Dori G.,ek Medical Center
Medical Hypotheses | Year: 2015
Cardiogenic pulmonary edema (PEd) is a life-threatening condition where fluid accumulates in the lungs due to increasing hydrostatic pressure building up in the pulmonary vasculature (PV): veins, venules and capillaries. Atrial fibrillation (AF) is accepted as an arrhythmia which triggers and promotes the pathophysiological processes leading to pulmonary congestion and its final expression: PEd. We propose a different view, where AF is actually a physiological solution temporarily protecting from PEd. We hypothesize that the compliance of the left atrium (LA) increases with the onset of AF. Thus, it is possible that even if the volume of blood within the LA increases due to loss of atrial contraction, the pressure within the LA would still be lower than that prior to AF (because of the increased LA compliance during AF). Decreased LA pressure allows more blood to flow from the PV to the LA, abating the hydrostatic pressure buildup in the PV compartment. The ratio, R, between the LA volume gained from the transition to AF provided by the greater LA compliance, and the volume of blood retained in the LA due to loss of atrial contraction, determines the instant pressure in the LA, as AF begins. If R is >1, then the LA pressure will instantly decrease with the transition to AF and this may be beneficial in delaying PEd. © 2014 Elsevier Ltd.
Bennett M.,ek Medical Center |
Schechter G.P.,George Washington University
Seminars in Hematology | Year: 2010
Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy. © 2010.
Nevet M.J.,Technion - Israel Institute of Technology |
Shalev S.A.,Genetics Institute |
Zlotogora J.,Hebrew University of Jerusalem |
Mazzawi N.,ek Medical Center |
Ben-Yosef T.,Technion - Israel Institute of Technology
Journal of Medical Genetics | Year: 2010
Background: Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. At least 32 genes and loci have been implicated in non-syndromic autosomal recessive RP. Progressive rodecone degeneration is a canine form of autosomal recessive retinal degeneration, which serves as an animal model for human RP, and is caused by a missense mutation of the PRCD gene. The same homozygous PRCD mutation has been previously identified in a single human RP patient from Bangladesh. To date, this is the only RP-causing mutation of PRCD reported in humans. Methods: The cause of the high incidence rate of autosomal recessive RP in an isolated Muslim Arab village in Northern Israel was investigated by haplotype analysis in affected families. The underlying mutation was detected by direct sequencing of the causative gene, and its prevalence in affected and unaffected individuals from the village was determined. Patients who were homozygotes for this mutation underwent ophthalmic evaluation, including funduscopy and electroretinography. Results and conclusions: The identification of a novel pathogenic nonsense mutation of PRCD is reported. This founder mutation was found in a homozygous state in 18 patients from nine families, and its carrier frequency in the investigated village is 10%. The mutation is associated with a typical RP phenotype, including bone spicule-type pigment deposits and non-recordable electroretinograms. Additional findings include signs of macular degeneration and cataract. The identification of a second pathogenic mutation of PRCD in multiple RP patients confirms the role of PRCD in the aetiology of RP in humans.
Klein A.,ek Medical Center |
Klein A.,Rambam Healthcare Campus |
Gralnek I.M.,ek Medical Center
Current Opinion in Critical Care | Year: 2015
Purpose of review Acute, nonvariceal upper gastrointestinal bleeding (UGIB) is a common medical emergency encountered worldwide. Despite medical and technological advances, it remains associated with significant morbidity and mortality. Recent findings Rapid patient assessment and management are paramount. When indicated, upper endoscopy in patients presenting with acute UGIB is effective for both diagnosis of the bleeding site and provision of endoscopic hemostasis. Endoscopic hemostasis significantly reduces rebleeding rates, blood transfusion requirements, length of hospital stay, surgery, and mortality. Furthermore, early upper endoscopy, defined as being performed within 24h of patient presentation, improves patient outcomes. Summary A structured approach to the patient with acute UGIB that includes early hemodynamic resuscitation and stabilization, preendoscopic risk stratification using validated instruments, pharmacologic and endoscopic intervention, and postendoscopy therapy is important to optimize patient outcome and assure efficient use of medical resources. © Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Saliba W.,ek Medical Center
Harefuah | Year: 2012
Anemia is common in diabetes. The role of hepcidin in diabetic anemia is unknown. To assess the relationship between serum hepcidin and anemia in diabetic patients without renal failure. We prospectively studied 86 consecutive type II diabetic patients--39 with anemia (cases) and 47 without anemia (controls). Patients with renal failure, iron and vitamin B12 deficiency and chronic inflammatory diseases were excluded. Univariate analyses showed that patients with anemia were older and had longer duration of diabetes compared to patients without anemia (P < 0.051). The median hepcidin level was 15 ng/mL (2-140 ng/ml) in patients with anemia compared to 14 ng/mL (2-128 ng/ml) in patients without anemia (P = 0.386]) Serum erythropoietin and creatinine levels were higher in patients with anemia compared to patients without anemia (P < 0.05). Patients with anemia had tower HbA1c levels (P = 0.035), and greater usage of anti-diabetic drugs; metformin 73% versus 46.8% (P = 0.016), and sulfonylurea 47.2% versus 19.1% (P = 0.006). After adjusting for age, the two groups still differed in duration of diabetes (P = 0.043), erythropoietin (P = 0.007) creatinine (P < 0.001), and usage of metformin, sulfonylurea and insulin (P < 0.05). Subjects with diabetic anemia have Longer diabetes duration than subjects with diabetes without anemia. Based on the results of this small study, hepcidin was not associated with diabetic anemia.
Saliba W.,Technion - Israel Institute of Technology |
Saliba W.,ek Medical Center |
Barnett-Griness O.,Technion - Israel Institute of Technology |
Rennert G.,Technion - Israel Institute of Technology |
Rennert G.,Clalit Health Services Headquarters
Osteoporosis International | Year: 2013
Summary: This study examines the relationship between obesity and the increase in serum 25(OH)D levels in response to vitamin D supplementation among adults with baseline serum 25(OH)D levels <50 nmol/L. This study revealed that the increase in serum 25(OH)D in response to vitamin D supplementation was higher in lean subjects as compared to obese subjects. Introduction: Serum 25(OH)D is lower among obese than non-obese. This study examines the relationship between obesity and the increase in serum 25(OH)D in response to vitamin D supplementation in a large sample of adults with baseline serum 25(OH)D <50 nmol/L, relatively long average treatment duration and large average daily cholecalciferol. Methods: The computerized database of the Clalit Health Services, which the largest nonprofit health maintenance organization in Israel, was retrospectively searched for all subjects aged ≥20 years who performed serum 25(OH)D test in 2011. Subjects with more than one test at different occasions in 2011 were identified and were included if the result of the first test was <50 nmol/L, and were treated with cholecalciferol between the first and the last test in 2011 (n = 16,540 subjects). Results: The mean increase in serum 25(OH)D level after treatment was 28.7 (95 % confidence interval (CI), 28.0-29.4) nmol/L, 23.6 (23.0-24.2) nmol/L, and 20.1 (19.6-20.6) nmol/L in subject with BMI of <25, 25-29.9, and ≥30 kg/m2, respectively (P < 0.001). The results were similar after adjustment for the potential confounders. Similarly, the proportion of subjects who achieved serum 25(OH)D ≥ 50 nmol/L after treatment was inversely associated with BMI; 65.1, 58.3, and 49.1 % for BMI of <25, 25-29.9, and ≥ 30 kg/m2, respectively. Compared to BMI of ≥30 kg/m2, the adjusted odds ratio for achieving levels of ≥50 nmol/L were 2.12 (95 % CI, 1.94-2.31) and 1.42 (1.31-1.54) for BMI of <25 kg/m2, and BMI of 25-29.9 kg/m2, respectively. Conclusions: BMI is inversely associated with the increase in serum 25(OH)D levels in response to vitamin D supplementation. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.
Markel A.,ek Medical Center
Israel Medical Association Journal | Year: 2011
Hypercholesterolemia is one of the main factors in the development of atherosclerotic cardiovascular disease. The advent of statins led to huge progress in the treatment of hypercholesterolemia, yet the proportion of patients with prohibitive lipid values and the high incidence of cardiovascular events despite treatment are still very high. Niacin, one of the older drugs used to treat hyperlipidemia, was shown to reduce low-density lipoprotein-cholesterol (LDL-C) and triglycerides and to markedly increase high density lipoprotein-cholesterol (HDL-C) levels. This drug came into disuse owing to frequent side effects, mainly flushing, but in recent years a reemergence of its application has occurred, and multiple clinical trials have shown its effectiveness in the treatment of hyperlipidemia and in the reduction of cardiovascular events. New formulations such as extended-release niacin (ERN) have been developed with the purpose of reducing side effects. Lately, a new compound, laropiprant, which selectively antagonizes the prostaglandin 2 (PGD2) receptor responsible for flushing, has been developed. Laropiprant, when combined with ERN, significantly reduces the incidence of flushing. New and ongoing trials will definitively prove in the long term whether this drug combination significantly reduces the severity of flushing and the incidence of cardiovascular events.
Hilo W.,ek Medical Center
Harefuah | Year: 2013
Lebers hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by subacute severe visual loss in both eyes, which usually manifests in young adulthood. The disease has maternal inheritance due to mitochondrial DNA mutation. The final diagnosis is genetic. There is still no proven treatment, but there is significant progress in developments on the genetics of the disease to reach gene therapy. In this article we review the latest literature relevant to this disease.
DiMauro S.,Columbia University |
Spiegel R.,ek Medical Center
Acta Myologica | Year: 2011
In this selective review, we consider a number of unsolved questions regarding the glycogen storage diseases (GSD). Thus, the pathogenesis of Pompe disease (GSD II) is not simply explained by excessive intralysosomal glycogen storage and may relate to a more general dysfunction of autophagy. It is not clear why debrancher deficiency (GSD HI) causes fixed myopathy rather than exercise intolerance, unless this is due to the frequent accompanying neuropathy. The infantile neuromuscular presentation of branching enzyme deficiency (GSD IV) is underdiagnosed and is finally getting the attention it deserves. On the other hand, the late-onset variant of GSD IV (adult polyglucosan body disease APBD) is one of several polyglucosan disorders (including Lafore disease) due to different etiologies. We still do not understand the clinical heterogeneity of McArdle disease (GSD V) or the molecular basis of the rare fatal infantile form. Similarly, the multisystemic infantile presentation of phosphofructokinase deficiency (GSD VII) is a conundrum. We observed an interesting association between phosphoglycerate kinase deficiency (GSD IX) and juvenile Parkinsonism, which is probably causal rather than casual. Also unexplained is the frequent and apparently specific association of phosphoglycerate mutase deficiency (GSD X) and tubular aggregates. By paying more attention to problems than to progress, we aimed to look to the future rather than to the past.
Salim R.,ek Medical Center |
Shalev E.,ek Medical Center
Reproductive Biology and Endocrinology | Year: 2010
Background: The literature is nearly unanimous in recommending elective cesarean delivery at 39 weeks of gestation because of the lower rates of neonatal respiratory complications compared to 38 weeks. However, elective cesarean delivery at 39 weeks or more may have maternal and other fetal consequences compared to delivery at 38 weeks, which are not always addressed in these studies.Discussion: Between 38 and 39 weeks of gestation, approximately 10% - 14% of women go into spontaneous labor; meaning that a considerable number of women scheduled for an elective cesarean delivery at 39 weeks will deliver earlier in an unscheduled, frequently emergency, cesarean delivery. The incidence of maternal morbidity and mortality is higher among women undergoing non-elective cesarean deliveries than among those undergoing elective ones. Complications may be greater among women after numerous repeat cesarean deliveries and among older women. Other than reducing the frequency of non-elective cesarean deliveries, bringing forward the timing of elective cesarean delivery to 38 weeks, may occasionally prevent intrauterine fetal demise which has been shown to increase with increasing gestational age and to avoid other fetal consequences related to the emergency delivery. All these considerations need to be weighed against the medical and the economic impact of the increase in neonatal morbidity resulting from births at 38 weeks compared to 39 weeks.Summary: Until prospective randomized trials are conducted, we are unlikely to be able to precisely answer all risk:benefit questions as to the best timing of scheduled elective cesarean delivery. Older women, and women with numerous prior cesarean deliveries, are of particular concern. It is reasonable to inform the pregnant women of the risk of each of the above options and to respect her autonomy and decision-making. © 2010 Salim and Shalev; licensee BioMed Central Ltd.