Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial.

The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = -34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

Juvenile glaucoma linked to the GLC1A gene on chromosome 1q in a Panamanian family.

PURPOSE: To characterize clinically and genetically autosomal dominant juvenile-onset primary open-angle glaucoma in a Panamanian family. METHODS: Twenty members of a six-generation family underwent ophthalmologic examination and genetic screening with markers near the GLC1A gene on chromosome 1q. RESULTS: Linkage analysis disclosed evidence linking primary open-angle glaucoma in this family to the GLC1A gene on chromosome 1q, with a maximum lod score of 3.75 for marker D1S431 at an estimated recombination fraction of 0.00. CONCLUSIONS: This is the first report of a Panamanian family in which primary open-angle glaucoma is linked to the GLC1A gene on chromosome 1q.

Accelerated nodulosis during methotrexate therapy for juvenile rheumatoid arthritis.

We describe two patients with rheumatoid factor-positive, polyarticular-onset juvenile rheumatoid arthritis in whom accelerated nodulosis developed during methotrexate therapy. Although they had only a few nodules at diagnosis, the nodules increased in number and size 3 to 4 months after the start of methotrexate therapy in both patients. The nodules regressed after withdrawal of methotrexate therapy in one patient and were arrested with the addition of hydroxychloroquine in the other. Physicians treating patients with methotrexate for juvenile rheumatoid arthritis must be aware of this extraarticular side effect.

Juvenile glaucoma linked to GLCIA in a Panamanian family.

PURPOSE: To carry out clinical and genetic characterization of juvenile-onset primary open-angle glaucoma (POAG) inherited as an autosomal dominant trait in a Panamanian family. METHODS: Twenty-two members of a six-generation Panamanian family underwent an ophthalmologic evaluation. Blood samples were collected from 20 of these individuals for preparation of DNA for use in screening of microsatellite repeat genetic markers via polymerase chain reaction. RESULTS: Eleven living family members covering 4 generations were diagnosed as affected with open-angle glaucoma of primarily juvenile onset. Four of 6 other at-risk individuals examined and enrolled were characterized as unaffected and two as indeterminate. Two additional individuals were not included in this study because they were too young to characterize or to provide a blood sample. Three spouses of affected family members were also examined and found not to have glaucoma. Of clinical importance was the finding of markedly elevated intraocular pressure (IOP) in 2 affected brothers, both of whom were advised to have urgent filtration surgery; the finding of elevated IOP in the only seeing eye of the mother of these brothers, causing us to advise her to pursue more aggressive treatment; and the finding of early signs of glaucoma in a previously undiagnosed 9-year-old family member. Linkage analysis using selected microsatellite repeat markers in the 1q21-q31 region revealed strong evidence for linkage to the GLC1A gene with a maximum lod score of 3.75 for marker D1S431 at a recombination fraction of 0.00. CONCLUSIONS: The most likely interpretation of our data is that a mutation in the GLC1A gene is responsible for juvenile-onset POAG in this Panamanian family, thus expanding the countries of origin where this gene has been found to exist. The numbers of families with GLC1A glaucoma now reported from only a few centers worldwide raise questions about whether this disease may be more common than once thought. Evaluation of treatment histories and clinical outcomes in members of this and other previously reported families indicates that ophthalmologists need to understand the necessity for urgent filtration surgery in most cases of GLC1A glaucoma if vision is to be preserved.