Preparation of Stable Intermediate-Purity Factor VIII Concentrate with a Note on High-Purity Factor VIII

Cryoprecipitate prepared by a rapid thawing technique was pooled in batches of 600--720 donor units and washed with ice-cold Tris-citrate-NaCl solution. After dissolving at 37 degrees C, it was adsorbed with Al(OH)3 and kaolin, and cleared by centrifugation. The supernatant, diluted with 5% dextrose was passed repeatedly through a bed of Celite, filtered through a 293 mm X 0.3 micrometer membrane disc and lyophilized. Typical composition was 15 U . ml-1 factor VII, and 40 mg . ml-1 protein with a yield of 300 U/l of starting plasma. The crude factor VIII concentrate was also a suitable material for preparation of high-purity factor VIII by controlled pore glass chromatography.     

Huntington's disease like-2: review and update

Huntington's Disease-like 2 (HDL2), like Huntington's disease (HD), is an adult onset, progressive, neurodegenerative autosomal dominant disorder clinically characterized by abnormal movements, dementia, and psychiatric syndromes. Like HD, the neuropathology of HDL2 features prominent cortical and striatal atrophy and intranuclear inclusions. HDL2 is generally rare, accounting for only a few percent of HD-like cases in which the HD mutation has already been excluded. However, the rate is considerably higher among individuals of African ancestry, and is almost as common as HD in Black South Africans. The disorder is caused by a CTG/CAG expansion mutation on chromosome 16q24.3, with normal and expanded repeat ranges similar to HD, and a correlation between repeat length and onset age very similar to HD. Surprisingly, the available evidence suggests that HDL2 is not a polyglutamine disease. Rather, the repeat expansion is located within Junctophilin-3 in the CTG orientation. The phenotypic similarities between HD and HDL2 suggest that understanding the pathobiology of HDL2 may shed new light on the pathogenesis of HD and other disorders of striatal neurodegeneration.     

Vaccine safety controversies and the future of vaccination programs

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.     

Effect of maternal antibody on immunogenicity of hepatitis A vaccine in infants

OBJECTIVE: To determine the effect of maternal antibody on hepatitis A vaccine immunogenicity in infants.Study design Infants of mothers negative for antibody to hepatitis A virus (anti-HAV; group 1) were administered hepatitis A vaccine at 2, 4, and 6 months of age, and infants of anti-HAV-positive mothers were randomized to receive either hepatitis A vaccine (group 2) or hepatitis B vaccine (group 3) on the same schedule. Group 3 infants subsequently received hepatitis A vaccine at 8 and 10 months of age. RESULTS: At 15 months of age, 100% of infants in group 1, 93% in group 2, and 92% in group 3 had protective levels of antibody. However, there were significant differences in the geometric mean concentration (GMC) of anti-HAV between groups. Group 1 GMC was 231 mIU/mL, compared with 85 mIU/mL for group 2 and 84 mIU/mL for group 3 (P<.001, group 1 vs group 3). CONCLUSIONS: Passively acquired maternal anti-HAV resulted in a significantly lower final antibody response when infants were administered hepatitis A vaccine at 2, 4, and 6 months of age or at 8 and 10 months of age.     

Adenoviral vector-mediated rescue of the OMP-null behavioral phenotype: enhancement of odorant threshold sensitivity

Mice from which the olfactory marker protein (OMP) gene has been deleted demonstrate a number of neurophysiologic and behavioral defects that suggest OMP is an important component in olfactory signal transduction and is critically involved in odor processing. Recently, the potential pleiotropic effects of gene deletion were addressed by adenoviral vector-mediated rescue of the neurophysiologic defects, in vivo. As a complement to this study, the authors used a recombinant adenoviral vector to transiently introduce OMP into olfactory sensory neurons of adult OMP-null mice and, using psychophysical methods, demonstrated the resulting reacquisition of behavioral function subsequent to gene replacement. The rescue of the OMP-null behavioral phenotype further supports the hypothesis that OMP is an important component in olfactory signal amplification and/or transduction processing.     

Malignant infantile osteopetrosis & primary pulmonary hypertension: A new combination?

Malignant infantile osteopetrosis (MIOP), a rare genetic disorder of the osteoclast, is fatal without hematopoietic stem cell transplantation. Primary pulmonary hypertension (PPH), a rare progressive disorder of the pulmonary circulation, is predominantly fatal in the absence of successful therapy. A clinical association between these two disorders has not been recognized and a pathophysiologic link between osteoclast function and pulmonary vascular pressure as a rationale for such an association is not readily apparent. Here, we report five infants with MIOP, without cardiac abnormalities, who were found to have PPH after undergoing stem cell transplantation. We suggest that PPH may be linked to a specific variant of MIOP and recognizing the potential for pulmonary hypertension in children with MIOP may lead to a more rapid diagnosis and life-saving intervention.