RESUMEN
The aim of this study was to evaluate the surgical treatment of esophago-tracheobronchial fistulas (ETBFs) that occurred after esophagectomy with gastric conduit reconstruction in a tertiary referral center for esophageal surgery. All patients who underwent surgical repair for an ETBF after esophagectomy with gastric conduit reconstruction were included in a tertiary referral center. The primary outcome was successful recovery after surgical treatment for ETBF, defined as a patent airway at 90 days after the surgical fistula repair. Secondary outcomes were details on the clinical presentation, diagnostics, and postoperative course after fistula repair. Between 2007 and 2022, 14 patients who underwent surgical repair for an ETBF were included. Out of 14 patients, 9 had undergone esophagectomy with cervical anastomosis and 5 esophagectomy with intrathoracic anastomosis after which 13 patients had developed anastomotic leakage. Surgical treatment consisted of thoracotomy to cover the defect with a pericardial patch and intercostal flap in 11 patients, a patch without interposition of healthy tissue in 1 patient, and fistula repair via cervical incision with only a pectoral muscle flap in 2 patients. After surgical treatment, 12 patients recovered (86%). Mortality occurred in two patients (14%) due to multiple organ failure. This study evaluated the techniques and outcomes of surgical repair of ETBFs following esophagectomy with gastric conduit reconstruction in 14 patients. Treatment was successful in 12 patients (86%) and generally consisted of thoracotomy and coverage of the defect with a bovine pericardial patch followed by interposition with an intercostal muscle.
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Neoplasias Esofágicas , Fístula , Humanos , Animales , Bovinos , Esofagectomía/efectos adversos , Esofagectomía/métodos , Esófago/cirugía , Fístula/etiología , Fístula/cirugía , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Anastomosis Quirúrgica/efectos adversos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/etiologíaRESUMEN
BACKGROUND: Initiation of veno-arterial (VA) Extracorporeal Membrane Oxygenator (ECMO) is associated with severe complications. It is unknown whether these adverse consequences occur more often after initiations during out of hours service compared to working hours. METHODS: All patients receiving VA-ECMO for cardiogenic shock between 2009 and 2020 were categorized into a working hours group (between 8 am and 5 pm on weekdays) and an out of hours service group (between 5 pm and 8 am, or between Friday 5 pm and Monday 8 am). Primary outcome was all-cause mortality at 30 days. Secondary outcomes included vascular complications (including limb ischemia and/or bleeding), bloodstream infections and length of ICU stay. Propensity scores were used to adjust for potential confounding effects. RESULTS: Among 250 patients (median (IQR) age 56 (42-64) years) receiving VA-ECMO (median duration 3.5 (1.0-9.0) days), 160 (64%) runs were initiated between 5 pm and 8 am whereas the remainder (36%) started during working hours. Characteristic did not differ between the working hours- and out of hours-group. By day 30, 37 (41.1%), and 68 (42.5%) patients in either group had died, respectively (p = 0.831). VA-ECMO support duration and length of stay on the ICU did not differ significantly in both crude and adjusted analyses. More complications occurred during out of hours service (p = 0.039). CONCLUSIONS: Out of hours- versus working hours-initiation of VA-ECMO for cardiogenic shock was not associated with higher mortality, longer VA-ECMO support duration, or longer length of stay on the intensive care. Vascular complications were more common in the out of hours group.
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Atención Posterior , Oxigenación por Membrana Extracorpórea , Oxigenación por Membrana Extracorpórea/efectos adversos , Mortalidad Hospitalaria , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Choque Cardiogénico/etiologíaRESUMEN
INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.
RESUMEN
A reduced forced expiratory volume in one second (FEV1) is a well-recognized risk factor for complications after esophagectomy. Lung diffusing capacity for carbon monoxide (DLCO) is not routinely integrated in the risk assessment of esophagectomy. The aim of this study is to evaluate the association of preoperative pulmonary function tests with major postoperative complications after esophagectomy for cancer. In order to achieve this aim, 459 patients with newly diagnosed esophageal cancer who underwent elective transthoracic (n = 352) or transhiatal (n = 107) surgical resection of the esophagus with cervical anastomosis between 2003 and 2015 were analyzed. Multivariable logistic regression analysis was performed to assess the association of preoperative pulmonary function tests (expressed as % of predicted) with major complications after esophagectomy, adjusted for previously identified predictors. Major complications were defined as Clavien-Dindo grade IIIb or higher. Of the 459 included patients, 114 (24.8%) developed major complications. In univariable analysis FEV1, forced vital capacity (FVC), vital capacity (VC), and DLCO were associated with major complications. After adjusting each pulmonary function test for age, American Society of Anesthesiologists (ASA) score, cardiac comorbidity, diabetes mellitus, peripheral vascular disease, and surgical approach, FVC (OR: 1.24 per 10% decrease; 95% CI: 1.06-1.45; P = 0.004), VC (OR: 1.19 per 10% decrease; 95% CI: 1.02-1.39; P = 0.025) and DLCO (OR: 1.16 per 10% decrease; 95%CI: 1.02-1.33; P = 0.025) remained predictive factors for major surgical complications. In multivariable analysis in which all pulmonary functions tests were combined, DLCO was the strongest predictor of major complications (OR: 1.14 per 10% increase; 95% CI: 1.01-1.30; P = 0.046). The ideal cut-off for DLCO% of predicted was determined at <84% (OR: 1.97; 95% CI: 1.28-3.03; P = 0.002). These data indicate that DLCO is an independent predictor of major complications after esophagectomy for cancer. This pulmonary function test deserves greater consideration in prediction research of major complications after esophagectomy.
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Neoplasias Esofágicas/fisiopatología , Esofagectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Capacidad de Difusión Pulmonar , Pruebas de Función Respiratoria/estadística & datos numéricos , Anciano , Neoplasias Esofágicas/cirugía , Femenino , Volumen Espiratorio Forzado , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Estudios Prospectivos , Valores de Referencia , Factores de Riesgo , Resultado del TratamientoRESUMEN
Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.
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Oxigenación por Membrana Extracorpórea/métodos , Trasplante de Pulmón , Periodo Preoperatorio , Insuficiencia Respiratoria/terapia , Adulto , Terapia por Ejercicio , Femenino , Humanos , Masculino , Fuerza Muscular , Ventilación no Invasiva/métodos , Insuficiencia Respiratoria/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Methods: Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. Recommendations: The article is focused on a suggested glycemic control end point such that a blood glucose ≥150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ≤70 mg/dL) and to minimize glycemic variability. Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and standardized approaches to infusion preparation, provision of consistent carbohydrate calories and nutritional support, and dextrose replacement for hypoglycemia prevention and treatment. Quality improvement of glycemic management programs should include analysis of hypoglycemia rates, run charts of glucose values <150 and 180 mg/dL. The literature is inadequate to support recommendations regarding glycemic control in pediatric patients. Conclusions: While the benefits of tight glycemic control have not been definitive, there are patients who will receive insulin infusion therapy, and the suggestions in this article provide the structure for safe and effective use of this therapy.
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Humanos , Procedimientos Quirúrgicos Cardiovasculares , Cuidados Críticos , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Heridas y Lesiones/sangre , Traumatismos del Sistema Nervioso/sangreRESUMEN
Neurofibrillary tangles composed of hyperphosphorylated tau are a major hallmark of Alzheimer's Disease. This phosphorylated tau may be a root cause of the disorder and therefore understanding its regulation is important for therapeutic intervention. To model this pathology, Okadaic acid (OA) has been used in primary cultured hippocampal neurons to investigate effects on tau, and the role of the JNK pathway in tau phosphorylation. The use of high content screening has allowed us to quantitatively assess the profound spatiotemporal profile of these proteins, finding dramatic and inhibitable changes. Furthermore, in vitro phosphorylation experiments show that the JNK3 isoform, which is predominantly expressed in the brain, can strongly autophosphorylate itself. This has profound implications on the importance of JNK3 in the CNS and its ability to sustain signaling both towards tau and other apoptotic targets. Together these data provide novel insights into the JNK pathway and a high resolution perspective on how this pathway influences tau phosphorylation and dynamics in neurons.
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Hipocampo/fisiología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas/fisiología , Proteínas tau/metabolismo , Secuencia de Aminoácidos , Animales , Antracenos/administración & dosificación , Antracenos/farmacología , Western Blotting , Células Cultivadas , Dendritas/efectos de los fármacos , Dendritas/enzimología , Dendritas/fisiología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Inmunohistoquímica , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína Quinasa 10 Activada por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/enzimología , Ácido Ocadaico/farmacología , Fosforilación , Ratas , Factores de Tiempo , Proteínas tau/genéticaRESUMEN
BACKGROUND: Spinal anesthesia for knee arthroscopy can be produced with a low dose of bupivacaine, but additional intrathecal drugs are often required to lower the risk of failed blocks. We investigated the effect of the addition of clonidine (0, 15 or 30 microg) to 5 mg hyperbaric bupivacaine on the duration of the motor block, analgesic quality and ability to void after the surgery in a randomized controlled trial. METHODS: Seventy-five patients received spinal anesthesia using either 5 mg hyperbaric bupivacaine (B5C0), 5 mg hyperbaric bupivacaine with 15 microg clonidine (B5C15) or 5 mg hyperbaric bupivacaine with 30 microg clonidine (B5C30). The primary outcome was the duration of the motor block. Secondary outcomes included the time until spontaneous voiding, and the need for additional analgesia or general anesthesia. RESULTS: The mean time to complete regression of motor block was 70 (+/-43) min in group B5C0. Adding 15 and 30 microg of clonidine increased the motor block duration by 25 [95% confidence interval (CI): 2-48] and 34 (95% CI: 11-57) min, respectively, but resulted in better analgesic quality. The mean time until spontaneous voiding was 177 min in the B5C0 group. This time increased with 18 (95% CI -13 to 49) and 44 (95% CI 15-74) min in group B5C15 and group B5C30, respectively. CONCLUSION: The addition of 15 microg clonidine to 5 mg of intrathecal hyperbaric bupivacaine prolongs the duration of motor block and improves the quality of the block.
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Analgésicos/administración & dosificación , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Clonidina/administración & dosificación , Adulto , Procedimientos Quirúrgicos Ambulatorios , Artroscopía , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Rodilla/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon.
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Hiperandrogenismo/etiología , Insulinoma/complicaciones , Neoplasias Pancreáticas/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Adolescente , Femenino , Hirsutismo/etiología , Humanos , Hiperandrogenismo/patología , Insulinoma/patología , Insulinoma/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Resultado del TratamientoRESUMEN
Despite research and public education, myocardial disease, infarction, and death from cardiac arrest continue to be one of the top public health issues. Many patients experiencing AMIs access health care and receive initial treatment from EMS personnel in the prehospital setting. Prompt identification and diagnosis of these patients, relief of chest pain, and shortening delays to definitive care can decrease morbidity and mortality. Prehospital diagnosis of AMI is enhanced with the use of 12-lead electrocardiograms, which can shorten time to thrombolysis or angiography. Prehospital use of thrombolytic agents has not gained widespread use in this country; it is, however, commonplace in Europe, where research suggests improved outcomes when thrombolysis is initiated prior to hospital arrival. Resuscitation of out-of-hospital cardiac arrest patients is difficult, resulting in dismal survival rates. Factors that appear to be associated with enhanced survival are witnessed arrest, bystander CPR, and short response times to defibrillation.
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Servicios Médicos de Urgencia , Infarto del Miocardio/terapia , Ambulancias , Diagnóstico Diferencial , Paro Cardíaco , Humanos , Infarto del Miocardio/diagnóstico , PronósticoRESUMEN
OBJECTIVE: To report a case of virilizing ovarian hilus cell hyperplasia detected postmenopausally in association with a simple cyst and to review the related literature, including four similar cases. METHODS: Hormonal and pathologic studies were conducted, and ovarian venous catheterization was performed during total abdominal hysterectomy. RESULTS: In our 69-year-old female patient, serum testosterone levels were 508, >3,200, and 11 ng/dL, respectively, in peripheral blood preoperatively, in ovarian venous blood obtained intraoperatively, and in peripheral blood postoperatively. The wall of the cyst contained several clusters of hilus cells, which were also found asymmetrically lateralized to the affected ovary. CONCLUSION: Hilus cell hyperplasia should be suspected in any case of postmenopausal virilization in which ultrasonography or magnetic resonance imaging suggests the presence of a simple ovarian cyst.
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Quistes Ováricos/complicaciones , Ovario/patología , Posmenopausia , Virilismo/etiología , Anciano , Androstenodiona/sangre , Estradiol/sangre , Femenino , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/etiología , Hiperplasia , Leiomioma/patología , Imagen por Resonancia Magnética , Quistes Ováricos/diagnóstico , Testosterona/sangre , Ultrasonografía , Neoplasias Uterinas/patología , Virilismo/diagnósticoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of four doses of pioglitazone monotherapy in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 408 patients randomized in this multicenter double-blind placebo-controlled clinical trial. Patients who had HbA1c > or = 7.0%, fasting plasma glucose (FPG) > or = 140 mg/dl, and C-peptide > 1 ng/ml were randomized to receive placebo or 7.5, 15, 30, or 45 mg pioglitazone administered once a day for 26 weeks. RESULTS: Patients treated with 15, 30, or 45 mg pioglitazone had significant mean decreases in HbA1c (range -1.00 to -1.60% difference from placebo) and FPG (-39.1 to -65.3 mg/dl difference from placebo). The decreases in FPG were observed as early as the second week of therapy; maximal decreases occurred after 10-14 weeks and were maintained until the end of therapy (week 26). In the 15-, 30-, or 45-mg pioglitazone groups, there were significant mean percent decreases in triglycerides, significant mean percent increases in HDL cholesterol, and only small percent changes in total cholesterol and LDL. The subset of patients naive to therapy had greater improvements in HbA1c and FPG (difference from placebo of -2.55% and -79.9 mg/dl for the 45-mg group) compared with previously treated patients. The overall adverse event profile of pioglitazone was similar to that of placebo. There was no evidence of drug-induced hepatotoxicity or drug-induced elevations of alanine aminotransferase levels in this study CONCLUSIONS: Pioglitazone monotherapy significantly improves HbA1c and FPG while producing beneficial effects on serum lipids in patients with type 2 diabetes with no evidence of drug-induced hepatotoxicity.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Tiazoles/uso terapéutico , Tiazolidinedionas , Adulto , Anciano , Glucemia/efectos de los fármacos , Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Etnicidad , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Pioglitazona , Placebos , Grupos Raciales , Estados UnidosRESUMEN
The G-protein-coupled metabotropic glutamate receptor subtype 7a (mGluR7a) is a member of group III metabotropic glutamate receptors that plays an important role as a presynaptic receptor in regulating transmitter release at glutamatergic synapses. Here we report that the protein interacting with C-kinase (PICK1) binds to the C terminus (ct) of mGluR7a. In the yeast two-hybrid system, the extreme ct of mGluR7a was shown to interact with the PSD-95/Discs large/ZO-1 (PDZ) domain of PICK1. Pull-down assays indicated that PICK1 was retained by a glutathione S-transferase fusion of ct-mGluR7a. Furthermore, recombinant and native PICK1/mGluR7a complexes were coimmunoprecipitated from COS-7 cells and rat brain tissue, respectively. Confocal microscopy showed that both PICK1 and mGluR7a displayed synaptic colocalization in cultured hippocampal neurons. PICK1 has previously been shown to bind protein kinase C alpha-subunit (PKCalpha), and mGluR7a is known to be phosphorylated by PKC. We show a relationship between these three proteins using recombinant PICK1, mGluR7, and PKCalpha, where they were co-immunoprecipitated as a complex from COS-7 cells. In addition, PICK1 caused a reduction in PKCalpha-evoked phosphorylation of mGluR7a in in vitro phosphorylation assays. These results suggest a role for PICK1 in modulating PKCalpha-evoked phosphorylation of mGluR7a.
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Proteínas Portadoras/metabolismo , Isoenzimas/metabolismo , Proteínas Nucleares/metabolismo , Proteína Quinasa C/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animales , Encéfalo/metabolismo , Células COS , Proteínas Portadoras/genética , Células Cultivadas , Proteínas del Citoesqueleto , Glutatión Transferasa/genética , Hipocampo/citología , Hipocampo/metabolismo , Mutagénesis Sitio-Dirigida , Proteínas Nucleares/genética , Fosforilación , Pruebas de Precipitina , Unión Proteica/genética , Isoformas de Proteínas/metabolismo , Proteína Quinasa C-alfa , Estructura Terciaria de Proteína , Ratas , Receptores de Glutamato Metabotrópico/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transfección , Técnicas del Sistema de Dos HíbridosRESUMEN
Exploitation of resident physicians still occurs and can result in working conditions so unfavorable that patients are endangered. Because residents are vulnerable to exploitation, and because they are not fully accountable for patient care or for fully developed professionalism until they have completed their training, for just ends it is morally acceptable for residents to strike. Given that the ultimate responsibility for every patient rests not with the residents but with the attending and staff physicians, in the event of a resident strike the attending and staff physician supervisors should cover patient care, at least with respect to essential services. It is not morally acceptable for attending or staff physicians who are employees to strike. Attending and staff physicians should make every effort to resolve concerns about patient care without the use of confrontation. However, it may be necessary to consider collective actions to secure certain professional interests, including an interest in patient care. For such ends, patient endangerment is an unacceptable means and contrary to the professional virtue of altruism. The strategy for a just collective action is to identify the things that physicians normally do for their employer and collectively to withhold all of them, with the single exception of patient care.
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Negociación Colectiva , Ética Médica , Internado y Residencia/normas , Cuerpo Médico de Hospitales/normas , Huelga de Empleados , Hospitales de Enseñanza/organización & administración , Humanos , Práctica Institucional/organización & administración , Internado y Residencia/organización & administración , Cuerpo Médico de Hospitales/organización & administración , Principios Morales , Negociación , Atención al Paciente/normas , Responsabilidad Social , Estados UnidosAsunto(s)
Proteínas de Fase Aguda/inmunología , Calcitonina/sangre , Calcitonina/inmunología , Precursores de Proteínas/sangre , Precursores de Proteínas/inmunología , Sepsis/inmunología , Biomarcadores/sangre , Calcitonina/química , Calcitonina/uso terapéutico , Péptido Relacionado con Gen de Calcitonina , Humanos , Inflamación , Precursores de Proteínas/química , Precursores de Proteínas/uso terapéutico , Sepsis/sangreRESUMEN
alpha-Amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors mediate most fast excitatory synaptic transmission in the mammalian CNS. They play a central role in synapse stabilisation and plasticity and their prolonged activation is potently neurotoxic. Developmental and activity-dependent changes in the functional synaptic expression of these receptors are subject to tight cellular regulation. The molecular and cellular mechanisms which control the postsynaptic insertion and arrangement of individual AMPA receptor variants are therefore the subject of intense investigation and in the last two years there has been significant progress towards elucidating some of the processes involved. Much of the new information has come from the application of the yeast two-hybrid assay, which has led to the discovery of a hitherto unexpected complexity of proteins which selectively interact with individual AMPA receptor subunits. These proteins have been implicated in the regulation of AMPA receptor post-translational modification, targeting and trafficking, surface expression and anchoring. The aim of this article is to present an overview of the major interacting proteins described so far and to place these in the context of how they may participate in the well ordered series of events controlling the cell biology of AMPA receptors.
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Proteínas del Tejido Nervioso/metabolismo , Receptores AMPA/metabolismo , Proteínas de Transporte Vesicular , Proteínas Adaptadoras Transductoras de Señales , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/metabolismo , Homólogo 1 de la Proteína Discs Large , Humanos , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Proteínas Nucleares/metabolismo , Receptores AMPA/química , Proteínas Solubles de Unión al Factor Sensible a la N-Etilmaleimida , Sinapsis/metabolismo , Familia-src Quinasas/metabolismoRESUMEN
Research is needed on the frequency of bad outcomes in transplantation. Allocation policies and professional or institutional self-interest may affect the incidence of bad outcomes, and the need for reform is stressed. Transplant recipients who have had a bad outcome often continue to receive aggressive care. The humanistic care of patients having bad outcomes requires attention to advance directives, discussion with patient and family of alternatives to aggressive treatment, and provision of an option for home hospice care. Finally, it must be reemphasized that the average typical good outcome is extraordinarily good, restoring function of a vital organ, extending and improving quality of life, and sometimes restoring near-normal health. In no way should the fact of bad outcomes reduce our commitment to producing good outcomes.
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Asignación de Recursos para la Atención de Salud/normas , Selección de Paciente , Asignación de Recursos , Obtención de Tejidos y Órganos/normas , Trasplantes/provisión & distribución , Miembro de Comité , Toma de Decisiones en la Organización , Humanos , Difusión de la Información , Política Organizacional , Control Social Formal , Donantes de Tejidos/psicología , Obtención de Tejidos y Órganos/organización & administración , Resultado del Tratamiento , Estados UnidosRESUMEN
Although it is well established that kainate receptors constitute an entirely separate group of proteins from AMPA receptors, their physiological functions remain unclear. The molecular cloning of subunits that form kainate receptors and the ability to study recombinant receptors is leading to an increased understanding of their functional properties. Furthermore, the development of kainate receptor-selective agonists and antagonists over the past few years is now allowing the physiological roles of these receptors and, in some cases, specific subunits to be investigated. As a consequence, the synaptic activation of postsynaptic kainate receptors and the presence of presynaptic kainate receptors that serve to regulate excitatory and inhibitory synaptic transmission have been described, and will be discussed in this article by Ramesh Chittajallu, Steven Braithwaite, Vernon Clarke and Jeremy Henley.
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Receptores de Ácido Kaínico/fisiología , Sinapsis/metabolismo , Animales , Clonación Molecular , Humanos , Receptores de Ácido Kaínico/genética , Receptores de Ácido Kaínico/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transmisión Sináptica/fisiologíaRESUMEN
Although glucocorticoid therapy carries a risk of promoting or exacerbating hyperglycemia, there are currently no established medical guidelines for detecting or managing diabetes in patients starting such therapy. The authors use three case reports to illustrate a relatively simple strategy that can be used to manage preexisting and new-onset diabetes in the primary care setting.