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1.
Musculoskelet Surg ; 108(1): 11-20, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987959

RESUMO

A differential diagnosis with emphasis on the common indications for revision should be utilized in the workup of painful total knee arthroplasty (TKA). The physician should identify the exact etiology of the patient's pain to maximize outcomes from treatment. Evaluation for infection should be completed using the Musculoskeletal Infection Society (MSIS) criteria. When common causes of revision TKA do not appear to be the cause of the pain, less likely causes should be not be ignored. Further advancements such as pressure sensing devices may be able to improve patient satisfaction and decrease the incidence of pain following TKA.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Reoperação , Dor , Satisfação do Paciente , Diagnóstico Diferencial , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
2.
Eur J Orthop Surg Traumatol ; 33(2): 381-384, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35024951

RESUMO

BACKGROUND: Femoral intramedullary nailing is traditionally performed with the patient supine on a fracture table. We aimed to describe a case series of femoral intramedullary nailing for fracture in the lateral position, with discussion of the operative technique. METHODS: A retrospective analysis identified 52 patients who underwent femoral intramedullary nailing performed in a lateral position without traction over a 5-year period at a single level 1 trauma center. Medical records were reviewed for demographics, blood loss including need for transfusion, operative duration, complications, length of stay, fracture union, re-operation and death. RESULTS: There were 24 subtrochanteric, 16 peri-trochanteric and 12 diaphyseal femoral fractures. Mean operative time was 136.2 ± 101.4 min with a mean estimated blood loss of 372.5 ± 349.6 ml. Seventeen patients required blood transfusion. Mean length of stay was 10.3 ± 8.1 days. There were 3 (5.8%) surgical (compartment syndrome, infection and retained drain) and 12 (23.1%) medical complications, with a 30-day mortality rate of 3.8% (2). Mean follow-up was 9.9 ± 8.7 months. The union rate was 94.2% (49) and 3.8% (2) patients required revision fixation (hardware exchange for irritation and exchange nailing for non-union). Discharge destination was home, rehabilitation center and specialized nursing facility in 21 (40.4%), 16 (30.8%) and 15 (28.8%) patients, respectively. DISCUSSION AND CONCLUSION: Femoral intramedullary nailing in the lateral decubitus position is a useful technique of managing peri-trochanteric, subtrochanteric and diaphyseal femoral fractures. We describe a known technique with technical tips, which has distinct advantages over traditional supine positioning especially in certain patient and fracture types. In addition, operative times, blood loss, length of stay, revision and outcomes were comparable to the literature.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Humanos , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Estudos Retrospectivos , Fêmur , Fraturas do Fêmur/cirurgia , Tração , Resultado do Tratamento , Pinos Ortopédicos
3.
Eur J Orthop Surg Traumatol ; 31(4): 791-795, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33211232

RESUMO

INTRODUCTION: Femoral head fractures with associated acetabular fractures are uncommon injuries usually resulting from high-energy mechanisms such as motor vehicle collisions. Outcomes of Pipkin type IV fractures have been historically poor, with high rates of osteonecrosis, post-traumatic arthritis, and heterotopic ossification. The objective of this study was to define the outcomes of operatively treated Pipkin type IV fractures In addition, we reviewed the available literature of this uncommon injury pattern. METHODS: A retrospective chart review at a single level 1 trauma center from 2007 to 2016 identified 10 patients with Pipkin IV femoral head fractures. Demographic information, fracture type, associated injuries, operative details, and complications were evaluated. Clinical and radiological outcomes were assessed at latest follow-up including conversion to total hip arthroplasty. RESULTS: Six of the seven patients were treated with open reduction and internal fixation of the femoral head fracture and acetabular fracture through a Kocher-Langenbeck approach aided by a trochanteric flip and one had fragment excision. Six patients (87.5%) developed post-traumatic arthritis. Four (57.1%) later underwent conversion to total hip arthroplasty (THA) a mean of 20.5 months after index procedure. CONCLUSION: Our study shows a rate of osteonecrosis and osteoarthritis that is even higher than the previously reported studies. The former may relate to longer-term follow-up and the latter possibly due to associated comminuted posterior wall fracture.


Assuntos
Fraturas do Fêmur , Fraturas do Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Fixação Interna de Fraturas , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
Bone Joint Res ; 5(10): 470-480, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27756738

RESUMO

OBJECTIVES: The objective of this study was to perform a meta-analysis of all randomised controlled trials (RCTs) comparing surgical and non-surgical management of fractures of the proximal humerus, and to determine whether further analyses based on complexity of fracture, or the type of surgical intervention, produced disparate findings on patient outcomes. METHODS: A systematic review of the literature was performed identifying all RCTs that compared surgical and non-surgical management of fractures of the proximal humerus. Meta-analysis of clinical outcomes was performed where possible. Subgroup analysis based on the type of fracture, and a sensitivity analysis based on the type of surgical intervention, were also performed. RESULTS: Seven studies including 528 patients were included. The overall meta-analysis found that there was no difference in clinical outcomes. However, subgroup and sensitivity analyses found improved patient outcomes for more complex fractures managed surgically. Four-part fractures that underwent surgery had improved long-term health utility scores (mean difference, MD 95% CI 0.04 to 0.28; p = 0.007). They were also less likely to result in osteoarthritis, osteonecrosis and non/malunion (OR 7.38, 95% CI 1.97 to 27.60; p = 0.003). Another significant subgroup finding was that secondary surgery was more common for patients that underwent internal fixation compared with conservative management within the studies with predominantly three-part fractures (OR 0.15, 95% CI 0.04 to 0.63; p = 0.009). CONCLUSION: This meta-analysis has demonstrated that differences in the type of fracture and surgical treatment result in outcomes that are distinct from those generated from analysis of all types of fracture and surgical treatments grouped together. This has important implications for clinical decision making and should highlight the need for future trials to adopt more specific inclusion criteria.Cite this article: S. Sabharwal, N. K. Patel, D. Griffiths, T. Athanasiou, C. M. Gupte, P. Reilly. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus: Findings of a meta-analysisBone Joint Res 2016;5:470-480. DOI: 10.1302/2046-3758.510.2000638.

5.
J Oncol Pharm Pract ; 22(2): 303-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25567517

RESUMO

Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum ß-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant organism. However, prompt de-escalation of carbapenem therapy needs to be reiterated within hospital practice.


Assuntos
Bacteriemia/etiologia , Cefalosporinas/efeitos adversos , Fluoroquinolonas/administração & dosagem , Leucemia/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Profilaxia Pós-Exposição/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Cefepima , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Distribuição Aleatória , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
6.
Knee ; 22(4): 286-91, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26006772

RESUMO

BACKGROUND: There has been a significant rise in the number and value of claims against the National Health Service (NHS), with limited studies on litigation in orthopaedic surgery and none in knee surgery alone. We aimed to examine claims against the NHS involving all aspects of knee surgery with respect to costs and trends. CLINICAL RELEVANCE: To raise awareness of the reasons for litigation in knee surgery, thus potentially improve patient care and reduce future claims. METHODS: We analysed the NHS litigation authority (NHSLA) database for all orthopaedic surgery claims reported to the NHSLA between 2005 and 2010, with calculation of litigation success rates and odds ratios for those relating to knee surgery. RESULTS: There were 515 cases identified from the 4609 orthopaedic cases in the NHSLA database (11.2%): 298 (58%) involving total knee replacements (TKRs), 11 (2%) involving unicondylar knee replacements, and 90 cases (30%) remaining open. The total pay out for closed cases was £10.45 million and amputation following TKR resulted in the highest single pay out. Litigation success rates for claimants were highest for retained drains (100%), incorrect prosthesis/prosthesis size (78%), renal failure (75%), poor outcome requiring further surgery (74%) and malalignment (71%). There were also 60 cases of delayed diagnosis which resulted in pay outs totalling £2.90 million. Based on these data, projected future pay out costs for the open TKR cases were estimated to be £2.71 million. CONCLUSION: Litigation success rates for TKR were highest following technical errors such as malalignment compared to events less under the surgeon's control, such as infection. The number of claims involving incorrect prosthesis/size continues to be of concern. Despite the increased availability of imaging modalities, missed diagnosis also resulted in substantial pay outs.


Assuntos
Artroplastia do Joelho/legislação & jurisprudência , Responsabilidade Legal/economia , Imperícia/legislação & jurisprudência , Ortopedia/legislação & jurisprudência , Artroplastia do Joelho/economia , Custos e Análise de Custo , Humanos , Imperícia/economia , Ortopedia/economia , Medicina Estatal , Reino Unido
7.
Ann R Coll Surg Engl ; 96(1): 67-72, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24417834

RESUMO

INTRODUCTION: Few studies have reported the outcome of hip resurfacing arthroplasty (HRA) with respect to implant characteristics from non-specialist centres. We report the survival, clinical and radiological outcomes of a single surgeon series of HRA with an average follow-up duration of five years. METHODS: All consecutive HRAs performed by a single surgeon between 2003 and 2011 at a district general hospital were retrospectively examined clinically and radiologically. RESULTS: A total of 85 patients underwent 109 HRAs (58 male [53.2%] and 51 female patients [46.8%]) with a mean follow-up period of 62 months (range: 12-102 months). The median age was 57 years (range: 25-75 years). The mean acetabular and femoral head component sizes were 54 mm (range: 48-64 mm) and 48 mm (range: 42-58 mm) respectively with a mean acetabular inclination angle of 42.9° (range: 20-75°). The survival rate was 95% with five revisions due to aseptic loosening (n=3) and fracture (n=2): these were predominantly for female patients (n=4), with significantly smaller mean acetabular (51 mm, p=0.04) and femoral (44 mm, p=0.02) implant sizes. Furthermore, they had a higher mean acetabular inclination angle of 48.1° (p=0.74). The mean Oxford hip score was 43.8 (range: 25-48) and the mean University of California Los Angeles (UCLA) activity score was 6.8 (range: 3-10). Radiological findings included heterotopic ossification in 13 (11.9%), radiolucent lines in 6 (5.5%), femoral neck thinning in 2 (1.8%) and femoral neck notching in 5 patients (4.6%). CONCLUSIONS: We have shown that HRA at a non-specialist centre has short to medium-term outcomes comparable with those at specialist centres. HRA therefore remains a viable option although vigilance is required in case selection and follow-up according to national guidance.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Próteses Articulares Metal-Metal , Acetábulo , Adulto , Idoso , Artrite Reumatoide/cirurgia , Feminino , Luxação Congênita de Quadril/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/etiologia , Osteoartrite do Quadril/cirurgia , Cuidados Pós-Operatórios , Falha de Prótese , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
8.
Musculoskelet Surg ; 98(1): 81-3, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22684539

RESUMO

We present a case of chronic posterior hip dislocation after severe joint destruction following septic arthritis. In the absence of trauma, infection must be considered in the differential diagnosis of a dislocated joint particularly in patients with risk factors such as intravenous drug abuse and immune compromise. Excision arthroplasty of the hip was performed with good pain relief and functional outcomes. This is an excellent temporary or permanent solution in managing such complex cases although alternative management options are discussed.


Assuntos
Artrite Infecciosa/complicações , Luxação do Quadril/etiologia , Articulação do Quadril , Infecções Estafilocócicas/complicações , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Artroplastia , Ceftriaxona/uso terapêutico , Clindamicina/uso terapêutico , Desbridamento , Floxacilina/uso terapêutico , Dependência de Heroína/complicações , Dependência de Heroína/reabilitação , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Osteomielite/tratamento farmacológico , Osteomielite/etiologia , Radiografia , Infecções Estafilocócicas/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/reabilitação
9.
Musculoskelet Surg ; 97(1): 9-20, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23546858

RESUMO

The Achilles tendon (AT) is the most frequently ruptured tendon in the human body yet the aetiology remains poorly understood. Despite the extensively published literature, controversy still surrounds the optimum treatment of complete rupture. Both non-operative management and percutaneous repair are attractive alternatives to open surgery, which carries the highest complication and cost profile. However, the lack of a universally accepted scoring system has limited any evaluation of treatment options. A typical UK district general hospital treats approximately 3 cases of AT rupture a month. It is therefore important for orthopaedic surgeons to correctly diagnose and treat these injuries with respect to the best current evidence-based practice. In this review article, we discuss the relevant pathophysiology and diagnosis of the ruptured AT and summarize the current evidence for treatment.


Assuntos
Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/patologia , Tendão do Calcâneo/fisiopatologia , Medicina Baseada em Evidências , Humanos , Equipamentos Ortopédicos , Procedimentos Ortopédicos , Fatores de Risco , Ruptura/cirurgia , Resultado do Tratamento
11.
Palliat Med ; 22(5): 668-70, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18612034

RESUMO

We report the displacement of a tunnelled intrathecal catheter causing significant cerebrospinal fluid (CSF) leak, resulting in partial coning and a sixth nerve palsy. The patient had advanced malignant mesothelioma and all other methods of pain control had been unsuccessful. As far as we are aware, there are no published reports of early replacement of an intrathecal catheter in patients with neurological sequelae. Surgical re-siting of the intrathecal catheter produced good pain relief for many months. Doctors involved in the use of indwelling intrathecal catheters for pain control must be aware of the risk of significant neurological sequelae but should not dismiss re-establishment of intrathecal therapy in the presence of significant neurological complications.


Assuntos
Analgesia , Cateteres de Demora/efeitos adversos , Falha de Equipamento , Doenças do Nervo Abducente/etiologia , Líquido Cefalorraquidiano , Humanos , Bombas de Infusão Implantáveis , Masculino , Mesotelioma/complicações , Pessoa de Meia-Idade , Dor Intratável/tratamento farmacológico , Neoplasias Peritoneais/complicações
13.
J Laryngol Otol ; 121(1): 28-30, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17040601

RESUMO

This paper describes a new application for radiofrequency ablation in head and neck surgery. Two patients with extensive laryngeal papillomata were successfully treated using this technology. The technique is described in detail, highlighting the main benefits of this approach as compared with existing techniques. These advantages include limited damage to underlying tissues and a bloodless field.


Assuntos
Ablação por Cateter/métodos , Neoplasias Laríngeas/cirurgia , Papiloma/cirurgia , Adulto , Feminino , Humanos , Masculino , Resultado do Tratamento
14.
Br J Neurosurg ; 19(6): 463-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16574557

RESUMO

The role of trigeminal ganglion percutaneous injection and radio-frequency lesioning procedures for the treatment of trigeminal neuralgia (TGN) in multiple sclerosis (MS) is well established. There is general acceptance that microvascular decompression (MVD) cannot be an appropriate treatment due to the view that the underlying aetiology is a demyelinating plaque affecting the root entry zone of the trigeminal pathway. Recently, MR-imaging has been used in the preoperative investigation of this group of patients demonstrating that neurovascular compression can occasionally be the responsible mechanism and that MVD can be the treatment of choice. We present five cases with MS and TGN. All the patients had failed to respond to medical treatment or percutaneous procedures. Magnetic resonance imaging demonstrated evidence of neurovascular compression in four cases. All the patients underwent MVD. Postoperatively four of the five patients made an uncomplicated recovery, were pain-free and fully satisfied with the result (mean follow-up 38.75 months; range 8-59 months). One patient developed recurrent pain 1 week following surgery and went on to have a total sensory rhizotomy. TGN in MS can be caused by neurovascular compression, which may be identified on MR-imaging. MVD has offered satisfactory short-term outcome for at least 2 years and does not inflict sensory loss. Longer follow-up will determine whether the outcome in MS patients will be as successful as in the TGN patients who do not suffer from MS.


Assuntos
Descompressão Cirúrgica/métodos , Esclerose Múltipla/complicações , Neuralgia do Trigêmeo/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/complicações , Síndromes de Compressão Nervosa/cirurgia , Resultado do Tratamento , Neuralgia do Trigêmeo/etiologia
15.
Br J Neurosurg ; 17(1): 60-4, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12779203

RESUMO

Ninety-two patients with trigeminal neuralgia (TGN) were investigated prior to posterior fossa surgery with magnetic resonance imaging (MRI) and contrast-enhanced magnetic resonance angiography (MRA). The preoperative investigation was matched to one consultant neuroradiologist (co-author) who was blinded to the side of symptomotology. The imaging results were compared with the operative findings in all patients. In 76 patients MRA showed present neurovascular compression in accordance with surgical findings. Eight cases had no compression either on MRA or intraoperatively. Eight predictions of no compression were false and there was no false positive. Based on surgical findings, the sensitivity of MRA was 90.5% and the specificity 100%. In 19 cases MRA predicted bilateral compression of the trigeminal nerves. Only two cases had clinically bilateral TGN. We conclude that MRA with gadolinium enhancement is an extremely sensitive and specific method for demonstrating compression in TGN. As a result posterior fossa surgery can be recommended with confidence, and microvascular decompression remains the treatment of choice for TGN at the authors' centre.


Assuntos
Angiografia por Ressonância Magnética/métodos , Síndromes de Compressão Nervosa/complicações , Neuralgia do Trigêmeo/etiologia , Meios de Contraste , Descompressão Cirúrgica/métodos , Gadolínio , Humanos , Síndromes de Compressão Nervosa/diagnóstico , Procedimentos Neurocirúrgicos/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Método Simples-Cego , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/cirurgia
16.
Histopathology ; 41(1): 50-5, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12121237

RESUMO

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.


Assuntos
Colite Ulcerativa/patologia , Doença de Crohn/patologia , Granuloma/patologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Colite Ulcerativa/metabolismo , Colo/citologia , Doença de Crohn/metabolismo , Diagnóstico Diferencial , Células Gigantes/metabolismo , Células Gigantes/patologia , Granuloma/metabolismo , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Macrófagos/metabolismo , Macrófagos/patologia
17.
Infect Immun ; 69(8): 4799-807, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11447153

RESUMO

Decorin binding protein A (DbpA) has been shown by several laboratories to be a protective antigen for the prevention of experimental Borrelia burgdorferi infection in the mouse model of Lyme borreliosis. However, different recombinant forms of the antigen having either lipidated amino termini, approximating the natural secretion and posttranslational processing, or nonprocessed cytosolic forms have elicited disparate levels of protection in the mouse model. We have now used the unique functional properties of this molecule to investigate the structural requirements needed to elicit a protective immune response. Genetic and physicochemical alterations to DbpA showed that the ability to bind to the ligand decorin is indicative of a potent immunogen but is not conclusive. By mutating the two carboxy-terminal nonconserved cysteines of DbpA from B. burgdorferi strain N40, we have determined that the stability afforded by the putative disulfide bond is essential for the generation of protective antibodies. This mutated protein was more sensitive to thermal denaturation and proteolysis, suggesting that it is in a less ordered state. Immunization with DbpA that was thermally denatured and functionally inactivated stimulated an immune response that was not protective and lacked bactericidal antibodies. Antibodies against conformationally altered forms of DbpA also failed to kill heterologous B. garinii and B. afzelii strains. Additionally, nonsecreted recombinant forms of DbpA(N40) were found to be inferior to secreted lipoprotein DbpA(N40) in terms of functional activity and antigenic potency. These data suggest that elicitation of a bactericidal and protective immune response to DbpA requires a properly folded conformation for the production of functional antibodies.


Assuntos
Adesinas Bacterianas , Anticorpos Antibacterianos/biossíntese , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias , Grupo Borrelia Burgdorferi/imunologia , Proteínas de Transporte/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Reações Cruzadas , Modelos Animais de Doenças , Feminino , Doença de Lyme/prevenção & controle , Vacinas contra Doença de Lyme/imunologia , Camundongos , Camundongos Endogâmicos C3H , Dados de Sequência Molecular , Conformação Proteica , Vacinação , Vacinas Sintéticas/imunologia
18.
Am J Pathol ; 157(4): 1219-27, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11021826

RESUMO

The urokinase-type plasminogen activator (uPA) system has been implicated in tumor spread. We have used immunohistochemistry to examine three components of this system, ie, uPA, uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in a pilot study on 142 cases of breast carcinoma. We wished to determine whether there were any relationships between expression of the proteins in either tumor cells or fibroblasts and clinical and pathological features. Strong uPA expression in each cell type was significantly related to high tumor grade (P = 0.013 and 0.008, respectively), and was more common in invasive than in in situ carcinomas (P < 0.0001). Fibroblastic expression of uPAR was only related to the presence of invasion (P < 0.0001). Strong PAI-1 expression in both cell types was seen in high-grade tumors (tumor cells, P = 0.012; fibroblasts, P < 0.001), but only fibroblastic expression was related to the presence of invasion (P = 0.042). Fibroblastic expression of both uPA and uPAR were positively correlated with tumor size. Although patients with strong fibroblastic expression of uPA showed a tendency toward a shorter time to relapse, none of the plasminogen activator proteins were significantly associated with relapse-free survival. These results suggest that strong expression of uPA, uPAR, and PAI-1 in fibroblasts rather than in tumor cells have the most impact on the clinical behavior of breast cancer. Larger prospective studies are needed to confirm these findings.


Assuntos
Neoplasias da Mama/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Receptores de Superfície Celular/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/metabolismo , Doenças Mamárias/metabolismo , Neoplasias da Mama/patologia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfonodos/patologia , Pessoa de Meia-Idade , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Valores de Referência , Coloração e Rotulagem , Análise de Sobrevida
19.
Cancer ; 86(10): 2053-8, 1999 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-10570431

RESUMO

BACKGROUND: Premenopausal breast carcinoma patients who undergo tumor excision during the follicular phase of their menstrual cycle may have a significantly worse prognosis than those whose tumors are excised in other phases of the menstrual cycle. METHODS: Outcome was determined in a series of 112 premenopausal women with operable breast carcinoma in relation to the timing of surgery within the menstrual cycle and the estrogen receptor (ER) and progesterone receptor (PR) status of their primary tumors as determined by immunohistochemistry. RESULTS: Those patients with ER positive tumors who underwent surgery in the early and luteal phase of the cycle had a significantly better survival than women with ER negative tumors (chi-square test = 15.56; P < 0.001). This also was true for PR status (chi-square test = 18.21; P < 0.001). After follicular phase surgery, tumor receptor status had no effect on overall survival. Patients with the best prognosis had ER/PR positive tumors excised on Days 0-2 and 13-32 but even those women with ER or PR negative tumors removed during the luteal phase of their menstrual cycle fared better than patients whose tumors were removed during the follicular phase. CONCLUSIONS: There was a better survival rate for patients with both ER/PR positive and negative tumors treated during the luteal phase of the menstrual cycle. This could be the result of progesterone acting on the surrounding peritumoral normal tissue, thereby exerting a straitjacket effect and improving cohesion of the primary carcinoma. Unopposed estrogen in the follicular phase of the cycle may enable more tumor emboli to escape and successfully establish micrometastases.


Assuntos
Neoplasias da Mama/cirurgia , Ciclo Menstrual/fisiologia , Pré-Menopausa , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Mama/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estudos Retrospectivos , Taxa de Sobrevida
20.
Am J Dermatopathol ; 20(6): 541-6, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9855348

RESUMO

Epithelioid hemangioendothelioma arising in the skin is extremely rare, and the majority of documented cases have developed in association with an underlying bone tumor. We report eight patients with an age range of 29-84 years (mean 53), who presented with primary cutaneous tumors at a variety of sites including the palm, shin, neck, knee, nose, back, and penis with a duration of between 6 and 12 months. Histologically, all eight cases presented as circumscribed nodules with an overlying acanthotic epidermis, three showing striking acrosyringeal proliferation, reminiscent of eccrine syringofibroadenoma. The tumors were composed of an admixture of slightly pleomorphic spindle and epithelioid cells with abundant, sharply defined eosinophilic cytoplasm and vesicular nuclei containing single nucleoli. Mitoses were generally sparse. All tumors showed intracytoplasmic lumina and intraluminal erythrocytes were occasionally apparent. The tumor cells were embedded in a myxoid or hyaline matrix. In contrast to visceral lesions, a vascular origin was not evident in any of our cases. The tumor cells variably expressed CD31, CD34, factor VIII-Rag, and smooth-muscle actin but not pankeratin or epithelial membrane antigen. Follow-up ranged from 4 months to 3 years. None of the lesions has thus far recurred and there have been no metastases.


Assuntos
Hemangioendotelioma Epitelioide/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Feminino , Hemangioendotelioma Epitelioide/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Pele/química , Pele/patologia , Neoplasias Cutâneas/metabolismo
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