Kaplan Hospital

Rehovot, Israel

Kaplan Hospital

Rehovot, Israel
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Shapiro S.D.,RCA | Eros Y.,Kaplan Hospital | Abrahami Y.,Kaplan Hospital | Leviav A.,Kaplan Hospital
Lasers in Surgery and Medicine | Year: 2012

Introduction Patient demand for non-surgical, non-invasive, and no-downtime wrinkle reduction treatment procedures has grown dramatically over the past decade as new treatments and technologies have been introduced. This study was performed in order to evaluate the safety and efficacy of the TriPollar radiofrequency (RF) technology and intended for wrinkle reduction treatment. Methods Thirty-seven Subjects were recruited in two sites and were treated for the reduction of facial wrinkles and rhytides and followed for 3 months after the last treatment. The safety of using the TriPollar system was established by the physicians' assessments and observations of adverse events after each treatment. To evaluate treatment efficacy, pre- and post-treatment photos were assessed using a blinded evaluation by two uninvolved physicians. Results No unexpected adverse side effects were detected or reported. All subjects participating in the study reported no pain or mild pain during the treatments. The photographic analysis of pre- and post-treatment by the two blinded physicians revealed improvement (downgrade of at least 1 score according to the Fitzpatrick scale) in 94% (according to first reviewer) and 97% (according to second reviewer) of study subjects. All patients (100%) were satisfied from treatment results to a different extent. Conclusions The results of this study clearly indicate that the TriPollar system offers a non-invasive, effective, safe and virtually painless wrinkle and rhytides reduction treatment. Copyright © 2012 Wiley Periodicals, Inc.


Ginsberg G.M.,Ministry of Health | Eidelman A.I.,Shaare Zedek Medical Center | Shinwell E.,Kaplan Hospital | Anis E.,Hebrew University of Jerusalem | And 2 more authors.
Israel Journal of Health Policy Research | Year: 2013

Background: In Israel, an average of 37 children are born each year with sepsis and another four with meningitis as a result of Group B Streptococcal (GBS) disease. Israel currently only screens mothers with defined risk factors (around 15% of all pregnancies) in order to identify candidates for Intrapartum Antiobiotic Prophyhlaxis (IAP) of GBS. This paper presents a cost-utility analysis of implementing an alternative strategy, which would expand the current protocol to one aiming to screen all pregnant women at 35-37 weeks gestation based on taking a vaginal culture for GBS.Methods: A spreadsheet model was built incorporating technical, epidemiological, health service costs, demographic and economic data based primarily on Israeli sources.Results: The intervention of universal screening (compared with the current scenario) would increase screening costs from 580,000 NIS to 3,278,000 million NIS. In addition, the intervention would also increase penicillin costs from 39,000 NIS to 221,000 NIS. Current culture screening of approximately 15% of mothers-to-be with high risk factors resulted in 42 GBS births in 2008-9 (0.253/1000 births). Expanding culture screening to 85% of mothers-to-be, will decrease the number of GBS births to 17.3 (0.104/1000 births). The initial 2.9 million NIS incremental intervention costs are offset by decreased treatment costs of 1.9 million NIS and work productivity gains of 811,000 NIS as a result of a decrease in neurological sequelae from GBS caused meningitis. Thus the resultant net cost of the intervention is only around 134,000 NIS. Culture based screening will reduce the burden of disease by 12.6 discounted Quality Adjusted Life Years (QALYS), giving a very cost effective baseline incremental cost per QALY (cf. risk factor screening) of 10,641 NIS per QALY. The data was very sensitive to rates of anaphylactic shock and changes in the percentage of meningitis cases that had associated long term-sequelae.Conclusion: It is recommended that Israel adopt universal culture-based GBS screening. © 2013 Ginsberg et al; licensee BioMed Central Ltd.


PubMed | Bonus BioGroup Ltd., Kaplan Hospital and Technion - Israel Institute of Technology
Type: | Journal: Stem cell research & therapy | Year: 2016

Adipose-derived mesenchymal stem cells (MSCs) have been gaining fame mainly due to their vast clinical potential, simple isolation methods and minimal donor site morbidity. Adipose-derived MSCs and microvascular endothelial cells have been shown to bear angiogenic and vasculogenic capabilities. We hypothesized that co-culture of human adipose-derived MSCs with human adipose-derived microvascular endothelial cells (HAMECs) will serve as an effective cell pair to induce angiogenesis and vessel-like network formation in three-dimensional scaffolds in vitro.HAMECs or human umbilical vein endothelial cells (HUVECs) were co-cultured on scaffolds with either MSCs or human neonatal dermal fibroblasts. Cells were immunofluorescently stained within the scaffolds at different time points post-seeding. Various analyses were performed to determine vessel length, complexity and degree of maturity.The HAMEC:MSC combination yielded the most organized and complex vascular elements within scaffolds, and in the shortest period of time, when compared to the other tested cell combinations. These differences were manifested by higher network complexity, more tube alignment and higher -smooth muscle actin expression. Moreover, these generated microvessels further matured and developed during the 14-day incubation period within the three-dimensional microenvironment.These data demonstrate optimal vascular network formation upon co-culture of microvascular endothelial cells and adipose-derived MSCs in vitro and constitute a significant step in appreciation of the potential of microvascular endothelial cells and MSCs in different tissue engineering applications that can also be advantageous in in vivo studies.


Bretz N.P.,German Cancer Research Center | Salnikov A.V.,German Cancer Research Center | Perne C.,German Cancer Research Center | Keller S.,German Cancer Research Center | And 7 more authors.
Cellular and Molecular Life Sciences | Year: 2012

CD24 is a glycosyl-phosphatidylinositolanchored membrane protein that is frequently over-expressed in a variety of human carcinomas and is correlated with poor prognosis. In cancer cell lines, changes of CD24 expression can alter several cellular properties in vitro and tumor growth in vivo. However, little is known about how CD24 mediates these effects. Here we have analyzed the functional consequences of CD24 knock-down or over-expression in human cancer cell lines. Depletion of CD24 reduced cell proliferation and adhesion, enhanced apoptosis, and regulated the expression of various genes some of which were identified as STAT3 target genes. Loss of CD24 reduced STAT3 andFAK phosphorylation. Diminished STAT3 activity was confirmed by specific reporter assays. We found that reduced STAT3 activity after CD24 knock-down was accompanied by altered Src phosphorylation. Silencing of Src, similar to CD24, targeted the expression of prototype STAT3-regulated genes. Likewise, the over-expression of CD24 augmented Src-Y416 phosphorylation, the recruitment of Src into lipid rafts and the expression of STAT3-dependent target genes. An antibody to CD24 was effective in reducing tumor growth of A549 lung cancer and BxPC3 pancreatic cancer xenografts in mice. Antibody treatment affected the level of Src-phosphorylation in the tumor and altered the expression of STAT3 target genes. Our results provide evidence that CD24 regulates STAT3 andFAKactivity and suggest an important role of Src in this process. Finally, the targeting of CD24 by antibodies could represent a novel route for tumor therapy. © 2012 Springer Basel AG.


Shandalov Y.,Technion - Israel Institute of Technology | Egozi D.,Kaplan Hospital | Freiman A.,Technion - Israel Institute of Technology | Rosenfeld D.,Technion - Israel Institute of Technology | Levenberg S.,Technion - Israel Institute of Technology
Methods | Year: 2015

Abdominal wall reconstruction following extensive tissue loss is essential and can be achieved using autologous flaps. However, their use is limited due to their inadequate availability and due to post-operative donor site scarification. This work presents a step-by-step technique for fabrication of a vascularized muscle flap, to be applied in full-thickness abdominal wall defect reconstruction. Poly l-lactic acid/poly lactic-co-glycolic acid scaffolds, prepared using a salt leaching technique, were used as the supporting matrix in vitro for simultaneously seeded endothelial cells, fibroblasts and myoblasts. The cell-embedded graft was then implanted around femoral artery and vein vessels, which provided a central blood supply. Vascularization and perfusion were achieved by capillary sprouting from the main host vessel into the graft. A thick and vascularized tissue was formed within one week, and was then transferred as an autologous flap together with its main vessels, to a full-thickness abdominal wall defect. The flap remained viable after transfer and featured sufficient mechanical strength to support the abdominal viscera. Thus, this engineered muscle flap can be used as an alternative source for autologous flaps to reconstruct full-thickness abdominal wall defects. © 2015 Elsevier Inc.


Sarig R.,Weizmann Institute of Science | Fuchs O.,Weizmann Institute of Science | Tencer L.,Weizmann Institute of Science | Panski A.,Kaplan Hospital | And 2 more authors.
PLoS ONE | Year: 2010

Background: The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population. Methodology/Principal Findings: We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content. Conclusions: These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases. © 2010 Sarig et al.


PubMed | Kaplan Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

3153 Background:The A3 adenosine Gi protein-coupled receptor is highly expressed in malignant compared to normal cells. Activating the A3 adenosine receptor (A3AR) with the highly selective non-cytotoxic agonist, CF101 (methyl 1-[N6-(3-iodobenzyl)-adenin-9-yl]--D-ibofuronamide, IB-MECA), induces growth inhibition of colon carcinoma and other tumor cell types via down-regulation of the Wnt and NF-B related pathways. Oral CF101 has been shown to inhibit human colon and prostate cancer growth in nude mice. A Phase I study in healthy volunteers showed that CF101 at doses up to 4 mg PO BID, produced no drug-related toxicity with linear pharmacokinetics and good bioavailability.A phase II dose finding, randomized, blinded study of oral CF101 (0.1, 1 & 4 mg PO BID) was conducted to define activity and safety in a heavily pre-treated metastatic colorectal cancer pts. From 6/1/2003-12/1/2003, 61 pts (25 F, 36 M), median age 61 (range 30-83) with measurable colorectal cancer, PS 2 were enrolled. 14 pts progressed after irinotecan and 47 pts after both irinotecan and oxaliplatin-based regimens. The study is still ongoing.By 12/1/2003, 46 pts completed at least 8 weeks (W) of treatment or were withdrawn due to disease progression. The median time on treatment was 8.7W (1-19.7+). PR/CR was not observed; however, SD for at least 8W duration was achieved in 16 pts (35%). Three pts are still on treatment without disease progression after 16W. Four pts died within 8W of treatment (2, 3, 4 & 1W). Two of these pts were found to be ineligible, were removed from study and died of PD. One patient deteriorated due to PD while on study and was withdrawn from treatment prior to death. The forth, died suddenly while on study. In the other pts, there were no obvious treatment related serious adverse events.The interim blinded results from this ongoing study, shows that CF101 appears to be well tolerated and may stabilize disease for at least 2 months in 35% of the pts. The data justifies a continued investigation of CF101 in the treatment of refractory metastatic colorectal cancer. [Table: see text].


PubMed | Weizmann Institute of Science, Asaf Harofeh Hospital and Kaplan Hospital
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The ciliary epithelium in the eye consists of pigmented epithelial cells that express the 11 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the 23 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for 23 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human 21 over 11 (up to 7.5-fold). When applied topically, the most 2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the 1 subunit, Gln84, suggesting a role for in digoxin binding. Gln84 in 1 is replaced by Val88 in 3. Assuming that alkyl substituents might interact with 3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for 23 over 11 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that 23-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy.


PubMed | Kaplan Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

13082 Background: The AA phase II dose-finding, randomized, blinded study of oral CF101 (0.1, 1& 4 mg PO BID), was conducted to define activity and safety in heavily pre-treated metastatic colorectal cancer pts. From 6/1/2003-7/4/2004, 70 pts, median age 62 with measurable colorectal cancer, PS 2 were enrolled, 21 pts progressed after irinotecan and 49 pts after both irinotecan and oxaliplatin-based regimens.The median time on treatment was 10.3 weeks. No objective response was observed; however, SD for 8 wks duration was achieved in 24 pts (34%), for 16 weeks in 8 pts (11%) and 2 pts were treated for more than 24 weeks. The median time to treatment progression was 72 days and for overall survival was 254 days without any significant difference among the 3 trial doses [8 survivors till today]. There were no obvious treatment related serious adverse events.The final results of the study show that CF101 is well tolerated and may stabilize disease for at least 2 months in 35% of the pts. The median survival time (8 months) compared with other targeted therapy investigated lately is encouraging. Combining CF101 with chemotherapy may be beneficial in the treatment of metastatic colorectal cancer. No significant financial relationships to disclose.


PubMed | Kaplan Hospital and Technion - Israel Institute of Technology
Type: | Journal: Methods (San Diego, Calif.) | Year: 2015

Abdominal wall reconstruction following extensive tissue loss is essential and can be achieved using autologous flaps. However, their use is limited due to their inadequate availability and due to post-operative donor site scarification. This work presents a step-by-step technique for fabrication of a vascularized muscle flap, to be applied in full-thickness abdominal wall defect reconstruction. Poly L-lactic acid/poly lactic-co-glycolic acid scaffolds, prepared using a salt leaching technique, were used as the supporting matrix in vitro for simultaneously seeded endothelial cells, fibroblasts and myoblasts. The cell-embedded graft was then implanted around femoral artery and vein vessels, which provided a central blood supply. Vascularization and perfusion were achieved by capillary sprouting from the main host vessel into the graft. A thick and vascularized tissue was formed within one week, and was then transferred as an autologous flap together with its main vessels, to a full-thickness abdominal wall defect. The flap remained viable after transfer and featured sufficient mechanical strength to support the abdominal viscera. Thus, this engineered muscle flap can be used as an alternative source for autologous flaps to reconstruct full-thickness abdominal wall defects.

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