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1.  Differences in Iris Thickness Among African Americans, Caucasian Americans, Hispanic Americans, Chinese Americans, and Filipino-Americans 
Journal of glaucoma  2013;22(9):10.1097/IJG.0b013e318264ba68.
To evaluate the capability of iris thickness parameters to explain the difference in primary angle closure glaucoma prevalence among the different racial groups.
In this prospective study, 436 patients with open- and narrow-angles that met inclusion criteria were consecutively recruited from the UCSF general ophthalmology and glaucoma clinics to receive anterior segment optical coherence tomography imaging under standardized dark conditions. Images from 11 patients were removed due to poor visibility of the scleral spurs and the remaining images were analyzed using the Zhongshan Angle Assessment Program to assess the following measurements for the nasal and temporal angle of the anterior chamber: iris thickness at 750 μm and 2000 μm from the scleral spurs and the maximum iris thickness at middle one third of the iris. Iris thickness parameters were compared among and within the following five different racial groups: African-, Caucasian-, Hispanic-, Chinese-, and Filipino-Americans.
In comparing iris parameters among the open-angle racial groups, significant differences were found for nasal iris thickness at 750 and 2000 μm from the scleral spurs in which Chinese-Americans displayed the highest mean value (p=0.01, p<0.0001). Among the narrow-angle racial groups, significant difference was found for nasal iris thickness at 2000 μm from the scleral in which Chinese-Americans showed the highest mean value (p<0.0001). Significant difference was also found for temporal maximum iris thickness at middle one third of the iris in which African-Americans exhibited the highest mean value (p=0.021). Iris thickness was modeled as a function of angle status using linear mixed-effects regression, adjusting for age, gender, pupil diameter, spherical equivalent, ethnicity, and the use of both eyes in patients. The iris thickness difference between the narrow-angle and open-angle groups was significant (p=0.0007).
Racial groups that historically showed higher prevalence of primary angle closure glaucoma possess thicker irides.
PMCID: PMC3825747  PMID: 22828003
narrow-angle; open-angle; primary angle closure glaucoma; iris thickness; anterior segment optical coherence tomography; Zhongshan Angle Assessment Program
2.  The Association Between Compliance with Recommended Follow-up and Glaucomatous Disease Severity in a County Hospital Population 
American journal of ophthalmology  2013;156(2):362-369.
To assess the association between insufficient follow-up and clinical parameters such as disease severity and medication use among glaucoma patients at a metropolitan county hospital.
Cross-sectional study
Two-hundred and six patients with established glaucoma were recruited from San Francisco General Hospital. Subjects were classified based upon compliance with recommended follow-up examination intervals over the year preceding commencement of the study as determined by patient medical records. Glaucoma severity was determined based upon the American Academy of Ophthalmology Preferred Practice Patterns guidelines. Multivariate logistic regression analysis was used to assess the relationship between adherence with follow-up visits and disease severity.
After adjustment for the impact of potential confounding variables, subjects with severe glaucomatous disease were found to have been less adherent to their recommended follow-up than those patients with mild or moderate glaucomatous disease (adjusted OR 1.89, 95% CI 1.21–2.94; P = .01). Subjects who were on glaucoma medications were found to be less adherent to follow-up recommendations (adjusted OR 3.29, 95% CI 1.41–7.65, P = .01).
Subjects with poor follow-up adherence were significantly more likely to have severe glaucomatous disease suggesting that poor follow-up may contribute to disease worsening or, alternatively, those with more severe disease are less inclined to follow up at appropriate intervals.
PMCID: PMC3720821  PMID: 23601654
3.  Risk Factors for Glaucoma Suspicion in Healthy Young Asian and Caucasian Americans 
Journal of Ophthalmology  2014;2014:726760.
Purpose. To determine the prevalence of certain risk factors for glaucoma in a healthy, young population and to compare these risk factors between Asian Americans and Caucasians. Methods. 120 healthy graduate students (mean age 24.8 ± 3.0 years) underwent a comprehensive ophthalmic examination. Regression analyses controlling for age, sex, and refraction, comparing glaucoma risk factors in Asians (n = 54) and Caucasians (n = 41), were performed. Outcome variables included family history, intraocular pressure (IOP), spherical equivalent, central corneal thickness (CCT), mean deviation (MD) and pattern standard deviation (PSD), and disc and retinal nerve fiber layer (RNFL) parameters. Results. 61% of subjects were female; the mean spherical equivalent was −3.81 ± 3.2 D; and the mean axial length (AL) was 25.1 ± 1.7 mm. Regression analysis showed race affected spherical equivalent (P < 0.001), AL (P = 0.0073), IOP (P < 0.001), and cup to disc area ratio (CDAR) (P = 0.012). Family history, CCT, MD, and PSD did not vary between Asians and Caucasians (P > 0.05). In this study, we found Asian Americans, compared to Caucasians, had 2.95 ± 0.64 D greater myopia; greater IOP by 2.74 ± 0.62 mmHg; and larger CDAR by 0.12 ± 0.046. Conclusions. In our study population, young, healthy Asian Americans had greater myopia, IOP, and CDAR as compared to Caucasians, suggesting that racial variations can be important when diagnosing glaucoma.
PMCID: PMC4130190  PMID: 25143829
4.  Depletion of Arginine by Recombinant Arginine Deiminase Induces nNOS-Activated Neurotoxicity in Neuroblastoma Cells 
BioMed Research International  2014;2014:589424.
The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity.
PMCID: PMC4122191  PMID: 25126568
5.  Urinary kidney injury molecule-1 is related to pathologic involvement in IgA nephropathy with normotension, normal renal function and mild proteinuria 
BMC Nephrology  2014;15:107.
IgA nephropathy (IgAN) may progress to renal failure for some patients without any clinical risk factors and it is not unusual to find severe pathologic damage in clinically mild IgAN. We therefore investigated whether urinary kidney injury molecule-1 (KIM-1) was related to pathologic involvement in clinically mild IgAN.
Urinary KIM-1/creatinine of 51 IgAN patients with normotension, normal renal function and proteinuria < 1.0 g/24 h were tested. Relationships between urinary KIM-1 and pathologic features were analyzed.
Eighteen of the 51 patients had elevated urinary KIM-1. The tubular atrophy/interstitial fibrosis was more severe in patients with elevated urinary KIM-1 than that in patients with normal urinary KIM-1 (T0/T1/T2, 13/5/0 vs. 33/0/0, P = 0.004). Proportion of glomeruli containing cresecents was higher in patients with elevated urinary KIM-1 than that in patients with normal urinary KIM-1 (50% vs. 18%, P = 0.026). Urinary KIM-1 correlated with the proportion of total crescents (R = 0.303, p = 0.031) and fibrous crescents (R = 0.456, p = 0.001), but did not correlate with the proportion of cellular crescents or fibrocellular crescents. Although the proportion of vascular lesions was higher in patients with elevated urinary KIM-1 (44.4%) than that in patients with normal urinary KIM-1 (18.1%), the difference was not significant (p = 0.057). There was no difference of the response to treatment between patients with and without elevated urinary KIM-1 during a short-term follow-up.
Urinary KIM-1 is a reflection of tubularinstitial injury. For patients with clinically mild IgAN, high urinary KIM-1 is related to relatively severe pathologic involvement on renal biopsy.
PMCID: PMC4094891  PMID: 24998891
KIM-1; IgA nephropathy; Oxford classification
6.  Glaucoma Severity and Medication Adherence in a County Hospital Population 
Ophthalmology  2013;120(6):1150-1157.
To assess the association between disease severity and adherence with glaucoma medications in a county hospital population.
Cross-sectional study.
One hundred and twenty-six patients diagnosed with glaucoma receiving intraocular pressure (IOP) lowering medication were recruited from the San Francisco General Hospital Ophthalmology Clinic.
Subjects completed an oral questionnaire to assess demographic information, knowledge of glaucoma, and perceptions of glaucoma medication adherence. Glaucoma disease severity was classified according to the American Academy of Ophthalmology’s Preferred Practice Pattern guidelines. Medication adherence was measured for each patient by obtaining pharmacy refill data and calculating medication possession ratio (MPR)—ratio of total days’ supply of medication during a 365-day period. Adherence was measured retrospectively over the 18-month period prior to study entry. Subjects with a MPR > 80% were considered adherent.
Main Outcome Measure
Medication adherence
Subjects with mild or moderate glaucoma were more likely to be non-adherent to their prescribed glaucoma medications than those with severe disease (adjusted odds ratio (OR), 1.54; 95% confidence interval (CI), 1.03–2.31; P = 0.04). Age, gender, race, education level, years of glaucoma, number of medications and glaucoma diagnosis were not found to be statistically significantly associated with adherence.
Patients with severe glaucoma were more likely to adhere to their topical IOP lowering medication regimen than those with milder glaucomatous disease.
PMCID: PMC3674151  PMID: 23453512
7.  Comparison of Factors Associated With Occludable Angle Between American Caucasians and Ethnic Chinese 
To determine if factors associated with gonioscopy-determined occludable angle among American Caucasians are similar to those found in ethnic Chinese.
This is a prospective cross-sectional study with 120 American Caucasian, 116 American Chinese, and 116 mainland Chinese subjects. All three groups were matched for sex and age (40–80 years). Gonioscopy was performed for each subject (occludable angles = posterior trabecular meshwork not visible for ≥2 quadrants). Anterior segment optical coherence tomography and customized software was used to measure anterior segment biometry and iris parameters, including anterior chamber depth/width (ACD, ACW), lens vault (LV), and iris thickness/area/curvature.
In both Chinese and Caucasians, eyes with occludable angles had smaller ACD and ACW, and larger LV and iris curvature than eyes with open angles (all P < 0.005). Chinese eyes had smaller ACD and ACW than Caucasian eyes (both P < 0.01) in the occludable angle cohort. Iris characteristics did not differ significantly between Chinese and Caucasians in the occludable angle cohort. Based on multivariate logistic regression, gonioscopy-determined occludable angle was significantly associated with LV, iris area, and sex (all P < 0.03) in Chinese; and with LV, ACD, iris thickness, age, and sex (all P < 0.04) in Caucasians.
Several factors associated with occludable angle differed between Caucasians and Chinese, suggesting potentially different mechanisms in occludable angle development in the two racial groups. This is the first study to demonstrate that lens vault is an important anterior segment optical coherence tomography parameter in the screening for angle closure in Caucasians. In addition, iris thickness was a significant predictor for occludable angles in Caucasians but was not in ethnic Chinese.
Factors associated with occludable angle differed between Caucasians and Chinese. Lens vault is an important anterior segment optical coherence tomography parameter in the screening for angle closure in Chinese and Caucasians. Iris thickness is a significant predictor for occludable angles in Caucasians but not in ethnic Chinese.
PMCID: PMC3837633  PMID: 24168992
occludable angle; gonioscopy; ASOCT; angle closure glaucoma; multiethnicity
8.  High Expression of IGFBP7 in Fibroblasts Induced by Colorectal Cancer Cells Is Co-Regulated by TGF-β and Wnt Signaling in a Smad2/3-Dvl2/3-Dependent Manner 
PLoS ONE  2014;9(1):e85340.
Fibroblasts in the tumor microenvironment are a key determinant in cancer progression and may be a promising target for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is known as a tumor suppressor in colorectal cancer (CRC). The present study investigated the inductive mechanism of IGFBP7 expression in fibroblasts by supernatant from the CRC cell line, SW620. The results showed that the expression of IGFBP7 was up-regulated in the fibroblasts when treated with SW620 supernatant and exogenous TGF-β1. The IGFBP7 induced by SW620 supernatant or TGF-β1 was partially inhibited by the TGF-β1 specific antibody AF and TGF-β1 receptor antagonist SB431542. The Wnt signaling-targeted genes, c-Myc, CCND1 and the proteins Dvl2/3, were all up-regulated in fibroblasts expressing high levels of IGFBP7, and the up-regulation could be inhibited both by the Wnt signaling antagonist Dickkopf-1 (DKK1) and by the TGF-β1 receptor antagonist SB431542. In conclusion, CRC cells promote the high expression of IGFBP7 in fibroblasts, most likely through the co-regulation of TGF-β and Wnt signaling in a Smad2/3-Dvl2/3 dependent manner. Taken together, these data suggest that the fibroblasts could be a novel therapeutic target in tumor therapy.
PMCID: PMC3888407  PMID: 24427302
9.  Comparison of Iris Insertion Classification Among American Caucasian and Ethnic Chinese Using Ultrasound Biomicroscopy 
To qualitatively classify and compare types of iris insertion among American Caucasians, American Chinese, and mainland Chinese.
Prospective multicenter cross-sectional study. Sex- and age-matched Caucasian, American Chinese, and mainland Chinese cohorts were enrolled. Ultrasound biomicroscopy (UBM) images of the anterior chamber were acquired. Qualitative classification of iris insertion into basal, middle, and apical categories was performed. Proportions of each type of insertion were compared among racial groups. Multivariate logistic regression was carried out adjusting for potential confounders.
Data from 117, 129, and 112 subjects were available for American Caucasian, American Chinese, and mainland Chinese subjects, respectively. The most common type of iris insertion in the superior quadrant was basal insertion in both ethnic Chinese and Caucasians. In the inferior, nasal, and temporal quadrants, Chinese showed significantly higher proportions of nonbasal insertion (P = 0.048, P < 0.0001, P < 0.0001, respectively). After adjusting for confounders, nonbasal insertion was significantly associated with Chinese ethnicity in nasal and temporal quadrants (nasal, OR: 3.1, temporal, OR: 4.8). Increasing proportions of nonbasal insertion were found with advancing age in both Chinese and Caucasians.
Chinese have significantly higher proportions of nonbasal iris insertion in the nasal and temporal quadrants when compared with Caucasians, even after adjusting for ASOCT-measured anterior segment biometry and iris characteristics. Longitudinal studies in patients who have PAC/PACG are needed to fully elucidate the relationship between iris insertion and angle closure development.
Chinese have significantly higher proportions of nonbasal iris insertions in the inferior, nasal, and temporal quadrants when compared to Caucasians, after adjusting for ASOCT measured anterior chamber biometry and iris profile.
PMCID: PMC3671934  PMID: 23633662
UBM; interethnic comparison; iris insertion; angle closure; PACG
10.  Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress 
Scientific Reports  2013;3:3219.
Aberrant DNA hypermethylation is frequently found in tumor cells and inhibition of DNA methylation is an effective anticancer strategy. In this study, the therapeutic effect of DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) on colorectal cancer (CRC) was investigated. Zeb exhibited anticancer activity in cell cultures, tumor xenografts and mouse colitis-associated CRC model. It stabilizes p53 through ribosomal protein S7 (RPS7)/MDM2 pathways and DNA damage. Zeb-induced cell death was dependent on p53. Microarray analysis revealed that genes related to endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were affected by Zeb. Zeb induced p53-dependent ER stress and autophagy. Pro-survival markers of ER stress/UPR (GRP78) and autophagy (p62) were increased in tumor tissues of CRC patients, AOM/DSS-induced CRC mice and HCT116-derived colonospheres. Zeb downregulates GRP78 and p62, and upregulates a pro-apoptotic CHOP. Our results reveal a novel mechanism for the anticancer activity of Zeb.
PMCID: PMC3827606  PMID: 24225777
11.  Association Between Baseline Angle Width and Induced Angle Opening Following Prophylactic Laser Peripheral Iridotomy 
To evaluate the association between baseline angle width and laser peripheral iridotomy (LPI)-induced opening of the anterior chamber angle.
Anterior segment optical coherence tomography images captured before and after LPI were analyzed to determine the angle opening distance at 250 μm (AOD250), 500 μm (AOD500), and 750 μm (AOD750) from the scleral spur; trabecular–iris space area at 500 μm (TISA500) and 750 μm (TISA750) from the scleral spur; angle recess area at 750 μm (ARA750) from the scleral spur; and trabecular–iris angle (TIA). Differences in preoperative and postoperative measurements for the anterior chamber angle width parameters were compared by paired Student's t-tests. Univariate and linear mixed-effects regression models were used to examine the association between baseline and LPI-induced opening of anterior chamber angle width parameters.
Eighty-four eyes of 52 primary angle closure suspects were included in the analysis. AOD250, AOD500, AOD750, TISA500, TISA750, ARA750, and TIA significantly increased following LPI by paired Student's t-tests (all P < 0.0001). Lower baseline measurements were significantly associated with greater postoperative opening in all anterior chamber angle width parameters in both univariate and linear mixed-effects regression analyses (all P < 0.05).
Our results showed significant opening of the anterior chamber angle width after LPI and demonstrated an inverse association between baseline and LPI-induced opening of the anterior chamber angle width, such that eyes with a more crowded anterior chamber angle undergoing LPI had a greater magnitude of increase in anterior chamber angle width after the procedure.
Our study demonstrated an inverse relationship between baseline and laser peripheral iridotomy–induced widening of the anterior chamber angle, specifically showing that more angle crowding at baseline is correlated with a greater magnitude of increase in the width of the anterior chamber angle after the procedure.
PMCID: PMC3668805  PMID: 23661374
laser peripheral iridotomy; angle opening distance; trabecular–iris space area; angle recess area; trabecular–iris angle
12.  Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies 
BMC Nephrology  2013;14:199.
Vitamin D insufficiency correlates with mortality risk among patients with chronic kidney disease (CKD). The survival benefits of active vitamin D treatment have been assessed in patients with CKD not requiring dialysis and in patients with end stage renal disease (ESRD) requiring dialysis.
MEDLINE, Embase, the Cochrance Library, and article reference lists were searched for relevant observational trials. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) checklist. Pooled effects were calculated as hazard ratios (HR) using random-effects models.
Twenty studies (11 prospective cohorts, 6 historical cohorts and 3 retrospective cohorts) were included in the meta-analysis., Participants receiving vitamin D had lower mortality compared to those with no treatment (adjusted case mixed baseline model: HR, 0.74; 95% confidence interval [95% CI], 0.67-0.82; P <0.001; time-dependent Cox model: HR, 0.71; 95% CI, 0.57-0.89; P <0.001). Participants that received calcitriol (HR, 0.63; 95% CI, 0.50-0.79; P <0.001) and paricalcitol (HR, 0.43 95% CI, 0.29-0.63; P <0.001) had a lower cardiovascular mortality. Patients receiving paricalcitol had a survival advantage over those that received calcitriol (HR, 0.95; 95% CI, 0.91-0.99; P <0.001).
Vitamin D treatment was associated with decreased risk of all-cause and cardiovascular mortality in patients with CKD not requiring dialysis and patients with end stage renal disease (ESRD) requiring dialysis. There was a slight difference in survival depending on the type of vitamin D analogue. Well-designed randomized controlled trials are necessary to assess the survival benefits of vitamin D.
PMCID: PMC3851063  PMID: 24066946
Vitamin D; Mortality; Calcitriol; Paricalcitol; Chronic kidney disease
13.  Optic Nerve Head and Retinal Nerve Fiber Layer Analysis 
Ophthalmology  2007;114(10):1937-1949.
To evaluate the current published literature on the use of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) measurement devices in diagnosing open-angle glaucoma and detecting progression.
A search of peer-reviewed literature was conducted on February 15, 2006 in PubMed and the Cochrane Library for the period January 2003 to February 2006. The search was limited to studies of adults in English-language journals and yielded 442 citations. The panel reviewed the abstracts of these articles and selected 159 articles of possible clinical relevance for review. Of these 159 full-text articles, 82 were determined to be relevant for the first author and methodologist to review and rate according to the quality of evidence.
There were no studies classified as having the highest level of evidence (level I). The ONH and RNFL imaging instruments reviewed in this assessment were determined to be highly effective in distinguishing eyes with glaucomatous visual field (VF) loss from normal eyes without VF loss, based on level II evidence. In addition, some studies demonstrated that parameters from ONH or RNFL imaging predicted the development of VF defects among glaucoma suspects. Studies on detecting glaucoma progression showed that although there was often agreement on progression between the structural and functional (VF) tests, a significant proportion of glaucoma patients progressed by either the structural or the functional test alone.
The ONH and RNFL imaging devices provide quantitative information for the clinician. Based on studies that have compared the various available technologies directly, there is no single imaging device that outperforms the others in distinguishing patients with glaucoma from controls. Ongoing advances in imaging and related software, as well as the impracticalities associated with obtaining and assessing optic nerve stereophotographs, have made imaging increasingly important in many practice settings. The information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant parameters that define glaucoma diagnosis and progression.
PMCID: PMC3780976  PMID: 17908595
14.  Prevalence and predictors of depression among participants with glaucoma in a nationally representative population sample 
American journal of ophthalmology  2012;154(3):436-444.e2.
To investigate the prevalence of and risk factors for depression among participants with glaucoma and the predictive value of glaucoma for depression.
Cross-sectional study.
This study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, age ≥40 years, who reported a presence or absence of glaucoma. Demographic and disease-related information was obtained by interview. Self-reported measures of vision were ascertained via items from the Visual Function Questionnaire (VFQ-25). Participants underwent visual acuity examination, fundus photography, and visual field testing with screening frequency doubling technology (FDT N-30-5). The main outcome was presence of depression, as determined by a score ≥10 on the Patient Health Questionnaire-9 (PHQ-9).
Prevalence of depression among participants with and without glaucoma was 10.9% (SEM 2.2%) and 6.9% (SEM 0.62%), respectively. While the presence of glaucoma was significantly associated with depression after adjustment for demographic factors (OR 1.80, 95% CI 1.16 - 2.79), this association was not significant after adjustment for self-reported general health condition (OR 1.35, 95% CI 0.822-2.23). Among participants with glaucoma, objective measures of glaucoma severity were not significant predictors for depression. However, several self-reported measures of visual function were significantly associated with depression.
Glaucoma is a significant predictor of depression after adjustment for demographic factors and multiple comorbidities, but not after adjustment for self-reported general health condition. Among participants with glaucoma, self-reported measures of vision were significant risk factors for depression, whereas objective measures of vision were not.
PMCID: PMC3422443  PMID: 22789562
15.  Twelve Weeks of Pioglitazone Therapy Significantly Attenuates Dysmetabolism and Reduces Inflammation in Continuous Ambulatory Peritoneal Dialysis Patients—a Randomized Crossover Trial 
♦ Background: The aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients.
♦ Methods: In this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP).
♦ Results: All 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 μg/mL (range: 2.59 - 34.48 μg/mL) vs 30.44 μg/mL (3.47 - 93.41 μg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function.
♦ Conclusions: Blood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.
PMCID: PMC3524878  PMID: 22383630
Pioglitazone; lipid dysmetabolism; insulin resistance; inflammation; adipocytokines
16.  Association between Myopia and Glaucoma in the United States Population 
To investigate the association between myopia and the prevalence of glaucoma.
This cross-sectional study included 5277 participants from the 2005 to 2008 National Health and Nutrition Examination Survey, greater than or equal to 40 years old, without history of cataract or refractive surgery, who underwent auto-refraction measurement. The predictor was refractive status; emmetropia (−0.99 to +0.99 diopters [D]), mild myopia (−1.00 to −2.99 D), moderate myopia (−3.00 to −5.99 D), severe myopia (> −6.00 D), and hyperopia (> 1.00 D). The outcomes were self-reported glaucoma, vertical cup-to-disc ratio and visual field defects as found on frequency doubling technology (FDT) testing
Odds of self-reported glaucoma were not significantly increased in mild (odds ratio [OR] 0.90, confidence interval [CI] 0.56–1.45), moderate (OR 1.40, CI 0.62–3.16), or severe (OR 0.26, CI 0.08–0.80) myopes compared with emmetropes. Odds of vertical cup-to-disc ratio greater than or equal to 0.7 were not significantly increased in mild (OR 0.84, CI 0.31–2.25), moderate (OR 0.37, CI 0.04–3.57), or severe (OR 0.85, CI 0.09–8.42) myopes compared with emmetropes. Odds of any visual field defects were significantly increased in mild (OR 2.02, CI 1.28–3.19), moderate (OR 3.09, CI 1.42–6.72), and severe (OR 14.43, CI 5.13–40.61) myopes compared with emmetropes. The χ2 test indicated a significant difference (P = 0.001) in the distribution of subjects with each category of visual field status across subjects with each refractive status; the proportion of subjects with worse visual field defects increased with worsening myopia severity.
The association between myopia and visual field defects may represent an increased risk of glaucoma among myopes, and the lack of association with self-reported glaucoma may suggest a need for greater glaucoma surveillance in this population.
This study found an association between myopia and visual field defects, which may represent an increased risk of glaucoma among myopes, and the lack of association between myopia and self-reported glaucoma may suggest a need for greater glaucoma surveillance in this population.
PMCID: PMC3562121  PMID: 23299483
17.  Spica prunellae promotes cancer cell apoptosis, inhibits cell proliferation and tumor angiogenesis in a mouse model of colorectal cancer via suppression of stat3 pathway 
Constitutive activation of STAT3 is one of the major oncogenic pathways involved in the development of various types of malignancies including colorectal cancer (CRC); and thus becomes a promising therapeutic target. Spica Prunellae has long been used as an important component in many traditional Chinese medicine formulas to clinically treat CRC. Previously, we found that Spica Prunellae inhibits CRC cell growth through mitochondrion-mediated apoptosis. Furthermore, we demonstrated its anti-angiogenic activities in vivo and in vitro. To further elucidate the precise mechanism of the potential tumoricidal activity of Spica Prunellae, using a CRC mouse xenograft model, in this study we evaluated its therapeutic efficacy against CRC and investigated the underlying molecular mechanisms.
CRC mouse xenograft model was generated by subcutaneous injection of human colon carcinoma HT-29 cells into nude mice. Animals were given intra-gastric administration with 6 g/kg of the ethanol extract of Spica Prunellae (EESP) daily, 5 days a week for 16 days. Body weight and tumor growth were measured every two days. Tumor growth in vivo was determined by measuring the tumor volume and weight. HT-29 cell viability was examined by MTT assay. Cell apoptosis and proliferation in tumors from CRC xenograft mice was evaluated via immunohistochemical staining (IHS) for TUNEL and PCNA, and the intratumoral microvessel density (MVD) was examined by using IHS for the endothelial cell-specific marker CD31. The activation of STAT3 was evaluated by determining its phosphorylation level using IHS. The mRNA and protein expression of Bcl-2, Bax, Cyclin D1, VEGF-A and VEGFR2 was measured by RT-PCR and IHS, respectively.
EESP treatment reduced tumor volume and tumor weight but had no effect on body weight change in CRC mice; decreased HT-29 cell viability in a dose-dependent manner, suggesting that EESP displays therapeutic efficacy against colon cancer growth in vivo and in vitro, without apparent toxicity. In addition, EESP significantly inhibited the phosphorylation of STAT3 in tumor tissues, indicating its suppressive action on the activation of STAT3 signaling. Consequently, the inhibitory effect of EESP on STAT3 activation resulted in an increase in the pro-apoptotic Bax/Bcl-2 ratio, decrease in the expression of the pro-proliferative Cyclin D1 and CDK4, as well as down-regulation of pro-angiogenic VEGF-A and VEGFR-2 expression. Finally, these molecular effects led to the induction of apoptosis, the inhibition of cell proliferation and tumor angiogenesis.
Spica Prunellae possesses a broad range of anti-cancer activities due to its ability to affect STAT3 pathway, suggesting that Spica Prunellae could be a novel potent therapeutic agent for the treatment of CRC.
PMCID: PMC3729539  PMID: 23800091
Spica prunellae; Colorectal cancer; Herbal medicine; STAT3 pathway; Apoptosis; Proliferation; Angiogenesis
18.  Clear lens extraction in angle-closure glaucoma patients 
To describe the results of 5 consecutive cases of clear lens extraction in angle closure patients for the treatment of elevated intraocular pressure (IOP).
Retrospective observational case series. All angle closure patients were on two or more topical glaucoma medications and had prior laser iridotomy. Eyes underwent clear lens extraction by phacoemulsification with intraocular lens implantation.
All five patients in this case series carried the diagnosis of angle-closure glaucoma and had uncontrolled IOP prior to surgery despite topical medications. After clear lens extraction three of the cases had good IOP control (IOP<22mmHg) without the need for topical medications. In one case the IOP was better controlled after surgery, however, topical medications were required. The desired IOP was not met in one case despite restarting maximum topical therapy.
This case series suggests that there may be a role for therapeutic clear lens extraction in select cases of angle-closure glaucoma.
PMCID: PMC3693029  PMID: 23826542
clear lens; glaucoma; cataract; angle closure
19.  Lentivirus-mediated RNA interference targeting the H19 gene inhibits cell proliferation and apoptosis in human choriocarcinoma cell line JAR 
BMC Cell Biology  2013;14:26.
H19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes.
H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells.
The finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.
PMCID: PMC3679798  PMID: 23711233
H19; JAR cells; Choriocarcinoma; HES-1; DUSP5; IGF2
20.  Association of biometric factors with anterior chamber angle widening and intraocular pressure reduction after uneventful phacoemulsification for cataract 
To evaluate anterior chamber biometric factors associated with the degree of angle widening and intraocular pressure (IOP) reduction after phacoemulsification.
University of California, San Francisco, California, USA.
Case series.
Anterior chamber parameters obtained by anterior segment coherence tomography were compared preoperatively and 3 months postoperatively. Measurements included the angle opening distance 500 μm anterior to the scleral spur (AOD500), trabecular–iris space area 500 μm from the scleral spur (TISA500), iris curvature (I-Curv), anterior chamber angle (ACA), trabecular–iris space area, anterior chamber volume, anterior chamber width, and lens vault (LV).
The study enrolled 73 eyes. The mean patient age was 77.45 years ± 7.84 (SD); 65.75% of patients were women. From preoperatively to 3 months postoperatively, the mean AOD500 increased significantly (0.254 ± 0.105 to 0.433 ± 0.108 mm) and the mean IOP decreased significantly (14.97 ± 3.35 to 12.62 ± 3.37 mm Hg) (P < .001). The reduction in IOP was correlated with the increase in AOD500 (r = 0.240, P = .041) and preoperative LV (r = 0.235, P = .045). After adjusting for related factors, AOD500 widening was positively correlated with LV (β = 0.458, P = .044) and I-Curv (β = 0.235, P = .043) and negatively correlated with preoperative TISA500 (β = −0.269, P = .025) and ACA (β = −0.919, P = .027).
Surgically induced AOD widening was significantly correlated with anterior chamber biometric factors. Preoperative LV appears to be a significant factor in angle widening and IOP reduction after phacoemulsification.
PMCID: PMC3258487  PMID: 22055073
21.  Ethnic Difference of the Anterior Chamber Area and Volume and Its Association with Angle Width 
To compare the anterior chamber area/volume (ACA/ACV) and their relationship with the drainage angle between adult Caucasians and Chinese.
Study groups were comprised of four age- and sex-matched cohorts: American Caucasians, American Chinese, southern mainland Chinese, and northern mainland Chinese. All subjects were consecutively recruited from general ophthalmology clinics except for southern mainland Chinese participants who were drawn from an ongoing population-based study. Anterior segment optical coherence tomography (ASOCT) images were obtained under dark conditions. Customized software was used to analyze structural indices including ACA/ACV, angle opening distance (AOD), anterior chamber depth (ACD), anterior chamber width (ACW), lens vault (LV), corneal arc depth (CAD), iris thickness (IT), iris curvature (ICurv), and iris area (IArea).
Data from 121, 124, 121, and 120 participants were obtained of American Caucasians, American Chinese, and southern and northern mainland Chinese, respectively. After multiple linear regression analysis, adjusting for age, sex, pupil diameter (PD), and axial length (AL), ACA/ACV was positively associated with ACD, ACW, CAD, and corneal radius of curvature (CR) but negatively related with ICurv and IArea. Ethnic Chinese had significantly smaller ACA (β = −0.18, P = 0.022) and ACV (β = −3.9, P = 0.001) than Caucasians. ACV contributes the most to AOD variation for both Chinese (standardized regression coefficient [SRC] = 0.47, P < 0.001) and Caucasians (SRC = 0.59, P < 0.001).
Compared with Caucasians, ethnic Chinese had smaller ACA/ACV independent of ACD, ACW, ICurv, IArea, PD, CR, and AL. ACA/ACV is the most prominent contributor to angle width variation for both Chinese and Caucasians in this study.
ACA/ACV is the most prominent contributor to angle width in both Chinese and Whites. Chinese tended to have smaller ACA/ACV than did whites. Anterior chamber depth, anterior chamber width, and iris curvature are the most important factors associated with ACA/ACV.
PMCID: PMC3383186  PMID: 22531702
22.  Reproducibility of Scleral Spur Identification and Angle Measurements Using Fourier Domain Anterior Segment Optical Coherence Tomography 
Journal of Ophthalmology  2012;2012:487309.
Purpose. To evaluate intraobserver and interobserver agreement in locating the scleral spur landmark (SSL) and anterior chamber angle measurements obtained using Fourier Domain Anterior Segment Optical Coherence Tomography (ASOCT) images. Methods. Two independent, masked observers (SR and AZC) identified SSLs on ASOCT images from 31 eyes with open and nonopen angles. A third independent reader, NPB, adjudicated SSL placement if identifications differed by more than 80 μm. Nine months later, SR reidentified SSLs. Intraobserver and interobserver agreement in SSL placement, trabecular-iris space area (TISA750), and angle opening distance (AOD750) were calculated. Results. In 84% of quadrants, SR's SSL placements during 2 sessions were within 80 μm in both the X- and Y-axes, and in 77% of quadrants, SR and AZC were within 80 μm in both axes. In adjudicated images, 90% of all quadrants were within 80 μm, 88% in nonopen-angle eyes, and 92% in open-angle eyes. The intraobserver and interobserver correlation coefficients (with and without adjudication) were above 0.9 for TISA750 and AOD750 for all quadrants. Conclusions. Reproducible identification of the SSL from images obtained with FD-ASOCT is possible. The ability to identify the SSL allows reproducible measurement of the anterior chamber angle using TISA750 and AOD750.
PMCID: PMC3503366  PMID: 23209880
23.  A randomized controlled trial of long term effect of BCM guided fluid management in MHD patients (BOCOMO study): rationales and study design 
BMC Nephrology  2012;13:120.
Bioimpedance analysis (BIA) has been reported as helpful in identifying hypervolemia. Observation data showed that hypervolemic maintenance hemodialysis (MHD) patients identified using BIA methods have higher mortality risk. However, it is not known if BIA-guided fluid management can improve MHD patients’ survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management compared with standard care.
This is a multicenter, prospective, randomized, controlled trial. More than 1300 participants from 16 clinical sites will be included in the study. The enrolment period will last 6 months, and minimum length of follow-up will be 36 months. MHD patients aged between 18 years and 80 years who have been on MHD for at least 3 months and meet eligibility criteria will be invited to participate in the study. Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arms of the study. In the BIA arm, additional BCM measurements will be performed every 2 months. The primary intent-to-treat analysis will compare outcomes for a composite endpoint of death, acute myocardial infarction, stroke or incident peripheral arterial occlusive disease between groups. Secondary endpoints will include left ventricular wall thickness, blood pressure, medications, and incidence and length of hospitalization.
Previous results regarding the benefit of strict fluid control are conflicting due to small sample sizes and unstable dry weight estimating methods. To our knowledge this is the first large-scale, multicentre, prospective, randomized controlled trial to assess whether BIS-guided volume management improves outcomes of MHD patients. The endpoints of the BOCOMO study are of utmost importance to health care providers. In order to obtain that aim, the study was designed with very careful important considerations related to the endpoints, sample size, inclusion criteria, exclusion criteria and so on. For example, annual mortality of Beijing MHD patients was around 10%. To reach statistical significance, the sample size will be very large. By using composite endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to patients with urine volume less than 800 ml/day the day before dialysis session will limit confounding due to residual renal function effects on the measured parameters. Patients who had received BIS measurement within 3 months prior to enrolment are excluded as data from such measurements might lead to protocol violation. Although not all patients enrolled will be incident patients, we will record the vintage of dialysis in the multivariable analysis.
Trial registration
Current Controlled Trials NCT01509937
PMCID: PMC3489516  PMID: 23006960
Hemodialysis; Bioimpedance; Dry weight; Body composition monitor; Randomized controlled trial
24.  The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron 
This study of a U.S. population-based sample of adults older than 40 years showed that participants who consumed ≥800 mg/day of supplementary calcium or ≥18 mg/day of supplementary iron had significantly higher odds of self-reported glaucoma compared with those who reported no supplemental intake.
To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma.
This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview.
Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found.
These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.
PMCID: PMC3317417  PMID: 22247455
25.  Differences in Baseline Dark and the Dark-to-Light Changes in Anterior Chamber Angle Parameters in Whites and Ethnic Chinese 
When measured by anterior segment optical coherence tomography, the anterior chamber angle in the Chinese tends to be narrower in the dark, but the dark-to-light change is greater than in whites, independent of refractive status and anterior segment ocular dimensions.
To assess the anterior chamber drainage angle width in the dark and the dark-to-light change (Δ) between Caucasians and Chinese aged 40 years and older.
The study groups comprised four age- and sex-matched cohorts: American Caucasians, American Chinese, southern mainland Chinese, and northern mainland Chinese. Anterior segment optical coherence tomography (ASOCT) images of the anterior chamber angles were obtained under both light and dark conditions. The parameters analyzed included angle opening distance (AOD), angle recess area (ARA), and trabecular–iris space area (TISA).
Data were obtained from 121, 124, 121, and 120 participants who were American Caucasians, American Chinese, and southern and northern mainland Chinese, respectively. In a multiple linear regression analysis, adjusted for age, sex, refractive status, pupil size, lens location, and anterior chamber depth (ACD) and width (ACW), the ethnic Chinese had significantly smaller ARAs (regression coefficient, β = −0.06, P < 0.001) and TISAs (β = −0.01, P = 0.039), as well as greater ΔAODs (β = 0.03, P = 0.009) and ΔTISAs (β = 0.02, P = 0.029) than did the Caucasians. For the dark-to-light change analysis, the independent associations between angle width and iris thickness (IT) and iris curvature (ICurv) were identified only in the Chinese.
Compared with the Caucasians, the ethnic Chinese had smaller ARA and TISA, but greater dark-to-light changes in AOD and TISA, independent of refractive status and overall ocular anterior segment dimensions.
PMCID: PMC3293413  PMID: 22076986

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