ABSTRACT
OBJECTIVE: We aimed to determine the frequency of all known forms of congenital muscular dystrophy (CMD) in a large Australasian cohort. METHODS: We screened 101 patients with CMD with a combination of immunofluorescence, Western blotting, and DNA sequencing to identify disease-associated abnormalities in glycosylated alpha-dystroglycan, collagen VI, laminin alpha2, alpha7-integrin, and selenoprotein. RESULTS: A total of 45% of the CMD cohort were assigned to an immunofluorescent subgroup based on their abnormal staining pattern. Abnormal staining for glycosylated alpha-dystroglycan was present in 25% of patients, and approximately half of these had reduced glycosylated alpha-dystroglycan by Western blot. Sequencing of the FKRP, fukutin, POMGnT1, and POMT1 genes in all patients with abnormal alpha-dystroglycan immunofluorescence identified mutations in one patient for each of these genes and two patients had mutations in POMT2. Twelve percent of patients had abnormalities in collagen VI immunofluorescence, and we identified disease-causing COL6 mutations in eight of nine patients in whom the genes were sequenced. Laminin alpha2 deficiency accounted for only 8% of CMD. alpha7-Integrin staining was absent in 12 of 45 patients studied, and ITGA7 gene mutations were excluded in all of these patients. CONCLUSIONS: We define the distribution of different forms of congenital muscular dystrophy in a large cohort of mixed ethnicity and demonstrate the utility and limitations of current diagnostic techniques.
Subject(s)
Genetic Predisposition to Disease/genetics , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscular Dystrophies/congenital , Muscular Dystrophies/genetics , Mutation/genetics , Australasia/ethnology , Blotting, Western , Child, Preschool , Cohort Studies , Collagen Type VI/genetics , DNA Mutational Analysis , Diagnosis, Differential , Dystroglycans/deficiency , Dystroglycans/genetics , Ethnicity/genetics , Female , Fluorescent Antibody Technique , Genetic Testing , Genotype , Humans , Infant , Infant, Newborn , Male , Mannosyltransferases/genetics , Membrane Proteins/genetics , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophies/diagnosis , N-Acetylglucosaminyltransferases/geneticsABSTRACT
La perforación espontánea de la vía biliar es una entidad poco frecuente y de etiología variable. Se presentan dos pacientes tratadas en el Servicio de cirugía Pediátrica de Hospital Italiano de Buenos Aires. Las manifestaciones clínicas comunes a los dos pacientes fueron: distensión abdominal, ictericia, acolia y ascitis biliosa. La conducta fue inicialmente quirúrgica, realizándose el diagnóstico de certeza mediante una colecistocolangiografía intraoperatoria. El tratamiento fue con drenaje del área colecistocoledociana y derivación de la vía biliar por colecistomía,obteniéndose una recuperación satisfactoria de ambos pacientes
Subject(s)
Humans , Child , Biliary Tract Diseases , Biliary Tract Diseases/surgery , Biliary Tract Diseases/diagnosisABSTRACT
La perforación espontánea de la vía biliar es una entidad poco frecuente y de etiología variable. Se presentan dos pacientes tratadas en el Servicio de cirugía Pediátrica de Hospital Italiano de Buenos Aires. Las manifestaciones clínicas comunes a los dos pacientes fueron: distensión abdominal, ictericia, acolia y ascitis biliosa. La conducta fue inicialmente quirúrgica, realizándose el diagnóstico de certeza mediante una colecistocolangiografía intraoperatoria. El tratamiento fue con drenaje del área colecistocoledociana y derivación de la vía biliar por colecistomía,obteniéndose una recuperación satisfactoria de ambos pacientes
Subject(s)
Humans , Child , Biliary Tract Diseases , Biliary Tract Diseases/surgery , Biliary Tract Diseases/diagnosisABSTRACT
BACKGROUND: There is no evidence that the results of laparoscopic fundoplication in children match those of the open procedure. In the current report, pre- and postoperative function of the antireflux barrier is examined in children having laparoscopic fundoplication for gastroesophageal reflux. METHODS: Twenty-seven patients with gastroesophageal reflux, aged 7.2+/-4.5 years, were operated on for unremitting gastrointestinal symptoms (n = 24), with respiratory tract disease (n = 11), cystic fibrosis (n = 2), or brain damage (n = 11). Gastrostomy was added in 5 cases. Barium contrast study, pH-metering, endoscopic examination, and biopsy were performed before and after a median of 19 months (range, 8 to 46) after operation. RESULTS: At diagnosis, 15 of 21 patients had esophagitis that was moderate or severe in 11 (1 with Barrett's esophagus). Symptoms disappeared after fundoplication in all but 2 patients, in whom they became milder. The reflux index decreased from 20.2+/-20% to 4.9+/-9% and became normal in all except 4 children (2 with brain damage and 1 with cystic fibrosis). Open repair of the failed wrap was considered necessary in only 1 of them. CONCLUSIONS: Laparoscopic fundoplication is as effective as the open procedure (14% overall failure rate). However, the failure rate in neurologic patients (18%) suggests that before reaching conclusions on the benefits of this approach, careful long-term assessment of the functional results is necessary.
Subject(s)
Fundoplication , Gastroesophageal Reflux/surgery , Laparoscopy , Treatment Outcome , Biopsy , Brain Injuries/complications , Child, Preschool , Cystic Fibrosis/complications , Female , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/pathology , Gastrostomy , Humans , Infant , Male , Respiratory Tract Diseases/complicationsABSTRACT
Sera from 899 hepatitis B surface antigen (HBsAg) carriers from four separate ethnic groups (Caucasian, Australian Aboriginal, Melanesian, and Asian) were studied for their correlation for hepatitis B virus deoxyribonucleic acid (HBV DNA) and hepatitis B e antigen (HBeAg). Discordance, as signified by the absence of HBV DNA despite the presence of HBeAg, was unusual in Caucasians but frequently occurred in the other three ethnic groups (11-25%). Analysis by age showed that it occurred occasionally during childhood and, in this age group, may simply be part of the process of seroconversion with impending loss of HBeAg, whereas its greater prevalence in patients with liver disease may have a different mechanism. In sera obtained from Melanesians with hepatocellular carcinoma and Asians with chronic hepatitis, discordance was a common feature with HBV DNA being undetectable in those with HBeAg in 87% and 72%, respectively. A number of important implications flow from these observations pertinent to the use of HBeAg to detect replicating virus and the prognostic significance of HBeAg in HBsAg carriers when HBV DNA is undetectable.
Subject(s)
Hepatitis B e Antigens/analysis , Hepatitis B virus/immunology , Child , Chronic Disease , DNA, Viral/immunology , Ethnicity , Female , Hepatitis , Hepatitis B virus/genetics , Hepatitis B virus/growth & development , Heterozygote , Humans , Male , Pregnancy , Virus Replication , White PeopleABSTRACT
Sera from 20 Chinese patients with chronic hepatitis B were examined for hepatitis B e antigen and hepatitis B virus (HBV) DNA. There was considerable discordance with HBV DNA not being detectable in 10 out of 13 (77%) patients who were hepatitis B e antigen positive. Further testing for anti-HBe and HBV-DNA polymerase activity confirmed the results. Possible reasons for this discordance are discussed but neither hepatitis D (delta) infection nor the acquired immunodeficiency syndrome (AIDS) could be implicated.
