Approach and management considerations in low phospholipid associated cholelithiasis (LPAC) syndrome

Low phospholipid associated cholelithiasis (LPAC) syndrome, first described in 2001, could be the causality in a significant number of young patients with cholelithiasis, who have a recurrence of symptoms despite cholecystectomy. A mutation of the ABCB4/MDR3 gene, causes a disruption in the translocation of phosphatidylcholine, resulting in bile acid mediated biliary tract injury. The ABCB4 gene is also implicated in other diseases such as progressive familial intrahepatic cholestasis type 3, which is greater in severity and tools like genotyping can aid the physician in prognostication, as well as determining the response to medical therapy. A few symptomatic patients develop features of biliary obstruction due to intrahepatic calculi, and they require interventions-which may be endoscopic or surgical in nature. Although a majority of patients with LPAC syndrome respond well to ursodeoxycholic acid (UDCA) therapy, close monitoring is warranted to keep a check on disease progression

Effect of fluidics on corneal endothelial cell density, central corneal thickness, and central macular thickness after phacoemulsification with torsional ultrasound

Aim: To study the relative effects of high and low fluidic parameters on endothelial cell density (ECD), central corneal thickness (CCT), and central macular thickness (CMT) after phacoemulsification with torsional ultrasound. Settings and Design: Prospective, randomized clinical trial based on a tertiary eye hospital. Subjects and Methods: The study included 65 patients in each group. Patients were randomized to either the high or the low flow group using a computerized random number table. The study was patient and examiner masked. All patients underwent phacoemulsification with torsional ultrasound. Visual acuity, ECD, CCT, and CMT were measured for all patients preoperatively at 2 weeks and 6 weeks postoperatively. Statistical Analysis Used: The Shapiro–Wilks test was used to assess the normality of the data. Mann–Whitney U-test with the P value set at 0.05 was used to compare the two groups. Results: Cumulative dissipated energy was significantly higher in the low flow group (16.44 ± 9.07 vs. 11.74 ± 6.68; P = 0.002). No statistically significant difference was noted between the two groups in the ECD, CCT, CMT, or corrected distance visual acuity at the end of 6 weeks. Conclusions: No significant difference was noted in the postoperative outcome between high and low flow groups. Parameters can be modified to suit the surgeon's preference, as both high and low flow parameters were found to have comparable postoperative outcomes

Two novel missense substitutions in the VSX1 gene: clinical and genetic analysis of families with Keratoconus from India

BACKGROUND: Visual system homeobox gene (VSX1) plays a major role in the early development of craniofacial and ocular tissues including cone opsin gene in the human retina. To date, few disease-causing mutations of VSX1 have been linked to familial and sporadic keratoconus (KC) in humans. In this study, we describe the clinical features and screening for VSX1 gene in families with KC from India. METHODS: Clinical data and genomic DNA were collected from patients with clinically diagnosed KC and their family members. The study was conducted on 20 subjects of eight families from India. The coding exons of VSX1 gene were amplified using PCR and amplicons were analyzed by direct sequencing. Predictive effect of the mutations was performed using Polyphen-2, SIFT and mutation assessor algorithms. Additionally, haplotypes of VSX1 gene were constructed for affected and unaffected individuals using SNPs. RESULTS: In the coding region of VSX1, one novel missense heterozygous change (p.Leu268His) was identified in five KC patients from two unrelated families. Another family of three members had a novel heterozygous change (p.Ser251Thr). These variants co-segregated with the disease phenotype in all affected individuals but not in the unaffected family members and 105 normal controls. In silico analysis suggested that p.Leu268His could have a deleterious effect on the protein coded by VSX1, while p.Ser251Thr has a neutral effect on the functional properties of VSX1. Haplotype examination revealed common SNPs around the missense change (p.Leu268His) in two unrelated KC families. CONCLUSIONS: In this study, we add p.Leu268His, a novel missense variation in the coding region of VSX1 to the existing repertoire of VSX1 coding variations observed in Indian patients with the characteristic phenotype of KC. The variant p.Ser251Thr might be a benign polymorphism, but further biophysical studies are necessary to evaluate its molecular mechanism. The shared haplotype by two families with the same variant suggests the possibility of a founder effect, which requires further elucidation. We suggest that p.Leu268His might be involved in the pathogenesis of KC, which may help in the genetic counselling of patients and their family