Prolonged asystole following adenosine. Was it necessary?

A77-year-old woman presented with interchangeable episodes of both fast and slow heart rate.Past history was notable for paroxysmal atrial fibrillation treated with eliquis and tambocor and atrial septal defect closure 35 years ago.Except for mild tachycardia,vitals and physical examination were unremarkable.The 12-lead electrocardiogram(Figure 1)showed narrow complex tachycardia at 106 beats/min without obvious P-waves.

The role of multimodality imaging in calcified valves with infective endocarditis

A 68-years old woman presented with ahistory of recurrent fever of 38-39°ac-companied by chills and weakness over the past month.Her physical examination was unremarkable except for an audible 3/6 ejection murmur at the 2nd right intercostal space.Her vital signs were normal with no fever at presentation.Laboratory tests showed elevated white blood count of 11,800cells/mm3 with a remarkable neutrophilia and elevated C-reactive protein of 14 mg/dL.Blood glucose,renal and liver function tests were all normal.

Masquerading bundle branch block with intermittent right ventricular pacing in a patient with acute coronary syndrome

The relatively uncommon masquerading bundle branch block(MBBB),a concept initially introduced in 1958 by UNGER,et al.[1]and colleagues,refers to a conduction abnormality that consists of the right bundle branch block(RBBB)pattern in the precordial leads,whereas in the limb leads it resembles a left bundle branch block(LBBB).

Advanced paternal age and reproductive outcome

Women have been increasingly delaying the start of motherhood in recent decades. The same trend is seen also for men. The influence of maternal age on fertility, chromosomal anomalies, pregnancy complications, and impaired perinatal and post-natal outcome of offspring, has been thoroughly investigated, and these aspectsare clinically applied during fertility and pregestational counseling. Male aging and reproductive outcome has gained relatively less attention. The purpose of this review is to evaluate updated and relevant literature on the effect of paternal age on reproductive outcome.

Role of antibiotics for treatment of inflammatory boweldisease

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.

Long-term follow-up of distal intestinal obstruction syndrome in cystic fibrosis

AIM: To investigate the long-term follow-up of distal intestinal obstruction syndrome(DIOS) in Israeli cystic fibrosis(CF) patients.METHODS: This is a multi-center,comparative,retrospective study in which we reviewed the medical records of all CF patients from three major CF centers in Israel who were treated in the period from 1980 to 2012.Patients diagnosed with DIOS were defined as the study group.The patients were diagnosed with DIOS based on their clinical presentation and typical findings on either abdominal X-ray or computerized tomography scan.For the control group,CF patients with no DIOS were matched to the patients in the study group for age,sex,and cystic fibrosis transmembrane conductance regulator(CFTR) mutations.For both groups,the collected data included age,sex,CFTR genotype,weight,height,and body mass index.Clinical data included respiratory function tests in the last five years prior to the study,respiratory function test immediately before and after the DIOS event,number of hospitalizations,sputum culture results,and CFrelated conditions diagnosed according to the CF clinical practice guidelines.In the study group,data on the DIOS treatment and tendency for DIOS recurrence were also analyzed.RESULTS: The medical charts for a total of 350 CF patients were reviewed.Of the 350 CF patients,26(7.4%) were diagnosed with DIOS.The control group included 31 CF patients with no DIOS diagnosis.The mean follow-up period was 21.6 ± 8.2 years.The total of DIOS episodes in the follow-up period was 60.The distribution of DIOS episodes was as follows: 6/26(23.1%) study patients had one episode of DIOS intheir lifetime,7/26(26.9%) had two episodes,7/26(26.9%) had three episodes,and 6/26(23.1%) had four or more episodes.Compared to the control group,DIOS patients had a significantly higher incidence of meconium ileus in the past(65.4% vs 0%,respectively,P < 0.02),more Aspergillus spp.colonization(34.6% vs 3.2%,respectively,P < 0.02),and a higher number of hospitalizations due to respiratory exacerbations(8.6 vs 6.2 mean total hospitalizations per follow-up period,respectively,P < 0.02).No other significant differences were found between the control and study groups.The conservative treatment of DIOS,which mainly includes hydration and stool softeners,was successful in 82% of the episodes.The survival rate was similar for both groups.CONCLUSION: CF patients with DIOS suffer from recurrent hospitalizations and airway pathogen acquisition.Although recurrence of DIOS is common,conservative treatment is successful in most patients.

Coronary angiography in the very old: impact of diabetes on long-term revascularization and mortality

Background Diabetes is often associated with coronary artery disease,leading to adverse clinical outcomes.Real-world data is limited regarding the impact of diabetes in very old patients undergoing coronary angiography on the risk for late or repeated coronary revascularization and mortality.Methods Retrospective analysis of 1,353 consecutive patients>80 years who were admitted to the cardiac unit and further underwent coronary angiography.Subsequent revascularization procedures and all-cause mortality were recorded over a median fbllow-up of 47 months and their relation to diabetic status and presentation with acute coronary syndrome(ACS)was studied.Results Diabetes was present in 31%of the patients undergoing coronary angiography,and was associated with higher rates of obesity,hypertension,hyperlipidemia,chronic kidney disease and female gender.ACS was the presenting diagnosis in 71%of the patients and was associated with worse survival(1-year mortality 20%in ACS vs.6.2%in non-ACS patients,P<0.0001).Increase in long-term mortality rates was seen in diabetic subjects compared to non-diabetic subjects presenting with ACS(log-rank P=0.005),but not in the non-ACS setting(P=0」99).In a multivariable model,additionally adjusting for acuity of presentation,the presence of diabetes was associated with an adjusted hazard ratio of 1.60(95%confidence interval:12-2.28),P=0.011,for the need of late or repeat coronary revascularization and 1.48(1.26-1.74),P<0.0001 for all-cause mortality,during long-term follow-up.Conclusions In very old patients undergoing coronary angiography,presentation with ACS was associated with worse survival.Diabetes was an independent predictor of late or repeated revascularization and long-term mortality.

Benign ovarian cysts in reproductive-age women undergoing assisted reproductive technology treatment

The scope of this review is to focus on the management of benign ovarian cyst in the reproductive-age group of women undergoing ART. Ovarian cysts are a common occurrence in this patient population. The differential diagnosis includes functional cysts, dermoid cysts, endometrioma. The appropriate evaluation includes medical history and physical examination, laboratory tests and imaging. The treatment options include conservative follow-up, medical treatment and surgery. This review will explore the differential diagnosis, appropriate work-up and treatment options to the various cyst types encountered.

In Vitro Fertilization Outcomes Following Assisted Hatching of Embryos with Thick Zona Pellucida—A Prospective Randomized Study

Purpose: Impaired hatching is associated with implantation failure following in vitro fertilization (IVF). Thickening or hardening of the zona pellucida (ZP) has been proposed as a factor in this impairment. We examined whether selective assisted hatching (AH) is beneficial with embryos having a thick ZP. Methods: This prospective, randomized controlled study was performed in the IVF unit of an obstetrics and gynecology department in a university-affiliated hospital. Only patients undergoing IVF and having a ZP thickness of ≥17 μm measured in all their embryos were included. In the intervention group, AH was applied to all embryos, before their transfer. In the control group, embryos were transferred without AH. Implantation, clinical pregnancy and live birth rates were the study endpoints. Results: Both study arms were comparable in most baseline parameters. The two groups did not differ in implantation rates (14.1% control vs. 8.92% intervention, odds ratio (OR) = 0.5974, 95% confidence interval (CI) 0.325 - 1.1), clinical pregnancy rates (36.7% vs. 25.8%, OR = 0.6025, 95% CI 0.274 - 1.325), or live birth rates (25% vs. 18.9%, OR = 0.7021, 95% CI 0.291 - 1.691). Conclusions: Selecting embryos for AH by their ZP thickness as a sole parameter was not found to be beneficial and to improve IVF outcome.

Role of microRNA in regulation of myeloma-related angiogenesis and survival

Multiple myeloma(MM)is a malignant disease causedby clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage.Despite the uniform clinical signs,the disease is very diverse in terms of the nature and sequence of the underlying molecular events.Multiple cellular processes are involved in helping the malignant cells to remain viable and maintain proliferative properties in the hypoxic microenvironment of the bone marrow.Specifically,the process of angiogenesis,triggered by the interactions between the malignant MM cells and the stroma cells around them,was found to be critical for MM progression.In this review we highlight the current understanding about the epigenetic regulation of the proliferation and apoptosis of MM cells and its dependency on angiogenesis in the bone marrow that is carried out by different micro RNAs.

ECHOTHIOPHATE IODIDE FOR UNCON-TROLLED GLAUCOMA IN APHAKIA AND PSEUDOPHAKIA

Puprose: To evaluate the current intraocular pressure (IOP) control in patients whose glaucoma had been controlled on echothio-phate iodide (PI) therapy until the drug was no longer available. Methods: Twenty six patients with open-angle glaucoma in aphakia or pseudophakia whose IOP was uncontrolled on maximal tolerated medical therapy and who were thus candidates

PHACOEMULSIFICATION WITH A SMALL CORNEAL INCISION DECREASES IN-TRAOCULAR PRESSURE IN OPEN-ANGLE GLAUCOMA PATIENTS AND IN NORMAL CONTROLS

Purpose: To study IOP changes following phacoemulsification with a small corneal incision in OAG patients and in normal controls. Methods: Change in IOP and the number of medications required to control IOP were determined following pha-coemulsification in 58 OAG (POAG and PXF glaucoma) and 287 normal eyes. Follow up period ranged from 12 to 40 months.

MANAGEMENT OF LEAKING FILTERING BLEBS WITH THE DIODE LASER

Objective: To present a method for treating hypotony and bleb leaks using the diode laser. Methods: Prospective study of 7 patients who underwent diode laser bleb revision. Results: Seven eyes of 7 patients were analyzed. All patients had an oversized bleb and an associated late-onset leaking bleb. Diode laser energy using the G probe was applied to the bleb to close the leak. In four eyes two laser treatments were required to seal the leak. Af-

RETINAL ARTERIOLAR OBSTRUCTION IN A PATIENT WITH SICKLE CELL TRAIT AND GLAUCOMA SECONDARY TO TRAU-MATIC HYPHEMA

Purpose: To report an acute monocular retinal vascular occlusion in a patient with sickle cell trait and glaucoma secondary to traumatic hyphema. Methods and Results: Case report. A 35 year old Arab man who sustained blunt trauma to his right eye was hospitalized with hyphema, increased intraocular pres-

Nutritional deficiencies in the pediatric age group in a multicultural developed country,Israel

Nutrient deficiencies are prevalent worldwide.Diseases and morbid conditions have been described to result from nutritional deficiencies.It is essential to address nutrient deficiencies as these may lead to chronic longterm health problems such as rickets,iron deficiency anemia,goiter,obesity,coronary heart disease,type2 diabetes,stroke,cancer and osteoporosis.In the present review we surveyed the extent and severity of nutritional deficiencies in Israel through a selective and comprehensive Medline review of previous reports and studies performed during the last 40 years.Israel populations have multiple nutritional deficiencies,including iron,calcium,zinc,folic acid,and vitamins B12,C,D and E,spanning all age groups,several minorities,and specific regions.In Israel,some of the nutrients are mandatorily implemented and many of them are implemented voluntarily by local industries.We suggest ways to prevent and treat the nutritional deficiencies,as a step to promote food fortification in Israel.

MUSCARINIC BLOCKERS POTENTIATE BETA -ADRENERGIC RELAXATION OF BOVINE IRIS SPHINCTER

Purpose: To investigate the interactions between muscarinic and beta-adrenergic drugs in the iris sphincter relaxation Methods: Intact bovine iris sphincters were incubated in organ bath and challenged with appropriate beta-adrenergic agonists and/or muscarinic antagonists. Tension was measured by a force trans-

<i>N-myc</i>Downstream Regulated Gene 1 Increases Differentiation Factors Level in Human Prostate Cancer Cells without Affecting Cell Proliferation and Cell Cycle Profiles

N-myc downstream regulated gene 1 (NDRG1), also known as differentiation related gene 1, was previously identified as an up-regulated gene upon cellular differentiation. Even though its sequence along with its expressional pattern in cancer cell lines are evident, the functional aspects concerning cell proliferation, viability, differentiation and cell cycle regulation of NDRG1 remains vague. The aim of the present study was to elucidate the functional role of NDRG1 in human prostate cancer. Our results showed basal levels of NDRG1 expression in PC-3 (poorly differentiated, null p53), DU-145 (moderately differentiated, mutant p53) and LNCaP (well-differentiated, wiled type p53). Nevertheless, NDRG1 sequencing assay disclosed no mutations in the gene. Furthermore, human cDNA of NDRG1 from normal placenta was cloned into a eukaryotic expression vector and transfected into the three cancer cell lines. This resulted in over-expression of NDRG1, which in turn markedly up regulated two differentiation markers of the prostate tissue, p21 and cytokeratin 8/18. Unpredictably, cell cycle progression, cell proliferation and DNA synthesis were unaffected following NDRG1 expression. These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. However, the pathway downstream NDRG1, involving p21 and c8/18, regulating cell cycle progression and DNA synthesis is unfunctional. Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. Further studies are required to clarify the intra cellular molecular pathways affecting NDRG1 function in human prostate cancer.

Equivocal Differential Effect of NDRG1 in Human Ovarian Cancer Cells

Inactivation of tumor suppressor genes is a key factor in cancer regulation. N-myc downstream regulated gene 1 (NDRG1) is a tumor suppressor gene well known to be involved in carcinogenesis of numerous cancer types. The present study was designed to investigate the role of NDRG1 in human ovarian cancer, using SKOV-3 and SW626 (moderately and well differentiated cancer cells, respectively). Our results revealed that over-expressed NDRG1 significantly up-regulated the differentiation marker p21, in the ovarian cancer cell lines. This regulation led to decrease in cell viability and DNA synthesis rates in SW626 cells (83% and 89.5%, respectively). However, no effect on viability or on DNA synthesis was observed in SKOV-3 NDRG1-transfected cells. These findings prove that NDRG1 is indubitably functional in human ovarian cancer cells, as it up-regulated p21 expression. Nevertheless, this regulation showed differential effect on cell viability and DNA formation thus promoting the perception that downstream regulation of p21 could be inefficient in some cancer cells, a concept that needs to be further explored in order to understand its disability to play as regulator of cell cycle progression.

An Autoantibody Based Protein Microarray Blood Test to Enhance the Specificity of a Negative Screening Mammogram

Background: Current screening mammography for breast cancer is associated with misdiagnosis in as many as 30% of cases. Objectives: To develop and clinically evaluate a unique autoantibody based protein microarray blood test to improve the accuracy of breast cancer screening. Materials and Methods: A microarray was constructed from commercial antigens and antigens selected from screened cDNA libraries of breast cancer tissue samples. A training set containing 439 healthy controls and 276 biopsy proven breast cancer cases was used to establish a set of separating models between the two groups. These models were used to assign a diagnosis to 285 blind samples from 120 breast cancer patients and 165 healthy controls. Results: The test identified 82 of the 120 breast cancer patients and 160 of the 165 healthy controls. These results can be translated into a sensitivity of 68.3% [CI: 59% -77%] and a specificity of 97% [CI: 93% -99%], with a PPV for this validation set of 94.3% (CI: 87.10% -98.11%), NPV of 80.81% [CI: 74.62% -86.05%] and an AUC of 89.2% [CI: 78% -87%]. Conclusions: The protein microarray can be utilized to reduce the false negative rate of routine screening mammography. Women with a negative mammography and a negative blood test can be reassured and encouraged to continue routine breast cancer screening. A positive test should alert the physician about the possible presence of a breast cancer not detected by routine screening mammography and drive to perform additional investigation, such as breast ultrasound and MRI.

APC I1307K基因多态性携带者与结肠直肠息肉

PURPOSE: The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD: Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS: The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than non-carriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION: Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors.