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Biomedical subjects

Tova Chajek-Shaul

Publications and source records attributed to Tova Chajek-Shaul.

At least 19 recordsLinked to original sources
PubMed2006

Echocardiographic manifestations of Adamantiades-Behcet's disease.

Adamantiades-Behcet disease (ABD) is a multisystemic, chronic inflammatory disorder of unknown etiology with diffuse clinical manifestations including those involving the cardiovascular system. While the disease is most prevalent in the Mediterranean region, the Middle East and the Far East, its prevalence is increasing in Western countries due to migration patterns. Cardiovascular involvement in ABD may include myocardial disease, venous disease and disease of the aorta and great vessels. Use of echocardiography in these patients is crucial to assess their pathology and in this article we review the spectrum of echocardiographic findings in patients with ABD.

Adult↗
PubMed2006

Chronicle of a death foretold: a case of catastrophic vascular Behcet's disease.

A 20-year-old man with Behcet's disease characterized by recurrent arterial aneurysms presented with a new aortic root aneurysm. This patient previously had aneurysms of the coronary arteries and vein, as well as ruptured renal artery aneurysm. Chronic maintenance immunosuppressive therapy was recommended due to the catastrophic nature of the disease, which the patient refused to take. The patient died shortly after admission. This case demonstrates the unique catastrophic natural history of vascular Behcet's disease with recurrent life-threatening arterial events, and this case stresses the therapeutic dilemma of maintenance immunosuppressive therapy in selected patients.

Adult↗
PubMed2006

The use of low-dose insulin in cardiogenic shock due to combined overdose of verapamil, enalapril and metoprolol.

We describe a case of severe heart failure due to the combined effect of verapamil and enalapril overdose in a patient treated regularly with metoprolol. The patient was dependent for 2 days on glucagon and dopamine infusion but remained oliguric, with deteriorating renal function. Marked improvement in all hemodynamic parameters was noted a short time after initiation of treatment with low-dose insulin infusion (1-2 units/h), which allowed the prompt withdrawal of glucagon and dopamine. We discuss the efficacy of glucose-insulin treatment in toxic cardiac depression and suggest that a low dose may be beneficial in similar cases.

Antihypertensive Agents↗
PubMed2006

ST-deviation patterns in recurrent myocardial infarctions.

Myocardial infarction (MI) may be classified as ST-elevation MI (STEMI) or non-STEMI (NSTEMI). We used the term "recurrent MI" (RMI) to denote repeat MI episodes in a particular patient in which a different coronary site is responsible for each episode. We investigated whether the type of RMI is more likely to be of the same type as the index MI or whether patients may have the 2 types of MI at random. The analysis included 305 patients who had >or=2 MI episodes. Acute MIs were classified as STEMI or NSTEMI. We attempted to include only MIs of native vessels, without the presence of extracardiac conditions that intensify myocardial ischemia. Most patients (76%) had repeat episodes of the same MI type, i.e., STEMI or NSTEMI. Recurrent STEMI occurred in 44% of patients, recurrent NSTEMI in 32%, and STEMI and NSTEMI in 24%. Thus, most patients with RMI episodes will have STEMIs or NSTEMIs but not the 2 types, suggesting a predilection of some patients to repeat episodes of occlusive thrombi and others to repeat episodes of nonocclusive thrombi.

Aged↗
PubMed2006

Heparanase is expressed in osteoblastic cells and stimulates bone formation and bone mass.

Heparan sulfate proteoglycans (HSPGs) are ubiquitous macromolecules. In bone, they are associated with cell surfaces and the extracellular matrix (ECM). The heparan sulfate (HS) chains of HSPGs bind a multitude of bioactive molecules, thereby controlling normal and pathologic processes. The HS-degrading endoglycosidase, heparanase, has been implicated in processes such as inflammation, vascularization associated with wound healing and malignancies, and cancer metastasis. Here we show progressive mRNA expression of the hpa gene (encoding heparanase) in murine bone marrow stromal cells undergoing osteoblastic (bone forming) differentiation and in primary calvarial osteoblasts. Bone marrow stromal cells derived from transgenic mice expressing recombinant human heparanase (rh-heparanase) and MC3T3 E1 osteoblastic cells exposed to soluble rh-heparanase spontaneously undergo osteogenic differentiation. In addition, the transgenic bone marrow stromal cells degrade HS chains. In wild-type (WT) and hpa-transgenic (hpa-tg) mice, heparanase is weakly expressed throughout the bone marrow with a substantial increase in osteoblasts and osteocytes, especially in the hpa-tg mice. Heparanase expression was absent in osteoclasts. Micro-computed tomographic and histomorphometric skeletal analyses in male and female hpa-tg versus WT mice show markedly increased trabecular bone mass, cortical thickness, and bone formation rate, but no difference in osteoclast number. Collectively, our data suggest that proteoglycans tonically suppress osteoblast function and that this inhibition is alleviated by HS degradation with heparanase.

Animals↗
PubMed2006

Spleen rupture secondary to anticonvulsant hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare complication associated with the use of anti-epileptic medications. The syndrome's main symptoms are cutaneous eruptions, fever, hepatitis, and lymphadenopathy. We describe a 23-year-old woman who developed AHS 2 months after starting phenytoin therapy. She presented with fever, orofacial edema, skin rash, and lymphadenopathy. Four days after admission, she developed agonizing epigastric pain with diffuse epigastric tenderness. An abdominal CT scan demonstrated splenomegaly with a large, hypodense area involving the upper half of the spleen, consistent with splenic rupture. She was managed medically in an effort to avoid splenectomy. There are no other documented cases of spleen rupture linked to AHS. A possible mechanism is the alteration of lymphocytic function due to the accumulation of cytotoxic metabolites and infiltration of the spleen with lymphocytic cells, distending the capsule and predisposing it for rupture. We believe that the case presented here should increase awareness of the potentially life-threatening complications associated with AHS.

Journal Article↗
PubMed2006

Physicians underdiagnose and undertreat obesity in ishemic heart disease patients: data from the HOLEM Study Group.

BACKGROUND: Obesity is an independent risk factor for ischemic heart disease and affects the status of other risk factors for cardiovascular disease. OBJECTIVE: To study the attitude of physicians to obesity by examining discharge letters of overweight patients with ischemic heart disease. METHODS: We used the HOLEM database for this analysis. The HOLEM project was designed to study the NCEP (National Cholesterol Education Program) guideline implementation among patients with IHD at hospital discharge. We documented the recording of risk factors and treatment recommendations for IHD by reviewing the discharge letters of 2994 IHD patients admitted to four central hospitals in Israel between 1998 and 2000. A follow-up visit was held 6-8 weeks after discharge, at which time the diagnosis of IHD was verified, risk factor status was checked, height and weight were measured and drug treatment was reviewed. RESULTS: Mean body mass index was 28.3 kg/m2 and 32% were obese (BMI > or = 30 kg/m2). Only 39.6% of the obese patients and 65.8% of the morbidly obese patients (BMI > or = 40 kg/m2) had "obesity" noted in their discharge letters, and weight loss recommendation was written in only 15% of the obese patients' discharge letters. Acute episodes like acute myocardial infarction and unstable angina did not influence the notation of obesity, and only BMI and the number of additional risk factors were positively correlated with the notation of this risk factor. CONCLUSIONS: Despite the importance of obesity, weight status was not noted and weight loss was not recommended in most of the discharge letters of obese IHD patients.

Aged↗
PubMed2005

Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred.

Endoglin (CD105) is a proliferation-associated protein that is strongly expressed in endothelial tissue and has a role in tumor angiogenesis. Mutations in endoglin are also linked to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disease associated with aberrant angiogenesis. We report an unusual association of HHT1 and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in the same kindred. Genetic analysis indicates that these 2 syndromes are genetically unrelated and separately segregated within the family. The mutation in the endoglin gene leads to a truncated protein. The mutation in the mismatch repair gene MLH1 causes a splicing defect, giving synthesis to an unstable mRNA from this mutated allele. The potential protective role of an endoglin mutation in patients with HNPCC is discussed.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Cardiovascular risk assessment and treatment to target low density lipoprotein levels in hospitalized ischemic heart disease patients: results of the HOLEM study.

BACKGROUND: Hypercholesterolemia control status is lacking throughout the western world. OBJECTIVES: To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli medical societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines. METHODS: We included consecutive IHD patients admitted to four central hospitals in Israel between 1998 and 2000. The study was conducted in two phases. In phase 1, we reviewed discharge letters to document treatment recommendations given to each patient. In phase 2 we educated the practitioners by reviewing the Israeli medical societies and the NCEP guidelines and the quality of their recommendations in phase 1, after which we reevaluated the discharge letters. RESULTS: The study included 2,994 patients: 627 in phase 1 and 2,367 in phase 2. Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels, 37.4% were not prescribed such drugs at discharge (under-treatment group). This proportion was reduced by education to 26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the target LDLgoal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01), but the percent of patients reaching' LDL levels <100 was not different in phase 2 after adjusting for age and gender (the odds ratio for reaching target LDL was 1.16, with 95% confidence interval of 0.95-1.43). CONCLUSIONS: Physician recommendations to IHD patients discharged from hospital were suboptimal. We documented a high proportion of under-treated and under-dosaged patients. Brief educational sessions have a beneficial effect on the usage of statins; however, additional effort in guideline implementations is needed.

Arteriosclerosis↗
PubMed2004

Inhibition of hepatic gluconeogenesis and enhanced glucose uptake contribute to the development of hypoglycemia in mice bearing interleukin-1beta- secreting tumor.

Mice bearing IL-1beta-secreting tumor were used to study the chronic effect of IL-1beta on glucose metabolism. Mice were injected with syngeneic tumor cells transduced with the human IL-1beta gene. Serum IL-1beta levels increased exponentially with time. Secretion of IL-1beta from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Body composition analysis revealed that IL-1beta caused a significant loss in fat tissue without affecting lean body mass and water content. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities and mRNA levels of these enzymes were reduced, and 2-deoxy-glucose uptake by peripheral tissues was enhanced. mRNA levels of glucose transporters (Gluts) in the liver were determined by real-time PCR analysis. Glut-3 mRNA levels were up-regulated by IL-1beta. Glut-1 and Glut-4 mRNA levels in IL-1beta mice were similar to mRNA levels in pair-fed mice bearing nonsecreting tumor. mRNA level of Glut-2, the major Glut of the liver, was down-regulated by IL-1beta. We concluded that both decreased glucose production by the liver and enhanced glucose disposal lead to the development of hypoglycemia in mice bearing IL-1beta-secreting tumor. The observed changes in expression of hepatic Gluts that are not dependent on insulin may contribute to the increased glucose uptake.

Animals↗
PubMed2004

Does any lower gastrointestinal bleeding in patients suffering from hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) necessitate a full colonic visualization?

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) (the Osler-Weber-Rendu syndrome) is a rare autosomal dominant disease characterized by telangiectasias and arteriovenous malformations of the upper and lower respiratory tract, gastrointestinal tract, skin and central nervous system. Several previous reports have documented the appearance of a concomitant neoplasm in patients with this syndrome. AIMS: To study the occurrence and the clinical characterization of colonic neoplasm in patients with HHT. METHODS: We retrospectively reviewed the computerized database of the Hadassah University Hospitals (Jerusalem, Israel) for all patients with the diagnosis of HHT between January 1st, 1980 and July 30th, 2002. Cases of neoplasm were documented by review of medical charts and pathology reports. RESULTS: Six of the 24 patients developed malignancy. Three of the cases had extra colonic malignancy (melanoma in two patients and adenocarcinoma of urinary bladder in one patient) and three patients had adenocarcinoma of the colon. An additional three patients developed multiple colonic polyps (one patient had melanoma and one patient had adenocarcinoma of urinary bladder). CONCLUSIONS: HHT may be associated with the development of colonic adenocarcinoma and polyps. Therefore, in patients with HHT who present with new-onset anemia or gastrointestinal bleeding a lower gastrointestinal tract evaluation should be performed, even if their blood loss is suspected to be a manifestation of gastrointestinal HHT.

Adenocarcinoma↗
PubMed2004

Anterior uveitis as a complication of treatment with high dose cytosine-arabinoside.

We present a case of a 21-year-old woman suffering from diffuse large B-cell lymphoma who developed acute anterior uveitis shortly after completing chemotherapeutic course with HYPER-CVAD protocol (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) alternating with methotrexate and high-dose cytosine-arabinoside (HIDAC), with poor adherence to recommended prophylactic treatment with saline eye drops. Complete resolution of her symptoms was achieved within a few days of treatment with topical steroids. To our knowledge this is the first report of acute anterior uveitis secondary to treatment with HIDAC. Differential diagnosis and a suggested mechanism are discussed.

Adult↗
PubMed2004

Transgenic expression of mammalian heparanase uncovers physiological functions of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior.

We have generated homozygous transgenic mice (hpa-tg) overexpressing human heparanase (endo-beta-D-glucuronidase) in all tissues and characterized the involvement of the enzyme in tissue morphogenesis, vascularization, and energy metabolism. Biochemical analysis of heparan sulfate (HS) isolated from newborn mice and adult tissues revealed a profound decrease in the size of HS chains derived from hpa-tg vs. control mice. Despite this, the mice appeared normal, were fertile, and exhibited a normal life span. A significant increase in the number of implanted embryos was noted in the hpa-tg vs. control mice. Overexpression of heparanase resulted in increased levels of urinary protein and creatinine, suggesting an effect on kidney function, reflected also by electron microscopy examination of the kidney tissue. The hpa-tg mice exhibited a reduced food consumption and body weight compared with control mice. The effect of heparanase on tissue remodeling and morphogenesis was best demonstrated by the phenotype of the hpa-tg mammary glands, showing excess branching and widening of ducts associated with enhanced neovascularization and disruption of the epithelial basement membrane. The hpa-tg mice exhibited an accelerated rate of hair growth, correlated with high expression of heparanase in hair follicle keratinocytes and increased vascularization. Altogether, characterization of the hpa-tg mice emphasizes the involvement of heparanase and HS in processes such as embryonic implantation, food consumption, tissue remodeling, and vascularization.

Animals↗
PubMed2003

A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair.

OBJECTIVES: The goal of this study was to analyze the genetic disorder of a family with cardiomyopathy, skin disorder, and woolly hair. BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder causing arrhythmia and sudden cardiac death. We report a patient with familial autosomal recessive ARVD, woolly hair, and a pemphigous-like skin disorder with a new mutation in the desmoplakin gene. METHODS: Genomic deoxyribonucleic acid was extracted from the patient's blood and 12 first- and second-degree family members, and was amplified by polymerase chain reaction. Linkage analysis with polymorphic microsatellites was performed for 11 genes that code for structural desmosomal proteins. The genetic locus of the disease in this family was mapped to the chromosomal region 6p24 that contains the desmoplakin gene. Exons of the desmoplakin gene were analyzed by single-strand conformational polymorphism and direct sequencing. Confirmation of the mutation was carried out by restriction enzyme analysis. RESULTS: We identified in the patient a homozygous missense mutation in exon 24 of the desmoplakin gene, leading to a Gly2375Arg substitution in the C-terminal of the protein where the binding site to intermediate filaments is located. Eight of 12 family members without hair or skin abnormalities were heterozygous for this mutation. The remaining 4, as well as 90 unrelated healthy control individuals of the same ethnic origin, were homozygous for the normal allele. CONCLUSIONS: We have described a new mutation in the desmoplakin gene that causes familial ARVD. These findings suggest that desmosomal proteins play an important role in the integrity and function of the myocardium. Dysfunction of these proteins can lead to the development of cardiomyopathies and arrhythmias.

Abnormalities, Multiple↗
PubMed2003

Licorice consumption causing severe hypokalemic paralysis.

Hypokalemic paralysis due to licorice consumption is extremely rare, with only 40 cases in the English literature describing paralysis secondary to exposure to licorice in candies, medications, chewing tobacco, and herbal preparations. We describe a patient who suffered life-threatening hypokalemic paralysis caused by consumption of licorice in the form of a tea sweetener superimposed on long-term consumption of licorice candy. Aggressive fluid and potassium replenishment produced complete and lasting recovery. To our knowledge, this is the first report of hypokalemic paralysis due to exposure to licorice as a tea sweetener, a common custom among the Arab population. The case emphasizes the importance of considering patients' cultural backgrounds and local customs, which often may lead the treating physician to the correct clinical diagnosis.

Adult↗