The M694V mutation in Armenian-Americans: a 10-year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA.

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto-inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin-encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian-American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.

Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2.

We previously have described a model of multiple sclerosis (MS) in which constitutive expression of murine interleukin (IL)-2 by herpes simplex virus type 1 (HSV-1) (HSV-IL-2) causes central nervous system (CNS) demyelination in different strains of mice. In the current study, we investigated whether this HSV-IL-2-induced demyelination can be blocked using recombinant viruses expressing different cytokines or by injection of plasmid DNA. We have found that coinfection of HSV-IL-2-infected mice with recombinant viruses expressing IL-12p35, IL-12p40 or IL-12p35+IL-12p40 did not block the CNS demyelination, and that coinfection with a recombinant virus expressing interferon (IFN)-γ exacerbated it. In contrast, coinfection with a recombinant virus expressing IL-4 reduced demyelination, whereas coinfection of HSV-IL-2-infected mice with a recombinant HSV-1 expressing the IL-12 heterodimer (HSV-IL-12p70) blocked the CNS demyelination in a dose-dependent manner. Similarly, injection of IL-12p70 DNA blocked HSV-IL-2-induced CNS demyelination in a dose-dependent manner and injection of IL-35 DNA significantly reduced CNS demyelination. Injection of mice with IL-12p35 DNA, IL-12p40 DNA, IL-12p35+IL-12p40 DNA or IL-23 DNA did not have any effect on HSV-IL-2-induced demyelination, whereas injection of IL-27 DNA increased the severity of the CNS demyelination in the HSV-IL-2-infected mice. This study demonstrates for the first time that IL-12p70 can block HSV-IL-2-induced CNS demyelination and that IL-35 can also reduce this demyelination, whereas IFN-γ and IL-27 exacerbated the demyelination in the CNS of the HSV-IL-2-infected mice. Our results suggest a potential role for IL-12p70 and IL-35 signaling in the inhibition of HSV-IL-2-induced immunopathology by preventing development of autoaggressive T cells.

Relationship of diabetic macular oedema with glycosylated haemoglobin.

PURPOSE: To evaluate the correlation between glycosylated haemoglobin (HbA1c) and central foveal thickness as measured by optical coherence tomography (OCT) in patients with diabetes. METHODS: Retrospectively review of medical records of central foveal thickness as measured by OCT and laboratory data of glycosylated haemoglobin. HbA1c was compared with foveal thickness measured by OCT within the preceding 3 months. Clinically significant macular oedema (CSME) was diagnosed if central foveal retinal thickness was greater than 325 mum in OCT. RESULTS: One hundred and two eyes of 102 patients were included in this cross-sectional study. Univariate analysis revealed that the CSME diagnosed by OCT in diabetes was not statistically significant with sex, right or left eye, DM duration over 10 years or not, and AC sugar level (over 140 or not). The HbA1C level (8 or over) and age (50 or less) showed a significant (P=0.005 and 0.006, respectively) and positive association with macular thickness in OCT. A trend towards higher risk was seen for factors of age or=8%. CONCLUSIONS: Patients with HbA1c of 8 or above had an increase in macular thickness in type 2 diabetic eyes and there was a statistical significant correlation between younger age, shorter DM duration and thicker macular thickness. Strict sugar control decreased the risk of diabetic macular retinopathy, and OCT could be an excellent detector of early diabetic macular oedema.

A different approach to assess resident phacoemulsification learning curve: analysis of both completion and complication rates.

PURPOSE: To assess phacoemulsification learning curve by analysing residents' surgical completion and complication rates. METHODS: This prospective study included 226 cases of phacoemulsification performed by 11 senior residents under a single supervisor during a 27-month period. Both completion and complication rates were collected to assess their surgical results. 'Short-term completion rate (STCR)', the frequency of the surgeries completed exclusively by the residents during every five consecutive cases, was used in the evaluation of the learning curve parameter. RESULTS: These residents could complete phacoemulsification independently in 101 surgeries (44.7%). Intraoperative complications occurred in 62 cases (27.4%), of which 11 cases were complicated with vitreous loss (4.9%). By tracing different residents' individual STCRs, we found that the learning curve for phacoemulsification surgery to be of an exponential pattern, and the first STCR of 60% to be a good representation of the exponential point. Before the residents' first STCR of 60%, their average completion rate was only 16.7% and complication rate was as high as 39.2%. While after that point, the average completion rate accelerated to 76.4% and complication rate decreased to 14.2%. CONCLUSION: The learning curve of phacoemulsification is of an exponential pattern and the trainees' STCR can be a useful parameter to evaluate their surgical performance.

One-stage correction for blepharophimosis syndrome.

PURPOSE: To classify the severity of blepharophimosis, describe associated features and their effects on the incidence of amblyopia and to recommend guidelines for surgical treatment and management of surgical complications. METHODS: The case records of 23 patients with blepharophimosis syndrome were examined retrospectively. Patients' photographs and measurements were reviewed to analyse the severity of blepharophimosis, surgical techniques undertaken, surgical outcomes, and complications. Statistical analyses were performed using paired-sample t-tests to evaluate the surgical outcome and Spearman correlation to examine the influence of blepharophimosis on the interpalpebral fissure height (PFH). RESULTS: Eighteen out of 23 (78%) patients underwent one-stage surgery before the age of 5 years. About 31% of these patients had amblyopia. Only two patients had a blepharophimosis ratio greater than 1.5 as poor result. Two out of 18 (11%) patients with PFHs more than 2 mm needed a repeat operation, but all five (100%) patients with s less than 2 mm (very severe ptosis) needed repeat operations. CONCLUSIONS: The one-stage corrective procedure provided acceptable results both in function and cosmesis. However, patients with very severe ptosis required multiple stages of reconstruction for ptosis correction at an earlier age, after which correction of telecanthus and small horizontal palpebral fissure length followed at an older age.