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1.
Ceylon Med J ; 60(1): 25-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25804916

RESUMO

Ingestion of corrosives with accidental or suicidal intent is a common problem in Sri Lanka. Management options and outcomes of corrosive injuries on stomach are not well documented in our setting. The clinical presentation, complications and management outcomes of nine patients with corrosive injury to stomach are presented. Gastric outlet obstruction seen in majority, was managed with bypass procedure (n=5) or resection (n=4). The outcomes of management were successful with both methods.


Assuntos
Queimaduras Químicas/cirurgia , Cáusticos/toxicidade , Obstrução da Saída Gástrica/cirurgia , Estômago/lesões , Ácido Acético/toxicidade , Adolescente , Adulto , Queimaduras Químicas/complicações , Estudos de Coortes , Ingestão de Alimentos , Feminino , Gastrectomia , Derivação Gástrica , Obstrução da Saída Gástrica/etiologia , Humanos , Masculino , Ácido Nítrico/toxicidade , Estudos Retrospectivos , Sri Lanka , Estômago/cirurgia , Gastropatias/etiologia , Gastropatias/cirurgia , Ácidos Sulfúricos/toxicidade , Adulto Jovem
2.
J Hosp Infect ; 88(2): 96-102, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25123634

RESUMO

BACKGROUND: Mediastinitis is a devastating complication of cardiac surgery. Previous studies have often observed small populations, been retrospective in design, and used a variety of definitions for mediastinitis. AIM: To identify risk factors for mediastinitis, and strategies to minimize its incidence. METHODS: A prospective cohort study of 4883 adult patients who underwent cardiac surgery between October 2003 and February 2009, comparing pre- and peri-operative risk factors, microbial aetiology, requirement for re-admission, length of stay and mortality between patients with and without mediastinitis. FINDINGS: Ninety (1.8%) patients were diagnosed with mediastinitis. Microbial aetiology was defined for 75 patients. Staphlyocococcus aureus was the most common isolate (30 episodes; 15 due to meticillin-resistant S. aureus). Univariate analysis revealed the following pre-operative factors associated with mediastinitis: age; body mass index; diabetes; modified logistic European System for Cardiac Operative Risk Evaluation score; urgent admission; and longer pre-operative stay (P < 0.05). Associated peri-operative factors were: combined coronary artery bypass grafting plus aortic valve replacement; longer aortic cross-clamp time; and longer cardiopulmonary bypass time (P < 0.005). Multi-variate analysis revealed that higher body mass index, combined coronary artery bypass grafting plus aortic valve replacement, and older age were associated with mediastinitis (P < 0.05). Mediastinitis was associated with re-admission to hospital, longer inpatient stay and reduced long-term survival (P < 0.05). CONCLUSION: Mediastinitis is associated with worse short-term outcomes (re-admission, length of stay) and reduced long-term survival. Obesity is the only modifiable pre-operative risk factor for mediastinitis. It may be possible to reduce risk through pre-operative weight loss programmes before elective surgery.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mediastinite/etiologia , Obesidade/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/microbiologia , Feminino , Humanos , Masculino , Mediastinite/epidemiologia , Mediastinite/microbiologia , Pessoa de Meia-Idade , Período Perioperatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
3.
Ceylon Med J ; 58(4): 142-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24385054

RESUMO

OBJECTIVES: To study the early pathological changes in renal lesions of asymptomatic patients with kidney diseases, with no definite aetiology living in regions endemic for chronic kidney disease of unknown etiology (CKDUe). Design Retrospective study. SETTING: Regions endemic for CKDUe in and around the North Central Province of Sri Lanka. STUDY POPULATION: Two hundred and eleven asymptomatic patients living in endemic regions detected with renal disease by screening for proteinuria using the dipstick method. Those with long standing hypertension, diabetes mellitus, histological diagnosis of primary glomerular diseases, immunocomplex mediated diseases or renal lesions secondary to systemic diseases were excluded. MEASUREMENTS: Renal lesions were divided into seven histological categories depending on the pathological changes: Category 0: no detectable changes. Category 1: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; no glomerulosclerosis. Category 2: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; glomerulosclerosis. Category 3: Moderate or severe interstitial fibrosis, interstitial inflammation and tubular atrophy ± glomerulosclerosis; Category 4: Interstitial inflammation ± tubular atrophy ± glomerulosclerosis; no interstitial fibrosis. Category 5: The prominent change is interstitial inflammation with tubulitis. Category 6: Severely scarred kidney. Histological categories were compared with calculated glomerular filtration rates and age of the patients. RESULTS: Number of cases in histological categories 0 to 6 were: 7 (3.3%), 71 (33.6%), 53 (25.1%), 63 (29.9%), 0, 2 (0.9%) and 15 (7.1%) respectively. The mean glomerular filtration rate was >90 ml/min in patients in category 0 and 1 and declined progressively in categories 2 and 3. Apart from category 0, all had interstitial fibrosis and in category 1, 62 (87.3%) had interstitial fibrosis without inflammation. Severity of interstitial inflammation increased from category 1 to 3. CONCLUSIONS: The early disease among asymptomatic patients is characterized by interstitial fibrosis without significant interstitial inflammation and glomerular sclerosis with preserved glomerular function. Although the role of interstitial inflammation in the initiation of the disease is not clear, it appears to have a role in the progression of the disease.


Assuntos
Doenças Assintomáticas , Rim/patologia , Insuficiência Renal Crônica/patologia , Adolescente , Adulto , Idoso , Atrofia/patologia , Criança , Feminino , Fibrose , Taxa de Filtração Glomerular , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Sri Lanka , Adulto Jovem
4.
Ceylon Med J ; 55(4): 106-11, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21341622

RESUMO

UNLABELLED: INTRODUCTION; Cutaneous leishmaniasis is endemic in Sri Lanka. The immunopathogenesis of these lesions in Sri Lankans has not been documented. OBJECTIVES: To classify skin lesions into histological groups, to assess parasitic load, density of each inflammatory cell type and necrosis and to characterise the lymphocytic reaction in cutaneous leishmaniasis in comparison to leprosy. METHODS: Skin biopsies from 31 patients with demonstrable amastigotes in smears or tissue sections were studied. The lesions were classified by two independent observers into four distinct histological groups based on different cell types in the inflammatory infiltrate and formation of granulomata. Parasitic load and the presence of necrosis were recorded. Immunohistochemical staining for CD45RO and CD20 for counting T and B cells respectively was done. RESULTS: Histological groups of cutaneous leishmaniasis ranging from group I-IV were similar to that of the spectrum in leprosy ranging from lepromatous to tuberculoid leprosy. The histological groups from I-IV showed a significant inverse relationship with the mean parasitic index. Necrosis was not a prominent feature. The mean percentage of T cells in the histological spectrum from group I-IV in leishmaniasis was similar to the spectrum from lepromatous to tuberculoid leprosy. Mean percentage of T cells were 20.1% in group I, 20.5% in group II, 33.8% in group III and 47.8% in group IV. Lepromatous, borderline tuberculoid and tuberculoid leprosy had 21.3%, 33.4% and 48.0% T cells respectively. CONCLUSION: Cutaneous leishmaniasis is a spectral disease similar to leprosy. The mean percentage T cells from group I-IV were similar to those in the spectrum of leprosy and mean percentage B cells varied in a narrow range.


Assuntos
Leishmaniose Cutânea/patologia , Humanos , Leishmaniose Cutânea/sangue , Leishmaniose Cutânea/parasitologia , Contagem de Linfócitos , Necrose , Sri Lanka , Linfócitos T
5.
BMJ Case Rep ; 2009: bcr2006087965, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21687104
7.
Interact Cardiovasc Thorac Surg ; 3(3): 475-8, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17670290

RESUMO

Gut ischaemia following cardiac surgery carries a high mortality and is usually due to non-occlusive mesenteric ischaemia. We reviewed 4464 patients undergoing cardiac surgery over a 5-year period. Sixteen of them developed gut ischaemia post-operatively, 13 of whom were discovered at laparotomies while the remaining 3 were post-mortem diagnoses. Eleven patients were found to have extensive ischaemia and all 11 died irrespective of the treatment and the delay in diagnosis. In five patients ischaemia was localized, involving the caecum in three and terminal ileum in two. They all underwent local resections and survived. The differences in the groups were analysed and the average time between onset of symptoms and laparotomies was longer in the localized ischaemia group compared to the extensive ischaemia group. Our experience illustrates the continuing difficulty in diagnosis of mesenteric ischaemia before gut infarction has occurred. We conclude that different pathologies might be involved in post-cardiac surgery gut ischaemia and although early diagnosis and treatment is considered to be crucial, early laparotomies do not necessarily equate to survival in cases of extensive ischaemia. There is a need to evaluate aggressive strategies for early diagnosis if prognosis is to be improved in these cases.

8.
J Cardiovasc Surg (Torino) ; 43(5): 697-700, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12386587

RESUMO

Blunt innominate artery injury is a rare but often lethal complication of severe deceleration trauma. We report the case of a 38-year-old man with such an injury who was successfully operated on an emergency basis. In cases of brachiocephalic vessel trauma, a high index of suspicion in chest deceleration injuries may lead to a proper investigative process and an accurate diagnosis. Clinical signs as blood pressure gradient between the arms and widening of the mediastinum on chest X-ray is highly suggestive of trauma of the thoracic aorta and its great vessels. A chest CT scan may contribute to the diagnosis and can rule out major trauma of the aorta, but the procedure of choice for the definite diagnosis is usually the angiography. Subsequent early repair is favorable to avoid complications and fatal events. Cardiopulmonary bypass use in selected cases favors the outcome.


Assuntos
Tronco Braquiocefálico/lesões , Ferimentos não Penetrantes/cirurgia , Acidentes de Trânsito , Adulto , Desaceleração , Humanos , Masculino , Ferimentos não Penetrantes/etiologia
9.
J Heart Valve Dis ; 10(5): 689-90, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11603611

RESUMO

Active prosthetic valve endocarditis (PVE) as a complication of acupuncture requiring valve surgery has not been reported previously. We report a case of PVE in a patient with Marfan's syndrome as a complication of acupuncture, who underwent emergency redo aortic root and valve replacement with a homograft. This report highlights the need for prophylactic antibiotics before acupuncture in patients with prosthetic valves, and also describes the use of a homograft as an effective surgical strategy.


Assuntos
Terapia por Acupuntura/efeitos adversos , Endocardite Bacteriana/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Síndrome de Marfan/complicações , Síndrome de Marfan/terapia , Infecções Relacionadas à Prótese/etiologia , Adulto , Antibioticoprofilaxia , Valva Aórtica/transplante , Feminino , Humanos , Infecções Estafilocócicas/etiologia , Staphylococcus aureus , Transplante Homólogo
11.
J Thorac Cardiovasc Surg ; 121(6): 1083-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11385375

RESUMO

OBJECTIVES: The effect of mild-to-moderate elevation of preoperative serum creatinine levels on morbidity and mortality from coronary artery bypass grafting has not been investigated in a large multivariable model incorporating preoperative and intraoperative variables. Our first objective was to ascertain the effect of a mild-to-moderate elevation in the preoperative serum creatinine level on the need for mechanical renal support; the duration of special care and total postoperative stay; the occurrence of infective, respiratory, and neurologic complications; and hospital mortality. Our second objective was to ascertain which patient variables contributed to an increase in the serum creatinine level in association with coronary artery bypass grafting. METHODS: A total of 1427 patients who had no known pre-existing renal disease and who were undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass were recruited for the study. Patients were divided, on the basis of preoperative serum creatinine level, into 3 groups as follows: creatinine level of less than 130 micromol. L(-1); creatinine level of 130 to 149 micromol. L(-1); and creatinine level of 150 micromol. L(-1) or greater. A multivariable stepwise logistic regression analysis was used, and variables significant at the 5% level were included when developing the final multivariable models. RESULTS: Multivariable analysis showed that elevation of the preoperative serum creatinine level to 130 micromol. L(-1) or greater increased the likelihood of needing mechanical renal support postoperatively (P <.001), as well as the need for postoperative special care (P <.001) and total hospital stay (P <.001). In-hospital mortality was also significantly elevated as the preoperative creatinine level rose to 130 to 149 micromol. L(-1) (P =.045) and to 150 micromol. L(-1) or greater (P <.001). It was further observed that patients with preoperative serum creatinine levels of 130 to 149 micromol. L(-1) (P =.02), patients with preoperative serum creatinine levels of 150 micromol. L(-1) or greater (P =.001), hypertensive patients (P =.007), patients with angina of New York Heart Association class III or greater (P =.001), patients having a nonelective operation (P =.002), and patients having a prolonged cardiopulmonary bypass time (P =.008) had a significantly greater increase in the serum creatinine level as a result of coronary artery bypass grafting. Of particular note was the finding that the method of myocardial protection (cardioplegia or crossclamp fibrillation) did not significantly influence in-hospital mortality, need for mechanical renal support, or special care or total postoperative hospital stay. CONCLUSIONS: A mild elevation (130-149 micromol. L(-1)) in the preoperative serum creatinine level significantly increases the need for mechanical renal support, the duration of special care and total postoperative stay, and the in-hospital mortality. As the preoperative serum creatinine level increases further (> or =150 micromol. L(-1)), this effect is more pronounced. No significant difference in outcome was observed between the use of cardioplegia or crossclamp fibrillation for myocardial protection.


Assuntos
Ponte de Artéria Coronária/mortalidade , Doença das Coronárias/complicações , Doença das Coronárias/cirurgia , Creatinina/sangue , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ponte de Artéria Coronária/métodos , Doença das Coronárias/mortalidade , Feminino , Humanos , Testes de Função Renal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Análise Multivariada , Cuidados Pré-Operatórios , Probabilidade , Insuficiência Renal/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
12.
Ann Thorac Surg ; 71(5): 1503-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11383790

RESUMO

BACKGROUND: The long saphenous vein remains the commonest conduit used in coronary artery bypass grafting procedures. Surgical trauma during vein harvesting can cause endothelial and smooth muscle injury that has important implications for vein graft longevity. Minimally invasive vein harvesting is advocated to reduce wound morbidity. However, the functional consequences of increased handling and traction, with potentially detrimental effects, remain unknown. METHODS: Forty patients were prospectively randomized into either a minimally invasive (minimal) or traditional (open) saphenous vein harvest group. Smooth muscle contractile function was assessed by responses to potassium chloride and phenylephrine. Endothelial cell function was assessed by responses to serial escalations in concentration of acetylcholine, bradykinin, calcium ionophore, sodium nitroprusside, and N-nitro-L-arginine using isometric tension studies. RESULTS: Harvest times were similar for both groups. The total incision length in the minimal group was significantly shorter than in the open group. There were no differences in smooth muscle contractions to either receptor-independent or receptor-mediated agonists between the two groups. Similarly, vasorelaxation in response to both endothelium-dependent and endothelium-independent agonists were similar in both groups. CONCLUSIONS: Minimally invasive saphenous vein harvesting is associated with similar medial smooth muscle and endothelial function as open harvesting. These findings suggest that minimally invasive harvesting techniques can be used without major detrimental effects on vascular integrity.


Assuntos
Ponte de Artéria Coronária , Endotélio Vascular/fisiopatologia , Procedimentos Cirúrgicos Minimamente Invasivos , Músculo Liso Vascular/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Coleta de Tecidos e Órgãos , Veias/transplante , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/fisiologia , Estudos Prospectivos , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Veias/fisiopatologia
13.
Am J Med Genet ; 100(2): 130-7, 2001 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-11298374

RESUMO

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), plays important roles in normal vascular homeostasis, and reduced endothelial NO bioactivity is an important feature of vascular disease states. The Glu298Asp (G894T) polymorphic variant of eNOS has been associated with vascular disease, but functional data are lacking. Accordingly, we examined the relationships between NO-mediated endothelial function, the presence of the eNOS Glu298Asp variant, and clinical risk factors for atherosclerosis. Endothelium-dependent vasorelaxations to different agonists were determined in human saphenous veins obtained from patients with coronary artery disease and identified risk factors (n = 104). Patients were genotyped for the eNOS G894T polymorphism. Nitric oxide-mediated endothelial vasorelaxations were highly variable between patients. Reduced vasorelaxations were associated with increased number of clinical risk factors for atherosclerosis (r = - 0.54, P < 0.001), whereas the Glu298Asp variant was not associated with any differences in contractions to phenylephrine, NO-mediated vasorelaxations to acetylcholine, bradykinin or calcium ionophore, or relaxations to the NO donor sodium nitroprusside. Increased atherosclerotic risk factors, but not the presence of the eNOS Glu298Asp variant, are associated with impaired nitric oxide-mediated endothelial vasomotor function, suggesting that this polymorphism does not have a major direct functional effect on vascular eNOS activity in human atherosclerosis.


Assuntos
Arteriosclerose/genética , Endotélio Vascular/fisiopatologia , Óxido Nítrico Sintase/genética , Óxido Nítrico/fisiologia , Idoso , Substituição de Aminoácidos , Ácido Aspártico/genética , Feminino , Genótipo , Ácido Glutâmico/genética , Humanos , Masculino , Óxido Nítrico Sintase Tipo III , Polimorfismo Genético , Fatores de Risco , Veia Safena/fisiopatologia , Sistema Vasomotor/fisiopatologia
14.
Semin Thorac Cardiovasc Surg ; 13(4 Suppl 1): 163-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11805966

RESUMO

Long-term clinical and hemodynamic performance is a key consideration in using a stentless aortic bioprosthesis. This study reports clinical and hemodynamic performance of Prima stentless aortic valve during our 8-year follow-up. In the study, 85 patients underwent aortic valve replacement (Edwards Prima or Prima plus stentless valve) and had follow-up at discharge and then annually up to 8 years. The mean age at operation was 72 +/- 5 yrs, 49 were male and 25% underwent concomitant CABG. Doppler Echo studies were performed to determine mean pressure gradient (mPG), effective orifice area (EOA) and the degree of regurgitation of stentless valves. Aortic root geometry was assessed by the ratio of sinotubular junction to valve size at peak systole. Patient survival rate was 82% +/- 5% at 5th year and 72% +/- 6% at 8th year. The freedom from valve structure failure was 97% +/- 2% at 5th and 8th year. Valve mPG and EOA at 8 years remained significantly better than those at discharge (6.8 +/- 4.4 mm Hg v 9.7 +/- 6.2 mm Hg; 1.91 +/- 0.54 cm(2) v 1.63 +/- 0.71 cm(2), both P <.01), and did not differ from those at 3-year follow-up. Mean sinotubular junction diameter remained below valve size (0.96 +/- 0.14). Mild degree of valvular regurgitation was present in 17% of patients, but this did not progress over the period of follow-up. After aortic valve replacement with the Prima stentless valves, excellent valve hemodynamics and normal root geometry were well maintained up to 8 years, but longer-term follow-up of a larger cohort remains essential.


Assuntos
Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas , Função Ventricular Esquerda/fisiologia , Idoso , Valva Aórtica/diagnóstico por imagem , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Próteses Valvulares Cardíacas/estatística & dados numéricos , Hemodinâmica , Humanos , Masculino , Desenho de Prótese , Taxa de Sobrevida
15.
Circulation ; 102(15): 1744-7, 2000 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-11023926

RESUMO

BACKGROUND: Increased superoxide anion production increases oxidative stress and reduces nitric oxide bioactivity in vascular disease states. NAD(P)H oxidase is an important source of superoxide in human blood vessels, and some studies suggest a possible association between polymorphisms in the NAD(P)H oxidase CYBA gene and atherosclerosis; however, no functional data address this hypothesis. We examined the relationships between the CYBA C242T polymorphism and direct measurements of superoxide production in human blood vessels. METHODS AND RESULTS: Vascular NAD(P)H oxidase activity was determined in human saphenous veins obtained from 110 patients with coronary artery disease and identified risk factors. Immunoblotting, reverse-transcription polymerase chain reaction, and DNA sequencing showed that p22phox protein, mRNA, and 242C/T allelic variants are expressed in human blood vessels. Vascular superoxide production, both basal and NADH-stimulated, was highly variable between patients, but the presence of the CYBA 242T allele was associated with significantly reduced vascular NAD(P)H oxidase activity, independent of other clinical risk factors for atherosclerosis. CONCLUSIONS: Association of the CYBA 242T allele with reduced NAD(P)H oxidase activity in human blood vessels suggests that genetic variation in NAD(P)H oxidase components may play a significant role in modulating superoxide production in human atherosclerosis.


Assuntos
Arteriosclerose/genética , Proteínas de Membrana Transportadoras , NADPH Desidrogenase/genética , Fosfoproteínas/genética , Polimorfismo Genético , Superóxidos/metabolismo , Idoso , Alelos , Arteriosclerose/enzimologia , Arteriosclerose/metabolismo , Vasos Sanguíneos/metabolismo , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Desidrogenase/biossíntese , NADPH Desidrogenase/fisiologia , NADPH Oxidases/metabolismo , Fosfoproteínas/biossíntese , Fosfoproteínas/fisiologia , RNA Mensageiro/biossíntese , Fatores de Risco
16.
Eur J Cardiothorac Surg ; 18(3): 357-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10973548

RESUMO

We describe the case of tension chylothorax in a 29-year-old man following blunt chest trauma sustained in a road traffic accident. This presented with respiratory and haemodynamic compromise. Conservative treatment was attempted but definitive surgical intervention was required.


Assuntos
Quilotórax/etiologia , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Adulto , Quilotórax/diagnóstico , Quilotórax/cirurgia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Sucção , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/cirurgia , Toracotomia/métodos , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/cirurgia
17.
J Thorac Cardiovasc Surg ; 120(2): 361-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10917955

RESUMO

BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It has also been used in trials aimed at reducing the systemic inflammatory response to cardiopulmonary bypass. It remains unclear whether the anti-inflammatory action of aprotinin is related to its general ability to suppress leukocyte activation or whether aprotinin can exercise effects during the leukocyte-endothelial cell adhesion cascade. METHODS: We used intravital microscopy to study the 3 main stages of the adhesion cascade (leukocyte rolling, firm adhesion, and extravasation) within the mesenteric microcirculation of rats. This in vivo technique allows leukocyte recruitment to be viewed directly through the transparent mesentery of anesthetized animals. RESULTS: Aprotinin, given by continuous infusion at a clinically relevant dose, exerted no effect on the rolling or firm adhesion responses toward local chemoattractant N -formyl-methyl-leucyl-phenylalanine but significantly inhibited extravasation of leukocytes (73% at 40 minutes, P =.04) into surrounding tissues. In parallel in vitro experiments, aprotinin (used at 200, 800, and 1600 kIU/mL) dose dependently inhibited neutrophil transmigration through cultured endothelial cells in response to 3 different chemoattractants: N -formyl-methyl-leucyl-phenylalanine (P <.001 at 800 and 1600 kIU/mL), interleukin 8 (P <.05 at 200 kIU/mL and P <.001 at 800 and 1600 kIU/mL), and platelet-activating factor (P <.05 at 1600 kIU/mL). CONCLUSIONS: Our studies have therefore revealed a novel anti-inflammatory mechanism of aprotinin operating at the level of leukocyte extravasation. These findings may be relevant in the prevention of systemic inflammation after cardiopulmonary bypass through the use of protease inhibitors.


Assuntos
Aprotinina/farmacologia , Adesão Celular/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Análise de Variância , Animais , Adesão Celular/fisiologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Leucócitos/fisiologia , Masculino , Microcirculação , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/fisiologia , Peroxidase/sangue , Ratos , Ratos Sprague-Dawley , Circulação Esplâncnica , Estatísticas não Paramétricas
18.
Circ Res ; 86(9): 1008, 2000 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-10807875

RESUMO

Superoxide anion plays important roles in vascular disease states. Increased superoxide production contributes to reduced nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of vascular disease. We measured superoxide production by NAD(P)H oxidase in human blood vessels and examined the relationships between NAD(P)H oxidase activity, NO-mediated endothelial function, and clinical risk factors for atherosclerosis. Endothelium-dependent vasorelaxations and direct measurements of vascular superoxide production were determined in human saphenous veins obtained from 133 patients with coronary artery disease and identified risk factors. The predominant source of vascular superoxide production was an NAD(P)H-dependent oxidase. Increased vascular NAD(P)H oxidase activity was associated with reduced NO-mediated vasorelaxation. Furthermore, reduced endothelial vasorelaxations and increased vascular NAD(P)H oxidase activity were both associated with increased clinical risk factors for atherosclerosis. Diabetes and hypercholesterolemia were independently associated with increased NADH-dependent superoxide production. The association of increased vascular NAD(P)H oxidase activity with endothelial dysfunction and with clinical risk factors suggests an important role for NAD(P)H oxidase-mediated superoxide production in human atherosclerosis. The full text of this article is available at http://www.circresaha.org. Key Words:atherosclerosis endothelium superoxide nitric oxide diabetes Two Distinct Congenital Arrhythmias Evoked by a Multidysfunctional Na(+) Channel Marieke W. Veldkamp, Prakash C. Viswanathan, Connie Bezzina, Antonius Baartscheer, Arthur A.M. Wilde, Jeffrey R. Balser Abstract-The congenital long-QT syndrome (LQT3) and the Brugada syndrome are distinct, life-threatening rhythm disorders linked to autosomal dominant mutations in SCN5A, the gene encoding the human cardiac Na(+) channel. It is believed that these two syndromes result from opposite molecular effects: LQT3 mutations induce a gain of function, whereas Brugada syndrome mutations reduce Na(+) channel function. Paradoxically, an inherited C-terminal SCN5A mutation causes affected individuals to manifest electrocardiographic features of both syndromes: QT-interval prolongation (LQT3) at slow heart rates and distinctive ST-segment elevations (Brugada syndrome) with exercise. In the present study, we show that the insertion of the amino acid 1795insD has opposite effects on two distinct kinetic components of Na(+) channel gating (fast and slow inactivation) that render unique, simultaneous effects on cardiac excitability. The mutation disrupts fast inactivation, causing sustained Na(+) current throughout the action potential plateau and prolonging cardiac repolarization at slow heart rates. At the same time, 1795insD augments slow inactivation, delaying recovery of Na(+) channel availability between stimuli and reducing the Na(+) current at rapid heart rates. Our findings reveal a novel molecular mechanism for the Brugada syndrome and identify a new dual mechanism whereby single SCN5A mutations may evoke multiple cardiac arrhythmia syndromes by influencing diverse components of Na(+) channel gating function. The full text of this article is available at http://www.circresaha.org. Key Words: Na(+) channel inactivation long-QT syndrome Brugada syndrome

19.
Circ Res ; 86(9): E85-90, 2000 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-10807876

RESUMO

Superoxide anion plays important roles in vascular disease states. Increased superoxide production contributes to reduced nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of vascular disease. We measured superoxide production by NAD(P)H oxidase in human blood vessels and examined the relationships between NAD(P)H oxidase activity, NO-mediated endothelial function, and clinical risk factors for atherosclerosis. Endothelium-dependent vasorelaxations and direct measurements of vascular superoxide production were determined in human saphenous veins obtained from 133 patients with coronary artery disease and identified risk factors. The predominant source of vascular superoxide production was an NAD(P)H-dependent oxidase. Increased vascular NAD(P)H oxidase activity was associated with reduced NO-mediated vasorelaxation. Furthermore, reduced endothelial vasorelaxations and increased vascular NAD(P)H oxidase activity were both associated with increased clinical risk factors for atherosclerosis. Diabetes and hypercholesterolemia were independently associated with increased NADH-dependent superoxide production. The association of increased vascular NAD(P)H oxidase activity with endothelial dysfunction and with clinical risk factors suggests an important role for NAD(P)H oxidase-mediated superoxide production in human atherosclerosis. The full text of this article is available at http://www.circresaha.org.


Assuntos
Endotélio Vascular/química , NADH NADPH Oxirredutases/farmacologia , Superóxidos/metabolismo , Acetilcolina/farmacologia , Idoso , Análise de Variância , Arteriosclerose/epidemiologia , Arteriosclerose/etiologia , Calcimicina/farmacologia , Endotélio Vascular/inervação , Feminino , Humanos , Ionóforos/farmacologia , Masculino , Pessoa de Meia-Idade , NADPH Oxidases , Nitroprussiato/farmacologia , Fatores de Risco , Veia Safena/química , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiologia
20.
Ann Thorac Surg ; 70(6): 2155-6, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11156144
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