantable hypoglossus nerve stimulation multicenter study was published in 2001. Significant reduction in apnea-hypopnea index (AHI) was reported in seven of the eight implanted OSA patients, but technical faults precluded prolonged follow-up. Over the past 2 years, three new hypoglossus nerve stimulation systems have been evaluated in more than 60 OSA patients. In adequately selected patients, a more than 50% reduction in AHI was observed. Usually, a decrease in OSA severity from moderate-severe to mild-minimal can be achieved. Summary: Ongoing research, including recent initiation of a large multicenter phase-III study, suggests that hypoglossus nerve stimulators are likely to be available as a new treatment modality within a few years. Additional data are needed to define which OSA patients are most likely to benefit from hypoglossus nerve stimulation. Continuous refinement of electrodes design is likely to improve stimulation efficacy in coming years. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Vadasz Z.,Bnai Zion Medical Center | Haj T.,Bnai Zion Medical Center | Kessel A.,Bnai Zion Medical Center | Toubi E.,Bnai Zion Medical Center
BMC Medicine | Year: 2013

Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells. The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections. © 2013 Vadasz et al.; licensee BioMed Central Ltd.


Kugelman A.,Bnai Zion Medical Center | Colin A.A.,University of Miami
Pediatrics | Year: 2013

Late preterm (LP) infants are defined as those born at 34-0/7 to 36-6/7 weeks' gestational age. LP infants were previously referred to as near term infants. The change in terminology resulted from the understanding that these infants are not fully mature and that the last 6 weeks of gestation represent a critical period of growth and development of the fetal brain and lungs, and of other systems. There is accumulating evidence of higher risks for health complications in these infants, including serious morbidity and a threefold higher infant mortality rate compared with term infants. This information is of critical importance because of its scientific merits and practical implications. However, it warrants a critical and balanced review, given the apparent overall uncomplicated outcome for the majority of LP infants. Others reviewed the characteristics of LP infants that predispose them to a higher risk of morbidity at the neonatal period. This review focuses on the long-term neurodevelopmental and respiratory outcomes, with the main aim to suggest putative prenatal, neonatal, developmental, and environmental causes for these increased morbidities. It demonstrates parallelism in the trajectories of pulmonary and neurologic development and evolution as a model for fetal and neonatal maturation. These may suggest the critical developmental time period as the common pathway that leads to the outcomes. Disruption in this pathway with potential long-term consequences in both systems may occur if the intrauterine milieu is disturbed. Finally, the review addresses the practical implications on perinatal and neonatal care during infancy and childhood. © 2013 by the American Academy of Pediatrics.


Vadasz Z.,Bnai Zion Medical Center | Haj T.,Bnai Zion Medical Center | Kessel A.,Bnai Zion Medical Center | Toubi E.,Bnai Zion Medical Center
FEBS Letters | Year: 2013

B cells are a source of inhibitory cytokines such as IL-10 and TGF-β. The ability of being B-regulatory cells (B-regs) was shown to be driven by many stimulatory factors such as toll-like receptors, CD40-ligand and others. However, the characterization of B-regs is still underway. B-regs express high levels of CD25, CD86, IL-10 and TGF-β. In addition, we propose that semaphorin3A is a regulatory molecule and therefore can serve as one of the additional markers for B-regs. This subset of B cells was able to suppress Th1 proliferation, thus contributing to the maintenance of self-tolerance. Finally, the potentiation of B-reg function should become the aim of many immunomodulatory drugs, contributing to a better control of autoimmune diseases. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Kaly L.,Bnai Zion Medical Center | Rosner I.,Bnai Zion Medical Center | Rosner I.,Technion - Israel Institute of Technology
Best Practice and Research: Clinical Rheumatology | Year: 2012

In the past decade, tocilizumab, an anti interleukin-6 agent, has been successfully developed as a therapeutic agent for the treatment of rheumatoid arthritis and systemic onset juvenile idiopathic arthritis. In addition to countering inflammation, tocilizumab is also known affect B cell as well as T cell function, thus modulating immune function, and impact osteoclasts, as well as vascular endothelial growth factor. As such, its efficacy is currently being explored in a large number of autoiommune conditions including a number of vasculitides, systemic lupus erythematosus, systemic sclerosis, polymyositis, graft versus host disease, relapsing polychondritis, as well as Behcet's syndrome, spondyloarthropathies, and tumor necrosis factor receptor associated periodic syndrome. © 2012 Elsevier Ltd. All rights reserved.


Vadasz Z.,Bnai Zion Medical Center | Toubi E.,Bnai Zion Medical Center
Clinical Reviews in Allergy and Immunology | Year: 2014

The semaphorin family members were originally considered to play a role in neurodevelopment, angiogenesis, tumor development, and metastasis. Over the past few years, a growing body of data indicates that semaphorins are involved in the regulation of the immune system, identified in this case as the "immune semaphorins." These semaphorins are involved in almost all phases of both normal and pathological immune responses and were demonstrated to participate in allergic diseases as well as in auto-immune pathologies. Some of them, such as semaphorin 3A (sema3A), is important in downregulating autoimmune diseases by suppressing the over-activity of both T and B cell autoimmunity. In addition, sema3A was shown to enhance the ability of T and B cell regulatory properties and by doing so to control autoimmune diseases, such as systemic lupus erythematosus. Other semaphorins, such as semaphorins 4D and 4A are important in stimulating T and B cells, thus keeping these immune responses on-going. However, when overexpressed, they can induce the induction of many immune-mediated diseases. The importance of all this is to develop targeting therapies that could possibly enhance or alternatively suppress these molecules. In this review, we will focus on several immune semaphorins - their role in immune homeostasis and in immune-mediated diseases. © 2013 Springer Science+Business Media.


Kessel A.,Bnai Zion Medical Center | Vadasz Z.,Bnai Zion Medical Center | Toubi E.,Bnai Zion Medical Center
Autoimmunity Reviews | Year: 2014

Non-syphilitic keratitis, coexisting with vestiboloauditory symptoms namely hearing loss and dizziness was first reported by Morgan and Baumgartner back in 1934. It was then ten years later when D.G. Cogan, an ophthalmologist (1908-1993) described 4 patients having the same symptoms but in addition, attacks of vertigo, tinnitus, hearing loss and ocular symptoms. This was published in Archives of Ophthalmology in 1945 and later named Cogan's syndrome (CS). Almost 20. years later on, bilateral recurrent episcleritis associated with vestiboloauditory symptoms were defined to be the atypical form of CS occurring in association with rheumatoid arthritis (RA). During the coming two decades the division of CS into typical (classical) and atypical variants, based mainly on the clinical presentation of this syndrome was accepted. Typical CS manifests primarily with interstitial keratitis and hearing loss, whereas atypical CS is usually presented with scleritis, chroiditis and more frequently with systemic inflammation. Approximately, 70% of these patients have systemic manifestations, of which vasculitis is considered the pathogenic mechanism and therefore carries a less favorable prognosis than typical CS. Since then, CS was considered by many to be autoimmune or immune mediated in origin, supported mainly by the beneficial response to corticosteroids. It was only later, using well developed assays such as western blotting and immunofluorescence (IF) when antibodies to inner ear antigens, anti neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial antibodies were found and described to be associated with CS. © 2014 Elsevier B.V.


Genizi J.,Bnai Zion Medical Center
The journal of headache and pain | Year: 2013

Primary headaches and Learning difficulties are both common in the pediatric population. The goal of our study was to assess the prevalence of learning disabilities and attention deficit disorder in children and adolescents with migraine and tension type headaches. Retrospective review of medical records of children and adolescents who presented with headache to the outpatient pediatric neurology clinics of Bnai-Zion Medical Center and Meyer Children's Hospital, Haifa, during the years 2009-2010. Demographics, Headache type, attention deficit disorder (ADHD), learning disabilities and academic achievements were assessed. 243 patients met the inclusion criteria and were assessed: 135 (55.6%) females and 108 (44.4%) males. 44% were diagnosed with migraine (35.8% of the males, 64.2% of the females, p = 0.04), 47.7% were diagnosed with tension type headache (50.4% of the males, 49.6% of the females). Among patients presenting with headache for the first time, 24% were formerly diagnosed with learning disabilities and 28% were diagnosed with attention deficit disorder (ADHD). ADHD was more prevalent among patients with tension type headache when compared with patients with migraine (36.5% vs. 19.8%, p = 0.006). Poor to average school academic performance was more prevalent among children with tension type headache, whereas good to excellent academic performance was more prevalent among those with migraine. Learning disabilities and ADHD are more common in children and adolescents who are referred for neurological assessment due to primary headaches than is described in the general pediatric population. There is an association between headache diagnosis and school achievements.

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