Comparison of 10-2 and 24-2 Perimetry to Diagnose Glaucoma Using OCT as an Independent Reference Standard.

PURPOSE: To compare the performance of the 10-2 test versus 24-2 standard automated perimetry (SAP) test for the diagnosis of glaucoma using OCT as an independent standard for glaucomatous damage. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 1375 pairs of 10-2 and 24-2 SAP tests from 569 eyes of 339 subjects were used for the analysis. A total of 440 (77%) eyes had a diagnosis of glaucoma, and 129 (23%) eyes were normal. All participants underwent 10-2 and 24-2 SAP tests within 30 days. METHODS: Glaucomatous severity was quantified based on OCT macula ganglion cell layer (mGCL) and circumpapillary retinal nerve fiber layer. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare 10-2 and 24-2 metrics for discriminating healthy eyes from those of glaucoma, at different levels of disease severity. MAIN OUTCOME MEASURES: Areas under the ROC curves and sensitivities at fixed specificities of 80% and 95%. RESULTS: The overall AUC for mean deviation (MD) for the 24-2 test (0.808) was significantly higher than that of the 10-2 test (0.742; P < 0.001). When compared at different stages of the disease, the 24-2 test performed generally better than the 10-2 test, notably in the earlier stages of the disease. For early damage (first quartile), the 24-2 MD had an AUC of 0.658 versus 0.590 for 10-2 MD (P = 0.018). For advanced damage (fourth quartile), corresponding values were 0.954 vs. 0.903 (P = 0.013). Similar trends were observed when glaucoma severity was defined based on structural macular damage with mGCL thickness. CONCLUSIONS: The 24-2 SAP test had better diagnostic accuracy compared with that of the 10-2 test for detecting equivalent levels of glaucomatous damage, as measured by quantitative assessment of retinal nerve fiber layer and macula by OCT. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Evaluation of the cytotoxic and antitumour effects of the essential oil from Mentha x villosa and its main compound, rotundifolone.

OBJECTIVES: The aim of this study was to investigate the cytotoxic and antitumour effects of the essential oil from the leaves of Mentha x villosa (EOMV) and its main component (rotundifolone). METHODS: In-vitro cytotoxic activity of the EOMV and rotundifolone was determined on cultured tumour cells. In-vivo antitumour activity of the EOMV was assessed in sarcoma 180-bearing mice. KEY FINDINGS: The EOMV displayed cytotoxicity against human tumour cell lines, showing IC50 values in the range of 0.57-1.02 µg/ml in the HCT-116 and SF-295 cell lines, respectively. Rotundifolone showed weak cytotoxicity against HCT-116, SF-295 and OVCAR-8 cell lines (IC50 > 25.00 µg/ml). Tumour growth inhibition rates were 29.4-40.5% and 25.0-45.2% for the EOMV treatment by intraperitoneal (50-100 mg/kg/day) and oral (100-200 mg/kg/day) administration, respectively. The EOMV did not significantly affect body mass and macroscopy of the organs. CONCLUSIONS: The EOMV possesses significant antitumour activity with low systemic toxicity, possibly due to the synergistic action of its minor constituents.

Advective transport of nitric oxide in a mathematical model of the afferent arteriole.

Endothelium-derived nitric oxide (NO) is thought to be short-lived in blood because of rapid removal from plasma, mainly by binding to Hb. The extent to which removal limits NO advection is unclear, especially for blood flow in the renal afferent arteriole (AA), which has a transit time of 3-30 ms. A mathematical model of AA fluid dynamics and myogenic response that includes NO diffusion, advection, degradation, and vasorelaxant action was used to estimate NO advective transport. Model simulations indicate that advective transport of locally produced NO is sufficient to yield physiologically significant NO concentrations along much of the AA. Advective transport is insensitive to NO scavenging by Hb because the NO-Hb binding rate is slow relative to AA transit time. Hence, plasma NO concentration near the vessel wall is influenced by both diffusion from endothelial cells and advection from upstream sites. Simulations also suggest that NO advection may constitute a mechanism to stabilize arteriolar flow in response to a localized vasoconstriction accompanied by enhanced NO release.

The role of selection bias in comparing cesarean birth rates between physician and midwifery management.

OBJECTIVE: The midwifery service at our hospital has been observed to have a 2% cesarean birth rate consistently over a 10-year period. There are substantial differences in labor management style between the midwives and physicians. We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias. METHODS: A randomized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management. The provider responsible for labor management was unable to determine group assignment. Patients in the midwifery group were managed by previously established protocols, and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management. Route of delivery was the primary outcome measurement. Continuous variables were analyzed using Student t test and discrete variables using chi 2. RESULTS: There were no demographic differences between the groups, and the admission pelvic examinations were the same. The patients assigned to the midwifery group had a 2.1% cesarean birth rate, whereas those assigned to physician management had a 0.4% rate. The higher rate of operative vaginal deliveries in the physician group was statistically significant. There were no differences in neonatal outcomes. The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions. CONCLUSIONS: The 2% cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias. A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population.

Constitutive apical secretion of an 80-kD sulfated glycoprotein complex in the polarized epithelial Madin-Darby canine kidney cell line.

The biosynthesis, processing, and apical secretion of a group of polypeptides (Kondor-Koch, C., R. Bravo, S. D. Fuller, D. Cutler, and H. Garoff. 1985. Cell. 43:297-306) are studied in MDCK cells using a specific polyclonal antiserum. These polypeptides are synthesized as a precursor protein which has an apparent Mr of 65,000 in its high mannose form. This precursor is converted into a protein with an apparent Mr of 80,000 containing complex carbohydrates and sulfate. After intracellular cleavage of the 80-kD protein, the 35-45-kD subunits are secreted as an 80-kD glycoprotein complex (gp 80) linked together by disulfide bonds. Secretion of the protein complex occurs by a constitutive pathway at the apical surface of the epithelial monolayer. Since the immediate post-translational precursor, the 65-kD protein, is hydrophilic in nature as shown by its partitioning behavior in a phase-separated Triton X-114 solution, gp 80 is segregated into the apical exocytotic pathway as a soluble molecule. The proteolytic maturation of gp 80 is blocked in the presence of chloroquine and its secretion is retarded. The 80-kD precursor is released at the apical cell surface, demonstrating that proteolytic processing is not necessary for the apical secretion of this protein. If N-glycosylation is inhibited by tunicamycin treatment the protein is secreted in equal amounts at both cell surfaces, indicating a role of the carbohydrate moieties in the vectorial transport of this protein.

Capacity for biosynthesis of prostaglandin-related compounds: distribution and properties of the rate-limiting enzyme in hydrocorals, gorgoniants, and other coelenterates of the Caribbean and Pacific.

A convenient and reliable assay is described for PGEP synthetase, the rate-limiting enzyme determining the total capacity for biosynthesis of prostaglandin-related compounds. Results of such assays, performed withe fresh specimens under both field and laboratory conditions, newly identify several marine coelenterate species as potentially important resources of PGRCs for research and possible development. Properties of the typical marine coelenterate PGEP synthetase, and the reaction which this enzyme catalyzes, have been further characterized.

Proton nuclear magnetic resonance study of the effect of pH on tRNA structure.

The low-field 220-MHz proton nuclear magnetic resonance (NMR) spectra of four tRNA molecules, Escherichia coli tRNAPhe, tRNA1Val, and tRNAfMet1, and yeast tRNAPhe, at neutral and mildly acidic pH are compared. We find a net increase in the number of resonances contributing to the -9.9-ppm peak (downfield from sodium 4,4-dimethyl-4-silapentanesulfonate) in three of these tRNAs at pH 6, while tRNAfMet1 does not clearly exhibit this behavior. The increase in intensity at this resonance position is half-completed at pH 6.2 in the case of yeast tRNAPhe. An alteration at the 5'-phosphate terminus is not involved, since removal of the terminal phosphate does not affect the gain in intensity at -9.9 ppm. Based on a survey of the tertiary interactions in the four molecules, assuming that they possess tertiary structures like that of yeast tRNAPhe at neutral pH, we tentatively attribute this altered resonance in E. coli and yeast tRNAPhe to the protonation of the N3 of the adenine residue at position 9 which results in the stabilization of the tertiary triple A23-U12-A9. This intepretation is supported by model studies on the lowfield proton NMR spectrum of AN oligomers at acid pH, which reveal an exchanging proton resonance at -9.4 ppm if the chain length N greater than or equal to 6.