Into the looking glass: factors and opportunities to reshape eye care in the next 25 years.
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Delivery of Health Care↗
Biomedical subjects
Paul Lee
Publications and source records attributed to Paul Lee.
Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism.
Reactive oxygen species (ROS) have been implicated in the development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the levels of platelet activating factor (PAF) and cytokines which are known to stimulate granulocytes and endothelial cells to produce ROS. Pentoxifylline (PTX) is an inhibitor of cytokines and PAF and would reduce the generation of ROS by granulocytes and endothelial cells. PTX therefore would be expected to reduce the development of hypercholesterolemic atherosclerosis. New Zealand white female rabbits were assigned to four groups: Group I (n=12), control; Group II (n=5), PTX control (40 mg/kg body weight daily orally); Group III (n=13), 0.5% cholesterol; Group IV (n=9), 0.5% cholesterol+PTX (40 mg/kg body weight daily orally). Blood samples were collected before (0 time) and after 1 and 2 months on experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of 2 months the aorta was removed for measurement of atherosclerotic plaques, MDA, and aortic tissue chemiluminescence (Ao-CL), a marker for antioxidant reserve. Rabbits in Group III developed atherosclerosis (56.61+/-6.90% of the intimal surface of aorta was covered with atherosclerotic plaques) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, TC/HDL-C, MDA and aortic MDA and antioxidant reserve. PTX reduced the development of atherosclerosis by 38.1% and this was associated with decreases in serum MDA by 32%, aortic MDA by 37%, and antioxidant reserve by 17.3% without changes in the serum lipids. These results suggest that ROS generated during hypercholesterolemia via cytokines and PAF may in part contribute to the development of hypercholesterolemic atherosclerosis and that suppression of production and activity of cytokines and PAF may reduce the development of hypercholesterolemic atherosclerosis.
Animals↗
Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa.
The duodenum is the site of mixing of massive amounts of gastric H+ with secreted HCO3-, generating CO2 and H2O accompanied by the neutralization of H+. We examined the role of membrane-bound and soluble carbonic anhydrases (CA) by which H+ is neutralized, CO2 is absorbed, and HCO3- is secreted. Rat duodena were perfused with solutions of different pH and PCO2 with or without a cell-permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors. Flow-through pH and PCO2 electrodes simultaneously measured perfusate and effluent pH and PCO2. High CO2 (34.7 kPa) perfusion increased net CO2 loss from the perfusate compared with controls (pH 6.4 saline, PCO2 approximately 0) accompanied by portal venous (PV) acidification and PCO2 increase. Impermeant CA inhibitors abolished net perfusate CO2 loss and increased net HCO3- gain, whereas all CA inhibitors inhibited PV acidification and PCO2 increase. The changes in luminal and PV pH and [CO2] were also inhibited by the Na+-H+ exchanger-1 (NHE1) inhibitor dimethylamiloride, but not by the NHE3 inhibitor S3226. Luminal acid decreased total CO2 output and increased H+ loss with PV acidification and PCO2 increase, all inhibited by all CA inhibitors. During perfusion of a 30% CO2 buffer, loss of CO2 from the lumen was CA dependent as was transepithelial transport of perfused 13CO2. H+ and CO2 loss from the perfusate were accompanied by increases of PV H+ and tracer CO2, but unchanged PV total CO2, consistent with CA-dependent transmucosal H+ and CO2 movement. Inhibition of membrane-bound CAs augments the apparent rate of net basal HCO3- secretion. Luminal H+ traverses the apical membrane as CO2, is converted back to cytosolic H+, which is extruded via NHE1. Membrane-bound and cytosolic CAs cooperatively facilitate secretion of HCO3- into the lumen and CO2 diffusion into duodenal mucosa, serving as important acid-base regulators.
Acid-Base Equilibrium↗
Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction.
Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem/progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly elucidate the mechanistic contributions of c-kit+ bone marrow-derived hematopoetic stem/progenitor cells in the maintenance and repair of damaged myocardium after MI. Using c-kit-deficient mice, we demonstrate the importance of c-kit signaling in preventing ventricular dilation and hypertrophy, and the maintenance of cardiac function after MI in c-kit-deficient mice. Furthermore, we show phenotypic rescue of cardiac repair after MI of c-kit-deficient mice by bone marrow transplantation of wild-type HSPCs. The transplanted group also had reduced apoptosis and collagen deposition, along with an increase in neovascularization. To better understand the mechanisms underlying this phenotypic rescue, we investigated the gene expression pattern within the infarcted region by using microarray analysis. This analysis suggested activation of inflammatory pathways, specifically natural killer (NK) cell-mediated mobilization after MI in rescued hearts. This finding was confirmed by immunohistology and by using an NK blocker. Thus, our investigation revealed a previously uncharacterized role for c-kit signaling after infarction by mediating bone marrow-derived NK and angiogenic cell mobilization, which contributes to improved remodeling and cardiac function after MI.
Animals↗
On the statistics of ultrasonic spectral parameters.
Several factors affect the accuracy and precision of ultrasonic spectrum analysis, which is used for characterization of normal and diseased tissue in a variety of organs. For example, averaging procedures and the sequence of operations affect the accuracy and precision of spectrum analysis. Averaging procedures and logarithmic conversion (i.e., conversion to dB) introduce a constant bias that affects spectral amplitudes and the values of intercept and midband fit; the bias depends on the sequencing of the log conversion and averaging as well as the number of independent spectra or spectral parameters that are averaged. We derive expressions that permit correction of such biases. Furthermore, we show that standard deviations for slope and midband-fit estimation can be minimized by averaging spectra before dB conversion and before computing spectral parameters by linear regression. Experimental results using phantoms agree remarkably with theoretical predictions for the data window functions studied in this article, Hamming and rectangular.
Humans↗
Regionalization reigns--but is care being delivered accordingly? An evaluation of perinatal care delivery in a regionalized child health network.
The Child Health Network for the Greater Toronto Area (CHN), a network of 20 hospitals and 9 community care access centres, assessed one component of its early progress in building a regionalized system of perinatal care. Focusing on the relationship between hospital level of care and gestational age, the study showed that most births occurred at appropriately designated facilities. However, a quarter of newborns of gestational age <32 weeks were delivered at a lower level of care than is considered optimal. CHN's ongoing research will offer opportunities to assess the impact of regional models on their foremost goal--quality clinical care.
Cooperative Behavior↗
Coronavirus HKU1 and other coronavirus infections in Hong Kong.
We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.
Acute Disease↗
Children should be seen and heard: self-report of feelings and behaviors in primary-school-age children with ADHD.
OBJECTIVE: The belief that children with externalizing disorders have difficulties with self-awareness raises the question of whether children with externalizing disorders are good informants of their own behavior. METHOD: This study investigates how children with ADHD rate their behaviors compared to children without ADHD on a new rating scale (the Self-Evaluation Scale for Children). RESULTS: Preliminary results indicate that this rating scale has acceptable reliability and validity. Furthermore, children with ADHD are found to provide useful information about their feelings and behaviors. Compared to children without ADHD, children with ADHD report more disorganized, disruptive, and impulsive behaviors; poorer self-perception; and poorer social and communication skills. They do not report any less interest in school activities nor more anxiety than the children without ADHD. CONCLUSION: These findings suggest that children with ADHD are more self-aware than previously thought, and this information should inform our clinical and research practice.
Adolescent↗
Covalently bound hole-injecting nanostructures. Systematics of molecular architecture, thickness, saturation, and electron-blocking characteristics on organic light-emitting diode luminance, turn-on voltage, and quantum efficiency.
Hole transporting materials are widely used in multilayer organic and polymer light-emitting diodes (OLEDs, PLEDs, respectively) and are indispensable if device electroluminescent response and durability are to be truly optimized. This contribution analyzes the relative effects of tin-doped indium oxide (ITO) anode-hole transporting layer (HTL) contact versus the intrinsic HTL materials properties on OLED performance. Two siloxane-based HTL materials, N,N'-bis(p-trichlorosilylpropyl)-naphthalen-1-yl)-N,N'-diphenyl-biphenyl-4,4'-diamine (NPB-Si(2)) and 4,4'-bis[(p-trichlorosilylpropylphenyl)phenylamino]biphenyl (TPD-Si(2)), are designed and synthesized. They have the same hole transporting triarylamine cores as conventional HTL materials such as 1,4-bis(1-naphthylphenylamino)biphenyl (NPB) and N,N-diphenyl-N,N-bis(3-methylphenyl)-1,1-biphenyl)-4,4-diamine (TPD), respectively. However, they covalently bind to the ITO anode, forming anode-HTL contacts that are intrinsically different from those of the anode to TPD and NPB. Applied to archetypical tris(8-hydroxyquinolato)aluminum(III) (Alq)-based OLEDs as (1) the sole HTLs or (2) anode-NPB HTL interlayers, NPB-Si(2) and TPD-Si(2) enhance device electroluminescent response significantly versus comparable devices based on NPB alone. In the first case, OLEDs with 36 000 cd/m(2) luminance, 1.6% forward external quantum efficiency (eta(ext)), and 5 V turn-on voltages are achieved, affording a 250% increase in luminance and approximately 50% reduction in turn-on voltage, as compared to NPB-based devices. In the second case, even more dramatic enhancement is observed (64 000 cd/m(2) luminance; 2.3% eta(ext); turn-on voltages as low as 3.5 V). The importance of the anode-HTL material contact is further explored by replacing NPB with saturated hydrocarbon siloxane monolayers that covalently bind to the anode, without sacrificing device performance (30 000 cd/m(2) luminance; 2.0% eta(ext); 4.0 V turn-on voltage). These results suggest new strategies for developing OLED hole transporting structures.
Journal Article↗
High-performance hole-transport layers for polymer light-emitting diodes. Implementation of organosiloxane cross-linking chemistry in polymeric electroluminescent devices.
This contribution describes an organosiloxane cross-linking approach to robust, efficient, adherent hole-transport layers (HTLs) for polymer light-emitting diodes (PLEDs). An example is 4,4'-bis[(p-trichlorosilylpropylphenyl)phenylamino]biphenyl (TPDSi(2)), which combines the hole-transporting efficiency of N,N-diphenyl-N,N-bis(3-methylphenyl)-1,1-biphenyl)-4,4-diamine) (TPD, prototypical small-molecule HTL material) and the strong cross-linking/densification tendencies of organosilanol groups. Covalent chemical bonding of TPDSi(2) to PLED anodes (e.g., indium tin oxide, ITO) and its self-cross-linking enable fabrication of three generations of insoluble PLED HTLs: (1) self-assembled monolayers (SAMs) of TPDSi(2) on ITO; (2) cross-linked blend networks consisting of TPDSi(2) + a hole transporting polymer (e.g., poly(9,9-dioctylfluorene-co-N-(4-(3-methylpropyl))diphenylamine), TFB) on ITO; (3) TPDSi(2) + TFB blends on ITO substrates precoated with a conventional PLED HTL, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS). PLED devices fabricated using these new HTLs exhibit comparable or superior performance vs comparable devices based on PEDOT-PSS alone. With these new HTLs, current efficiencies as high as approximately 17 cd/A and luminances as high as approximately 140,000 cd/m(2) have been achieved. Further experiments demonstrate that not only do these HTLs enhance PLED anode hole injection but they also exhibit significantly greater electron-blocking capacity than PEDOT-PSS. The present organosiloxane HTL approach offers many other attractions such as convenience of fabrication, flexibility in choosing HTL components, and reduced HTL-induced luminescence quenching, and can be applied as a general strategy to enhance PLED performance.
Journal Article↗
Transatrial septal catheterization using a new radiofrequency probe.
Percutaneous therapeutic techniques requiring transseptal catheterization have increased in recent years. The traditional and current method for transseptal catheterization involves needle puncture, an effective but complicated technique, which is associated with a small but significant incidence of both perforation of structures adjacent to the atrial septum and pericardial tamponade. Enhanced imaging has reduced but not eliminated the risk of these complications. We have used an alternative method for transseptal access to the left atrium, which employs a novel radiofrequency catheter system. In this report, we describe the system and its use in our initial series of patients.
Adolescent↗
Symptoms of musculoskeletal disorders in ophthalmologists.
OBJECTIVE: To describe the presence of musculoskeletal disorders (MSDs) of the neck, low back, and upper extremity among ophthalmologists. DESIGN: Survey. METHODS: Mail survey using a pretested instrument to 2,529 ophthalmologists in the Northeastern United States; 697 ophthalmologists (28%) returned a completed survey. RESULTS: Self-reported prevalence of neck, upper body, or lower back symptoms in the prior month was 51.8%. Low back pain was present in 39% of respondents, followed by upper extremity symptoms (32.9%) and neck pain (32.6%). Approximately 15% of ophthalmologists were slightly to moderately limited in their work as a result of these symptoms. CONCLUSION: MSD symptoms appear to be common among ophthalmologists. With a relatively low response rate, however, it is plausible that asymptomatic subjects represent a large percentage of the nonrespondents. Additional investigation is warranted to evaluate ergonomic risk factor exposure and establish injury prevention guidelines.
Back Pain↗
Inhibition of return in children with Tourette's syndrome and comorbid forms: a preliminary study.
BACKGROUND: This study investigated the nature and functioning of the visual-spatial inhibition of return (IOR) phenomenon in children with "pure" Tourette's syndrome (TS), and those with comorbid forms of TS. METHOD: Children with TS-only and "TS + comorbid" (TS + ADHD +/- OCD) and matched controls performed the inhibition of return (IOR) task, which involved responding to left and right visual targets appearing on a computer screen that were preceded by congruent or incongruent exogenous visual cues. RESULTS: The TS-only group performed similarly on the IOR task to the controls. When the TS-only group was subdivided into children with mild and severe TS symptoms, a post hoc comparison between the controls and severe TS symptom children revealed that these TS children had a reduced magnitude of IOR for targets appearing in the right visual field. The comparison between the TS + comorbid and controls revealed an atypical IOR pattern for the TS + comorbid group. They displayed a loss of normal facilitatory and inhibitory effects for right visual field targets. CONCLUSIONS: The findings suggest abnormalities in attentional "disengage" and "move" mechanisms in TS when directing attention to the right visual field, which may reflect left posterior parietal, superior colliculus, and midbrain pathology.
Adolescent↗
Motor preparation, motor execution, attention, and executive functions in attention deficit/hyperactivity disorder (ADHD).
Attention and executive functions were investigated in medicated and unmedicated children with ADHD combined type using a novel selective reaching task. This task involved responding as rapidly as possible to a target while at times having to ignore a distractor. Results indicated that unmedicated children with ADHD showed slow and inaccurate responding. Slow responding reflected problems at the stage of movement preparation but not movement execution. An attentional impairment, rather than a motor planning problem per se, appeared to underlie the slow movement preparation. Inaccurate responding reflected problems with response inhibition and selective attention, impulsivity, set-shifting, and difficulties in maintaining vigilance. Although medicated children with ADHD did not show slow movement preparation, they did show some response inaccuracy, resulting especially from impulsive responding. These findings suggest that ADHD is characterized by slow motor preparation (but not motor execution), and deficits in selective attention, vigilance, and executive functions. Preliminary results suggest that stimulant medication may resolve some of these motor, attentional and executive function deficits.
Attention↗
Interlaboratory comparison of ultrasonic backscatter coefficient measurements from 2 to 9 MHz.
OBJECTIVE: As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz. METHODS: Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed. RESULTS: Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power). CONCLUSIONS: Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude.
1-Propanol↗
Intracoronary brachytherapy for in-stent restenosis using long sources reduces restenosis.
Edge restenosis (candy wrapper effect) and late thrombosis remain a problem in various randomized intracoronary brachytherapy (ICBT) trials for the treatment of in-stent restenosis (ISR). Target vessel revascularization (TVR) due to target lesion revascularization (TLR) and edge restenosis can be decreased with the use of longer ICBT sources and debulking devices and has not been systematically studied. We analyzed 226 patients with ISR (240 vessels of 264 lesions; average lesion length 17.5+/-8.9 mm) who had lesion debulking followed by 90 Strontium (Sr) beta-irradiation using the Novoste Betacath system (30 mm source in 144 vessels and 40 mm source in 96 vessels). Dual antiplatelet therapy was recommended for one year. At follow-up of 12+/-2 months, clinical TVR occurred in 9.7%, with TLR in 7.1% and non-TLR in 2.6% of cases. There was no delayed or late subacute thrombosis. Beta-irradiation using a longer 90Sr source after lesion modification with cutting balloon (CB) and or rotational atherectomy (RA), along with the use of long-term dual antiplatelet therapy is safe and associated with single-digit clinical restenosis.
Angioplasty, Balloon, Coronary↗
The type I Hsp40 zinc finger-like region is required for Hsp70 to capture non-native polypeptides from Ydj1.
The cytosolic yeast Hsp40 Ydj1 contains a conserved zinc finger-like region (ZFLR), which has two zinc-binding domains (ZBD), that helps regulate and specify Hsp70 function. To investigate the mechanism for Ydj1 ZFLR action, ZBDI and ZBDII mutants were constructed and characterized. ZBDII mutants exhibited temperature-sensitive growth defects, but yeast tolerated mutation of ZBDI. However, ZBDI and ZBDII mutants were defective at facilitating androgen receptor (AR) folding. Defective AR folding was associated with the accumulation of complexes between AR and Ydj1 ZFLR mutants and a reduction in Hsp70.AR complex formation. Purified Ydj1 ZBDI and ZBDII mutants could bind non-native polypeptides but could not deliver luciferase to Hsp70 and were defective at luciferase refolding. Interestingly, the ability of Ydj1 to synergize with Hsp70 to suppress thermally induced protein aggregation was blocked by mutation of ZBDII, but not ZBDI. Hence, ZBDII is required for yeast to survive heat stress because it is essential for Ydj1 to cooperate with Hsp70 to suppress protein aggregation. On the other hand, protein folding is dependent upon the action of both ZBDI and ZBDII because each is required for Hsp70 to capture non-native polypeptides from Ydj1.
Binding Sites↗
Inflammatory cytokines and postmyocardial infarction remodeling.
Inflammatory response and cytokine elaboration are particularly active after myocardial infarction and contribute to cardiac remodeling and eventual host outcome. The triggers of cytokine release in the acute postinfarction period include mechanical deformation, ischemic stimulus, reactive oxygen species (ROS), and cytokine self-amplification pathways. Acutely, the elaboration of tumor necrosis factor, IL-1 and IL-6, transforming growth factor families of cytokines, contribute to survival or deaths of myocytes, modulation of cardiac contractility, alterations of vascular endothelium, and recruitment of additional circulating cells of inflammation to the injured myocardium. This leads to further local oxidative stress and remodeling but also initiates the processes of wound healing. Chronically, sustained presence of cytokines leads to myocyte phenotype transition and activation of matrix metalloproteinases that modifies interstitial matrix, augmenting further the remodeling process. This in turn alters the local collagen composition and also the integrins that constitute the interface between myocytes and the matrix. These processes ultimately, when favorable, pave the way for angiogenesis and cellular regeneration. Thus, the insightful modulation of cytokines through current and future therapies could promote improved healing and cardiac remodeling postmyocardial infarction.
Animals↗