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עמוד בית
Thu, 18.07.24

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October 2012
A. Wasserman, J. Ben-Shoshan, M. Entin-Meer, S. Maysel-Auslender, H. Guzner-Gur and G. Keren

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

September 2012
E. Ballanti, G. Di Muzio, L. Novelli, C. Perricone and R. Perricone

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.
 

August 2012
S. Bezalel, I. Asher, D. Elbirt and Z.M. Sthoeger

Current treatments for systemic lupus erythematosus (SLE) are effective in reducing morbidity and mortality but are not specific and have severe adverse effects. Based on understanding of the different dysregulated immunological pathways involved in SLE pathogenesis, specific targeted therapies were developed. This review presents the current and the near-future novel biological immune targeted treatments, such as B cell-targeted therapy, cytokine blockade, peptide-based treatments and other novel treatments for SLE.
 

July 2012
E. Baharav and A. Weinberger
Background: The human lymphocyte antigen (HLA) molecule B*5101 is a functioning receptor of the immune system and is generally accepted as a genetic marker for Behçet disease (BD), a multi-organ, chronic inflammatory disorder. The role of the HLA-B*5101 in the pathogenesis of BD is elusive. The assumption that HLA-B*5101 has an active role in BD is suggestive, but no antigen has yet been identified.

Objectives: To evaluate the potential binding capacity of various antigens to the HLA-B*5101 molecule.

Methods: Using bioinformatics programs, we studied the binding capacity of HLA-B*5101 and its corresponding rat molecule RT.A1 to the following antigens: heat shock protein-60 (HSP-60), major histocompatibility complex class I chain-related gene A (MICA), retinal S-antigen (S-Ag), HLA-B-27 molecule and its peptide (PD) and tropomyosin (TPM), all of which serve as antigens in animal models corresponding to BD.

Results: In each protein including the B*5101 molecule itself, the computerized programs revealed several short sequences with potential high binding capacity to HLA-B*5101 with the exception of B-27PD. The rat MHC RT1.Al had no binding capacity to S-Ag.

Conclusions: The evaluated proteins have the potential to bind to and to serve as potential antigens to the HLA-B*5101 and the rat MHC RT1.Al molecules. The pathogenicity of these suggested short peptides should be evaluated in animal models of BD.
G. Twig, A. Furer, G. Yaniv, L. Michael, R. Karplus and H. Amital
June 2012
I. Shlomi Polachek, L. Huller Harari, M. Baum and R.D. Strous

Background: While many are familiar with postpartum depression, the phenomenon of postpartum post-traumatic stress disorder (PTSD) is less well known and investigated. Objectives: To assess the prevalence of postpartum PTSD in a cohort of women in Israel, and to examine factors affecting its development.

Methods: Eighty-nine women completed several ratings immediately after delivery and one month later. The factors examined related to the pregnancy, childbirth expectations, and delivery. Rating scales comprised evaluations of attachment, personality, PTSD, and demographic variables.

Results: The prevalence of post-partum PTSD was 3.4% (complete PTSD), 7.9% nearly complete PTSD, and 25.9% significant partial disorder. Women who developed PTSD symptoms had a higher prevalence of "traumatic" previous childbirth, with subsequent depression and anxiety. They also reported more medical complications and “mental crises” during pregnancy as well as anticipating more childbirth pain and fear. Instrumental or cesarean deliveries were not associated with PTSD. Most of the women who developed PTSD symptoms delivered vaginally but received fewer analgesics with stronger reported pain. Women with PTSD reported more discomfort with the undressed state, stronger feelings of danger, and higher rates of not wanting more children.

Conclusions: The study results indicate a) the importance of inquiring about previous pregnancy and birthing experiences, b) the need to identify at-risk populations, and c) increased awareness of the disorder. The importance of addressing anticipatory concerns of pain prior to delivery and of respecting the woman’s dignity and minimizing the undressed state during childbirth should not be underestimated. A short questionnaire following childbirth may enable rapid identification of symptoms relevant to PTSD.
 

L. Barski, L. Shalev, M. Zektser, H. Malada-Mazri, D. Abramov and Y. Rafaely

Background: Establishing the etiology of a large pericardial effusion is of crucial importance since it is likely the result of a serious underlying disease. However, there is a paucity of literature on the diagnostic management of patients with large hemorrhagic effusions.

Objectives: To analyze the management of patients with large hemorrhagic pericardial effusion.

Methods: We reviewed seven cases of large hemorrhagic pericardial effusions hospitalized in Soroka University Medical Center in 2010.

Results: All seven patients underwent a comprehensive evaluation followed by pericardiocentesis. Six of the seven cases demonstrated echocardiographic signs of tamponade. Large amounts of hemorrhagic pericardial effusion (> 600 ml) were aspirated from each patient. A pericardial window was performed in two of the seven patients. The causes for the hemorrhagic effusions were malignancy, streptococcal infection, familial Mediterranean fever exacerbation, and idiopathic. Four patients completely recovered. The condition of one patient improved after initiation of chemotherapy for lung cancer, and two patients with progressive malignancies passed away shortly after discharge. Two cases of massive pulmonary embolism were diagnosed which resolved spontaneously without anticoagulation therapy after the effusion was treated.

Conclusions: All cases of pericardial effusion resolved after rapid diagnosis and initiation of specific treatment. Pulmonary embolism in situ may be a complication of large pericardial effusions that does not require anticoagulation treatment after the effusion resolves.
 

May 2012
D. Amital, H. Amital, G. Shohat, Y. Soffer and Y. Bar-Dayan

Background: On 4 February 2008, two terrorists armed with suicide bombs arrived at the open market in the southern Israeli city of Dimona. One detonated his bomb at approximately 10:30 a.m. causing multiple casualties. Short-term emotional effects and acute stress reactions usually appear among survivors after such incidents.

Objectives: To compare the differences in emotions and in disturbances of daily life activities that emerge a couple of days following such an event and to identify patterns of stress development among resilient and low-resilient members of the population in Dimona and in the general population of Israel.

Methods: A telephone survey of two randomly selected representative samples of adults (428 Israeli residents and 250 Dimona residents) was conducted 2 days after the event.

Results: A higher prevalence of stress and fear and a lower prevalence of joy were reported among the population of Dimona compared to the general population in Israel (P < 0.05). Differences were also recorded when the population of Dimona was categorized by their personal degree of resilience (P < 0.05). A higher prevalence of disturbances in daily life activities and changes in leisure activity was found in the low-resilient population in Dimona (P < 0.01).

Conclusions: This study demonstrates that following a public terror event, self-reported low-resilient subjects have a higher prevalence of disturbances in daily life activities, as well as adverse emotional responses. These differences must be addressed by the relevant social service agencies for immediate public intervention

E. Moisseiev, D. Goldenberg, D. Gold, M. Neuderfer and Z. Habot-Wilner
L. Barski, R. Nevzorov, E. Rabaev, A.B. Jotkowitz, I. Harman-Boehm, M. Zektser, L. Zeller, E. Shleyfer and Y. Almog

Background: Diabetic ketoacidosis (DKA) is a common and serious complication of diabetes mellitus (DM).

Objectives: To evaluate the clinical characteristics, hospital management and outcomes of patients with DKA.

Methods: We performed a retrospective cohort study of patients hospitalized with DKA during the period 1 January 2003 to 1 January 2010. Three groups were compared: patients with mild DKA, with moderate DKA, and with severe DKA. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30 days all-cause mortality, length of hospital stay, and complication rate.

Results: The study population comprised 220 patients with DKA. In the mild (78 patients) and moderate (116 patients) groups there was a higher proportion of patients with type 1 DM (75.6%, 79.3%) compared with 57.7% in the severe group (26 patients, P = 0.08). HbA1C levels prior to admission were high in all three groups, without significant difference (10.9 ± 2.2, 10.7 ± 1.9, and 10.6 ± 2.4 respectively, P = 0.9). In all groups the most frequent precipitating factors were related to insulin therapy and infections. The patients with severe DKA had more electrolyte abnormalities (hypokalemia, hypomagnesemia, hypophosphatemia) compared with the mild and moderate forms of the disease. While 72.7% of the entire cohort was hospitalized in the general medical ward, 80.8% of those with severe DKA were admitted to the intensive care unit. The in-hospital mortality rate for the entire cohort was 4.1%, comparable with previous data from experienced centers. Advanced age, mechanical ventilation and bedridden state were independent predictors associated with 30 day mortality: hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02–1.11; HR 6.8, 95% CI 2.03–23.1; and HR 3.8, 95% CI 1.13–12.7, respectively.

Conclusions: Patients with DKA in our study were generally poorly controlled prior to their admission, as reflected by high HbA1c levels. Type 2 DM is frequently associated with DKA including the severe form of the disease. The most common precipitating factors for the development of DKA were related to insulin therapy and infections. Advanced age, mechanical ventilation and bedridden state were independent predictors of 30 day mortality.
 

April 2012
I. Ben-Zvi, I. Danilesko, G. Yahalom, O. Kukuy, R. Rahamimov, A. Livneh and S. Kivity

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation in some patients.

Objectives: To assess demographic, clinical and genetic risk factors for the development of FMF amyloidosis in a subset of kidney-transplanted patients and to evaluate the impact of transplantation on the FMF course.

Methods: Demographic, clinical and genetic data were abstracted from the files, interviews and examinations of 16 kidney-transplanted FMF amyloidosis patients and compared with the data of 18 FMF patients without amyloidosis.

Results: Age at disease onset and clinical severity of the FMF amyloidosis patients prior to transplantation were similar to FMF patients without amyloidosis. Compliance with colchicine treatment, however, was much lower (50% vs. 98 %). Post-transplantation, FMF amyloidosis patients experienced fewer of the typical serosal attacks than did their counterparts (mean 2214 days since last attack vs. 143 days). Patients with FMF amyloidosis carried only M694V mutations in the FMF gene, while FMF without amyloidosis featured other mutations as well.

Conclusions: Compliance with treatment and genetic makeup but not severity of FMF constitutes major risk factors for the development of amyloidosis in FMF. Transplantation seems to prevent FMF attacks. The protective role of immunosuppressive therapy cannot be excluded.

 

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