Exploiting flow dynamics for super-resolution in contrast-enhanced ultrasound

Ultrasound localization microscopy offers new radiation-free diagnostic tools for vascular imaging deep within the tissue. Sequential localization of echoes returned from inert microbubbles with low-concentration within the bloodstream reveal the vasculature with capillary resolution. Despite its high spatial resolution, low microbubble concentrations dictate the acquisition of tens of thousands of images, over the course of several seconds to tens of seconds, to produce a single super-resolved image. %since each echo is required to be well separated from adjacent microbubbles. Such long acquisition times and stringent constraints on microbubble concentration are undesirable in many clinical scenarios. To address these restrictions, sparsity-based approaches have recently been developed. These methods reduce the total acquisition time dramatically, while maintaining good spatial resolution in settings with considerable microbubble overlap. %Yet, non of the reported methods exploit the fact that microbubbles actually flow within the bloodstream. % to improve recovery. Here, we further improve sparsity-based super-resolution ultrasound imaging by exploiting the inherent flow of microbubbles and utilize their motion kinematics. While doing so, we also provide quantitative measurements of microbubble velocities. Our method relies on simultaneous tracking and super-localization of individual microbubbles in a frame-by-frame manner, and as such, may be suitable for real-time implementation. We demonstrate the effectiveness of the proposed approach on both simulations and {\it in-vivo} contrast enhanced human prostate scans, acquired with a clinically approved scanner.Comment: 11 pages, 9 figure

Antibody Titers And Response To Vaccination Against Hepatitis A And B In Pediatric Patients With Portal Hypertension

In Brazil, approximately 130 new cases of hepatitis A per 100,000 inhabitants occur annually and 15% of the population has been in contact with hepatitis B virus. Portal hypertension causes hypersplenism and reduces T cell production, which may lead to less effective response to hepatitis vaccination. The objective of the study was to evaluate the response to hepatitis A and B vaccination in patients with portal hypertension secondary to chronic liver disease or portal vein thrombosis. Twenty-three patients (2 to 18 years) with portal hypertension seen at the Pediatric Hepatology Service of Hospital das Clínicas, Universidade Estadual de Campinas, between 1994 and 2006 were studied. Hepatitis A and B serology was tested in all patients. Patients who had not been vaccinated before their visits received the vaccines during the study period. Patients who had been vaccinated before but had negative anti-HB antibodies received a booster dose, and their serology was repeated. Blood counts were performed in each patient to assess for immunosuppression. Eighteen patients received hepatitis A vaccine and all became positive for anti-HAV antibodies. All patients had received hepatitis B vaccine and 17 (73.9%) were anti-HBs positive at the time of the study. The other 6 received a booster dose and became anti-HBs positive afterward. The anti-HBs-positive and -negative patients did not differ significantly in age, leukocytes, lymphocytes, or duration between the vaccination and positive serology. In this study, hepatitis A vaccines elicited a 100% response and hepatitis B vaccine conferred protection and induced an anamnestic response in pediatric patients with portal hypertension.383187193Brasil. Ministério da Saúde. Tópicos de saúde - Hepatites, , http://portal.saude.gov.br/portal/saude/visualizar-texto.cfm?idtext=22248, on line] 2006 [Accessed January 10, 2006] Available atPrevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) (1999) MMWR, 48, pp. 26-27. , Centers for Disease Control and PreventionAkriviadis, E.A., Redeker, A.G., Fulminant hepatitis A in intravenous drug users with chronic liver disease (1989) Ann Int Med, 110, pp. 838-839Keeffe, E.B., Is hepatitis A more severe in patients with chronic hepatitis B and other liver diseases? (1995) Am J Gastroenterol, 90, pp. 201-205Vento, S., Garofano, T., Renzini, C., Cainelli, F., Casali, F., Ghironzi, G., Ferraro, T., Concia, E., Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C (1998) N Engl J Med, 338, pp. 286-290Clemens, R., Safary, A., Hepburn, A., Roche, C., Stanbury, W.J., André, F.E., A clinical experience with an inactivated hepatitis A vaccine (1995) J Infect Dis, 171, pp. S44-S49Ferreira, C.T., Targa, C., Silveira, T.R., Hepatites virais: Aspectos da epidemiologia e da prevenção. (2004) Revista Brasileira de Epidemiologia, 7, pp. 473-487Foccacia, R., Conceição, O.J.G., Sette Junior, H., Sabino, E., Bassit, L., Nitrini, D.R., Lomar, A.V., Fisher, D., Estimated prevalence of viral hepatitis in the general population of the municipality of São Paulo, measures by a serological survey of a stratified, randomized and residence based population (1998) Braz J Infect Dis, 2, pp. 269-284Lee, W.M., Hepatitis B virus infection (1997) N Engl J Med, 337, pp. 1733-1745Kline, M.W., Shearer, W.T., Active and passive immunization in the prevention of infectious diseases (1996) Immunologic disorders in infants and children, pp. 916-938. , Stiehm ER, ed, 4a ed. Philadelphia: Saunders Company;Alper, C.A., Kruskall, M.S., Marcus-Bagley, D., Craven, D.E., Katz, A.J., Brink, S.J., Dienstag, J.L., Yunis, E.J., Genetic prediction of nonresponse to hepatitis B vaccine (1989) N Engl J Med, 321, pp. 708-712Craven, D.E., Awdeh, Z.L., Kunches, L.M., Yunes, E.J., Dienstag, J.L., Werner, B.G., Polk, F., Alper, C.A., Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings (1986) Ann Intern Med, 105, pp. 356-360Idilman, R., Colantoni, A., De Maria, N., Ustun, C., Sam, R., Ingin, T.S., Akan, H., Thiel, D.H.V., Impaired antibody response rates after high dose short interval hepatitis B vaccination of immunosuppressed individuals (2003) Hepato Gastroenterol, 50, pp. 217-221Karasu, Z., Ozacar, T., Akarca, U., Ersoz, G., Erensoy, S., Gunsar, F., Kobat, A., Batur, Y., HBV vaccination in liver transplant patients: Not an effective strategy in the prophylaxis of HBV recurrence (2005) J Viral Hepat, 12, pp. 212-215Lo, C.M., Liu, C.L., Chan, S.C., Lau, G.K., Fan, S.T., Failure of hepatitis B vaccination in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B (2005) J Hepatol, 43, pp. 283-287Henderson, JM. Portal Hypertension. In: Corson J, Williamson R, eds. Surgery [on line] London: Mosby2000 October [Accessed September 12, 2006]. Available at: http:///www.elsevier-international.com/e-books/pdf/8.pdfPinto RB, Silveira TR. Trombose de veia porta em crianças e adolescentes: série de 14 casos. AMRIGS, Porto Alegre 2002;46:45-72Martinelli, A.L.C., Hipertensão portal. (2004) Medicina (Ribeirão Preto), 37, pp. 253-261Schettino, G.C.M., Fagundes, E.D.T., Roquete, M.L.V., Ferreira, A.R., Penna, F.J., Portal vein thrombosis in children and adolescents (2006) J Pediatr (Rio J), 82, pp. 171-178Jacob, H.S., Erythrocyte disorders - anemias related to hyperactivity of the reticuloendothelial system (1972) Hematology, pp. 511-520. , Williams WJ, Beutler E, Erslev AJ, Rundles RW, eds, New York: McGraw-Hill;MacGahan, J.P., Phillips, H.E., Cox, K.L., Sonography of the normal pediatrics gallbladdes an biliary tract (1982) Radiology, 144, pp. 873-875Patriquin, H., Tessier, G., Grignon, A., Boivert, J., Lesser omental thickness in normal children: Baseline for detection of portal hypertension (1985) AJR, 145, pp. 693-696Irigoyen, N., A importância da medida ecográfica do pequeno epíplon no diagnóstico da hipertensão portal em pediatria. (1991) Rev Imagem, 13, pp. 145-148West, M.S., Garra, B.S., Horii, S.C., Hayes, W.S., Cooper, C., Silverman, P.M., Zeman, R.K., Gallbladder varices: Imaging findings in patients with portal hypertension (1991) Radiology, 179, pp. 179-182Hoffbrand, A.V., Pettit, J.E., Moss, P.A.H., (2003) Essential Haematology, p. 331. , 4a ed. Massachusetts: Blackwell Science;Conover WJ. The use of ranks. Two independent samples. In: Conover WJ. Practical Nonparametric Statistics, 1a ed. New York: John Wiley & Sons Inc1971.p.223-236Ferreira, C.T., Taniguchi, A.N., Vieira, S.M., Pereira-Lima, J., da Silveira, T.R., Prevalência do anticorpo da hepatite A em hepatopatia crônica. (2002) J Pediatr (Rio J), 78, pp. 503-508Ferreira, C.T., Silveira, T.R., Vieira, S.M., Taniguchi, A., Pereira-Lima, J., Immunogenicity and safety of hepatitis A vaccine in children with chronic liver disease (2003) J Ped Gastroenterol Nutr, 37, pp. 258-261Arslan, M., Wiesner, R.H., Poterucha, J.J., Zein, N.N., Safety and efficacy of hepatitis A vaccination in liver transplantation recipients (2001) Transplantation, 72, pp. 272-276Dumot, J.A., Barnes, D.S., Younossi, Z., Gordon, S.M., Avery, R.K., Domen, R.E., Henderson, J.M., Carey, W.D., Immunogenicity of hepatitis A vaccine in decompensated liver disease (1999) Am J Gastroenterol, 94, pp. 1601-1604Stark, K., Günther, M., Neuhaus, R., Reinke, P., Schröder, K., Linnig, S., Bienzle, U., Immunogenicity and safety of hepatitis A vaccine in liver and renal transplant patients (1999) J Infect Dis, 180, pp. 2014-2017Keeffe, E.B., Iwarson, S., McMahon, B.J., Lindsay, K.L., Koff, R.S., Manns, M., Baumgarten, R., Krause, D.S., Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease (1998) Hepatology, 27, pp. 881-886Aziz, A., Aziz, S., Li, D.S., Murphy, L., Leone, N., Kennedy, M., Dhillon, S., Van Thiel, D.H., Efficacy of repeated high-dose hepatitis B vaccine in patients with chronic liver disease (2006) J Viral Hepat, 13, pp. 217-221De Maria, N., Idilman, R., Colantoni, A., Van Thiel, D.H., Increased effective immunogenicity to high-dose and short-interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis (2001) J Viral Hepat, 8, pp. 372-376Wiedmann, M., Liebert, U.G., Oesen, U., Porst, H., Wiese, M., Schroeder, S., Halm, U., Berr, F., Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C (2000) Hepatology, 31, pp. 230-234Ferrante, A., Davidson, G.P., Beard, L.J., Goh, D.H.B., Alterations in function and subpopulations of peripheral blood mononuclear leukocytes in children with portal hypertension (1989) Int Arch Allergy Appl Immunol, 88, pp. 348-352McGovern, B., Golan, Y., Lopez, M., Pratt, D., Lawton, A., Moore, G., Epstein, M., Knox, T.A., The impact of cirrhosis on CD4+ cell counts in HIV-seronegative patients (2007) Clin Infect Dis, 44, pp. 431-437Tokushige, K., Yamauchi, K., Komatsu, T., Takasaki, K., Hayashi, N., Predominant T helper 1 cells in patients with idiopathic portal hypertension (2000) J Gastroenterol Hepatol, 15, pp. 1312-1317Williams, I.T., Goldstein, S.T., Tufa, J., Tauillii, S., Margolis, H.S., Mahoney, F.J., Long term antibody response to hepatitis B vaccination beginning at birth and to subsequent booster vaccination (2003) Pediatr Infect Dis J, 22, pp. 157-163Boxall, E.H., Sira, J.A., El-Shunkri, N., Kelly, D.A., Long-term persistence of immunity to Hepatitis B after vaccination during infancy in a country where endemicity is low (2004) J Infect Dis, 90, pp. 1264-126

Steatosis Of Indeterminate Cause In A Pediatric Group: Is It A Primary Mitochondrial Hepatopathy? [esteatose De Causa Não Determinada Em Grupo Pediátrico: Hepatopatia Mitocondrial Primária?]

CONTEXT AND OBJECTIVE: In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. DESIGN AND SETTING: Cross-sectional study at the Departments of Pathology of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). METHODS: Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. RESULTS: "Pure" steatosis was detected, unaccompanied by fbrosis or any other histological alteration. Microvesicular steatosis predominated, with a signifcant increase in mean mitochondrial surface area. CONCLUSION: Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of β-oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders.1294217223Browning, J.D., Horton, J.D., Molecular mediators of hepatic steatosis and liver injury (2004) J Clin Invest, 114 (2), pp. 147-152Zafrani, E.S., Non-alcoholic fatty liver disease: An emerging pathological spectrum (2004) Virchows Arch, 444 (1), pp. 3-12Nobili, V., Marcellini, M., Devito, R., NAFLD in children: A prospective clinical-pathological study and efect of lifestyle advice (2006) Hepatology, 44 (2), pp. 458-465da Silva, G.H., Coelho, K.I., Coelho, C.A., Escanhoela, C.A., Mitochondrial alterations in nonalcoholic fatty liver disease. Pediatric case description of three submitted sequential biopsies (2009) J Gastrointest Liver Dis, 18 (2), pp. 215-219Zhou, Y.J., Li, Y.Y., Nie, Y.Q., Prevalence of fatty liver disease and its risk factors in the population of South China (2007) World J Gastroenterol, 13 (47), pp. 6419-6424Imhof, A., Kratzer, W., Boehm, B., Prevalence of non-alcoholic fatty liver and characteristics in overweight adolescents in the general population (2007) Eur J Epidemiol, 22 (12), pp. 889-897Sagi, R., Reif, S., Neuman, G., Nonalcoholic fatty liver disease in overweight children and adolescents (2007) Acta Paediatr, 96 (8), pp. 1209-1213Ciba, I., Widhalm, K., The association between non-alcoholic fatty liver disease and insulin resistance in 20 obese children and adolescents (2007) Acta Paediatr, 96 (1), pp. 109-112Radetti, G., Kleon, W., Stuefer, J., Pittschieler, K., Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging (2006) Acta Paediatr, 95 (7), pp. 833-837Zou, C.C., Liang, L., Hong, F., Fu, J.F., Zhao, Z.Y., Serum adiponectin, resistin levels and non-alcoholic fatty liver disease in obese children (2005) Endocr J, 52 (5), pp. 519-524Louthan, M.V., Theriot, J.A., Zimmerman, E., Stutts, J.T., McClain, C.J., Decreased prevalence of nonalcoholic fatty liver disease in black obese children (2005) J Pediatr Gastroenterol Nutr, 41 (4), pp. 426-429Fishbein, M., Mogren, J., Mogren, C., Cox, S., Jennings, R., Undetected hepatomegaly in obese children by primary care physicians: A pitfall in the diagnosis of pediatric nonalcoholic fatty liver disease (2005) Clin Pediatr (Phila), 44 (2), pp. 135-141Schwimmer, J.B., Behling, C., Newbury, R., Histopathology of pediatric nonalcoholic fatty liver disease (2005) Hepatology, 42 (3), pp. 641-649Marion, A.W., Baker, A.J., Dhawan, A., Fatty liver disease in children (2004) Arch Dis Child, 89 (7), pp. 648-652Rashid, M., Roberts, E.A., Nonalcoholic steatohepatitis in children (2000) J Pediatr Gastroenterol Nutr, 30 (1), pp. 48-53Molleston, J.P., White, F., Teckman, J., Fitzgerald, J.F., Obese children with steatohepatitis can develop cirrhosis in childhood (2002) Am J Gastroenterol, 97 (9), pp. 2460-2462Mandel, H., Hartman, C., Berkowitz, D., The hepatic mitochondrial DNA depletion syndrome: Ultrastructural changes in liver biopsies (2001) Hepatology, 34 (4 PART 1), pp. 776-784Bioulac-Sage, P., Parrot-Roulaud, F., Mazat, J.P., Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation defciency): A light and electron microscopic study of the liver (1993) Hepatology, 18 (4), pp. 839-846Ghadially, F.N., (1997) Ultrastuctural Pathology of the Cell and Matrix, , 4 th ed. Boston: Butterworth-HeinemannPérez-Carreras, M., del Hoyo, P., Martín, M.A., Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis (2003) Hepatology, 38 (4), pp. 999-1007Morris, A.A., Mitochondrial respiratory chain disorders and the liver (1999) Liver, 19 (5), pp. 357-368Hensley, K., Kotake, Y., Sang, H., Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria (2000) Carcinogenesis, 21 (5), pp. 983-989Pessayre, D., Mansouri, A., Haouzi, D., Fromenty, B., Hepatotoxicity due to mitochondrial dysfunction (1999) Cell Biol Toxicol, 15 (6), pp. 367-373Oleszczuk, A., Spannbauer, M., Tannapfel, A., Regenerative capacity difers between micro- and macrovesicular hepatic steatosis (2007) Exp Toxicol Pathol, 59 (3-4), pp. 205-213Reid, A.E., Nonalcoholic steatohepatitis (2001) Gastroenterology, 121 (3), pp. 710-723Sanyal, A.J., AGA technical review on nonalcoholic fatty liver disease (2002) Gastroenterology, 123 (5), pp. 1705-1725. , Sanyal AJAmerican Gastroenterological AssociationSokol, R.J., Treem, W.R., Mitochondria and childhood liver diseases (1999) J Pediat Gastroenterol Nut, 28 (1), pp. 4-16Natarajan, S.K., Eapen, C.E., Pullimood, A.B., Balasubramanian, K.A., Oxidative stress in experimental liver microvesicular steatosis: Role of mitochondria and peroxisomes (2006) J Gastroenterol Hepatol, 21 (8), pp. 1240-1249Fromenty, B., Pessayre, D., Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity (1995) Pharmacol Ther, 67 (1), pp. 101-154Sherlock, S., Dooley, J., Nutritional and metabolic liver diseases (2002) Diseases of the Liver and Biliary System, pp. 423-452. , In: Sherlock S, Dooley J eds., 11 th ed. Oxford: Blackwell ScienceSternlieb, I., Berger JE. Optical difraction studies of crystalline structures in electron micrographs. II. Crystalline inclusions in mitochondria of human hepatocytes (1969) J Cell Biol, 43 (3), pp. 448-455Caldwell, S.H., Swerdlow, R.H., Khan, E.M., Mitochondrial abnormalities in non-alcoholic steatohepatitis (1999) J Hepatol, 31 (3), pp. 430-434Sanyal, A.J., Campbell-Sargent, C., Mirshahi, F., Nonalcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnormalities (2001) Gastroenterology, 120 (5), pp. 1183-1192Le, T.H., Caldwell, S.H., Redick, J.A., The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis (2004) Hepatology, 39 (5), pp. 1423-1429Day, C.P., James, O.F., Steatohepatitis: A tale of two "hits"? (1998) Gastroenterology, 114 (4), pp. 842-845Gentile, C.L., Pagliassotti, M.J., The role of fatty acids in the development and progression of nonalcoholic fatty liver disease (2008) J Nutr Biochem, 19 (9), pp. 567-57

Clinical and pathological challenges in the diagnosis of late-onset biliary atresia: four case studies

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age49

Uniaxial and biaxial soft deformations of nematic elastomers

We give a geometric interpretation of the soft elastic deformation modes of nematic elastomers, with explicit examples, for both uniaxial and biaxial nematic order. We show the importance of body rotations in this non-classical elasticity and how the invariance under rotations of the reference and target states gives soft elasticity (the Golubovic and Lubensky theorem). The role of rotations makes the Polar Decomposition Theorem vital for decomposing general deformations into body rotations and symmetric strains. The role of the square roots of tensors is discussed in this context and that of finding explicit forms for soft deformations (the approach of Olmsted).Comment: 10 pages, 10 figures, RevTex, AmsTe

Gastric emptying in rats with acetaminophen-induced hepatitis

The objective of this work was to study the gastric emptying (GE) of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise) was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each). Group I was fed a sucrose diet throughout the experiment (66 h) while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each). Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg). Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml) than in group IB (87 µg/ml). The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values). The correlation between gastric retention and AST levels was significant (P<0.05) for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.1133113

Enhanced second harmonic generation from resonant GaAs gratings

We study second harmonic generation in nonlinear, GaAs gratings. We find large enhancement of conversion efficiency when the pump field excites the guided mode resonances of the grating. Under these circumstances the spectrum near the pump wavelength displays sharp resonances characterized by dramatic enhancements of local fields and favorable conditions for second harmonic generation, even in regimes of strong linear absorption at the harmonic wavelength. In particular, in a GaAs grating pumped at 1064nm, we predict second harmonic conversion efficiencies approximately five orders of magnitude larger than conversion rates achievable in either bulk or etalon structures of the same material.Comment: 8 page

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