12 research outputs found
Diagnosis Of Alpha-1-antitrypsin Deficiency By Dna Analysis Of Children With Liver Disease
Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele) and Taq 1 (Z allele). Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ) and two had the S allele with another allele (*S) different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%). A correct diagnosis is important for effective clinical follow-up and for genetic counseling.3816368Alagille, D., Cholestasis in the first three months of life (1979) Prog Liver Dis, 6, pp. 471-485Andresen, B.S., Knudsen, I., Jensen, P.K.A., Gregersen, N., Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha-1-antitrypsin gene (1992) Clin Chem, 38, pp. 2100-2107Balistreri, W.F., Schubert, W.K., Liver disease in infancy and childhood (1993) Diseases of the Liver. 7.ed., pp. 1099-1203. , Schiff L, Schiff ER, editors. Philadelphia: LippincottBillingsley, G.D., Cox, D.W., Functional assessment of genetic variants of alpha 1-antitrypsin (1982) Hum Genet, 61, pp. 118-122Brantly, M., Nukiwa, T., Crystal, R.G., Molecular basis of alpha-1-antitrypsin deficiency (1988) Am J Med, 84, pp. 13-31Carlson, J.A., Rogers, R.B., Sifers, R., Acumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice (1989) J Clin Invest, 83, pp. 1183-1190Carrel, R.W., Alpha 1-antitrypsin: Molecular pathology, leukocytes and tissue damage (1986) J Clin Invest, 78, pp. 1427-1431Cox, D.W., Woo, S.L., Mansfield, T., DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z (1985) Nature, 316, pp. 79-81Crystal, R.G., Brantly, M.L., Hubbard, R.C., Curiel, D.T., States, D.J., Holmes, M.D., The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy (1989) Chest, 95, pp. 196-208Crystal, R.G., Ferrans, V.J., Basset, F., Biologic basis of pulmonary fibrosis (1991) The Lung: Scientific Foundations, pp. 2031-2046. , Crystal RG, West JB, Barnes PJ, Cherniack S, editors. New YorkRaven PressCuriel, D., Brantly, M., Curiel, E., Crystal, R.G., Alpha-1-antitrypsin deficiency caused by the alpha-1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha-1-antitrypsin gene incapable of producing alpha-1-antitrypsin (1989) J Clin Invest, 83, pp. 1144-1152Dermer, S.J., Johnson, E.M., Rapid DNA analysis of alpha 1-antitrypsin deficiency: Application of an improved method for amplifying mutated gene sequence (1988) Lab Invest, 59, pp. 403-408Deutsch, J., Becker, H., Auböck, L., Histopathological features of liver disease in alpha 1-antitrypsin deficiency (1994) Acta Paediatr, 393 (SUPPL.), pp. 8-12Dubel, J.R., Finwick, R., Hejtmancik, J.F., Denaturing gradient gel electrophoresis of the alpha 1-antitrypsin gene: Application to prenatal diagnosis (1991) Am J Med Genet, 41, pp. 39-43Evans, H.E., Levi, M., Mandl, I., Serum enzyme inhibitor concentrations in the respiratory distress syndrome (1970) Am Rev Resp Dis, 101, pp. 359-363Fagerhol, M.K., Cox, D.W., The PI polimorphism: Genetic, biochemical and clinical aspects of human alpha-1-antitrypsin (1981) Human Genetic, pp. 1-62. , Harris H, Hirchorn, K, editors. New York: PlenumGartner, J.C., Zitelli, B.J., Malatak, J.J., Shaw, B.W., Iwatsuki, S., Starzl, T.E., Orthotopic liver transplantation in children: Two-year experience with 47 patients (1984) Pediatrics, 74, pp. 140-145Ishak, K.G., Hepatic morphology in inherited metabolic diseases (1986) Sem Liver Dis, 6, pp. 246-258Jeppsson, J.O., Laurell, C.B., Fagerhol, M.K., Properties of isolated alpha-1-antitrypsin of Pi types M, S and Z (1978) Eur J Biochem, 83, pp. 143-153Lai, E.C., Kao, F.T., Law, M.L., Woo, S.L., Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromossome 14 by molecular hybridization (1983) Am J Hum Genet, 35, pp. 385-392Laurell, C.B., Eriksson, S., The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antitrypsin deficiency (1963) Scand J Clin Lab Invest, 15, pp. 132-140Laurell, C.B., Kullander, S., Thorell, J., Effect of administration of a combined strogen-progestin contraceptive on the level of individual plasma proteins (1968) Scand J Clin Lab Invest, 21, pp. 337-343Massi, G., Chiarelli, C., Alpha 1-antitrypsin: Molecular and the Pi system (1994) Acta Paediatr, 393 (SUPPL.), pp. 1-4Mowat, A.P., Avaliação laboratorial das afecções hepatobiliares (1991) Doenças Hepáticas Em Pediatria. 2.ed., pp. 410-430. , Mowat AP. Rio de Janeiro: RevinterNukiwa, T., Brantly, M., Ogushi, F., Crystal, R.G., Characterization of the M1(ala 213) type of alpha-1-antitrypsin, a newly recognized common "normal" alpha-1-antitrypsin haplotype (1987) Biochemistry, 26, pp. 5259-5267Okayama, H., Curiel, D.T., Brantly, M.L., Holmes, M.D., Crystal, R.G., Rapid nonradioactive detection of mutations in the human genome by allele-specific amplification (1989) J Lab Clin Med, 114, pp. 105-113Perlmutter, D.H., The cellular basis for liver injury in alpha-1-antitrypsin deficiency (1991) Hepatology, 13, pp. 172-185Perlmutter, D.H., Clinical manifestations of alpha 1-antitrypsin deficiency (1995) Gastroenterol Clin North Am, 24, pp. 27-43Schroeder, W.T., Miller, M.F., Woo, S.L., Saunders, G.F., Chromosomal localization of the human alpha 1-antitrypsin gene (PI) to 14q31-32 (1985) Am J Hum Genet, 37, pp. 868-872Serra, H.G., (1998) Identificação Molecular Dos Alelos S e Z Do Gene Da Alfa-1-antitripsina Em Um Grupo de Pacientes Portadores de Doença Pulmonar Crônica [tese de Doutorado], , Campinas, SP: Instituto de Biologia da Universidade Estadual de CampinasSilverman, E.K., Miletich, J.P., Pierce, J.A., Sherman, L.A., Endicott, S.K., Broze, G.J., Campbell, E.J., Alpha-1-antitrypsin deficiency. High prevalence in the St. Louis area determined by direct population screening (1989) Am Rev Respir Dis, 140, pp. 961-966Sveger, T., Liver disease in alpha 1-antitrypsin deficiency detected by screening of 200,000 infants (1976) N Engl J Med, 294, pp. 1316-1321Sveger, T., The natural history of liver disease in alpha 1-antitrypsin deficient children (1988) Acta Paediatr Scand, 77, pp. 847-851Sveger, T., Ericksson, S., The liver in adolescents with alpha 1-antitrypsin deficiency (1995) Hepatology, 22, pp. 514-517Talbot, I.C., Mowat, A.P., Liver disease in infancy. Histological features and relationship to alpha 1-antitrypsin phenotype (1975) J Clin Pathol, 28, pp. 559-563Travis, J., Salvesen, G.S., Human plasma proteinase inhibitors (1983) Annu Rev Biochem, 52, pp. 655-709Van Steenbergen, W., Alpha 1-antitrypsin deficiency: An overview (1993) Acta Clin Belg, 48 (3), pp. 171-189Wewers, M.D., Casolaro, M.A., Sellers, S.E., Swayze, S.C., McPhaul, K.M., Wittes, J.T., Crystal, R.G., Replacement therapy deficiency associated with emphysema (1987) N Engl J Med, 316, pp. 1055-1062Woodhead, J.L., Fallon, R., Figuered, H., Longdale, J., Malcom, A.D.B., Alternative methodology of gene diagnosis (1986) Human Genetic Diseases - a Pratical Approach, pp. 51-64. , Davies KE, editor. Oxford: IRL Pres
Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease:a multicenter international study
Background and aims Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aim to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPTIC-IBD. Methods We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, classifications of colonic lesions, utilizing still images and videos. We invited gastroenterologists from Canada, Italy, and the UK, with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions following training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. Results One hundred seventeen participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (p 0.002) following training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between pre- and post-course (
Spin dynamics from time-dependent density functional perturbation theory
We present a new method to model spin-wave excitations in magnetic solids, based on the Liouville-Lanczos approach to time-dependent density functional perturbation theory. This method avoids computationally expensive sums over empty states and naturally deals with the coupling between spin and charge fluctuations, without ever explicitly computing charge-density susceptibilities. Spin-wave excitations are obtained with one Lanczos chain per magnon wave-number and polarization, avoiding the solution of the linear-response problem for every individual value of frequency, as other state-of-the-art approaches do. Our method is validated by computing magnon dispersions in bulk Fe and Ni, resulting in agreement with previous theoretical studies in both cases, and with experiment in the case of Fe. The disagreement in the case of Ni is also comparable with that of previous computations
In Situ Hydrogel Extraction with Dual-Enzyme Digestion of Proteinaceous Binders: the Key for Reliable Mass Spectrometry Investigations of Artworks
Comparison of serum myoglobin and creatine kinase MB isoenzyme in early diagnosis of acute myocardial infarction.
Non-invasive detection of ischemic left ventricular dysfunction using rest gated SPECT: expectation of simultaneous evaluation of both myocardial perfusion and wall motion abnormality
Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.
The Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an \u2018Official MDS translation,\u2019 the Comparative Fit Index (CFI) had to be 650.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was 650.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages