Utah Project on Exfoliation Syndrome (UPEXS): Insight Into Systemic Diseases Associated With Exfoliation Syndrome.

The Utah Project on Exfoliation Syndrome (UPEXS) study was created to investigate the association between exfoliation syndrome (XFS) and systemic disorders or pathologies. The study utilizes the resources of the Utah Population Database, which is linked to the Utah genealogy, a compilation of large pedigrees extending back 3 to ≥11 generations, representing most families in the state. These family members medical and health records are linked to vital records and can be used effectively to identify familial clustering of disorders, like XFS, with comorbid diseases or health-related data. There is growing evidence that XFS patients have an increased risk for systemic disorders that may reflect the systemic tissue involvement of this disease. Epidemiologic studies of individuals with XFS have reported an increased risk of various pathologies that have abnormalities in extracellular matrix metabolism and repair. For this reason, the UPEXS has focused on disorders that involve the extracellular matrix in general and elastin specifically, such as pelvic organ prolapse, atrial fibrillation, inguinal hernias, and chronic obstructive pulmonary disease. In this paper we present our results from the analysis of pelvic organ prolapse, as well as, preliminary data for atrial fibrillation.

Simultaneous Implantation of an Ahmed and Baerveldt Glaucoma Drainage Device for Uncontrolled Intraocular Pressure in Advanced Glaucoma.

PURPOSE: To evaluate efficacy and safety of a novel technique, simultaneous implantation of Ahmed and Baerveldt shunts, for improved control of intraocular pressure (IOP) in advanced glaucoma with visual field defects threatening central fixation. PATIENTS AND METHODS: Retrospective case series; all patients receiving simultaneous Ahmed and Baerveldt implantation at a single institution between October 2004 and October 2009 were included. Records were reviewed preoperatively and at postoperative day 1, week 1, month 1, month 3, month 6, year 1, and yearly until year 5. Outcome measures included IOP, best-corrected visual acuity, visual field mean deviation, cup to disc ratio, number of glaucoma medications, and complications. RESULTS: Fifty-nine eyes were identified; mean (±SD) follow-up was 26±23 months. Primary open-angle glaucoma was most common (n=37, 63%). Forty-six eyes (78%) had prior incisional surgery. Mean preoperative IOP was 25.5±9.8 mm Hg. IOP was reduced 50% day 1 (P<0.001, mean 12.7±7.0 mm Hg), which persisted throughout follow-up. At year 1, cup to disc ratio and mean deviation were stable with decreased best-corrected visual acuity from logMAR 0.72±0.72(20/100) to 1.06±1.13(20/200) (P=0.007). The Kaplan-Meier survival analysis showed median and mean survival of 1205 and 829±91 days, respectively. Complication rate was 47%. CONCLUSIONS: IOP is markedly reduced postoperative day 1 following double glaucoma tube implantation with effects persisting over postoperative year 1 and up to year 5. Complications were higher than that seen in reports of single shunt implantation, which may be explained by patient complexity in this cohort. This technique may prove a promising novel approach for management of uncontrolled IOP in advanced glaucoma.

Characterization of the poly-T variant in the TOMM40 gene in diverse populations.

We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined for rs10524523, hereafter '523', based on the number of 'T'-residues: 'Short' (S, T≤19), 'Long' (L, 20≤T≤29) and 'Very Long' (VL, T≥30). Homopolymers, particularly long homopolymers like '523', are difficult to genotype because 'slippage' occurs during PCR-amplification. We initially genotyped this locus by PCR-amplification followed by Sanger-sequencing. However, we recognized the need to develop a higher-throughput genotyping method that is also accurate and reliable. Here we describe a new '523' genotyping assay that is simple and inexpensive to perform in a standard molecular genetics laboratory. The assay is based on the detection of differences in PCR-fragment length using capillary electrophoresis. We discuss technical problems, solutions, and the steps taken for validation. We employed the novel assay to investigate the '523' allele frequencies in different ethnicities. Whites and Hispanics have similar frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, respectively). In African-Americans, the frequency of the L-allele (0.10) is similar to Whites and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele is concomitantly less frequent (0.25). The allele frequencies determined using the new methodology are compared to previous reports for Ghanaian, Japanese, Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between TOMM40-'523' and APOE alleles. In Whites and Hispanics, consistent with previous reports, the L is primarily linked to ε4, while the majority of the VL and S are linked to ε3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the '523'S-APOEε4 haplotype. These data may be used as references for '523' allele and '523'-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials.