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The mean annual incidence of hemolytic uremic syndrome in persons

The reactogenicity and immunogenicity of a tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HB) vaccine (SmithKline Beecham) were studied in 565 infants immunized according to one of two different schedules, at 2, 4 and 6 months of age (group A n = 208) or at 3, 5 and 11 months of age (group B n = 357). The incidences of local and general reactions within the first 8 days after vaccination were similar in the two groups of infants, the vast majority being mild in intensity and occurring within 2-3 days of vaccine administration. Severe local symptoms were rare: pain after 0.6% of all doses, redness after 0.5% and 1.3%, and swelling after 0.3% and 1.5%, in group A and B, respectively. Only one infant in group A and one in group B had a temperature39.0 degrees C. Both schedules proved satisfactory in obtaining high levels of antibodies against all antigens. The rates of serologic response against the different antigens reached 100% in both groups. Antibody titres against all vaccine components were elevated following both schedules, but after the third dose of vaccine geometric mean antibody titres (GMTs) against D toxoid, filamentous haemagglutinin (FHA), pertactin (PRN) and hepatitis B (HB) were significantly higher in the 3, 5, 11 group than after the 2, 4, 6 schedule. Antibody titres measured at 7 months of age in the group immunized at 2, 4 and 6 months were higher than those reached at 6 months of age in infants immunized at 3, 5 and 11 months, but FHA and PRN were within the range of DTPa vaccine with proven efficacy. We conclude that DTPa-HB vaccine was safe, well tolerated and highly immunogenic. Both vaccination schedules (2, 4, 6 and 3, 5, 11) can be considered suitable for mass immunization programmes.

We evaluated the immune status against diphtheria (D), tetanus (T) and polio viruses (PV) and the immune response to re-administration of the respective vaccines in a series of 23 transplanted homozygous beta-thalassemic patients, aged 5-17 years (mean age 12.1 +/- 3.1 years). They had been given compulsory DT toxoids and types 1, 2 and 3 PV vaccine in infancy and had been successfully submitted to allogeneic BMT 2-6 years previously. Prior to revaccination, a high percentage of subjects (from 48% for type 2 PV to 83% for D) had antibody levels below the protective levels and low geometric mean titers (GMTs). After revaccination (three doses of DT toxoids and of inactivated PV vaccine) the percentage of subjects with protective levels of antibodies rose to 86-100% and the GMTs increased markedly. We conclude that: (1) the protection afforded by compulsory DT and PV vaccines administered in infancy is almost entirely lost in beta-thalassemic patients for several years after BMT, (2) revaccination is necessary in these subjects, and (3) at least three doses of DT and PV vaccines must be administered to recover adequate protection.

Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A--T transversion. The translation product of the mutant allele was predicted to be a receptor with an in-frame insertion of 6 amino acids in repeat B of the epidermal growth factor precursor homology domain. Analysis of LDL-receptor activity in the proband's fibroblasts showed a 50% reduction of 125I-labeled LDL binding and pulse-chase studies suggested that little, if any, of the mutant protein was processed to the mature form. The second mutation was a 7 kb duplication (from intron 2 to intron 6) of exons 3 through 6, predicted to encode an elongated receptor with the duplication of repeats 2-7 of the ligand binding domain. The elongated receptor was processed slightly more slowly than the normal receptor, but was converted to a mature form of the expected size. This mature, mutant receptor was degraded more rapidly than the normal receptor. On ligand blotting the elongated receptor bound twice as much LDL or beta-very low density lipoprotein (betaVLDL) as the normal receptor. In contrast, maximum binding of LDL to proband's cells was decreased to approximately 70% of the normal cells with a significant increase in apparent affinity. Cell association at 37 degrees C, internalization, and degradation showed a similar reduced maximum. Thus these mutations demonstrate that duplications of amino acid sequences in the low density lipoprotein LDL-receptor may disrupt the LDL-receptor pathway at different levels.

Benign familial hematuria (BFH: MIM141200) is an autosomal-dominant disease accounting for one-fifth of all hematuria of unknown cause in children. Previous observations suggest that BFH may be allelic to recessive Alport syndrome (AS: MIM 203780) with a mutation in the COL4A3/COL4A4 locus. However, it is not clear whether all cases of BFH are due to heterozygous mutation of COL4A3/COL4A4 genes. We report here the exclusion of linkage between BFH and COL4A3/COL4A4 loci at 2q35-37 in a restricted population from Sicily (Italy). Total lod score is –9.6 at theta 0. Furthermore, in some cases exclusion of linkage is evident even considering single families. We conclude that BFH is genetically heterogeneous.