Kfar Saba, Israel
Kfar Saba, Israel

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Schwartz N.,Meir Hospital | Chaudhri R.A.,Georgia Institute of Technology | Chaudhri R.A.,Clinical Translational Science Institute | Hadadi A.,Georgia Institute of Technology | And 5 more authors.
Hormones and Cancer | Year: 2014

17β-estradiol (E2) plays a key role in tumorigenesis by enhancing cell survivability and metastasis through its cytoplasmic receptors. Recently, a variant of estrogen receptor alpha, ERα36 has been implicated as a substantial mediator of E2's proliferative and antiapoptotic effects through rapid membrane-associated signaling, and cancers previously regarded as hormone-independent due to the absence of traditional receptors, may in fact be susceptible to E2. Despite rising from a secondary sex organ and having a clear gender disposition, laryngeal cancer is not uniformly accepted as hormone dependent, even in the face of compelling evidence of E2 responsiveness. The aim of this study was to further elucidate the role of E2 in the tumorigenesis of laryngeal cancer, both in vitro and in vivo. ERα36 presence was evaluated in membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal tumor samples. In vitro ERα36 was found to mediate rapid activation of protein kinase C and phospholipase D by E2, leading to increased proliferation and protection against chemotherapy-induced apoptosis. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors was observed. Clinical analysis of laryngeal tumors revealed a similar association between the amount of ERα36 and VEGF and indicated a role in lymph node metastasis. These findings present compelling evidence of ERα36-dependent E2 signaling in laryngeal cancer. Thus, targeting ERα36 may reduce the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the importance of antiestrogen therapy or the production of novel drugs that specifically target ERα36. © 2013 Springer Science+Business Media New York.


Nemet A.Y.,Meir Hospital | Vinker S.,Clalit Health Services | Vinker S.,Tel Aviv University | Bahar I.,Rabin Medical Center | And 2 more authors.
Cornea | Year: 2010

Purpose: To evaluate the association between keratoconus (KC) and immune disorders (IDs). Methods: A retrospective observational case-control study of all the members in the Central District of Clalit Health Services in Israel who were diagnosed to have KC (years 2000-2007; n = 426) and 1704 age-and gender-matched controls. We calculated the prevalence of the following IDs: rheumatoid arthritis, ulcerative colitis, arthropathy, amyloidosis, systemic lupus erythematosus, celiac disease, multiple sclerosis, myasthenia gravis, polymyalgia rheumatica, idiopathic thrombocytopenic purpura, Crohn disease, Hashimoto thyroiditis, autoimmune hepatitis, irritable bowel syndrome, asthma, and environmental allergy. The odds ratio (OR) of having IDs among patients with KC was compared with controls. Results: The association between KC and the following IDs was statistically significant: rheumatoid arthritis [OR = 8.1; 95% (confidence interval) CI: 1.5-44.2], ulcerative colitis (OR = 12.1; CI: 1.3-116), autoimmune chronic active hepatitis (OR = 6; CI: 1.01-36), Hashimoto thyroiditis (OR = 2.0; CI: 1.2-3.3), arthropathy (OR = 1.4; CI: 1.1-1.8), asthma (OR = 2.1; CI: 1.4-3.2), environmental allergy (OR = 1.3; CI: 1.02-1.75), and irritable bowel syndrome (OR = 5; CI: 2.1-12.1). Two autoimmune diseases, multiple sclerosis (OR = 2; CI: 0.2-22) and Crohn disease (OR = 1.6; CI: 0.3-8.3), were more prevalent among patients with KC but did not reach statistical significance. Conclusion: Some strong associations between KC and several immune conditions of autoimmune diseases and allergic IDs may point to the role of the immune system in the pathogenesis of KC. Copyright © 2010 by Lippincott Williams & Wilkins.


Voichanski S.,Hypertension Unit | Grossman C.,Meir Hospital | Leibowitz A.,Hypertension Unit | Peleg E.,Hypertension Unit | And 4 more authors.
American Journal of Hypertension | Year: 2012

Background The circadian pattern of blood pressure (BP) has yet to be defined among individuals with orthostatic hypotension (OH). The objective of this study was to evaluate whether OH is associated with nocturnal change in systolic BP. Methods In a prospective study, we evaluated patients who were referred for 24-h ambulatory blood pressure monitoring (ABPM). All subjects underwent orthostatic BP testing before recording their respective 24-h ABPM. Results The study includes 185 subjects, 114 males, mean age 58 ± 18 years (range 19-89). Participants were classified, based on pattern of systolic BP changes at night, as dippers (greater than 10% decrease; n = 74), nondippers (0-10% decrease; n = 77), and reverse-dippers (increase; n = 34). Nineteen patients (10.3%) had OH. Almost all participants with OH (95%) had an abnormal diurnal BP pattern, and most of them (58%) were reverse-dippers, whereas only 56% of the participants without OH had an abnormal diurnal BP variation, and only 14% were reverse-dippers (P< 0.001). Systolic BP decreased with upright posture by 12 and 2mmHg in the reverse-dippers and the nondippers, respectively, and increased by 2mmHg in the dippers (P< 0.001). Postural changes in systolic BP were inversely related to the changes between day and night BP readings(r =-0.43; P< 0.01). In a multivariate linear regression analysis, orthostatic BP change, use of ≥2 antihypertensive drugs and female sex were related to nocturnal BP changes. Conclusions The decrease in BP during upright posture may be a marker of nondipping or reverse-dipping pattern of diurnal BP. © 2012 American Journal of Hypertension, Ltd.


Schwartz N.,Meir Hospital | Hazkani I.,Meir Hospital | Goshen S.,Meir Hospital
American Journal of Otolaryngology - Head and Neck Medicine and Surgery | Year: 2015

Purpose Sialolithiasis is the primary cause of obstructive sialadenitis, affecting the submandibular gland in 80-90% of cases. Sialendoscopy has dramatically changed the diagnosis and management of salivary gland diseases. However, in cases in which endoluminal removal via sialendoscopy is not successful, a combined approach using a limited intraoral incision under guidance of sialendoscopy can facilitate stone removal. We reviewed our institution's experience with combined approach sialendoscopy and evaluated its role in managing sialolithiasis of the submandibular gland. Materials and methods Retrospective study of the treatment of sialolithiasis in the submandibular gland via combined approach sialendoscopy from January 2010 through March 2014. Demographics, clinical data, intraoperative findings and post-operative course were reviewed. Results Most sialoliths (56.5%) were over 10 mm in size and were in the hilus of the gland (56%). The success rate of the combined approach was 87%. No significant complications were documented. Symptoms resolved in 75.7% of patients; however, this did not correlate with placement of an intraductal stent (p=0.7) or steroid irrigation (p=0.1). An overall gland preservation rate of 94.9% was achieved. Conclusions Combined approach sialendoscopy offers a minimally invasive technique for treating refractory sialolithiasis not amenable to removal via sialendoscopy alone. The procedure is well-tolerated, performed under local anesthesia with low morbidity and a high success rate. © 2015 Elsevier Inc.


Solomon E.,Weizmann Institute of Science | Nissan N.,Weizmann Institute of Science | Furman-Haran E.,Weizmann Institute of Science | Seginer A.,Weizmann Institute of Science | And 3 more authors.
Magnetic Resonance in Medicine | Year: 2015

Purpose Evaluating the usefulness of diffusion-weighted spatio-temporal encoding (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)-based characterizations of healthy and malignant human breast tissues, in comparison with results obtained using techniques based on spin-echo echo planar imaging (SE-EPI). Methods Twelve healthy volunteers and six breast cancer patients were scanned at 3T using scanner-supplied diffusion-weighted imaging EPI sequences, as well as two fully refocused SPEN variants programmed in-house. Suitable codes were written to process the data, including calculations of the actual b-values and retrieval of the ADC maps. Results Systematically better images were afforded by the SPEN scans, with negligible geometrical distortions and markedly weaker ghosting artifacts arising from either fat tissues or from strongly emitting areas such as cysts. SPEN-derived images provided improved characterizations of the fibroglandular tissues and of the lesions' contours. When translated into the calculation of the ADC maps, there were no significant differences between the mean ADCs derived from SPEN and SE-EPI: if reliable images were available, both techniques showed that ADCs decreased by nearly two-fold in the malignant lesion areas. Conclusion SPEN-based sequences yielded diffusion-weighted breast images with minimal artifacts and distortions, enabling the calculation of improved ADC maps and the identification of decreased ADCs in malignant regions. Magn Reson Med 73:2163-2173, 2015. © 2014 Wiley Periodicals, Inc.


Kidron D.,Meir Hospital
Harefuah | Year: 2013

Fetal autopsies are effective in identifying the cause and/or mechanisms leading to death in cases of intrauterine fetal death. Autopsies for fetal anomalies are different. To summarize our experience with 569 autopsies of fetal anomalies which were performed during an 18-year period. Methods: A retrospective analysis of 569 autopsies of fetal anomalies was conducted, out of a total of 1067 fetal autopsies. The pregnancy weeks were 14 - 41. Among 569 cases, 88% were termination of pregnancies, 10% intrauterine death and 2% perinatal deaths. The diagnosis of a syndrome or disease process was made when a constellation of gross and/or histologic findings was met. Specific diagnoses were offered in cases of cystic diseases of kidneys, types of dwarfism, tumors and fetal hydrops. Teratogenic (acquired) processes, such as congenital infections, thrombosis and cerebral hemorrhages, were differentiated from malformations. In cases of multiple congenital anomalies, documentation of the entire spectrum of malformations facilitated the genetic counseling. First and foremost, the autopsy is performed in the interest of the parents, with their written consent and in accordance with limitations and requests which they pose. Autopsy results provide feedback to the prenatal imaging. They assist in focusing the genetic counseling. Autopsy reports provide tools of control for the health authorities. Autopsies for fetal anomalies are time consuming. They require skill and experience. They are helpfuL when the prenatal diagnosis raises differential diagnosis. They are Less helpful when the diagnosis is clear, i.e. chromosomal trisomy.


Leader A.,Meir Hospital | Pereg D.,Meir Medical Center | Lishner M.,Meir Hospital
Annals of Medicine | Year: 2012

Platelet size correlates with platelet activity and can be assessed by platelet volume indices (PVI). The PVI, mean platelet volume (MPV), is universally available with routine blood counts by automated hemograms and therefore is an attractive index to study in clinical scenarios. PVI are useful in assessing the etiology of thrombocytopenia. In addition, a normal platelet distribution width in the setting of thrombocytosis is highly suggestive of a reactive etiology. Higher MPV is also associated with the presence of cardiovascular risk factors, chest pain due to acute coronary syndrome, and adverse outcome after acute coronary syndrome. Results from studies evaluating MPV in patients with peripheral artery disease, unprovoked deep vein thrombosis, and pulmonary embolism further advocate a potential role for MPV in identifying patients at high risk of thrombosis. Nevertheless, most of these data come from retrospective studies some of which have small study populations and confounding factors influencing platelet volume. Moreover, the cut-off values derived from these retrospective studies have not been validated prospectively. Despite the potential for clinical utility evident from these studies, the above-mentioned flaws together with technical problems in measuring MPV currently limit its clinical usefulness. Our review provides a perspective on PVI's potential clinical use. © 2012 Informa UK, Ltd.


Netzer D.,Meir Hospital
Harefuah | Year: 2010

During the last decade, the production of medical information has doubled every 14 months. It is predicted that information will double at an even faster rate. This dramatic rate of changing medical knowledge presents a challenge for physicians to keep up to date. Physicians are usually eager for the latest medical information. The late British epidemiologist, Archie Cochrane, developed a relatively new approach using up-to-date medical information. His approach integrates individual clinical expertise with the best available external clinical evidence from systematic research. Through this method new information is located, identified and its significance evaluated. If the new information has been proven to be reliable and relevant, it is integrated into existing information systems to be used by physicians all over the world. This approach is called evidence-based medicine. This review will summarize the four leading clinical databases which are evidence based medicine oriented: Dynamed, Cochrane Library, Trip database and Attract, and short presentation of the best evidence based medicine "secondary literature".


Stauber T.,Meir Hospital | Confino-Cohen R.,Meir Hospital | Confino-Cohen R.,Tel Aviv University | Goldberg A.,Meir Hospital | Goldberg A.,Tel Aviv University
American Journal of Rhinology and Allergy | Year: 2014

Background: Angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs) is a well-known phenomenon and roughly accounts for one-third of angioedema cases presenting to the emergency departments. This study aimed to characterize the patients with severe reactions that required hospitalization and tried to identify the risk factors for these life-threatening events. Methods: The records of all patients hospitalized with the diagnosis of "angioedema" over a 10-year period were retrospectively analyzed. Patients' characteristics as well as the characteristics of the angioedema-induced hospitalizations were studied. Results: In 46 of 165 patients (28%) the angioedema was ACEI induced. The severity of the event was mild in 12 patients (26%), moderate in 25 patients (54%), and severe in 9 patients (19%). Twelve patients (26%) were admitted to the intensive care unit and six patients (13%) underwent intubation. Epinephrine was administered to 13 patients (29%), steroids were administered to 40 patients (87%), and anti-histamines were administered to 36 patients (78%). One patient died as a consequence of the event (2%). Twenty patients (45%), including the deceased patient, had recurrent events of angioedema before admission. Obese patients had significantly more recurrent events compared with nonobese patients (p = 0.03). There was also a tendency for more severe events in the obese patients (p = 0.079). Diabetes was significantly associated with moderate-to-severe events (p = 0.009) whereas treatment with beta-blockers or diuretics was significantly associated with milder events (p = 0.007 and p = 0.044, respectively). Conclusion: The high recurrence rate of ACEI-induced angioedema preceding subsequent life-threatening events suggests underdiagnosis of this potentially fatal adverse reaction. Diabetes and probably obesity are risk factors for more severe events. Physicians following patients receiving ACEI should be more aware of possible shortcomings associated with these medications. Copyright © 2014, OceanSide Publications, Inc.


Fractures of proximal femur are common among elderly people. They are associated with considerable morbidity and mortality. Identification of etiopathogenetic factors associated with fractures might facilitate prevention. Osteoporosis is commonly present in the heads of femurs. The prevalence of osteoarthritic changes in hip joints is controversial. Some authorities report low prevalence and even speculate on the protective effect of osteoarthritis against fractures. The goal of the study was to examine the association between osteoarthritic changes (radiologic and histologic) and fractures of the neck of the femur. The patient population included 41 patients undergoing replacement of femoral head for subcapital fracture; their ages ranged from 61 - 93 years of age. Radiologic criteria for osteoarthritis included: (a)narrowing of joint space (b) subchondral sclerosis (c) deformation of head of femur (d) subchondra cysts and (e] osteophytes. Osteoarthritic changes, usually mild, were present in 22 (54%) patients, regardless of age and gender The frequency of radioLogical changes was similar to the general population. HistoLogic findings included subchondral fibrosis and subchondral cysts. Mild subchondral fibrosis was present in 78% of cases. The findings support lack of association between osteoarthritic changes in hip joint and fracture of proximal femur, without a protective effect.

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