PubMed · 15511451
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Jarle Vaage. 2004. Invited commentary.. https://doi.org/10.1016/j.athoracsur.2004.03.051
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BACKGROUND: In neovascular age-related macular degeneration (AMD) new vessels grow under the retina distorting vision and leading to scarring. This is exacerbated if the blood vessels leak. Photodynamic therapy (PDT) has been investigated as a way to treat the neovascular membranes without affecting the retina. OBJECTIVES: The aim of this review was to examine the effects of PDT in the treatment of neovascular AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which includes the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005). We used the Science Citation Index to search for reports that cited relevant studies. We contacted experts in the field and searched the reference lists of relevant studies. SELECTION CRITERIA: We included randomised trials of PDT in people with choroidal neovascularisation due to AMD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. Relative risks were combined using a fixed-effect model after testing for heterogeneity. MAIN RESULTS: Two published trials were identified that randomised 948 participants to verteporfin therapy compared to 5% dextrose in water. Both trials were performed by the same investigators using largely the same clinical centres and funded by manufacturers of verteporfin. Outcome data were available at 12 and 24 months after the first treatment. Participants received on average five treatments over two years. The relative risk of losing three or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.77 (95% confidence interval 0.69 to 0.87). The relative risk of losing six or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12 months were similar to those at 24 months. The most serious adverse outcome, acute (within 7 days of treatment) severe visual acuity decrease, occurs in about one in 50 patients. AUTHORS' CONCLUSIONS: Photodynamic therapy in people with choroidal neovascularisation due to AMD is probably effective in preventing visual loss though there is doubt about the size of the effect. Outcomes and potential adverse effects of this treatment should be monitored closely. Further independent trials of verteporfin are required to establish that the effects seen in this study are consistent and to examine important issues not yet addressed, particularly relating to quality of life and cost.
A classic problem in analytical chemistry has been determination of individual components in a mixture without availability of the pure individual components. Measurement of the distribution of isotopomers in a labeled compound or mixture of labeled compounds is an example of this problem that is commonly encountered when stable isotopically labeled metabolites are used to determine in vivo kinetics and metabolism. We present a method that uses the measured mass spectral data of the unlabeled material to represent any and all combinations of isotopomer variations of that material and to determine abundances of these isotopomers. Although examples of the method are presented for gas chromatography/mass spectrometry, the method is applicable to any type of mass spectrometry data. The method also accounts for errors induced by mass spectrometer ionization and resolution effects. To demonstrate this method, we determined the isotopomer distributions of samples of 13C-labeled leucine and glucose for both highly enriched isotopomers and labeled isotopomers present in low abundance against a natural isotopic abundance background. The method accurately and precisely determined isotopomer identity and abundance in the labeled materials without adding noise or error that was not inherent in the original mass spectral data. In examples shown here, isotopomer uncertainties were calculated with relative standard errors of <1% from good quality mass spectral data.
Five water molecules were placed in 37 different configurations around alpha- and beta-D-glucopyranose in the gt, gg, and tg conformational states, and the glucose-water complexes were geometry optimized using density functionals at the B3LYP/6-311++G** level of theory. The five water molecules were organized in space and energy minimized using an empirical potential, AMB02C, and then further geometry optimized using DFT algorithms to minimum energy positions. Electronic energy, zero point vibrational energy, enthalpy, entropy, stress energy on glucose and the water cluster, hydrogen-bond energy, and relative free energy were obtained for each configuration using thermodynamic procedures and an analytical Hessian program. The lowest energy complex was that of a clustering of water molecules around the 1- and 6-hydroxyl positions of the beta-gt anomer. Configurations in which the water molecules created a favorable network completely around and under glucose were found to have low energy for both alpha and beta anomers. Calculation of the alpha/beta anomeric ratio using the zero point corrected energy gave, approximately 32/68%, highly favoring the beta anomer in agreement with the experimental approximately 36/64% value. This ratio is better than the approximately 50/50% ratio found in our previous monohydrate study. An approximate hydroxymethyl population was obtained by noting average relative energies among the three conformational states, gt, gg, and tg. In the beta anomer complexes the gt conformation was favored over the gg state, while in the alpha anomer complexes the gg state was favored over the gt conformation, with the tg conformations all being of higher energy making little or no contribution to the rotamer population. Some geometry variances, found between glucose in vacuo and glucose after interaction with water molecules, are described and account for some observed C-5-C-6 bond length anomalies reported by us previously for the vacuum glucose structures.