RESUMO
It is important to delineate factors which influence in-hospital mortality rates following a hip fracture. The current study aimed to identify the nature and frequency of comorbidities prevalent in this patient cohort. A retrospective chart review of cases of in-patient mortality following admission for a hip fracture was performed. These cases (n=127) were characterized for comorbidities, complications, medical status indicators, and other contributory factors. Cardiovascular 104 (81.9%), respiratory 66 (52.0%), genitourinary 41 (32.3%), psychiatric 41 (32.3%), vascular 40 (31.5%), and gastrointestinal 40 (31.5%), are the physiological systems, most commonly associated with comorbidity amongst hip fracture patients who succumb to in-hospital mortality. Renal failure, pneumonia, sepsis, myocardial infarction, congestive cardiac failure (CCF), respiratory failure, and Clostridium difficile infection are conditions which are associated with postoperative complications leading to in-patient mortality. Analysis of medical status indicators illustrated an inverse correlation between ASA scores and postoperative survival time, in this cohort-of hip fracture patients (R2 = 0.9485).
Assuntos
Fraturas do Quadril , Procedimentos Ortopédicos/mortalidade , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Disparidades nos Níveis de Saúde , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Mortalidade Hospitalar , Humanos , Irlanda/epidemiologia , Masculino , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estatística como Assunto , Análise de SobrevidaRESUMO
IgG4 tubulointerstitial nephritis (IgG4-TIN) is the most common form of IgG4 renal disease. When IgG4-TIN is accompanied by other systemic manifestations the disease is known as IgG4-related systemic disease (IgG4-RSD). IgG4-RSD is well recognised in the form of tubulointerstitial nephritis (IgG4-related TIN) and may present with renal failure by mimicking neoplasms (tumefactive lesions) or with both features. We describe a case of IgG4-RSD initially presenting as a submandibular mass and subsequently presenting two years later with secondary infiltration of the kidney causing tubulointerstitial nephritis. This case highlights the importance of recognising IgG4-RSD as a non-malignant disease with presentations having commonly shared features including tumour-like swelling of involved organs and its ability to mimic many systemic diseases. In the majority of patients it can be treated successfully with corticosteroids.
Assuntos
Imunoglobulina G/sangue , Nefrite Intersticial/diagnóstico , Sialadenite/diagnóstico , Creatinina/sangue , Diagnóstico Diferencial , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/complicações , Nefrite Intersticial/imunologia , Sialadenite/etiologiaRESUMO
INTRODUCTION: Selecting the correct tibial nail length is essential for satisfactory outcomes. Nails that are inserted and are found to be of inappropriate length should be removed. Accurate preoperative nail estimation has the potential to reduce intra-operative errors, operative time and radiation exposure. METHODS: We compared the most commonly used radiological, anthropometric and intra-operative techniques to determine ideal nail lengths for 16 paired cadaveric tibiae. Five different anthropometric measurements were taken from each intact cadaver including: knee joint line to ankle joint line distance (JJD), medial knee joint line to medial malleolus distance (MMD), tibial tuberosity to medial malleolus distance (TMD), olecranon to 5th metacarpal head distance (OMD) and body height (BHR). Each tibia also underwent antero-posterior (AP) and lateral scanograms. Computerised tomography was used to determine the ideal nail length for each tibia. Each anthropometric and radiological measurement was recorded by two orthopaedic surgeons independently. An expert tibial nail was then inserted after nail length estimation was performed using a guidewire technique and an intra-operative radiographic ruler. RESULTS: The AP scanogram was found to be 100% accurate in selecting ideal nail length. The lateral scanogram was also found to be reasonably accurate but in 19% (3/16) of cases it led to a nail being too long. The intra-operative radiographic ruler was found to give a good indication of the ideal nail size, as did the guidewire technique, with only 6% (1/16) of cases producing an incorrect nail size. In general, the anatomical measurements gave a poor indication of ideal nail size compared with the other techniques. The following accuracies were noted: JJD 56%, MMD 50%, TMD 38%, BHR 13% and OMD 56%. CONCLUSIONS: We found that radiological methods such as using an AP radiograph with known magnification and intra-operative radiographic ruler were able to predict nail length very accurately and we suggest that these measurements should be performed routinely. The guidewire technique was also effective but we recommend that it not be used in isolation as errors can occur. We found that anatomical measurements are not accurate for predicting tibial nail length.
Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Cuidados Pré-Operatórios/instrumentação , Tíbia/anatomia & histologia , Fraturas da Tíbia/cirurgia , Antropometria , Cadáver , Desenho de Equipamento , Feminino , Humanos , Masculino , Cuidados Pré-Operatórios/métodosRESUMO
BACKGROUND: There are little data available on complication rates following primary total hip arthroplasty (THA) surgery in Ireland. AIMS: To determine self-reported complication rates and national data for primary THA. METHODS: A postal questionnaire surveyed Irish orthopaedic association consultant members. Additional data were obtained from the economic and social research institute (ESRI). RESULTS: We achieved an 83% response rate. 5,424 THAs were self-reported. Mean dislocation rates were 1%, but higher using a posterior surgical approach (p < 0.05). Mean deep infection rates were 0.4%. 29% were MRSA. No reduction was reported from additional barrier prophylaxes. Mean venous thrombo-embolism (VTE) rates were 3.5%. No reduction was reported from commencing prophylaxis preoperatively or extending treatment duration. National rates for dislocation, deep infection and VTE were 25.7, 0.87, and <0.1%, respectively. CONCLUSIONS: The creation of a National Hip Register is strongly recommended. A register would improve surgical practices and patient outcomes, and provide significant healthcare savings.
Assuntos
Artroplastia de Quadril/efeitos adversos , Humanos , Irlanda/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Padrões de Prática Médica , Infecções Relacionadas à Prótese/epidemiologia , Sistema de Registros , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controleRESUMO
Antiplatelet agents are widely prescribed for the primary and secondary prevention of cardiovascular events. A common clinical problem facing orthopaedic and trauma surgeons is how to manage patients receiving these agents who require surgery, either electively or following trauma. The dilemma is to balance the risk of increased blood loss if the antiplatelet agents are continued peri-operatively against the risk of coronary artery/stent thrombosis and/or other vascular event if the drugs are stopped. The traditional approach of stopping these medications up to two weeks before surgery appears to pose significant danger to patients and may require review. This paper covers the important aspects regarding the two most commonly prescribed antiplatelet agents, aspirin and clopidogrel.
Assuntos
Aspirina/uso terapêutico , Ortopedia/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Doenças Cardiovasculares/prevenção & controle , Clopidogrel , Quimioterapia Combinada , Humanos , Assistência Perioperatória , Cuidados Pré-Operatórios , Stents/efeitos adversos , Ticlopidina/uso terapêuticoRESUMO
PURPOSE: To compare the quantity of bone removed from the acetabulum during resurfacing hip arthroplasty versus uncemented total hip arthroplasty (THA). METHODS: 62 consecutive patients with osteoarthritis of the hip were prospectively studied. 24 men and 7 women aged 40 to 86 (mean, 59) years underwent Birmingham hip resurfacing. 13 men and 18 women aged 34 to 88 (mean, 61) years underwent uncemented THA using the trident acetabular cup. Obese elderly women at risk of femoral neck fracture and patients with large subchondral pseudocysts or a history of avascular necrosis of the femoral head were assigned to uncemented THA. Acetabular reamings were collected; marginal osteophytes were not included. The reamings were dehydrated, defatted, and weighed. RESULTS: The mean weight of acetabular reamings was not significantly different between patients undergoing hip resurfacing and uncemented THA (p=0.57). CONCLUSION: In hip resurfacing, the use of an appropriately small femoral component avoids oversizing the acetabular component and removal of excessive bone stock.
Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Cimentação , Osteoartrite do Quadril/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cabeça do Fêmur/patologia , Cabeça do Fêmur/cirurgia , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/patologia , Estudos Prospectivos , Desenho de Prótese , Resultado do TratamentoRESUMO
PURPOSE: To assess the risk of surgical delay in elderly hip fracture patients on anti-platelet agents. METHODS: Records of 180 patients aged over 65 years with either an intertrochanteric or femoral neck fracture were reviewed. The clopidogrel group included 10 patients on clopidogrel alone and 11 others on clopidogrel and aspirin, whereas the control group included 69 on aspirin alone and the remaining 90 not on any anti-coagulants. The 2 groups were compared with regard to time to surgery, preoperative American Society of Anesthesiologists (ASA) score, pre- and post-operative haemoglobin levels, in-patient complication rates, duration of hospital stay, and 30-day mortality. RESULTS: In the clopidogrel and control groups respectively, the mean times to surgery were 7.2 and 2.1 days (p=0.03, t-test), the mean preoperative ASA scores were 3.35 and 2.8 (p=0.29, t-test), the mean preoperative haemoglobin levels were 119 and 115 g/l (p=0.5, t-test), the mean postoperative haemoglobin levels were 98 and 96 g/l (p=0.68, t-test), the mean durations of hospital stay were 7.4 and 3.1 days (p=0.02, t-test). The 30-day mortalities were 6/21 (29%) and 6/159 (4%) [p=0.0003, Fisher's exact test]. CONCLUSION: Surgical delay in elderly patients on anti-platelet agents with hip fracture was associated with higher mortality. Despite the risk of increased blood loss, we suggest early surgery be carried out by an experienced surgeon to expedite the operating time. Pooled platelets should be given intravenously one to 2 hours preoperatively.
Assuntos
Aspirina/administração & dosagem , Fraturas do Quadril/cirurgia , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Feminino , Humanos , Masculino , Contagem de Plaquetas , Estudos Retrospectivos , Ticlopidina/administração & dosagem , Fatores de TempoAssuntos
Displasia Fibromuscular/diagnóstico , Infarto/patologia , Nefropatias/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Displasia Fibromuscular/patologia , Seguimentos , Humanos , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Angiografia por Ressonância Magnética , Radiografia , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: Numerous reports in the literature refer to the femoral neck fracture rate in hip resurfacing. The aim of this study was to determine the bone mineral density and evidence of stress shielding around the femoral component of the Birmingham resurfacing prosthesis. MATERIAL AND METHODS: Twenty-eight patients with primary unilateral osteoarthritis had a Birmingham resurfacing prosthesis. DEXA analysis of the proximal femur and femoral neck was performed and compared with the opposite unaffected side. RESULTS: Total periprosthetic bone mineral density was 0.49% greater than the control, but this did not achieve statistical significance. Although the BMD of the femoral neck was slightly increased on the prosthetic side (1.002 g/cm2) as opposed to the control side, this difference did not reach statistical significance. CONCLUSION: The Birmingham resurfacing prosthesis does not appear to reduce femoral neck bone mineral density in comparison to the normal femoral neck bone density. We conclude that femoral neck fractures are unlikely to be due to stress shielding related to the prosthesis.
Assuntos
Absorciometria de Fóton , Artroplastia de Quadril/instrumentação , Densidade Óssea , Prótese de Quadril , Procedimentos Ortopédicos/instrumentação , Cabeça do Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia , Estresse MecânicoRESUMO
Soy isoflavones display estrogenic activity in humans and animals, and thus are referred to as phytoestrogens. This study was performed to observe the effects of the soy isoflavones genistein, daidzein, and glycitein on cell cultures of rat skeletal muscles. [3H]Thymidine incorporation was used to determine cell proliferation, while protein synthesis and degradation were determined by tracking radiolabeled leucine. For the proliferation studies, insulin, estradiol, genistein, daidzein, or glycitein was supplemented at 0, 0.04, 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, or 20 microM, respectively, or in combinations with final concentrations of 0, 0.1, 1, or 10 microM. Genistein reacted most similarly to estradiol, inhibiting proliferation at > or = 1 microM (P < .001). A combination of phytoestrogens resulted in significant inhibition of cell proliferation, but not to the extent observed with genistein alone. For the protein synthesis and degradation experiments, treatments of 0.1 microM dexamethasone or 1 microM concentrations of insulin, genistein, daidzein, or glycitein were used. Phytoestrogens did not inhibit or stimulate protein degradation or synthesis (P > .05). A one-tailed univariate analysis of variance revealed a trend (P < or = .1) in protein stimulation with genistein and glycitein treatments. These results suggest that the tyrosine kinase inhibiting activity of genistein may be affecting phosphorylation of the mitosis-promoting factor, preventing the advancement of the mitotic cell cycle. In addition, at higher total combined concentrations, daidzein and glycitein may be able to outcompete genistein for receptor sites. These results suggest that soy isoflavones in the diet may potentially modulate normal growth and development in humans and animals that ingest soy-based products.
Assuntos
Glycine max/química , Músculo Esquelético/efeitos dos fármacos , Fitoestrógenos/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Estradiol/farmacologia , Genisteína/farmacologia , Insulina/farmacologia , Isoflavonas/farmacologia , Proteínas Musculares/biossíntese , Proteínas Musculares/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Fosforilação , RatosRESUMO
OBJECTIVES: This study aimed to evaluate the necessity for further radiological investigation in patients with suspected traumatic rotatory subluxation of the atlanto-axial complex on plain radiography following acute cervical trauma and outline guidelines for assessment of patients with atlanto-axial asymmetry on plain radiography. METHODS: A retrospective review of all patients who had undergone atlanto-axial CT scanning as a result of radiographic C1-C2 asymmetry following cervical spine trauma. The plain x ray and CT images were reviewed retrospectively and correlated with the clinical presentation and outcome. RESULTS AND CONCLUSION: Records of 29 patients (16 men, 13 women; age range 21-44 years) were reviewed. All patients were found to have atlanto-odontoid asymmetry on the initial plain x ray. CT images of none of the patients revealed rotatory subluxation. Ten patients (32%) were found to have congenital odontoid lateral mass asymmetry. All patients were treated conservatively without any further intervention. On review, in 19 patients the orientation of the x ray beam in combination with head rotation was found to be at fault. Approximately 1050 trauma cervical spine x rays were taken in the department where this study was conducted over the period 1999-2001. This study identified 10 patients out of a total of 29 as having congenital odontoid lateral mass asymmetry. This represents approximately 1% of the patients attending the emergency department. Thus congenital odontoid lateral mass asymmetry should be considered in the differential diagnosis following acute cervical trauma.
Assuntos
Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/lesões , Processo Odontoide/lesões , Procedimentos Desnecessários , Adulto , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Processo Odontoide/anormalidades , Processo Odontoide/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Torcicolo/diagnóstico por imagem , Torcicolo/etiologiaRESUMO
Primary total hip replacement (THR) surgery is the most commonly performed and successful reconstructive procedure in orthopaedic surgery. We performed a survey of Irish Orthopaedic consultants to elucidate current practices of primary THR in elderly and young patients and identify changing trends. There was an 83% response rate. Most respondents use a cemented THR in elderly patients. 69% use a different THR in younger patients compared to older patients. 9% refer younger patients to hip replacement specialist consultant colleagues. 70% report changing to a new implant or new technique in younger patients and 45% use a hybrid THR, 15% an uncemented THR, 15% perform hip resurfacing and 47% use different bearing surfaces. Only 17% use the Charnley hip prosthesis in younger patients. Young and active patients will place high demands on a new THR and newer techniques, implants and bearing surfaces are being adopted in the hope of better outcomes.
Assuntos
Artroplastia de Quadril/tendências , Padrões de Prática Médica/estatística & dados numéricos , Atitude do Pessoal de Saúde , Prótese de Quadril/tendências , Humanos , Irlanda , Inquéritos e QuestionáriosRESUMO
PURPOSE: To analyse the characteristics of patients who underwent surgery for fractures of the upper thoracic spine (T1-T6) in our institution. The thoracic spine is supported by the rib cage and associated ligaments; therefore, displacement and fracture of the upper thoracic spine in healthy young adults require a great force. The relatively narrow spinal canal around the spinal cord in this area could result in severe neurological deficit should fractures occur. METHODS: The treatment course of 32 patients (26 men and 6 women) who underwent surgery for fractures of the upper thoracic spine between February 1995 and March 2001 was retrospectively reviewed. Parameters of injuries and treatment methods were evaluated. RESULTS: Of the 32 patients, 29 were injured in traffic accidents (15 motorcycle and 14 vehicle), 2 in falls, and one by a heavy door falling on his back. 29 patients had spinal fractures at more than one level. 23 patients had complete, 7 had incomplete, and 2 had no neurological deficit. 30 patients required multiple modalities of radiological imaging (in addition to plain radiography) for diagnosis. 20 patients sustained other injuries apart from spinal fractures, 15 of them had associated chest injuries. CONCLUSION: High-velocity fractures of the upper thoracic spine are injuries with devastating consequences, and can result in severe neurological deficit and concomitant injuries. These patients are best treated by a multidisciplinary approach.
Assuntos
Equipe de Assistência ao Paciente , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Procedimentos Ortopédicos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Ferimentos não Penetrantes/complicaçõesRESUMO
The development of malignant lesions in the acetabulum can lead to painful and disabling bone destruction. Lytic metastases of the acetabulum are frequent, causing pathologic fractures, pain and disability. The literature is sparse in relation to the exact indications and technique for this procedure. Percutaneous injection of methylmethacrylate or ethanol may provide marked pain relief or bone strengthening in patients, with malignant acetabular destruction, who are unable to tolerate surgery. Injection of methylmethacrylate is usually indicated when the weight-bearing part of the acetabulum is involved. The goals of treatment are pain relief and mechanical strengthening of the acetabulum. Radiography and computed tomography must be performed prior to therapeutic percutaneous injection to assess the location and extent of the lytic process, the presence of cortical destruction or fracture, and the presence of soft-tissue involvement. We report a case of a 39-year-old woman with a secondary acetabular lesion, which was treated successfully with percutaneous acetabular cementoplasty. We describe a novel technique used to inject cement into the lesion, allowing for greater cement volume and pressurisation within the lesion.
Assuntos
Cimentos Ósseos/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Articulação do Quadril/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/patologia , Acetábulo/diagnóstico por imagem , Acetábulo/patologia , Adulto , Feminino , Articulação do Quadril/patologia , Humanos , Injeções Intralesionais , Procedimentos Ortopédicos/métodos , Medição da Dor , Cuidados Paliativos/métodos , Prognóstico , Cintilografia , Medição de Risco , Suporte de CargaRESUMO
In vivo priming of CD8(+) T lymphocytes against exogenously processed model Ags requires CD4(+) T cell help, specifically interactions between CD40 ligand (CD40L) expressed by activated CD4(+) T cells and CD40, which is present on professional APC such as dendritic cells (DCs). To address this issue in the context of bacterial infection, we examined CD40L-CD40 interactions in CD8(+) T cell priming against an exogenously processed, nonsecreted bacterial Ag. CD40L interactions were blocked by in vivo treatment with anti-CD40L mAb MR-1, which inhibited germinal center formation and CD8(+) T cell cross-priming against an exogenous model Ag, OVA. In contrast, MR-1 treatment did not interfere with CD8(+) T cell priming against a nonsecreted or secreted recombinant Ag expressed by Listeria monocytogenes. Memory and secondary responses of CD8(+) T cells against nonsecreted and secreted bacterial Ags were also largely unimpaired by transient MR-1 treatment. When MR-1-treated mice were concurrently immunized with L. monocytogenes and OVA-loaded splenocytes, cross-priming of OVA-specific naive CD8(+) T cells occurred. No significant decline in cross-priming against OVA was measured when either TNF or IFN-gamma was neutralized in L. monocytogenes-infected animals, demonstrating that multiple signals exist to overcome CD40L blockade of CD8(+) T cell cross-priming during bacterial infection. These data support a model in which DCs can be stimulated in vivo through signals other than CD40, becoming APC that can effectively stimulate CD8(+) T cell responses against exogenous Ags during infection.
Assuntos
Apresentação de Antígeno , Ligante de CD40/fisiologia , Linfócitos T CD8-Positivos/imunologia , Listeriose/imunologia , Animais , Anticorpos/farmacologia , Antígenos de Bactérias/imunologia , Ligante de CD40/imunologia , Linhagem Celular , Células Cultivadas , Feminino , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interferon gama/fisiologia , Listeria monocytogenes/genética , Listeria monocytogenes/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Proteínas Recombinantes/imunologia , Baço/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Endocarditis is a recognised complication ofhemodialysis. This is generally only thought of in terms of infective vegetations. We present a case of right-sided NBTE in a patient with an indwelling venous catheter who also had advanced pelvic malignancy. The unusual side of this patient's endocarditic lesions implicates a role for the venous catheter in determining the site of non-bacterial thrombus formation. It is also a reminder that endocarditis is always a risk when using central venous catheters, even after appropriate sterile precautions have been taken.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Endocardite/etiologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Pélvicas/complicações , Diálise Renal , Neoplasias das Glândulas Sebáceas/complicações , Trombose/etiologia , Adulto , Cateteres de Demora , Endocardite/diagnóstico , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Neoplasias Pélvicas/genética , Neoplasias das Glândulas Sebáceas/genética , SíndromeRESUMO
Based on recent advances in techniques that can detect and enumerate antigen-specific CD8+ T cells, it is evident that these cells can differentially regulate CD8+ T cell effector mechanisms at the single-cell level. Interplay between effector mechanisms that are employed by antigen-specific CD8+ T cells during the immune response in vivo can be addressed with different techniques that "count" cells either directly (T cell receptor (TCR) expression) or indirectly (antigen-specific cytokine production).
Assuntos
Linfócitos T CD8-Positivos/imunologia , Animais , Antígenos/metabolismo , Citocinas/biossíntese , Citotoxicidade Imunológica , Humanos , Técnicas Imunológicas , Técnicas In Vitro , Interferon gama/biossíntese , Contagem de Leucócitos , Camundongos , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Although they are known for their capacity to kill infected cells, Ag-specific CD8(+) T cells elaborate other effector mechanisms, including TNF and IFN-gamma, that contribute to defense against infection. Ag-specific CD8(+) T cells rapidly turn ON and turn OFF IFN-gamma production in direct response to Ag contact, presumably to minimize the potential immunopathology that could result from inappropriate secretion of this inflammatory mediator. In this study, we show, using in vitro propagated and directly ex vivo-analyzed Ag-specific CD8(+) T cells, that in contrast to Ag-dependent ON/OFF cycling of IFN-gamma production, the cessation of TNF production by the same IFN-gamma producing cells is rapid and Ag independent.
Assuntos
Antígenos T-Independentes/fisiologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Epitopos de Linfócito T/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Linhagem Celular , Imunidade Celular , Interferon gama/biossíntese , Cinética , Listeriose/imunologia , Coriomeningite Linfocítica/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Tumorais CultivadasRESUMO
Tumor necrosis factor (TNF) and the type I TNF receptor (TNFRI), p55, are critical for resistance against primary infections with the intracellular bacterial pathogen Listeria monocytogenes. Importantly, however, susceptibility to primary listeriosis in cytokine-deficient mice does not preclude the development or expression of effective adaptive immunity against virulent L. monocytogenes. We used TNFRI(-/-) mice to study adaptive antilisterial immunity in the absence of interactions between TNF and TNFRI. Our experiments indicate that TNFRI(-/-) mice survive and clear high-dose challenges with an attenuated strain of L. monocytogenes that is incapable of cell-to-cell spread. Furthermore, TNFRI(-/-) mice immunized with attenuated L. monocytogenes go on to develop potent adaptive immunity to subsequent high-dose challenges with virulent L. monocytogenes. Interestingly, CD8(+) T-cell depletion in vivo inhibits immunity to L. monocytogenes in the spleen but not in the liver of TNFRI(-/-) mice. The adaptive immune response in these animals is characterized by activation of listeriolysin O-specific CD8(+) T cells, which are capable of transferring antilisterial immunity to naive wild-type C57BL/6 host mice. These experiments demonstrate the development and expression of potent CD8(+) T-cell-mediated antilisterial immunity in the absence of TNFRI.
Assuntos
Adaptação Biológica , Antígenos CD/genética , Toxinas Bacterianas , Listeriose/imunologia , Receptores do Fator de Necrose Tumoral/genética , Vacinação , Transferência Adotiva , Animais , Vacinas Bacterianas , Linfócitos T CD8-Positivos/imunologia , Proteínas de Choque Térmico/imunologia , Proteínas Hemolisinas , Imunidade Celular , Listeriose/mortalidade , Fígado/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Receptores Tipo I de Fatores de Necrose Tumoral , Baço/imunologiaRESUMO
The mechanisms by which CD8+ T cells mediate immunity against bacterial pathogens remain largely unknown. Perforin-dependent cytolysis plays a role, but is not required for CD8+ T cell-mediated immunity against Listeria monocytogenes. TNF is essential for CD8+ T cell immunity to L. monocytogenes, but the cellular source of TNF is undefined. TNF-deficient and TNF/perforin double-deficient mice were used to generate CD8+ T cells specific for an L. monocytogenes-derived Ag. Wild-type and TNF-deficient CD8+ T cells mediated antilisterial immunity in wild-type but not TNF-deficient host mice, revealing that CD8+ T cell-derived TNF is not required for CD8+ T cell-mediated antilisterial immunity, but demonstrating a role for TNF derived from other cell types. TNF/perforin double-deficient CD8+ T cells mediated antilisterial immunity in the liver, but not in the spleen, of wild-type recipient mice, suggesting that perforin-independent immunity in the spleen requires CD8+ T cell-derived TNF.