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עמוד בית
Fri, 05.12.25

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April 2007
Y. Shapira, D. E. Weisenberg, M. Vaturi, E. Sharoni, E. Raanani, G. Sahar, B. A. Vidne, A. Battler and A. Sagie

Backgound: The use of intraoperative transesophageal echocardiogram in patients with infective endocarditis is usually reserved for cases of inadequate preoperative testing or suspected extension to perivalvular tissue.

Objectives: To explore the impact of routine intraoperative TEE[1] in patients with infective endocarditis.

Methods: The impact of intraoperative TEE on the operative plan, anatomic-physiologic results, and hemodynamic assessment or de-airing was analyzed in 59 patients (38 males, 21 females, mean age 57.7 ± 16.8 years, range 20–82) operated for active infective endocarditis over 56 months.

Results: Immediate pre-pump echocardiography was available in 52 operations (86.7%), and changed the operative plan in 6 of them (11.5%). Immediate post-pump study was available in 59 patients (98.3%) and accounted for second pump-run in 6 (10.2%): perivalvular leak (3 cases), and immobilized leaflet, significant mitral regurgitation following vegetectomy, and failing right ventricle requiring addition of vein graft (1 case each). Prolonged de-airing was necessary in 6 patients (10.2%). In 5 patients (8.5%) the postoperative study aided in the evaluation and treatment of difficult weaning from the cardiopulmonary bypass pump. In 21 patients (35.6%) the application of intraoperative TEE affected at least one of the four pre-specified parameters.
Conclusions: Intraoperative TEE has an important role in surgery for infective endocarditis and should be routinely implemented







[1] TEE = transesophageal echocardiogram


February 2007
Y. Har Shai, I. Metanes, S. Badarny, P. Cuzin, T. Gil, S. Mayblum, B. Aman, D. Labbé
April 2006
Y. Mosesson and Y. Yarden

Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.

 

 
 

March 2006
H. Schayek, M. Krupsky, P. Yaron, A. Yellin, D.A. Simansky and E. Friedman

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.






[1] NSCLC = non-small cell lung cancer

[2] DNA-MMR = DNA mismatch repair

[3] MSI = microsatellite instability

[4] LOH = loss of heterozygosity


August 2005
Y. Niv
 Colorectal cancers develop as a consequence of genomic instability. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and in most hereditary non-polyposis cancers. High frequency MSI[1] has been associated with a favorable prognosis, however it is not clear whether this is because MSI-H[2] tumors are inherently less aggressive or because they are more sensitive to chemotherapy. Chemotherapy with a combination of 5-fluorouracil and leukovorin or levamizole has been the standard of care for high risk stage II and stage III CRC[3]; it is also used in stage IV CRC. Several in vitro studies have shown that colon cancer cell lines displaying MSI-H are less responsive to fluorouracil than microsatellite-stable cell lines. Human studies, all of them retrospective, yielded conflicting results. The selection of patients with CRC for 5-FU[4] treatment has been based so far on the stage of tumor rather than the biology of the tumor. Although surgical staging is highly predictive of survival, there are indications that the form of genomic instability within a patient’s colorectal tumor has clinical implications, with and without 5-FU treatment. This review suggests that patients with MSI-H colorectal tumors may not benefit from 5-FU-based chemotherapy and can avoid its potential side effects (nausea, diarrhea, stomatitis, dermatitis, alopecia, and neurologic symptoms) that occur in half the treated patients. If confirmed by future prospective randomized controlled studies, these findings would indicate that microsatellite-instability testing should be conducted routinely and the results used to direct rational adjuvant chemotherapy in colon cancer.


 


[1] MSI = microsatellite instability

[2] MSI-H - high frequency MSI

[3] CRC = colorectal cancer

[4] 5-FU = 5-fluorouracil


July 2005
G.P. Georghiou, Y. Shapira, A. Tobar, B.A. Vidne and G. Sahar
January 2005
Y.S. Brin, H. Reuveni, S. Greenberg Dotan, A. Tal and A. Tarasiuk

Background: Continuous positive airway pressure is the treatment of choice for patients with obstructive sleep apnea syndrome.

Objective: To determine the factors influencing treatment initiation with a CPAP[1] device in a healthcare system in which co-payment is required.

Methods: A total of 400 adult patients with OSAS[2] who required CPAP therapy completed questionnaires at three different stages of the diagnostic and therapeutic process: CPAP titration study (stage 1), patient adaptation trial (stage 2), and purchase of a CPAP device (stage 3). Logistic regression was used to analyze the variables influencing CPAP use at the different stages of the diagnostic and therapeutic processes.

Results: Only 32% of the patients who underwent CPAP titration study purchased a CPAP device. The number of subjects who purchased a CPAP device increased gradually as monthly income increased, 28% vs. 62% in the “very low” and “very high” income levels respectively. Reporting for the titration increased in patients with excessive daytime sleepiness and an Epworth Sleepiness Scale score above 9 (odds ratio = 1.9, P = 0.015). Higher socioeconomic status increased reporting to stage 2 (OR[3] = 1.23, P = 0.03) and CPAP purchase (stage 3, OR = 1.35, P = 0.002). Excessive daytime sleepiness increased reporting to stage 2 (OR = 2.28, P = 0.006). Respiratory disturbance index above 35 increased CPAP purchasing (OR = 2.01, P = 0.022). Support from the bed partner, referring physician and sleep laboratory team increased CPAP purchasing.

Conclusions: A supportive environment for a patient with OSAS requiring CPAP is crucial to increase initiation of CPAP treatment. Minimizing cost sharing for the CPAP device will reduce inequality and may increase CPAP treatment initiation.






[1] CPAP = continuous positive airway pressure

[2] OSAS = obstructive sleep apnea syndrome

[3] OR = odds ratio


October 2004
I. Lejbkowicz, Y. Denekamp, S. Reis and D. Goldenberg

Background: Various medical centers in Israel have recently incorporated electronic medical record systems. Knowing the EMR[1] systems’ features and pattern of use is an essential step for developing locally and nationally integrated systems.

Objectives: To evaluate the status of EMR systems in all major general hospitals in Israel in terms of the applications used and the patterns of use.

Methods: Structured questionnaires were sent to hospital directors and directors of medical informatics units of 26 general and pediatric hospitals serving the vast majority of the population in Israel. The qheuestionnaire included questions pertaining to the EMR systems, their usage and the attitude of the participants to data security issues.

Results: Of the 26 general hospitals 23 (88.4%) returned the questionnaires. Of these, 21 (91.3%) use EMR systems. Twenty-seven different types of systems are in use in Israeli hospitals, and generally more than one type is used in a hospital. [YD1] Physicians work with EMR systems in over 98% of the departments. Also, the EMR systems are used for clinical admission and discharge in over 90% of the departments and for medical daily follow-up in about 45%.

Conclusions: Most of the hospitals in Israel use EMR systems but there is no standard data model. Physicians are the main users but the amount of data entered is still limited. Adoption of standards is essential for integration of electronic patient records across Israeli healthcare organizations.






[1] EMR = electronic medical record

[YD1] The reader does’t know at this stage the security concerns abroad


January 2004
H. Elinav, E. Israeli, O. Shibolet, A. Hershko, C. Sela, A. Migdal and Y. Ilan
August 2003
June 2003
Winkler and D. Tzivoni

Background: Prior studies have suggested that women are at higher risk for morbidity and mortality during coronary angioplasty, although long-term prognosis is similar after successful procedures.

Objectives: To examine the role of gender in coronary stenting, including immediate procedural success as well as early and late outcomes.

Methods: The study group comprised 560 consecutive patients (119 women and 441 men) who had undergone stenting over a 3 year period.

Results: The indications for coronary stenting were similar among women and men, and stents were successfully deployed at similar rates without complications (92 vs. 90% respectively). Cardiac death or myocardial infarction within 30 days of the procedure was observed in 5% of women and men, whereas none of the women, compared to 1.4% of men, had early revascularization. Bleeding complications occurred in 4% of women and 2% of men. During 10 ± 2.8 months of follow-up, 58% of women and men underwent repeat cardiac catheterization, revealing similar rates of restenosis, 36 vs. 32% respectively. During the study period, 3.3% of women as compared to 0.9% of men had a cardiac death (not significant). Cardiac death or myocardial infarction was observed in 7% of women and 8% of men, and the combined endpoint of death, myocardial infarction or revascularization, was noted in 24% and 26% respectively. Multivariate Cox analyses of the clinical, angiographic and procedural characteristics revealed that multiple stent deployment was the only predictor of major adverse cardiac event among men, whereas none of these characteristics predicted outcome in women.

Conclusion: Coronary stenting is performed with similar success rates among women and men, with similar restenosis rates, as well as early and late major adverse cardiac events.
 

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