RESUMEN
BACKGROUND: Abnormal voiding dynamics may be a modifiable risk factor for prosthetic joint infection (PJI) after total joint arthroplasty (TJA), but the cost-effectiveness of their optimization in the perioperative setting is unknown. Using a break-even analysis, we calculated the economic viability of perioperative voiding optimization for infection prevention after TJA in patients with symptomatic benign prostatic hyperplasia (BPH). METHODS: A perioperative voiding optimization algorithm was created to represent a common approach to treating symptomatic BPH before TJA. Treatment is initiated with a 6-week trial of tamsulosin (pathway 1), followed by 6 months of combination tamsulosin/finasteride therapy (pathway 2) if symptoms persist. Patients with unremitting symptoms after medical management undergo surgical correction with transurethral resection of the prostate (pathway 3). Costs associated with each pathway were derived from the literature and institutional purchasing records. A break-even economic model was constructed to calculate the absolute risk reduction (ARR) in the infection rate and number needed to treat necessary for cost-effectiveness. RESULTS: Pathway 1 was cost-effective if it prevented 1 infection of 113 (ARR = 0.883%) TKAs or 140 (ARR = 0.714%) THAs. Pathway 2 was cost-effective if it obviated infection in 1 of 69 TKAs (ARR = 1.445%) or 86 THAs (ARR = 1.169%). Pathway 3 was only deemed cost-effective assuming a cost of $400,000 to treat a PJI (number needed to treat = 71, ARR = 1.406%). Cost-effectiveness for pathways 1 and 2 was maintained with varying voiding optimization costs, infection rates, and PJI costs. CONCLUSION: Perioperative medical management of symptomatic BPH is an economically justified PJI prevention strategy, whereas surgical interventions appear to be financially substantiated only when considering the long-term societal costs of a PJI.
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Artroplastia de Reemplazo de Cadera , Hiperplasia Prostática , Resección Transuretral de la Próstata , Análisis Costo-Beneficio , Humanos , Masculino , Hiperplasia Prostática/cirugía , TamsulosinaRESUMEN
BACKGROUND: Reduced food intake is prevalent in people in residential and hospital care settings. Little is known about the use of finger foods (i.e. foods eaten without cutlery) with respect to increasing feeding independence and food intake. The Social Care Institute for Excellence (Malnutrition Task Force: State of the Nation, 2017) recommends the use of finger foods to enable mealtime independence and to prevent loss of dignity and embarrassment when eating in front of others. The aim of this review is to identify and evaluate the existing literature regarding the use and effectiveness of finger foods among adults in health and social care settings. METHODS: An integrative review methodology was used. A systematic search of electronic databases for published empirical research was undertaken in October 2018. Following screening of titles and abstracts, the full texts of publications, which investigated outcomes associated with the provision of finger foods in adult care settings, were retrieved and assessed for inclusion. Two independent investigators conducted data extraction and quality assessment using Critical Appraisal Skills Programme checklists. Thematic analysis was used to summarise the findings. RESULTS: Six studies met the inclusion criteria. Four themes were identified: Finger food menu implementation; Importance of a team approach; Effect on nutrition; and Influence on wellbeing. Study designs were poorly reported, with small sample sizes. CONCLUSIONS: There is some evidence that the provision of finger foods may positively affect patient outcomes in long-term care settings. There is a paucity of research evaluating the use of a finger food menu in acute care settings, including economic evaluation. Future high quality trials are required.
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Conducta Alimentaria/psicología , Servicio de Alimentación en Hospital/estadística & datos numéricos , Alimentos Especializados/estadística & datos numéricos , Planificación de Menú/tendencias , Instituciones Residenciales/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Desnutrición/prevención & control , Persona de Mediana EdadRESUMEN
BACKGROUND: Yoga is growing in popularity as a form of exercise throughout the world. Orthopedic patients participate in yoga, yet little is known about the ranges-of-motion of the hip within various yoga poses. Orthopedic surgeons are unsure about what potential positions their patients are placing their hips during a yoga practice. The aim of this study is to quantify the degree of hip motion with common yoga poses. METHODS: Twenty healthy, regular practitioners of yoga performed 11 different yoga poses in a standardized fashion. Motion analysis was used to capture range-of-motion of the hip during each pose. RESULTS: Many yoga poses put the hip in extremes of motion. Poses such as downward dog, forward fold, seated twist, and pigeon stressed the hip in flexion. Warrior 1, warrior 2, crescent lunge, pigeon, and triangle stressed the hip in extension. Eagle and seated twist put the hip in higher adduction, while half moon, eagle, and triangle produced more hip internal rotation. CONCLUSION: Many poses were found to reach extremes of hip motion. This study may help guide the orthopedic surgeon in counseling hip arthroplasty and hip impingement patients about yoga-related activity. By knowing which poses potentially stress the hip in particular planes of motion, surgeons may better inform their patients who are returning to yoga after injury or surgery.
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Ejercicio Físico/fisiología , Articulación de la Cadera/fisiología , Rango del Movimiento Articular , Yoga , Fenómenos Biomecánicos , Femenino , Voluntarios Sanos , Cadera , Humanos , Articulaciones , Masculino , Recreación , RotaciónRESUMEN
BACKGROUND: Health and life expectancy for people with hemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services. AIM: This paper aims to highlight such challenges and propose practical solutions. METHODS: Nine hemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in hemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these. RESULTS: Demography, optimizing treatment and assessing treatment success were identified as broad areas of challenge which included: comorbidities in ageing patients; transitioning from pediatric to adult care; equity of care for remote populations; weight-based dosing in obese patients; tailoring prophylaxis; accurate diagnosis of acute joint pain; managing chronic arthropathy; providing psychosocial support; consistency in definitions and assessment; and quantifiable outcome measures. Practice points included increased cross-specialty coordination and including psychologists and rheumatologists as part of comprehensive care teams; close collaboration between pediatric and adult centers to facilitate transition of care; systems such as telehealth that ensure continuity of care for remote populations; using pharmacokinetic data to tailor therapy; rapid and accurate diagnosis of acute joint pain; using data from bleeding registries to assess treatment effects and help with service planning; and ensuring consistency through benchmarking and standardization of HTCs. SUMMARY: Achieving treatment equity, optimal outcomes and cost savings may be possible through investing in national governance structures, expanding the comprehensive model of care and implementing innovative solutions tailored to local needs.
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Hemofilia A/terapia , Transición a la Atención de Adultos , Adulto , Australia , Niño , Consenso , Humanos , Nueva Zelanda , PediatríaRESUMEN
Postoperative stiffness is a relatively uncommon issue in total knee arthroplasty (TKA). However, it can be a debilitating complication when it occurs. Manipulation under anesthesia (MUA) is commonly used as the primary treatment modality following failed physiotherapy. The Advance medial pivot knee (Wright Medical Technology) was created in an effort to prevent stiffness postoperatively and increase range of motion. The Evolution medial pivot knee is a second-generation design that builds on the technology of the Advance knee. This article presents a retrospective review of prospectively collected data on 881 primary medial pivot knees (592 Advance knees, 289 Evolution knees). It was theorized that the design changes made to the Evolution knees might contribute toward reducing the need for MUA. It was found that the Evolution knees required significantly fewer manipulations under anesthesia (p = .036). The design modifications made to the Evolution knees may have contributed to the lower rate of MUA.
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Artroplastia de Reemplazo de Rodilla/instrumentación , Prótesis de la Rodilla/estadística & datos numéricos , Manipulaciones Musculoesqueléticas/estadística & datos numéricos , Complicaciones Posoperatorias/prevención & control , Humanos , Articulación de la Rodilla/fisiología , Complicaciones Posoperatorias/epidemiología , Diseño de Prótesis , Rango del Movimiento Articular , Estudios RetrospectivosRESUMEN
Postoperative pain control after total knee arthroplasty is a major contributing factor to patient satisfaction, rehabilitation, and length of stay. Current clinical practice guidelines recommend a multimodal pain management protocol, including the use of regional anesthesia. Periarticular injection (PAI) has been shown to provide excellent pain relief after total knee arthroplasty. Recently, liposomal bupivacaine has been introduced as a long-acting alternative to traditional local anesthetics, such as bupivacaine or ropivacaine. Liposomal bupivacaine is a sustained-release preparation designed to provide local analgesia up to 72 hours after initial application. The efficacy of PAI relies significantly on a meticulous, systematic injection technique. This article details recommendations for solution preparation and injection during total knee arthroplasty on the basis of the experience of a high-volume orthopaedic reconstruction service.
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Anestesia Local/métodos , Artroplastia de Reemplazo de Rodilla , Bupivacaína/administración & dosificación , Manejo del Dolor/métodos , Dolor Postoperatorio/terapia , Anestésicos Locales/administración & dosificación , Humanos , Periodo Intraoperatorio , Articulación de la Rodilla , Liposomas , Dimensión del Dolor , Dolor Postoperatorio/diagnósticoRESUMEN
Understanding how the hippocampus processes episodic memory information during neuropathological conditions is important for treatment and prevention applications. Previous data have shown that during chronic neuroinflammation the expression of the plasticity related behaviourally-induced immediate early gene Arc is altered within the CA3 and the dentate gyrus; both of these hippocampal regions show a pronounced increase in activated microglia. Low doses of memantine, a low to moderate affinity open channel uncompetitive N-Methyl-d-aspartate receptor antagonist, reduce neuroinflammation, return Arc expression to control levels and attenuate cognitive deficits induced by lipopolysaccharide. Here we investigate whether neuroinflammation affects the accuracy of information processing in the CA3 and CA1 hippocampal regions and if this is modified by memantine treatment. Using the immediate early gene-based brain-imaging method called cellular analysis of temporal activity by fluorescence in situ hybridization, it is possible to detect primary transcripts at the genomic alleles; this provides exceptional temporal and cellular resolution and facilitates the mapping of neuronal activity. Here, we use this method to compare the neuronal populations activated by two separate experiences in CA1 and CA3 and evaluate the accuracy of information processing during chronic neuroinflammation. Our results show that the CA3 pyramidal neuron activity is not stable between two exposures to the same environment context or two different contexts. CA1 networks, however, do not differ from control conditions. These data suggest that during chronic neuroinflammation, the CA3 networks show a disrupted ability to encode spatial information, and that CA1 neurons can work independently of CA3. Importantly, memantine treatment is able to partially normalize information processing in the hippocampus, suggesting that when given early during the development of the pathology memantine confers neuronal and cognitive protection while indirectly prevents pathological microglial activation.
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Antagonistas de Aminoácidos Excitadores/uso terapéutico , Hipocampo/fisiopatología , Memantina/uso terapéutico , Inflamación Neurogénica/fisiopatología , Animales , Mapeo Encefálico/métodos , Células Cultivadas , Enfermedad Crónica , Proteínas del Citoesqueleto/biosíntesis , Proteínas del Citoesqueleto/genética , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Antagonistas de Aminoácidos Excitadores/farmacología , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Expresión Génica , Genes Inmediatos-Precoces , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hibridación Fluorescente in Situ , Lipopolisacáridos , Masculino , Memantina/farmacología , Microglía/efectos de los fármacos , Red Nerviosa/fisiopatología , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Inflamación Neurogénica/tratamiento farmacológico , Inflamación Neurogénica/psicología , Neuronas/metabolismo , ARN Mensajero/genética , Ratas , Ratas Endogámicas F344 , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
PURPOSE: Post-carotid endarterectomy, thrombosis, and intimal hyperplasia may be decreased by the inhibition of platelet adhesion and activation. In this study, a novel agent, saratin, was used to inhibit platelet-to-collagen adhesion in a rat carotid endarterectomy model. Saratin is a recombinant protein isolated from the saliva of the medicinal leech Hirudo medicinalis, which is thought to act by binding to collagen, and inhibits von Willebrand factor-collagen interaction under conditions of increased shear and therefore, the adherence and activation of platelets at the vessel wall. Saratin has the advantage of being a nonsystemic, site-specific topical application. METHODS: A rat carotid endarterectomy model was used in which an open technique with arteriotomy and intimectomy was used. Saratin was applied to the endarterectomized surface of the carotid artery before arterial closure. End point measurements included platelet adhesion, thrombosis rate, intimal hyperplasia development, bleeding times, and platelet counts. Electron micrographs of carotid arteries were used for quantitative analysis of platelet aggregation and platelet counts. Intimal hyperplasia and thrombosis were assessed with computer-assisted morphometric analysis of elastin-stained carotid artery sections with direct measurement of the intimal hyperplasia area. RESULTS: The topical application of saratin significantly decreased platelet adhesion compared with controls at 3 hours after carotid endarterectomy (64 +/- 17 vs 155 +/- 33 platelets per grid, P = .05), and 24 hours after carotid endarterectomy (35 +/- 11 vs 149 +/- 37 platelets per grid, P = .0110), respectively. A percent luminal stenosis, as a measure of intimal hyperplasia, was significantly decreased with saratin application compared with controls (10.9% +/- 1.8% vs 29.8% +/- 6.8%, P = .0042). This decrease in intimal hyperplasia formation correlated with the inhibition of platelet adhesion. Thirty-three percent of control arteries were found to be thrombosed 2 weeks after carotid endarterectomy compared with a 0% thrombosis rate in the saratin-treated group (P = .0156). No increased bleeding was encountered along the arterial suture line in the saratin group. Bleeding times and systemic platelet counts were not found to change significantly in the saratin-treated rats compared with control rats at 3 and 24 hours after endarterectomy. CONCLUSION: Saratin significantly decreased platelet adhesion, intimal hyperplasia, luminal stenosis, and thrombosis after carotid endarterectomy in rats. Saratin did not increase suture line bleeding or bleeding times, and did not decrease platelet counts. Saratin may serve as a topical agent to be used for the site-specific inhibition of thrombosis and intimal hyperplasia after vascular manipulation.
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Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/ultraestructura , Estenosis Carotídea/etiología , Estenosis Carotídea/prevención & control , Colágeno/efectos de los fármacos , Modelos Animales de Enfermedad , Endarterectomía Carotidea/efectos adversos , Adhesividad Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Proteínas y Péptidos Salivales/uso terapéutico , Trombosis/etiología , Trombosis/prevención & control , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Factor de von Willebrand/antagonistas & inhibidores , Administración Tópica , Animales , Tiempo de Sangría , Estenosis Carotídea/cirugía , Colágeno/fisiología , Evaluación Preclínica de Medicamentos , Hiperplasia , Inhibidores de Agregación Plaquetaria/farmacología , Recuento de Plaquetas , Ratas , Ratas Sprague-Dawley , Recurrencia , Proteínas y Péptidos Salivales/farmacología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Trombosis/metabolismo , Factores de Tiempo , Túnica Íntima/lesiones , Túnica Íntima/ultraestructuraRESUMEN
To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.
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Contaminantes Ocupacionales del Aire/toxicidad , Conducta Animal/efectos de los fármacos , Hidrocarburos/toxicidad , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Petróleo/toxicidad , Administración por Inhalación , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Endogámicas F344RESUMEN
INTRODUCTION: Ragweed pollen is one of the major causes of allergic rhinitis in the midwest United States. Previous studies have demonstrated that ragweed pollen production begins after sunrise and airborne pollen levels peak several hours later. Variations in this pattern that may be of clinical importance within a small region and the effect of weather on these variations have not been investigated. METHODS: Volumetric pollen collectors were stationed at four sites around the metropolitan area. Ten-minute grab samples were taken at each location every 2 hours for continuous 24-hour periods during the 1997 ragweed season. The downtown location had a weather station that logged meteorological conditions at hourly intervals during this time. Ragweed pollen grains were counted microscopically at 400 x. Uninterrupted data covering at least 20 days during the season were evaluated for each collection site. RESULTS: The lowest ragweed pollen counts occur at 6:00 AM and the highest occur at noon for both suburban and urban sites. Rainfall was seen to be the most influential weather-related factor. Significant rainfall events effectively removed pollen grains from the air. CONCLUSIONS: Though ragweed pollen emission begins at 6:00 AM, peak pollen exposure occurs at midday. This observation is in agreement with many other studies. The myth that highest ragweed exposure occurs in the early morning hours is not supported by this or previous studies.
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Contaminación del Aire/análisis , Polen/citología , Contaminación del Aire/estadística & datos numéricos , Recuento de Células , Ritmo Circadiano , Humanos , Kansas/epidemiología , Variaciones Dependientes del Observador , Salud UrbanaRESUMEN
BACKGROUND: The Burkard sampler is a widely used volumetric pollen and spore collector, in part, because it is wind-oriented, it has consistent flow characteristics, and it permits time-discrimination of collected particles. Its main disadvantages are that it is heavy, expensive, and visual counting is very time-consuming. A less-expensive volumetric collector with time discrimination capabilities could permit more widespread particle counting which would enhance our understanding of aerobiology. OBJECTIVE: The objective of this study is to compare the collection recoveries of the Burkard sampler with a less-expensive non-wind oriented collector, the Allergenco MK-3, under various wind speeds. METHODS: Pollen and spore counts were compared on 20 sampling days during the spring pollen season using a Burkard and Allergenco MK-3 located next to each other on the roof of a 5-story hospital building. A weather station was placed nearby and wind velocity was concurrently measured. RESULTS: The median wind velocity was 6 miles/hour with a maximum of 35 miles/hour. The Burkard and Allergenco MK-3 collectors displayed similar collection characteristics at all wind velocities for both pollen and spores. The Burkard gave lower counts than the Allergenco when absolute particle counts were low and similar values at higher absolute counts. CONCLUSIONS: Given our data, we conclude that ambient wind speed has no significant effect on collection efficiency at velocities commonly found on the roof of our hospital and that the collection characteristics of the Burkard and Allergenco MK-3 are comparable.
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Contaminantes Atmosféricos/análisis , Polen , Esporas , Control de CalidadRESUMEN
INTRODUCTION: Spore and pollen counts have been used traditionally to determine aeroallergen exposure. Using a liquid based collector and enzyme immunoassays, we have developed methods for measuring airborne allergen concentrations. In this work we test the hypothesis that airborne allergen concentrations are directly related to spore and pollen counts. METHODS: Test samplers used included a high-volume cyclonic liquid impinger (SpinCon) and a standard spore trap (Burkard). Samples were collected on a weekly basis from May to October and were analyzed microscopically for spores and pollen grains. The liquid samples were analyzed by enzyme-linked immunoassay for the presence of allergens from Alternaria, Cladosporium, Aspergillus, oak, fescue, ragweed, and plantain. Specific Alternaria allergens Alt al and GP70 also were measured. RESULTS: Pollen counts for the SpinCon and Burkard collectors were similar, though spore counts were lower with the SpinCon. Detectable amounts of three of the seven allergenic species including fescue, ragweed, and Alternaria were present in air samples. Concentrations of pollens were seen in their respective seasons while fungal allergen levels varied throughout the period. Allergen levels generally agreed with particle counts, however peak allergen levels and peak particle counts for individual species did not correlate well. CONCLUSIONS: At flow rates of 236 L/min, the SpinCon is comparable to the Burkard for counting airborne pollen and spores. Samples collected by the SpinCon permit quantitative determination of allergen levels in outdoor air. The poor correlation between measured airborne allergen and related particles indicates the potential for significant allergen exposure in the absence of identifiable particles in air.
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Contaminantes Atmosféricos/análisis , Alérgenos/análisis , Polen , Esporas , Control de CalidadRESUMEN
Many studies employ bronchoalveolar lavage fluid for assessment of biologically active substances secreted from the lung. However, investigators continue to search for a useful reference standard to correct for the inevitable but variable degree of dilution of this fluid. The glycoprotein, soluble secretory component of IgA, may serve as a valid reference protein. We report a simplified method for the purification of secretory component from colostrum. Soluble secretory component was isolated from human colostrum using serial centrifugation, size-exclusion fractionation and ion-exchange chromatography. Secretory component rich fractions were assayed by enzyme immunoassay. They were also evaluated for total amino acid content and distribution and sequence determination with satisfactory agreement with published results. We then demonstrated that soluble secretory component concentration in tracheal aspirate fluid did not correlate with either albumin or with total protein measured in the same samples. Therefore, we conclude that the secretory component of IgA serves as a useful reference marker because its use may avoid errors resulting from leakage of plasma proteins into epithelial lining fluid. Advantages of this method for establishing a standard for secretory component include ready availability of soluble secretory component, simplicity of the method and relative rapidity of the techniques.
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Calostro/química , Inmunoglobulina A/química , Componente Secretorio/aislamiento & purificación , Tráquea/metabolismo , Fraccionamiento Químico , Cromatografía en Gel , Cromatografía Líquida de Alta Presión/métodos , Cromatografía por Intercambio Iónico , Humanos , Técnicas para Inmunoenzimas , Recién Nacido , Estándares de Referencia , SucciónRESUMEN
Experiments were designed to test the hypothesis that short-term feeding of a high polyunsaturated fatty acid (PUFA) diet would increase susceptibility to lipid peroxidation in an age-dependent manner. Young (6 month) and old (24 month) male B6C3F1 mice were fed modified AIN-76 diets containing either 5% corn oil (CO, N = 5 per age group) or 19% fish oil plus 1% corn oil (FO, N = 20 per age group) for two weeks. Five CO and five FO diet mice per age received an intraperitoneal injection of normal saline and were sacrificed one hour later; the remaining FO diet mice (N = 15 per age) were challenged with an acute systemic oxidative stress by intraperitoneal injection of 125 mg iron/kg body weight as iron dextran, and were sacrificed 1, 5, and 24 hours post-injection. Microsomal membrane fatty acid analysis revealed that increased age and a FO diet significantly increased membrane PUFA content. Serum iron levels increased significantly following iron treatment, peaking at 5 hours in both age groups. Formation of microsomal malondialdehyde (MDA), a product of lipid peroxidation, was significantly greater in the livers of the young mice. The temporal patterns of serum iron and microsomal MDA concentrations were significantly correlated in young mice, but not in old mice. Histochemical examination showed that liver iron accumulation following iron injection was similar in both age groups, but was associated with a significant temporal increase in liver apoptotic cells in young mice, but not in old mice. Thus, both age groups had similar iron exposure and iron accumulation, and the liver microsomal membranes of old mice were more unsaturated, yet there was significantly greater peroxidative damage (MDA formation) and cell death (apoptosis) in the young mouse livers. These findings suggest that the older animals have upregulated antioxidant defenses.
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Envejecimiento/fisiología , Grasas de la Dieta/farmacología , Ácidos Grasos Insaturados/farmacología , Estrés Oxidativo/fisiología , Envejecimiento/metabolismo , Animales , Apoptosis/fisiología , Ácidos Grasos Insaturados/metabolismo , Hierro/sangre , Hierro/metabolismo , Masculino , Malondialdehído/metabolismo , Membranas/metabolismo , Ratones , Ratones Endogámicos , Microsomas Hepáticos/metabolismoRESUMEN
Lipid peroxidation products can be cytotoxic. Our objectives were (1) to use two pro-oxidants (iron and a pro-oxidative drug) to selectively increase lipid peroxidation in the implanted human breast tumours of mice consuming fish oil and (2) to kill the cancer cells without harming normal host tissues. The theoretical basis for selective cytotoxicity is that normal cells are better able to handle oxidative stress than cancer cells. Male athymic nude mice, consuming an AIN-76 diet, were injected s.c. with MDA-MB 231 human breast carcinoma cells. Three weeks later, all mice had palpable tumours, 3-10 mm in diameter, and diets were changed to modified AIN-76 diets containing 19% menhaden fish oil and 1% corn oil with or without supplemental 0.3% ferric citrate. After 2 weeks, half of the mice on each diet (19% fish oil with or without supplemental ferric citrate) were injected (three times per week for 2 weeks) with the ether-lipid drug edelfosine (ET-18-OCH3). The concentration of lipid peroxidation products in tumours (as measured by thiobarbituric acid-reactive substances, TBARS) was significantly increased by both ferric citrate and ET-18-OCH3. The TBARS in livers were not increased, nor was there evidence of other harmful side-effects to the host mice. The addition of iron enhanced tumour cell death whereas ET-18-OCH3 suppressed tumour cell mitosis. The use of iron supplementation combined with ET-18-OCH3 resulted in the slowest growth rate, lowest mitotic index, highest level of lipid peroxidation products and increased the cytotoxic index in tumours without detectable harm to the host. That iron supplementation increased tumour suppression beyond that expected from the increase in the concentration of TBARS in the tumour merits further investigation.
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Neoplasias de la Mama/patología , Grasas Insaturadas en la Dieta/metabolismo , Aceites de Pescado/metabolismo , Hierro/metabolismo , Peróxidos Lipídicos/metabolismo , Neoplasias Experimentales/patología , Éteres Fosfolípidos/farmacología , Animales , Neoplasias de la Mama/tratamiento farmacológico , Eicosanoides/metabolismo , Inhibidores de Crecimiento/farmacología , Humanos , Hierro/farmacología , Masculino , Ratones , Ratones Desnudos , Mitosis/efectos de los fármacos , Trasplante de Neoplasias , Neoplasias Experimentales/dietoterapia , Neoplasias Experimentales/tratamiento farmacológicoRESUMEN
Nifedipine gastrointestinal therapeutic system (GITS) is an extended-release dosage formulation that provides sustained blood concentrations of nifedipine over 24 hours. A 20-week, postmarketing surveillance study of the effectiveness and patient tolerability of nifedipine GITS 30 or 60 mg was conducted in the offices of 187 Canadian general practitioners from September 1992 to March 1994. A total of 1700 patients previously or newly diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure, 95 to 114 mm Hg) were included. The 20-week treatment period was completed by 1326 patients. Patients received nifedipine GITS 30 mg initially; the dose could be titrated upward to 60 mg after 3 and 6 weeks. Of all patients entered, 605 (35.6%) reported one or more adverse events. The three most frequently occurring adverse events were headache (12.2%), peripheral edema (8.1%), and dizziness (2.9%). The frequency of adverse events was highest in the first 3 weeks and decreased subsequently. The overall incidence of adverse events was 29.8% in patients receiving 30 mg of nifedipine GITS and 25.3% in those receiving 60 mg; adverse events were the cause of study discontinuation in 12.3% of patients. The overall health status of patients as measured by the SF-36 questionnaire was comparable to that previously reported for healthy individuals. At baseline, mean (+/- SE) systolic/diastolic blood pressure values for all patients were 160.1 +/- 0.4/97.4 +/- 0.2 mm Hg. Final blood pressure readings after 20 weeks of treatment in the 30-mg group (141.5 +/- 0.4/84.8 +/- 0.2 mm Hg) and the 60-mg group (146.6 +/- 0.8/88.8 +/- 0.4 mm Hg) were significantly decreased from baseline. At week 20, the 30-mg dose was sufficient to maintain blood pressure in 74.5% of patients; 25.5% of patients required 60 mg. Subgroup analysis revealed similar responses in patients who had received blood pressure medication before study initiation and those who had not. Response was also independent of age and type of previous antihypertensive therapy. In general medical practice, the 30-mg and 60-mg doses of nifedipine GITS were both effective and well tolerated and had minimal or no negative effects on the overall health status of treated individuals.
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Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Nifedipino/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Preparaciones de Acción Retardada , Edema/inducido químicamente , Femenino , Cefalea/inducido químicamente , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Atención Primaria de Salud , Vigilancia de Productos ComercializadosRESUMEN
INTRODUCTION: A comparative evaluation of four air samplers was performed using bioaerosol collection in the outdoor environment. METHODS: Test samplers used included a Rotorod, a Kramer-Collins suction trap, an all-glass impinger (AGI-30), and a high-volume cyclonic liquid impinger (SpinCon). All samples were analyzed microscopically for spores and pollen. The two collectors providing a liquid sample (AGI-30 and SpinCon) also were analyzed for specific allergen content by enzyme-linked immunoassay. RESULTS: The SpinCon collected a larger number of spores than the other devices. The number of spores collected by this unit per volume of air sampled was comparable to the AGI-30. The Rotorod and Kramer-Collins collected a lower number of spores per unit of air but collected a larger number of pollen grains per volume sampled. Alternaria allergens Alt a I and GP70 were collected by both liquid impingers; however, the SpinCon collected more Alt a I and the AGI-30 collected more GP70. CONCLUSIONS: The SpinCon is a device that is capable of efficiently sampling a high volume of air and concentrating it in a form that can be analyzed for the presence of spores and fungal allergens. It is less useful for collecting intact pollen grains. Pollen allergen quantitation has not yet been performed on the SpinCon effluent.
Asunto(s)
Microbiología del Aire , Alérgenos/análisis , Alternaria/aislamiento & purificación , Monitoreo del Ambiente/instrumentación , Polen , Aerosoles , Alternaria/inmunología , Ensayo de Inmunoadsorción Enzimática , Estudios de Evaluación como Asunto , EsporasRESUMEN
Stimulus-linked RNA and protein synthesis is required for establishment of long-term neuroplasticity. To identify molecular mechanisms underlying long-term neuroplasticity, we have used differential cDNA techniques to clone a novel immediate-early gene (IEG) that is rapidly induced in neurons of the hippocampus and cortex by physiological synaptic activity. Analysis of the deduced amino acid sequence indicates homology to members of the pentraxin family of secreted lectins that include C-reactive protein and serum amyloid P component. Regions of homology include an 8 amino acid "pentraxin signature" sequence and a characteristic pentraxin calcium-binding domain. We have termed this gene and the encoded protein Narp (from neuronal activity-regulated pentraxin). Biochemical analyses confirm the presence of a functional signal sequence, and Narp is secreted by transfected COS-1 cells in culture. Additionally, Narp binds to agar matrix in a calcium-dependent manner consistent with the lectin properties of the pentraxin family. When cocultured with Narp-secreting COS-1 cells, neurons of cortical explants exhibit enhanced growth of neuronal dendritic processes. Neurite outgrowth-promoting activity is also observed using partially purified Narp and can be specifically immunodepleted, demonstrating that Narp is the active principle. Narp is fully active at a concentration of approximately 40 ng/ml, indicating a potency similar to known peptide growth factors. Because Narp is rapidly regulated by neuronal activity, its lectin and growth-promoting activities are likely to play role in the modification of cellular properties that underlie long-term plasticity.
Asunto(s)
Genes Inmediatos-Precoces , Neuritas/metabolismo , Plasticidad Neuronal/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Calcio/metabolismo , Clonación Molecular , ADN Complementario , Hipocampo/metabolismo , Masculino , Datos de Secuencia Molecular , Neuritas/fisiología , ARN Mensajero/análisis , Ratas , Ratas Endogámicas F344 , Ratas Sprague-DawleyRESUMEN
Certain forms of neuronal plasticity have been found to be expressed through alterations in brain protein phosphorylation, and its regulation by protein kinase activity. Of interest in this regard is the possibility that the decline in neuronal plasticity and cognitive function that occurs in advanced age may result in part from altered phosphorylation of specific proteins. As a first attempt to identify age-related changes in phosphoproteins, we assayed in vitro phosphorylation of proteins in hippocampus, cerebellum, entorhinal cortex, and frontal cortex from Fischer-344 rats of 5 months, 11 months, and 25 months of age. Compared to the middle-aged animals, the aged rats showed a selective 46% decline in phosphorylation of the 47 kDa protein (F1) in hippocampus, with no change in the phosphorylation of other proteins measured in this structure. Aged animals also showed decreased phosphorylation relative to young animals. No age-related change was observed in any protein band for the other brain areas examined. Since protein F1 is phosphorylated by protein kinase C (PKC), the cytosolic and membrane distribution of this enzyme was compared across age groups. The activity of PKC in hippocampus did not change across age. The explanation of this age-related decline in protein F1 phosphorylation is likely to be a decline in the substrate protein itself. The results are discussed in terms of protein F1's possible role in age-related decline of hippocampal synaptic plasticity.