Biomedical subjects
Publications and source records attributed to Michael J Cooney.
Nile Red, a dye that fluoresces at defined wavelengths depending upon the polarity of the surrounding medium, has been proposed to determine the neutral lipid content of microalgal cells. Herein we communicate modifications to this technique that facilitate its use as a high-throughput screening technology, as well as improving its accuracy and versatility.
PURPOSE: To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: We conducted a retrospective study of patients with CNV secondary to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg) during a 3-month period. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits. RESULTS: There were 266 consecutive eyes of 266 patients who received injections, and follow-up information was available for 251 (94.4%). The mean age of the patients was 80.3 years, the mean baseline visual acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods of treatment. At the 1-month follow-up (data available for 244 patients), the mean visual acuity was 20/137 (P < 0.001 as compared with baseline), and 74 (30.3%) of patients had improvement in visual acuity as defined by a halving of the visual angle. At the 2-month follow-up (data available for 222 patients), the mean visual acuity was 20/122 (P < 0.001), and 78 (31.1%) of patients had visual improvement. At the 3-month follow-up (data available for 141 patients), the mean visual acuity was 20/109 (P < 0.001), and 54 (38.3%) of patients had visual acuity improvement. The mean central macular thickness at baseline was 340 mum and decreased to a mean of 247 microm at month 1 (P < 0.001) and 213 microm at month 3 (P < 0.001). At 1 month, two patients had mild vitritis, as did one patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis, increased intraocular pressure, retinal tear, or retinal detachment occurred. The risk for thromboembolic disorders did not seem to be different than reported previously in studies concerning macular degeneration. CONCLUSION: There were no apparent short-term safety concerns for intravitreal bevacizumab injection for CNV. Treated eyes had a significant decrease in macular thickness and improvement in visual acuity. The follow-up was too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.
AIM: To review the outcomes of eyes with neovascular age-related macular degeneration (AMD) treated with photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide injection. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of consecutive eyes with neovascular AMD that received an intravitreal triamcinolone injection within 1 week of their first PDT and had at least 6 months of follow-up. Eyes were retreated with PDT at 3-month intervals if angiographic leakage was present. RESULTS: Twenty-six eyes from 24 patients were identified. The mean visual acuity at baseline was 20/118 (median 20/112). The mean visual acuity decreased to 20/138 at 9 months (P = 0.24, n = 15) and to 20/174 at 12 months (P = 0.23, n = 8). The change in visual acuity from baseline was not statistically significant at any time point. The mean central foveal thickness by OCT measured 342 microm at baseline and decreased to 296 microm at 12 months (P = 0.31). Sixty-two per cent of eyes required no additional PDT at 12 months. Nineteen per cent of 26 eyes had a rise in intraocular pressure that was controlled with topical medication alone. CONCLUSION: Photodynamic therapy with verteporfin combined with intravitreal triamcinolone injection in the treatment of neovascular AMD may be superior to PDT alone by decreasing visual loss and reducing the number or retreatments.
OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) beta, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications. DATA SOURCES: Primary literature was obtained via a MEDLINE search (1966-August 2004) and through review of pertinent abstracts and presentations at major medical meetings. STUDY SELECTION AND DATA EXTRACTION: Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed. DATA SYNTHESIS: PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC beta 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC beta, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy. CONCLUSIONS: Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.
Explore the source record for details and available documents.
A starvation-based dissolved oxygen (DO) transient controller was developed to supply growth-limiting substrate to high cell density fed-batch cultures of recombinant Escherichia coli. The algorithm adjusted a preexisting feed rate in proportion to the culture's oxygen demand, which was estimated from transients in the DO concentration after short periods of feed interruption. In this manner, the addition of glucose feed was precisely controlled at a rate that did not exceed the acetate production threshold, thus preventing acetate accumulation. In comparison to exponential feed algorithms commonly used in industry, the implementation of the new feeding strategy increased the final cell density from 32 to 44 g (dry cell weight).L(-1), with less than 16 mM acetate accumulated, producing an ideal culture for subsequent induction. Despite a constant starvation level and relatively low levels of acetate, experimental cultivations still tended to produce acetate towards the end of the process. The use of a simple Monod model provided an explanation as to why this may occur in high cell density cultivations and suggests how it may be overcome.
Explore the source record for details and available documents.
DO-transient nutrient controllers use the dissolved oxygen signal to attempt acetate threshold tracking during fed-batch cultivation of recombinant E. coli. Here we apply DO-transient control to the production of Jembrana disease virus protein in complex Super Luria medium and compare performance against a high-limit pH-stat controller. For induction at medium cell density (harvest between 31 and 32.5 g dcw L) a total productivity of 0.27 g L h was achieved as compared to 0.24 g L h with the high-limit pH-stat. For induction at high cell density (harvest at 60 g dcw L), decreased productivity (0.12 g L h) was attributed to the effect of acetate accumulation on recombinant protein formation and a concomitant lowering of the critical growth rate. Our results suggest that complex media provides a difficult environment for the application of acetate threshold tracking DO-transient control because of difficulties in re-oxidizing acetate, and apparent localized production of acetate below the production threshold (as detected by the DO-transient controller as SPOUR(crit)). Configuring the DO-transient controller to avoid aggressive threshold probing is suggested as a means to improve performance and reduce acetate accumulation in complex media.
Explore the source record for details and available documents.
In this work feed hardware for fed-batch cultivation is presented (broth recycle feed injection system or BRFIS). BRFIS proved superior to conventional submerged or dripped feed systems in reducing dissolved oxygen (DO) oscillations during Escherichia coli fed-batch cultivation (5 min coefficient of variation of 0.7% for BRFIS as compared to 26% or greater for conventional feeding hardware in a 2 L test reactor). Hence, BRFIS is useful for fed-batch cultivation systems where the DO signal is used in measurement or control.
PURPOSE: To compare the preferential hyperacuity perimeter (PHP) with an Amsler grid in detection of age-related macular degeneration (AMD). METHODS: Patients underwent refraction, visual acuity examination, PHP, Amsler grid examination, and macular photography. RESULTS: One hundred fifty patients participated in the trial. Of 19 eyes with neovascular AMD, 19 (100%) were positive on the PHP, and 10 (53%), on the Amsler grid. Of 27 eyes with geographic atrophy, 26 (96%) were positive on the PHP, and 12 (44%), on the Amsler grid. Of 20 eyes with intermediate AMD, 14 (70%) were positive on the PHP, and 4 (20%), on the Amsler grid. Of 51 eyes with early AMD, 21 (41%) were positive on the PHP, and 4 (8%), on the Amsler grid. Of 33 eyes with no AMD, 6 (18%) were positive on the PHP, and none, on the Amsler grid. Thus, 80 (68%) of 117 patients with AMD had a positive PHP, while 30 (26%) had positive results of Amsler grid examination (P < 0.001, McNemar test). CONCLUSION: The PHP had greater sensitivity, although with a relatively high rate of false-positive results for healthy individuals, than the Amsler grid in detecting AMD-related lesions.
Explore the source record for details and available documents.