RESUMEN
BACKGROUND: To determine predisposing factors that may lead to the development of compartment syndrome (CS) in patients with acute lower limb ischemia (ALLI) managed with intra-arterial catheter-directed thrombolysis (CDT). METHODS: This is a retrospective study of patients admitted between 01/2002 and 12/2015 to three university hospitals in Tampere, Turku, and Oulu, Finland, with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb). Patients managed with CDT and aspiration thrombectomies (AT) as an adjunct to CDT were included in the study. Multivariable binary logistic regression models were used to detect possible risk factors for the development of CS and its impact on the limb salvage and survival. Amputation-free survival (AFS) rates of CS and non-CS patients were compared using Kaplan-Meier survival analysis. The length of hospitalization was calculated and compared between the CS and non-CS groups. RESULTS: A total of 292 CDTs with or without ATs were performed on patients with a mean age of 71 years (standard deviation 13 years), 151 (51.7%) being male. Altogether, 12/292 (4.1%) treatment-related CS cases were registered. Renal insufficiency (odds ratio [OR] 4.27, P = 0.07) was associated with an increased risk of CS. All CS cases were managed with fasciotomies. Treatment with fasciotomy was associated with a prolonged hospitalization of a median of 7 days versus the 4 days for non-CS patients, P < 0.001. During the median follow-up of 51 months (interquartile range 72 months), 152/292 (52.1%) patients died and 51/292 (17.5%) underwent major amputations. CS was not associated with an increased risk of mortality, but it was associated with a higher risk of major amputation (OR 3.87, P = 0.027). The AFS rates of patients with or without CS did not significantly differ from each other in the long term. CONCLUSIONS: CS after CDT for the treatment of ALLI is uncommon. Renal insufficiency is associated with an increased risk of CS. Fasciotomy prolongs the hospitalization. Patients with CS are exposed to an increased risk of major amputation.
Asunto(s)
Arteriopatías Oclusivas , Síndromes Compartimentales , Enfermedad Arterial Periférica , Insuficiencia Renal , Anciano , Arteriopatías Oclusivas/cirugía , Catéteres , Síndromes Compartimentales/etiología , Femenino , Fibrinolíticos/efectos adversos , Humanos , Isquemia/tratamiento farmacológico , Isquemia/terapia , Recuperación del Miembro , Extremidad Inferior/cirugía , Masculino , Orlistat/uso terapéutico , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Pronóstico , Insuficiencia Renal/etiología , Estudios Retrospectivos , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Femoral endarterectomies are often performed by means of longitudinal arteriotomies with patching. Autologous and synthetic patches can be used. Synthetic patches in the groin may expose patients to infection. We present two alternative techniques for the treatment of femoral atherosclerotic lesions. MATERIAL AND METHODS: The alternative endarterectomies (AE) included eversion (EE) and semi-closed endarterectomies (SCE). An EE with an oblique transection of a femoral bifurcation (FB) was used for lesions extending to the FB. The artery was reconstructed in an end-to-end manner. An SCE with a bovine pericardium patch (BPP) was used for lesions extending further. An arteriotomy was made from the superficial femoral artery just past the level of the profunda femoris opening (PFO). The plaque was cut proximally to the PFO, dissected circularly with a Swedish-type dissector, and then removed with Crile forceps. The distally remaining plaque was endarterectomized in a conventional manner. The arteriotomy was closed with a BPP. RESULTS: A total of 21 AEs were performed, 8 of which were accomplished in a hybrid setting. There were no periprocedural complications. One distal embolization after a balloon dilatation was registered during the early postoperative period. The median follow-up was 3 months. There were no deep wound infections, pseudoaneurysms, amputations, or deaths. A total of 20/21 patients reported complete symptom relief, with one requiring an additional femoro-popliteal bypass grafting owing to poor outflow. The primary patency rate of the endarterectomized segments was 100%. CONCLUSION: Alternative methods of local endarterectomy can extend the available range of procedures for patients suffering from chronic lower-limb ischemia. According to our results, these endarterectomy techniques are safe and could be taken into consideration, as they provide some advantages over conventional methods.
Asunto(s)
Endarterectomía , Arteria Ilíaca , Animales , Bovinos , Arteria Femoral/cirugía , Humanos , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Respuesta al Choque Térmico , Riñón/fisiopatología , Condicionamiento Físico Animal , Animales , Chaperonina 60/metabolismo , Proteínas del Choque Térmico HSP72/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Interleucina-6/metabolismo , Masculino , Proteínas Mitocondriales/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE/BACKGROUND: Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. METHODS: This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques (n = 68) and left internal thoracic (LITA) controls (n = 28) and plaque histological severity assessed. Correlation and hierarchical cluster analysis was utilised. RESULTS: HDAC9 was associated with MMP12 expression in carotid plaques (r = .46, p = .012) and controls (r = -.44, p = .034). HDAC9 and MMP12 clustered with inflammatory macrophage markers but not with smooth muscle cell (SMC) rich markers. In plaques from all arterial sites, MMP12 but not HDAC9 showed positive correlation (p < .05) with M2 and M4 polarized macrophage markers, and negative correlation with SMC rich signatures. In the carotid plaques, all M4 macrophage markers associated with MMP12 and HDAC9. The negative association of MMP12 with SMC rich signatures was pronounced in the carotid plaques. Neither HDAC9 nor MMP12 associated consistently with plaque stabilisation or thrombosis related genes. Immunohistochemistry further supported the association between HDAC9 and MMP12 in atherosclerotic plaques. CONCLUSION: M4 macrophages are a possible source for HDAC9 and MMP12 expression in advanced human plaques.
Asunto(s)
Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/genética , Histona Desacetilasas/genética , Macrófagos/enzimología , Metaloproteinasa 12 de la Matriz/genética , Placa Aterosclerótica , Proteínas Represoras/genética , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/patología , Estudios de Casos y Controles , Análisis por Conglomerados , Perfilación de la Expresión Génica/métodos , Estudio de Asociación del Genoma Completo , Humanos , Inmunohistoquímica , Macrófagos/patología , Microscopía Confocal , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Estudios Prospectivos , ARN Mensajero/genéticaRESUMEN
BACKGROUND: White matter changes (WMCs), a surrogate for small-vessel disease (SVD), have been shown to be associated with a major negative influence on cognition, mood and functioning in daily life. We aimed to investigate whether severe WMCs are a risk factor for recurrent ischemic stroke in a long-term follow-up. METHODS: 320 consecutive patients admitted to hospital with a first-ever ischemic stroke were included in the study and followed up for 12 years using extensive national registers. Patients were aged between 55 and 85 years, with a mean age of 70.8 years. WMCs were rated using MRI and stratified into two grades: absent to moderate WMCs versus severe WMCs. Univariate analysis was performed using binary logistic regression analysis, Kaplan-Meier log rank analysis and life table function. To control for factors such as age, education and cardiovascular risk factors, a multivariate Cox regression proportional hazards analysis was made with forced entry. RESULTS: At least one recurrent stroke, nonfatal or fatal, was diagnosed in 76 (23.8%) patients at 5 years and in 127 (39.7%) patients at 12 years. In univariate analysis, only advancing age was associated with WMCs. The cumulative 5-year recurrence risk was 24.5% [95% confidence interval (95% CI) 23.8-25.2] for patients with absent to moderate WMCs and 39.1% (95% CI 38.1-40.1) for patients with severe WMCs. The cumulative 12-year recurrence risk was 48.1% (95% CI 45.5-50.7) for patients with absent to moderate WMCs and 60.9% (95% CI 56.7-65.1) for patients with severe WMCs. In Cox regression proportional hazards analysis, independent predictors of recurrent stroke at 5 years were severe WMCs [hazard ratio (HR) 1.80, 95% CI 1.11-2.95], atrial fibrillation (HR 1.81, 95% CI 1.09-3.02), hypertension (HR 1.69, 95% CI 1.05-2.71) and peripheral arterial disease (HR 1.89, 95% CI 1.06-3.38). At 12 years, only increasing age remained as an independent predictor (HR 1.04, 95% CI 1.02-1.07). In receiver operating characteristic analysis, the area under the curve for severe WMCs was 0.58 (95% CI 0.51-0.65) for the prediction of stroke recurrence within 5 years. CONCLUSIONS: In our well-defined cohort of poststroke patients, the presence of severe WMCs was an indicator of stroke recurrence up to 5 years after a first-ever ischemic stroke. WMCs can be considered as an SVD marker that summarizes the effects of several classical risk factors on the small-vessel brain network and therefore can be used as a score for risk stratification of stroke recurrence. Our findings further underline the poor long-term prognosis of cerebral SVD.
Asunto(s)
Encéfalo/patología , Imagen por Resonancia Magnética , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/patología , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND: The microcirculation regulates the supply of oxygen and nutrients to tissues. The sublingual region is frequently used as a window to microcirculation in critically ill patients. Numerous studies have reported impaired sublingual microcirculatory flow. We hypothesized that the quality of sidestream dark field imaging (SDF) recordings could be systematically analyzed to justify the monitoring of sublingual microcirculation in interventional studies or in clinical practice. METHODS: The sublingual microcirculation in critically ill patients with septic shock, open heart surgery, or alcoholic pancreatitis, and healthy subjects was recorded with a hand held SDF device by one trained investigator in observational setting. A total of 82 video recording sessions were performed and 240 video clips eligible for quality assessment were identified. Quality assessment was performed offline by two investigators independently and blinded for the origin of the video file. RESULTS: Of the 240 clips, pressure artifact was detected in 86 (36%), major blood in 5 (2.1%), major saliva in 21 (8.8%) and extreme brightness causing loss of visible capillaries in 16 (6.7%) clips. The dominating vessel architecture was multiple size vessels in 228 (95%) and repeating capillary loop motif in 12 (5.0%). The mean (± SD) relative size reduction during stabilization was -6.9% (± 4.7%). Excellent technical quality was detected in 74 of 240 (30.8%) recordings. CONCLUSIONS: Our findings highlight the need of a comprehensive training period and reporting of data quality before findings with SDF imaging can be accepted as surrogate end points in interventional studies or as guidance in clinical practice.
Asunto(s)
Enfermedad Crítica , Microcirculación/fisiología , Suelo de la Boca/irrigación sanguínea , Artefactos , Procedimientos Quirúrgicos Cardíacos , Diagnóstico por Imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Microscopía por Video , Variaciones Dependientes del Observador , Pancreatitis Alcohólica/fisiopatología , Estudios Prospectivos , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Saliva/metabolismo , Sepsis/fisiopatología , Choque Séptico/fisiopatologíaRESUMEN
BACKGROUND: Constituents of vascular endothelial surface layer (glycocalyx), e.g. an anchor protein syndecan-1 (SDC-1), can be detected in plasma in many inflammatory conditions. In inflammation, vascular adhesion protein-1 (VAP-1) is rapidly translocated to the apical side of the endothelial cells and may be released to plasma in a soluble form. We hypothesized that glycocalyx injury coincides with VAP-1 activation on endothelial cells. To test the hypothesis, we measured SDC-1 and VAP-1 levels in 20 patients with septic shock. METHODS: A prospective observational study was conducted in two multidisciplinary critical care units in two tertiary academic teaching hospitals with 20 mechanically ventilated adult patients with septic shock, on days 1 and 4 of treatment. Twenty healthy adults were enrolled as a control group. Plasma SDC-1 content, serum VAP-1 activity, platelets, and leukocyte count were measured in septic shock group at baseline and at 72 h and compared with those of healthy controls. RESULTS: VAP-1 activity and SDC-1 content were significantly increased in septic patients' group (P < 0.01) in comparison with controls. VAP-1 activity and SDC-1 content correlated positively to each other, and negatively to platelet count. In the septic shock group SDC-1 correlated on day 1 to SOFA score. CONCLUSIONS: We found increased VAP-1 activity and SDC-1 content in critically ill patients with septic shock. Based on our results, the role of VAP-1 in shock pathogenesis should be studied with semicarbazide-sensitive amine oxidase activity blocking agents and substrate affinity testing.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/sangre , Moléculas de Adhesión Celular/sangre , Choque Séptico/sangre , Sindecano-1/sangre , Adulto , Anciano , Biomarcadores , Enfermedad Crítica , Ensayo de Inmunoadsorción Enzimática , Femenino , Glicocálix/metabolismo , Glicocálix/patología , Humanos , Infecciones/complicaciones , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Respiración ArtificialRESUMEN
BACKGROUND AND AIMS: Good long term result after Nissen fundoplication is achieved in most of the patients in specialized centres. Still failure occurs in some cases and reoperation after failed conservative treatment is done in 3-6% of the cases. Reoperation is more dangerous and results worse than after primary fundoplication. Therefore we wanted to analyze factors related to failure of Nissen fundoplication with special emphasis on utilization of crural closure, anchor-ing of the fundic wrap and the use of fibrin glue. MATERIAL AND METHODS: Patients records of 258 patients were analyzed by an independent ob-server. Defective fundic wrap, recurrent oesophagitis and hiatal hernia were defined as failure. RESULTS: Failure after Nissen fundoplication was found in 29 patients (14.9%). Crural closure (p = 0.021), anchoring of the wrap (p = 0.020) and fibrin glue (p = 0.029) decreased the incidence of failure. However, only crural closure (p = 0.010) and fibrin glue (p = 0.019) were independent factors in the prevention of failure. CONCLUSIONS: Fibrin glue as a new method might be worth utilizing to further decrease the incidence of failure after Nissen fundoplication. Because our study was retrospective, prospective randomized study should be performed before universal use of fibrin glue in the prevention of failure after fundoplication.
Asunto(s)
Esofagitis/prevención & control , Adhesivo de Tejido de Fibrina/uso terapéutico , Fundoplicación/métodos , Reflujo Gastroesofágico/cirugía , Complicaciones Posoperatorias/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Endoscopía Gastrointestinal , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reoperación , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. METHODS: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. RESULTS: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). CONCLUSIONS: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.
Asunto(s)
Esófago/patología , Fundoplicación , Reflujo Gastroesofágico/patología , Reflujo Gastroesofágico/cirugía , Adenocarcinoma/prevención & control , Adulto , Anciano , Apoptosis , Esófago de Barrett/metabolismo , Esófago de Barrett/patología , Esófago de Barrett/cirugía , Biomarcadores/metabolismo , Proliferación Celular , Neoplasias Esofágicas/prevención & control , Esófago/metabolismo , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: We sought to compare ultra-long-term poststroke survival in small-vessel disease (SVD) vs non-SVD subtype of stroke. METHODS: We followed patients hospitalized with acute ischemic stroke (age 55-85) for 12 years. The diagnosis of SVD was based on the criteria of Trial of Org 10172 in Acute Stroke Treatment. A detailed medical history regarding the relevant risk factors was obtained. Stroke severity was assessed with the modified Rankin Scale (mRS) at 3 months. Influence of the SVD subtype of stroke was analyzed using Kaplan-Meier log-rank analysis with endpoint all-cause death, and Cox regression proportional hazards model was constructed for multivariate analysis. The association between SVD and causes of death (cardiac, brain-related, all other) was analyzed using Kaplan-Meier log-rank analysis. RESULTS: Of the 486 patients, stroke etiology was SVD in 63 patients (13.0%). Median survival was 4.3 years for SVD and 7.9 years for non-SVD (p ≤ 0.001). In the stepwise Cox regression analysis adjusted for relevant confounders, independent predictors of death were SVD (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.06-2.41), advanced age (HR 1.07, 95% CI 1.05-1.09), stroke severity (mRS 3-5 vs 1-2; HR 2.02, 95% CI 1.58-2.58), smoking (HR 1.44, 95% CI 1.10-1.88), and cardiac failure (HR 1.53, 95% CI 1.14-2.06). SVD was associated with cardiac cause of death (p = 0.021). CONCLUSIONS: In this well-characterized ischemic stroke cohort of patients aged 55-85 years with a 12-year follow-up, acute index stroke attributable to SVD was associated with poorer long-term survival and higher risk for cardiac death than other stroke subtypes.
Asunto(s)
Encéfalo/patología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/mortalidad , Vasculitis del Sistema Nervioso Central/etiología , Anciano , Anciano de 80 o más Años , Escolaridad , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Vasculitis del Sistema Nervioso Central/clasificación , Vasculitis del Sistema Nervioso Central/diagnósticoRESUMEN
BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a risk factor for oesophageal adenocarcinoma. Although fundoplication cures reflux symptoms and oesophagitis, it remains controversial whether it is capable of preventing the development of oesophageal adenocarcinoma. Hsp27 and Hsp70 are associated with the development of cancer, whereas the effect of fundoplication on them is not known. METHODS: The expression of Hsp27 and Hsp70 was assessed semiquantitatively from biopsies of oesophageal mucosa for a prospective cohort of 19 patients with GERD treated with fundoplication and 7 controls without GERD. Upper gastrointestinal endoscopy with biopsies from the oesophagogastric junction (EGJ) and the distal and proximal oesophagus were performed preoperatively (19 patients) and after recovery from GERD at 6 (19 patients) and 48 months (16 patients) postoperatively. RESULTS: The expressions of both Hsp27 (p = 0.001) and Hsp70 (p = 0.002) in the distal oesophagus were lower in patients preoperatively and at 48 months postoperatively (p < 0.001 for both) than in controls. The patients' Hsp27 and Hsp70 levels were lower preoperatively in the proximal oesophagus (p = 0.048 for both) than in controls. Both Hsp27 (p = 0.002) and Hsp70 (p = 0.003) were lower in the distal oesophagus preoperatively and at 48 months postoperatively (p = 0.003 for Hsp27, p = 0.004 for Hsp70) than in the proximal oesophagus. CONCLUSIONS: Our results indicate that there may be some factor interfering with the mucosal defence system of the distal oesophagus in GERD that is uninfluenced by fundoplication and not associated with the acid-reflux-normalizing effect.
Asunto(s)
Esófago/metabolismo , Reflujo Gastroesofágico/genética , Reflujo Gastroesofágico/cirugía , Proteínas de Choque Térmico HSP27/genética , Proteínas HSP70 de Choque Térmico/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Fundoplicación , Expresión Génica , Proteínas de Choque Térmico , Humanos , Masculino , Persona de Mediana Edad , Chaperonas Moleculares , Membrana MucosaRESUMEN
BACKGROUND: Global warm ischemia of transplanted cardiac grafts is associated with apoptosis and subsequent tissue necrosis. It is suggested that postconditioning (PostC) may ameliorate the early outcome of cardiac grafts after ischemia-reperfusion. We investigated whether PostC and remote postconditioning (RPostC) have a histopathologic impact after transplantation of warm ischemic rat cardiac grafts. MATERIALS AND METHODS: Thirteen rats were randomized to undergo either PostC or RPostC after heterotopic transplantation of ischemic cardiac grafts. Six rats without intervention besides transplantation served as controls (control). The recipient rats were sacrificed 24 h after transplantation to evaluate histopathology and apoptotic index. RESULTS: No significant differences were observed between the study groups in terms of graft heat shock protein 70 and oxygen radical absorbing capacity, an indicator of antioxidant capacity. While apoptosis and PCARB, a marker of protein oxidation and oxidative stress, decreased after RPostC (p < 0.05), contraction band necrosis was less prominent in both PostC and RPostC. CONCLUSION: Both PostC and RPostC have a histopathologic impact after 24 h of reperfusion of warm ischemic rat cardiac grafts.
Asunto(s)
Trasplante de Corazón/métodos , Poscondicionamiento Isquémico/métodos , Isquemia Miocárdica/etiología , Animales , Apoptosis , Coagulación Sanguínea , Proteínas HSP70 de Choque Térmico/metabolismo , Masculino , Contracción Miocárdica/fisiología , Isquemia Miocárdica/patología , Necrosis , Estrés Oxidativo , Ratas , Ratas Endogámicas F344 , Daño por Reperfusión/patología , Trasplante Isogénico/métodosRESUMEN
OBJECTIVES: Despite peripheral arterial disease (PAD), defined as ankle-brachial index (ABI)
Asunto(s)
Índice Tobillo Braquial/métodos , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Enfermedades Vasculares Periféricas/epidemiología , Anciano , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
In diabetes, defense systems against cellular stress are impaired. Heat shock proteins (HSPs) function primarily as molecular chaperones. Factors that raise tissue HSP levels may slow progression of diabetes and improve diabetic complications that also affect brain tissue. This study tested the effect of an 8-week exercise training on brain HSP response in rats with or without streptozotocin-induced diabetes (SID). In untrained animals, the HSP levels were not different between SID and non-diabetic groups. Endurance training, however, increased HSP72 and HSP90 protein in non-diabetic rats, whereas SID significantly decreased the effect of training on these HSPs. At the mRNA level, HSP60, HSP90 and GRP75 were increased due to training, whereas HSP72 mRNA was only increased in exercise-trained diabetic animals. Training or diabetes had no effect on protein carbonyl content, a marker of oxidative damage. Altogether, our findings suggest that endurance training increases HSP expression in the brain, and that experimental diabetes is associated with an incomplete HSP response at the protein level.
Asunto(s)
Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estrés Oxidativo/fisiología , Condicionamiento Físico Animal/fisiología , Animales , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico , Masculino , Proteínas de la Membrana/metabolismo , Factor 1 de Elongación Peptídica/metabolismo , Factor 2 de Elongación Peptídica/metabolismo , Resistencia Física/fisiología , Carbonilación Proteica/fisiología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Poststroke global cognitive decline and dementia have been related to poor long-term survival. Whether deficits in specific cognitive domains are associated with long-term survival in patients with ischaemic stroke is not known in detail. METHODS: Patients with acute stroke subjected to comprehensive neuropsychological evaluation were included in the study (n = 409) and followed up for up to 12 years. RESULTS: In Kaplan-Meier analysis, impairments in following cognitive domains predicted poor poststroke survival (estimated years): executive functions (48.2%) (5.8 vs 10.1 years, p<0.0001), memory (59.9%) (6.8 vs 9.3 years, p = 0.009), language (28.9%) (5.3 vs 8.6 years, p = 0.004) and visuospatial/constructional abilities (55.2%) (5.6 vs 10.1 years, p<0.0001). Low Mini Mental Status Examination (MMSE) Asunto(s)
Trastornos del Conocimiento/psicología
, Accidente Cerebrovascular/mortalidad
, Anciano
, Anciano de 80 o más Años
, Causas de Muerte
, Cognición
, Trastornos del Conocimiento/complicaciones
, Femenino
, Estudios de Seguimiento
, Humanos
, Hipoxia-Isquemia Encefálica/complicaciones
, Hipoxia-Isquemia Encefálica/psicología
, Estimación de Kaplan-Meier
, Lenguaje
, Masculino
, Memoria
, Persona de Mediana Edad
, Pruebas Neuropsicológicas
, Pronóstico
, Factores de Riesgo
, Accidente Cerebrovascular/complicaciones
RESUMEN
Heat shock protein (HSP) expression is an adaptive mechanism against the disruption of cell homeostasis during exercise. Several antioxidant supplementation strategies have been used to enhance tissue protection. In this study, we examined the effects of a redox modulator, alpha-lipoic acid (LA) on HSP responses in six standardbred trotters following intense aerobic exercise. DL-LA supplementation (25 mg kg(-1) d(-1)) for five weeks increased the resting levels of HSP90 (1.02+/-0.155 in control and 1.26+/-0.090 after supplementation in arbitrary units) and the recovery levels of inducible HSP70 (0.89+/-0.056 in control and 1.05+/-0.089 after supplementation in arbitrary units) in skeletal muscle. Furthermore, LA increased skeletal muscle citrate synthase activity at rest and lowered the blood lactate concentration during exercise without any changes in the heart rate. LA had no effect on concentrations of HSP60, HSP25 or GRP75 in skeletal muscle. LA decreased the exercise-induced increases in plasma aspartate aminotransferase and creatine kinase concentrations during recovery. Our results suggest that LA supplementation may enhance tissue protection and increase oxidative capacity of the muscle in horse.
Asunto(s)
Proteínas de Choque Térmico/metabolismo , Caballos/fisiología , Ácido Láctico/sangre , Condicionamiento Físico Animal/efectos adversos , Ácido Tióctico/farmacología , Alimentación Animal , Animales , Dieta/veterinaria , Suplementos Dietéticos , Femenino , MasculinoRESUMEN
OBJECTIVE: Recurrent strokes and functional decline are predicted by age related white matter changes (ARWMC). Whether they are associated with long term survival among hospital patients referred for acute stroke is not known. METHODS: A total of 396 consecutive acute stroke patients subjected to MRI were included in the study and followed-up for up to 12 years. RESULTS: 28% had mild, 18% had moderate and 54% had severe ARWMCs. In Kaplan-Meier analysis, poor survival was predicted by severe ARWMCs (p<0.0001), cardiac failure (CF, p<0.0001), atrial fibrillation (AF, p<0.0001), other arrhythmias (p = 0.003), peripheral arterial disease (PAD, p = 0.004) and poor modified Rankin score (mRS) (p<0.0001). ARWMC was related to death by all brain related causes, especially ischaemic stroke (p<0.0001). In stepwise Cox regression analysis adjusted with significant risk factors, severe ARWMCs (hazard ratio (HR) 1.34, 95% CI 1.03 to 1.73; p = 0.029), age (HR 1.07, 95% CI 1.05 to 1.09; p<0.0001), CF (HR 1.59, 95% CI 1.17 to 2.15; p = 0.003), AF (HR 1.68, 95% CI 1.24 to 2.27; p = 0.001), PAD (HR 1.59, 95% CI 1.11 to 2.26; p = 0.011), diabetes (HR 1.44, 95% CI 1.08 to 1.92; p = 0.013), smoking (HR 1.60, 95% CI 1.23 to 2.08; p<0.0001) and mRS (HR 1.65, 95% CI 1.26 to 2.14; p<0.0001) were independently associated with death from all causes. Severe ARWMCs (HR 1.80, 95% CI 1.10 to 2.96; p = 0.019), age (HR 1.05, 95% CI 1.01 to 1.09; p = 0.009), AF (HR 1.82, 95% CI 1.08 to 3.07; p = 0.026), PAD (HR 2.17, 95% CI 1.19 to 3.95; p = 0.012) and mRS (HR 2.75, 95% CI 1.67 to 4.54; p<0.0001) were specifically associated with death from brain related causes. CONCLUSIONS: In patients with acute stroke, ARWMC seems to be a significant predictor of poor long term survival and death by ischaemic stroke.
Asunto(s)
Envejecimiento/patología , Encéfalo/patología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/patología , Enfermedad Aguda , Anciano , Arritmias Cardíacas/complicaciones , Fibrilación Atrial/complicaciones , Diabetes Mellitus/fisiopatología , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Enfermedades Vasculares Periféricas/complicaciones , Pronóstico , Análisis de Regresión , Medición de Riesgo , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
BACKGROUND: The aim of this study was to investigate the influence of poststroke dementia on long-term survival after acute stroke and also to assess the possible influence of prestroke cognitive decline and previous stroke on this relationship. METHODS: A total of 451 consecutive patients with acute ischaemic stroke admitted to hospital were included in the study and followed up for 12 years. Dementia was diagnosed 3 months after stroke in 115 patients (25.5%). RESULTS: In Kaplan-Meier analysis, poststroke dementia predicted poor long-term survival (5.1 years vs 8.8 years in patients who did not have poststroke dementia; p<0.001). Prestroke cognitive decline had a negative influence on survival in patients with poststroke dementia (3.8 years vs 5.8 years; p<0.001); however, previous stroke did not affect survival in these patients (p = 0.676). In stepwise Cox regression proportional hazards analysis adjusted for significant covariates, poststroke dementia (hazard ratio (HR) 1.53; p = 0.003), advanced age (HR 1.07; p<0.001), severity of stroke (HR 1.91; p<0.001), smoking (HR 1.35; p = 0.035), cardiac failure (HR 1.61; p = 0.003) and atrial fibrillation (HR 1.89; p = 0.035) were all independent predictors of poor long-term survival. Poststroke dementia (HR 2.33; p<0.001), advanced age (HR 1.07; p<0.001) and poor Rankin score (HR 2.15; p = 0.001) were associated with death from brain-related causes, including infarction, haemorrhage and dementia. CONCLUSIONS: Long-term follow-up of our large well-defined poststroke cohort indicated that in patients with acute stroke, dementia is a significant predictor of poor long-term survival and death from brain-associated causes. Prestroke cognitive decline seems to have an additional negative influence on survival, but previous stroke does not seem to affect survival.
Asunto(s)
Trastornos del Conocimiento/etiología , Demencia/etiología , Accidente Cerebrovascular/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Causas de Muerte , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Interpretación Estadística de Datos , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sesgo de Selección , Factores Sexuales , Factores Socioeconómicos , Sobrevida , Análisis de SupervivenciaRESUMEN
BACKGROUND: We aimed to study whether variations in vasoregulatory endothelial nitric oxide synthase (eNOS 4a/b) and tissue-injury-associated inducible nitric oxide synthase (iNOS R5/4) genes and smoking might explain gender differences in long-term survival after stroke. METHODS: A total of 486 consecutive acute stroke patients, subjected to MRI, were followed up for a mean of 7.6 years. The eNOS 4a/b (n = 300) and iNOS R5/4 (n = 310) genotypes were determined by PCR. Of these patients, 213/300 (71.0%; eNOS 4a/b) and 223/310 (71.9%; iNOS R5/4) had died. RESULTS: Despite the fact that women were older than men (72.3 vs. 69.5 years, p = 0.001) at recruitment, poor long-term survival was not sex-related, but instead predicted by age (p < 0.0001), cardiac failure (p = 0.004), smoking (p = 0.017), diabetes (p = 0.049), and variation in the eNOS gene locus (p = 0.033). Smoking and variations in both eNOS [hazard ratio (HR) = 1.53, p = 0.011] and iNOS loci (HR = 1.52, p = 0.073) were found to impact upon poor survival. We found a strong interaction between smoking, female sex, and the iNOS R5/4 genotype with the risk of death (HR = 3.23, CI = 1.51-6.90, p = 0.002). Compared with nonsmoking noncarriers, postmenopausal women who had been smokers and carried either the rare iNOS R5 allele (17.1%; HR = 4.23, CI = 1.84-9.75, p = 0.001) or the common eNOS 4b allele (71%; HR = 3.14, CI = 1.49-6.62, p = 0.003) were at a higher risk of death during the follow-up. These interactions were independent of each other, and were not found among men. CONCLUSIONS: The interaction between smoking and genetic variants of eNOS and iNOS predicts survival after stroke, especially among postmenopausal women.
Asunto(s)
Isquemia Encefálica/complicaciones , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo II/genética , Polimorfismo Genético , Fumar/efectos adversos , Accidente Cerebrovascular/etiología , Sobrevivientes , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/enzimología , Isquemia Encefálica/genética , Isquemia Encefálica/mortalidad , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fenotipo , Posmenopausia , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Accidente Cerebrovascular/enzimología , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/mortalidad , Factores de TiempoRESUMEN
BACKGROUND: During the past 20 years medical therapy of peptic ulcer disease (PUD) has dramatically improved. Simultaneously there has been a significant improvement in living and dietary habits. Quite presumably, all these significant events are reflected in the incidence and results of surgery for peptic ulcerations. AIM: To study the incidence, methods and mortality of surgery for PUD. METHODS: The nationwide data between 1987 and 1999 were obtained from the National Research and Development Centre for Welfare and Health. In the analysis the codes of the ICD 9-10 were used. RESULTS: The annual incidence of elective surgery for PUD decreased from 15.7 to 1.7 operations (per 10(5) inhabitants, mean of 2 consecutive years) between 1987 and 1999 (p < 0.05). Simultaneously, the annual incidence of emergency surgery increased from 5.2 to 7.0 operations (per 10(5) inhabitants, p < 0.05). In 1987, local procedures (duodeno-/gastrorrhaphy or duodeno-/gastrostomy and suture) were applied in 25% of operations for PUD, whereas in 1999 they were 90% of the methods in PUD surgery. The overall annual mortality from PUD surgery remained 8% between 1987 and 1999. CONCLUSIONS: Elective ulcer surgery has virtually disappeared and parietal cell vagotomy has become history, whereas the incidence of emergency surgery increased significantly between 1987 and 2000, with the exception of the most recent years. Local procedures are overwhelmingly applied in emergency surgery and more extensive surgery is unnecessary. Nevertheless, the overall surgical mortality remained 8% between 1987 and 1999.