34 results on '"Pinsk V"'
Search Results
2. Premarketing Surveillance of Oral Ibuprofen Solution in Febrile Children
- Author
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Berkovitch, M., Press, J., Bulkowstein, M., Even, L., Barash, J., Brik, R., Tasher, D., Marom, R., Luder, A. S., Hecht, Y., Rubinshtein, M., Mosleh, M., Ben-Shachar, S., Talmor, R., Zviel, A., Kiro, A., Piglansky, L., Pinsk, V., and Uziel, Y.
- Published
- 2001
- Full Text
- View/download PDF
3. The role of sweat in the composition of skin microbiome: lessons learned from patients with congenital insensitivity to pain with anhidrosis
- Author
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Brandwein, M., primary, Horev, A., additional, Bogen, B., additional, Fuks, G., additional, Israel, A., additional, Shalom, G., additional, Pinsk, V., additional, Steinberg, D., additional, Bentwich, Z., additional, Shental, N., additional, and Meshner, S., additional
- Published
- 2020
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4. A novel mutation in the SLC17A5 gene causing both severe and mild phenotypes of free sialic acid storage disease in one inbred Bedouin kindred
- Author
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Landau, D, Cohen, D, Shalev, H, Pinsk, V, Yerushalmi, B, Zeigler, M, and Birk, O.S
- Published
- 2004
- Full Text
- View/download PDF
5. Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
- Author
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Barzaghi, F., Hernandez, L.C.A., Neven, B., Ricci, S., Kucuk, Z.Y., Bleesing, J.J., Nademi, Z., Slatter, M.A., Ulloa, E.R., Shcherbina, A., Roppelt, A., Worth, A., Silva, J., Aiuti, A., Murguia-Favela, L., Speckmann, C., Carneiro-Sampaio, M., Fernandes, J.F., Baris, S., Ozen, A., Karakoc-Aydiner, E., Kiykim, A., Schulz, A., Steinmann, S., Notarangelo, L.D., Gambineri, E., Lionetti, P., Shearer, W.T., Forbes, L.R., Martinez, C., Moshous, D., Blanche, S., Fisher, A., Ruemmele, F.M., Tissandier, C., Ouachee-Chardin, M., Rieux-Laucat, F., Cavazzana, M., Qasim, W., Lucarelli, B., Albert, M.H., Kobayashi, I., Alonso, L., Heredia, C.D. de, Kanegane, H., Lawitschka, A., Seo, J.J., Gonzalez-Vicent, M., Diaz, M.A., Goyal, R.K., Sauer, M.G., Yesilipek, A., Kim, M., Yilmaz-Demirdag, Y., Bhatia, M., Khlevner, J., Padilla, E.J.R., Martino, S., Montin, D., Neth, O., Molinos-Quintana, A., Valverde-Fernandez, J., Broides, A., Pinsk, V., Ballauf, A., Haerynck, F., Bordon, V., Dhooge, C., Garcia-Lloret, M.L., Bredius, R.G., Kawak, K., Haddad, E., Seidel, M.G., Duckers, G., Pai, S.Y., Dvorak, C.C., Ehl, S., Locatelli, F., Goldman, F., Gennery, A.R., Cowan, M.J., Roncarolo, M.G., Bacchetta, R., PIDTC, IEWP, European Soc Blood Marrow, Barzaghi, Federica, Hernandez, Laura Cristina Amaya, Neven, Benedicte, Ricci, Silvia, Kucuk, Zeynep Yesim, Bleesing, Jack J., Nademi, Zohreh, Slatter, Mary Anne, Ulloa, Erlinda Rose, Shcherbina, Anna, Roppelt, Anna, Worth, Austen, Silva, Juliana, Aiuti, Alessandro, Murguia-Favela, Luis, Speckmann, Carsten, Carneiro-Sampaio, Magda, Fernandes, Juliana Folloni, Baris, Safa, Ozen, Ahmet, Karakoc-Aydiner, Elif, Kiykim, Ayca, Schulz, Ansgar, Steinmann, Sandra, Notarangelo, Lucia Dora, Gambineri, Eleonora, Lionetti, Paolo, Shearer, William Thomas, Forbes, Lisa R., Martinez, Caridad, Moshous, Despina, Blanche, Stephane, Fisher, Alain, Ruemmele, Frank M., Tissandier, Come, Ouachee-Chardin, Marie, Rieux-Laucat, Frederic, Cavazzana, Marina, Qasim, Waseem, Lucarelli, Barbarella, Albert, Michael H., Kobayashi, Ichiro, Alonso, Laura, De Heredia, Cristina Diaz, Kanegane, Hirokazu, Lawitschka, Anita, Seo, Jong Jin, Gonzalez-Vicent, Marta, Diaz, Miguel Angel, Goyal, Rakesh Kumar, Sauer, Martin G., Yesilipek, Akif, Kim, Minsoo, Yilmaz-Demirdag, Yesim, Bhatia, Monica, Khlevner, Julie, Padilla, Erick J. Richmond, Martino, Silvana, Montin, Davide, Neth, Olaf, Molinos-Quintana, Agueda, Valverde-Fernandez, Justo, Broides, Arnon, Pinsk, Vered, Ballauf, Antje, Haerynck, Filomeen, Bordon, Victoria, Dhooge, Catharina, Garcia-Lloret, Maria Laura, Bredius, Robbert G., Kalwak, Krzysztof, Haddad, Elie, Seidel, Markus Gerhard, Duckers, Gregor, Pai, Sung-Yun, Dvorak, Christopher C., Ehl, Stephan, Locatelli, Franco, Goldman, Frederick, Gennery, Andrew Richard, Cowan, Mort J., Roncarolo, Maria-Grazia, Bacchetta, Rosa, Amaya Hernandez, Laura Cristina, Murguia-Favela, Lui, Shearer, William Thoma, Rieux-Laucat, Frédéric, Diaz De Heredia, Cristina, Richmond Padilla, Erick J., and Kałwak, Krzysztof
- Subjects
0301 basic medicine ,Male ,Allergy ,medicine.medical_treatment ,Medizin ,Disease ,Hematopoietic stem cell transplantation ,SIROLIMUS ,Regenerative Medicine ,primary immune deficiency ,Medicine and Health Sciences ,IPEX ,Immunology and Allergy ,2.1 Biological and endogenous factors ,Enteropathy ,Aetiology ,POLYENDOCRINOPATHY ,Child ,Pediatric ,CÉLULAS-TRONCO ,immunosuppression ,Hematopoietic Stem Cell Transplantation ,Genetic Diseases, X-Linked ,Immunosuppression ,Forkhead Transcription Factors ,X-LINKED SYNDROME ,Allografts ,Survival Rate ,surgical procedures, operative ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Immune System Diseases ,Genetic Diseases ,Child, Preschool ,hematopoietic stem cell transplantation ,Female ,hematopoietic stem ,neonatal diabetes ,FOXP3 ,Primary Immune Deficiency ,Treg cells ,enteropathy ,genetic autoimmunity ,rapamycin ,Type 1 ,Diarrhea ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Neonatal onset ,Article ,Disease-Free Survival ,03 medical and health sciences ,Neonatal diabete ,Clinical Research ,Internal medicine ,IMMUNODYSREGULATION ,medicine ,Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation ,Diabetes Mellitus ,Genetics ,Humans ,REGULATORY T-CELLS ,cell transplantation ,Preschool ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,IMMUNE DYSREGULATION ,business.industry ,MUTATIONS ,Infant ,Retrospective cohort study ,STEM-CELL TRANSPLANTATION ,IPEX syndrome ,X-Linked ,medicine.disease ,Stem Cell Research ,BONE-MARROW-TRANSPLANTATION ,Treg cell ,FOXP3 MUTATIONS ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,ENGRAFTMENT ,Mutation ,business ,Follow-Up Studies - Abstract
Background Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen., GRAPHICAL ABSTRACT
- Published
- 2018
6. P498 A nationwide quality improvement program in children with Crohn's disease improves outcomes within 12 months
- Author
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Turner, D, primary, Nehemia, C, additional, Yerushalmy-Feler, A, additional, Assa, A, additional, Slae, M, additional, Kori, M, additional, Elenberg, Y, additional, Shaoul, R, additional, Zifman, E, additional, Shamaly, H, additional, Berkowitz, D, additional, Peleg, S, additional, Yerushalmi, B, additional, Broide, E, additional, Aon, A, additional, Elkayam, O, additional, Bayan, H, additional, Gorodnichenko, A, additional, Pinsk, V, additional, and Shouval, D, additional
- Published
- 2019
- Full Text
- View/download PDF
7. Decreased First Phase Insulin Response in Children with Congenital Insensitivity to Pain with Anhidrosis
- Author
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Schreiber, R., primary, Levy, J., additional, Loewenthal, N., additional, Pinsk, V., additional, and Hershkovitz, E., additional
- Published
- 2005
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8. A Randomized Placebo Controlled Sequential Trial of Vitamin A in Bronchiolitis. 84
- Author
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Gorodischer, R., primary, Bearman, J E, additional, Sarov, B, additional, Friedman, M, additional, Haikin, H, additional, Aviram, M, additional, Arshid, F, additional, Avner, M, additional, Gazala, E, additional, Greenberg, D, additional, Igbaria, K, additional, Pinsk, V, additional, Tal, A, additional, and Smith, H, additional
- Published
- 1997
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9. Premarketing Surveillance of Oral Ibuprofen Solution in Febrile Children.
- Author
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Hecht, Y., Rubinshtein, M., Mosleh, M., Ben-Shachar, S., Talmor, R., Zviel, A., Kiro, A., Piglansky, L., Pinsk, V., Uziel, Y., Berkovitch, M., Press, J., Bulkowstein, M., Even, L., Barash, J., Brik, R., Tasher, D., Marom, R., and Luder, A.S.
- Subjects
IBUPROFEN ,FEVER in children ,PHYSIOLOGY ,THERAPEUTICS - Abstract
Objective: Ibuprofen is as effective as paracetamol (acetaminophen) as an antipyretic and analgesic agent in paediatric patients. Ibuprofen is considered to be well tolerated; however, there are reports on gastrointestinal bleeding or renal adverse effects among children treated with ibuprofen. Oral ibuprofen suspension was recently registered and approved by the Ministry of Health in Israel as an antipyretic and analgesic agent. Before distribution of the drug to pharmacies, we aimed to follow possible adverse effects among children receiving ibuprofen suspension in several paediatric wards and clinics. Design: Children with fever needing antipyretic medication received ibuprofen oral suspension 5 to 10 mg/kg/dose. In each case the age of the patient, gender, diagnosis, number of ibuprofen doses, duration of treatment and any adverse reactions were reported. Results: 1564 children from 14 paediatric wards (11 hospitals) and from five paediatric and family clinics participated in the study; 882 males and 682 females. The patients, aged 3.6 ± 4.2 years (range 1 month to 16.5 years), received 2.4 ± 3 (range 1 to 22) doses of ibuprofen suspension for 1.56 ± 2.11 (range 1 to 20) days. Adverse reactions were reported among 26 patients (1.66%) [95% confidence interval (CI) 1.1-2.4]; 18 children (1.15%) [95% CI 0.7-1.8] vomited immediately after the administration of the drug and it was not readministered. Two children (0.12%) [95% CI 0.02-0.46] had abdominal pain that resolved spontaneously, two patients reported nausea, and two other children had diarrhoea. Eight children (0.51%) reported experiencing a ‘bitter taste’ from the medication, of whom one patient discontinued the medication while the other seven continued it. Conclusions: The adverse reactions following administration of oral ibuprofen suspension reported in our study were low in frequency, mild and disappeared spontaneously. However, continuing reporting on its tolerability is needed. [ABSTRACT FROM AUTHOR]
- Published
- 2001
10. Neurophysiologic studies in congenital insensitivity to pain with anhidrosis
- Author
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Shorer, Z., Moses, S. W., Hershkovitz, E., Pinsk, V., and Levy, J.
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- 2001
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11. Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.
- Author
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Yogev D, Shosberger A, Nehemia C, Harel S, Yerushalmy-Feler A, Ledder O, Orlanski-Meyer E, Assa A, Slae M, Kori M, Elenberg Y, Shaoul R, Zifman E, Shamaly H, Berkowitz D, Sarit P, Yerushalmi B, Broide E, On A, Elkayam O, Bayan H, Gorodnichenko A, Pinsk V, Shouval DS, and Turner D
- Subjects
- Adolescent, Biomarkers, Child, Feces, Humans, Leukocyte L1 Antigen Complex, Quality Improvement, Crohn Disease therapy, Inflammatory Bowel Diseases
- Abstract
Objectives: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country., Methods: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values., Results: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ± 3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 μg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001)., Conclusions: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
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- 2021
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12. A Pilot Study to Reduce Central Line-Associated Bloodstream Infections in Children From Extremely Low-Income Settings With Intestinal Failure-Meeting the Challenge.
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Fuchs I, Rosenbaum D, Klein I, Einhorn M, Pinsk V, Shelef Y, Sherf A, Press Y, and Yerushalmi B
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- Catheter-Related Infections etiology, Health Care Costs, Historically Controlled Study, House Calls, Infection Control methods, Inservice Training, Israel, Length of Stay, Parenteral Nutrition, Home economics, Parenteral Nutrition, Home methods, Pilot Projects, Poverty, Catheter-Related Infections prevention & control, Central Venous Catheters adverse effects, Disinfectants administration & dosage, Ethanol administration & dosage, Parenteral Nutrition, Home adverse effects
- Abstract
Background: Central line-associated bloodstream infections (CLABSIs) are major sources of morbidity, death, and healthcare costs in patients who receive home parenteral nutrition (HPN). The majority of HPN-dependent children in southern Israel reside in poor communities with substandard living conditions, which creates significant challenges for the safe provision of HPN. We developed a pilot intervention that aimed to reduce the rates of CLABSI and central venous catheter (CVC) replacements in this vulnerable population in our region., Methods: Between 2012 and 2014, all HPN-dependent children with intestinal failure who were treated in our center, received HPN through a Hickman catheter, and experienced at least 1 previous CLABSI episode participated in the intervention. The intervention included home visits to assess the caregivers' CVC-handling technique, instillation of prophylactic ethanol lock solution, and the convening of regular multidisciplinary staff debriefings. We calculated CLABSI and CVC-replacement rates before and after the intervention., Results: Eight patients who served as their own historical controls were included in the intervention (total of 2544 catheter-days during the intervention period). The mean CLABSI rate decreased from 9.62 to 0.79 CLABSI episodes per 1000 catheter-days; the CVC-replacement rate decreased from 2.5 to 1.2 replacements per 1000 catheter-days in the preintervention and intervention periods respectively. The median hospital length of stay and individual monthly cost of medical care decreased compared to those found in the preintervention period., Conclusions: The results of this study offer a proof of concept for a strategy to reduce CLABSI rates in pediatric patients who reside in remote and low-resource environments and are undergoing HPN., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2020
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13. Seasonality of birth affects paediatric coeliac disease.
- Author
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Daniel S, Kalansky A, Tsur A, Pinsk V, Ling G, Rannan R, and Yerushalmi B
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- Child, Female, Humans, Israel epidemiology, Male, Parturition, Retrospective Studies, Celiac Disease epidemiology, Seasons
- Abstract
Aim: This study investigated the seasonality of birth in children diagnosed with coeliac disease (CD) at a tertiary University hospital in Southern Israel., Methods: This was a population-based retrospective time series analysis study from January 1988 to December 2014. There were 308 903 live births at Soroka University Medical Centre during the study period and 699 were diagnosed with CD. We combined three databases covering births, CD diagnoses and weather indices. The daily proportion of births that resulted in CD for the different four seasons and high seasons were compared to the weather indices on the day of birth using negative binomial regression., Results: Statistically significant associations were found between the season of birth and the rate of CD, with autumn births being associated with a higher risk for the development of CD than births during the summer, with an incidence ratio of 1.22. The association was further increased when the defined summer and autumn high seasons were used, with an incidence ratio of 1.40. No association was found between CD and the mean temperature and global radiation., Conclusion: Coeliac disease was associated with birth during the autumn and the autumn high season posed an even more significant risk factor., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)
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- 2019
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14. EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome.
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Pathak SJ, Mueller JL, Okamoto K, Das B, Hertecant J, Greenhalgh L, Cole T, Pinsk V, Yerushalmi B, Gurkan OE, Yourshaw M, Hernandez E, Oesterreicher S, Naik S, Sanderson IR, Axelsson I, Agardh D, Boland CR, Martin MG, Putnam CD, and Sivagnanam M
- Subjects
- Colorectal Neoplasms, Hereditary Nonpolyposis pathology, Diarrhea, Infantile pathology, Epithelial Cell Adhesion Molecule genetics, Epithelial Cells metabolism, Genetic Association Studies, Humans, Malabsorption Syndromes pathology, MutS Homolog 2 Protein genetics, Mutation, Missense genetics, RNA Splice Sites genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Diarrhea, Infantile genetics, Epithelial Cell Adhesion Molecule chemistry, Malabsorption Syndromes genetics, Models, Molecular
- Abstract
The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype-phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome., (© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.)
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- 2019
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15. Mycophenolate Mofetil Alone and in Combination with Tacrolimus Inhibits the Proliferation of HT-29 Human Colonic Adenocarcinoma Cell Line and Might Interfere with Colonic Tumorigenesis.
- Author
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Ling G, Lamprecht S, Shubinsky G, Osyntsov L, Yerushalmi B, Pinsk I, Pinsk V, and Ling E
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- Adenocarcinoma drug therapy, Adenocarcinoma metabolism, Adenocarcinoma pathology, Adenomatous Polyposis Coli drug therapy, Adenomatous Polyposis Coli metabolism, Adenomatous Polyposis Coli pathology, Antibiotics, Antineoplastic administration & dosage, Antibiotics, Antineoplastic pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Cycle Checkpoints drug effects, Colon pathology, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Drug Synergism, HT29 Cells, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacology, Ki-67 Antigen metabolism, Mycophenolic Acid administration & dosage, Tacrolimus administration & dosage, Carcinogenesis drug effects, Cell Proliferation drug effects, Colon drug effects, Mycophenolic Acid pharmacology, Tacrolimus pharmacology
- Abstract
Background/aim: Familial adenomatous polyposis (FAP) was found to be completely reversed in a patient treated with mycophenolate mofetil (MMF) and tacrolimus following kidney transplantation. In this preliminary study, we assessed whether MMF and tacrolimus alone or in combination interfere with the cell cycle and proliferation in a human colonic adenocarcinoma cell line and in the colonic polyps of the patient with FAP., Materials and Methods: Human colonic adenocarcinoma HT-29 cells were treated with tacrolimus and MMF alone and in combination at different concentrations. Cell viability and proliferation were assessed using the MTT assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of Ki-67, a marker of mitotic activity, was evaluated in the patient's colonic polyps before and under drug treatment., Results: MMF in combination with tacrolimus induced S-phase cell-cycle arrest and markedly inhibited HT-29 cell proliferation. Ki-67 expression in the patient's colonic polyps was significantly reduced following combined tacrolimus and MMF treatment., Conclusion: MMF and tacrolimus synergistically inhibited proliferation of a human colonic adenocarcinoma cell line and interfered with the expansion of colonic crypt proliferation in the polyp from a patient with FAP. The results confirm our clinical observation and indicate the possibility of novel approach to therapy of colorectal neoplasia., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2018
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16. Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.
- Author
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Barzaghi F, Amaya Hernandez LC, Neven B, Ricci S, Kucuk ZY, Bleesing JJ, Nademi Z, Slatter MA, Ulloa ER, Shcherbina A, Roppelt A, Worth A, Silva J, Aiuti A, Murguia-Favela L, Speckmann C, Carneiro-Sampaio M, Fernandes JF, Baris S, Ozen A, Karakoc-Aydiner E, Kiykim A, Schulz A, Steinmann S, Notarangelo LD, Gambineri E, Lionetti P, Shearer WT, Forbes LR, Martinez C, Moshous D, Blanche S, Fisher A, Ruemmele FM, Tissandier C, Ouachee-Chardin M, Rieux-Laucat F, Cavazzana M, Qasim W, Lucarelli B, Albert MH, Kobayashi I, Alonso L, Diaz De Heredia C, Kanegane H, Lawitschka A, Seo JJ, Gonzalez-Vicent M, Diaz MA, Goyal RK, Sauer MG, Yesilipek A, Kim M, Yilmaz-Demirdag Y, Bhatia M, Khlevner J, Richmond Padilla EJ, Martino S, Montin D, Neth O, Molinos-Quintana A, Valverde-Fernandez J, Broides A, Pinsk V, Ballauf A, Haerynck F, Bordon V, Dhooge C, Garcia-Lloret ML, Bredius RG, Kałwak K, Haddad E, Seidel MG, Duckers G, Pai SY, Dvorak CC, Ehl S, Locatelli F, Goldman F, Gennery AR, Cowan MJ, Roncarolo MG, and Bacchetta R
- Subjects
- Adolescent, Adult, Allografts, Child, Child, Preschool, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 mortality, Diabetes Mellitus, Type 1 therapy, Disease-Free Survival, Female, Follow-Up Studies, Humans, Immune System Diseases genetics, Immune System Diseases immunology, Immune System Diseases mortality, Immune System Diseases therapy, Infant, Male, Retrospective Studies, Survival Rate, Diabetes Mellitus, Type 1 congenital, Diarrhea genetics, Diarrhea immunology, Diarrhea mortality, Diarrhea therapy, Forkhead Transcription Factors genetics, Forkhead Transcription Factors immunology, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked immunology, Genetic Diseases, X-Linked mortality, Genetic Diseases, X-Linked therapy, Hematopoietic Stem Cell Transplantation, Immune System Diseases congenital, Immunosuppression Therapy, Mutation
- Abstract
Background: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined., Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors., Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed., Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS., Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
17. A case of cryopyrin-associated periodic fever syndrome due to Q703K mutation in the NLRP3 gene.
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Ling E, Ling G, and Pinsk V
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- Arthritis, Juvenile diagnosis, Child, Cryopyrin-Associated Periodic Syndromes diagnosis, Cryopyrin-Associated Periodic Syndromes drug therapy, Diagnosis, Differential, Female, Genetic Predisposition to Disease, Humans, Immunosuppressive Agents therapeutic use, Phenotype, Predictive Value of Tests, Treatment Outcome, Cryopyrin-Associated Periodic Syndromes genetics, Mutation, NLR Family, Pyrin Domain-Containing 3 Protein genetics
- Published
- 2017
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18. Complete Reversion of Familial Adenomatous Polyposis Phenotype Associated with Tacrolimus and Mycophenolate Mofetil Treatment Following Kidney Transplantation.
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Pinsk V, Pinsk I, Ling G, Yerushalmi B, Osyntsov L, and Ling E
- Subjects
- Adenomatous Polyposis Coli diagnosis, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli pathology, Adolescent, Adult, Colon pathology, Drug Therapy, Combination, Female, Genetic Predisposition to Disease, Heredity, Humans, Male, Middle Aged, Pedigree, Phenotype, Remission Induction, Treatment Outcome, Young Adult, Adenomatous Polyposis Coli drug therapy, Adenomatous Polyposis Coli Protein genetics, Antineoplastic Agents therapeutic use, Calcineurin Inhibitors therapeutic use, Colon drug effects, Germ-Line Mutation, Immunosuppressive Agents therapeutic use, Kidney Transplantation, Mycophenolic Acid therapeutic use, Tacrolimus therapeutic use
- Abstract
Numerous germline mutations in the adenomatous polyposis coli (APC) tumor-suppressor gene are responsible for development of multiple adenomatous colorectal polyps with their inevitable progression to cancer. Multiple attempts at dietary and pharmacological prevention of colorectal carcinoma development in patients with familial adenomatous polyposis (FAP) have provided conflicting results. Immunosuppressive treatment with tacrolimus is known to be associated with an increased risk of malignancy and should be avoided in patients with high propensity for development of neoplasia. We observed a complete reversion of FAP phenotype in a male teenager carrying a germline mutation in APC gene who underwent a kidney transplant due to end-stage kidney disease secondary to congenital dysplastic kidneys. The patient was treated with tacrolimus and mycophenolate mofetil after transplantation. The possible chemopreventative role of these agents should be evaluated and confirmed in a larger cohort. The elucidation of molecular mechanisms underpinning the observed chemopreventative effect of tacrolimus and mycophenolate mofetil might lead to the development of a novel colorectal cancer therapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2017
- Full Text
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19. The clinical and laboratory spectrum of dedicator of cytokinesis 8 immunodeficiency syndrome in patients with a unique mutation.
- Author
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Broides A, Mandola AB, Levy J, Yerushalmi B, Pinsk V, Eldan M, Shubinsky G, Hadad N, Levy R, Nahum A, Ben-Harosh M, Lev A, Simon A, and Somech R
- Subjects
- Adolescent, Age Factors, Arabs, Child, Child, Preschool, Consanguinity, Genotype, Humans, Immunoglobulin E blood, Infant, Job Syndrome genetics, Pedigree, Phenotype, Recurrence, Retrospective Studies, Young Adult, Asthma immunology, Bronchiectasis immunology, Eczema immunology, Guanine Nucleotide Exchange Factors genetics, Job Syndrome immunology, Mutation genetics, Pneumonia, Pneumococcal immunology
- Abstract
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis. Prior to the genetic diagnosis, the clinical diagnosis was "hyper IgE syndrome" in six patients and "anti-pneumococcal antibody deficiency," "recurrent pneumonia with bronchiectasis," and "asthma with hypereosinophilic syndrome" each diagnosed once. One additional patient was diagnosed due to family history. The age of presentation varied from 1 to 16 months. Eczema was diagnosed in all patients, food allergies in three, and severe herpes keratitis or malignancy or autoimmunity in two patients. Elevated IgE was recorded in nine patients; however, in six patients, the initial serum IgE concentration was equal to or less than three times the normal concentration for age, and in these patients, the median age at IgE evaluation was 7.5 months compared with 21.5 months in patients with an initial IgE concentration above three times the normal concentration for age (P = 0.067). The spectrum of disease manifestations in patients with a unique mutation in DOCK8 is variable. The genotype-phenotype correlations may be modified by genetic and/or epigenetic modifiers beyond the monogenic effect. Younger patients tend to have lower IgE concentrations at the initial measurement of IgE.
- Published
- 2017
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20. Management of Ingested Hijab-Pin.
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Hubara E, Ling G, Pinsk V, Lior Y, Daniel S, Zuckerman S, and Yerushalmi B
- Subjects
- Adolescent, Child, Female, Foreign Bodies diagnostic imaging, Humans, Remission, Spontaneous, Retrospective Studies, Duodenum, Endoscopy, Gastrointestinal, Foreign Bodies therapy, Stomach, Watchful Waiting
- Abstract
Background and Study Aims: Accidental swallowing of hijab (or turban) pin was reported mainly among adolescent girls. Current guidelines indicate emergent intervention endoscopy in case a long sharp object is found in the gastrointestinal tract. The aims of the current study are to present the results of an observational approach and to assess the need for intervention., Patients and Methods: A retrospective cohort study was conducted including all 5-18-year-old patients who presented with hijab-pin ingestion between 2003 and 2014. The need for intervention was assessed using both univariable and multivariable statistical analyses., Results: Two hundred three cases of hijab-pin ingestion were documented. In the majority of cases, the pin was observed in the stomach (137/203, 67.4%) upon arrival. Most pins that were located at the upper gastrointestinal tract (proximal to the ligament of Treitz) ejected spontaneously (120/169, 71%, Pv = 0.005). The absence of pin progression in an X-ray performed 12 h following presentation was significantly more frequent in the intervention group (46/51, 90%, Pv = 0.001)., Conclusions: In most cases, the outcome is spontaneous ejection from the digestive tract. However, if needle location remains unchanged on two consecutive X-rays, an endoscopic intervention is recommended.
- Published
- 2017
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21. Incidence of typically Severe Primary Immunodeficiency Diseases in Consanguineous and Non-consanguineous Populations.
- Author
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Broides A, Nahum A, Mandola AB, Rozner L, Pinsk V, Ling G, Yerushalmi B, Levy J, and Givon-Lavi N
- Subjects
- Arabs, Female, Genetic Predisposition to Disease, Hematopoietic Stem Cell Transplantation, Humans, Immunologic Deficiency Syndromes etiology, Immunologic Deficiency Syndromes therapy, Incidence, Judaism, Male, Mutation, Retrospective Studies, Severity of Illness Index, Consanguinity, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes epidemiology, Population Surveillance
- Abstract
Purpose: Primary immunodeficiency diseases are considered to be rare diseases; however, data on the exact birth incidences of these diseases are sparse. Southern Israel is inhabited by two major populations: a relatively non-consanguineous Jewish population and a highly consanguineous Muslim Bedouin population. We sought to calculate the incidences of typically severe primary immunodeficiency diseases and compare the incidences in these populations., Methods: A retrospective analysis of all typically severe primary immunodeficiency diseases evaluated at a single center from January 1, 1996 to December 31, 2016. The amount of live births by population was the denominator for calculating the incidences by population., Results: A total of 95 patients were included, 85 of Bedouin and 10 of Jewish ethnicities. There were 152,331 births in the Bedouin and 160,998 births in the Jewish populations. The total incidence of typically severe primary immunodeficiency diseases was higher in the Bedouin population than expected based on previous studies. The total incidences were 55.8/10
5 births in the Bedouin population compared with 6.2/105 births in the Jewish population (P < 0.001). The incidences of all combined immunodeficiency diseases, ataxia telangiectasia, and infantile IBD due to interleukin 10 receptor defects were all significantly higher in the Bedouin population (P < 0.001). The incidence of X-linked agammaglobulinemia was not significantly different between both populations (P = 0.11)., Conclusions: Typically, severe primary immunodeficiency diseases are not rare diseases in a consanguineous population; these diseases are significantly more common in the Bedouin population. This finding is probably also applicable to other consanguineous populations, and in these populations, primary immunodeficiency diseases should not be regarded as rare diseases.- Published
- 2017
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22. Subclinical intestinal inflammation in chronic granulomatous disease patients.
- Author
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Broides A, Sagi O, Pinsk V, Levy J, and Yerushalmi B
- Subjects
- Adolescent, Asymptomatic Diseases, Biomarkers analysis, Biomarkers metabolism, Child, Child, Preschool, Colitis complications, Colitis immunology, Feces chemistry, Female, Granulomatous Disease, Chronic complications, Granulomatous Disease, Chronic immunology, Humans, Leukocyte L1 Antigen Complex analysis, Male, Prognosis, Colitis diagnosis, Granulomatous Disease, Chronic diagnosis, Intestinal Mucosa immunology, Leukocyte L1 Antigen Complex metabolism, Neutrophils immunology
- Abstract
Chronic granulomatous disease is a primary immunodeficiency caused by impaired neutrophil production of reactive oxygen species. Non-infectious colitis is common in chronic granulomatous disease, and high levels of antimicrobial antibodies that are associated with Crohn's disease are common even without colitis. Fecal calprotectin concentration is a marker for intestinal inflammation. We sought to determine whether subclinical intestinal inflammation occurs in asymptomatic chronic granulomatous disease patients. Asymptomatic chronic granulomatous disease patients without overt gastrointestinal symptoms suggestive of colitis at the time of enrollment were studied for fecal calprotectin concentration, antibodies associated with Crohn's disease and systemic inflammatory markers. Eight patients were included, aged 54-176 months. In 7/8 (87.5 %) fecal calprotectin concentration was normal (<50) and elevated (137 mg/kg) in only one patient. This patient later developed colitis. In 7/8 (87.5 %) anti-Saccharomyces cerevisiae antibody was positive. C-reactive protein, albumin, complete blood count and p-anti-neutrophil cytoplasmic antibody were normal in all 8 patients. Subclinical colitis is not evident in most asymptomatic chronic granulomatous disease patients; however, in some patients, fecal calprotectin concentration may be elevated, possibly indicating the presence of subclinical colitis and predicting the occurrence of clinically relevant colitis. Serum anti-Saccharomyces cerevisiae antibody concentrations do not seem to correlate with fecal calprotectin concentration in asymptomatic chronic granulomatous disease patients.
- Published
- 2016
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23. Acute Liver Failure in a Pediatric Patient with Congenital Dysery-Thropoietic Anemia Type I Treated with Deferasirox.
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Ling G, Pinsk V, Golan-Tripto I, and Ling E
- Abstract
Congenital dyserythropoietic anemias (CDA) represent a heterogeneous group of disorders characterized by morphological abnormalities of erythroid precursor cells and various degrees of hemolysis. Iron overload is a result of continuous hemolysis and recurrent transfusions. It is treated with iron chelators, including deferasirox. We present here a case of acute liver failure in a 12 years old girl with CDA type I treated with deferasirox and discuss the approach to treatment.
- Published
- 2015
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24. Variation of muscular structure in congenital insensitivity to pain and anhidrosis.
- Author
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Shorer Z, Shaco-Levy R, Pinsk V, Kachko L, and Levy J
- Subjects
- Adolescent, Child, Cohort Studies, Female, Hereditary Sensory and Autonomic Neuropathies genetics, Hereditary Sensory and Autonomic Neuropathies physiopathology, Humans, Male, Muscle, Skeletal physiopathology, Retrospective Studies, Hereditary Sensory and Autonomic Neuropathies diagnosis, Muscle, Skeletal pathology
- Abstract
Congenital insensitivity to pain with anhidrosis is a rare disease affecting the nervous system. The patients present with unexplained fever from poor thermoregulation and inability to sweat. Because of the indifference to pain, they manifest frequent traumatic and infectious injuries. Evaluations of these patients include investigation of the hypotonia and weakness evident in this group of patients. We report four patients presenting characteristic features of congenital insensitivity to pain with anhidrosis who carry an identical mutation in the TRK-A gene and who underwent nerve and skeletal muscle biopsies. All four patients had normal sensory and motor conduction studies but lacked sympathetic skin responses. Examination of the skeletal muscles biopsies obtained from two of the patients disclosed marked myopathic changes. The muscle biopsy of a third patient showed mild variation in muscle fibers and the fourth patient's muscle biopsy showed type 1 fiber predominance. Electron microscopy studies revealed remarkable decrease in the number of small caliber-myelinated and unmyelinated nerve fibers. We assume that the variable histological findings in the muscle biopsies of these patients reflect a variation in congenital insensitivity to pain with anhidrosis patients that is not related to their genetic mutation., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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25. Abnormal neutrophil chemotactic activity in children with congenital insensitivity to pain with anhidrosis (CIPA): the role of nerve growth factor.
- Author
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Beigelman A, Levy J, Hadad N, Pinsk V, Haim A, Fruchtman Y, and Levy R
- Subjects
- Adolescent, Adult, Chemokines metabolism, Chemotaxis drug effects, Child, Child, Preschool, Enzyme Activation drug effects, Female, Humans, Infant, MAP Kinase Kinase 4 metabolism, Male, Mitogen-Activated Protein Kinase 3 metabolism, Nerve Growth Factor pharmacology, Pain Insensitivity, Congenital immunology, Young Adult, Hypohidrosis complications, Nerve Growth Factor metabolism, Neutrophils metabolism, Pain Insensitivity, Congenital complications, Pain Insensitivity, Congenital physiopathology
- Abstract
A 1926-ins-T mutation in the TrkA gene encoding the tyrosine kinase receptor for nerve growth factor (NGF) was previously documented in patients with congenital insensitivity to pain with anhidrosis (CIPA). These patients suffer from skin lacerations which often evolve into deep tissue infections. Abnormality in neutrophil functions may explain this high rate of severe infections. In this study we show that chemotaxis was significantly (P<0.001) suppressed in patients' neutrophils, compared to healthy controls. Although NGF alone did not exert a chemotactic effect, its presence enhanced both migration toward fMLP and phosphorylation of MAP kinases (ERK and JNK) in neutrophils from healthy controls, but not in neutrophils from CIPA patients. The significantly impaired chemotactic activity of neutrophils from a CIPA patient, which has been attributed to the molecular defect in the TrkA receptor, may contribute to the high rate of infection.
- Published
- 2009
- Full Text
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26. Efficacy and safety of intravenous iron sucrose therapy in a group of children with iron deficiency anemia.
- Author
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Pinsk V, Levy J, Moser A, Yerushalmi B, and Kapelushnik J
- Subjects
- Adolescent, Anemia, Iron-Deficiency etiology, Child, Child, Preschool, Female, Ferric Oxide, Saccharated, Ferritins blood, Glucaric Acid, Hemoglobins analysis, Humans, Infant, Infusions, Intravenous, Male, Prospective Studies, Treatment Outcome, Anemia, Iron-Deficiency therapy, Ferric Compounds therapeutic use, Hematinics therapeutic use
- Abstract
Background: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration., Objectives: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy., Methods: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Day Care Unit where they received intravenous iron sucrose infusion., Results: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5-10.1 g/dl). Fourteen days after treatment it increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment., Conclusions: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.
- Published
- 2008
27. Inflammatory bowel disease in the South Asian pediatric population of British Columbia.
- Author
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Pinsk V, Lemberg DA, Grewal K, Barker CC, Schreiber RA, and Jacobson K
- Subjects
- Adolescent, Asia, Southeastern ethnology, British Columbia epidemiology, Child, Child, Preschool, Female, Humans, Incidence, Inflammatory Bowel Diseases ethnology, Interviews as Topic, Male, Prospective Studies, Retrospective Studies, Risk Factors, Sex Factors, Inflammatory Bowel Diseases epidemiology
- Abstract
Background: Geographical differences, population migration, and changing demographics suggest an environmental role in prevalence, modulation, and phenotypic expression of inflammatory bowel disease (IBD)., Aim: To determine the incidence of IBD and disease subtype in the pediatric South Asian population in British Columbia (BC) compared with non-South Asian IBD patients in the same geographic area., Methods: Chart review with data collected for all patients
- Published
- 2007
- Full Text
- View/download PDF
28. [Clinical and genetic aspects of congenital insensitivity to pain with anhidrosis].
- Author
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Schwarzkopf R, Pinsk V, Weisel Y, Atar D, and Gorzak Y
- Subjects
- Child, Humans, Hypohidrosis congenital, Intellectual Disability complications, Nerve Growth Factors genetics, Nerve Growth Factors physiology, Hypohidrosis genetics, Hypohidrosis therapy, Pain Insensitivity, Congenital genetics, Pain Insensitivity, Congenital therapy
- Abstract
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease, which is characterized by recurrent episodes of fever, anhidrosis, self mutilation, absence of reaction to noxious stimuli, prolonged healing times and mental retardation. The absence of pain sensation combined with mental retardation predisposes the children to recurrent wound infections and deep ulcers that heal at a slower pace than seen in healthy people. The anomalous pain is due to the absence of dorsal root ganglia that are responsible for pain sensation and absence of afferent neurons activated by tissue damaging stimuli. Nerve Growth Factor (NGF) is a growth factor that supports the survival of nociceptive sensory and autonomic sympathetic neurons. Neurotrophin Tyrosine Receptor (NTRK1) encodes a receptor tyrosine kinase that is activated in response to NGF. NTRK1 mutations have been found in mice that presented with clinical signs similar to CIPA, subsequently CIPA patients have been examined for these mutations as well. Currently, 37 different mutations at the NTRK1 are known which cause CIPA. The above syndrome is so rare that until the year 2000 only 84 cases have been reported, not including 28 known cases of CIPA patients from Israeli Bedouins. Since no cure is available, prenatal screening, as conducted in our institution, is the only available preventive option to avoid the birth of an affected child.
- Published
- 2005
29. Nerve growth factor-tyrosine kinase A pathway is involved in thermoregulation and adaptation to stress: studies on patients with hereditary sensory and autonomic neuropathy type IV.
- Author
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Loewenthal N, Levy J, Schreiber R, Pinsk V, Perry Z, Shorer Z, and Hershkovitz E
- Subjects
- Child, Child, Preschool, Endocrine System physiology, Female, Hereditary Sensory and Autonomic Neuropathies genetics, Hereditary Sensory and Autonomic Neuropathies mortality, Hereditary Sensory and Autonomic Neuropathies physiopathology, Homeostasis, Humans, Infant, Male, Receptor, trkA metabolism, Body Temperature Regulation physiology, Hereditary Sensory and Autonomic Neuropathies metabolism, Nerve Growth Factor metabolism, Receptor, trkA genetics, Signal Transduction physiology, Stress, Physiological metabolism
- Abstract
Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is caused by mutations in the tyrosin kinase A (TrkA) gene, encoding for the high-affinity receptor of nerve growth factor (NGF). The NGF-TrkA system is expressed in many endocrine glands. We hypothesized that HSAN IV represents a natural model for impaired NGF effect on the neuroendocrine system in humans. We have documented the clinical outcome of 31 HSAN IV patients in a single medical center, and investigated their basal endocrine system status. The endocrine system response to thirst was compared between six patients and six healthy children. High rates of mortality (22%) and severe morbidity (30%) have been found in HSAN IV patients. Hypothermia was noted in 40% of the patients and unexplained fever was observed in 56%. Subnormal adrenal function was demonstrated in six (30%) of the patients studied. Furthermore, we found lower plasma norepinephrine (NE) levels in six HSAN IV patients compared with a control group after the thirst test. Our findings emphasize the importance of NGF-TrkA pathway in the physiology of the neuroendocrine system and its response to stress. Inadequate response to stress might contribute to the observed significant mortality, morbidity, and temperature instability in HSAN IV patients.
- Published
- 2005
- Full Text
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30. Orofacial manifestations of congenital insensitivity to pain with anhidrosis: a report of 24 cases.
- Author
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Bodner L, Woldenberg Y, Pinsk V, and Levy J
- Subjects
- Arabs, Bites, Human etiology, Child, Child, Preschool, Female, Finger Injuries etiology, Humans, Infant, Israel, Lip injuries, Lip Diseases etiology, Male, Mandibular Diseases etiology, Mouth Mucosa injuries, Oral Ulcer etiology, Osteomyelitis etiology, Self Mutilation etiology, Tongue injuries, Tongue Diseases etiology, Tooth Avulsion etiology, Tooth Loss etiology, Hereditary Sensory and Autonomic Neuropathies complications, Mouth Diseases etiology, Tooth Diseases etiology
- Abstract
Purpose: To report the incidence and severity of the oral and dental manifestations associated with congenital insensitivity to pain with anhidrosis (CIPA)., Methods: Young children with CIPA underwent orofacial examination. The tongue, lips, and buccal mucosa were examined for soft tissue disorder. Missing and luxated teeth were recorded., Results: Twenty four patients (14 males and 10 females, mean age 60 months, range 9-144 months) with CIPA showed moderate to severe self-mutilation. Oral self-mutilation, such as biting injuries and scarring of soft tissues (tongue, lip, and buccal mucosa) were found in all patients. Fingertip biting was also found in most patients. Among infant patients, the mutilation was typically characterized by decubital ulcers of the tongue. Many edentulous areas due to previously extracted teeth were also found., Conclusions: Early diagnosis and specific dental care for patients with CIPA can be helpful in prevention of the fingertip biting and orofacial manifestations seen in this disorder.
- Published
- 2002
31. Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies.
- Author
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Shatzky S, Moses S, Levy J, Pinsk V, Hershkovitz E, Herzog L, Shorer Z, Luder A, and Parvari R
- Subjects
- Base Sequence, DNA Primers, Female, Genetic Linkage, Humans, Hypohidrosis diagnosis, Hypohidrosis physiopathology, Israel, Male, Pain Insensitivity, Congenital diagnosis, Pain Insensitivity, Congenital physiopathology, Prenatal Diagnosis, Arabs genetics, Genetic Heterogeneity, Hypohidrosis genetics, Mutation, Neural Conduction, Pain Insensitivity, Congenital genetics, Receptor, trkA genetics
- Abstract
Congenital insensitivity to pain with anhidrosis (CIPA), a rare and severe disorder, comprises absence of sensation to noxious stimuli, inability to sweat, and recurrent episodes of hyperthermia. It has a relatively high prevalence in the consanguineous Israeli-Bedouins. Clinical studies of 28 patients are reported here. Using the linkage analysis approach, we linked the disease in 9 of 10 unrelated Israeli-Bedouin families with CIPA to the TrkA gene, which encodes the receptor for nerve growth factor. In one family, linkage was excluded, implying that another gene, yet unidentified, is involved. Two new mutations in the tyrosine kinase domain of the TrkA gene were identified in our CIPA patients: a 1926-ins-T in most of the southern Israeli-Negev CIPA patients, and a Pro- 689-Leu mutation in a different isolate of Bedouins in northern Israel. Eight prenatal diagnoses were made in the southern Israeli-Negev Bedouins, two by linkage analysis and six by checking directly for the 1926-ins-T mutation. Three polymorphisms in the TrkA protein kinase encoding domain were also observed., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF
32. A comparison of multiple regimens of pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers.
- Author
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Blum MD, Dagan R, Mendelman PM, Pinsk V, Giordani M, Li S, Bohidar N, and McNeely TB
- Subjects
- Antibodies, Bacterial blood, Bacterial Vaccines adverse effects, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Immunization, Secondary, Infant, Opsonin Proteins blood, Pneumococcal Infections immunology, Pneumococcal Infections prevention & control, Pneumococcal Vaccines, Safety, Streptococcus pneumoniae immunology, Vaccines, Conjugate adverse effects, Bacterial Vaccines administration & dosage, Meningococcal Vaccines, Vaccines, Conjugate administration & dosage
- Abstract
Children who had been randomized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PCV) or 23-valent pneumococcal polysaccharide vaccine (PN23) at 12, 15, or 18 months of age were subsequently randomized to receive a booster injection of either PCV or PN23 12 months later. For those children who received a priming dose of PCV (N=75) compared to PN23 (N=48) at 12, 15, or 18 months of age, higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested (p<0.001). Within the group of children receiving a priming dose of PCV, those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B, yet more frequent erythema (p=0.030) and pain or soreness (p=0.024) at the injection site compared to those boosted with PCV. In conclusion, a single dose of PCV at 12-18 months of age primed for responses to booster doses of either PCV or PN23 12 months later. For those children who received a priming dose of PCV, boosting with PN23 resulted in more frequent injection site pain and erythema than boosting with PCV, yet higher antibody concentrations for most of the serotypes tested.
- Published
- 2000
- Full Text
- View/download PDF
33. Safety and immunogenicity of a new formulation of an inactivated hepatitis A vaccine.
- Author
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Dagan R, Greenberg D, Goldenbertg-Gehtman P, Vidor E, Briantais P, Pinsk V, Athias O, and Dumas R
- Subjects
- Adolescent, Child, Child, Preschool, Female, Hepatitis A Antibodies, Hepatitis A Vaccines, Humans, Immunization, Secondary, Infant, Male, Radioimmunoassay, Single-Blind Method, Vaccines, Inactivated administration & dosage, Vaccines, Inactivated adverse effects, Vaccines, Inactivated immunology, Viral Hepatitis Vaccines administration & dosage, Hepatitis Antibodies blood, Hepatovirus immunology, Viral Hepatitis Vaccines adverse effects, Viral Hepatitis Vaccines immunology
- Abstract
The safety and immunogenicity of a new formulation of the inactivated hepatitis A vaccine, Avaxim, was evaluated in 189 children, aged 18 months to 15 years in a monocentric, open trial. Two vaccinations were given six months apart. Enrollment was balanced within three age groups: 18 months to 3 years, 4-8 years and 9-15 years. Antibody titers were measured blindly by an independent laboratory using a modified radioimmunoassay. Two weeks after the first dose, seroconversion was achieved by 94.6, 94.3 and 96.4% of initially HAV-seronegative subjects (antibody titre <20 mIU/ml) in each age group (youngest to oldest, respectively), with corresponding geometric mean titre concentrations (GMC) of 72.2, 54.3 and 47.1 mIU/ml. Just before the booster dose, the seroconversion rate was 100% in all groups, and the corresponding GMC values were 163, 169 and 111 mIU/ml. All groups included, a 22.6-fold rise in GMC from prebooster levels was observed four weeks after the booster dose. An explanatory analysis suggested a tendency for higher antibody levels in younger children at all vaccination time points. Local reactions were noted in 18.2% of the vaccinees after the first dose and in 8.5% after the booster dose. The rates of systemic reactions were 23.8% after the first dose and 11.4% after the booster dose. Overall, this trial demonstrated the good safety and immunogenicity profile of this vaccine in children aged 18 months to 15 years of age.
- Published
- 1999
- Full Text
- View/download PDF
34. No response to recombinant human erythropoietin therapy in patients with congenital dyserythropoietic anemia type I.
- Author
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Tamary H, Shalev H, Pinsk V, Zoldan M, and Zaizov R
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Recombinant Proteins, Treatment Failure, Anemia, Dyserythropoietic, Congenital drug therapy, Erythropoietin therapeutic use
- Abstract
Congenital dyserythropoietic anemia (CDA) type I is a rare inherited bone marrow disorder characterized by moderate to severe macrocytic anemia with pathognomonic cytopathology of nucleated red blood cells. Previous studies have suggested that serum erythropoietin levels in affected patients are lower than expected for the degree of anemia. An earlier study demonstrated a substantial increase in the number of CFU-E in CDA type I pattern on addition of exogenous erythropoietin. The present study reports on the response to recombinant human erythropoietin in 8 patients with CDA type I. Eighteen weeks of treatment, starting at 300 IU/kg twice a week and gradually increasing to 500 IU/kg three times a week, did not have a substantial effect on the mean hemoglobin value. These results indicate that recombinant human erythropoietin (rHuEpo) is not beneficial to patients with CDA type I and that the relatively low levels of serum erythropoietin probably play no major role in the pathogenesis of the disease.
- Published
- 1999
- Full Text
- View/download PDF
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