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1.
Med Oral Patol Oral Cir Bucal ; 27(1): e85-e93, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34874924

RESUMO

BACKGROUND: This study reviews the demographic, clinical and radiographic features of adenomatoid odontogenic tumor(AOT) diagnosed in an Indian population over 50 years and also evaluate and compare follicular AOT(F-AOT) and extra-follicular AOT(EF-AOT). MATERIAL AND METHODS: 55 diagnosed cases of AOT from 1971-2020 were studied retrospectively. The data regarding the age, sex, location, variant of AOT, duration, clinical features, radiographic appearance, treatment and recurrence were collected and analysed. RESULTS: Of the 722 odontogenic tumors diagnosed, 7.6% were AOTs with higher prevalence of extra-follicular (67.3%) than follicular (32.7%) variant. All the tumors were intraosseous with a marked predilection for maxilla over mandible, ratio 2:1. The patients mean age was 19.8 years with slightly higher female predilection (male:female ratio - 1:1.5). The anterior region (76.4%) was more frequently affected and entire quadrant was involved in 21.8% cases. Clinically, asymptomatic, slow-growing swelling was seen in 81.8% cases with duration of 15 days to 10 years. Radiographically, AOT appeared as well-corticated radiolucent lesion. Canine was the most commonly impacted tooth. Recurrence was seen in 3 cases. CONCLUSIONS: Interestingly, in this series extra-follicular was twice more common than follicular AOT. Few cases involved the entire quadrant or crossed the midline of either jaws.


Assuntos
Ameloblastoma , Tumores Odontogênicos , Dente Impactado , Adolescente , Adulto , Criança , Feminino , Humanos , Índia , Masculino , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/epidemiologia , Estudos Retrospectivos , Adulto Jovem
2.
Br J Surg ; 108(4): 441-447, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33615351

RESUMO

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.


Assuntos
Regras de Decisão Clínica , Infecções Intra-Abdominais/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Recidiva , Fatores de Risco
3.
Colorectal Dis ; 22(12): 2123-2132, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32940414

RESUMO

AIM: The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications. METHOD: From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres. RESULTS: All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate-volume (sPCI 13-20) and high-volume (sPCI > 20) disease than for low-volume disease (sPCI 0-12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six. CONCLUSION: The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate-volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Peritônio/diagnóstico por imagem , Peritônio/cirurgia , Estudos Prospectivos
4.
Br J Surg ; 107(13): 1832-1837, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32671825

RESUMO

BACKGROUND: Anastomotic leak is a common complication after colorectal surgery, associated with increased morbidity and mortality, and poorer long-term survival after oncological resections. Early diagnosis improves short-term outcomes, and may translate into reduced cancer recurrence. Multiple studies have attempted to identify biomarkers to enable earlier diagnosis of anastomotic leak. One study demonstrated that the trajectory of C-reactive protein (CRP) levels was highly predictive of anastomotic leak requiring intervention, with an area under the curve of 0·961. The aim of the present study was to validate this finding externally. METHODS: This was a prospective international multicentre observational study of adults undergoing elective colorectal resection with an anastomosis. CRP levels were measured before operation and for 5 days afterwards, or until day of discharge if earlier than this. The primary outcome was anastomotic leak requiring operative or radiological intervention. RESULTS: Between March 2017 and July 2018, 933 patients were recruited from 20 hospitals across Australia, New Zealand, England and Scotland. Some 833 patients had complete CRP data and were included in the primary analysis, of whom 41 (4·9 per cent) developed an anastomotic leak. A change in CRP level exceeding 50 mg/l between any two postoperative days had a sensitivity of 0·85 for detecting a leak, and a high negative predictive value of 0·99 for ruling it out. A change in CRP concentration of more than 50 mg/l between either days 3 and 4 or days 4 and 5 after surgery had a high specificity of 0·96-0·97, with positive likelihood ratios of 4·99-6·44 for a leak requiring intervention. CONCLUSION: This study confirmed the value of CRP trajectory in accurately ruling out an anastomotic leak after colorectal resection.


ANTECEDENTES: La fuga anastomótica es una complicación frecuente después de la cirugía colorrectal que se asocia con morbilidad y mortalidad, con una peor supervivencia a largo plazo tras resecciones oncológicas. El diagnóstico precoz mejora los resultados a corto plazo y puede traducirse en una reducción de la recidiva del cáncer. Múltiples estudios han tratado de identificar biomarcadores para lograr un diagnóstico precoz de la fuga anastomótica. Un estudio demostró que la evolución de la proteína C reactiva (PCR) era altamente predictiva de una fuga anastomótica que requería intervención, con un área bajo la curva de 0,961. Nuestro estudio tuvo como objetivo validar externamente este hallazgo. MÉTODOS: Se llevó a cabo un estudio internacional prospectivo observacional y multicéntrico de pacientes adultos sometidos a resección colorrectal electiva con anastomosis. Los niveles de PCR se midieron antes de la operación y diariamente hasta el día 5 después de la cirugía, o hasta el día del alta si fue anterior. El criterio de valoración principal fue la fuga anastomótica que requirió intervención quirúrgica o radiológica. RESULTADOS: Entre marzo de 2017 y julio de 2018, se reclutaron 933 pacientes de 20 hospitales de Australia, Nueva Zelanda, Inglaterra y Escocia. Se obtuvieron datos completos de PCR en 833 pacientes y se incluyeron en el análisis primario, de los cuales 41 (4,9%) presentaron una fuga anastomótica. Un aumento de la PCR > 50 mg/L entre dos días del postoperatorio fue sensible para detectar una fuga (0,85) y tuvo un alto valor predictivo negativo para descartarla (0,99). El porcentaje de cambio de PCR > 50 mg/L por día entre los días 3-4 o 4-5 después de la operación fue altamente específico (0,96) con un cociente de probabilidad positivo > 5,0 para las fugas que requirieron una intervención. CONCLUSIÓN: Este estudio confirma la utilidad de la evolución de la PCR para descartar con precisión una fuga anastomótica después de una resección colorrectal.


Assuntos
Fístula Anastomótica/diagnóstico , Proteína C-Reativa/metabolismo , Colo/cirurgia , Reto/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Fístula Anastomótica/sangue , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Br J Haematol ; 188(6): 872-880, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31702049

RESUMO

Chronic lymphocytic leukaemia (CLL) patients often have abnormal expansions of CD4+ and CD8+ T cells and this can be associated with progressive disease. To characterise the key T-cell populations involved in this phenomenon, we used flow cytometry and 11 phenotypic markers to study 74 CLL patients and 14 controls. T cells of CLL patients were more phenotypically complex than those of healthy controls with significant increases in the frequencies of CD4 and CD8 memory T cells expressing exhaustion-, activation- and senescence-associated markers. Multivariate analysis of 111 different T-cell subsets showed that high frequencies of four subsets (three CD8 and one CD4) were associated with shorter progression-free survival. The most significant association was with CD4+ HLA-DR+ PD-1+ T cells, and patients could be stratified into high- and low-risk groups based on the frequency of these T cells. The expansion of this CD4+ subset could not be accounted for by age, cytomegalovirus infection or increases in Treg cells. Overall, these results highlight two relatively simple biomarkers, percentage CD8+ and percentage CD4+ PD-1+ HLA-DR+ T cells, which can be used to risk-stratify CLL patients, independent of other tumour-associated markers. They also provide further evidence for the pivotal role of T cells in modulating the pathology of CLL.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Antígenos HLA-DR/metabolismo , Leucemia Linfocítica Crônica de Células B/genética , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade
8.
Biol Reprod ; 100(2): 390-397, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30304517

RESUMO

Cell fusion is involved in the development of some adult organs, is implicated in the pathogenesis of specific types of cancer, and is known to participate in repair/regeneration processes mediated by bone-marrow-derived cells (BMDCs). Endometriosis is a disease characterized by growth of functional endometrial tissue outside of the uterine cavity. Endometriosis shares some molecular properties with cancer and BMDCs home to endometriosis lesions in a mouse model. Our objective was to determine if cell fusion can occur in endometriosis and establish whether bone-marrow-derived cells participate in cell fusion events in lesions. We employed a Cre-Lox system to identify cell fusion events in a mouse model of endometriosis. Fused cells were detected in endometriotic lesions, albeit at a low frequency (∼1 in 400 cells), localized to the stromal compartment, and displayed restricted proliferation. Using 5-fluorouracil-based nongonadotoxic bone marrow transplantation model, we demonstrate that bone marrow cells represent a principal cell source for fusion events in lesions. Cell fusion progeny uniformly lacked expression of selected markers of hematopoietic, endothelial, and epithelial markers, though they expressed the mesenchymal/stromal markers Sca-1 and CD29. This study is the first to describe the phenomenon of cell fusion in endometriosis and points to a mesenchymal population derived from cell fusion events with limited proliferative activity, properties previously attributed to endometrial stem cells. Their putative role in the pathogenesis of the disease remains to be elucidated.


Assuntos
Fusão Celular , Endometriose/patologia , Animais , Modelos Animais de Doenças , Endométrio/citologia , Feminino , Citometria de Fluxo , Camundongos , Mutação
9.
Radiography (Lond) ; 23(3): 249-255, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687294

RESUMO

INTRODUCTION: Increasingly patients and clients of health services are using social media to locate information about medical procedures and outcomes. There is increasing pressure for health professionals to engage in on-line spaces to provide clear and accurate information to their patient community. Research suggests there are some anxieties on the part of practitioners to do this. This study aimed to explore the attitudes of the NHS breast screening programme workforce towards engaging in online discussions with clients about breast screening. METHOD: 78 practitioners, representing a range of professional roles within the NHS Breast Screening Programme, attended one of 4 workshops. We used a Nominal Group Technique to identify and rank responses to the question: "What are the challenges that practitioners face in using SoME as part of their role?" Responses were categorised into themes. Participants were also asked to identify solutions to these challenges. RESULTS: Challenges: We identified two overarching themes: (1) Working within boundaries: which was further categorised into (a) Professional/legal accountability; (b) Information accuracy and (c)Time as a boundary, and (2) Support: further categorised into (a) Employer and (b) Manager. Solutions: These included: training in technical and interactional aspects of on-line communication and a responsibility to better understand employer and professional body SoMe policies. CONCLUSION: The study participants appeared willing and motivated to engage in SoMe. However, in keeping with the literature from other disciplines, a number of challenges need to be overcome for its use to be adopted more widely by breast screening professionals.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias da Mama/diagnóstico por imagem , Mamografia , Programas de Rastreamento , Educação de Pacientes como Assunto , Mídias Sociais/estatística & dados numéricos , Inglaterra , Feminino , Humanos , Relações Profissional-Paciente
10.
Radiography (Lond) ; 23(3): 235-241, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28687292

RESUMO

INTRODUCTION: Despite National Health Service (NHS) information strategy promoting the use of Social Media (SoMe) to encourage greater engagement between service users and providers, a team investigating online SoMe interaction between breast screening practitioners and clients found that practitioners alleged discouragement from employers' policies. This study aimed to investigate whether this barrier was genuine, and illuminate whether local policy differed from national strategy. METHOD: The study used a qualitative grounded theory approach to generate a theory. Nine policies from the North West of England were analysed. A framework was derived from the data, and an analysis of policy tone followed by a detailed coding of policy content was undertaken. Comparative analysis continued by reviewing the literature, and a condensed framework revealed five broad categories that policies addressed. RESULTS: The analysis revealed the policies varied in content, but not in tone, which was mostly discouraging. Coding the content revealed that the most frequently addressed point was that of protecting the employers' reputation, and after further analysis, the resultant condensed framework showed that policies were imbalanced and heavily skewed towards Security, Conduct & Behaviour and Reputation. CONCLUSION: Practitioners within breast screening services are discouraged by overly prohibitive and prescriptive SoMe policies; with these varying tremendously in comprehensiveness, but with a narrow focus on security and employers reputation; in contrast with national strategy. Recommendations are that policy revision is undertaken with consultation by more than one stakeholder, and SoMe training is offered for all members of NHS staff.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Programas de Rastreamento , Política Organizacional , Mídias Sociais/estatística & dados numéricos , Medicina Estatal , Inglaterra , Feminino , Teoria Fundamentada , Humanos , Pesquisa Qualitativa
11.
J Clin Pharm Ther ; 42(5): 646-648, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28543822

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio® (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio® was discontinued and liver enzymes normalized. A liver biopsy revealed mild periportal cholestatic reaction suggesting potential drug-induced aetiology. WHAT IS NEW AND CONCLUSION: This is the first description of liver injury secondary to garlic supplementation. Therefore, this garlic supplement should be listed as a potential cause of acute drug-induced liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Suplementos Nutricionais/efeitos adversos , Alho/efeitos adversos , Transplante de Fígado , Adulto , Alho/química , Síndrome Hepatopulmonar/cirurgia , Humanos , Testes de Função Hepática , Masculino
13.
Indian J Exp Biol ; 54(4): 286-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27295926

RESUMO

Heavy metal contamination, particularly of cultivable lands, is a matter of concern. Bioremediation helps in reversing such contamination to certain extent. Here, we report isolation, polyphasic identification and the role of siderophore producing rhizobacteria Alcaligenes feacalis RZS2 and Pseudomonas aeruginosa RZS3 in bioremediation of heavy metal contaminated soil and plant growth promotion activity in such contaminated soil. Siderophore produced by A. feacalis RZS2 and P. aeruginosa RZS3 strains chelated various heavy metal ions like MnCl2.4H2O, NiCl2.6H2O, ZnCl2, CuCl2 and CoCl2 other than FeCl3.6H2O at batch scale. Their bioremediation potential was superior over the chemical ion chelators like EDTA and citric acid. These isolates also promoted growth of wheat and peanut seeds sown in heavy metal contaminated soil. Effective root colonizing ability of these isolates was observed in wheat and peanut plants.


Assuntos
Biodegradação Ambiental , Recuperação e Remediação Ambiental , Metais Pesados/metabolismo , Desenvolvimento Vegetal/fisiologia , Rhizobiaceae/fisiologia , Poluentes do Solo/metabolismo
14.
Eur J Microbiol Immunol (Bp) ; 6(1): 9-24, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27141311

RESUMO

Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues.

15.
3 Biotech ; 6(1): 69, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28330140

RESUMO

We report the enhanced production of siderophore in succinate medium by applying two-stage statistical approach, i.e., Plackett-Burman design and response surface methodology (RSM) using central composite design (CCD). In the first stage of optimization, out of 11 variable components of succinate medium, succinic acid, pH and temperature were found as significant components that influenced the siderophore production in Pseudomonas aeruginosa RZS9. The second stage of RSM using CCD consisted of optimizing the concentrations of the variables. Here, 0.49 g/100 ml concentration of succinic acid, pH 7.08 and temperature of 27.80 °C yielded the maximum (68.41 %) siderophore units. All the significant components exhibited quadratic effect on siderophore production. The F value of 28.63, multiple correlation coefficient (R 2) of 0.9626, percent coefficient of variation of 8.81 values indicated that the model was significant and that the experimental data was satisfactorily adjusted to the quadratic model. During validation of these experiments, 6.10 % increase in siderophore yield was obtained. Scale-up of this protocol optimized at shake  flask level up to 5 L-capacity reactor further enhanced the siderophore yield. We claim it to be the first report on statistical optimization of siderophore production by P. aeruginosa RZS9.

16.
3 Biotech ; 6(2): 179, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28330251

RESUMO

This paper reports an isolation and identification of novel poly-ß-hydroxybutyrate (PHB) degrading bacterium Stenotrophomonas sp. RZS 7 and studies on its extracellular PHB degrading depolymerase enzyme. The bacterium isolated from soil samples of plastic contaminated sites of municipal area in Shahada, Maharashtra, Western India. It was identified as Stenotrophomonas sp. RZS 7 based on polyphasic approach. The bacterium grew well in minimal salt medium (MSM) and produced a zone (4.2 mm) of PHB hydrolysis on MSM containing PHB as the only source of nutrient. An optimum yield of enzyme was obtained on the fifth day of incubation at 37 °C and at pH 6.0. Further increase in enzyme production was recorded with Ca2+ ions, while other metal ions like Fe2+ (1 mM) and chemical viz. mercaptoethanol severally affected the production of enzyme.

17.
Arthritis Care Res (Hoboken) ; 67(2): 151-60, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25302624

RESUMO

OBJECTIVE: To investigate clinical efficacy and safety of 2 certolizumab pegol (CZP) maintenance dosing regimens plus methotrexate (MTX) in active rheumatoid arthritis (RA) patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) after the CZP 200 mg every 2 weeks open-label run-in period. METHODS: DOSEFLEX (dosing flexibility) was a double-blind, placebo-controlled randomized study with an open-label run-in phase. During the run-in phase, all patients received CZP 400 mg (weeks 0, 2, and 4) and 200 mg every 2 weeks to week 16. Week 16 ACR20 responders were randomized 1:1:1 at week 18 to CZP 200 mg every 2 weeks, 400 mg every 4 weeks, or placebo. RESULTS: A total of 209 (of 333) patients were randomized at week 18 (CZP: 200 mg, n = 70; 400 mg, n = 70; placebo, n = 69). Groups had similar baseline characteristics (week 0). Week 34 ACR20 response rates were comparable between the CZP 200 mg every 2 weeks and the 400 mg every 4 weeks groups (67.1% versus 65.2%), which was significantly higher than placebo (44.9%; P = 0.009 and P = 0.017). ACR50/70 and remission criteria were met more frequently in CZP groups than placebo at week 34, with similar responses between anti-tumor necrosis factor-experienced and naive patients. Improvements from baseline Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and Health Assessment Questionnaire disability index scores were maintained in CZP groups from week 16 to 34 while worsening on placebo. Adverse event (AE) rates in the double-blind phase were 62.9% versus 60.9% versus 62.3%; serious AE rates were 7.1% versus 2.9% versus 0.0% (CZP 200 mg, 400 mg, and placebo groups). CONCLUSION: In active RA patients with an incomplete MTX response, CZP 200 mg every 2 weeks and 400 mg every 4 weeks were comparable and better than placebo for maintaining clinical response to week 4 following a 16-week, open-label run-in phase.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Imunossupressores/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Certolizumab Pegol , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Resultado do Tratamento
18.
Clin Exp Immunol ; 179(1): 90-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25169121

RESUMO

B-1 and B-2 B cell subsets carry out a diverse array of functions that range broadly from responding to innate stimuli, antigen presentation, cytokine secretion and antibody production. In this review, we first cover the functional roles of the major murine B cell subsets. We then highlight emerging evidence, primarily in preclinical rodent studies, to show that select B cell subsets are a therapeutic target in obesity and its associated co-morbidities. High fat diets promote accumulation of select murine B cell phenotypes in visceral adipose tissue. As a consequence, B cells exacerbate inflammation and thereby insulin sensitivity through the production of autoantibodies and via cross-talk with select adipose resident macrophages, CD4(+) and CD8(+) T cells. In contrast, interleukin (IL)-10-secreting regulatory B cells counteract the proinflammatory profile and improve glucose sensitivity. We subsequently review data from rodent studies that show pharmacological supplementation of obesogenic diets with long chain n-3 polyunsaturated fatty acids or specialized pro-resolving lipid mediators synthesized from endogenous n-3 polyunsaturated fatty acids boost B cell activation and antibody production. This may have potential benefits for improving inflammation in addition to combating the increased risk of viral infection that is an associated complication of obesity and type II diabetes. Finally, we propose potential underlying mechanisms throughout the review by which B cell activity could be differentially regulated in response to high fat diets.


Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Dieta , Obesidade/etiologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Animais , Antígenos de Superfície/metabolismo , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/citologia , Diferenciação Celular , Comorbidade , Ácidos Graxos Insaturados/metabolismo , Humanos , Imunidade Humoral , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
19.
J Laryngol Otol ; 128(8): 709-13, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25076139

RESUMO

BACKGROUND: Haemorrhage is the most common major complication of endoscopic sinus surgery. Post-operative absorbable or non-absorbable nasal packing can cause pain and blockage. Haemostatic powders or gels may prevent this problem. However, when based on factors in the clotting cascade, they induce an inflammatory reaction and can cause post-operative synechiae. Oxidised cellulose powder produces haemostasis without inducing synechiae formation, but has not been trialled for sinus surgery. METHOD: A randomised clinical trial was performed to compare cellulose powder to non-absorbable packing following sinus surgery. Participants were 50 consecutive patients undergoing sinus surgery, 47 of whom completed the study. The main outcome measures were post-operative bleeding, pain scores and synechiae formation. RESULTS: Cellulose powder was effective at stopping bleeding, and was associated with less pain than nasal packing, with no evidence of increased synechiae formation. CONCLUSION: Cellulose powder appears to be a good haemostatic agent following sinus surgery. A larger trial would allow more accurate quantification of its effectiveness.


Assuntos
Celulose Oxidada/administração & dosagem , Hemostasia/efeitos dos fármacos , Seios Paranasais/cirurgia , Adulto , Idoso , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cuidados Pós-Operatórios , Hemorragia Pós-Operatória/prevenção & controle , Pós , Resultado do Tratamento
20.
Br J Surg ; 101(4): 363-70, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24536009

RESUMO

BACKGROUND: Fluorine-18-labelled fluoroxdeoxyglucose (FDG) positron emission tomography (PET) has been used to evaluate atherosclerotic plaque metabolic activity, and through its uptake by macrophages is believed to have the potential to identify vulnerable plaques. The aims were to compare FDG uptake in carotid plaques from patients who had sustained a recent thromboembolic cerebrovascular event with that in femoral artery plaques from patients with leg ischaemia, and to correlate FDG uptake with the proportion of M1 and M2 macrophages present. METHODS: Consecutive patients who had carotid endarterectomy for symptomatic, significant carotid stenosis and patients with severe leg ischaemia and significant stenosis of the common femoral artery underwent FDG-PET and histological plaque analysis. The voxel with the greatest activity in the region of interest was calculated using the Patlak method over 60 min. Plaques were dual-stained for CD68, and M1 and M2 macrophage subsets. RESULTS: There were 29 carotid and 25 femoral artery plaques for study. The maximum dynamic uptake was similar in carotid compared with femoral plaques: median (range) 9·7 (7·1-12·2) versus 10·0 (7·4-16·6) respectively (P = 0·281). CD68 macrophage counts were significantly increased in carotid compared with femoral plaques (39·5 (33·9-50·1) versus 11·5 (7·7-21·3) respectively; P < 0·001), as was the proportion of M1 proinflammatory macrophages. The degree of carotid stenosis correlated with the maximum dynamic FDG uptake (rs = 0·48, P = 0·008). CONCLUSION: FDG uptake was no greater in symptomatic carotid plaques than in the less inflammatory femoral plaques. In patients on statin therapy. FDG uptake occurred in areas of significant arterial stenosis, irrespective of the degree of inflammation.


Assuntos
Estenose das Carótidas/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Artéria Femoral/diagnóstico por imagem , Fluordesoxiglucose F18 , Perna (Membro)/irrigação sanguínea , Placa Aterosclerótica/diagnóstico por imagem , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/metabolismo , Estenose das Carótidas/cirurgia , Transtornos Cerebrovasculares/metabolismo , Endarterectomia , Endarterectomia das Carótidas , Feminino , Artéria Femoral/metabolismo , Fluordesoxiglucose F18/farmacocinética , Humanos , Imuno-Histoquímica , Isquemia/diagnóstico por imagem , Isquemia/metabolismo , Isquemia/cirurgia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Tromboembolia/diagnóstico por imagem , Tromboembolia/metabolismo
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