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1.
BMJ Open Respir Res ; 8(1)2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34376398

RESUMEN

BACKGROUND: Lung cancer survival rates in the UK are among the lowest in Europe, principally due to late-stage diagnosis. Alternative routes to earlier diagnosis of lung cancer are needed in socioeconomically deprived communities that are disproportionately affected by poor lung cancer outcomes. We assessed the feasibility and acceptability of a community-based pharmacy referral service to encourage earlier symptomatic referral for chest X-rays. METHODS: Seventeen community pharmacies located in a deprived area of Wales participated between March 2019 and March 2020. Stakeholder interviews were conducted with four patients, seven pharmacy professionals and one general practitioner. Four focus groups were conducted, including one with healthcare professionals (n=6) and three with members of the public who were current and former smokers (n=13). Quantitative data regarding patient characteristics and clinical outcomes were collected from hospital records and patient referral questionnaires completed by pharmacists and analysed using descriptive statistics. Qualitative data sets were analysed thematically and triangulated. RESULTS: Twelve patients used the pharmacy referral service, all of whom were male. Average length of the pharmacy consultation was 13 min, with a mean 3 days to accessing chest X-rays in secondary care. Patients experienced a mean 46-day wait for results, with no lung cancer detected. Participants found the service to be acceptable and considered the pharmacy element to be broadly feasible. Perceived barriers included low awareness of the service and concerns about the role and capacity of pharmacists to deliver the service. Facilitators included perceived approachability and accessibility of pharmacists. A well-publicised, multifaceted awareness campaign was recommended. CONCLUSIONS: A community pharmacy referral service for lung symptoms was considered an acceptable alternative pathway to symptomatic diagnosis of lung cancer in deprived communities. Wider implementation of the service would require workforce capacity and training to be addressed to ensure optimum utilisation and promotion of the service.


Asunto(s)
Servicios Comunitarios de Farmacia , Neoplasias Pulmonares , Farmacias , Estudios de Factibilidad , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Derivación y Consulta
2.
Med Phys ; 45(4): 1631-1644, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29405301

RESUMEN

PURPOSE: The purpose of this study is to develop and employ a Monte Carlo (MC) simulation model of associated particle neutron elemental imaging (APNEI) in order to determine the three-dimensional (3D) imaging resolution of such a system by examining relevant physical and technological parameters and to thereby begin to explore the range of clinical applicability of APNEI to fields such as medical diagnostics, intervention, and etiological research. METHODS: The presented APNEI model was defined in MCNP by a Gaussian-distributed and isotropic surface source emitting deuterium + deuterium (DD) neutrons, iron as the target element, nine iron-containing voxels (1 cm3 volume each) arranged in a 3-by-3 array as the interrogated volume of interest, and finally, by high-purity germanium (HPGe) gamma-ray detectors anterior and posterior to the 9-voxel array. The MCNP f8 pulse height tally was employed in conjunction with the PTRAC particle tracking function to not only determine the signal acquired from iron inelastic scatter gamma-rays but also to quantitate each of the nine target voxels' contribution to the overall iron signal - each detected iron inelastic scatter gamma-ray being traced to the source neutron which incited its emission. RESULTS: With the spatial, vector, and timing information of the series of events for each relevant neutron history as collected by PTRAC, realistic grayscale images of the distribution of iron concentration in the 9-voxel array were simulated in both the projective and depth dimensions. With an overall 225 ps timing resolution, 6.25 mm2 imaging plate pixels assumed to have well localized scintillation, and a DD neutron, Gaussian-distributed source spot with a diameter of 2 mm, projective and depth resolutions of < 1 cm and <3 cm are achievable, respectively, for iron-containing voxels on the order of 1,000 ppm Fe. CONCLUSIONS: The imaging resolution offered by APNEI of target elements such as iron lends itself to potential applications in disease diagnosis and treatment planning (high resolution) as well as to ordnance and contraband detection (low resolution). However, experimental study beyond simulation is required to optimize the layout and electronic configuration of APNEI system components - including realistic shielding and phantom materials - for background signal reduction in order to accurately determine the detection limits and spatial resolution of iron and other elements of interest on a case-by-case basis.


Asunto(s)
Imagenología Tridimensional/métodos , Método de Montecarlo , Neutrones , Simulación por Computador
3.
Med Phys ; 43(11): 5964, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27806586

RESUMEN

PURPOSE: The purpose of this study is to develop a Monte Carlo simulation model for in vivo associated particle neutron elemental imaging (APNEI) and to study the feasibility of using APNEI to determine the iron distribution in a human liver with the defined model. METHODS: The model presented in this study was defined in mcnp by the basic geometry of the human body, the use of D + D source neutrons, iron as the element of interest, an iron-containing voxel in the liver as the target region, and 2 large germanium detectors anterior and posterior to the trunk of the body. The f8 pulse height tally was employed in mcnp to determine the signal acquired from iron inelastic scatter gamma rays at various iron concentrations in the target liver voxel. Correspondingly, the f4 average flux tally in mcnp was modified by a dose function such that the equivalent dose to the whole liver and the effective dose to the whole body could be estimated and used as the basis for a limiting number of neutron histories which could feasibly allow for the collection of a sufficient volume of data to construct a 2D image of iron distribution in the liver voxel. RESULTS: Assuming an allowable equivalent dose to the liver of 5 mSv, 143 inelastic scatter iron gamma ray counts (at ∼847 keV) would ideally be registered at the germanium detectors for a 1 cm3 cube-shaped liver voxel with an iron concentration of 1000 ppm. According to the simulation model, an image of iron distribution in the liver can be constructed with a 1 cm resolution at the level of 1000 ppm iron. Collecting such an image would yield an estimated whole body dose of 0.82 mSv. The mathematical introduction of image uncertainty resulting from source spot diameter and detector timing resolution more closely approximates the result of real world application. CONCLUSIONS: APNEI of certain elements in vivo appears feasible given several timing, sensitivity, and resolution caveats. However, further study is required to determine what the detection limit of iron would be and what image resolution would be in an experimental setup as the present model contains idealized assumptions which overestimate the signal attributable to iron inelastic scatter gamma rays.


Asunto(s)
Imagen Molecular/métodos , Neutrones , Estudios de Factibilidad , Humanos , Hígado/diagnóstico por imagen , Hígado/metabolismo , Método de Montecarlo
4.
Case Rep Nephrol ; 2015: 120762, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26558120

RESUMEN

Renal involvement in systemic lupus erythematosus (SLE) is usually immune complex mediated and may have multiple different presentations. Pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) refers to extensive glomerular inflammation with few or no immune deposits that may result in rapid decline in renal function. We report a case of a 79-year-old Hispanic male with a history of secondary membranous nephropathy (diagnosed by renal biopsy 15 years previously) who was admitted with acute kidney injury and active urinary sediment. P-ANCA titers and anti-myeloperoxidase antibodies were positive. The renal biopsy was diagnostic for NCGN superimposed on a secondary membranous nephropathy. A previous diagnosis of SLE based on American College of Rheumatology criteria was discovered via Veteran's Administration records review after the completion of treatment for pauci-immune NCGN. ANCAs are detected in 20-31% of patients with SLE. There may be an association between SLE and ANCA seropositivity. In patients with lupus nephritis and biopsy findings of necrotizing and crescentic glomerulonephritis, without significant immune complex deposition, ANCA testing should be performed. In patients with secondary membranous nephropathy SLE should be excluded.

5.
Environ Toxicol Chem ; 34(7): 1505-10, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25663380

RESUMEN

Northern bobwhite (Colinus virginianus) and scaled quail (Callipepla squamata) from the Rolling Plains ecoregion in Texas and Oklahoma were evaluated for organochlorine pesticides, Pb, and Hg. Of all organochlorine pesticides analyzed, only p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and p,p'-dichlorodiphenyldichloroethane (p,p'-DDD) were found in a few composite liver samples. Similarly, a small fraction of tissue samples had detectable levels of Hg (liver and breast) or Pb exceeding background concentrations (femur). Lead concentrations in a few individuals fell within the range associated with moderate toxicity.


Asunto(s)
Colinus/metabolismo , Galliformes/metabolismo , Hidrocarburos Clorados/análisis , Plomo/análisis , Mercurio/análisis , Plaguicidas/análisis , Animales , Mama/química , Mama/metabolismo , Cromatografía de Gases , Diclorodifenil Dicloroetileno/análisis , Diclorodifenildicloroetano/análisis , Femenino , Hígado/química , Hígado/metabolismo , Masculino , Oklahoma , Espectrofotometría Atómica , Texas
6.
Environ Toxicol Chem ; 30(5): 1153-62, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21305578

RESUMEN

We studied the biomagnification of total mercury and methylmercury in a subtropical freshwater lake, Caddo Lake, Texas and Louisiana, USA. The present study is unique in that it not only included invertebrates (seven species) and fish (six species) but also an amphibian (one species), reptiles (three species), and mammals (three species). Nonfish vertebrates such as those included in the present study are often not included in assessments of trophic transfer of Hg. Mean trophic position (determined using stable isotopes of nitrogen) ranged from 2.0 (indicative of a primary consumer) to 3.8 (indicative of a tertiary consumer). Mean total Hg concentrations ranged from 36 to 3,292 ng/g dry weight in muscle and whole body and from 150 to 30,171 ng/g dry weight in liver. Most of the Hg in muscle and whole-body tissue was found as methylmercury, and at least 50% of the Hg found in liver was in the inorganic form (with the exception of largemouth bass, Micropterus salmoides). Mercury concentrations were positively correlated with trophic position, indicating that biomagnification occurs in the food web of Caddo Lake. The food web magnification factors (FWMFs; slope of the relationship between mean Hg concentration and trophic position) for both total Hg and methylmercury were similar to those observed in other studies. Because most of the total Hg in consumers was methylmercury, the FWMF for methylmercury was not significantly different from the FWMF for total Hg. Some vertebrates examined in the present study had low Hg concentrations in their tissues similar to those observed in invertebrates, whereas others had concentrations of Hg in their tissues that in previous studies have been associated with negative health consequences in fish.


Asunto(s)
Cadena Alimentaria , Agua Dulce/química , Mercurio/análisis , Contaminantes Químicos del Agua/análisis , Anfibios/metabolismo , Animales , Ecosistema , Monitoreo del Ambiente , Peces/metabolismo , Invertebrados/metabolismo , Louisiana , Mamíferos/metabolismo , Mercurio/metabolismo , Texas , Contaminantes Químicos del Agua/metabolismo , Contaminación Química del Agua/estadística & datos numéricos
7.
Environ Toxicol Chem ; 29(7): 1429-37, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20821590

RESUMEN

During the last four years, significant effort has been devoted to understanding the effects that Hurricanes Katrina and Rita had on contaminant distribution and redistribution in New Orleans, Louisiana, USA, and the surrounding Gulf Coast area. Elevated concentrations were found for inorganic contaminants (including As, Fe, Pb, and V), several organic pollutants (polycyclic aromatic hydrocarbons, pesticides, and volatiles) and high concentration of bioaerosols, particularly Aeromonas and Vibrio. Data from different research groups confirm that some contaminant concentrations are elevated, that existing concentrations are similar to historical data, and that contaminants such as Pb and As may pose human health risks. Two data sets have been compiled in this article to serve as the foundation for preliminary risk assessments within greater New Orleans. Research from the present study suggests that children in highly contaminated areas of New Orleans may experience Pb exposure from soil ranging from 1.37 microg/d to 102 microg/d. These data are critical in the evaluation of children's health.


Asunto(s)
Tormentas Ciclónicas , Plomo/análisis , Plomo/toxicidad , Microbiología del Aire , Louisiana , Medición de Riesgo
8.
Chemosphere ; 80(1): 67-73, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20385401

RESUMEN

The long-term environmental impact and potential human health hazards resulting from Hurricanes Katrina and Rita throughout much of the United States Gulf Coast, particularly in the New Orleans, Louisiana, USA area are still being assessed and realized after more than four years. Numerous government agencies and private entities have collected environmental samples from throughout New Orleans and found concentrations of contaminants exceeding human health screening values as established by the United States Environmental Protection Agency (USEPA) for air, soil, and water. To further assess risks of exposure to toxic concentrations of soil contaminants for citizens, particularly children, returning to live in New Orleans following the storms, soils collected from schoolyards prior to Hurricane Katrina and after Hurricane Rita were screened for 26 metals. Concentrations exceeding USEPA Regional Screening Levels (USEPA-RSL), total exposure, non-cancer endpoints, for residential soils for arsenic (As), iron (Fe), lead (Pb), and thallium (Tl) were detected in soil samples collected from schoolyards both prior to Hurricane Katrina and after Hurricane Rita. Approximately 43% (9/21) of schoolyard soils collected prior to Hurricane Katrina contained Pb concentrations greater than 400mgkg(-1), and samples from four schoolyards collected after Hurricane Rita contained detectable Pb concentrations, with two exceeding 1700mgkg(-1). Thallium concentrations exceeded USEPA-RSL in samples collected from five schoolyards after Hurricane Rita. Based upon these findings and the known increased susceptibility of children to the effects of Pb exposure, a more extensive assessment of the soils in schoolyards, public parks and other residential areas of New Orleans for metal contaminants is warranted.


Asunto(s)
Metales/análisis , Contaminantes del Suelo/análisis , Arsénico/análisis , Tormentas Ciclónicas , Monitoreo del Ambiente , Hierro/análisis , Plomo/análisis , Louisiana , Metales/química , Nueva Orleans , Factores de Riesgo , Contaminantes del Suelo/química , Talio/análisis
9.
Environ Geochem Health ; 32(5): 379-89, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20054703

RESUMEN

Immediately following hurricane Katrina concern was raised over the environmental impact of floodwaters on the city of New Orleans, especially in regard to human health. Several studies were conducted to determine the actual contaminant distribution throughout the city and surrounding wetlands by analyzing soil, sediment, and water for a variety of contaminants including organics, inorganics, and biologics. Preliminary investigations by The Institute of Environmental and Human Health at Texas Tech University concluded that soils and sediments contained pesticides, semi-volatiles, and metals, specifically arsenic, iron, and lead, at concentrations that could pose a significant risk to human health. Additional studies on New Orleans floodwaters revealed similar constituents as well as compounds commonly found in gasoline. More recently, it has been revealed that lead (Pb), arsenic, and vanadium are found intermittently throughout the city at concentrations greater than the human health soil screening levels (HHSSLs) of 400, 22 (non-cancer endpoint) and 390 µg/g, respectively. Of these, Pb appears to present the greatest exposure hazard to humans as a result of its extensive distribution in city soils. In this study, we spatially evaluated Pb concentrations across greater New Orleans surface soils. We established 128 sampling sites throughout New Orleans at approximately half-mile intervals. A soil sample was collected at each site and analyzed for Pb by ICP-AES. Soils from 19 (15%) of the sites had Pb concentrations exceeding the HHSSL threshold of 400 µg/g. It was determined that the highest concentrations of Pb were found in the south and west portions of the city. Pb concentrations found throughout New Orleans in this study were then incorporated into a geographic information system to create a spatial distribution model that can be further used to predict Pb exposure to humans in the city.


Asunto(s)
Monitoreo del Ambiente , Sedimentos Geológicos/química , Plomo/análisis , Contaminantes del Suelo/análisis , Suelo/análisis , Arsénico/análisis , Arsénico/química , Liberación de Peligros Químicos , Inundaciones , Geografía , Humanos , Plomo/química , Louisiana , Nueva Orleans , Suelo/química , Contaminantes del Suelo/química , Espectrofotometría Atómica , Vanadio/análisis , Vanadio/química
10.
Am J Primatol ; 71(12): 998-1010, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19746443

RESUMEN

Like most of Madagascar's endemic primates, ring-tailed lemurs (Lemur catta) face a number of threats to their survival. Although habitat loss is of greatest concern, other anthropogenic factors including environmental contamination may also affect lemur health and survival. In this study, we examined ring-tailed lemurs from the Beza Mahafaly Special Reserve (BMSR), southern Madagascar for exposure to organochlorine (OC) pesticides and metals and examined differences in contaminant concentrations between sexes and among age groups, troops, and habitats. A total of 14 pesticides and 13 metals was detected in lemur blood (24 individuals) and hair (65 individuals) samples, respectively. p,p'-DDT, heptachlor, aldrin, heptachlor epoxide, endrin aldehyde, and endrin were among the most prevalent pesticides detected. Surprisingly, the persistent metabolite of p,p'-DDT, p,p'-DDE, was not detected. The most commonly detected metals were aluminum, zinc, boron, phosphorus, silicon, and copper, whereas metals considered more hazardous to wildlife (e.g. arsenic, cadmium, lead, selenium, vanadium) were not found above detection limits. Overall, concentrations of OC pesticides and metals were low and similar to those considered to be background concentrations in other studies examining the ecotoxicology of wild mammals. Few inter-sex, -age, -troop, and -habitat differences in contaminant concentrations were observed, suggesting a uniform distribution of contaminants within the reserve. Several statistically significant relationships between lemur body size and contaminant concentrations were observed, but owing to the lack of supportive data regarding contaminant exposure in wild primates, the biological significance of these findings remains uncertain. Results of this study document exposure of ring-tailed lemurs at BMSR to multiple OC pesticides and metals and provide essential baseline data for future health and toxicological evaluations of lemurs and other wild primates, especially those in regions with expanding agricultural and mining operations.


Asunto(s)
Contaminantes Ambientales/sangre , Hidrocarburos Clorados/sangre , Lemur/sangre , Metales/sangre , Plaguicidas/sangre , Animales , Monitoreo del Ambiente , Contaminantes Ambientales/metabolismo , Femenino , Hidrocarburos Clorados/metabolismo , Madagascar , Masculino , Metales/metabolismo , Plaguicidas/metabolismo
11.
Dis Colon Rectum ; 52(4): 692-7, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19404076

RESUMEN

PURPOSE: Treatments for transsphincteric, cryptoglandular anal fistulas pose risks for high recurrence rates and impaired anal continence. Anal fistula plugs have gained popularity because of reports of success without compromising the anal sphincter. To examine the benefit of the anal fistula plug, we compared its success rate with a standard treatment for transsphincteric fistulas with similar indications, the transanal mucosal advancement flap. METHODS: We examined the outcomes of all patients with transsphincteric fistulas who underwent anal fistula plug repair from July 2005 to December 2006, excluding those with Crohn's disease or less than three months of follow-up. They were compared with a historical control group of patients (2001-2005) with similar transsphincteric fistulas who underwent a transanal mucosal advancement flap procedure because the anal fistula plug was not available. The same surgeons performed both procedures. Outcome was assessed from medical records or telephone follow-up. RESULTS: Twenty-nine patients underwent an anal fistula plug repair, and 26 patients underwent a flap procedure. Fistula closure rates were 34 percent for plugs and 62 percent for flaps (P = 0.045). The groups were similar in all respects except that 3 percent of plug patients and 58 percent of flap patients had postoperative inpatient stays and the median follow-up was longer (279 vs. 819 days) for the flap group. CONCLUSION: Fistula closure rates were significantly lower with anal fistula plugs than with advancement flaps. Although the low success rates for fistula plugs could be a result of patient selection, more data needs to be accrued before fistula plugs can be recommended as definitive first-line treatment for transsphincteric fistulas.


Asunto(s)
Bioprótesis , Fístula Rectal/cirugía , Adulto , Colágeno/administración & dosificación , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Colgajos Quirúrgicos , Técnicas de Sutura , Tampones Quirúrgicos , Resultado del Tratamiento
12.
Environ Toxicol Chem ; 26(10): 2108-14, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17867879

RESUMEN

During January 2006, soil and sediment samples from 75 sites in the New Orleans (LA, USA) area were collected and tested for 26 inorganic elements. The study design was intended to provide a spatial pattern of metal concentrations within the city following hurricanes Katrina and Rita. The sampling design included four transects that traversed the city in a north-south direction and three transects that traversed the city in an east-west direction. Contaminant concentrations were determined at multiple sites within each transect and compared to U.S. Environmental Protection Agency soil screening criteria pertaining to human health. Concentrations of Pb and As exceeded the criteria indiscriminately throughout the city. Of the 75 sites, 14 (19%) exceeded the soil screening criteria for Pb, and 73 (97%) exceeded the criteria for As. Forty-three of the 75 sites coincided with a previous sampling event in October 2005. Metal concentrations were evaluated for temporal comparisons using a pair sampled t test. Arsenic concentrations differed significantly over time, but Pb concentrations did not.


Asunto(s)
Desastres , Sedimentos Geológicos/química , Contaminantes del Suelo/análisis , Louisiana
13.
Environ Sci Technol ; 40(15): 4571-7, 2006 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-16913108

RESUMEN

In late October 2005, twenty-seven metals were determined in soils and sediment layers deposited by floodwaters (flood sediments) within New Orleans, Louisiana. Samples originated from 43 sites along four transects, at an industrial canal, and near the Superdome. The sampling design encompassed flooded and nonflooded areas as well as differing economic strata within the city. Results from this effort confirmed findings of our previous study designed to quantify contaminant profiles in the aftermath of Hurricane Katrina. The expanded sampling from this most recent investigation revealed that arsenic (As) and lead (Pb) concentrations exceeded United States Environmental Protection Agency (USEPA) soil screening criteria indiscriminately throughout the city. However, As and Pb concentrations were lower along St. Charles Avenue, an area largely unaffected by hurricane related flooding. Toxicant concentrations did not exceed soil screening criteria values for lead within any flood sediments or for 32 of 37 soil samples, but arsenic concentrations in 40 of 43 samples exceeded screening criteria.


Asunto(s)
Desastres , Sedimentos Geológicos/análisis , Metales/análisis , Contaminantes del Suelo/análisis , Arsénico/análisis , Estudios de Seguimiento , Plomo/análisis , Louisiana
14.
Environ Sci Technol ; 40(2): 468-74, 2006 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-16468391

RESUMEN

Storm surge associated with Hurricane Katrina and the breach of levees protecting New Orleans, Louisiana allowed floodwaters from Lake Pontchartrain to inundate 80% of the city. Environmental samples were collected during September 16-18, 2005 to determine immediate human and wildlife health hazards from pathogens and toxicants in the floodwaters. Baseline information on potential long-term environmental damage resulting from contaminants in water and sediments pumped into Lake Pontchartrain was also collected. Concentrations of aldrin, arsenic, lead, and seven semivolatile organic compounds in sediments/soils exceeded one or more United States Environmental Protection Agency (USEPA) thresholds for human health soil screening levels and high priority bright line screening levels. High numbers of Aeromonas spp., pathogenic Vibrio spp., and other coliform bacteria were found in floodwater samples. Alligator and snake tissues did not contain excessive toxicant concentrations. Initial findings suggest numerous environmental contaminants are present in New Orleans and support the need for further evaluation of the extent of those threats.


Asunto(s)
Desastres , Contaminantes Ambientales/análisis , Microbiología del Suelo , Microbiología del Agua , Animales , Animales Salvajes , Calibración , Cromatografía de Gases y Espectrometría de Masas , Louisiana
15.
J Rheumatol ; 31(12): 2429-32, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15570646

RESUMEN

OBJECTIVE: The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practiced despite lack of proven benefit. We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares. METHODS: Patients starting allopurinol for crystal-proven chronic gouty arthritis were randomized to receive colchicine 0.6 mg po bid or placebo in a randomized, prospective, double blind, placebo controlled trial. Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl. Treatment arms were analyzed regarding frequency of flares, likelihood of any flare or multiple flares, severity of flares on the visual analog scale (VAS), and length of flares in days. RESULTS: Forty-three subjects were studied. Subjects treated with colchicine experienced fewer total flares (0.52 vs 2.91, p = 0.008), fewer flares from 0 to 3 months (0.57 vs 1.91, p = 0.022), fewer flares 3-6 months (0 vs 1.05, p = 0.033), less severe flares as reported on VAS (3.64 vs 5.08, p = 0.018), and fewer recurrent gout flares (p = 0.001). Colchicine was well tolerated. CONCLUSION: Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares, and reduces the likelihood of recurrent flares. Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data.


Asunto(s)
Artritis Gotosa/tratamiento farmacológico , Colchicina/administración & dosificación , Artritis Gotosa/diagnóstico , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Prevención Secundaria , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Resultado del Tratamiento
16.
J Steroid Biochem Mol Biol ; 85(2-5): 209-19, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12943706

RESUMEN

Progesterone receptors (PR) are present in two isoforms, PR-A and PR-B. The B-upstream segment (BUS) of PR-B is a 164 amino acid N-terminal extension that is missing in PR-A and is responsible for the functional differences reported between the two isoforms. BUS contains an activation function (AF3) which is defined by a core domain between residues 54-154 whose activity is dependent upon a single Trp residue and two LXXLL motifs. We have also identified sites both within and outside of BUS that repress the strong synergism between AF3 and AF1 in the N-terminal region and AF2 in the hormone binding domain. One of these repressor sites is a consensus binding motif for the small ubiquitin-like modifier protein, SUMO-1 (387IKEE). The DNA binding domain (DBD) structure is also important for function. When BUS is linked to the glucocorticoid receptor DBD, AF3 activity is substantially attenuated, suggesting that binding to a DNA response element results in allosteric communication between the DBD and N-terminal functional regions. Lastly, biochemical and biophysical analyses of highly purified PR-B and PR-A N-terminal regions reveal that they are unstructured unless the DBD is present. Thus, the DBD stabilizes N-terminal structure. We propose a model in which the DBD through DNA binding, and BUS through protein-protein interactions, stabilize active receptor conformers within an ensemble distribution of active and inactive conformational states. This would explain why PR-B are stronger transactivators than PR-A.


Asunto(s)
Receptores de Progesterona/química , Receptores de Progesterona/fisiología , Secuencia de Aminoácidos , Animales , Sitios de Unión , Células COS , Chlorocebus aethiops , Células HeLa , Humanos , Datos de Secuencia Molecular , Mutagénesis , Fragmentos de Péptidos/química , Isoformas de Proteínas/química , Isoformas de Proteínas/fisiología , Receptores de Progesterona/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Transcripción Genética , Transfección
17.
Binocul Vis Strabismus Q ; 18(1): 29-30, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12597766

RESUMEN

BACKGROUND AND PURPOSE: INO in SLE is uncommon, affecting < 5% of hospitalized SLE patients. A MEDLINE search 1966-2001 revealed only 22 reported cases. INO also rarely presents with diplopia. We report such a case. CASE REPORT: A 35 year old woman with long standing SLE developed the abrupt onset of diplopia, vertigo and ataxia. Physical examination was remarkable only for the neurologic examination with a left INO and abnormal cerebellar testing. Treatment with corticosteroids and intravenous cyclophosphamide resulted in resolution of her cerebellar and ocular symptoms.


Asunto(s)
Diplopía/etiología , Lupus Eritematoso Sistémico/complicaciones , Trastornos de la Motilidad Ocular/etiología , Adulto , Ciclofosfamida/uso terapéutico , Diplopía/diagnóstico , Diplopía/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéutico , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/tratamiento farmacológico , Resultado del Tratamiento
18.
Arthritis Rheum ; 47(1): 67-72, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11932880

RESUMEN

OBJECTIVE: To evaluate the reliability and validity of the number of deformed joints (NDJ) as a surrogate measure of joint damage in rheumatoid arthritis (RA). METHODS: We tested interrater reliability and validity in determining the NDJ as a surrogate for joint damage in consecutive patients with RA. We rated each of 48 joints as normal or abnormal in terms of alignment and range of motion, and expressed the results as the total number of deformed joints. We compared the NDJ with the severity of damage on a plain radiograph of the hands, scored using Sharp's technique, as the gold standard measure of joint damage. We also compared the correlation between the NDJ and radiographic joint damage, on the one hand, and disease duration, performance-based measures of physical function, and the self-reported level of disability. RESULTS: The interrater reliability of the NDJ was excellent, with an intraclass correlation among four examiners of 0.94. To assess validity of the NDJ, we studied 273 RA patients from 5 clinical settings. Their average NDJ was 14 (range 0-43), and their average Sharp's score for joint space narrowing and erosions combined was 106 (range 4-309). The NDJ and the total Sharp's score were highly correlated (r = 0.83). Both measures were correlated to a similar degree with disease duration (r = 0.51 for each measure), grip strength (r = -0.49 for NDJ, and r = -0.51 for Sharp's score), walking velocity (r = -0.44 for NDJ, and r = -0.45 for Sharp's score), the timed button test (r = -0.62 for NDJ, and r = -0.57 for Sharp's score), and the Modified Health Assessment Questionnaire (r = 0.38 for NDJ, and r = 0.38 for Sharp's score). Both the Sharp's score and the NDJ worsened significantly in 38 patients for whom 1-2 year followup data were available. CONCLUSION: The NDJ is reliable and is strongly associated with the standard measure of joint damage in RA. Because it is easily performed in a clinical setting, it could be used as an economical surrogate of joint damage in studies of the long-term outcome of RA.


Asunto(s)
Artritis Reumatoide/diagnóstico , Articulaciones/patología , Actividades Cotidianas , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/fisiopatología , Artrografía , Evaluación de la Discapacidad , Femenino , Estado de Salud , Humanos , Articulaciones/fisiopatología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Rango del Movimiento Articular/fisiología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
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