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1.
Br Med Bull ; 139(1): 48-58, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34227647

RESUMO

INTRODUCTION: Open tibial fractures are the most common open long bone fracture, despite this, the management of these complex injuries still remains a topic of discussion amongst orthopaedic surgeons. SOURCES OF DATA: We searched the EMBASE, MEDLINE and Google Scholar and a systematic review of 7500 articles, leaving 23 after exclusion criteria were applied, in order to analyse the management of open tibial fractures. AREAS OF AGREEMENT AND CONTROVERSY: Infection was noted to be the most significant concern amongst authors, with definitive external fixation having a high rate of superficial pin-site infection and internal fixation having a high deep infection rate. GROWING POINTS: It is essential to have a combined ortho-plastic approach to the management of these fractures as muscle flaps were the most common form of soft tissue coverage. AREAS TIMELY FOR DEVELOPING RESEARCH: A national pragmatic trial into the management of open tibial fractures is required looking at fixation methods and soft tissue coverage, with at least a 2-year follow-up in order to ascertain the most appropriate management of these fractures and patient-related outcomes.


Assuntos
Fraturas Expostas , Fraturas da Tíbia , Adulto , Fixação Interna de Fraturas , Fraturas Expostas/cirurgia , Humanos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/terapia , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
2.
Br Med Bull ; 122(1): 135-149, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28444129

RESUMO

Introduction: This review aims to provide information on return rates and times to sport following stress fractures of the great toe sesamoids (SFGTSs). Sources of data: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Scopus, SPORTDiscus and Web of Science was performed using the keywords 'stress', 'fractures', 'great', 'toe', 'sesamoid', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. Areas of agreement: Fourteen studies were included: three studies reported on the outcome of conservatively-managed SFGTSs; thirteen studies reported on the outcome of surgically-managed SFGTSs. The management principles were to attempt conservative management for 2-6 months using activity modification, analgesia, orthotics and physiotherapy; if symptoms persisted following this, surgical management was to be recommended, either with internal fixation or sesamoidectomy. Areas of controversy: The optimal treatment modalities for SFGTSs remain to be defined. Growing points: Internal fixation shows the best return to full-level sport rates with low rates of complications. Areas timely for developing research: Future prospective studies should aim to establish the optimal treatment modalities for SFGTSs.


Assuntos
Fraturas de Estresse/terapia , Hallux/lesões , Volta ao Esporte , Humanos , Estudos Prospectivos , Esportes
3.
J R Nav Med Serv ; 103(1): 35-8, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30088738

RESUMO

We present a case series of patients with patellofemoral joint (PFJ) chondral injuries presenting as anterior knee pain secondary to participation in high-intensity functional training programmes. We aim to highlight PFJ chondral injuries as a potential complication of military servicemen engaging in high-intensity functional training programmes. This may allow medical staff to identify the injuries early, and highlight this possible injury mechanism to Physical Training staff to help educate participants and mitigate the risk of injury.


Assuntos
Cartilagem Articular/lesões , Treinamento Intervalado de Alta Intensidade/efeitos adversos , Militares , Articulação Patelofemoral/lesões , Adulto , Artralgia/etiologia , Cartilagem Articular/diagnóstico por imagem , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Masculino , Articulação Patelofemoral/diagnóstico por imagem , Fatores de Risco
4.
Br Med Bull ; 119(1): 111-28, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27554280

RESUMO

INTRODUCTION: This review aims to provide information on the return rates and return times to sport following clavicle fractures. SOURCES OF DATA: A systematic search of Medline, EMBASE, CINAHAL, Cochrane, Web of Science, PEDro, SPORTDiscus, Scopus and Google Scholar was performed using the keywords 'clavicle', 'clavicular', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative', 'return to sport'. AREAS OF AGREEMENT: Twenty-three studies were included: 10 reported on mid-shaft fractures, 14 on lateral fractures. The management principles for athletic patients were to attempt non-operative management for undisplaced fractures to undertake operative intervention for displaced lateral fractures and to recommend operative intervention for displaced mid-shaft fractures. AREAS OF CONTROVERSY: The optimal surgical modality for mid-shaft and lateral clavicle fractures. GROWING POINTS: Operative management of displaced mid-shaft fractures offers improved return rates and times to sport compared to non-operative management. Suture fixation and non-acromio-clavicular joint (ACJ)-spanning plate fixation of displaced lateral fractures show promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for clavicle fractures.


Assuntos
Traumatismos em Atletas/reabilitação , Clavícula/lesões , Tratamento Conservador/métodos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/reabilitação , Volta ao Esporte/estatística & dados numéricos , Traumatismos em Atletas/terapia , Placas Ósseas , Clavícula/patologia , Fixação Interna de Fraturas/reabilitação , Fraturas Ósseas/terapia , Humanos , Período Pós-Operatório , Resultado do Tratamento
5.
J R Army Med Corps ; 162(6): 413-418, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26941219

RESUMO

INTRODUCTION: Cold injuries have been a recurrent feature of warfare for millennia and continue to present during British Military operations today. Those affecting the peripheries are divided into freezing cold injury (FCI) and non-FCI. FCI occurs when tissue fluids freeze at around -0.5°C and is commonly referred to as frostnip or frostbite. METHOD: All FMED7 notes held at the Institute of Naval Medicine's Cold Weather Injury Clinic (CIC) from 2002 to 2014 were searched for the terms 'frostbite' and 'frostnip' and then analysed to identify common themes. RESULTS: In total 245 results were found and from these, 149 patients with a positive FCI diagnosis were identified and formed the cohort of this study. Royal Marines (RM) represented over 50% of patients and Arctic training in Norway accounted for over two thirds of the total cases. The extremities were almost always those areas which were affected by FCI. Further analysis of the RM cases showed the majority of those injured were of the most junior rank (Marine/Private or Lance Corporal). CONCLUSIONS: A lack of supporting climatic and activity data meant that it was difficult to draw additional conclusions from the data collected. In future, a greater emphasis should be placed on collection of climatic and additional data when FCIs are diagnosed. These data should be collated at the end of each deployment and published as was regularly done historically. It is hoped that these data could then be used as the starting point for an annual climatic study day, where issues related to FCIs could be discussed in a Tri-Service environment and lessons learned disseminated around all British Forces personnel.


Assuntos
Traumatismos Faciais/epidemiologia , Traumatismos do Pé/epidemiologia , Congelamento das Extremidades/epidemiologia , Traumatismos da Mão/epidemiologia , Militares , Estudos de Coortes , Bases de Dados Factuais , Humanos , Noruega/epidemiologia , Reino Unido/epidemiologia
6.
Br Med Bull ; 114(1): 95-111, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25712999

RESUMO

INTRODUCTION: This review aims to provide information on the time taken to resume sport following tibial diaphyseal stress fractures (TDSFs). SOURCES OF DATA: A systematic search of Medline, EMBASE, CINHAL, Cochrane, Web of Science, PEDro, Sports Discus, Scopus and Google Scholar was performed using the keywords 'tibial', 'tibia', 'stress', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. AREAS OF AGREEMENT: Twenty-seven studies were included: 16 reported specifically on anterior TDSFs and 5 on posterior TDSFs. The general principles were to primarily attempt non-operative management for all TDSFs and to consider operative intervention for anterior TDSFs that remained symptomatic after 3-6 months. Anterior TDSFs showed a prolonged return to sport. AREAS OF CONTROVERSY: The best time to return to sport and the optimal management modalities for TDSFs remain undefined. GROWING POINTS: Management of TDSFs should include a full assessment of training methods, equipment and diet to modify pre-disposing factors. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for TDSFs.


Assuntos
Traumatismos em Atletas/reabilitação , Fraturas de Estresse/reabilitação , Volta ao Esporte , Fraturas da Tíbia/reabilitação , Diáfises/lesões , Humanos , Recuperação de Função Fisiológica , Fatores de Tempo
7.
BJOG ; 122(11): 1525-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25626593

RESUMO

OBJECTIVE: To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 1980-2008, and to determine whether the pattern varied according to the cause of the preterm birth. DESIGN: Linked birth databases. SETTING: All Scottish NHS hospitals. POPULATION: A total of 732 719 nulliparous women with a first live birth between 1980 and 2008. METHODS: Risk was estimated using logistic regression. MAIN OUTCOME MEASURES: Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre-eclampsia, or induced without a diagnosis of pre-eclampsia) and severity [extreme (24-28 weeks of gestation), moderate (29-32 weeks of gestation), and mild (33-36 weeks of gestation)]. RESULTS: Consistent with previous studies, previous miscarriage was associated with an increased risk of all-cause preterm birth (adjusted odds ratio, aOR 1.26; 95% confidence interval, 95% CI 1.22-1.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR 1.73; 95% CI 1.57-1.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all-cause preterm birth (aOR 2.14; 95% CI 1.93-2.38), and the strongest association was with extreme preterm birth (aOR 3.87; 95% CI 2.85-5.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre-eclampsia. CONCLUSIONS: The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 1980-2008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage.


Assuntos
Aborto Espontâneo/epidemiologia , Nascimento Prematuro/epidemiologia , Aborto Habitual/epidemiologia , Adulto , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Gravidez , Modelos de Riscos Proporcionais , Risco , Escócia/epidemiologia , Adulto Jovem
8.
BJOG ; 122(11): 1467-74, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26033155

RESUMO

OBJECTIVE: To determine whether caesarean delivery in the first pregnancy is a risk factor for unexplained antepartum stillbirth in a second pregnancy. DESIGN: A population-based retrospective cohort study and meta-analysis. SETTING: All maternity units in Scotland. PARTICIPANTS: A cohort of 128 585 second births, 1999-2008. METHODS: Time-to-event analysis and random-effects meta-analysis. MAIN OUTCOME MEASURE: Risk of unexplained antepartum stillbirth in a second pregnancy. RESULTS: There were 88 stillbirths among 23 688 women with a previous caesarean delivery (2.34 per 10 000 women per week) and 288 stillbirths in 104 897 women who had previously delivered vaginally (1.67 per 10 000 women per week, P = 0.002). When analysed by cause, women with a previous caesarean delivery had an increased risk of unexplained stillbirth (hazard ratio, HR 1.47; 95% confidence interval, 95% CI 1.12-1.94; P = 0.006) and, as previously observed, the excess risk was apparent from 34 weeks of gestation onwards. The risk did not differ in relation to the indication of the caesarean delivery, and was independent of maternal characteristics and previous obstetric complications. We identified three other comparable studies (two in North America and one in Europe), and meta-analysis of these studies showed a statistically significant association between previous caesarean delivery and the risk of antepartum stillbirth in the second pregnancy (pooled HR 1.40; 95% CI 1.10-1.77; P = 0.006). CONCLUSIONS: Women who have had a previous caesarean delivery are at increased risk of unexplained stillbirth in the second pregnancy. TWEETABLE ABSTRACT: Caesarean first delivery is associated with an increased risk of unexplained stillbirth in the next pregnancy.


Assuntos
Cesárea/efeitos adversos , Natimorto/epidemiologia , Adulto , Cesárea/estatística & dados numéricos , Estudos de Coortes , Feminino , Idade Gestacional , Número de Gestações , Humanos , Gravidez , Sistema de Registros , Estudos Retrospectivos , Risco , Escócia/epidemiologia , Nascimento a Termo
9.
J R Nav Med Serv ; 101(2): 182-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26867421

RESUMO

This article describes stress fractures that are seen in military training, and reviews the relevant literature. The information is vital for medical personnel who work with the United Kingdom (UK) Armed Forces, particularly those working in training establishments. The author suggests areas for further research and discusses some of the issues in current UK Armed Forces training.


Assuntos
Fraturas de Estresse/diagnóstico , Fraturas de Estresse/etiologia , Ossos da Perna/lesões , Militares , Fraturas de Estresse/terapia , Humanos
10.
Avian Pathol ; 43(5): 473-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25175532

RESUMO

Typhlohepatitis was observed in a flock of 2500 red-legged partridges in Great Britain, characterized by the sudden deaths of 15 birds within 2 days. Necropsy of five dead birds revealed severe lesions in the caeca with thickened caecal walls, a reddened lining and bloody contents. The livers contained multiple miliary lesions and similar pathological changes were found in the spleens of some birds. Microscopic examination of intestinal contents showed the occurrence of coccidial oocysts in two partridges. Different methods for the detection of bacteria from liver and intestine samples were conducted without positive results. Histopathological examination revealed the presence of protozoan parasites in the caecum, liver and spleen of the affected birds. In situ hybridization (ISH) for the detection of trichomonads resulted in positive findings and polymerase chain reaction (PCR) confirmed the presence of Tetratrichomonas gallinarum in the lesions. Additionally, archived tissues of red-legged partridges from different flocks suffering from severe typhlohepatitis in Great Britain in 2008 and 2009 were re-investigated by ISH and PCR. Beside the sporadic occurrence of histomonosis, in most of the cases trichomonads were detected by ISH in the caecum and liver of affected birds. Furthermore, dissemination of the flagellate into the lung and bursa of Fabricius could be demonstrated. Analyses of T. gallinarum DNA obtained from the different cases resulted in homologous nucleotide sequences. Altogether, the results demonstrate the circulation of a virulent strain of T. gallinarum in reared red-legged partridges.


Assuntos
Galliformes , Hepatite Animal/parasitologia , Doenças das Aves Domésticas/parasitologia , Infecções Protozoárias em Animais/parasitologia , Trichomonadida/classificação , Animais , DNA de Protozoário/genética , DNA Espaçador Ribossômico/genética , Hepatite Animal/epidemiologia , Hepatite Animal/mortalidade , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/mortalidade , Infecções Protozoárias em Animais/epidemiologia , Infecções Protozoárias em Animais/mortalidade , RNA de Protozoário/genética , RNA Ribossômico 18S/genética , Trichomonadida/genética , Reino Unido/epidemiologia
11.
Occup Environ Med ; 71(2): 104-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24306365

RESUMO

OBJECTIVES: To quantify changes in vitamin D and matrix metalloproteinase-9 (MMP9) in submariners over a single long patrol and compare the data to a group of non-deploying servicemen from their base port. METHODS: A prospective time-series analysis was performed. Blood samples were taken from 49 submariners deploying on patrol and 43 shore-side controls from the base port (naval officers from base or non-deploying submariners), following a winter ashore at latitude 56° north. Samples were drawn immediately before the submarine sailed, in January, and again in the final week of patrol 85 days later. Paired pre-patrol and late samples from each individual were assayed together and changes in vitamin D and MMP9 were assessed. RESULTS: Mean pre-patrol vitamin D concentrations were 58 and 49 nmol/L for the controls and submariners, respectively. Mean vitamin D concentrations increased in controls as expected (mean increase 12.6 nmol/L), but not in the submariners (mean decrease 1.6 nmol/L). MMP9 levels were significantly higher in submariners pre-patrol, and increased significantly during the patrol. There was a significant inverse correlation between MMP9 and vitamin D levels (r=-0.41, p=0.01). CONCLUSIONS: This is the first study to quantify vitamin D and MMP levels in submariners. Circulating vitamin D concentrations on board were insufficient to prevent a rise in MMP. This has potential for adverse health effects and requires further study.


Assuntos
Metaloproteinase 9 da Matriz/sangue , Medicina Submarina , Vitamina D/sangue , Adulto , Análise de Variância , Biomarcadores/sangue , Feminino , Humanos , Masculino , Militares , Estudos Prospectivos , Fatores de Tempo
12.
J R Nav Med Serv ; 100(3): 288-92, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25895409

RESUMO

Patients presenting with an acutely swollen ankle are common in both the military and civilian settings. Accurate diagnosis is vital, as there are various potentially serious causes. This article aims to review the common causes of an acutely swollen ankle, as well as the rarer causes, with their significant consequences.


Assuntos
Articulação do Tornozelo/fisiopatologia , Edema/etiologia , Edema/fisiopatologia , Militares , Doença Aguda , Traumatismos do Tornozelo/complicações , Artrite/complicações , Humanos , Anamnese , Exame Físico
13.
J R Nav Med Serv ; 99(1): 25-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23691860

RESUMO

We report the injuries and medical issues incurred during a rowing expedition conducted along the Zambezi River in May 2011. All injuries and illnesses requiring medical intervention were recorded during a 30-day expedition. There were 22 rowers and 8 support staff sustaining 32 injuries, an injury incidence of 36 per 1000 days. We discuss the medical issues regarding conducting an expedition along the Zambezi and the medical preparation and education required to successfully support wilderness expeditions.


Assuntos
Expedições , Gastroenteropatias/epidemiologia , Dermatopatias/epidemiologia , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , África , Feminino , Gastroenteropatias/parasitologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Rios , Dermatopatias/microbiologia , Adulto Jovem
14.
J R Nav Med Serv ; 99(3): 111-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24511792

RESUMO

The use of the alpha angle to help the diagnosis of Femoral Acetabular Impingement (FAI) is common. However, there is currently no standard value available across an asymptomatic pre-arthritic population. We present the first large cohort of Computerised Tomography (CT) based alpha angles in patients with no history of hip pathology, including intra- and interobserver validation. We carried out a retrospective analysis of 73 consecutive individuals (146 hip joints) with ages ranging from 18 to 39 years. The age range 18-39 represents 82.4% of those currently serving in the UK Armed Forces. The cohort was drawn from those patients who had received a CT scan in the Lothian Region between 1 Jan 2011 and 31 Dec 2011 due to abdominal pathology. These patients had their electronic patient record checked to rule out any hip-related problems. The alpha angle of Nötzli was measured on the axial view bilaterally. The mean value for the 18-39 age range was found to be 51.89 degree for the left hip and 52.53 degree for the right. Femoral alpha angle is a reproducible measurement for assessing the femoral neck. However, there is wide variability in the alpha angle for patients, irrespective of the presence of symptoms. Our results would suggest that the alpha angle alone should not be used to diagnose FAI in service personnel, as even large angles may be normal.


Assuntos
Acetábulo/patologia , Fêmur/patologia , Adolescente , Adulto , Feminino , Impacto Femoroacetabular , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
15.
J R Nav Med Serv ; 98(2): 27-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22970643

RESUMO

We report the delay in diagnosis of a Neck of Femur (NOF) stress fracture in mixed sex basic military training. Stress fractures are common in military training with the incidence reported as ranging between 3.2-31%. NOF stress fractures, whilst only representing around 8% of stress fractures are associated with a high morbidity. It is imperative that medical officers looking after military recruits have a sound knowledge of the potential signs, symptoms and presentation of these injuries. Medical officers should always remains vigilant for stress fractures especially in mixed military training.


Assuntos
Fraturas do Colo Femoral/diagnóstico , Fraturas de Estresse/diagnóstico , Militares , Adulto , Diagnóstico Tardio , Feminino , Fraturas do Colo Femoral/reabilitação , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Fraturas de Estresse/reabilitação , Fraturas de Estresse/cirurgia , Humanos , Imageamento por Ressonância Magnética
16.
Nat Aging ; 2(2): 170-179, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-37117760

RESUMO

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.


Assuntos
Bancos de Espécimes Biológicos , Etnicidade , Recém-Nascido , Humanos , Masculino , Feminino , Leucócitos , Telômero/genética , Reino Unido
17.
Thorax ; 66(3): 205-10, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21228423

RESUMO

BACKGROUND: Vitamin D-binding protein (DBP) genetic polymorphisms have been associated with chronic obstructive pulmonary disease (COPD). DBP has an indirect role in macrophage activation; thus it was hypothesised that DBP is present in the airway and contributes to lung disease by this mechanism. METHODS: 471 PiZZ subjects with α1-antitrypsin deficiency (AATD) were genotyped for tag single nucleotide polymorphisms (SNPs) covering the DBP gene (GC), together with known functional variants, prior to seeking association with COPD phenotypes. 140 subjects with usual COPD and 480 controls were available for replication. Vitamin D and DBP levels were measured by tandem mass spectrometry and ELISA, respectively, in serum and DBP in the sol phase of sputum in a subset of 60 patients. Concentrations were related to phenotype and to alveolar macrophage activation. RESULTS: rs2070741 was associated with airway bacterial colonisation (p=0.04) and bronchiectasis (p=0.01), as was rs7041 (p=0.03) which also influenced vitamin D concentrations (p=0.01). The GC2 variant predisposed to bronchiectasis in AATD (p=0.04) and protected against COPD (p=0.05); the latter association was replicated in usual COPD versus controls (p=0.04). Circulating DBP related inversely to forced expiratory volume in 1 s (FEV(1)) (p=0.02), in direct contrast to vitamin D, where deficiency related to low FEV(1) (p=0.04). Sol DBP related directly to alveolar macrophage activation (p=0.004). CONCLUSIONS: The genetic association of DBP with COPD may be mediated by effects on macrophage activation, since DBP relates to FEV(1), and affects macrophage activation. Vitamin D effects may be independent of this, relating more strongly to innate immunity.


Assuntos
Ativação de Macrófagos/fisiologia , Macrófagos Alveolares/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Proteína de Ligação a Vitamina D/fisiologia , Adulto , Feminino , Volume Expiratório Forçado/fisiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/genética , Capacidade Vital/fisiologia , Deficiência de Vitamina D/complicações , Proteína de Ligação a Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/genética
18.
Eur Respir J ; 38(6): 1461-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21700608

RESUMO

In this article, we outline the current state of knowledge about the balance between collagen production and degradation in idiopathic pulmonary fibrosis (IPF). The dysregulated action of metalloproteinases implicated in IPF may play a central role in IPF pathogenesis. Inhibiting metalloproteinases in IPF may, therefore, have therapeutic potential, but our knowledge of their pathophysiological role is held back by limited animal models and the lack of specific inhibitors.


Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Metaloproteinases da Matriz/metabolismo , Animais , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Transgênicos , Ratos
19.
Eur Respir J ; 37(1): 32-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20525711

RESUMO

Liberation of elastin peptides from damaged lung may be a mechanism of autoimmune lung disease. Citrullination, and anti-citrullinated protein antibody formation occurs in smokers, but the role of smoking in autoantibody generation relevant to pulmonary disease is unclear. Anti-elastin, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies were measured in 257 subjects with α1-antitrypsin deficiency (AATD), 113 subjects with usual chronic obstructive pulmonary disease (COPD) and 22 healthy nonsmokers. Levels were compared between groups, against phenotypic features and against smoke exposure. Anti-elastin antibodies were higher in controls relative to AATD (p = 0.008) and usual COPD (p < 0.00001), and in AATD relative to usual COPD (p < 0.00001). Anti-elastin levels showed a threshold at 10 pack-yrs, being higher in those who had smoked less (p = 0.004). No relationships between antibody levels and clinical phenotype were seen after adjustment for smoke exposure. Anti-CCP antibodies were higher in usual COPD than AATD (p = 0.002) but the relationship to smoke exposure was less clear. Smoke exposure is the main determinant of anti-elastin antibody levels, which fall after 10 pack-yrs. Local antibody complexes may be a better measure of elastin directed autoimmunity than circulating levels.


Assuntos
Elastina/imunologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/efeitos adversos , Deficiência de alfa 1-Antitripsina/imunologia , Adulto , Idoso , Doenças Autoimunes/imunologia , Elastina/metabolismo , Feminino , Volume Expiratório Forçado , Humanos , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Risco , Fatores de Tempo
20.
Ann Rheum Dis ; 70(10): 1851-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21821620

RESUMO

BACKGROUND: Small studies have linked α1 antitrypsin (α1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). OBJECTIVE: To test the validity and the mechanism of this association between α1AT and AAV. METHODS: The distribution of α1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geographic and ethnically matched healthy controls. Genotyping was performed by allelic discrimination assay. RESULTS: were compared between cases and controls using χ(2) tests. The serum and renal biopsies for α1AT polymers were compared using the polymer-specific 2C1 antibody. The role of α1AT polymers in promoting inflammation was investigated by examining their ability to prime neutrophils for ANCA activation as assessed by CD62L shedding, superoxide production and myeloperoxidase degranulation. Results The Z but not the S allele was over-represented in the patients compared with controls (HR=2.25, 95% CI 1.60 to 3.19). Higher concentrations of polymers of α1AT were detected in serum from patients carrying the Z allele than in those not carrying the Z allele (median (IQR) 1.40 (0.91-3.32) mg/dl vs 0.17 (0.06-0.28) mg/dl, p<0.001); polymers of α1AT were also seen in the renal biopsy of a patient with vasculitic glomerulonephritis. Polymers of α1AT primed neutrophils with CD62L shedding and increased superoxide production following ANCA activation. Carriage of the Z allele was not associated with disease severity, survival or relapse. CONCLUSIONS: The Z but not the S deficiency allele is associated with AAV. Polymers of α1AT are present in the serum and glomeruli of at least some patients with the Z allele, which may promote inflammation through priming of neutrophils.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Deficiência de alfa 1-Antitripsina/complicações , alfa 1-Antitripsina/genética , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Biópsia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Heterozigoto , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , alfa 1-Antitripsina/sangue , Deficiência de alfa 1-Antitripsina/genética
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