Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
COPD ; 17(6): 706-710, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33169617

RESUMEN

International Classification of Disease 10 (ICD-10) codes record hospital admissions. We aimed to measure the accuracy of COPD exacerbation (ECOPD) codes and examine coding practices for COPD exacerbation.Prospective screening and ICD-10 codes were used to identify potential ECOPD within the DECAF internal validation cohort. Two coding searches were performed. The first search identified patients with an ECOPD discharge code, and a second, broad search was developed to identify all clinically confirmed ECOPD.717 of 1,122 (64%) patients with an ECOPD code had confirmed ECOPD. Common reasons for misclassification in the 405 patients who did not have an ECOPD included: lack of obstructive spirometry to diagnose COPD; and hospital admission due to progressive malignancy, asthma or cardiovascular disease. The broad search identified an additional 297 patients with ECOPD missed by the ECOPD codes. The vast majority of this group had pneumonia complicating ECOPD.ECOPD codes are insufficiently reliable to identify patients with clinically confirmed ECOPD for the purposes of audit or research. Search strategies should include pneumonia codes, specialist review of medical notes and spirometry confirmation of COPD.


Asunto(s)
Codificación Clínica , Clasificación Internacional de Enfermedades , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Reproducibilidad de los Resultados
2.
J Appl Microbiol ; 126(2): 468-479, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30412324

RESUMEN

AIMS: To investigate the mechanisms of action of natural products with bactericidal (cinnamon root powder, peppermint oil, trans-cinnamaldehyde, menthol and zingerone) or bacteriostatic (fresh garlic bulb extract, garlic clove powder, Leptospermum honey and allicin) activity against two Clostridium difficile strains. METHODS AND RESULTS: Bactericidal products significantly reduced intracellular ATP after 1 h (P ≤ 0·01), quantified using the BacTiter-Glo reagent, and damaged the cell membrane, shown by the leakage of both 260-nm-absorbing materials and protein, and the uptake of propidium iodide. Bacteriolysis was not observed, determined by measuring optical density of treated cell suspensions at 620-nm. The effect of three bacteriostatic products on protein synthesis was quantified using an Escherichia coli S30 extract system, with Leptospermum honey (16% w/v) showing significant inhibition (P < 0·01). Lastly, no products showed elevated minimum inhibitory concentrations against antimicrobial-resistant C. difficile, determined by broth microdilution. CONCLUSIONS: Cytoplasmic membrane damage was identified as a mechanism of action that may contribute to the activity of several natural products against C. difficile. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the possible mechanisms of action of natural products against C. difficile, yet the efficacy in vivo to be determined.


Asunto(s)
Antibacterianos/farmacología , Productos Biológicos/farmacología , Clostridioides difficile/efectos de los fármacos , Extractos Vegetales/farmacología
3.
Thorax ; 72(8): 686-693, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28235886

RESUMEN

BACKGROUND: One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. METHODS: In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. RESULTS: Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. CONCLUSIONS: The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.


Asunto(s)
Readmisión del Paciente/tendencias , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Medición de Riesgo , Enfermedad Aguda , Anciano , Causas de Muerte/tendencias , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Curva ROC , Factores de Riesgo , Tasa de Supervivencia/tendencias , Reino Unido/epidemiología
4.
Thorax ; 71(2): 133-40, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26769015

RESUMEN

BACKGROUND: Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. METHODS: The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. RESULTS: In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. CONCLUSIONS: DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Medición de Riesgo , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Reino Unido/epidemiología
5.
Front Rehabil Sci ; 5: 1354069, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071770

RESUMEN

Background: Transtibial prosthetic sockets are often grouped into patella tendon bearing (PTB) or total surface bearing (TSB) designs, but many variations in rectifications are used to apply these principles to an individual's personalised socket. Prosthetists currently have little objective evidence to assist them as they make design choices. Aims: To compare rectifications made by experienced prosthetists across a range of patient demographics and limb shapes to improve understanding of socket design strategies. Methodology: 163 residual limb surface scans and corresponding CAD/CAM sockets were analysed for 134 randomly selected individuals in a UK prosthetics service. This included 142 PTB and 21 TSB designs. The limb and socket scans were compared to determine the location and size of rectifications. Rectifications were compiled for PTB and TSB designs, and associations between different rectification sizes were assessed using a variety of methods including linear regression, kernel density estimation (KDE) and a Naïve Bayes (NB) classification. Results: Differences in design features were apparent between PTB and TSB sockets, notably for paratibial carves, gross volume reduction and distal end elongation. However, socket designs varied across a spectrum, with most showing a hybrid of the PTB and TSB principles. Pairwise correlations were observed between the size of some rectifications (e.g., paratibial carves; fibular head build and gross volume reduction). Conversely, the patellar tendon carve depth was not associated significantly with any other rectification, indicating its relative design insensitivity. The Naïve Bayes classifier produced design patterns consistent with expert clinician practice. For example, subtle local rectifications were associated with a large volume reduction (i.e., a TSB-like design), whereas more substantial local rectifications (i.e., a PTB-like design) were associated with a low volume reduction. Clinical implications: This study demonstrates how we might learn from design records to support education and enhance evidence-based socket design. The method could be used to predict design features for newly presenting patients, based on categorisations of their limb shape and other demographics, implemented alongside expert clinical judgement as smart CAD/CAM design templates.

6.
Biomed Eng Lett ; 12(1): 59-73, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35186360

RESUMEN

To perform activities of daily living (ADL), people with lower limb amputation depend on the prosthetic socket for stability and proprioceptive feedback. Poorly fitting sockets can cause discomfort, pain, limb tissue injuries, limited device usage, and potential rejection. Semi-passively controlled adjustable socket technologies exist, but these depend upon the user's perception to determine safe interfacial pressure levels. This paper presents a framework for automatic control of an adjustable transtibial prosthetic socket that enables active adaptation of residuum-socket interfacial loading through localized actuators, based on soft tissue injury risk estimation. Using finite element analysis, local interfacial pressure vs. compressive tissue strain relationships were estimated for three discrete anatomical actuator locations, for tissue injury risk assessment within a control structure. Generalized Predictive Control of multiple actuators was implemented to maintain interfacial pressure within estimated safe and functional limits. Controller simulation predicted satisfactory dynamic performance in several scenarios. Actuation rates of 0.06-1.51 kPa/s with 0.67% maximum overshoot, and 0.75-1.58 kPa/s were estimated for continuous walking, and for a demonstrative loading sequence of ADL, respectively. The developed platform could be useful for extending recent efforts in adjustable lower limb prosthetic socket design, particularly for individuals with residuum sensory impairment.

7.
Biomech Model Mechanobiol ; 19(4): 1331-1346, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31256276

RESUMEN

It has been proposed that finite element analysis can complement clinical decision making for the appropriate design and manufacture of prosthetic sockets for amputees. However, clinical translation has not been achieved, in part due to lengthy solver times and the complexity involved in model development. In this study, a parametric model was created, informed by variation in (i) population-driven residuum shape morphology, (ii) soft tissue compliance and (iii) prosthetic socket design. A Kriging surrogate model was fitted to the response of the analyses across the design space enabling prediction for new residual limb morphologies and socket designs. It was predicted that morphological variability and prosthetic socket design had a substantial effect on socket-limb interfacial pressure and shear conditions as well as sub-dermal soft tissue strains. These relationships were investigated with a higher resolution of anatomical, surgical and design variability than previously reported, with a reduction in computational expense of six orders of magnitude. This enabled real-time predictions (1.6 ms) with error vs the analytical solutions of < 4 kPa in pressure at residuum tip, and < 3% in soft tissue strain. As such, this framework represents a substantial step towards implementation of finite element analysis in the prosthetics clinic.


Asunto(s)
Miembros Artificiales , Modelos Biológicos , Diseño de Prótesis , Tibia/cirugía , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Humanos , Presión , Análisis de Componente Principal , Análisis de Regresión
8.
Biomech Model Mechanobiol ; 19(4): 1347-1360, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31741116

RESUMEN

In post-amputation rehabilitation, a common goal is to return to ambulation using a prosthetic limb, suspended by a customised socket. Prosthetic socket design aims to optimise load transfer between the residual limb and mechanical limb, by customisation to the user. This is a time-consuming process, and with the increase in people requiring these prosthetics, it is vital that these personalised devices can be produced rapidly while maintaining excellent fit, to maximise function and comfort. Prosthetic sockets are designed by capturing the residual limb's shape and applying a series of geometrical modifications, called rectifications. Expert knowledge is required to achieve a comfortable fit in this iterative process. A variety of rectifications can be made, grouped into established strategies [e.g. in transtibial sockets: patellar tendon bearing (PTB) and total surface bearing (TSB)], creating a complex design space. To date, adoption of advanced engineering solutions to support fitting has been limited. One method is numerical optimisation, which allows the designer a number of likely candidate solutions to start the design process. Numerical optimisation is commonly used in many industries but not prevalent in the design of prosthetic sockets. This paper therefore presents candidate shape optimisation methods which might benefit the prosthetist and the limb user, by blending the state of the art from prosthetic mechanical design, surrogate modelling and evolutionary computation. The result of the analysis is a series of prosthetic socket designs that preferentially load and unload the pressure tolerant and intolerant regions of the residual limb. This spectrum is bounded by the general forms of the PTB and TSB designs, with a series of variations in between that represent a compromise between these accepted approaches. This results in a difference in pressure of up to 31 kPa over the fibula head and 14 kPa over the residuum tip. The presented methods would allow a trained prosthetist to rapidly assess these likely candidates and then to make final detailed modifications and fine-tuning. Importantly, insights gained about the design should be seen as a compliment, not a replacement, for the prosthetist's skill and experience. We propose instead that this method might reduce the time spent on the early stages of socket design and allow prosthetists to focus on the most skilled and creative tasks of fine-tuning the design, in face-to-face consultation with their client.


Asunto(s)
Algoritmos , Diseño de Prótesis , Miembros Artificiales , Automatización , Humanos , Presión
9.
J Hosp Infect ; 106(1): 10-19, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32652212

RESUMEN

BACKGROUND: In the wake of the SARS-CoV-2 pandemic and unprecedented global demand, clinicians are struggling to source adequate access to personal protective equipment. Respirators can be in short supply, though are necessary to protect workers from SARS-CoV-2 exposure. Rapid decontamination and reuse of respirators may provide relief for the strained procurement situation. METHOD: In this study, we investigated the suitability of 70°C dry heat and microwave-generated steam (MGS) for reprocessing of FFP2/N95-type respirators, and Type-II surgical face masks. Staphylococcus aureus was used as a surrogate as it is less susceptible than enveloped viruses to chemical and physical processes. RESULTS: We observed >4 log10 reductions in the viability of dry S. aureus treated by dry heat for 90 min at 70°C and >6 log10 reductions by MGS for 90 s. After 3 reprocessing cycles, neither process was found to negatively impact the bacterial or NaCl filtration efficiency of the respirators that were tested. However, MGS was incompatible with Type-II surgical masks tested, as we confirmed that bacterial filtration capacity was completely lost following reprocessing. MGS was observed to be incompatible with some respirator types due to arcing observed around some types of metal nose clips and by loss of adhesion of clips to the mask. CONCLUSION: Considering the advantages and disadvantages of each approach, we propose a reprocessing personal protective equipment/face mask workflow for use in medical areas.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Descontaminación/métodos , Equipo Reutilizado/normas , Calor , Máscaras/virología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Dispositivos de Protección Respiratoria/virología , Vapor , Betacoronavirus , COVID-19 , Guías como Asunto , Humanos , Microondas , SARS-CoV-2
10.
Clin Microbiol Infect ; 26(10): 1347-1354, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32220636

RESUMEN

OBJECTIVES: Bloodstream infection has a high mortality rate. It is not clear whether laboratory-based rapid identification of the organisms involved would improve outcome. METHODS: The RAPIDO trial was an open parallel-group multicentre randomized controlled trial. We tested all positive blood cultures from hospitalized adults by conventional methods of microbial identification and those from patients randomized (1:1) to rapid diagnosis in addition to matrix-assisted desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) performed directly on positive blood cultures. The only primary outcome was 28-day mortality. Clinical advice on patient management was provided to members of both groups by infection specialists. RESULTS: First positive blood culture samples from 8628 patients were randomized, 4312 into rapid diagnosis and 4136 into conventional diagnosis. After prespecified postrandomization exclusions, 2740 in the rapid diagnosis arm and 2810 in the conventional arm were included in the mortality analysis. There was no significant difference in 28-day survival (81.5% 2233/2740 rapid vs. 82.3% 2313/2810 conventional; hazard ratio 1.05, 95% confidence interval 0.93-1.19, p 0.42). Microbial identification was quicker in the rapid diagnosis group (median (interquartile range) 38.5 (26.7-50.3) hours after blood sampling vs. 50.3 (47.1-72.9) hours after blood sampling, p < 0.01), but times to effective antimicrobial therapy were no shorter (respectively median (interquartile range) 24 (2-78) hours vs. 13 (2-69) hours). There were no significant differences in 7-day mortality or total antibiotic consumption; times to resolution of fever, discharge from hospital or de-escalation of broad-spectrum therapy or 28-day Clostridioides difficile incidence. CONCLUSIONS: Rapid identification of bloodstream pathogens by MALDI-TOF MS in this trial did not reduce patient mortality despite delivering laboratory data to clinicians sooner.


Asunto(s)
Bacteriemia/diagnóstico , Bacteriemia/mortalidad , Bacterias/clasificación , Técnicas de Tipificación Bacteriana/métodos , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacterias/aislamiento & purificación , Cultivo de Sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Factores de Tiempo , Resultado del Tratamiento
11.
Cytokine Growth Factor Rev ; 12(1): 73-90, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11312120

RESUMEN

The cyclins are a family of proteins that are centrally involved in cell cycle regulation and which are structurally identified by conserved "cyclin box" regions. They are regulatory subunits of holoenzyme cyclin-dependent kinase (CDK) complexes controlling progression through cell cycle checkpoints by phosphorylating and inactivating target substrates. CDK activity is controlled by cyclin abundance and subcellular location and by the activity of two families of inhibitors, the cyclin-dependent kinase inhibitors (CKI). Many hormones and growth factors influence cell growth through signal transduction pathways that modify the activity of the cyclins. Dysregulated cyclin activity in transformed cells contributes to accelerated cell cycle progression and may arise because of dysregulated activity in pathways that control the abundance of a cyclin or because of loss-of-function mutations in inhibitory proteins.Analysis of transformed cells and cells undergoing mitogen-stimulated growth implicate proteins of the NF-kappaB family in cell cycle regulation, through actions on the CDK/CKI system. The mammalian members of this family are Rel-A (p65), NF-kappaB(1) (p50; p105), NF-kappaB(2) (p52; p100), c-Rel and Rel-B. These proteins are structurally identified by an amino-terminal region of about 300 amino acids, known as the Rel-homology domain. They exist in cytoplasmic complexes with inhibitory proteins of the IkappaB family, and translocate to the nucleus to act as transcription factors when activated. NF-kappaB pathway activation occurs during transformation induced by a number of classical oncogenes, including Bcr/Abl, Ras and Rac, and is necessary for full transforming potential. The avian viral oncogene, v-Rel is an NF-kappaB protein. The best explored link between NF-kappaB activation and cell cycle progression involves cyclin D(1), a cyclin which is expressed relatively early in the cell cycle and which is crucial to commitment to DNA synthesis. This review examines the interactions between NF-kappaB signaling and the CDK/CKI system in cell cycle progression in normal and transformed cells. The growth-promoting actions of NF-kappaB factors are accompanied, in some instances, by inhibition of cellular differentiation and by inhibition of programmed cell death, which involve related response pathways and which contribute to the overall increase in mass of undifferentiated tissue.


Asunto(s)
Ciclo Celular/fisiología , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , FN-kappa B/metabolismo , Animales , Diferenciación Celular , División Celular/efectos de los fármacos , División Celular/fisiología , Transformación Celular Neoplásica , Ciclina D1/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Humanos , Mitógenos/farmacología , FN-kappa B/genética , Oncogenes
12.
Med Eng Phys ; 43: 1-18, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28285881

RESUMEN

The care and rehabilitation of individuals after lower limb amputation presents a substantial and growing socioeconomic challenge. Clinical outcome is closely linked to successful functional rehabilitation with a prosthetic limb, which depends upon comfortable prosthetic limb - residual limb load transfer. Despite early interest in the 1980s, the amputated limb has received considerably less attention in computational biomechanical analysis than other subjects, such as arthroplasty. This systematic literature review investigates the state of the art in residual limb finite element analysis published since 2000. The identified studies were grouped into the following categories: (1) residuum-prosthesis interface mechanics; (2) residuum soft tissue internal mechanics; (3) identification of residuum tissue characteristics; (4) proposals for incorporating FEA into the prosthesis fitting process; (5) analysis of the influence of prosthetic componentry concepts to improve load transfer to the residuum, such as the monolimb and structural socket compliance; and (6) analysis of osseointegrated (OI) prostheses. The state of the art is critically appraised in order to form recommendations for future modeling studies in terms of geometry, material properties, boundary conditions, interface models, and relevant but un-investigated issues. Finally, the practical implementation of these approaches is discussed.


Asunto(s)
Amputación Quirúrgica , Miembros Artificiales , Análisis de Elementos Finitos , Humanos , Fenómenos Mecánicos , Oseointegración , Diseño de Prótesis
13.
J Interferon Cytokine Res ; 15(11): 947-54, 1995 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8590306

RESUMEN

Soluble receptors for TNF (sTNF-R) are present at elevated concentrations in the synovial fluid of patients with rheumatoid arthritis. They are presumably released by cells of the synovial membrane, including the monocyte-derived synovial macrophages. Cytokines from the synovium, including IL-1 and TNF-alpha, may stimulate release. We therefore examined the release of sTNF-R from monocytes exposed to IL-1 and TNF-alpha. Elutriator-purified human blood monocytes spontaneously released both the p75 and the p55 sTNF-R (1011 +/- 199 and 177 +/- 20 pg/10(6) cells, respectively, mean +/- SEM) during 48 h of in vitro culture. TNF-alpha and IL-1 alpha induced time- and concentration-dependent increases in the release of sTNF-R75 from monocytes, but neither had a measurable effect on the release of sTNF-R55. The release of sTNF-R75 was inhibited by cycloheximide. Neither lymphocytes nor polymorphonuclear leukocytes (PMN) released measurable sTNF-R spontaneously or in response to stimulation with IL-1 alpha, but TNF-alpha stimulated the release of small amounts of sTNF-R75 by PMN. The timing, cycloheximide sensitivity, and selectivity of stimulated release of TNF-R75 by monocytes are consistent with previous observations on other cell types of late (8-20 h) increased synthesis and turnover of cell surface TNF-R75, but not TNF-R55, after stimulation with TNF-alpha or IL-1. These observations help to explain why elevated levels of sTNF-R in synovial fluid coexist with enhanced expression of cell surface TNF-R on synovial macrophages in rheumatoid arthritis.


Asunto(s)
Antígenos CD/efectos de los fármacos , Interleucina-1/farmacología , Monocitos/efectos de los fármacos , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Secuencia de Aminoácidos , Reacciones Antígeno-Anticuerpo , Antígenos CD/metabolismo , Humanos , Datos de Secuencia Molecular , Monocitos/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Estimulación Química , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunología
14.
J Interferon Cytokine Res ; 16(7): 511-7, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8836916

RESUMEN

The activities of monocyte-derived tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta are potentially modified by IL-1RA and soluble receptors for TNF (sTNF-R), which are themselves monocyte products. IL-4, IL-10, TGF-beta, and glucocorticoids (GC) all suppress the lipopolysaccharide (LPS)-stimulated release of TNF-alpha and IL-1beta but vary in their effects on IL-1RA and sTNF-R. This raises the prospect of interactions between the cytokines and glucocorticoids, which may be antagonistic or additive on IL-1 and TNF activity. We, therefore, studied the interactions of the GC dexamethasone (Dex) with IL-4, IL-10, and transforming growth factor (TGF)-beta on the release of TNF-alpha and IL-1RA by human monocytes and the monocytic THP-1 cell line. Low concentration of Dex (10(-8)-10(-7)M) acted additively with low concentrations of IL-4 (0.01-1 ng/ml), IL-10 (0.01-0.1 U/ml), or TGF-beta (0.01-1 ng/ml) to profoundly suppress LPS-stimulated release of TNF-alpha by whole blood and, to a lesser degree, THP-1 cells. Dex also suppressed spontaneous release of IL-1RA from PBMC and THP-1 cells, whereas IL-4 and IL-10, but not TGF-beta, stimulated release. Dex antagonized the enhanced release in IL-4 and IL-10-stimulated cultures. The capacity to stimulate release of IL-1RA may contribute to the anti-inflammatory potential of IL-4 and IL-10 in monocyte/macrophage-mediated disease. GC, therefore, do not uniquely enhance the suppressive functions of IL-4 and IL-10 on monokine activity. The therapeutic benefit of combinations of GC and IL-4, IL-10 or TGF-beta in disease may depend on the roles of the individual monokines and antagonists in pathogenesis.


Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Interleucina-10/farmacología , Interleucina-4/farmacología , Receptores de Interleucina-1/antagonistas & inhibidores , Sialoglicoproteínas/metabolismo , Adulto , Análisis de Varianza , Línea Celular , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-10/antagonistas & inhibidores , Interleucina-4/antagonistas & inhibidores , Lipopolisacáridos/antagonistas & inhibidores , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Proteínas Recombinantes/metabolismo , Valores de Referencia , Factor de Crecimiento Transformador beta/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
15.
J Hosp Infect ; 37(4): 305-16, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9457608

RESUMEN

Attachment of coagulase-negative staphylococci to plastic surfaces by means of hydrophobic interaction and slime production may be important in producing catheter associated infections. In continuous ambulatory peritoneal dialysis (CAPD), the relationship between these properties and disease is unclear and the effect of dialysate fluid is not considered. For a collection of coagulase-negative staphylococci from CAPD patients, slime production and adherence were measured by colorimetric methods and hydrophobicity was determined by autoaggregation in ammonium sulphate solution. Comparison of 73 nasal isolates with 69 isolates from peritonitis showed no significant differences with respect to three properties, with the exception of a greater adherence of peritoneal isolates in dialysate because of a greater proportion of staphylococcal species other than Staphylococcus epidermidis. Fewer strains showed adherence in dialysate (12/142 8.5%) than in broth (94/142 66%) but the proportion of strains producing slime was similar. The milieu of the bacteria rather than the organisms themselves may be of greater importance in the establishment of infection.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Infección Hospitalaria/microbiología , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/microbiología , Infecciones Estafilocócicas/microbiología , Adhesión Bacteriana , Estudios de Casos y Controles , Infección Hospitalaria/prevención & control , Femenino , Humanos , Técnicas In Vitro , Masculino , Mucosa Nasal/microbiología , Peritonitis/prevención & control , Infecciones Estafilocócicas/prevención & control , Staphylococcus epidermidis/fisiología , Estadísticas no Paramétricas
16.
J Neurol Sci ; 75(3): 343-51, 1986 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3772393

RESUMEN

The time course of protein degradation and the influence of extracellular calcium and the calcium-channel blocker verapamil were investigated by measuring tyrosine release from the isolated rat soleus muscle exposed to the local anaesthetic agent bupivacaine. Degradation rates were reduced during the first 60-90 min and subsequently increased in muscles treated with bupivacaine concentrations of 1.5 mM or higher. When calcium was omitted from the incubation medium the initial reduction in degradation was greater and the subsequent increase was reduced or prevented. Overall, verapamil (10(-5)M or 10(-6)M) did not significantly alter the degree or time-course of protein degradation.


Asunto(s)
Bupivacaína/farmacología , Calcio/fisiología , Proteínas Musculares/metabolismo , Músculos/efectos de los fármacos , Animales , Femenino , Músculos/metabolismo , Ratas , Ratas Endogámicas WF , Tirosina/metabolismo , Verapamilo/farmacología
17.
J Neurol Sci ; 73(2): 205-17, 1986 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3701376

RESUMEN

To investigate the role of extracellular calcium in bupivacaine-induced muscle injury, the effects of the drug on creatine kinase (CK) release and muscle ultrastructure were studied in the isolated rat soleus in the presence and absence of calcium and of the Ca-channel blockers verapamil and nifedipine. Control muscles maintained a constant CK release rate and normal morphology for at least 3 hours. CK release rates increased markedly after exposure to 1.5 mM and 5 mM bupivacaine and electron microscopy showed evidence of damage to mitochondria, sarcoplasmic reticulum and the plasmalemma of muscle fibres with disruption of the Z-lines, I-bands and M-lines of myofibrils. When calcium was omitted from the incubation medium, there was a 3-fold reduction in CK release rates; the morphological changes were less severe initially but by 120 min were comparable to those in muscles incubated with bupivacaine and calcium. Neither 10(-6) M verapamil nor 10(-6) M nifedipine reduced CK release or muscle fibre damage. Verapamil (10(-5) M) reduced CK release but not the severity of muscle damage. The findings indicate that extracellular calcium plays a part in mediating the muscle damage caused by bupivacaine but that other factors must also be involved, and that Ca-channel blockers do not prevent muscle damage.


Asunto(s)
Bupivacaína/toxicidad , Calcio/metabolismo , Enfermedades Musculares/inducido químicamente , Animales , Bloqueadores de los Canales de Calcio , Creatina Quinasa/metabolismo , Espacio Extracelular/metabolismo , Femenino , Músculos/metabolismo , Músculos/ultraestructura , Enfermedades Musculares/patología , Ratas , Ratas Endogámicas
18.
Burns ; 22(3): 173-6, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8726252

RESUMEN

The diagnosis and treatment of burn wound infection is commonly determined by clinical impression and the qualitative results of surface swabs. It has been suggested that quantitative bacteriology from burn wound biopsies confirms burn wound infection and improves patient management. Methods for quantitating surface flora have been described, but comparisons with biopsy specimens have been contradictory. The quantitative and qualitative results of 141 pairs of biopsies and surface swabs, from 74 burn patients, were compared. Staph. aureus was the commonest organism isolated (29 per cent of biopsies and 35 per cent of swabs). Recovery of the same set of species from biopsy and swab occurred in 54 per cent of pairs. There was a significant correlation between the bacterial count obtained by biopsy and by surface swab (P < 0.001), but using various threshold values, the predictive value of the counts obtained by one method to predict the counts obtained by the other was poor. Parallel cultures taken on 18 occasions, showed a significant correlation between bacterial counts obtained from two biopsies or two swabs taken simultaneously (P < 0.002), but there was wide variation in bacterial densities from the same burn wound at the same time. Recovery of the same set of species from both biopsies occurred in 56 per cent of pairs, and from both swabs in 50 per cent of pairs. The use of quantitative microbiology in burns is limited by the unreliability of a single surface swab or biopsy to represent the whole burn wound.


Asunto(s)
Alginatos , Bacterias/aislamiento & purificación , Biopsia , Quemaduras/microbiología , Acinetobacter/aislamiento & purificación , Infecciones por Acinetobacter/diagnóstico , Recuento de Colonia Microbiana , Medios de Cultivo , Predicción , Humanos , Modelos Lineales , Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Reproducibilidad de los Resultados , Infecciones Estafilocócicas/diagnóstico , Staphylococcus aureus/aislamiento & purificación , Infección de Heridas/diagnóstico
19.
Burns ; 22(3): 177-81, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8726253

RESUMEN

The use of quantitative bacteriology in the burns unit has been thought to be efficient in predicting sepsis or graft loss. To examine the relationship between clinical outcome and bacterial densities on and in the burn wound, 69 biopsy/surface swab pairs were collected from 47 patients on 64 occasions, either immediately prior to excision and grafting, or at routine change of dressings. The mean per cent TBSA burn was 16 (range 1-65). There was a significant correlation between log total bacterial count by biopsy with total white cell count and age (P = 0.028), and a significant negative correlation between total bacterial count by swab with per cent TBSA (P = 0.006). There was no significant difference in bacterial counts between patients judged to be a clinical success or clinical failure (72 h follow-up), either after undergoing excision and grafting, or change of dressings, and no difference in counts between patients with perioperative bacteraemia and those without. With burns > 15 per cent TBSA, a relationship between bacterial counts and subsequent sepsis or graft loss still was not demonstrated. It is suggested that quantitative bacteriology by burn wound biopsy or surface swab does not aid the prediction of sepsis or graft loss.


Asunto(s)
Alginatos , Bacterias/aislamiento & purificación , Vendajes , Biopsia , Quemaduras/microbiología , Recuento de Colonia Microbiana , Factores de Edad , Antiinfecciosos Locales/uso terapéutico , Bacteriemia/microbiología , Superficie Corporal , Quemaduras/patología , Quemaduras/cirugía , Cerio/uso terapéutico , Clorhexidina/uso terapéutico , Estudios de Seguimiento , Predicción , Supervivencia de Injerto , Humanos , Recuento de Leucocitos , Modelos Lineales , Povidona Yodada/uso terapéutico , Infecciones por Pseudomonas , Sulfadiazina de Plata/uso terapéutico , Trasplante de Piel , Infecciones Estafilocócicas , Insuficiencia del Tratamiento , Resultado del Tratamiento , Infección de Heridas/microbiología
20.
Hernia ; 17(6): 779-89, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23780573

RESUMEN

PURPOSE: Prosthetic infections, although relatively uncommon in hernia surgery, are a source of considerable morbidity and cost. The aims of this experimental study were to assess the influence of the morphological properties of the mesh on bacterial adherence in vitro. The morphological properties assessed were the polymer type, filament type, filament diameter, mesh weight, mean pore size, and the addition of silver chlorhexidine and titanium coatings. In addition, the study assessed the effect on bacterial adherence of adding a commonly used suture to the mesh and compared adherence rates to self-gripping mesh that does not require suture fixation. METHODS: Eight commercially sourced flat hernia meshes with different material characteristics were included in the study. These were Prolene(®) (Ethicon(®)), DualMesh(®) (Gore(®)), DualMesh(®) Plus (Gore(®)), Parietex™ ProGrip (Covidien™), TiMesh(®) Light (GfE Medical), Bard(®) Soft Mesh (Bard(®)), Vypro(®) (Ethicon(®)), and Omyra(®) (Braun(®)). Individual meshes were inoculated with Staphylococcus epidermidis and Staphylococcus aureus with a bacterial inoculum of 10(2) bacteria. To assess the effect of suture material on bacterial adhesion, a sterile piece of commonly used monofilament suture material (2.0 Prolene(®), ZB370 Ethicon(®)) was sutured to selected meshes (chosen to represent different commonly used polymers and/or the presence of an antibacterial coating). Inoculated meshes were incubated for 18 h in tryptone soy broth and then analysed using scanning electron microscopy. A previously validated method for enumeration of bacteria using automated stage movement electron microscopy was used for direct bacterial counting. The final fraction of the bacteria adherent to the mesh was compared between the meshes and for each morphological variable. One-way analysis of variance (ANOVA) was performed on the bacterial counts. Tukey's test was used to determine the difference between the different biomaterials in the event the ANOVA was significant. RESULTS: Properties that significantly increased the mean bacterial adherence were the expanded polytetrafluoroethylene polymer (P < 0.001); multifilament meshes (P < 0.001); increased filament diameter (P < 0.001); increased mesh weight (P < 0.001); and smaller mean pore size (P < 0.001). In contrast, mesh coating with antibacterial silver chlorhexidine significantly reduced bacterial adhesion (S. epidermidis mean bacterial count 140.7 ± 19.1 SE with DualMesh(®) vs. 2.3 ± 1.2 SE with DualMesh(®) Plus, P < 0.001; S. aureus mean bacterial count 371.7 ± 22.7 SE with DualMesh(®) vs. 19.3 ± 4.7 SE with DualMesh(®) Plus, P = 0.002). The addition of 2.0 Prolene suture material significantly increased the mean number of adherent bacteria independent of the mesh polymer or mesh coating (P = 0.04 to <0.001). CONCLUSION: The present study demonstrates the significant influence of the prosthetic load on bacterial adherence. In patients at increased risk of infection, low prosthetic load materials, i.e., lightweight meshes with large pores, may be beneficial. Furthermore self-fixing meshes, which avoid increasing the prosthetic load and antibacterial impregnated meshes, may have an advantage in this setting.


Asunto(s)
Adhesión Bacteriana , Staphylococcus aureus/aislamiento & purificación , Staphylococcus epidermidis/aislamiento & purificación , Mallas Quirúrgicas/microbiología , Suturas/microbiología , Carga Bacteriana , Humanos , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Polipropilenos , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiología
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda