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Biomedical subjects

John Marshall

Publications and source records attributed to John Marshall.

At least 37 records · Page 2Linked to original sources
PubMed2006

Laser subepithelial keratomileusis for the correction of high myopia with the Schwind ESIRIS scanning spot laser.

PURPOSE: To investigate the efficacy of laser subepithelial keratomileusis (LASEK) for the correction of high myopia with the Schwind ESIRIS scanning spot laser (Schwind eye-tech-solutions Gmbh & Co, Kleinostheim, Germany). METHODS: Fifty-one patients (76 eyes) were treated with a mean preoperative spherical equivalent refraction of -7.55 diopters (D) (range: -6.0 to -10.75 D). All eyes received a LASEK technique using 15% alcohol with a 20-second application. RESULTS: An intact epithelial flap was obtained in 73 (96%) eyes. At 1 week, uncorrected visual acuity (UCVA) was > or =20/30 in 53 (70%) eyes and > or =20/60 in all eyes. At 6 months (n=76), the mean SE was +0.08 D (range: -1.00 to +1.875 D) with 73 (96%) eyes within +/-1.0 D of the intended correction and 60 (79%) eyes within +/-0.5 D. At 12 months (n=46), the mean SE was -0.07 D (range: -1.375 to +2.0 D) with 44 (96%) eyes within +/-1.0 D of the intended correction and 37 (80%) eyes within +/-0.5 D. Myopic cylindrical corrections were attempted in 68 eyes (range: -0.25 to -4.25 D) with vector analysis demonstrating a mean 85% correction. At last follow-up, UCVA was > or =20/20 in 47 (62%) eyes, > or =20/25 in 63 (83%) eyes, and > or =20/40 in 75 (99%) eyes. Three (4%) eyes gained two lines of Snellen decimal equivalent best spectacle-corrected visual acuity compared to preoperative levels, 68 (89%) eyes showed no change or gained one line, and 5 (7%) eyes lost one line. None lost more than one line. Only 2 (3%) eyes at 6 to 12 months had more than +1 axial corneal haze and 50 (66%) showed no evidence of haze on slit-lamp examination. CONCLUSIONS: Laser subepithelial keratomileusis for myopia up to -11.00 D with the Schwind ESIRIS laser provides good refractive and visual outcomes, with acceptable visual recovery and minimal complications.

Adult↗
PubMed2006

Levels of care in the intensive care unit: a research program.

A multidisciplinary research program on levels of care was conducted in 15 adult intensive care units in North America, Europe, and Australia. The program addressed advance directives for cardiopulmonary resuscitation, provision of advanced life support, and clinicians' discomfort with evolving treatment plans. The results indicated that the factors that determined the establishment of directives for advance life support differed from the factors that informed a decision to limit or withdraw support after admission to an intensive care unit. In addition, clinicians' prognoses were imprecise and often an underestimation of the probability of short-term survival. Finally, some degree of discomfort was common in care providers in the intensive care unit, most often because they thought interventions were excessive and not compatible with an acceptable future quality of life. The provision of advanced life support mandates explicit decision making about how life-support measures should be used.

Adult↗
PubMed2005

Central retinal thickness is positively correlated with macular pigment optical density.

Macular pigment (MP) has been suggested to have a protective role in age-related macular degeneration by reducing the amount of oxidative stress on the retina. MP levels peak at the foveal center, where it is found predominantly in the receptor axon and inner plexiform layers of the retina. The purpose of this study was to investigate the relationship between central retinal thickness and macular pigment optical density in a group of healthy subjects. We report that macular pigment optical density (MPOD) has a significant and positive relationship with central retinal thickness as measured by optical coherence tomography. The strength of the observed relationship (r approximately 0.30) was independent of the technique used to measure MPOD, whether heterochromatic flicker photometry (HFP) or 2-wavelength autofluorescence (AF). Of note, there was no statistically demonstrable relationship between MPOD at an eccentricity of 1- or 2-degrees and central retinal thickness. This finding has important implications for future studies investigating MPOD, and its response to dietary modification/supplementation.

Adult↗
PubMed2005

Effect of taurine and apical potassium concentration on electrophysiologic parameters of bovine retinal pigment epithelium.

The purpose of this study was to assess the effect of taurine and apical potassium concentration modelling in vivo light evoked changes on the transepithelial potential (TEP) and the transepithelial resistance (TER) of isolated bovine retinal pigment epithelium (RPE). Isolated specimens of bovine non-tapetal RPE-Bruch's-choroid (RPE-BC) were mounted in modified Ussing chambers. The apical and the basolateral side of the preparations were exposed to 10 mm and 10 microm concentrations of taurine in Krebs' medium with either 6.04 or 2.2 mm potassium in the apical compartment. TEP and TER were recorded over 140 min. TEP and TER decreased with exposure to taurine over the course of 1 hr followed by a stabilisation. The degree of this response did not depend on the concentration of taurine but was more pronounced when taurine was added to the apical compartment. Lowering apical potassium from 6.04 to 2.2 mm further pronounced the decrease of TEP and TER. The data show that light-induced release of taurine from the outer retina and light-induced decrease of the potassium concentration in the subretinal space synergistically lead to a temporary decrease in TEP and TER. Thereby, taurine uptake into the RPE is reduced probably by a reduction of the activity of the electrogenic Na+/taurine co-transporter of the apical RPE cell membrane. The findings suggest a mechanism whereby the sustained presence of taurine in the interphotoreceptor matrix following exposure to light may protect photoreceptor outer segments from light-induced oxidative stress.

Animals↗
PubMed2005

An experimental method for testing novel retinal vital stains.

There is uncertainty surrounding the safety of the vital stains currently used to assist macular surgery, and there may be other agents that are more suitable. This study aimed to validate a method of screening retinal vital stains for their potential surgical utility. Bovine retina was exposed to test agents at a range of concentrations. Masked observers determined the minimum dye concentration that reliably stained the retina, defined as the minimum visible concentration (MVC). Computer image analysis (CIE94 colour difference equation) was used to estimate the magnitude of the colour difference between stained and unstained retina. Agents that had favourable staining characteristics underwent safety testing using a retinal pigment epithelium and glial cell culture model. Cells were exposed to each agent and viability was assessed with a mitochondrial enzyme (MTT) assay, and fluorescent live-dead probe (ethidium homodimer-1/calcein-AM). Frozen sections were used to determine which retinal layers were stained. Techniques were tested on the following agents: alcian blue; diethyloxadicarbocyanine; Evan's blue; fast green; fluorescein; Janus green; methylene blue; naphthol green; neutral red; procian (reactive) yellow; rose bengal; and trypan blue. For most dyes, the results of image analysis showed that colour differences increased linearly with dye concentration, although some displayed a more exponential relationship. Five agents showed favourable staining characteristics: Evan's blue, rose bengal, naphthol green, neutral red, and trypan blue (MVC 0.02, 0.01, 0.1, 0.002, 0.01%, respectively). Safety testing of these five agents did not show toxicity, except in glial cells exposed to rose bengal. Relative to the negative control (saline), these showed a 48% reduction in viability using the MTT assay (p<0.001; t=4.71; CI 30-75%), and qualitative damage on fluorescence microscopy. Frozen sections showed that some agents produced diffuse staining of all retinal layers, others produced selective inner retinal staining. There are thousands of biological stains available and many of these may be more effective or safer than those currently used for retinal surgery. This study provides a means of screening potentially useful vital stains.

Animals↗
PubMed2005

Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.

Apoptosis of distal lung epithelial cells plays a pivotal role in the pathogenesis of acute lung injury. In this context, proteinases, either circulating or leukocyte-derived, may contribute to epithelial apoptosis and lung injury. We hypothesized that apoptosis of lung epithelial cells induced by leukocyte elastase is mediated via the proteinase activated receptor (PAR)-1. Leukocyte elastase, thrombin, and PAR-1-activating peptide, but not the control peptide, induced apoptosis in human airway and alveolar epithelial cells as assessed by increases in cytoplasmic histone-associated DNA fragments and TUNEL staining. These effects were largely prevented by a specific PAR-1 antagonist and by short interfering RNA directed against PAR-1. To ascertain the mechanism of epithelial apoptosis, we determined that PAR-1AP, thrombin, and leukocyte elastase dissipated mitochondrial membrane potential, induced translocation of cytochrome c to the cytosol, enhanced cleavage of caspase-9 and caspase-3, and led to JNK activation and Akt inhibition. In concert, these observations provide strong evidence that leukocyte elastase mediates apoptosis of human lung epithelial cells through PAR-1-dependent modulation of the intrinsic apoptotic pathway via alterations in mitochondrial permeability and by modulation of JNK and Akt.

Apoptosis↗
PubMed2005

Adjustment of guidelines for exposure of the eye to optical radiation from ocular instruments: statement from a task group of the International Commission on Non-Ionizing Radiation Protection (ICNIRP).

A variety of optical and electro-optical instruments are used for both diagnostic and therapeutic applications to the human eye. These generally expose ocular structures to either coherent or incoherent optical radiation (ultraviolet, visible, or infrared radiation) under unique conditions. We convert both laser and incoherent exposure guidelines derived for normal exposure conditions to the application of ophthalmic sources.

Eye Injuries↗
PubMed2005

Regulation of neuroprotective activity of myocyte-enhancer factor 2 by cAMP-protein kinase A signaling pathway in neuronal survival.

The transcription factor myocyte-enhancer factor 2 (MEF2) has been shown to be required for the survival of different types of neurons. However, the death- or survival-inducing second messenger pathways that regulate MEF2 activity remain to be fully elucidated. Membrane depolarization by KCl induces neuronal survival that is dependent upon MEF2-mediated gene transactivation. Here we report that membrane depolarizationinduced activation of MEF2 requires the cAMP-protein kinase A (PKA) pathway. Inhibition of the activity of cAMP-PKA pathway attenuates membrane depolarization-induced activation of MEF2 activity and neuronal survival, whereas enhancing the activity of this pathway prevents KCl withdrawal-induced inhibition of MEF2 and neuronal apoptosis. Moreover, PKA directly phosphorylates MEF2 at Thr-20 in vitro to increase MEF2 DNA binding activity. A mutation of Thr-20 to Ala renders MEF2 resistant to PKA phosphorylation in vitro and reduces its DNA binding activity. Transfection of this T20A mutant blocks survival and induces apoptosis in cultured cortical and cerebellar granule neurons. This study identifies the transcription factor MEF2 as a target of cAMP-PKA pathway and demonstrates that PKA phosphorylation of MEF2 is a key step in modulating its DNA binding activity and ability to promote neuronal survival.

Amino Acid Sequence↗
PubMed2005

Fellow eye comparison between the 1CU accommodative intraocular lens and the Acrysof MA30 monofocal intraocular lens.

PURPOSE: To examine the near visual clinical performance of an accommodative intraocular lens (IOL) when compared with a standard monofocal IOL in a fellow eye comparison. DESIGN: Prospective, randomized fellow eye comparison. METHODS: Thirty patients (60 eyes) with bilateral cataracts but otherwise normal eyes were recruited from a single university hospital cataract waiting list. Patients were randomized to receive either the 1CU accommodative IOL in their first eye or the Acrysof MA30 monofocal IOL. The alternative lens was then implanted in the second eye 4 to 6 weeks later. At all follow-up visits, a full assessment was made of distance, near and reading visual performance, and accommodative amplitude. RESULTS: Data are available for all patients at 6 months and 20 patients at 1 year. At 6 months, no difference was found in distance-corrected visual acuity between the two IOLs. Of the 1CU eyes, nine patients (30%) could read J6 or better at a reading speed of 80 words/min or better. In these nine patients, the mean difference in the amplitude of accommodation between the two eyes was 0.71 diopters. CONCLUSIONS: No measurable variable distinguished eyes that developed functional reading vision from those that did not. The accommodative IOL appears to produce improved near vision in some eyes, but it does not work in all eyes, and in eyes where there is apparent accommodation, there is a discrepancy between subjective reading performance and the modest measured increase of accommodative amplitude.

Accommodation, Ocular↗
PubMed2005

Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery.

PURPOSE: To develop a technique to quantify biomechanical changes in the cornea after microkeratome incisions as would be performed in laser in situ keratomileusis. SETTING: St Thomas' Hospital, London, and the Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom. METHODS: Corneal displacements of whole sheep eyes were studied under hydrostatic loading using electronic speckle pattern interferometry before and after microkeratome incisions. RESULTS: After hydrostatic loading, there was a 20.7% increase in corneal displacement in corneas with microkeratome incisions compared to unoperated corneas; this was statistically significant (P=.0068, unpaired t test). CONCLUSIONS: Results show that in the formation of the microkeratome flap, collagen fibers are severed and minimal biomechanical loading is distributed through the flap. Corneal biomechanical integrity is compromised after microkeratome incisions.

Animals↗
PubMed2005

Excimer laser photorefractive keratectomy for hyperopia: 7.5-year follow-up.

PURPOSE: To report the results of a long-term prospective study to evaluate refractive stability and safety of hyperopic photorefractive keratectomy (H-PRK). SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Twenty-one patients (49%) (40 eyes) of cohort of 43 patients who participated in 1 of the first clinical trials of H-PRK were assessed at a mean follow-up of 90.7 months (range 62 to 106 months). The H-PRK was performed using a Summit Technology Apex Plus Excimer laser (Summit Technology, Inc.). The mean preoperative spherical equivalent refraction (SEQ) was +4.70 diopters (D) (range +2.00 to +7.50 D). Patients were allocated to 1 of 4 treatment groups based on their preoperative refraction and received 1 of the following spherical corrections: +1.50 D, +3.00 D, +4.50 D, or +6.00 D. RESULTS: At 7.5 years, the refractive correction remained stable with a mean difference in SEQ between 1 year and 7.5 years of +0.28 D. The mean manifest SEQ was +0.83 D (range +5.00 to -3.00 D). Sixty-seven percent of eyes having corrections of +1.50 D and +3.00 D were within +/-1.00 D of the predicted correction. Predictability was poorer with +4.50 D and +6.00 D corrections, with 40% of eyes within +/-1.00 D of that expected. An improvement in uncorrected near acuity was achieved in 35 eyes (87.5%), and 35 eyes (87.5%) showed an improvement in uncorrected distance acuity from preoperative levels. Best spectacle-corrected visual acuity (BSCVA) was unchanged or improved from preoperative values in 25 eyes (62.5%). Three eyes (8%) lost 2 lines of Snellen BSCVA, which in 2 cases was attributable to cataract formation. A peripheral ring of haze, 6.5 mm in diameter, appeared in most eyes. Its intensity was greatest at 6 months and then diminished with time. In 10 eyes (25%), remnants of the haze ring were evident at 7.5 years and subepithelial iron rings, 6.5 mm in diameter were evident in 26 eyes (70%). No patient complained of night-vision problems and no eye developed ectasia. CONCLUSIONS: In H-PRK, refractive stability achieved at 1 year was maintained up to 7.5 years with no evidence of hyperopic shift, diurnal fluctuation, or late regression. Peripheral corneal haze decreased with time but was still evident in a number of eyes at the last follow-up visit.

Adult↗
PubMed2005

Clinical results of the blue-light filtering AcrySof Natural foldable acrylic intraocular lens.

PURPOSE: To verify the safety and effectiveness of the new AcrySof Natural (Alcon Laboratories, Inc.) blue-light filtering intraocular lens (IOL), which was designed to achieve a light-transmission spectrum similar to that of the natural human crystalline lens. SETTING: Multicenter U.S. clinical trial. METHODS: In a prospective randomized patient-masked multicenter study, 150 patients received the AcrySof Natural IOL and 147 patients received the AcrySof single-piece IOL as a control. Patients with bilateral age-related cataracts who were willing and able to wait at least 30 days between cataract procedures and had verified normal preoperative color vision were eligible for the study. Standardized surgery included a 4.0 to 5.0 mm capsulorhexis and phacoemulsification. All lenses were inserted in the capsular bag, with verification of in-the-bag placement of both haptics. In all bilateral implantation cases, the same model IOL was used in each eye. Postoperatively, contrast sensitivity and color perception were measured up to 180 days and up to 1 year (for visual acuity) after implantation. RESULTS: No statistically significant differences were discovered between the 2 patient groups in visual acuity, contrast sensitivity evaluated under mesopic and photopic conditions, or the number of patients who passed the Farnsworth D-15 color perception test. There were no lens-related adverse events in either group. CONCLUSIONS: The blue-light filtering AcrySof Natural IOL was equivalent to the conventional AcrySof lens in terms of postoperative visual performance. Additional long-term clinical studies should show whether the IOL actually provides the theoretical benefits to retinal health.

Acrylic Resins↗
PubMed2005

In vitro human corneal model to investigate stromal epithelial interactions following refractive surgery.

PURPOSE: To develop an in vitro human corneal model to evaluate stromal epithelial interactions following corneal refractive surgical procedures. SETTING: Department of Academic Ophthalmology, Rayne Institute, St. Thomas' Hospital, London, United Kingdom. METHODS: Fifty-six human donor corneas procured from the eye bank were placed in a specially designed acrylic corneal holder and were cultured using the air-interface organ culture technique for up to 4 weeks. Corneal refractive surgical procedures such as a simple epithelial defect, 4 diopter (D) and 9 D photorefractive keratectomy (PRK), 4 D and 9 D laser-assisted subepithelial keratectomy (LASEK), and 9 D laser in situ keratomileusis (LASIK) were performed on the model. Temporal events in epithelial and keratocyte cell kinetics were evaluated using digital imaging, confocal microscopy, and light microscopy. Two-way analysis of variance and Student t tests were used to assess statistical significance. RESULTS: Epithelial healing following PRK was completed by 92 hours +/- 10 (SD) at a rate of 0.58 +/- 0.45 mm2/hour. In LASEK, the epithelial flap was replaced by regenerating peripheral epithelium that showed significant delay in epithelial closure (120 +/- 5 hours) with prolonged latency (24 +/- 4 hours, P<.0001) in comparison with PRK. The magnitude of keratocyte loss corresponded to ablation depth, and keratocyte regeneration was dependent on epithelial closure. In comparison, LASIK corneas showed a lesser percentage of keratocyte loss with poor recovery of keratocyte density in the stromal flap. Epithelial viability and keratocyte density were well preserved in the in vitro human model as observed in control corneas for up to 4 weeks. CONCLUSIONS: The temporal events in stromal epithelial interactions in the in vitro human model closely mimicked in vivo observations. The human model further avoided species-specific variations and provided a suitable test bed for evaluating newer algorithms and therapeutic regimens following refractive surgery.

Aged↗
PubMed2005

5-year follow-up of LASIK for hyperopia.

PURPOSE: To assess the long-term efficacy and stability of LASIK for hyperopia (+0.75 to +7.00 diopters [D]). DESIGN: Retrospective follow-up study of a previous phase III multicenter clinical trial (unpublished data). PARTICIPANTS: Patients who had been treated for hyperopia (33 individuals, 47 eyes) attended follow-up 5 years after surgery. The preoperative mean spherical equivalent at the spectacle plane was +3.58 D (range, +0.75 to 7.00 D), and the attempted mean spherical correction at the corneal plane was +3.18 D (range, +1.00 to +6.00 D). INTERVENTION: Treatments were performed using a Moria LSK One microkeratome and a Summit Technology SVS Apex Plus excimer laser fitted with an Axicon. MAIN OUTCOME MEASURES: Manifest refraction, uncorrected visual acuity, best spectacle-corrected visual acuity, corneal transparency, complications, and patient satisfaction were recorded. RESULTS: At 5 years, for treatments between +1.00 to +3.00 D, 71.0% of eyes were within +/-1.00 D of the intended correction, and for treatments between +3.5 to +6.0 D, 37.5% of eyes were within +/-1.00 D of intended correction. From 12 to 54 months after surgery for all patients, there was a hyperopic shift of +0.53 D (range, -0.13 to +3.13 D), with 51.1% of eyes experiencing an increase of +0.50 D or more and 27.7% of eyes showing a hyperopic shift of more than +1.00 D. This hyperopic shift was +0.67 D (range, 0 to +1.125 D) for patients younger than 40 years of age and +0.44 D (range, -1.33 to +1.50 D) for patients between 43 and 55 years of age. CONCLUSIONS: LASIK was moderately effective for the correction of low degrees of hyperopia. However, there was regression throughout the 5-year follow-up that was greater than would be expected as a result of aging. Long-term stability of hyperopic LASIK refractive corrections, therefore, is uncertain.

Adult↗
PubMed2005

Fusarium graminearum, F. cortaderiae and F. pseudograminearum in New Zealand: molecular phylogenetic analysis, mycotoxin chemotypes and co-existence of species.

Fusarium graminearum and F. pseudograminearum are important plant pathogens in New Zealand and around the world. Headblight and crown rot diseases of cereals caused by these species are responsible for large economic losses due to reduction in seed quality and contamination of grain with tricothecene mycotoxins. In the current study we have used two different molecular phylogenetic approaches, AFLPs and gene genealogies, to gain insight into the evolutionary relationships between F. graminearum, and F. pseudograminearum in New Zealand. The worldwide genetic diversity of F. graminearum clade is represented by at least eight biogeographically distinct species (previously designated as lineages of F. graminearum). Our analysis demonstrated that this clade is represented by F. graminearum (= F. graminearum Lineage 7) and F. cortaderiae (= F. graminearum Lineage 8) in New Zealand. Through our analysis we also confirm the presence of F. pseudograminearum in New Zealand as a first record for this organism. Information on species is necessary for preventing the inadvertent intercontinental introduction of genetically unique foreign pathogens associated with world trade. The ability to place species information into a worldwide context enabled postulation that the New Zealand representatives of F. graminearum clade originated from at least two regions, and probably on at least two hosts. Correlation of species descriptions with biogeographical and host information revealed evidence for co-localisation of F. graminearum clade species with potential for genetic outcrossing in the field. Mycotoxin analysis showed F. graminearum (= lineage 7) isolates produce either nivalenol (NIV) or deoxnivalenol (DON). In contrast, F. cortaderiae isolates produced only NIV. These findings support earlier observations that mycotoxin production in the F. graminearum clade is not species specific, but suggest maintenance of chemotype diversity through speciation may have been restricted to a subset of species.

DNA, Fungal↗
PubMed2005

The role of bevacizumab as first-line therapy for colon cancer.

The addition of oxaliplatin and irinotecan to the armamentarium for the treatment of colorectal cancer (CRC) has resulted in significant improvements in response rates and survival. Targeted therapies directed at the epidermal growth factor pathway and the vascular endothelial growth factor pathway are beginning to play a role in the treatment of CRC. Bevacizumab is a monoclonal antibody that has been evaluated in randomized studies. In a randomized phase II study, the combination of 5-fluorouracil/leucovorin (5-FU/LV) was compared with 5-FU/LV plus bevacizumab, and a randomized phase III trial evaluated the addition of bevacizumab to the irinotecan/5-FU/LV (IFL) regimen compared with IFL plus placebo. The results of these studies will be reviewed in detail. The role of bevacizumab with other first-line combinations in the treatment of patients with advanced CRC is being evaluated in ongoing clinical trials. Additionally, the activity of bevacizumab is being evaluated for use in the second-line treatment setting for patients with CRC.

Adenocarcinoma↗
PubMed2005

Pediatric surgical site and soft tissue infections.

OBJECTIVE: The purpose of this review is to provide background and a concise set of definitions for pediatric surgical site and wound infections. DESIGN: The information discussed in this report is derived from a literature review and discussion at an international consensus conference on pediatric sepsis. MEASUREMENTS AND MAIN RESULTS: There is a paucity of literature on pediatric surgical site and wound infection definitions. Excluding burn wounds, surgical site and wound infections rarely lead to overwhelming sepsis. Nevertheless, surgical site or wound infections including pressure ulcers can lead to significant morbidity in the pediatric critical care setting. CONCLUSIONS: Although surgical site and wound infections rarely lead to intensive care unit admissions, definitions are still valuable for stratifying potential candidates for sepsis trials.

Burns↗