Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
JACC Case Rep ; 25: 102028, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38094203

RESUMO

Patients with anomalous aortic arch undergoing transcatheter aortic valve implantation may require modifications to the deployment protocols of cerebral protection device systems. We share the first reported case, to our knowledge, of a cerebral protection device via the left radial artery and using a distal basket alone in a patient with truncus bicaroticus and arteria lusoria. (Level of Difficulty: Intermediate.).

2.
Artigo em Inglês | MEDLINE | ID: mdl-34473280

RESUMO

BACKGROUND: Vaporous hyperoxia therapy (VHT), a patented US Food and Drug Administration 510 (k)-cleared technology, is an adjunct therapy used in conjunction with standard wound care (SWC). Vaporous hyperoxia therapy is said to improve the health of wounded tissue by administering a low-frequency, noncontact, nonthermal, ionic, antimicrobial hydrating mist alternating with concentrated topical oxygen therapy. METHODS: Vaporous hyperoxia therapy was used to treat 36 subjects with chronic diabetic foot ulcers (DFUs) that were previously treated unsuccessfully with SWC. The average age of DFUs in the study was 11 months and the average size was over 3 cm2. Wounds were Wagner grade 2 or 3 and most commonly on the plantar surface around the midfoot. Treatment consisted of twice-weekly applications of VHT and wound debridement. Subjects were followed to wound closure, 20 weeks, or 40 treatments, whichever came first. RESULTS: The combination of SWC and VHT in the group that met and maintained compliance throughout the study period achieved an 83% DFU closure rate within a 20-week period. The average time for DFU closure in this study was 9.4 weeks. CONCLUSIONS: Historical analysis of SWC shows a 30.9% healing rate of all wounds, not differentiating chronic wounds. Accordingly, SWC/VHT increases chronic diabetic foot ulcer healing rates by 2.85 times compared with SWC alone. The purpose of this study was two-fold: first, to observe the effect of VHT on healing rates and time to healing in previously nonhealing DFUs; and second, to compare VHT with SWC, topical oxygen therapy, hyperbaric oxygen therapy, and ultrasound therapy.


Assuntos
Diabetes Mellitus , Pé Diabético , Úlcera do Pé , Hiperóxia , Humanos , Lactente , Pé Diabético/tratamento farmacológico , Cicatrização , Oxigênio/farmacologia , Oxigênio/uso terapêutico , Resultado do Tratamento
3.
BMJ Case Rep ; 15(3)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351764

RESUMO

Coronary sinus thrombosis is a rare phenomenon, most commonly occurring following invasive cardiac procedures. Spontaneous thrombosis is extremely rare and little is known about the natural history or optimal management. We present a case of coronary sinus thrombosis occurring in the context of myocardial infarction with concealed ventricular wall rupture.


Assuntos
Trombose Coronária , Ruptura Cardíaca Pós-Infarto , Infarto do Miocárdio , Trombose dos Seios Intracranianos , Trombose Coronária/complicações , Trombose Coronária/diagnóstico por imagem , Ruptura Cardíaca Pós-Infarto/complicações , Ruptura Cardíaca Pós-Infarto/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Infarto do Miocárdio/complicações , Trombose dos Seios Intracranianos/complicações
4.
Can J Cardiol ; 37(10): 1530-1538, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34126226

RESUMO

BACKGROUND: Using fractional flow reserve (FFR) to guide percutaneous coronary intervention for patients with coronary artery disease (CAD) improves clinical decision making but remains underused. Virtual FFR (vFFR), computed from angiographic images, permits physiologic assessment without a pressure wire and can be extended to virtual coronary intervention (VCI) to facilitate treatment planning. This study investigated the effect of adding vFFR and VCI to angiography in patient assessment and management. METHODS: Two cardiologists independently reviewed clinical data and angiograms of 50 patients undergoing invasive management of coronary syndromes, and their management plans were recorded. The vFFRs were computed and disclosed, and the cardiologists submitted revised plans. Then, using VCI, the physiologic results of various interventional strategies were shown and further revision was invited. RESULTS: Disclosure of vFFR led to a change in strategy in 27%. VCI led to a change in stent size in 48%. Disclosure of vFFR and VCI resulted in an increase in operator confidence in their decision. Twelve cases were reviewed by 6 additional cardiologists. There was limited agreement in the management plans between cardiologists based on either angiography (kappa = 0.31) or vFFR (kappa = 0.39). CONCLUSIONS: vFFR has the potential to alter decision making, and VCI can guide stent sizing. However, variability in management strategy remains considerable between operators, even when presented with the same anatomic and physiologic data.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Cateteres Cardíacos , Vasos Coronários/cirurgia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Laboratórios , Intervenção Coronária Percutânea/métodos , Terapia de Exposição à Realidade Virtual/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Tomada de Decisão Clínica , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
5.
Platelets ; 32(4): 555-559, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32543247

RESUMO

A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients.


Assuntos
Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Alcaloides Opiáceos/uso terapêutico , Intervenção Coronária Percutânea/métodos , Enoxaparina/farmacologia , Estudos de Viabilidade , Feminino , Fibrinolíticos/farmacologia , Humanos , Masculino , Alcaloides Opiáceos/farmacologia
6.
Circulation ; 138(13): 1290-1300, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-29930021

RESUMO

BACKGROUND: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. METHODS: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. RESULTS: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5-46.9) ng/L for clopidogrel, 22.4 (5.5-53.8) ng/L for T60, and 17.7 (8.1-43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09). CONCLUSIONS: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02327624.

7.
Thromb Haemost ; 118(7): 1250-1256, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29874689

RESUMO

Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y12 inhibition.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Trombose Coronária/prevenção & controle , Enoxaparina/administração & dosagem , Fibrinolíticos/administração & dosagem , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Analgésicos Opioides/administração & dosagem , Anticoagulantes/efeitos adversos , Trombose Coronária/sangue , Trombose Coronária/etiologia , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Inglaterra , Enoxaparina/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Projetos Piloto , Inibidores da Agregação Plaquetária/administração & dosagem , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Stents , Tromboelastografia , Fatores de Tempo , Resultado do Tratamento
8.
J Foot Ankle Surg ; 56(1): 112-116, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27600488

RESUMO

Marjolin's ulcer is a rare and aggressive cutaneous malignancy arising from previously traumatized skin, most commonly at the site of previous burns. We present a unique case of Marjolin's ulceration secondary to an orthopedic injury and a nonburn history of trauma. The patient had been involved in a motorcycle accident >20 years earlier. For 17 months, the patient had refused to acknowledge the severity of his disease state. He had refused the standard of care and opted for local wound care only until a minor fall caused a pathologic fracture, leading to an above the knee amputation. Road traffic incidents remain an uncommon cause of subsequent Marjolin's transformation in developed countries. As such, we present the case of a patient with a unique combination of a continued lack of compliance after diagnosis and the unusual cause of his initial trauma.


Assuntos
Amputação Cirúrgica/métodos , Carcinoma de Células Escamosas/patologia , Traumatismos da Perna/fisiopatologia , Úlcera da Perna/patologia , Neoplasias Cutâneas/patologia , Acidentes de Trânsito , Biópsia por Agulha , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/cirurgia , Doença Crônica , Progressão da Doença , Fêmur/cirurgia , Seguimentos , Humanos , Imuno-Histoquímica , Escala de Gravidade do Ferimento , Traumatismos da Perna/complicações , Traumatismos da Perna/diagnóstico por imagem , Úlcera da Perna/fisiopatologia , Úlcera da Perna/terapia , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento , Recusa do Paciente ao Tratamento
9.
Opt Lett ; 40(11): 2521-4, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26030547

RESUMO

Recent developments in transformation optics have led to burgeoning research on gradient index lenses for novel optical systems. Such lenses hold great potential for the advancement of complex optics for a wide range of applications. Despite the plethora of literature on gradient index lenses, previous works have not yet considered the application of anti-reflective coatings to these systems. Reducing system reflections is crucial to the development of this technology for highly sensitive optical applications. Here, we present effective anti-reflective-coating designs for gradient index lens systems. Conventional anti-reflective-design methodologies are leveraged in conjunction with transformation optics to develop coatings that significantly reduce reflections of a flat gradient index lens. Finally, the resulting gradient-index anti-reflective coatings are compared and contrasted with conventional homogeneous anti-reflective coatings.

10.
Can J Cardiol ; 30(9): 1108.e1-3, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24629491

RESUMO

Transcatheter aortic valve implantation (TAVR) has grown rapidly over the past 10 years. Device and delivery catheter systems have evolved to facilitate the procedure and reduce the risk of associated complications, including those related to vascular access. It is important to understand the utility of the TAVR equipment in patients with more challenging anatomy to select the most appropriate technique for this complex procedure. We report the first case, to our knowledge, of a patient with dextrocardia situs inversus and previous coronary artery bypass grafting who underwent TAVR from the femoral route using the Edwards SAPIEN XT Novaflex+ Transfemoral System (Edwards Lifesciences, Irvine, CA).


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Dextrocardia/complicações , Ponte de Artéria Coronária , Artéria Femoral , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Situs Inversus/complicações
12.
Infect Immun ; 80(12): 4167-76, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22988020

RESUMO

Genetic factors that regulate the pathogenesis of pneumonia caused by the fungus Cryptococcus neoformans are poorly understood. Through a phenotypic strain survey we observed that inbred C3H/HeN mice develop a significantly greater lung fungal burden than mice of the resistant CBA/J strain 4 weeks following intratracheal infection with C. neoformans ATCC 24067. The aim of the present study was to characterize the inflammatory response of C3H/HeN mice following C. neoformans pulmonary infection and to identify genetic loci that regulate host defense. Following cryptococcal infection, C3H/HeN mice demonstrated a Th2 immune response with heightened airway and tissue eosinophilia, goblet cell metaplasia, and significantly higher lung interleukin-5 (IL-5) and IL-13 protein expression relative to CBA/J mice. Conversely, CBA/J mice exhibited greater airway and tissue neutrophilia that was associated with significantly higher pulmonary expression of gamma interferon, CXCL10, and IL-17 proteins than C3H/HeN mice. Using the fungal burden at 4 weeks postinfection as a phenotype, genome-wide quantitative trait locus (QTL) analysis among 435 segregating (C3H/HeN × CBA/J)F2 (C3HCBAF2) hybrids identified two significant QTLs on chromosomes 1 (Cnes4) and 9 (Cnes5) that control susceptibility to cryptococcal pneumonia in an additive manner. Susceptible C3H/HeN mice carry a resistance allele at Cnes4 and a susceptibility allele at Cnes5. These studies reveal additional genetic complexity of the host response to C. neoformans that is associated with divergent patterns of pulmonary inflammation.


Assuntos
Cromossomos de Mamíferos/genética , Criptococose/genética , Cryptococcus neoformans/patogenicidade , Predisposição Genética para Doença , Pneumopatias Fúngicas/genética , Locos de Características Quantitativas/genética , Animais , Criptococose/imunologia , Criptococose/microbiologia , Criptococose/patologia , Citocinas/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/patologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos CBA , Células Th1/imunologia , Células Th2/imunologia
13.
Cardiovasc Revasc Med ; 13(6): 335-40, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22995198

RESUMO

BACKGROUND: Anomalies of the origin and course of the circumflex artery are amongst the most common seen at coronary angiography. There is limited information regarding patient and procedural characteristics, technical feasibility and outcomes associated with percutaneous intervention (PCI) to these vessels. The aim of this study is to examine our experience with PCI to anomalous circumflex vessels and compare this to some aspects of percutaneous intervention on non-anomalous circumflex vessels. METHODS: Over a 41 month period, 20 PCI procedures on anomalous circumflex vessels were identified and 1550 PCI procedures on non-anomalous circumflex arteries. RESULTS: In 9 anomalous cases, the circumflex arose from the left coronary cusp, in 7 cases from the right coronary cusp, and in the remaining 4 cases from the proximal right coronary artery. There were no differences in demographics or pattern or severity of coronary disease between the 2 groups. A higher proportion of patients with anomalous vessels presented acutely. Screening times were longer in the anomalous group. All 20 procedures were associated with immediate procedural success. There was one peri-procedural myocardial infarction unrelated to anomalous circumflex intervention. After a median follow-up period of 7.3 months, the only major adverse cardiac event recorded in the anomalous group was an ischaemia-driven revascularisation to a non-target vessel branch. We describe techniques which can be used to improve support and facilitate successful PCI to anomalous circumflex vessels. CONCLUSION: PCI to anomalous circumflex vessels may be technically challenging, but is feasible and carries favourable short and long-term clinical outcomes. SUMMARY: This single centre observational study demonstrates that percutaneous coronary intervention to anomalous circumflex coronary arteries although technically challenging can be performed with satisfactory procedural success rates and favourable short and longer-term clinical outcomes. It describes various techniques that can be employed to optimise successful intervention.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/terapia , Idoso , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Resultado do Tratamento
14.
EuroIntervention ; 8(2): 267-74, 2012 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-22052084

RESUMO

AIMS: Modern drug-eluting stents are constructed with thin struts and are easy to deliver and highly conformable. However, although innovative designs have enabled maintenance of radial strength, longitudinal strength may be lower with these stents and there have been recent reports of longitudinal stent compression of ostially deployed stents. We report the experience in our centre on longitudinal stent deformation and explore mechanisms of this complication and its frequency with various drug-eluting stent platforms. METHODS AND RESULTS: Nine cases of longitudinal stent deformation were identified over a four year period representing 0.2% of cases and affected 0.097% of stents deployed. There were several mechanisms for this complication including compression by post-dilatation balloons, guide catheter extensions and proximal embolic protection devices. The rate of stent deformation varied from 0% in several stent types to 0.86% in the case of the Promus Element stent. There was one case of late stent thrombosis attributable to longitudinal stent deformation. CONCLUSIONS: Longitudinal stent deformation can occur secondary to a variety of mechanisms and identification is important as, left untreated, it may be associated with a risk of stent thrombosis. Although seen with several different stents, in our series it was more commonly observed with the Promus Element stent.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Stents/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Cardiology ; 119(2): 88-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21912120

RESUMO

Ticagrelor has been shown to be superior to clopidogrel in patients presenting with acute myocardial infarction who undergo early invasive treatment. We discuss a hitherto unreported use of ticagrelor in the management of a patient resistant to multiple thienopyridines at high risk of stent thrombosis.


Assuntos
Adenosina/análogos & derivados , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Trombose/prevenção & controle , Adenosina/administração & dosagem , Adenosina/uso terapêutico , Idoso de 80 Anos ou mais , Cateterismo Cardíaco , Clopidogrel , Stents Farmacológicos , Humanos , Masculino , Infarto do Miocárdio/terapia , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Tienopiridinas/uso terapêutico , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
16.
J Allergy Clin Immunol ; 127(3): 661-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21377035

RESUMO

BACKGROUND: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy. OBJECTIVE: To investigate the association between filaggrin loss-of-function mutations and peanut allergy. METHODS: Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥ 8 mm and/or peanut-specific IgE ≥ 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis. RESULTS: Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis. CONCLUSION: Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.


Assuntos
Predisposição Genética para Doença , Proteínas de Filamentos Intermediários/genética , Hipersensibilidade a Amendoim/genética , Canadá , Estudos de Casos e Controles , Europa (Continente) , Proteínas Filagrinas , Estudos de Associação Genética , Variação Genética , Humanos , Hipersensibilidade Imediata , Irlanda , Países Baixos , Fatores de Risco
17.
EuroIntervention ; 6(6): 748-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21205600

RESUMO

AIMS: Drug eluting stents (DES) have had a great impact in reducing in-stent restenosis (ISR) in de novo lesions. However, long-term data regarding effectiveness and safety of these stents in treating bare metal stent (BMS) ISR are limited. We report long-term clinical outcomes in a cohort of patients with BMS-ISR treated with DES between April 2002 and December 2003 at our institution. METHODS AND RESULTS: Sixty-nine consecutive patients with significant BMS-ISR were treated with DES implantation. Sirolimus DES were used in 43 patients and paclitaxel DES in 26. All patients were followed up to determine the incidence of major adverse cardiac event (MACE) rates (all-cause death, myocardial infarction, or target vessel revascularisation [TVR]), angina class and the need for clinically driven angiography. The mean age of the cohort was 58.6 ± 10.8 years; 68% were male, 33% were diabetic, 50% had hypertension, 78% were on statin therapy and 59% were current (19%) or previous (41%) smokers. The clinical presentation of ISR was with chronic stable angina in 54 patients, 12 had a non-ST elevation acute coronary syndrome and three presented with ST-elevation myocardial infarction. Multivessel stenting was performed in 21 patients and bifurcation stenting in seven patients. Over a mean follow period of 4.9 years, the first event MACE rate was 20% (17 events in 14 patients - eight deaths of which three were cardiac, two non-fatal myocardial infarctions and seven TVR). Excluding non-cardiac death, the adjusted MACE rate was 14.5% (12 events in 10 patients). At long-term follow-up, mean Canadian angina class decreased from 2.3 ± 0.7 pre-procedure to 1.2 ± 0.4, 65% of patients were angina free and 80% were free of MACE. No differences in long-term outcomes were observed between patients receiving paclitaxel and sirolimus DES. CONCLUSIONS: The use of DES for the treatment of BMS-ISR is safe and effective over a mean follow-up period of nearly five years. To our knowledge, this represents the longest follow-up data of real world patients treated in a single interventional centre.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Reestenose Coronária/terapia , Stents Farmacológicos , Metais , Stents , Idoso , Angina Pectoris/etiologia , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Fármacos Cardiovasculares/administração & dosagem , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/mortalidade , Intervalo Livre de Doença , Inglaterra , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Paclitaxel/administração & dosagem , Desenho de Prótese , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sirolimo/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
19.
PLoS One ; 5(12): e15672, 2010 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-21187935

RESUMO

BACKGROUND AND OBJECTIVES: Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD. METHODS AND PRINCIPAL RESULTS: A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10) genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD) age of the cases was 12.4 (±3.3) years. Most cases were male (56.4%), had ileo-colonic disease (L3±L4, 52.7%) and inflammatory behavior (B1±p, 87%) at diagnosis. One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG) (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR (recessive) = 0.56, 95% CI = 0.35-0.89; p = 0.01), rs2074902 (OR (trend) = 1.26, 95% CI = 1.00-1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00-2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) = 0.58, 95% CI = 0.30-1.13; p = 0.10) showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99-1.67; p = 0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0.14). CONCLUSIONS: Inherited variation in enzymes involved in the synthesis/metabolism of LTB(4) may be associated with CD. These findings implicate PUFA metabolism as a important pathway in the CD pathogenesis.


Assuntos
Doença de Crohn/genética , Doença de Crohn/metabolismo , Ácidos Graxos Insaturados/metabolismo , Adolescente , Adulto , Canadá , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Variação Genética , Haplótipos , Humanos , Inflamação , Leucotrieno B4/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único
20.
EuroIntervention ; 6(5): 596-603, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21044913

RESUMO

AIMS: The aim of this study is to use real-world data from West London to compare the cost-effectiveness of a contemporary primary angioplasty (PPCI) service to thrombolysis which it superseded over a time horizon of one year. Previous studies have depended on randomised trials and economic modelling. METHODS AND RESULTS: Resource and outcome data were collected on 400 consecutive patients treated for ST segment elevation myocardial infarction (STEMI) at the hub and two spoke sites over three years. After the first 200 received thrombolysis, the PPCI service was introduced providing treatment for the next 200 cases. The incidence of major adverse cardiac events was significantly less in the PPCI group at 30 days (46.2% versus 7.0%, adjusted odds ratio (AOR) 12 p<0.001) and one year (57.4% versus 13.2%, AOR 8.6 p<0.001) driven by reductions in mortality and ischaemia driven revascularisations. Mean index and one year cumulative costs did not differ significantly between thrombolysis and PPCI (£7,016 versus £6,802; p=0.653 and £8442 versus £7,731; p=0.213 respectively). Initial angioplasty costs were significantly higher in the PPCI group offset by reduced hospital stay (8.5 versus 4 days; p<0.001). CONCLUSIONS: This model of PPCI delivery is associated with larger than expected benefits and is cost-neutral when compared to thrombolysis.


Assuntos
Angioplastia Coronária com Balão/economia , Infarto do Miocárdio/terapia , Terapia Trombolítica/economia , Idoso , Análise Custo-Benefício , Eletrocardiografia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...