142 results on '"Yael Goldberg"'
Search Results
102. Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A
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Yael Goldberg, Elizabet Half, Ephrat Levy-Lahad, Lina Basel-Salmon, Lior H. Katz, Zohar Levy, Mahmud Mansur, Shlomi Cohen, Menachem Schechter, Ariela Tomer, Eliahu Golomb, Tamar Peretz, Tom Walsh, Rachel Beeri, Rachel Berger, Sari Lieberman, Harold Jacob, Mary Claire King, Suleyman Gulsuner, Dan Keret, and Inbal Kedar
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Male ,Esophageal Neoplasms ,Colorectal cancer ,Gastroenterology ,Loss of heterozygosity ,0302 clinical medicine ,Medicine ,Juvenile polyposis syndrome ,Israel ,Sequence Deletion ,Aged, 80 and over ,Genome ,biology ,Intestinal Polyposis ,Intestinal Polyps ,Middle Aged ,Pedigree ,3. Good health ,Phenotype ,Child, Preschool ,Gastritis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,Adult ,Heterozygote ,medicine.medical_specialty ,Adolescent ,Tumor suppressor gene ,Colon ,Article ,Young Adult ,03 medical and health sciences ,Testicular Neoplasms ,Neoplastic Syndromes, Hereditary ,Internal medicine ,Humans ,PTEN ,Alleles ,Bone Morphogenetic Protein Receptors, Type I ,Aged ,business.industry ,Juvenile Polyp ,Point mutation ,medicine.disease ,digestive system diseases ,BMPR1A ,Jews ,biology.protein ,business - Abstract
Juvenile polyposis syndrome (JPS, OMIM 174900) is a rare autosomal dominant disorder, affecting between 1 in 100,000 and 1 in 160,000 (1), characterized by hamartomatous polyps and increased risk of gastrointestinal (GI) cancer. JPS is diagnosed clinically when a person has any one of the following: (i) more than 5 juvenile polyps of the colon or rectum; (ii) juvenile polyps in other parts of the GI tract; or (iii) any number of juvenile polyps and one or more affected family members (National Comprehensive Cancer Network [NCCN] guidelines) (2). Up to 60% of individuals with clinically defined JPS are now found to exhibit mutations in SMAD4 or BMPR1A genes (3). JPS polyps are typically colonic with edematous, markedly inflamed lamina propria, with cystic dilation and smooth muscle proliferation. Although dysplastic polyps may appear with variable histology, one study reported “mixed polyposis syndrome” with polyps containing variable pathology of adenomatous, hyperplastic, and juvenile features caused by small base pair deletions in the BMPR1A gene (4); adenomas comprise less than 10% of JPS polyps (5). JPS can involve the entire GI tract. Although colonic phenotype is similar between patients with SMAD4 and BMPR1A mutations, upper GI and gastric polyposis is much more common in SMAD4 mutation (1,6,7). As reported by Aretz et al. (6), SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis than did patients with BMPR1A mutations (83% vs 8%, respectively). All cases of gastric cancer occurred in families with SMAD4 mutations (6,7). Lifetime risk estimates of GI cancers, mostly colorectal cancer (CRC), are highly variable, ranging from 14% to 55% in different series (1,8,9). Although surveillance guidelines exist, the NCCN guidelines for surveillance recommend referral of patients with JPS to a specialized team due to the rarity of the syndrome and complexities of diagnosis and management (2). The molecular alterations involved in polyp and tumor formation in JPS are attributed to defective BMP signaling, where aberrant BMP signaling disrupts stem cell self-renewal and differentiation, contributing to tumor formation (10). Loss of heterozygosity (LOH) was reported in half of BMPR1A-related polyps, compatible with BMPR1A acting as a tumor suppressor gene (11). However, BMPR1A LOH has not been documented yet in cancerous tumors. Most pathogenic variants in BMPR1A are point mutations or small deletions. Large deletions of BMPR1A are rare, accounting for approximately 6% of cases, many of them are contiguous with PTEN (6,12–14). Contiguous gene deletions may lead to more pronounced manifestations; however, the rarity and variability of BMPR1A deletions not including PTEN have made genotype-phenotype relationships of large BMPR1A deletions difficult to assess (14). We identified a deletion of the entire coding region of the BMPR1A gene among and investigated the clinical features in over 50 individuals from 7 unrelated families. This cohort enables expanding our knowledge about this rare predisposition syndrome.
- Published
- 2019
103. Traumatic Brain Injury, Boredom and Depression
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Yael Goldberg and James Danckert
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Traumatic brain injury ,lcsh:BF1-990 ,Development ,boredom ,050105 experimental psychology ,Developmental psychology ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Genetics ,medicine ,0501 psychology and cognitive sciences ,General Psychology ,Ecology, Evolution, Behavior and Systematics ,Depression (differential diagnoses) ,Brief Report ,traumatic brain injury ,05 social sciences ,Beck Depression Inventory ,Boredom ,medicine.disease ,lcsh:Psychology ,nervous system ,depression ,Disconnection ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Traumatic brain injury (TBI) often presents with co-morbid depression and elevated levels of boredom. We explored the relationship between boredom and depression in a group of mild (n = 38), moderate-to-severe TBI patients (n = 14) and healthy controls (n = 88), who completed the Beck Depression Inventory and Boredom Proneness Scales as part of a larger study. Results showed that the relationship between boredom and depression was strongest in moderate-to-severe TBI patients. We explored two boredom proneness factors that index an individual’s need for external or internal stimulation. Results indicated that the need for external stimulation was the critical driver in the relation between boredom and depression. Once again, this relationship was strongest in the moderate-to-severe TBI group. These results suggest that one common factor underlying boredom and depression is the need for stimulation from the external environment and, presumably, a failure to satisfy that need—a disconnection felt most strongly in moderate-to-severe TBI.
- Published
- 2013
104. P4‐329: Behavioural Neurology Assessment – Revised: Validation in Amnestic Mild Cognitive Impairment (AMCI)
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Michael Borrie, Morris Freedman, Sanjeev Kumar, Jennifer Fogarty, Suvendrini Lena, Yael Goldberg, David F. Tang-Wai, William E. Reichman, Kathryn A. Stokes, Tarek K. Rajji, Larry Leach, Ron Keren, Maria Carmela Tartaglia, Corinne E. Fischer, Michael Uri Wolf, Mohammad Alhaj, Nathan Herrmann, Nicolaas Paul L.G. Verhoeff, Sandra E. Black, Gary Naglie, and Barry D. Greenberg
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medicine.medical_specialty ,Neurology ,Epidemiology ,business.industry ,Health Policy ,Audiology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Cognitive impairment - Published
- 2016
105. P3‐208: Equivalence of Ipad and Paper Version of the Behavioural Neurology Assessment‐Revised
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Barry D. Greenberg, Tom Gee, Michelle Gyenes, Larry Leach, Robert Partridge, Mohammad Alhaj, Stephen C. Strother, Josh Kirstein, Kathryn A. Stokes, Alita Fernandez, Sandra E. Black, Nima Nourhaghighi, Morris Freedman, Ellie Aghdassi, Yael Goldberg, David F. Tang-Wai, Robyn Spring, and Jordana L. Waserman
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Cognitive science ,medicine.medical_specialty ,Neurology ,Epidemiology ,Health Policy ,Paper version ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology ,Equivalence (measure theory) - Published
- 2016
106. Polyposis Caused by Low APC Mosaicism
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Brian H. Shirts, Ariel A. Benson, Angela Jacobson, Harold Jacob, Colin C. Pritchard, Thomas J. Walsh, and Yael Goldberg
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Abdominal pain ,medicine.diagnostic_test ,Colorectal cancer ,Somatic cell ,business.industry ,Esophagogastroduodenoscopy ,Colonoscopy ,medicine.disease ,Omics ,Familial adenomatous polyposis ,03 medical and health sciences ,030104 developmental biology ,medicine ,Family history ,medicine.symptom ,business - Abstract
Purpose: To present a patient with familial adenomatous polyposis (FAP) caused by a low level of somatic mosaicism. Case description: A twenty-one year old female presented with rectal bleeding and abdominal pain. She underwent a colonoscopy and esophagogastroduodenoscopy which revealed extensive polyposis. There was no family history of polyps or early onset colon cancer in her family. Methodology: Next-generation sequencing (NGS) analysis was performed using the ColoSeqTM panel on DNA extracted from both peripheral blood lymphocytes and colonic polyps. RESULTS: Molecular analysis detected the p.E1408X deleterious mutation in the APC gene in in 12 of 276 (4%) reads of the DNA in the peripheral blood leukocytes and in 30% of the DNA from colonic polyps. Conclusion: We report that low level of 4% APC mosaicism led to florid polyposis. Our report highlights the power of deep next-generation sequencing to identify mosaic mutations that are missed by traditional approaches. Though somatic APC mosaicism has previously been reported to cause polyposis syndrome in a few cases, it has been underestimated as a cause of polyposis coli. This case should reinforce the need to search for mosaicism in all patients with a personal history of polyposis and no family history.
- Published
- 2016
107. Exploring the relationship between boredom and sustained attention
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James Danckert, Colleen Merrifield, Ela Malkovsky, and Yael Goldberg
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Male ,medicine.medical_specialty ,Neurology ,Adolescent ,Neuropsychological Tests ,Sensitivity and Specificity ,Developmental psychology ,Young Adult ,Cognition ,Bias ,Reaction Time ,medicine ,Humans ,Attention deficit hyperactivity disorder ,Attention ,Young adult ,Depression (differential diagnoses) ,Psychiatric Status Rating Scales ,Motivation ,Depression ,General Neuroscience ,Boredom ,medicine.disease ,Attention Deficit Disorder with Hyperactivity ,Decreased Sensitivity ,Psychiatric status rating scales ,Female ,medicine.symptom ,Psychology - Abstract
Boredom is a common experience, prevalent in neurological and psychiatric populations, yet its cognitive characteristics remain poorly understood. We explored the relationship between boredom proneness, sustained attention and adult symptoms of attention deficit hyperactivity disorder (ADHD). The results showed that high boredom-prone individuals (HBP) performed poorly on measures of sustained attention and showed increased symptoms of ADHD and depression. The results also showed that HBP individuals can be characterised as either apathetic-in which the individual is unconcerned with his/her environment, or as agitated-in which the individual is motivated to engage in meaningful activities, although attempts to do so fail to satisfy. Apathetic boredom proneness was associated with attention lapses, whereas agitated boredom proneness was associated with decreased sensitivity to errors of sustained attention, and increased symptoms of adult ADHD. Our results suggest there is a complex relationship between attention and boredom proneness.
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- 2012
108. Diagnosis of Lower Gastrointestinal Tumors by Transvaginal Sonography
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Reuven Keidar, Ron Auslender, Arie Biterrman, Shlomi Sagie, Ofer Lavie, Yakir Segev, and Yael Goldberg
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Mean diameter ,Retrospective review ,medicine.medical_specialty ,Gastrointestinal tumors ,Radiological and Ultrasound Technology ,business.industry ,Lumen (anatomy) ,medicine.disease ,Transvaginal sonography ,Carcinoma ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Rectosigmoid Carcinoma ,business - Abstract
Sonography plays a primary role in the diagnosis of gynecological diseases. A retrospective review of incidental findings report by transvaginal sonography (TVS) was performed to evaluate the ability of TVS to visualize rectosigmoid carcinoma. The authors performed a retrospective review of 450 women who were referred for TVS because of suspected gynecological indications to evaluate those with incidental findings. Of these, 15 with incidental findings were subsequently diagnosed with rectosigmoid carcinoma. The sonographic properties and clinical findings were systematically evaluated. TVS findings included solid nonhomogeneous lesions (mean diameter of 4 cm; range, 1.6–8 cm), distended rectal walls, and gas inside the gastrointestinal lumen in 53% ( n = 8) of the cases. Total wall invasion was suspected, and signs of edema were noticed in 60% ( n = 9) of the cases. All lesions seen by TVS were pathologically confirmed as carcinoma of gastrointestinal origin. Inspection of the rectosigmoid during a TVS examination has the ability to detect unsuspected rectosigmoid lesions.
- Published
- 2011
109. Complete remission, in BRCA2 mutation carrier with metastatic pancreatic adenocarcinoma, treated with cisplatin based therapy
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Luna Kadouri, Tamar Peretz, Yael Goldberg, Liat Appelbaum, Ayala Hubert, Amir Sonnenblick, and Michal Sagi
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Male ,Oncology ,Heterozygote ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,Adenocarcinoma ,Deoxycytidine ,Germline mutation ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Germ-Line Mutation ,BRCA2 Protein ,Pharmacology ,Cisplatin ,business.industry ,BRCA mutation ,Cancer ,Middle Aged ,Metastatic Pancreatic Adenocarcinoma ,medicine.disease ,Gemcitabine ,Pancreatic Neoplasms ,Treatment Outcome ,Molecular Medicine ,business ,medicine.drug - Abstract
Carriers of a germline mutation in the BRCA genes, in particular BRCA2, have an increased risk of developing pancreatic adenocarcinoma when compared with the general population. While the addition of cisplatin to gemcitabine did not produce survival benefit compared to single-agent gemcitabine in prospective trials it is postulated that the addition of DNA cross-linking agent such as cisplatin to standard gemcitabine chemotherapy should be considered in known BRCA mutation carriers. We report a case of pancreatic adenocarcinoma arising in a 60-year-old carrier of a rare BRCA2 (1153insertionT) germline mutation. The patient received gemcitabine without any response and actually progression of the disease had occurred. Therefore cisplatin was added in combination with gemcitabine. A dramatic complete response to therapy was encountered with no evidence of disease in both CT scans and markers (CA19-9). In conclusion, in patients with known BRCA mutation associated pancreatic adenocarcinoma, the addition of a DNA cross-linking agent such as cisplatin should be considered. Physicians should consider BRCA mutation testing when the diagnosis of pancreatic cancer is established, especially when the patient belongs to an ethnic group where founder mutations exist, and/or there is strong personal or family history of cancer. This may be applied also to other metastatic tumors diagnosed in BRCA1/2 carriers.
- Published
- 2011
110. Boredom: An Emotional Experience Distinct from Apathy, Anhedonia, or Depression
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John D. Eastwood, Yael Goldberg, James Danckert, and Jennifer G. LaGuardia
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Clinical Psychology ,Social Psychology ,medicine ,Anhedonia ,Apathy ,Boredom ,medicine.symptom ,Psychology ,Structural equation modeling ,Developmental psychology - Abstract
Boredom is a universal human experience which has received little empirical attention. Researchers have yet to agree on a unified definition of boredom and many see it as a secondary symptom to other psychological states (e.g., apathy depression). We explored the relationship between boredom and three phenomenologically related states; apathy, anhedonia and depression. Structural equation modeling revealed that although related to each state to varying degrees, boredom is empirically distinct. Establishing boredom as an independent construct provides an important step in bringing the field closer to a universally accepted definition of the experience, which will ultimately facilitate more effective assessment and treatment of boredom.
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- 2011
111. Two BRCA1/2 founder mutations in Jews of Sephardic origin
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Yael Goldberg, Tamar Peretz, Avital Eilat, Michal Sagi, Tamar Hamburger, Dani Bercovich, Israela Lerer, and Liat Ben Avi
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Adult ,Male ,Heterozygote ,Cancer Research ,endocrine system diseases ,Judaism ,Breast Neoplasms ,Middle East ,Young Adult ,Breast cancer ,Africa, Northern ,Risk Factors ,Ethnicity ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Family history ,skin and connective tissue diseases ,Genetics (clinical) ,Aged ,Genetic testing ,BRCA2 Protein ,Ovarian Neoplasms ,medicine.diagnostic_test ,BRCA1 Protein ,business.industry ,Haplotype ,Middle Aged ,medicine.disease ,Founder Effect ,humanities ,Ashkenazi jews ,Pedigree ,Haplotypes ,Oncology ,High risk families ,Jews ,Mutation ,Female ,business ,Founder effect - Abstract
Founder mutations in BRCA1/2 genes have been detected in several Jewish communities in Israel, including in Ashkenazi Jews and Jews who immigrated to Israel from Iraq, Yemen, Iran and Afghanistan. We analyzed DNA samples of patients of Sephardic origin (descendents of Jews from the Iberian Peninsula) with breast cancer (BC) and/or ovarian cancer (OC) and additional family history of these cancers. In this study we identified 2 mutations: p.A1708E in BRCA1 and c.67 + 1G > A (IVS2 + 1G > A) in BRCA2, each in 3 unrelated patients. The frequency of the two mutations was 26–31% among Sephardic high risk families and about 3% among the full cohort of 177 patients of this origin who were tested in our center. Based on haplotype analysis we concluded that these mutations are most probably founder mutations in Sephardic Jews. We recommend testing the two mutations in women of Sephardic origin who apply for BRCA testing because of personal and/or family history of BC and/or OC. Furthermore, we suggest adding them to the 5 mutations included in “The Jewish panel” of BRCA1/2 mutations that are being tested in Israel.
- Published
- 2010
112. EPID-09. CMMRD (CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY) ASSOCIATED-BRAIN TUMORS: REPORT FROM THE EUROPEAN C4CMMRD CONSORTIUM
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Pascale Varlet, Felipe Andreiuolo, Karin Dahan, Enrico Opocher, Vanesa Pérez Alonso, Jacques Grill, Sheila Unger, Christine Devalck, Michaela Kuhlen, Franck Bourdeaut, Laurence Brugières, Katharina Wimmer, Chrystelle Colas, Astrid-Marie Sehested, Maurizio Genuardi, Yael Goldberg, Léa Guerrini-Rousseau, and Irene Slavc
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Medulloblastoma ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,medicine.medical_specialty ,Hematology ,business.industry ,medicine.medical_treatment ,Childhood cancer ,Immunotherapy ,medicine.disease ,Abstracts ,Germline mutation ,Oncology ,Internal medicine ,medicine ,Cancer research ,MISMATCH REPAIR DEFICIENCY ,DNA mismatch repair ,Neurology (clinical) ,business ,Gene - Abstract
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome (OMIM#276300) due to biallelic germline mutations in MMR genes, leading to a broad spectrum of childhood malignancies including brain, hematologic and colorectal cancers associated with café-au-lait macules (CALM). METHODS: Malignant brain tumors (BT) were reported in 48/78 patients (10 countries), registered in the C4MMRD database. RESULTS: Overall, 55 BT (47 high-grade gliomas (HGG) and 8 embryonal tumors) were diagnosed in 48 patients between 1988-2017. Median age at the first BT was 9.1y (1.1-40.6) with 8 patients over 18y. Twenty-eight patients developed multiple malignancies (including 17 before the BT). Twenty/37 families were consanguineous. All patients had biallelic germline mutations in MMR genes: PMS2 (26pts), MSH6 (10pts), MSH2 (7pts) and MLH1 (5pts). All patients with available cutaneous data but one had CALM. In addition several patients presented developmental brain anomalies. Most patients received standard treatment before immunotherapy era, without unusual treatment-related toxicity. Median survival after the first BT was 2y. Five-year overall-survival was 23% (95%-CI, 12-41) and 45% (95%-CI, 17-76) for HGG and embryonal tumors respectively. Ten patients are alive (7 HGG and 3 medulloblastomas) at last follow-up. Among the 38 deaths, 33 patients died because of their BT (first BT=28, second BT=5) and 5 of other cancers. CONCLUSION: Despite a high risk of multiple malignancies, this series suggests that some patients may be long-term survivors. Prognosis could be improved by early recognition of this rare condition leading to more specific treatments including immunotherapy and screening for second malignancies.
- Published
- 2018
113. Dopamine Depletion Impairs Frontostriatal Functional Connectivity during a Set-Shifting Task
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Atsuko Nagano-Saito, Alain Dagher, Marco Leyton, Yael Goldberg, Oury Monchi, and Yong He
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Adult ,Male ,Dopamine ,Hippocampus ,Neuropsychological Tests ,Double-Blind Method ,Neural Pathways ,Basal ganglia ,Image Processing, Computer-Assisted ,Psychophysics ,Reaction Time ,medicine ,Humans ,Attention ,Amino Acids ,Prefrontal cortex ,Food, Formulated ,Brain Mapping ,medicine.diagnostic_test ,General Neuroscience ,Cognitive flexibility ,Psychophysiological Interaction ,Articles ,Magnetic Resonance Imaging ,Corpus Striatum ,Frontal Lobe ,Oxygen ,Posterior cingulate ,Female ,Psychology ,Functional magnetic resonance imaging ,Neuroscience ,medicine.drug - Abstract
We investigated the effect of transient dopamine depletion on functional connectivity during performance of the Wisconsin Card Sorting Task. Functional magnetic resonance imaging data were analyzed as a psychophysiological interaction, a statistical method used to identify functional connectivity during experimental manipulations. Nineteen healthy subjects were scanned, double blind, on 2 separate days: once after drinking an amino acid mixture deficient in the dopamine precursors tyrosine and phenylalanine, and once after drinking a nutritionally balanced mixture. In the balanced drink session, statistically significant connectivity between the frontal lobes and striatum was observed during set shifting, and the greater the prefrontostriatal connectivity, the faster the response time after a shift. Neither of these associations were observed after dopamine depletion. Moreover, dopamine depletion also reduced the degree of deactivation in areas normally suppressed during attention-demanding tasks, including the medial prefrontal cortex, posterior cingulate cortex, and hippocampus. Together, these results suggest that functional connectivity between the frontal lobes and basal ganglia during set shifting contributes to more efficient performance and that dopamine modulates this corticostriatal connectivity.
- Published
- 2008
114. Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity
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Hagit N, Baris, Inbal, Barnes-Kedar, Helen, Toledano, Marisa, Halpern, Dov, Hershkovitz, Alexander, Lossos, Israela, Lerer, Tamar, Peretz, Revital, Kariv, Shlomi, Cohen, Elizabeth E, Half, Nurit, Magal, Valerie, Drasinover, Katharina, Wimmer, Yael, Goldberg, Dani, Bercovich, and Zohar, Levi
- Subjects
Adenosine Triphosphatases ,Male ,Adolescent ,Lymphoma ,Cafe-au-Lait Spots ,Nuclear Proteins ,Colorectal Neoplasms, Hereditary Nonpolyposis ,DNA Mismatch Repair ,Immunohistochemistry ,Founder Effect ,Pedigree ,DNA-Binding Proteins ,Consanguinity ,Young Adult ,DNA Repair Enzymes ,MutS Homolog 2 Protein ,Child, Preschool ,Mutation ,Humans ,Female ,Israel ,Child ,MutL Protein Homolog 1 ,Adaptor Proteins, Signal Transducing ,Mismatch Repair Endonuclease PMS2 - Abstract
Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with café au lait spots and axillary freckling mimicking neurofibromatosis type 1.We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer.In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified.CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis.
- Published
- 2015
115. Prenatal Sonographic Diagnosis of Grebe Syndrome
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Dwight R. Cordero, Michael W. Kilpatrick, Susan Klugman, Susan J. Gross, Donald Basel, Yael Goldberg, and Petros Tsipouras
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Adult ,Grebe syndrome ,Axial skeleton ,Context (language use) ,Prenatal diagnosis ,Osteochondrodysplasias ,Ultrasonography, Prenatal ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Craniofacial ,Grebe ,Radiological and Ultrasound Technology ,Polydactyly ,biology ,business.industry ,Brachydactyly ,Syndrome ,Anatomy ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Pregnancy Trimester, Second ,Female ,business - Abstract
Grebe syndrome or Grebe-type chondrodysplasia, 1 first described in 2 sisters by Grebe, 2 , 3 is an autosomal recessive disorder resulting from abnormal skeletal development of the limbs. 4 The phenotype of this nonlethalchondrodysplasia is characterized by severe acromesomelic dysplasia and dysmorphic distal appendages in the context of normal development of the craniofacial and axial skeleton. Although considered a nonlethal chondrodysplasia, a number of cases of Grebe syndrome results in stillbirth or infant mortality. Children with Grebe syndrome have considerable physical limitations but normal intelligence. Obligate carriers have normal stature and can have a variety of mild skeletal abnormalities, including polydactyly, brachydactyly, and positional abnormalities. 4 , 5 Here, we report the prenatal diagnosis of Grebe syndrome based on targeted second-trimester sonography.
- Published
- 2006
116. An Unusual Uterine Cavity Phenomenon
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Eran Meir Segev, Yael Goldberg, and Ofer Lavie
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Pathology ,medicine.medical_specialty ,Text mining ,medicine.anatomical_structure ,business.industry ,MEDLINE ,medicine ,Obstetrics and Gynecology ,Uterine cavity ,business - Published
- 2015
117. Clinical and ultrasonographic weight estimation in large for gestational age fetus
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Yael Goldberg, Eliezer Shalev, Ronit Beck-Fruchter, Izhar Ben-Shlomo, and Zeev Weiner
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Shoulder ,medicine.medical_specialty ,Birth trauma ,Gestational Age ,Sensitivity and Specificity ,Ultrasonography, Prenatal ,Fetal Macrosomia ,Pregnancy ,Humans ,Medicine ,Prospective Studies ,Fetus ,Cesarean Section ,business.industry ,Obstetrics ,Ultrasound ,Pregnancy Outcome ,Follow up studies ,Obstetrics and Gynecology ,Gestational age ,Delivery, Obstetric ,medicine.disease ,Dystocia ,female genital diseases and pregnancy complications ,Fetal Weight ,Reproductive Medicine ,Weight estimation ,Gestation ,Female ,business - Abstract
To examine prospectively the effect on pregnancy outcome of a management protocol, that adds ultrasonographic weight estimation in fetuses suspected clinically as large.Prospective follow up study of all singleton deliveries during a 1 year period. All patients underwent routine clinical estimation of fetal weight. When clinical estimation of fetal weight wasor = 3700 g, patients were referred for ultrasonographic estimation of fetal weight. When the latter wasor = 4000 g the patient was informed about the risks of birth trauma. Cesarean section was recommended only whenor = 4500 g. Ultrasonography was repeated every 4 days when possible. Predictive values of clinical and ultrasonographic estimations of fetal weight for diagnosing macrosomia, defined for the purpose of this study as 4000 g or more, and their effect on the rate of cesarean sections.Five hundred fifty-five (14.4%) out of 3844 singletons were estimated as 3700 g or more. Only 315 fetuses had ultrasonographic estimation of weight within 3 days of delivery. The sensitivity of clinical and ultrasonographic prediction of macrosomia was 68 and 58%, respectively. Cesarean section rate in newborns weighing 4000 g or more was 22% when macrosomia was clinically suspected compared to 11% when it was not (P0.05). In fetuses estimated ultrasonographically as 4000 g or larger the cesarean section rate was doubled (50.7% versus 24.9%, P0.05) compared to those estimated as smaller than 4000 g, although actual weight of 4500 g or more was recorded in 10.6 and 8.5% of these groups, respectively. There were no cases of shoulder dystocia in macrosomic babies when macrosomia was not detected by ultrasound compared to two cases of shoulder dystocia (2.7%) when macrosomia was detected by ultrasound.Antenatal suspicion of macrosomia increased the cesarean section rate while the associated improvement in pregnancy outcome remains questionable. The contribution of ultrasound, added to routine clinical estimation of fetal weight, was clinically insignificant apart from a further increase in cesarean section rate.
- Published
- 2002
118. Unique Features of Grem1 Related Hereditary Mixed Polyposis in Four Ashkenazi Families and Their Implications for Screening Recommendations
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Sari Lieberman, Tomer Adar, Ephrat Levy Lahad, Menachem Schechter, Yael Goldberg, and Eran Goldin
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Hepatology ,Gastroenterology - Published
- 2017
119. 'I do not want my baby to suffer as I did'; prenatal and preimplantation genetic diagnosis for BRCA1/2 mutations: a case report and genetic counseling considerations
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Ruth Gershoni-Baruch, Efrat Dagan, Yael Goldberg, Alina Kurolap, and Georgeta Fried
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Adult ,Genetic Markers ,medicine.medical_specialty ,Genetic counseling ,Genes, BRCA2 ,Genetic Carrier Screening ,MEDLINE ,Genes, BRCA1 ,Prenatal diagnosis ,Breast Neoplasms ,Genetic Counseling ,Preimplantation genetic diagnosis ,Cancer syndrome ,Prenatal Diagnosis ,medicine ,Humans ,Psychiatry ,Genetics (clinical) ,Health policy ,Preimplantation Diagnosis ,business.industry ,General Medicine ,medicine.disease ,Mutation (genetic algorithm) ,Mutation ,Female ,business - Abstract
This article presents the complexity of prenatal genetic diagnosis and preimplantation genetic diagnosis for hereditary breast-ovarian cancer syndrome. These issues are discussed using a case report to highlight the genetic counseling process, together with decision-making considerations, in light of the clinical, psychological, and ethical perspectives, of both the mutation carriers and health professionals; and the health policy regarding these procedures in Israel compared to several European countries.
- Published
- 2014
120. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium 'Care for CMMR-D' (C4CMMR-D)
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Jan Loeffen, G Sebille, Birgit Burkhardt, Martine Muleris, Olivier Caron, Franck Bourdeaut, Zeinab Ghorbanoghli, Chrystelle Colas, Denisa Ilencikova, Laurence Brugières, Christian P. Kratz, Alex Duval, Natacha Entz-Werle, Noémie Lavoine, Hans F. A. Vasen, Odile Cabaret, Yael Goldberg, Katharina Wimmer, Fred H. Menko, Pediatrics, Human genetics, and CCA - Oncogenesis
- Subjects
Pediatrics ,medicine.medical_specialty ,CMMR-D ,Colorectal cancer ,Gene mutation ,Guidelines ,Digestive System Neoplasms ,Neoplasms ,Epidemiology ,Genetics ,PMS2 ,Medicine ,Humans ,Genetics (clinical) ,Tumour spectrum ,Leukemia ,Surveillance ,business.industry ,Brain Neoplasms ,Neurooncology ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,DNA Repair-Deficiency Disorders ,Lynch syndrome ,MSH6 ,MSH2 ,Population Surveillance ,Mutation ,business ,Colorectal Neoplasms ,Constitutional mismatch repair deficiency - Abstract
Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as ‘constitutional mismatch repair-deficiency’ (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.
- Published
- 2014
121. Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients
- Author
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Shai Rosenberg, Hanoch Goldshmidt, Hovav Nechushtan, Amir Sonnenblick, Mark Temper, Beatrice Uziely, David Edelman, Alexander Lossos, Yael Goldberg, Amichai Meirovitz, Ayala Hubert, Michal Lotem, Eli Pikarsky, Tamar Peretz, Eli Sapir, Iris Fried, Daniela Katz, Yakir Rottenberg, Ruth Finklstein, and Aviad Zick
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,precision medicine ,Genetic counseling ,neoplasms ,Observational Study ,Disease ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Treatment plan ,Internal medicine ,medicine ,Humans ,Mutation detection ,Medical history ,030212 general & internal medicine ,Young adult ,Stage (cooking) ,Aged ,Aged, 80 and over ,Massive parallel sequencing ,business.industry ,High-Throughput Nucleotide Sequencing ,Cancer ,General Medicine ,DNA ,Hematology ,Middle Aged ,Precision medicine ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,Mutation ,Retreatment ,Feasibility Studies ,Female ,business ,Research Article - Abstract
Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation. A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature. The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression. This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer patients.
- Published
- 2016
122. Internal Jugular Vein Blood Flow in Normal and Growth-Restricted Fetuses
- Author
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Zeev Weiner, Eliezer Shalev, and Yael Goldberg
- Subjects
Adult ,Duplex ultrasonography ,Pregnancy Trimester, Third ,Diastole ,Hemodynamics ,Gestational Age ,Inferior vena cava ,Ultrasonography, Prenatal ,Fetus ,Pregnancy ,medicine.artery ,Medicine ,Humans ,Internal jugular vein ,Fetal Growth Retardation ,business.industry ,Brain ,Obstetrics and Gynecology ,Umbilical artery ,Ultrasonography, Doppler ,Anatomy ,Blood flow ,Cerebral blood flow ,medicine.vein ,Regional Blood Flow ,Pregnancy Trimester, Second ,Pulsatile Flow ,cardiovascular system ,Female ,Jugular Veins ,business - Abstract
To assess internal jugular vein blood flow patterns during the second half of pregnancy in normal and growth-restricted fetuses.We did Doppler ultrasound studies of internal jugular veins and the inferior vena cavas longitudinally on 21 normal singleton fetuses from 20 weeks to term, and on eight growth-restricted fetuses with absent end-diastolic flow at the umbilical artery (UA). The three components of the venous flow velocity waveforms were used to calculate peak velocity ratio: Peak systolic velocity (S wave) minus reverse peak velocity (R wave) divided by peak velocity during early diastole (D wave) and velocity time integral ratio: systolic velocity time integral minus reverse velocity time integral divided by velocity time integral during early diastole. Statistical analysis of longitudinal measurements used K-related samples Friedman test; groups were compared with Mann-Whitney U test and chi(2) test.In normal fetuses we found significant increases in peak velocity ratio and velocity time integral ratio of internal jugular veins and the inferior vena cavas throughout gestation. The mean +/- standard deviation (SD) of the internal jugular veins peak velocity ratio (1.12 +/- 0.4 versus 1.46 +/- 0.15, P.05) and velocity time integral ratio (1.1 +/- 0.2 versus 1.55 +/- 0.17, P.05) were significantly lower in growth-restricted fetuses compared with normal fetuses at 28-32 weeks' gestation but inferior vena cava indices were not. None of the eight growth-restricted fetuses had umbilical venous pulsations or changes in inferior vena cava or ductus venosus blood flow patterns. All had arterial pH above 7.15 at birth.Growth-restricted fetuses with absent end-diastolic velocity in the UA have changes in internal jugular vein blood flow patterns that probably indicate increased cerebral blood flow, more evidence of redistribution of blood flow in growth-restricted fetuses that can be used to maintain them.
- Published
- 2000
123. Congenital pulmonary myofibroblastic tumor—pathology and prenatal sonographic appearance
- Author
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Ari Reiss, Yael Goldberg, Mariana Monichor, and Arie Drugan
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,medicine ,Obstetrics and Gynecology ,Radiology ,Tumor Pathology ,business ,Genetics (clinical) - Published
- 2005
124. Genetic predisposition to radiation induced sarcoma: possible role for BRCA and p53 mutations
- Author
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Israela Lerer, Tamar Hamburger, Tamar Peretz, Yael Goldberg, Luna Kadouri, and Michal Sagi
- Subjects
Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Pathology ,Heterozygote ,Neoplasms, Radiation-Induced ,Cancer-Predisposing Gene ,Population ,Breast Neoplasms ,Breast cancer ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Angiosarcoma ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,education ,BRCA2 Protein ,education.field_of_study ,Radiotherapy ,business.industry ,BRCA1 Protein ,Incidence (epidemiology) ,Sarcoma ,Middle Aged ,medicine.disease ,Genes, p53 ,Mutation (genetic algorithm) ,Mutation ,Female ,business ,Follow-Up Studies - Abstract
The estimated incidence of radiation-associated sarcoma (RAS) is 0.03–0.2 % in 5 years post treatment. Most cancer predisposing genes are involved in DNA repair; therefore, elevated RAS risk in these patients is plausible. Cases of angiosarcoma post breast cancer treatment were reported in BRCA1 and BRCA2 carriers. We report the genetic evaluation of seven cases with suspected RAS from patients counseled in our cancer-genetic clinic. Of 2,885 breast cancer patient, 470 were BRCA1 or two mutation carriers and three were p53 mutation carriers. Of them seven developed sarcoma in the field of irradiation; five in the chest wall and two in other sites. Genetic evaluation revealed BRCA1 mutation in two, BRCA2 mutation in additional patient and a carrier of p53 mutation. The estimation of risk for RAS in patients with genetic predisposition is limited due to the rarity of this event, and the bias in referral to the clinic toward younger age. With these limitations the rate of RAS is 0.43 % (2/470, 95 % CI −0.17 to 1.02, SE = 0.3) in this group in a median follow-up of 8.2 years (range 1 month to 51 years). If we assume irradiation for the breast in 80 % of the patients than rate of RAS in group is proximately 0.53 % (2/376, 95 % CI −0.21 to 1.26, SE = 0.37). A BRCA1 carrier which had sarcoma after irradiation to head and neck carcinoma was not included in these analyses. In conclusion, we found a high frequency of BRCA1/2 mutation among our patients diagnosed with RAS. However, we estimated approximately twofold increase in the risk of RAS in BRCA1/2 carriers which was not significant compared to reports in general population. Therefore, RAS is a rare event in BRCA carriers as in the general population, and should not be considered in the decision regarding irradiation treatment in this population.
- Published
- 2013
125. Neurofibromatosis Type 1—An Update and Review for the Primary Pediatrician
- Author
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Kurt M. Dibbern, Yael Goldberg, Jana Klein, Vincent M. Riccardi, and John M. Graham
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Neurofibromatosis 1 ,Genetic Counseling ,Primary care ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,030225 pediatrics ,Genes, Neurofibromatosis 1 ,medicine ,Humans ,Neurofibromatosis ,Child ,business.industry ,Incidence (epidemiology) ,Infant ,medicine.disease ,Multisystem disease ,El Niño ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,Delivery of Health Care - Abstract
With an incidence of 1 in 3,000, neurofibromatosis type 1 (NFl), or von Recklinghausen disease, is one of the most common genetic disorders encountered by primary care physicians. NFI is a multisystem disease that affects more than one million people worldwide (more than 80,000 in the United States). Although most pediatricians have patients with NFl in their practices, many affected individuals go undiagnosed as children. This article is intended to facilitate the diagnosis and management of young patients with NFl.
- Published
- 1996
126. [Management of hereditary non-polyposis syndrome (Lynch syndrome)]
- Author
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Revital, Kariv, Yael, Goldberg, Irit, Soler, Gie, Rosner, Elizabeth, Half, Menachem, Moshkowitz, Alex, Vilkin, Zohar, Levi, and Yaron, Niv
- Subjects
Risk ,Genetic Carrier Screening ,Jews ,Mutation ,Humans ,Genetic Predisposition to Disease ,Microsatellite Instability ,Genetic Testing ,Colorectal Neoplasms, Hereditary Nonpolyposis ,DNA Mismatch Repair - Abstract
Genetic background is suspected in about 20% of colorectal cancer (CRC) cases, in which either genetic polymorphisms or Mendelian heritable factors are involved. Currently known CRC syndromes include various polyposis syndromes (1% of total CRC cases) and Lynch syndrome (LS), previously termed hereditary nonpolyposis colorectal cancer (HNPCC, comprises 3-5% of all CRC cases). LS is caused by dominantly inherited mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and results in a very high lifetime risk (approximately 80%) for CRC and significantly increased risk for extracolonic tumors in regions such as the endometrium, ovary, urinary tract, lymphoma, stomach, pancreas small bowel and brain. Carriers are advised to undergo specific medical and intense endoscopic surveillance. Diagnosis of carriers is mandatory for providing appropriate recommendations for surveillance, which was shown to decrease morbidity, mortality and health costs. Diagnosis of LS dictates preventive surgical procedures for the colon endometrium and ovaries, and assists in decisions regarding CRC chemotherapy. Family members' screening and surveillance is determined by mutation testing. Diagnosis is performed, based on the clinical selection criteria of Amsterdam and Bethesda and according to typical histology of tumor tissue. Initially, tumor testing is performed by either microsatellite instability (MSI), immunohistochemistry (IHC) or both. Certain Jewish ethnical subgroups may undergo founder mutation testing. Ultimate identification of the mutation by sequencing and MLPA is performed according to the IHC results. In families with hereditary CRC criteria, in which workup for LS is negative, the surveillance protocol will be determined by an experienced multidisciplinary team, including a formal genetic consultation.
- Published
- 2011
127. [Guidelines for diagnosis, treatment, surveillance and prevention of cancer in patients with familial non-adenomatous polyposis]
- Author
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Elizabeth, Half, Yael, Goldberg, Revital, Kariv, Ornit, Cohen-Ezra, Alex, Vilkin, Zohar, Levi, Menachem, Moshkowitz, and Yaron, Niv
- Subjects
Patient Care Team ,Risk ,Hyperplasia ,Intestinal Polyposis ,Peutz-Jeghers Syndrome ,Colonic Polyps ,Humans ,Mass Screening ,Israel ,Colorectal Neoplasms - Abstract
Approximately 30% of colorectal cancers exhibit familial clustering. Currently, we recognize a number of different types of polyps and polyposis syndromes that are classified according to the histology of the typical polyp. We differentiate between adenomas, hyperplastic, and hamartomatous polyps as well as between syndromes that are manifested by 10-100 or above 100 polyps. It is essential to distinguish between these syndromes as each has a different mode of presentation, spectrum of signs and symptoms and cancer risk associated with them. With the knowledge accumulating, we now have the tools to lower the risk of cancer by performing specific screening programs that are tailored to each syndrome. In these guidelines we focus on the non-adenomatous polyps, hyperplastic and hamartomatous polyposis syndromes. We outline the importance of multi-sector team work that includes the family practitioner, gastroenterologist, pathologist, genetic counselor, surgeon, and social worker.
- Published
- 2011
128. [The Israeli recommendations for diagnosis, management, follow-up and prevention of colorectal cancer (CRC) in familial adenomatous polyposis]
- Author
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Elizabeth, Half, Yael, Goldberg, Revital, Kariv, Alex, Vilkin, Zohar, Levi, Menachem, Moshkowitz, and Yaron, Niv
- Subjects
Patient Care Team ,Risk ,Adenomatous Polyposis Coli ,Colonic Polyps ,Humans ,Mass Screening ,Israel ,Colorectal Neoplasms - Abstract
Approximately 30% of colorectal cancers exhibit familial clustering. We recognize different types of polyps and polyposis syndromes that are classified according to the histological diagnosis. We differentiate between adenomas, hyperplastic, and hamartomatous polyps as well as between syndromes that are manifested by 10-100 or above 100 polyps. Only about 1% of colorectaL cancers (CRCs) are due to adenomatous polyposis syndrome. It is essential to distinguish between these syndromes as each has a different mode of presentation, spectrum of signs and symptoms and cancer risk. With the knowledge that is accumulating we now have the tools to lower the risk of cancer by performing specific screening programs that are tailored to each syndrome specifically. We present the Israeli guidelines for management of adenomatous polyposis, based on the American and European experience and consensus. We outline the importance of mutti-sectorial team work that includes the family practitioner, gastroenterologist, pathologist, genetic counselor, surgeon and social worker.
- Published
- 2011
129. Limbic response to psychosocial stress in schizotypy: a functional magnetic resonance imaging study
- Author
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Josie Caro, Blaine Ditto, Elizabeth Streicker, Yael Goldberg, Alain Dagher, P. Vivien Rekkas, Gillian A. O'Driscoll, Alexandra Soliman, Jens C. Pruessner, and Ridha Joober
- Subjects
Male ,Psychosis ,Adolescent ,Hydrocortisone ,Personality Inventory ,Brain activity and meditation ,Schizotypy ,Striatum ,Schizotypal Personality Disorder ,Young Adult ,medicine ,Image Processing, Computer-Assisted ,Limbic System ,Humans ,Saliva ,Biological Psychiatry ,Psychiatric Status Rating Scales ,Brain Mapping ,medicine.diagnostic_test ,Dopaminergic ,Anhedonia ,medicine.disease ,Magnetic Resonance Imaging ,Oxygen ,Psychiatry and Mental health ,Schizophrenia ,Linear Models ,Female ,medicine.symptom ,Psychology ,Functional magnetic resonance imaging ,psychological phenomena and processes ,Stress, Psychological ,Clinical psychology - Abstract
Psychological stress causes dopamine release in the striatum and is thought to play a role in susceptibility to psychotic illness. Previous work suggests that an elevated dopaminergic response to stress may index vulnerability to psychosis in certain individuals. With functional magnetic resonance imaging, we measured stress-induced changes in brain activity in healthy individuals at elevated risk of developing psychosis. Participants were 15 controls and 25 psychometric schizotypes: 12 with positive symptom schizotypy (perceptual aberrations) and 13 with negative symptom schizotypy (physical anhedonia), as determined by questionnaires ( Chapman et al., 1976 , Chapman and Chapman, 1978 ). In the scanner, participants performed the Montreal Imaging Stress Task and a matched sensory-motor control task. Measures of self-reported stress and salivary cortisol levels were taken throughout the experiment. All three groups showed significant increases in self-reported stress and significant fMRI signal change in the striatal, limbic and cortical regions. However, the Physical Anhedonia group showed greater stress-induced striatal and limbic deactivation than the other two groups. Deactivation in the striatum was significantly correlated with Physical Anhedonia score across all subjects. Our findings suggest the presence of abnormalities in striatal response to stress in negative symptom schizotypy.
- Published
- 2010
130. Abstract P4-05-08: Oncotype Dx assay in BRCA positive ER positive breast cancer patients
- Author
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Tanir M. Allweis, L Kaduori, L Divinsky, Tamar Hamburger, Beatrice Uziely, Amir Sonnenblick, Daniela Katz, I Merlet, Michal Sagi, Bella Maly, Yael Goldberg, Naama Halpern, Tamar Peretz, and Einat Carmon
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,endocrine system diseases ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,BRCA mutation ,Cancer ,Estrogen receptor ,medicine.disease ,female genital diseases and pregnancy complications ,Breast cancer ,Internal medicine ,medicine ,Stage (cooking) ,skin and connective tissue diseases ,Oncotype DX ,business ,Tamoxifen ,medicine.drug - Abstract
Background: Oncotype DX is a 21-gene RT-PCR assay which quantifies the likelihood of breast cancer recurrence and the potential benefit of chemotherapy in patients with early stage, ER positive, Tamoxifen treated breast cancer. Breast cancer in BRCA carriers is considered more aggressive. The aim of our study was to evaluate whether Oncotype Dx recurrence score distribution is different in breast cancer patients with inherited BRCA mutation. Methods: The Oncotype DX assay has been used at Hadassah Medical Center since 2004 on specimens from over 450 patients. We analyzed and compared clinicopathological characteristics and Oncotype Dx recurrence scores of BRCA carriers versus non- BRCA or unknown status of BRCA patients. Results: Ten patients had validated inherited BRCA mutation, five of them are BRCA1 carriers and five BRCA2 carriers. There were no significant differences in the clinicopathological characteristics between the two groups. Oncotype Dx recurrence score distribution between low, intermediate and high risk groups was not significantly different. The mean recurrence score was 18.48 for the non- BRCA or unknown status of BRCA patients and 22.8 for the BRCA carriers patients. This difference was not statistically significant. Conclusion: Estrogen receptor positive breast cancer tumors from BRCA carriers does not display a significantly different Oncotype Dx recurrence score result distribution. These preliminary data suggest Oncotype Dx assay might be used to help tailor treatment in this subset of patients, although further follow up is needed. All patients evaluated for oncotype_DX All evaluated (except BRCA+) n = 456BRCA positiveP valueAgeMean57.4557.60.7 Median5857 Range56 (25-81)34 (42-76) T stageT167.7%70%0.9 T230.7%30% T31.6%0% Tumor sizeMean1.71.360.2 Median1.51.26 Range7.8 (0.2-8)1.3 (0.7-2) GradeGrade 1-278.8%60%0.15 Grade 321.2%40% RSLow50%40%0.57 Intermediate39.8%40% High10.2%20% RSMean18.4822.80.16 Median17.522.5 Range64 (0-64)27 (12-39) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-05-08.
- Published
- 2013
131. An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC
- Author
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Daliah Galinsky, Chen Shochat, Moran Savion, Yael Goldberg, Dvorah Abeliovich, Revital Kariiv, Dani Bercovich, Tamar Hamburger, Tamar Peretz, Liat Ben-Avi, Rinnat M. Porat, Hana Strul, Eli Pikarsky, Israela Lerer, Ayala Hubert, and Inbal Kedar
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Amsterdam criteria ,DNA Repair ,Genetic counseling ,Genes, BRCA2 ,MLH1 ,DNA Mismatch Repair ,Genetics ,Ethnicity ,Medicine ,Humans ,neoplasms ,Genetics (clinical) ,Aged ,Aged, 80 and over ,business.industry ,nutritional and metabolic diseases ,DNA Methylation ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,digestive system diseases ,Ashkenazi jews ,Lynch syndrome ,Pedigree ,MSH6 ,Oncology ,MSH2 ,Jews ,Mutation (genetic algorithm) ,Mutation ,Female ,business ,Gene Deletion - Abstract
Mutations in DNA mismatch repair genes underlie lynch syndrome (HNPCC). Lynch syndrome resulting from mutations in MSH6 is considered to be attenuated in comparison to that caused by mutations in MLH1 and MSH2, thus more likely to be under diagnosed. In this study we report of a common mutation in the MSH6 gene in Ashkenazi Jews. Genetic counseling and diagnostic work-up for HNPCC was conducted in families who attended the high risk clinic for inherited cancer. We identified the mutation c.3984_3987dup in the MSH6 gene in 19 members of four unrelated Ashkenazi families. This mutation results in truncation of the transcript and in loss of expression of the MSH6 protein in tumors. Tumor spectrum among carriers included colon, endometrial, gastric, ovarian, urinary, and breast cancer. All but one family qualified for the Bethesda guidelines and none fulfilled the Amsterdam Criteria. Members of one family also co-inherited the c.6174delT mutation in the BRCA2 gene. The c.3984_3987dup in the MSH6 gene is a mutation leading to HNPCC among Ashkenazi Jews. This is most probably a founder mutation. In contrast to the c.1906G>C founder mutation in the MSH2 gene, tumors tend to occur later in life, and none of the families qualified for the Amsterdam criteria. c.3984_3987dup is responsible for 1/6 of the mutations identified among Ashkenazi HNPCC families in our cohort. Both mutations: c.3984_3987dup and c.1906G>C account for 61% of HNPCC Ashkenazi families in this cohort. These findings are of great importance for counseling, diagnosis, management and surveillance for Ashkenazi families with Lynch syndrome.
- Published
- 2009
132. Homozygosity of MSH2 c.1906G--C germline mutation is associated with childhood colon cancer, astrocytoma and signs of Neurofibromatosis type I
- Author
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Eli Pikarsky, Helen Toledano, Isaac Yaniv, Hagit N. Baris, Dani Bercovich, Inbal Kedar-Barnes, Israela Lerer, Tamar Peretz, Chen Shochat, Rinnat M. Porat, Dvorah Abeliovich, and Yael Goldberg
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Neurofibromatosis 1 ,Adolescent ,Colorectal cancer ,DNA Mutational Analysis ,Biology ,Astrocytoma ,MLH1 ,medicine.disease_cause ,Germline mutation ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Child ,Genetics (clinical) ,Germ-Line Mutation ,Mutation ,Endometrial cancer ,Homozygote ,nutritional and metabolic diseases ,Microsatellite instability ,medicine.disease ,digestive system diseases ,Pedigree ,MSH6 ,DNA-Binding Proteins ,MutS Homolog 2 Protein ,Oncology ,MSH2 ,Colonic Neoplasms ,Female - Abstract
Hereditary non-polyposis colorectal cancer is a cancer predisposition syndrome known to be caused by heterozygous germline mutations in DNA mismatch repair genes (MMR) most commonly hMLH1, hMSH2, hMSH6. Heterozygous mutations in one of these genes confer an increased risk, mainly for colon and endometrial cancer. Recently, several publications identified that biallelic mutations in the MMR genes are associated with a more severe phenotype, including childhood malignancies and signs of neurofibromatosis type I (NF1). We report on a non-consanguineous Ashkenazi Jewish family with two affected siblings with features of NF1, colon cancer and astrocytoma at age 13 and 14. Their mother developed endometrial cancer at age 54. Their father had leukoplakia of the vocal cords with a family history of pancreatic cancer. Molecular and pathology studies were done on the tumor tissue and on genomic DNA of family members. Tumor testing demonstrated a high degree of microsatellite instability (MSI analysis), expression of MLH1 and absence of expression of both MSH2 and MSH6 proteins. A biallelic c.1906G > C (p.A636P) mutation in the hMSH2 gene was detected in the blood of one affected child. Parental genetic testing showed that each parent was heterozygote for the mutation. The c.1906G > C mutation is a founder mutation in the Ashkenazi Jewish population. To our knowledge this is the first report of homozygosity for this founder mutation.
- Published
- 2008
133. Resistance to activated protein C and the Leiden mutation: High prevalence in patients with abruptio placentae
- Author
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Yael Goldberg, Eliezer Shalev, Izhar Ben-Shlomo, and Zofnat Wiener-Megnagi
- Subjects
Adult ,medicine.medical_specialty ,Pregnancy Complications, Cardiovascular ,Thrombophilia ,Gastroenterology ,Pregnancy ,Internal medicine ,Prevalence ,medicine ,Factor V Leiden ,Humans ,Point Mutation ,Abruptio Placentae ,Activated Protein C Resistance ,business.industry ,Point mutation ,Factor V ,Obstetrics and Gynecology ,Odds ratio ,medicine.disease ,Case-Control Studies ,Mutation (genetic algorithm) ,Immunology ,Female ,Activated protein C resistance ,business ,Protein C ,medicine.drug - Abstract
Objective: The Leiden mutation, a point mutation in the gene encoding coagulation factor V, is associated with a high frequency of thromboembolic phenomena. It has recently been connected with adverse outcomes of pregnancy. We carried out this study to define its connection with abruptio placentae. Study Design: Twenty-seven women who had abruptio placentae and 29 control subjects matched for age, parity, and ethnic origin were studied. We studied all women for possible hypercoagulation defects. All women demonstrating resistance to activated protein C were studied for the presence of the factor V Leiden mutation. Results: Seventeen of 27 case patients had an activated protein C ratio ≤2.5, compared with 5 of 29 control subjects (odds ratio 8.16, 95% confidence interval 3.6-12.75, P = .00125). Participants with activated protein C ratios ≤2.5 underwent deoxyribonucleic acid analysis. Eight case patients were found to have the factor V Leiden mutation (5 heterozygous and 3 homozygous, 29.6%), compared with 1 heterozygote among the control subjects who were tested (3.4%). Conclusion: Factor V Leiden mutation was found quite frequently in patients with abruptio placentae. (Am J Obstet Gynecol 1998;179:1565-7.)
- Published
- 1998
134. Mutation spectrum in HNPCC in the Israeli population
- Author
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Israela Lerer, Rinnat M. Porat, Tamar Peretz, Suzan Mendelson, Dvorah Abeliovich, Aviram Nissan, Tamar Hamburger, Yael Goldberg, Ayala Hubert, Chen Shochat, Eli Pikarski, Inbal Kedar, Dani Bercovich, Avital Eilat, Michal Sagi, and Luna Kadouri
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Sequence analysis ,Population ,Biology ,DNA Mismatch Repair ,Population Groups ,Genetics ,medicine ,Humans ,Israel ,education ,Gene ,Genetics (clinical) ,Retrospective Studies ,education.field_of_study ,Microsatellite instability ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Ashkenazi jews ,Human genetics ,Pedigree ,Oncology ,Jews ,Mutation (genetic algorithm) ,Mutation ,DNA mismatch repair ,Female ,Algorithms - Abstract
Hereditary non-polyposis colon cancer is caused by mutations in DNA mismatch repair genes. The mutation spectrum in the Israeli population is poorly documented except for the c.1906G>C Ashkenazi founder mutation in the hMSH2 gene. To report our experience in HNPCC screening, the mutations detected and the clinical features among a cohort of Israeli patients. Diagnostic work-up was done in a multi-step process guided by clinical and ethnic information. Tumors of suspected patients were tested for microsatellite instability and immunohistochemistry. Based on tumor analyses, we proceeded to mutation screening by DHPLC followed by sequence analysis and multiplex ligase dependent probe amplification. Ashkenazi Jews were first tested for the c.1906G>C founder mutation. Of the 240 families, 24, including Arabs and Jews from different ethnic origins, were tested positive. All tumors that lost expression of mismatch repair proteins also showed microsatellite instability. There was evidence for involvement of hMSH2 (15) hMLH1 (6) and hMSH6 (3) genes. Mutations were identified in 17/24 (71%) patients: 6 Ashkenazi families harbored the c.1906G>C mutation. Eleven other mutations (2 nonsense, 3 splice site and 6 small deletions) were detected. Three of the mutations are novel. No gross deletions or insertions were detected. This is the first report that characterizes the profile of HNPCC in a cohort of patients in Israel. Tumor testing indicated that the 3 main MMR genes are involved, and that mutation spectrum is broad.
- Published
- 2007
135. Pelvic splenosis mimicking an ovarian mass: a non-invasive approach
- Author
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Yakir, Segev, Ofer, Lavie, Yael, Goldberg, Yuval, Kaufman, Gil, Peerl, Sara, Gips, Dorit, Eizenberg, and Ron, Auslander
- Subjects
Diagnosis, Differential ,Ovarian Neoplasms ,Technetium Tc 99m Sulfur Colloid ,Splenectomy ,Humans ,Female ,Middle Aged ,Radiopharmaceuticals ,Radionuclide Imaging ,Splenosis - Published
- 2007
136. [A new oncogenetic service of counseling and diagnosing for hereditary non-polyposis colorectal cancer (HNPCC)]
- Author
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Yael, Goldberg, Rinnat, Porat, Michal, Sagi, Avital, Eilat, Inbal, Kedar, Chen, Shochat, Suzan, Mendelson, Tamar, Hamburger, Aviram, Nissan, Ayala, Hubert, Stavit, Shalev, Dani, Bercovich, Eli, Pikarski, Israela, Lerer, Dvorah, Abeliovich, and Tamar, Pretetz
- Subjects
Male ,MutS Homolog 2 Protein ,Base Pair Mismatch ,Humans ,Nuclear Proteins ,Female ,Genetic Counseling ,MutL Protein Homolog 1 ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Hospital Units ,Chromatography, High Pressure Liquid ,Adaptor Proteins, Signal Transducing ,Probability - Abstract
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome associated with a high risk for colorectal cancer (up to 80%), endometrial cancer (up to 60%), and increased risk for other malignancies, mostly ovarian and urinary system tumors. HNPCC is caused by a germline mutation in one of the mismatch repair (MMR) genes, mainly hMLH1, hMSH2 and hMSH6. The tumors present with microsatellite instability (MSI) associated with loss of heterozygosity of the affected gene, and with loss of expression of the gene product. Diagnosis of HNPCC involves tumor testing for MSI, immunohistochemistry staining and germ line mutation analysis of the suspected gene. Proper genetic counseling is based on the synthesis of the clinical, pathological and molecular data. Directed surveillance shows significant reduction in colon cancer incidence, cancer mortality and overall mortality among HNPCC patients.To establish a multidisciplinary service for patients suspected of having HNPCC.We have established a service which is based on tight collaboration between clinical departments and laboratories. The clinical work-up was conducted by a special oncogenetic clinic and the laboratory service consisted of tissue testing for MSI and immunohistochemistry, denaturing high performance liquid chromatography (DHPLC) for suspected genes, and mutation testing.The efficiency of detection of patients with HNPCC was high, completed in a multistep process. In the first year of our collaborative work, we have provided genetic counseling to over 100 families and performed suitable tests for 46 families. Among them we have identified more than 16 families with HNPCC; 4 showed absence of hMLH1, 1 showed absence of hMSH6, and 11 showed absence of hMSH2. All tumors that showed MSI also showed absence of either one of the three MMR proteins. We present the clinical, pathological and molecular features of our patients and discuss the implication of this data on future recommendations.
- Published
- 2007
137. Antiphospholipid Syndrome Manifested by Ischemic Stroke in a Patient with Crohn's Disease
- Author
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Daniel Rachmilewitz, Yael Goldberg, John M. Gomori, and Dror Mevorach
- Subjects
Adult ,Crohn's disease ,medicine.medical_specialty ,Pathology ,Lupus anticoagulant ,Vascular disease ,business.industry ,Gastroenterology ,Ischemia ,Antiphospholipid Syndrome ,medicine.disease ,Inflammatory bowel disease ,Brain Ischemia ,Crohn Disease ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Cardiology ,Humans ,Female ,cardiovascular diseases ,Risk factor ,business ,Stroke - Abstract
Cerebrovascular accidents are rare but well documented in patients with Crohn's disease. Up to 10% of hypercoagulable state manifestations reported in association with inflammatory bowel disease are ischemic strokes. However, no clear mediating factor has thus far been suggested. A 44-year-old woman with Crohn's disease for 25 years developed a left temporal stroke associated with anticardiolipin antibody and lupus anticoagulant suggesting antiphospholipid syndrome. A thorough evaluation did not reveal any other risk factor for ischemic stroke. No possible sources of emboli were found in the carotids and heart, and no deficiencies of protein C and activated protein C, protein S, and anti-thrombin III leading to hypercoagulable state were present. There may be a possible association between antiphospholipid syndrome and hypercoagulable state in Crohn's disease.
- Published
- 1996
138. Right-Sided Endocarditis Due to Staphylococcus aureus
- Author
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Yael Goldberg, Ronen Jaffe, Naftali Kaminski, Izidore S. Lossos, and Mitchell J. Schwaber
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Infectious Diseases ,Right sided endocarditis ,Staphylococcus aureus ,business.industry ,medicine ,medicine.disease_cause ,business ,Surgery - Published
- 1995
139. Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation
- Author
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Ilana Chervinski, Rivka Ofir, Tamar Harel, Stavit A. Shalev, Yael Goldberg, and Ohad S. Birk
- Subjects
Adult ,Male ,Genetic Linkage ,DNA Mutational Analysis ,Mutation, Missense ,Consanguinity ,Biology ,Muscular Dystrophies ,Exon ,Genetic linkage ,Genetics ,medicine ,Missense mutation ,Humans ,Pentosyltransferases ,Muscular dystrophy ,Age of Onset ,Israel ,Genetics (clinical) ,Haplotype ,Genetic Variation ,Proteins ,medicine.disease ,Arabs ,Pedigree ,Phenotype ,Haplotypes ,Congenital muscular dystrophy ,Female ,Limb-girdle muscular dystrophy - Abstract
Limb-girdle muscular dystrophies (LGMDs) represent a group of diseases characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. The clinical heterogeneity is paralleled by molecular heterogeneity; each of the 10 forms of autosomal-recessive LGMD recognized to date is caused by mutations in a distinct gene. In a large consanguineous Bedouin tribe living in northern Israel, 15 individuals affected by LGMD demonstrate an autosomal recessive pattern of inheritance. A genome-wide screen followed by fine mapping in this family revealed linkage to a region on chromosome 19 harboring the fukutin-related protein gene (FKRP), with a maximal LOD score of 4.8 for D19S902. FKRP, encoding a putative glycosyltransferase, has been implicated in causing congenital muscular dystrophy 1C (MDC1C), and has recently been shown to be mutated in LGMD2I. We identified a novel missense mutation in exon 4 of the FKRP gene in all the patients studied. Although all affected individuals were homozygous for the same mutation, a marked phenotypic variability was apparent within the family. This finding may suggest a role of modifier genes and environmental factors in LGMD2I. Moreover, the demonstration that an identical, novel mutation in the FKRP gene can cause a muscle disease of either a congenital onset or of a later onset within a single family provides clinical support to the molecular evidence, suggesting that MDC1C and LGMD2I are overlapping ends of one and the same entity.
- Published
- 2003
140. First trimester diagnosis of conjoined twins in a triplet pregnancy after IVF and ICSI: case report
- Author
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Eliezer Shalev, Izhar Ben-Shlomo, Yael Goldberg, and E. Weiner
- Subjects
Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,medicine.medical_treatment ,Fertilization in Vitro ,Intracytoplasmic sperm injection ,Ultrasonography, Prenatal ,Pregnancy ,Conjoined twins ,medicine ,Triplet Pregnancy ,Humans ,Sperm Injections, Intracytoplasmic ,Twins, Conjoined ,Twin Pregnancy ,Gynecology ,Fetus ,Triplets ,Obstetrics ,business.industry ,Rehabilitation ,Obstetrics and Gynecology ,medicine.disease ,Pregnancy Reduction, Multifetal ,medicine.anatomical_structure ,Reproductive Medicine ,Vagina ,Gestation ,Female ,Pregnancy, Multiple ,business - Abstract
A case of conjoined twins in a triplet pregnancy after in-vitro fertilization and intracytoplasmic sperm injection is described. The diagnosis was made by high-resolution vaginal sonography, as early as the eighth week of gestation. The third fetus, of different chorionicity, was normal. Selective termination was successfully done at 12 weeks. The possible association between assisted reproduction and conjoined twinning is discussed. The importance of expert early vaginal sonography of pregnancy resulting from assisted reproduction technology is emphasized.
- Published
- 2000
141. Laparoscopic resection of ovarian benign cystic teratomas: experience with 84 cases
- Author
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Eliezer Shalev, Yael Goldberg, Izhar Ben-Shlomo, Shabtai Romano, and Moshe Bustan
- Subjects
Laparoscopic surgery ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Malignancy ,Cystectomy ,Medicine ,Humans ,Cyst ,Ovarian Teratoma ,Child ,Ultrasonography ,Ovarian Neoplasms ,business.industry ,Rehabilitation ,Teratoma ,Obstetrics and Gynecology ,Oophorectomy ,Middle Aged ,medicine.disease ,Surgery ,Reproductive Medicine ,Dermoid cyst ,Female ,Laparoscopy ,business - Abstract
Israel Laparoscopic treatment of benign cystic teratoma of the ovary has been recommended following the study of relatively small numbers of patients. We reviewed our experience with a prospective ongoing protocol for the treatment of benign ovarian teratomas, between January 1990 and December 1996. Sonography established the diagnosis, and biochemical markers were used to screen for possible malignancy. Surgery consisted of resecting the cyst and conserving the ovary if appropriate. The resected cyst was aspirated of its contents following insertion into an EndoCatch bag. Removal was accomplished via the narrowest incision possible by pulling the bag's margins through the incision and grasping the solid parts with conventional surgical instruments. The diameter of the cysts ranged from 2 to 15 cm. Cystectomy was performed in 47, and oophorectomy in 37, patients. Spillage occurred in 11 cases, but none developed peritonitis or fever. The mean duration of post-operative stay was 0.9 days (range 0.5-2). We conclude that laparoscopic resection of benign teratomas of the ovary is safe, well tolerated, and shortens hospital stay.
- Published
- 1998
142. High Frequency of BRCA 1/2 Mutations Among Israeli Non Ashkenazi Breast Cancer Patients
- Author
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Michal Sagi, Luna Kaduri, T. Peretz-Yablonski, Tamar Hamburger, F. Elyan, Azzam Salah, D. Bercovich, Yael Goldberg, Ofra Maimon, and Israela Lerer
- Subjects
Oncology ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Hematology ,Second primary cancer ,medicine.disease ,Ashkenazi jews ,Young age ,Breast cancer ,Internal medicine ,medicine ,Family history ,skin and connective tissue diseases ,business ,Ovarian cancer ,Pathological ,Founder mutation - Abstract
Background Inherited mutations in the breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with a high risk of developing breast (BC) and ovarian cancers (OC) in females of different age and ethnic groups. The spectrum of mutations in these genes varies between populations, with some showing a high frequency of unique mutations. Ashkenazi Jews have a high rate of founder mutations in BRCA1/2, in some other Jewish communities in Israel (Jews who immigrated to Israel from Iraq, Iran and Yemen), other founder mutations had been identified. Still high proportions of Israeli BC cases with strong family history have none of the known mutations at the BRCA1/2 genes. Methods and patients Over 3000 breast cancer patients were evaluated in the oncogentic clinic during 1997-2011. One hundred thirty seven of them underwent full sequencing of the BRCA1/2 genes due to strong family history of breast and/or ovarian cancer or young age at presentation. Clinical and pathological characteristics of these patients were evaluated. Result Sixty seven percent were non Ashkenazi Jews, Mean age at BC onset was 44 (22-77). In 20 patient (15%) BRCA 1(N = 8) or 2 (N = 12) mutations were identified. Three of the carriers had bilateral BC and 5 had OC as second primary .17 were of non Ashkenazi origin. Ninety five percent of the carriers had first degree family history of breast or ovarian cancer. The pathological information was available in half of the carriers. All had high grade (2-3) tumor, 90% of them were HER2 negative and 60% ER positive. Age at presentation had no effect on BRCA1/2 status. BRCAPRO is a predictive model to assess BRCA status and has assessed in 9 carriers, in 6 of them, the probability was >80% and in one - 5%. Conclusions A full sequence of the BRCA1/2 genes was performed in a selected group pf BC patient, who were negative for the common founder mutation in Israel. Fifteen percent were found to carry other BRCA1/2 mutations. We recommend that, patients with the following clinical features: Sephardic origin, first degree family history of BC or OC, high grade tumor, HER-2 negative, should be offered full BRCA1/2 testing. The role of BRCAPRO and other predictive model should be further evaluated. Disclosure All authors have declared no conflicts of interest.
- Published
- 2012
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