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1.
Sleep Med X ; 5: 100061, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36685675

RESUMO

Objective: The purpose of this project was to determine the positive predictive value of existing obstructive sleep apnea (OSA) screening tools in clinical use, in a real-world clinical population of gravidae, and to explore the development of a new questionnaire for screening for OSA during pregnancy. Methods: Pregnant people were administered sleep screening questionnaires as part of routine clinical care. These included Facco's four variable OSA screening tool, the STOP-BANG, and the Epworth Sleepiness Scale. Those who screened positive were referred for diagnostic sleep testing, typically with a type III home monitoring device. Here we analyzed the screening responses used by those who completed diagnostic testing to determine the positive predictive value of the existing tools. Results: 159 pregnant people completed diagnostic OSA testing and were included in this analysis. The positive predictive value of Facco's four variable sleep screening tool was 74.3%, STOP-BANG was 75.3%, and the Epworth Sleepiness Scale was 69.8%. Our sample size was insufficient to create a new screening tool. Conclusions: Here we calculated the positive predictive value of Facco's 4 variable screening tool for screening for OSA in pregnancy in a real-world pregnant population. While we were not able to generate a new screening tool for screening for OSA during pregnancy, both STOP-BANG and Facco's four variable tool had positive predictive values over 70% in our population which was characterized by high BMI and advanced maternal age. Increased clinical use of the pregnancy-specific tool may be warranted.

2.
AIDS Care ; 35(8): 1215-1223, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-33745403

RESUMO

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.


Assuntos
Dor Crônica , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Dor Crônica/epidemiologia , Comorbidade
7.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34083177

RESUMO

Posterior spinal instrumentation and fusion with pedicle screws inserted by free-hand technique and controlled by multimodal intraoperative monitoring is the most common technique in adolescent idiopathic scoliosis surgery. Pneumothorax is a described complication of this kind of procedure. Triggered electromyography is used to identify pedicle wall breakthrough and prevent neurological injuries. We report 2 clinical cases in which unilateral decrease in triggered electromyography values associate with ipsilateral pneumothorax. Postoperative chest radiographs need to be done in order to diagnose a pneumothorax. However, routinely performing a chest radiograph has been questioned because of the low incidence of this surgical complication. As a result of the association described in this article, we consider that when a unilateral decrease in triggered electromyography values is detected, a hidden pneumothorax should be suspected and ruled out.

8.
Clin Radiol ; 76(1): 77.e9-77.e15, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059852

RESUMO

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.


Assuntos
Biópsia Guiada por Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
9.
Sci Rep ; 10(1): 19247, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159135

RESUMO

As storms become increasingly intense and frequent due to climate change, we must better understand how they alter environmental conditions and impact species. However, storms are ephemeral and provide logistical challenges that prevent visual surveys commonly used to understand marine mammal ecology. Thus, relatively little is known about top predators' responses to such environmental disturbances. In this study, we utilized passive acoustic monitoring to characterize the response of bottlenose dolphins to intense storms offshore Maryland, USA between 2015 and 2017. During and following four autumnal storms, dolphins were detected less frequently and for shorter periods of time. However, dolphins spent a significantly higher percentage of their encounters feeding after the storm than they did before or during. This change in foraging may have resulted from altered distributions and behavior of their prey species, which are prone to responding to environmental changes, such as varied sea surface temperatures caused by storms. It is increasingly vital to determine how these intense storms alter oceanography, prey movements, and the behavior of top predators.


Assuntos
Golfinho Nariz-de-Garrafa/fisiologia , Ecossistema , Comportamento Predatório , Animais , Maryland
10.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 64(5): 291-300, sept.-oct. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-197607

RESUMO

ANTECEDENTES Y OBJETIVOS: El objetivo de este estudio es evaluar qué factores pueden influir en la supervivencia de la artroscopia de cadera a medio plazo en el contexto de patología degenerativa. MATERIAL Y MÉTODOS: Llevamos a cabo un estudio retrospectivo de 40 casos de una serie de 102 pacientes intervenidos de artroscopia de cadera en nuestro centro, desde agosto de 2007 a octubre de 2011. Al final del seguimiento, todos los pacientes cumplimentaron tres escalas funcionales: Hip Outcome Score-Activites of Daily Life (HOS-ADL), Hip Outcome Score-Sport (HOS-S) y Harris Hip Score modificado (HHSm). RESULTADOS: Finalmente se incluyó un total de 39 pacientes (40 caderas), con una edad media de 43,1 años y un tiempo de seguimiento medio de 6 años (43-130 meses). Los pacientes intervenidos con una edad inferior a 50 años obtuvieron mejor puntuación en las escalas HOS-S (25,2 puntos) y HHS-m (84,1 puntos) en comparación con aquellos intervenidos a partir de dicha edad (HOS-S [25,2 puntos]; HHS-m [84,1 puntos]). El tiempo de evolución también influyó significativamente en el resultado de nuestros pacientes, siendo mejor en aquellos en los que éste era menor a 12 meses (26,6 meses), en comparación con aquellos en los que era mayor (21,3 meses). Por otro lado, aquellos que presentaban una intervención quirúrgica lumbar previa obtuvieron peores resultados de HOS-ADL (49,3 puntos), respecto a aquellos que no presentaban este antecedente (56,5 puntos). El Patient acceptable symptom state (PASS) fue superado por 23 pacientes (57,5%), 22 pacientes (55%) y 25 pacientes (62,5%) en las escalas HHSm, HOS-ADL y HOS-S respectivamente. Ningún paciente presentó ninguna complicación mayor. Cuatro pacientes presentaron complicaciones menores. La supervivencia media obtenida fue de 97,1 meses (IC 95%, 85,1-109,1 meses), asociado con un 81% de pacientes (IC 95%, 69%-93%) que no precisó rescate quirúrgico a los 10 años. CONCLUSIONES: Creemos que los datos obtenidos en nuestra serie sugieren que la artroscopia de cadera en el contexto de patología degenerativa es una intervención quirúrgica segura con un resultado funcional fiable a corto-medio plazo. Por otro lado, dicha indicación debería hacerse con mayor precaución en pacientes sometidos previamente a cirugía lumbar. NIVEL DE EVIDENCIA: Nivel IV. Serie de casos


BACKGROUND AND PURPOSE: The purpose of this study is to identify which variables may have a significant impact in mid-term survivorship following hip arthroscopy. METHODS: This a single-centre single-surgeon retrospective study including 102 patients who underwent a hip arthroscopy procedure between August 2007 and October 2011. Each subject completed three questionnaires at final follow- up: Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sport (HOS-S) and Modified Harris Hip Score (m-HHS). RESULTS: Thirty-nine patients (40 hips) were finally included in our study. Mean age was 43.1 ± 9.9 years with a three-year minimum follow-up (75.43 ± 25.2 months). Younger patients and those with a shorter duration of symptoms obtained significantly higher HOS-S and m-HSS scores. Patients who had undergone previous lumbar spinal surgery obtained significantly worse HOS-ADL scores. Patient acceptable symptom state (PASS) was achieved in 23 patients (57.5%) for m-HHS, 22 patients (55%) for HOS-ADL and 25 patients for HOS-S scores. No major complication was observed. Only four patients had minor complications. Mean survival time was 97.1 months (95% CI, 85.1 to 109.1 months), with a survival at 8 years of 69% (95% CI, 53% to 85%). CONCLUSIONS: Our findings suggest that hip arthroscopy is a safe procedure with acceptable functional outcomes after a long follow-up. Care should be taken when treating patients with prior lumbar surgery. LEVEL OF EVIDENCE: Level IV. Case series


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Artroscopia/métodos , Osteoartrite do Quadril/cirurgia , Impacto Femoroacetabular/cirurgia , Estudos Retrospectivos , Diagnóstico Diferencial , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica , Taxa de Sobrevida
11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32654983

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study is to identify which variables may have a significant impact in mid-term survivorship following hip arthroscopy. METHODS: This a single-centre single-surgeon retrospective study including 102 patients who underwent a hip arthroscopy procedure between August 2007 and October 2011. Each subject completed three questionnaires at final follow- up: Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sport (HOS-S) and Modified Harris Hip Score (m-HHS). RESULTS: Thirty-nine patients (40 hips) were finally included in our study. Mean age was 43.1 ± 9.9 years with a three-year minimum follow-up (75.43 ± 25.2 months). Younger patients and those with a shorter duration of symptoms obtained significantly higher HOS-S and m-HSS scores. Patients who had undergone previous lumbar spinal surgery obtained significantly worse HOS-ADL scores. Patient acceptable symptom state (PASS) was achieved in 23 patients (57.5%) for m-HHS, 22 patients (55%) for HOS-ADL and 25 patients for HOS-S scores. No major complication was observed. Only four patients had minor complications. Mean survival time was 97.1 months (95% CI, 85.1 to 109.1 months), with a survival at 8 years of 69% (95% CI, 53% to 85%). CONCLUSIONS: Our findings suggest that hip arthroscopy is a safe procedure with acceptable functional outcomes after a long follow-up. Care should be taken when treating patients with prior lumbar surgery. LEVEL OF EVIDENCE: Level IV.


Assuntos
Artroscopia , Impacto Femoroacetabular/mortalidade , Impacto Femoroacetabular/cirurgia , Osteoartrite do Quadril/mortalidade , Osteoartrite do Quadril/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
Gene Ther ; 27(12): 579-590, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32669717

RESUMO

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Adulto , Estudos de Viabilidade , Terapia Genética , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Humanos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
13.
Breast Cancer Res Treat ; 182(2): 305-315, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458104

RESUMO

PURPOSE: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). METHODS: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. RESULTS: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. CONCLUSIONS: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.


Assuntos
Neoplasias da Mama/cirurgia , Hiperalgesia/diagnóstico , Hiperestesia/diagnóstico , Mastectomia/efeitos adversos , Neuralgia/diagnóstico , Dor Pós-Operatória/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Hiperestesia/tratamento farmacológico , Hiperestesia/etiologia , Hiperestesia/fisiopatologia , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Medição da Dor , Limiar da Dor/fisiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Sensação/fisiologia , Bloqueadores dos Canais de Sódio/uso terapêutico
14.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 63(4): 300-306, jul.-ago. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-188918

RESUMO

Objetivo: Describir las características y la evolución de la infección profunda en cirugía instrumentada de raquis toracolumbar (IPCITL) en nuestro centro en un periodo de 10años. Material y método: Estudio descriptivo retrospectivo. Se analizan datos del paciente (epidemiológicos/salud), datos operatorios, presentación de la infección, gérmenes cultivados, limpiezas quirúrgicas requeridas, extracción de los implantes y complicaciones significativas derivadas de la infección. Resultados: Se revisan 110 pacientes (80mujeres). El seguimiento medio tras el diagnóstico de infección fue de 3,6años. Etiologías más frecuentes: escoliosis idiopática del adolescente, deformidad del adulto y estenosis lumbar degenerativa. El 62% de pacientes presentaban algún dato clínico que les hacía proclives a la infección. La aparición de la infección fue precoz (0-3meses de la cirugía primaria) en el 60,4% de los casos, retardada (3-24meses) en el 11,7% y tardía (más de 24meses) en el 27%. Todos los pacientes fueron tratados mediante limpieza quirúrgica. El 25% necesitaron más de una limpieza. Se extrajeron los implantes en el 46% de los pacientes (en el 71% de ellos en la primera limpieza). Los gérmenes aislados con mayor frecuencia fueron Staphylococcus coagulasa-negativo, Propionibacterium acnes y Enterococcus. Hubo complicaciones significativas derivadas de la IPCITL en el 15% de casos. El 88% de ellas precisaron cirugías complejas para su tratamiento. Conclusiones: Las IPCITL tardías son más frecuentes de lo esperado según la literatura. En IPCITL globalmente predominan gérmenes cutáneos. Las IPCITL provocan una alta tasa de complicaciones, que habitualmente requieren tratamiento mediante cirugías complejas


Objective: To describe thee characteristics and evolution of deep surgical site infection following thoracolumbar instrumented spinal surgery (DSITIS) in our centre over a period of ten years. Material and method: Descriptive retrospective study. Patient data (epidemiological/health status), surgical data, infection characteristics/presentation, isolated microorganisms, required surgical debridements, implant removal and major complications linked to infection were evaluated. Results: We included 110 patients (80 females). Median follow-up after infection diagnosis was 3.6years. Adolescent idiopathic scoliosis, adult deformity and degenerative lumbar stenosis were the most frequent aetiologies. Sixty-two percent of the patients had at least one clinical feature that made them prone to infection. Infection presentation was early (0-3months from first surgery) in 60.4% of the cases, delayed (3-24months) in 11.7%, and late (more than 24months) in 27%. All patients were treated by surgical debridement. Twenty-five percent needed more than one surgical debridement. Implants were removed in 46% of the patients (71% in the first surgical debridement). The most frequent isolated microorganisms were coagulasa-negative Staphylococcus, Propionibacterium acnes and Enterococcus. Major complications appeared in 15% of the patients, and 88% of them required major surgeries. Conclusions: Late DSITIS is more frequent than previously reported. Skin microorganisms predominate among the DSITIS culprits. DSIITS produce a high rate of major complications that usually require major surgery for treatment


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Escoliose/cirurgia , Estenose Espinal/cirurgia , Coluna Vertebral/anormalidades , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Desbridamento/estatística & dados numéricos , Remoção de Dispositivo/estatística & dados numéricos , Enterococcus/isolamento & purificação , Propionibacterium acnes/isolamento & purificação , Estudos Retrospectivos , Pele/microbiologia , Staphylococcus/isolamento & purificação , Infecção da Ferida Cirúrgica/complicações , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo
15.
Ecology ; 100(8): e02743, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112299

RESUMO

When prey is patchily distributed, predators are expected to spend more time searching for food in proximity of recent prey captures before searching in other areas. This behavior, known as area-restricted search, results in predators remaining localized in areas where prey had been detected previously because of the higher probability of encountering additional prey. However, few studies have tested these predictions on marine species because of the difficulties of observing feeding behavior. In this study, we utilized passive acoustic detections of echolocating dolphins to identify foraging behavior. C-PODs (click train detectors) were deployed for two years with an acoustic recorder attached to the same mooring during the second year. The time series of feeding buzzes, indicative of foraging behavior, revealed that both bottlenose (Tursiops truncatus) and common dolphins (Delphinus delphis) were more likely to stay in the area longer when foraging activity was high at the beginning of the encounter. The probability of foraging was also higher following previous foraging activity. This suggests that dolphins were feeding on spatially patchy prey and previous foraging experience influenced their movement behavior. This is consistent with the predictions of area-restricted search behavior, a nonrandom foraging strategy.


Assuntos
Golfinho Nariz-de-Garrafa , Acústica , Animais , Comportamento Alimentar , Comportamento Predatório
16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30795999

RESUMO

OBJECTIVE: To describe the characteristics and evolution of deep surgical site infection following thoracolumbar instrumented spinal surgery (DSITIS) in our centre over a period of ten years. MATERIAL AND METHOD: Descriptive retrospective study. Patient data (epidemiological/health status), surgical data, infection characteristics/presentation, isolated microorganisms, required surgical debridements, implant removal and major complications linked to infection were evaluated. RESULTS: We included 110 patients (80 females). Median follow-up after infection diagnosis was 3.6years. Adolescent idiopathic scoliosis, adult deformity and degenerative lumbar stenosis were the most frequent aetiologies. Sixty-two percent of the patients had at least one clinical feature that made them prone to infection. Infection presentation was early (0-3months from first surgery) in 60.4% of the cases, delayed (3-24months) in 11.7%, and late (more than 24months) in 27%. All patients were treated by surgical debridement. Twenty-five percent needed more than one surgical debridement. Implants were removed in 46% of the patients (71% in the first surgical debridement). The most frequent isolated microorganisms were coagulasa-negative Staphylococcus, Propionibacterium acnes and Enterococcus. Major complications appeared in 15% of the patients, and 88% of them required major surgeries. CONCLUSIONS: Late DSITIS is more frequent than previously reported. Skin microorganisms predominate among the DSITIS culprits. DSIITS produce a high rate of major complications that usually require major surgery for treatment.


Assuntos
Escoliose/cirurgia , Estenose Espinal/cirurgia , Coluna Vertebral/anormalidades , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desbridamento/estatística & dados numéricos , Remoção de Dispositivo/estatística & dados numéricos , Enterococcus/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propionibacterium acnes/isolamento & purificação , Estudos Retrospectivos , Pele/microbiologia , Staphylococcus/isolamento & purificação , Infecção da Ferida Cirúrgica/complicações , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo , Adulto Jovem
17.
Oncogenesis ; 6(7): e352, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28671675

RESUMO

Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of ß-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance.

18.
Biochim Biophys Acta Biomembr ; 1859(10): 1941-1950, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28583830

RESUMO

Antimicrobial peptides (AMPs) are key components of the innate immune response and represent promising templates for the development of broad-spectrum alternatives to conventional antibiotics. Most AMPs are short, cationic peptides that interact more strongly with negatively charged prokaryotic membranes than net neutral eukaryotic ones. Both AMPs and synthetic analogues with arginine-like side chains are more active against bacteria than those with lysine-like amine groups, though the atomistic mechanism for this increase in potency remains unclear. To examine this, we conducted comparative molecular dynamics simulations of a model negatively-charged membrane system interacting with two mutants of the AMP KR-12: one with lysine residues mutated to arginines (R-KR12) and one with arginine residues mutated to lysine (K-KR12). Simulations show that both partition analogously to the bilayer and display similar preferences for hydrogen bonding with the anionic POPGs. However, R-KR12 binds stronger to the bilayer than K-KR12 and forms significantly more hydrogen bonds, leading to considerably longer interaction times. Additional simulations with methylated R-KR12 and charge-modified K-KR12 mutants show that the extensive interaction seen in the R-KR12 system is partly due to arginine's strong atomic charge distribution, rather than being purely an effect of the greater number of hydrogen bond donors. Finally, free energy simulations reveal that both peptides are disordered in solution but form an amphipathic α-helix when inserted into the bilayer headgroup region. Overall, these results highlight the role of charge and hydrogen bond strength in peptide bilayer insertion, and offer potential insights for designing more potent analogues in the future.


Assuntos
Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Arginina/química , Bicamadas Lipídicas/química , Lisina/química , Ânions/química , Ligação de Hidrogênio , Membranas/química , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice
19.
QJM ; 110(3): 131-139, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28069916

RESUMO

INTRODUCTION: 'Burning Feet Syndrome' affected up to one third of Far Eastern Prisoners of War in World War 2. Recently discovered medical records, produced by RAF Medical Officer Nowell Peach whilst in captivity, are the first to detail neurological examinations of patients with this condition. METHODS: The 54 sets of case notes produced at the time were analysed using modern diagnostic criteria to determine if the syndrome can be retrospectively classed as neuropathic pain. RESULTS: With a history of severe malnutrition raising the possibility of a peripheral polyneuropathy, and a neuroanatomically plausible pain distribution, this analysis showed that Burning Feet Syndrome can now be described as a 'possible' neuropathic pain syndrome. CONCLUSION: After 70 years, the data painstakingly gathered under the worst of circumstances have proved to be of interest and value in modern diagnostics of neuropathic pain.


Assuntos
Doenças do Pé/história , Neuralgia/história , Prisioneiros de Guerra/história , Ásia Oriental , Doenças do Pé/diagnóstico , Doenças do Pé/etiologia , Doenças do Pé/terapia , História do Século XX , Humanos , Desnutrição/complicações , Desnutrição/história , Registros Médicos , Medicina Militar/história , Neuralgia/diagnóstico , Neuralgia/etiologia , Neuralgia/terapia , Exame Físico/métodos , Síndrome
20.
J Thromb Haemost ; 14(10): 1931-1940, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27501440

RESUMO

Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen-Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. SUMMARY: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG1-4 , IgA, and IgE were detected significantly more often in patients with a positive Nijmegen-Bethesda assay (NBA). All NBA-positive samples were positive for IgG4 . Anti-FIX IgG4 demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4 is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.


Assuntos
Anticorpos Neutralizantes/imunologia , Fator IX/imunologia , Imunofluorescência , Hemofilia B/imunologia , Imunoglobulinas/imunologia , Adolescente , Adulto , Idoso , Coagulação Sanguínea , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Humanos , Imunoglobulina G/imunologia , Lactente , Isoanticorpos/imunologia , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Adulto Jovem
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