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ABSTRACT: Apolipoprotein E4 (apoE4) plays a major role in the pathogenesis of Alzheimer's disease. Brain amyloid-β (Aβ) accumulation depends on age and apoE isoforms (apoE4 > apoE3) both in humans and in transgenic mouse models. Brain apoE levels are also isoform dependent, but in the opposite direction (apoE4 < apoE3). Thus, one prevailing hypothesis is to increase brain apoE expression to reduce Aβ levels. To test this hypothesis, we generated mutant human amyloid precursor protein transgenic mice expressing one or two copies of the human APOE3 or APOE4 gene that was knocked in and flanked by LoxP sites. We report that reducing apoE3 or apoE4 expression by 50% in 6-month-old mice results in efficient Aβ clearance and does not increase Aβ accumulation. However, 12-month-old mice with one copy of the human APOE gene had significantly reduced Aβ levels and plaque loads compared with mice with two copies, regardless of which human apoE isoform was expressed, suggesting a gene dose-dependent effect of apoE on Aβ accumulation in aged mice. Additionally, 12-month-old mice expressing one or two copies of the human APOE4 gene had significantly higher levels of Aβ accumulation and plaque loads than age-matched mice expressing one or two copies of the human APOE3 gene, suggesting an isoform-dependent effect of apoE on Aβ accumulation in aged mice. Moreover, Cre-mediated APOE4 gene excision in hippocampal astrocytes significantly reduced insoluble Aβ in adult mice. Thus, reducing, rather than increasing, apoE expression is an attractive approach to lowering brain Aβ levels.
Journal of Neuroscience 04/2012; 32(14):4803-11. · 7.11 Impact Factor
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ABSTRACT: The evaluation and management (E/M) services for the physician and the hospital-based outpatient center ("facility") are calculated using different federal regulations. In addition, patients visiting outpatient wound care centers require different levels of care from the physician than the facility. The purpose of this study was to analyze and compare physician and facility E/M level-of-service coding using the electronic wound registry records from three geographically diverse, hospital-based outpatient wound centers. De-identified data on 9,985 patient visit level-of-service codes were prospectively collected using an electronic health record (EHR) system that internally and automatically audits the chart and calculates the physician and the facility E/M level of service based on the documentation present in the chart. Correlations were calculated using Kendall's tau b/Goodman-Kruskal gamma statistics. Correlations were weak between facility and physician E/M level-of-service codes, varying from 0.084 to 0.179 for follow-up and from 0.066 to 0.354 for initial visits. Although facility E/M levels of service followed a normal distribution, physician E/M visits were heavily skewed toward higher levels of care (3 to 5). These findings confirm that, especially during the initial visit, patients presenting at outpatient wound centers require different levels of care from the physician than from the facility. The finding that initial physician level of service coding was higher than facility E/M levels of service for both initial and follow-up visits is not unexpected, considering the high number of comorbidities in many wound patients and the general risk of their presenting problems.
Ostomy/wound management 03/2012; 58(3):20-2, 24, 26-8. · 1.08 Impact Factor
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ABSTRACT: An 87-year-old man presented 10 months following permanent pacemaker insertion with cellulitis-like inflammation around the impulse generator. Symptoms improved with oral flucloxacillin, but only days after stopping, the infection recurred, and he was admitted from clinic for intravenous antibiotics. Suspecting the source was likely Staphylococcal, intravenous flucloxacillin was started, and the patient's inflammatory markers responded adequately. Two samples of fluid were aspirated from the pacemaker site. These showed no bacterial growth using routine microbiological culture techniques. The samples were sent for 16S rDNA PCR and Dietzia species was detected in both samples. Dietzia species is an Actinomyces-like organism, which is not commonly associated with human infection, but is reported to have been isolated from clinical specimens and thus presumptively associated with human disease. The pacemaker was explanted and the pocket debrided with no complications. He made a full recovery after a prolonged course of flucloxacillin.
Case Reports 01/2012; 2012.
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ABSTRACT: Knowledge about practice patterns and optimal usage criteria for topical antimicrobial dressings is limited. A retrospective data analysis was conducted to evaluate: 1) the length of time these dressings are applied in a typical episode of wound care, 2) the number of episodes of antimicrobial dressing use, and 3) whether antimicrobial dressings are applied in consideration of signs and symptoms of infection. Wound care registry data from a level-4 electronic medical record were analyzed, providing information on 3,084 patients older than 17 years seen from July 2003 through December 2008 in 26 hospital-based, outpatient wound centers in 14 states. The 5,541 recorded wounds ranged in size from 0.3 to 225 cm2. One antimicrobial dressing use episode was recorded for 71% of wounds (4.7% had four or more). Mean treatment episode length was 32.5 days (median 21 days). Clinicians used these dressings for a longer period of time if patients had multiple comorbidities (P = .0001), a refractory wound (P <.00001), or were prescribed oral antibiotics (P <.0002); first dressing use was more common in wounds with signs and symptoms of infection (P <.00001). During an average of 16 (median 10) visits and a follow-up time of 269 days, 61.4% of wounds healed (range 42.2% for flaps or grafts to 67.9% for surgical wounds of all 5,541 wounds). Antimicrobial dressing use for 2 to 4 weeks was associated with a higher proportion of healed wounds, but in wounds that healed, longer dressing use was associated with a longer healing time. The practice pattern observed suggests that antimicrobial dressing usage generally is based on patient and wound assessment variables but prospective studies are needed to develop optimal guidelines of care.
Ostomy/wound management 03/2010; 56(3):28-42. · 1.08 Impact Factor
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ABSTRACT: "Doing the right thing" in wound care is not an easy task. Studies suggest that 3 factors determine compliance with performing basic wound care from an evidence-based medicine perspective: complexity, cognitive effort, and the compensation system. Two models were explored to investigate compliance with basic wound care at hospital based wound centers: offloading of diabetic foot ulcers (DFUs) and compression bandaging for venous leg ulcers. Using a very large wound-care registry it was determined that only 6% of DFU patients received the gold standard of care for offloading, i.e., total contact casting (TCC), but among those patients who received it, the average cost of treatment was half the cost of those who did not. Although inexpensive to administer, TCC is a relatively time-consuming procedure which is poorly reimbursed. Other DFU treatments such as bilaminate skin, are more costly but are reimbursed much more generously. Thus, the reimbursement system favors the use of more expensive therapies over more economical ones. In the case of venous leg ulcers (VLUs), only 17% of patients received adequate compression. Provision of adequate compression among VLU patients has been similarly hindered by inadequate reimbursement policy. Lack of familiarity with clinical practice guidelines increases the cognitive effort for clinicians. Improving the economic model to favor the provision of effective basic care, creating easier-to-use products, and making clinical practice guidelines available at the point of service may make it easier to "do the right thing(s)" in wound care.
Wound Repair and Regeneration 02/2010; 18(2):154-8. · 2.91 Impact Factor
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Case Reports 01/2010; 2010.
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ABSTRACT: To determine the percentage of individuals that would be excluded from wound care randomized controlled trials (RCTs) as a surrogate for applicability to general populations.
A representative sample of wound-care RCTs was selected from the literature in the past 10 years. Exclusion criteria from the trials were evaluated, and prevalence values for each excluded condition were obtained from a large wound-care population, as well as from the literature. The percentage of patients excluded on this basis was calculated.
Seventeen RCTs testing "high-technology" wound-care products were evaluated.
: Patients in the trials were treated for ulcers (venous, diabetic foot, and pressure ulcers).
A percentage of patients in the study population were excluded for each RCT.
More than 50% of the study population would have been excluded in 15 of the 17 RCTs. When less clinically relevant exclusion criteria were removed, 14 of 17 RCTs would still have excluded between 25% and 50% of the study population.
The results raise serious questions regarding the applicability of these RCTs to wound-care populations.
Advances in skin & wound care 07/2009; 22(7):316-24.
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ABSTRACT: The purpose of this project was to evaluate the safety of negative pressure wound therapy using the vacuum-assisted closure (V.A.C.) Therapy System (KCI, San Antonio, TX) in diabetic foot ulcers (DFUs) among wound centre outpatients. We defined events that could represent complications or adverse events (AEs) as a result of treatment with the V.A.C., including symptoms of infection, pain, bleeding and periwound skin breakdown. The frequency of these AEs among V.A.C. patients with DFUs was compared with those among similar non V.A.C. patients. This project prospectively queried data collected during routine clinical care from 16 outpatient wound centres using the Intellicure electronic medical record system. The electronic records were de-identified according to HIPAA requirements and pooled to create a data repository dedicated to research (the Intellicure Research Consortium). Analysis was performed on 1331 DFUs representing 16,438 outpatient visits. A total of 1299 non V.A.C. and 72 V.A.C. DFUs were available for analysis. There was either no statistical difference between the AEs of V.A.C. versus non V.A.C. patients or the V.A.C. exerted a protective effect. We conclude that the V.A.C. is safe in outpatient use.
International Wound Journal 07/2008; 5 Suppl 2:17-22. · 1.46 Impact Factor
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ABSTRACT: Outpatient wound center facility reimbursement for Medicare beneficiaries can be a challenge to determine and obtain. To compare methods of calculating facility service levels for outpatient wound centers and to demonstrate the advantages of an acuity-based billing system (one that incorporates components of facility work that is non-reimbursable by procedure codes and that represents an activity-based costing approach to medical billing), a retrospective study of 5,098 patient encounters contained in a wound care-specific electronic medical record database was conducted. Approximately 500 patient visits to the outpatient wound center of a Texas regional hospital between April 2003 and November 2004 were categorized by service level in documentation and facility management software. Visits previously billed using a time-based system were compared to the Centers for Medicare and Medicaid Services' proposed three-tiered wound size-based system. The time-based system also was compared to an acuity-based scoring system. The Pearson correlation coefficient between billed level of service by time and estimated level of service by acuity was 0.442 and the majority of follow-up visits were billed as Level 3 and above (on a time level of 1 to 5) , confirming that time is not a surrogate for actual work performed. Wound size also was found to be unrelated to service level (Pearson correlation = 0.017) and 97% of wound areas were < 100 cm2. The acuity-based scoring system produced a near-normal distribution of results, producing more mid-range billings than extremes; no other method produced this distribution. Hospital-based outpatient wound centers should develop, review, and refine acuity score-based models on which to determine billed level of service.
Ostomy/wound management 01/2007; 53(1):34-44. · 1.08 Impact Factor
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Ostomy/wound management 05/2004; 50(4A Suppl):28-31. · 1.08 Impact Factor
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ABSTRACT: The effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, was studied alone or in combination with postnatal hyperthermia, on the structural and neurochemical development of the postnatal brain at 1 and 8 weeks. Pregnant guinea pigs (n = 11) were exposed to 200 p.p.m CO for 10 h/day from midgestation until term (68 days), whereas control mothers (n = 10) breathed room air. On postnatal day 4, neonates from the control and CO-exposed pregnancies were exposed to hyperthermia (35°C) for 75 min or remained at ambient (23°C) temperature. Using semiquantitative immunohistochemical techniques the following neurotransmitter alterations were found in the medulla at 1 week: a decrease in met-enkephalin-immunoreactivity (IR) following postnatal hyperthermia and an increase in 5-hydroxytryptamine-IR following a combination of CO and hyperthermia. No alterations were observed in substance P- or tyrosine-hydroxylase-IR in any paradigm. At 8 weeks of age the combination of prenatal CO exposure followed by a brief hyperthermic stress postnatally resulted in lesions throughout the brain and an increase in glial fibrillary acidic protein-IR in the medulla. Such effects on brain development could be of relevance in cardiorespiratory control in the neonate and could have implications for the etiology of Sudden Infant Death Syndrome, where smoking and hyperthermia are major risk factors.
Experimental Neurology 05/2000; · 4.70 Impact Factor
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ABSTRACT: Hypoxia causes a reversible decrease in the level of respiratory, oculomotor and postural muscle activity in fetal sheep, an effect not seen in newborn lambs. We have used Fos immunohistochemistry to identify neurons which are activated by hypoxia and which may mediate this motor inhibition in the fetus. Pregnant sheep of either 117 or 138 days gestation were made hypoxic by allowing them to breathe 8–9% O2 for 2 h. Compared to age-matched control fetuses, hypoxia caused a significant increase in Fos-immunoreactivity in several medullary nuclei including the nucleus tractus solitarius, lateral reticular nucleus and the rostral ventrolateral medulla and also in the lateral parabrachial nucleus, locus coeruleus and subcoeruleus region in the pons. Hypoxia in newborn lambs, 7–18 days old, resulted in Fos staining in the same medullary and pontine nuclei with the exception of the subcoeruleus region which was devoid of Fos-immunoreactivity. In newborn lambs in which the carotid sinus nerves had been sectioned bilaterally, Fos-immunoreactivity was increased in the nucleus tractus solitarius in the medulla and in the locus coeruleus, lateral parabrachial and Kölliker–Fuse nuclei in the pons when compared to intact control newborn lambs. When carotid sinus nerve denervated-lambs were subjected to hypoxia the pattern of Fos-ir was similar to the pattern seen in the denervated control lambs but in addition staining was present in the subcoeruleus. These results suggest that a specific set of pontine neurons are activated by low oxygen levels in the fetus but not in the newborn lamb in the presence of an intact innervation from the carotid sinus. We hypothesise that: (a) in the fetus hypoxia activates neurons in the region of the subcoeruleus and this causes cessation of breathing movements and muscle atonia; and (b) that after birth stimulation of the carotid chemoreceptors by hypoxia normally inhibits activation of these subcoeruleus neurons.
Brain Research 03/1997; · 2.73 Impact Factor
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ABSTRACT: Protoplasts prepared from spinach leaves in May and June contained substantial amounts of ascorbate (1.330.28 mol mg-1 chlorophyll), of which 30–40% was localised in the chloroplasts. During illumination, the ascorbate content was maintained at approximately the same concentration as in the dark in both protoplasts and chloroplasts, even in the absence of CO2 when pseudocyclic electron flow would be expected to be maximal. The addition of the Mehler reagent, methyl viologen, to isolated chloroplasts caused a rapid oxidation of stromal ascorbate in the light such that less than 95% of the ascorbate was oxidised after illumination for 1 min. Similarly the stromal ascorbate pool was rapidly oxidised upon the addition of H2O2. We conclude that when the intracellular ascorbate concentration is high, photosynthetically generated H2O2 can be reduced at rates comparable to its synthesis via the ascorbate-glutathione cycle. The addition of methyl viologen which catalyses rapid production of the superoxide anion, O
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or the addition of excess H2O2, overwhelms the reductive cycle and the ascorbate system becomes partially or totally oxidised.
Planta 01/1983; 157(3):239-244. · 3.00 Impact Factor
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ABSTRACT: Of the total adenylate-kinase activity in 10-d-old barley and wheat leaves, 40–50% is localised in the chloroplasts, while in mature spinach leaves 50–70% of the enzyme is chloroplastic. The extra-chloroplastic adenylate-kinase activity is associated with the mitochondria, very little, if any, is freely soluble in the cytoplasm. The adenylate pool of the cytoplasm could have access to adenylate-kinase activity in the intermitochondrial space because of the free permeation of adenylates across the outer mitochondrial membrane. Thus the adenylate pool of the cytoplasm could be subject to adenylate-kinase equilibrium. The mitochondrial adenylate kinase appeared to the localised exclusively in the intermembrane space.
Planta 01/1982; 156(2):171-175. · 3.00 Impact Factor
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ABSTRACT: Ensuring adequate stocks of wound care supplies at wound care to be tied up, and too little can cause problems for patients. Most facilities maintain a "par" level for each item, which requires that supplies be ordered even if the "par" is numerically short by one item. In addition, due to the current just-in-time environment, if attention is not paid to the par level, unexpected shortages of supplies can develop. By using Inventory Trak software developed by Intellicure, facility managers will always know how much stock is presentfor each item, as individual item barcodes are registered in the system each time an item is used through software-linking scanners. The result is increased efficiency, reduced cost to the facility, and an assurance that the facility will not run out of critical items.
The Journal of medical practice management: MPM 23(3):174-6.
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ABSTRACT: Near liquidus experiments on peridotite and other olivine normative compositions from 1.7 to 6 GPa confirm the applicability of exchange-based empirical models of Ni and Co partitioning between olivine and silicate liquids with compositions close to the liquidus of peridotite. Given that most estimates of lunar bulk composition are peridotitic, the partitioning models thus lend themselves to calculation of olivine compositions produced during the early stages of magma ocean crystallization. Calculation of olivine compositions produced by fractional crystallization of a model lunar magma ocean, initially 700 km deep, reveals a prominent maximum in Ni concentration versus fraction crystallized or Mg’ (molar MgO/(MgO + FeO)), but a pattern of monotonically increasing Co concentration. These patterns qualitatively match the puzzling patterns of Ni and Co concentrations observed in lunar rocks in which forsteritic olivines in magnesian suite cumulates have lower Ni and Co abundances than do less magnesian olivines from low-Ti mare basalts, and olivines from the ferroan anorthosite suite (FAS) have lower Ni, but similar Co to mare basalt olivines.The Ni and Co abundances in olivines from the magnesian suite cumulates can be reconciled in terms of fractional crystallization of a deep magma ocean which initially produces a basal dunite comprised of the hottest and most magnesian olivine overlain by an olivine-orthopyroxene (harzburgite) layer that is in turn overlain by an upper zone of plagioclase-bearing cumulates. The ultramafic portion of the cumulate pile overturns sending the denser harzburgite layer, which later becomes a portion of the green glass source region, to the bottom of the cumulate pile with Ni- and Co-rich olivine. Meanwhile, the less dense, but hottest, most magnesian olivines with much lower Ni and Co abundances are transported upward to the base of the plagioclase-bearing cumulates where subsequent heat transfer leads to melting of mixtures of primary dunite, norite, and gabbronorite with KREEP (a K–REE–P enriched component widely believed to be derived from the very latest stage magma ocean liquid). These hybrid melts have Al2O3, Ni, and Co abundances and Mg’ appropriate for parent magmas of the magnesian suite. Ni and Co abundances in the FAS are consistent with either direct crystallization from the magma ocean or crystallization of melts of primary dunite–norite mixtures without KREEP.
Geochimica et Cosmochimica Acta.
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ABSTRACT: Intracerebroventricular (i.c.v.) administration of ovine corticotropin-releasing factor (CRF) in doses varying from 10 to 100 μg has been reported to produce the late onset of seizures that resembles those observed during electrical kindling of the amygdala 7,8. We assessed the effects of repeated CRF administration on seizure development and on subsequent electrical kindling of the amygdala. Rats were administered vehicle or CRF (100 μg in 10 μl of sterile water, i.c.v.) once daily for 5 consecutive days and were rated for seizures and aggressive behavior. On days 1 or 2, all animals receiving CRF developed major motor seizures of late onset (1–5 h post-injection), accompanied by spiking in the amygdala. By day 5, however, no rats had seizures, suggesting the development of tolerance. Defensive biting attacks were also observed following latencies of several hours and tolerance appeared to develop to these as well. After the CRF regimen, treated rats developed amygdala-kindled seizures following electrical stimulation approximately twice as fast as vehicle-injected controls (P < 0.03). In a second experiment, rats were electrically kindled or sham-kindled prior to receiving i.c.v. CRF (100 μg). Kindled animals were significantly less sensitive to the seizure-inducing effects of CRF (P < 0.03), but were more intensely aggressive than sham-kindled animals or naive rats receiving CRF for the first time.
Brain Research.
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ABSTRACT: Sulfur is a potential light element in the liquid outer core of the Earth. Its presence in segregating metal may have had an influence in distribution of metal-loving (siderophile) elements during early accretion and core formation events in the Earth. The observed “excess” abundance of siderophile elements in the terrestrial mantle, relative to an abundance expected from simple core-mantle equilibrium at low temperature and pressure, may indicate a reduction in the iron-loving tendency of siderophile elements in the presence of sulfur in the metallic phase. The present experimental partitioning study between iron-carbon-sulfur-siderophile element bearing liquid metal and liquid silicate shows that for some siderophile elements this sulfur effect may be significant enough to even change their character to lithophile. Large and intricate variations in metal-silicate partition coefficients () have been observed for many elements, e.g., Ni, Co, Ge, W, P, Au, and Re as a function of sulfur content. Moderately siderophile elements Ge, P, and W show the most significant response (sulfur-avoidance) by an enhanced segregation into the associated sulfur-deficient phases. Highly siderophile elements Ir, Pt, and Re show a different style of sulfur-avoidance (alloy-preference) by segregating as sulfur-poor, siderophile element-rich alloys. Both groups are chalcophobic. for Ni, Co, and Au moderately decreases with increasing sulfur-content in the liquid metal. for chalcophile element, Cr, in contrast, increases with sulfur. Irrespective of the sulfur-content, in the presence of a carbon-saturated liquid metal, P is always lithophile. The general nonmetal-avoidance tendency of siderophile elements (and acceptance of chalcophile elements) in the liquid metal, postulated by Jones and Malvin (1990) in the FeNiS(sulfur)M (siderophile) system is found to be present in the metal-silicate system as well. A sulfur-bearning liquid metal segregation can potentially reduce the metal-loving nature of many elements to explain the excess paradox. Sulfur-bearing core segregation, however, might require an efficient draining of exsolved immiscible sulfide liquids from the molten silicate, or an increasing siderophility of sulfur at high pressure to reduce the mantle sulfur content to the observed (<300 ppm) value. Moreover, the chondritic relative abundance pattern of many moderately or highly siderophile elements in the upper mantle is not explained by the presence of sulfur in the segregating metals. Core formation is more complex and intricate than equilibrium segregation.
Geochimica et Cosmochimica Acta.
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ABSTRACT: Liquid metal-liquid silicate partitioning of Fe, Ni, Co, P, Ge, W and Mo among a carbon-saturated metal and a variety of silicate melts (magnesian-tholeiitic-siliceous-aluminous-aluminosiliceous basalts) depends modestly to strongly upon silicate melt structure and composition. Low valency siderophile elements, Fe, Ni and Co, show a modest influence of silicate melt composition on partitioning. Germanium shows a moderate but consistent preference for the depolymerized magnesian melt. High valency siderophile elements, P, Mo, and W, show more than an order of magnitude decrease in metal-silicate partition coefficients as the silicate melt becomes more depolymerized. Detailed inspection of our and other published W data shows that polymerization state, temperature and pressure are more important controls on W partitioning than oxidation state. For this to be true for a high and variable valence element implies a secondary role in general for oxidation state, even though some role must be present. Equilibrium core segregation through a magma ocean of ‘ultrabasic’ composition can provide a resolution to the ‘excess’ abundances of Ge, P, W and Mo in the mantle, but the mantle composition alone cannot explain the excess abundances of nickel and cobalt in chondritic proportions.
Earth and Planetary Science Letters.
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ABSTRACT: 31P nuclear magnetic resonance spectroscopy was used to monitor changes of cytoplasmic and vacuolar pH values in leaf tissues from young pea plants which had been grown in hydroponic culture with either nitrate or ammonium salts as sources of nitrogen. When acid stress was applied by the addition of 15% CO2 to air (5.1 mM CO2 in solution), cytoplasmic pH values decreased fast by 0.5 pH units and then increased slowly without reaching the initial pH, while vacuolar pH values decreased by 0.1 pH units. Under anaerobic conditions, the cytoplasmic pH decreased by one pH unit and the vacuolar pH increased by almost 0.4 pH units. These changes were rapidly reversed when CO2 was removed from air or, after anaerobiosis, by aeration. However, with mannose present during and after anaerobiosis, aeration failed to bring pH values back to the levels observed before anaerobiosis. Simultaneously, mannose phosphates accumulated and cytoplasmic phosphate disappeared. Since loss of phosphate decreases ATP levels, the observations suggest that ATP-dependent pumping of protons into the vacuole restored the cytoplasmic pH partially during acidification by CO2 and fully after anaerobiosis. Photosynthesis was initially inhibited by high CO2 and then restored indicating that protons are exported not only across the tonoplast into the vacuole but also across the chloroplast envelope into the cytosol. No large differences in pH regulation were observed in leaves of pea plants which were grown with either nitrate or ammonium salts. Apparently, retarded growth of ammonium-fertilized plants cannot be attributed to ineffective pH regulation.
Biochimica et Biophysica Acta (BBA) - Bioenergetics.
