Continuous amnioinfusion for treatment of mid-trimester preterm premature rupture of membranes with oligoamnios.

AIM: Given the scarcity of relevant reports, this study aimed to elucidate whether pregnancy can be prolonged by maintaining the amniotic fluid volume with continuous transabdominal amnioinfusion (TA) for patients with mid-trimester preterm premature rupture of membranes (PPROM) and oligoamnios. METHODS: We retrospectively examined patients who were managed during hospitalization at our department after developing PPROM between week 22 day 0 and week 25 day 6 of gestation and subsequent oligoamnios (amniotic fluid index [AFI] <5 cm) within 7 days after PPROM onset. Cases between 2006 and 2011 comprised the conventional management group (n = 14); cases administered continuous TA between 2012 and 2017 comprised the continuous TA group (n = 14). The primary outcome was the number of days between PPROM and delivery. The secondary outcomes were the proportion of normal amniotic fluid volume (AFI ≥ 5 cm) maintained between PPROM and delivery and the perinatal prognosis for the mother and infant. RESULTS: The continuous TA group had significantly more days between PPROM and delivery and a significantly higher proportion of days that a normal amniotic fluid volume was maintained during that period, regardless of antimicrobial agents administered. Although no significant differences in the perinatal prognosis of disease were found between groups, there was a decreasing trend of composite perinatal mortality and morbidity, and the incidence rates were reduced by half. CONCLUSION: Continuous TA for PPROM with oligoamnios may allow significant prolongation of the gestation period while maintaining the amniotic fluid volume and may lead to improved perinatal prognosis.

Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population.

PURPOSE: To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients. DESIGN: A case-control study. PARTICIPANTS: A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls. METHODS: Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology. MAIN OUTCOME MEASURES: The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(-7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes. CONCLUSIONS: The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.

Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population.

PURPOSE: Ethnic variation has been reported in age-related macular degeneration (AMD)-associated Y402H polymorphism in complement factor H (CFH). This variation is evident in the Japanese population. Recently a strong association between a novel single-nucleotide polymorphism (SNP; rs1410996) in the CFH gene and AMD has been identified in Caucasian patients. The present study was undertaken to investigate whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients. METHODS: A total of 188 patients with AMD and 139 control subjects without AMD were recruited for the study. Four SNPs (rs800292, rs1061170, rs1410996, and rs2274700) in the CFH gene were assessed by genotyping assay. The information regarding systemic conditions and lifestyle including smoking were documented in each subject by standardized questionnaire. RESULTS: The intronic SNP (rs1410996) and the synonymous SNP (rs2274700) were associated with a significant risk of AMD (P = 2.37 x 10(-5) and 3.52 x 10(-5), respectively). A significant association was also noted between a coding variant (rs800292, I62V) and AMD (P = 8.63 x 10(-6)). In contrast, the Y402H variant showed no significant association with AMD (P = 0.101). Two common haplotypes also demonstrated significant association with AMD (P = 1.08 x 10(-3) and 2.00 x 10(-5)). Among the environmental factors, smoking alone had a significant association with AMD (P = 1.17 x 10(-4)). CONCLUSIONS: Although the Y402H variant was not significantly associated with AMD, other coding and noncoding variants in the CFH gene including rs1410996 and smoking moderately influenced the risk of AMD in a Japanese population.

Association of the HTRA1 gene variant with age-related macular degeneration in the Japanese population.

The purpose of this investigation was to determine whether the high-temperature requirement A-1 (HTRA1) gene polymorphism is associated with age-related macular degeneration (AMD) in native, unrelated Japanese patients. A total of 123 patients with AMD and 133 control subjects without AMD were recruited for this study. The single-nucleotide polymorphism (SNP) rs11200638 in the HTRA1 gene was assessed using a TaqMan assay. The risk A allele frequencies in the AMD cases and control patients were 0.577 and 0.380, respectively, and were associated with a significant risk of developing AMD (p=7.75x10(-6)). The results were more significant in subtype analyses with wet AMD (p=5.96x10(-7)). We conclude that the rs11200638 variant in the HTRA1 gene is strongly associated with AMD in the Japanese population. This result supports the hypothesis that the HTRA1 gene may increase susceptibility to AMD development and can participate in a potential new molecular pathway for AMD pathogenesis by extending this association across diverse ethnicities.

Determination of salivary 17-ketosteroid sulfates using liquid chromatography-electrospray ionization-mass spectrometry.

A simple and sensitive liquid chromatography-electrospray ionization-mass spectrometric (LC-ESI-MS) method for the simultaneous quantification of representative 17-ketosteroid sulfates, dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate and epiandrosterone sulfate, in human saliva has been developed and validated. The saliva was deproteinized with acetonitrile, purified using a solid-phase extraction cartridge and subjected to LC-MS. Deuterium-labeled DHEAS was used as the internal standard and quantification was based on the selected ion monitoring (SIM) mode of each deprotonated molecule. This method allowed the reproducible and accurate quantification of the salivary sulfates using a 100-microl sample; the intra- and inter-assay coefficients of variation were below 6.8 and 6.3%, respectively, and the % accuracy values were quantitative for all the sulfates. The limits of quantitation for all the sulfates were 100 pg/ml. No significant matrix effect or change in the measured value by freeze/thaw repetitions was observed. The developed method was applied to clinical studies, and produced satisfactory results.

[Intake of vitamin D and muscular volume].

Recently, the functions of vitamin D have been identified to prevent fractures and falls;the functions may be associated with improvement in muscular strength by high vitamin D intake. The higher vitamin D intake is considered to need to keep muscular volume and decrease risks of falls and fractures in elderly people. Moreover, it was suggested that intake of dietary vitamin D and calcium seemed to be benefit to increasing of muscle volume during weight loss in young women. Since many elderly people tend to have weight loss and be deficient in vitamin D, more intake of fish which is rich in vitamin D and taking sun exposure, are recommend for their bone health and maintenance of muscular volume.

Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and correlated with macular retinal thickness in type 2 diabetes.

Since vascular endothelial growth factor (VEGF) has a strong effect on induction of vascular permeability, VEGF is an attractive candidate gene for development of diabetic macular edema (ME). Among the 378 patients with type 2 diabetes studied, 203 patients had no retinopathy, 93 had non-proliferative diabetic retinopathy (NPDR), and 82 had proliferative diabetic retinopathy (PDR). ME was present in 16 patients with NPDR and 47 patients with PDR. We genotyped three VEGF polymorphisms: C-2,578A, G-1,154A, and C-634G. Genotype and allele distribution of C-634G, but not C-2,578A or G-1,154A, were significantly different between patients with and without diabetic retinopathy. Logistic regression analysis revealed that the C-634G genotype was a risk factor for DR (p = 0.002), and furthermore for ME (p = 0.047), independently from severity of DR, with the -634C allele increasing the risk. Macular thickness measured by optical coherence tomography was correlated with the C-634G genotype, with the trend increasing with the presence of more -634C alleles (p = 0.006). Stepwise regression analysis showed that duration of diabetes and presence of the C-634G genotype were independent predictors of macular thickness. In addition, basic transcriptional activity levels associated with the -634C allele were greater compared to those seen with the -634G allele in human glioma and lymphoblastic T-lymphocyte cells. These results demonstrate that the VEGF C-634G polymorphism is a genetic risk factor for ME as well as DR.