ABSTRACT
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A. Deficiency of this enzyme results in intralysosomal storage of sphingolipid cerebroside 3-sulfates (sulfatides), which are abundant in myelin and neurons. A pathological hallmark of MLD is demyelination and neurodegeneration, causing various and ultimately lethal neurological symptoms. This review discusses the potential therapeutic application of hematopoietic stem cell gene therapy and intracerebral gene transfer (brain gene therapy) in patients with MLD.
Subject(s)
Cerebroside-Sulfatase/genetics , Genetic Therapy/methods , Leukodystrophy, Metachromatic/therapy , Animals , Brain/enzymology , Brain/pathology , Cerebroside-Sulfatase/deficiency , Disease Models, Animal , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukodystrophy, Metachromatic/genetics , Leukodystrophy, Metachromatic/pathology , MicroinjectionsABSTRACT
BACKGROUND/AIMS: This study aimed to evaluate the Baveno II criteria defining key events in variceal bleeding. METHODS: These criteria were applied to 196 patients with cirrhosis admitted for upper gastrointestinal bleeding due to portal hypertension and enrolled in a trial. Blood pressure, heart rate, hematocrit and clinical signs of upper digestive tract hemorrhage were recorded for 5 days. The blind overall clinical judgment of hemodynamic stability was recorded separately by the Steering Committee. RESULTS: The evaluation of several hemodynamic criteria was left to the judgment of the clinician. The first time point for the control of bleeding, fixed at 6 h after admission, was impractical since 13% of the patients had not yet received specific treatment. The independent judgment did not agree in 38% of 82 cases without control of bleeding. In 15% of cases this was due to tachycardia. Calculation of several judgment criteria was not defined in the Baveno II criteria: survival without bleeding at 5 days, transfusion rate, and length of hospital stay. CONCLUSIONS: Although the Baveno II criteria have improved the definitions of key events, the criteria are hampered by limits such as false positive criteria of failure to control bleeding. We make several proposals for improvement.
