RESUMEN
BACKGROUND: Perianal fistula is a debilitating disease and challenging condition to treat. Recently, the use of stem cells has been shown to improve healing of fistulas. OBJECTIVE: The aim was to examine the use of an umbilical cord-derived stem cell graft in a pilot study as a novel scaffold/stem inlay implanted into fistula repairs for anovaginal fistula to examine healing rates. DESIGN: This was a pilot study. SETTINGS: This study took place in a colorectal surgery practice. PATIENTS: Patients with anovaginal fistula consented to participate. Cryopreserved umbilical cord tissue graft with viable cells was incorporated as an inlay using a previously reported technique by the authors. Demographic data including history of previous repairs and IBD were included. All patients were followed for a minimum of 6 weeks. MAIN OUTCOME MEASURES: The primary measures were safety and efficacy of novel stem cell graft in the treatment of anovaginal fistula. RESULTS: From September 2017 to September 2019, 15 patients underwent anovaginal fistula repair. Three of these patients underwent a second repair, for a total of 18 repairs. No patient was intentionally diverted, but 3 patients presented for repair with a preexisting stoma. The majority of repairs were previous repair failures (12; 67%), and 7 repairs were performed on 5 patients with IBD. Median follow-up was 30 (6-104) weeks. The safety profile for cryopreserved umbilical cord tissue graft was excellent as no adverse events occurred. Overall complete healing rate was 39%, and 12 (67%) repairs resulted in improvement of symptoms. LIMITATIONS: This was a small pilot study. CONCLUSIONS: This is the largest series using cryopreserved umbilical cord graft for anovaginal fistula repair. The use of umbilical cord was safe and effective at closing defects. Randomized studies are necessary to determine added benefits over current standard of care. See Video Abstract at http://links.lww.com/DCR/B896 . RESULTADOS CLNICOS INICIALES DEL USO DE INJERTOS DE TEJIDO DERIVADO DE PLACENTA PARA REPARACIN DE FSTULAS ANOVAGINALES: ANTECEDENTES:La fístula perianal es una enfermedad debilitante y una afección difícil de tratar. Recientemente, se ha demostrado que el uso de células madre mejora la curación de las fístulas.OBJETIVO:Deseamos examinar el uso de un injerto de células madre derivadas de cordón umbilical en un estudio piloto como una nueva matriz/injerto de células madre implantado en reparaciones de fístula para fístula anovaginal para examinar las tasas de curación.DISEÑO:Este fue un estudio piloto.ESCENARIO:Este estudio se llevó a cabo en una clínica de cirugía colorrectal.PACIENTES:Se obtuvo consentimiento informado de pacientes con fístula anovaginal. El injerto de tejido de cordón umbilical criopreservado con células viables se incorporó como incrustación utilizando una técnica previamente informada por los autores. Se incluyeron datos demográficos que incluían antecedentes de reparaciones previas y enfermedad inflamatoria intestinal. Todos los pacientes fueron seguidos durante un mínimo de 6 semanas.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas fueron la seguridad y la eficacia del nuevo injerto de células madre en el tratamiento de la fístula anovaginal.RESULTADOS:Desde 9/2017-9/2019, 15 pacientes fueron sometidas a reparación de fístula anovaginal. Tres de estos pacientes fueron sometidos a una segunda reparación, para un total de 18 reparaciones. Ningún paciente fue derivado intencionalmente mientras que 3 pacientes se presentaron para reparación con un estoma preexistente. La mayoría de las reparaciones fueron fallas de reparaciones previas (12, 67%) y se realizaron siete reparaciones en 5 pacientes con enfermedad inflamatoria intestinal (EII). La mediana de seguimiento fue de 30 semanas (6-104). El perfil de seguridad del injerto de tejido de cordón umbilical criopreservado fue excelente ya que no se produjeron efectos adversos. La tasa general de curación completa fue del 39% y 12 (67%) reparaciones dieron como resultado una mejoría de los síntomas.LIMITACIONES:Este fue un pequeño estudio piloto.CONCLUSIÓNES:Ésta es la serie más grande de utilización de injerto de cordón umbilical criopreservado para la reparación de una fístula anovaginal. La utilización del cordón umbilical resultó segura y eficaz para cerrar defectos. Se necesitan estudios aleatorizados para determinar los beneficios adicionales sobre el estándar de atención actual. Consulte Video Resumen en http://links.lww.com/DCR/B896 . (Traducción-Dr. Jorge Silva Velazco ).
Asunto(s)
Enfermedades Inflamatorias del Intestino , Fístula Rectal , Femenino , Humanos , Embarazo , Tejido Conectivo , Proyectos Piloto , Fístula Rectal/cirugíaRESUMEN
OBJECTIVE: To characterize transitional care needs (TCNs) after colorectal cancer (CRC) surgery and examine their association with age and impact on overall survival (OS). BACKGROUND: TCNs after cancer surgery represent additional burden for patients and are associated with higher short-term mortality. They are not well-characterized in CRC patients, particularly in the context of a growing elderly population, and their effect on long-term survival is unknown. METHODS: A retrospective cohort study of CRC patients (N = 486) having curative surgery at a tertiary referral center (2002-2011) was conducted. Outcomes included TCNs (home health or nonhome destination at discharge) and OS. Patients were compared on the basis of age: young (<65 years), old (65-74 years), and oldest (≥75 years). Multivariate logistic regression models were used to examine the association of age with TCNs, and OS was compared on the basis of TCNs and stage, using the Kaplan-Meier method. RESULTS: TCNs were required by 130 patients (27%). The oldest patients had highest TCNs (49%) compared with the other age groups (P < 0.01), with rehabilitation services as their primary TCNs (80%). After multivariate analysis, patients 75 years or older had significantly increased TCN risk (odds ratio, 4.7; 95% confidence interval, 2.6-8.5). TCN was associated with worse OS for patients with early- and advanced stage CRC (P < 0.001). CONCLUSIONS: TCNs after CRC surgery are common and significantly increased in patients 75 years or older, represent an outcome of postoperative recovery, and are associated with worse long-term survival. Preoperative identification of higher risk populations should be used for patient counseling, advanced preoperative planning, and to implement strategies targeted at minimizing TCNs.
Asunto(s)
Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Continuidad de la Atención al Paciente/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Cuidados Posoperatorios/mortalidad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Estadificación de Neoplasias , Oportunidad Relativa , Análisis de Regresión , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Measured transport properties of three representative cuprates are reproduced within the paradigm of two electron subsystems, itinerant and localized. The localized subsystem evolves continuously from the Cu 3d[Formula: see text] hole at half-filling and corresponds to the (pseudo)gapped parts of the Fermi surface. The itinerant subsystem is observed as a pure Fermi liquid (FL) with material-independent universal mobility across the doping/temperature phase diagram. The localized subsystem affects the itinerant one in our transport calculations solely by truncating the textbook FL integrals to the observed (doping- and temperature-dependent) Fermi arcs. With this extremely simple picture, we obtain the measured evolution of the resistivity and Hall coefficients in all three cases considered, including LSCO which undergoes a Lifshitz transition in the relevant doping range, a complication which turns out to be superficial. Our results imply that prior to evoking polaronic, quantum critical point, quantum dissipation, or even more exotic scenarios for the evolution of transport properties in cuprates, Fermi-surface properties must be addressed in realistic detail.
RESUMEN
Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 3308:2000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags' contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%-16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 µg/cig; under ISO yields ranged from 1.6 to 4.9 µg/cig under standardized smoking machine conditions. Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.
RESUMEN
BACKGROUND: Perianal Crohn's disease (pCD) is a debilitating complication affecting up to 30% of Crohn's disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied. AIM: To determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review. METHODS: A retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab. RESULTS: At 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response. CONCLUSION: Ustekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.
Asunto(s)
Enfermedad de Crohn , Fístula Rectal , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Estudios Prospectivos , Calidad de Vida , Fístula Rectal/tratamiento farmacológico , Fístula Rectal/etiología , Estudios Retrospectivos , Ustekinumab/uso terapéuticoRESUMEN
Purpose: Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Materials and Methods: Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Results: Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for <2 months of duration (P < 0.05). Conclusion: There was a significant increase in microsporidia infection in autoimmune disease patients undergoing treatment with TNF-α antagonists, and the duration of treatment is one of the risk factors. The study highlights the importance of microsporidia testing in immunocompromised patients, particularly those undergoing treatment with anti-TNF-α drugs and emphasises the need for awareness among clinicians regarding this opportunistic parasite.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Microsporidiosis/complicaciones , Estudios de Casos y Controles , Diarrea/etiología , Heces/microbiología , Femenino , Humanos , Masculino , Microsporidios/aislamiento & purificación , Microsporidiosis/tratamiento farmacológico , Microsporidiosis/inmunología , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
Immunology and immunotherapy of cancer is an expanding field in oncology, with recent great achievements obtained through the new successful approaches implemented to circumvent immune evasion, which is undoubtedly considered a novel hallmark of cancer. Translational research in this topic has revealed targets that can be modulated in the clinical setting with new compounds and strategies. Like most of the tumors, breast cancer is considered a complex and heterogeneous disease in which host immune responses have been also recently demonstrated of critical relevance. T infiltrating lymphocyte measurement is suggested as a powerful new tool necessary to predict early breast cancer evolution, especially for the her2-positive and triple-negative subtypes. Other biomarkers in tissue and peripheral blood are under intense scrutiny to ascertain their eventual role as prognostic and/or predictive factors. This background has fueled the interest in developing clinical research strategies to test activity of modern immunotherapy in breast cancer, which constitutes the main focus of this review.
Asunto(s)
Neoplasias de la Mama/terapia , Inmunoterapia/métodos , Inmunoterapia/tendencias , Femenino , HumanosRESUMEN
Although 2-nitropropane is a potentially harmful compound present in cigarette smoke, there are few fully-validated, modern methods to quantitate it in mainstream cigarette smoke. We developed an isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method for the detection of 2-nitropropane in mainstream cigarette smoke. The vapor fraction of mainstream cigarette smoke was collected in inert polyvinyl fluoride gas sampling bags and extracted with hexanes containing isotopically labeled internal standard, then purified and concentrated via solid-phase extraction using a normal phase silica adsorbent and a 100% dichloromethane eluant. This method is sensitive enough to measure vapor phase 2-nitropropane concentrations in the nanogram range, with a 19 ng per cigarette method limit of detection. Product variability estimated from the analysis of 15 cigarette products yielded relative standard deviations ranging from 5.4% to 15.7%, and estimates of precision from two quality control products yielded relative standard deviations of 9.49% and 14.9%. Under the Health Canada Intense smoking regimen, 2-nitropropane in machine-generated mainstream smoke from 15 cigarette products ranged from 98.3 to 363 ng per cigarette.
Bien que le 2-nitropropane soit un composé potentiellement nocif présent dans la fumée de cigarette, il y a peu de méthodes modernes qui sont completement validees pour determiner sa quantité principale dans la fumée de cigarette. Nous avons développé une méthode de spectrométrie de masse en tandem avec chromatographie en phase gazeuse à dilution isotopique (ID-GC-MS / MS) pour la détection du 2-nitropropane dans la fumée principale de cigarette. La fraction vapeur de la fumée principale du cigarette a été collectee dans des sacs d'échantillonnage inertes de fluorure de polyvinyle et extrait à l'hexane contenant un étalon intern marqué isotopiquement, puis purifiée et concentrée par extraction en phase solide en utilisant un adsorbant de silice en phase normale et un éluant à 100% de dichlorométhane. Cette méthode est suffisamment sensible pour mesurer les concentrations de 2-nitropropane en phase vapeur dans la gamme des nanogrammes, avec une limite de détection de 19 ng par cigarette. À partir de l'analyse de 15 produits de cigarette, la variabilité estimée des produits a donné des écarts-types relatifs compris entre 5,4% et 15,7% et les estimations de la précision de deux produits de contrôle de la qualité ont abouti à des écarts-types relatifs de 9,49% et 14,9%. Sous le régime de tabagisme intense de Santé Canada, la concentration de 2-nitropropane présente dans la fumée principale générée par machine à partir de 15 produits de cigarette variait de 98,3 à 363 ng par cigarette.
RESUMEN
Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been largely excluded from prior analysis due to difficulties with quantification. Quantifying harmful compounds in cigarette smoke is useful to compare products, to examine the impact of design parameters on delivery, and to help estimate exposures. A sensitive high-throughput method has been developed for quantifying nitrobenzene in machine-generated mainstream cigarette smoke using isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in the low nanogram range, with a 418â¯pg/cig method limit of detection. Precision estimates from two quality control cigarette products resulted in percent relative standard deviations of 11.5% and 14.9%; product variability estimates from 13 cigarette products resulted in percent relative standard deviations ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream smoke from 15 cigarette products are reported and range from 18 to 38â¯ng/cig under the Health Canada Intense smoking regimen.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Nicotiana/química , Nitrobencenos/análisis , Contaminación por Humo de Tabaco/análisis , Calibración , Canadá , Iones , Límite de Detección , Material Particulado/análisis , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem , Productos de Tabaco/análisisRESUMEN
PURPOSE: Multidisciplinary evaluation (MDE) of hepatocellular cancer (HCC) is the current standard, often provided through a tumor board (TB) forum; this standard is limited by oncology workforce shortages and lack of a TB at every institution. Virtual TBs (VTBs) may help overcome these limitations. Our study aim was to assess the impact of a regional VTB on the MDE process for patients with HCC. METHODS: A retrospective cohort study was conducted, including patients with HCC referred to a tertiary cancer center from regional facilities (2009 to 2013). Baseline characteristics and outcomes were compared based on the referral mechanism: VTB versus subspecialty consultation (non-VTB). The primary outcome was comprehensive MDE (all required specialists present and key topics discussed). Secondary outcomes included timeliness of MDE and travel burden to complete MDE. Univariable and multivariable logistic regressions were performed to examine the association of a VTB with comprehensive MDE. RESULTS: A total of 116 patients were included in the study; 48 (41.4%) were evaluated through the VTB. A higher proportion of VTB patients received comprehensive MDE (91.7% v 64.7%; P = .001); the VTB was independently associated with higher odds of accomplishing comprehensive MDE (odds ratio, 6.0; 95% CI, 1.2 to 29.9; P = .02). VTB patients completed MDE significantly faster (median, 23 v 39 days; P < .001), with lower travel burden (median, 0 v 683 miles traveled; P < .001). CONCLUSION: This VTB program positively affected the process of care for patients with HCC by improving the quality and timeliness of the MDE process, while avoiding the burden arising from travel needs. Future studies should focus on implementation of VTB programs on a wider scale.
Asunto(s)
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Manejo de Atención al Paciente/organización & administración , Consulta Remota/organización & administración , Anciano , Estudios de Cohortes , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Manejo de Atención al Paciente/métodos , Derivación y Consulta/organización & administración , Derivación y Consulta/estadística & datos numéricos , Consulta Remota/métodos , Estudios Retrospectivos , Estados Unidos , United States Department of Veterans Affairs , Comunicación por VideoconferenciaRESUMEN
The extent of growth suppression and recovery following exposure to 4,5',8-trimethylpsoralen (TMP) plus UV-A irradiation was studied in 3 diploid human fibroblast strains. Inhibition of cellular proliferation was dose-dependent within the concentration range of TMP that was tested (1-4 X 10(-7) M), using a constant level of UV-A (0.24 J/cm2). The population generation (doubling) times for all cell strains were progressively lengthened under these conditions while maximal cell densities were reduced. At 2-4 X 10(-7) M TMP in the presence of UV-A, there was a triphasic pattern of growth which consisted of (1) proliferative activity during the first 24-36 hr, followed by; (2) complete growth inhibition for variable periods of time and; (3) a recovery period of log phase proliferation that was not as vigorous as measured for untreated cells. There were also declines in the percentage of cells labeled with 3H-Tdr at various times after TMP-UV-A treatment. These measurements were essentially identical for the three fibroblast strains evaluated. In that the cells employed for these investigations were derived from embryonic pulmonary tissue, neonatal foreskin and the buttock skin of an adult male, it seems unlikely that donor age and tissue source were important variables in determining growth response patterns after TMP-UV-A exposure. Because proliferative recovery was attenuated after this photochemical injury, we conclude that the biologic effect(s) of TMP-UV-A extend beyond the known period of psoralen-DNA cross-link removal.
Asunto(s)
Fibroblastos/efectos de los fármacos , Furocumarinas/farmacología , Trioxsaleno/farmacología , Rayos Ultravioleta , Adulto , Nalgas , División Celular/efectos de los fármacos , Células Cultivadas , Replicación del ADN/efectos de los fármacos , Diploidia , Humanos , Recién Nacido , Pulmón , Masculino , Pene , Piel/citologíaRESUMEN
The author describes the development and practice of program whose purpose is to increase the quality of at home care for post-hospitalized patients and to improve the relationship between Primary Health Care Centers and Specialized Health Care Centers. To this end, a Combined Report for a Certificate of Being Cured has been developed. As this program has been established and developed, its results have improved: More patients who leave the Hospital with a certificate of being cured are registered in Primary Health Care Centers in order to carry out the necessary treatment they require. As time passes, there is a higher degree of identification of the Hospital Service and the Health Center, as well as the Nursing Professional, so that there may be bilateral communication (Hospital/Center to Health-Center to Health/Hospital). Nursing care for this type of patient is becoming quicker all the time especially if we bear in mind the date of the hospital certificate of being cured and the contact date between the patient and the primary Health Center after the patient's release from the hospital.
Asunto(s)
Servicios de Atención de Salud a Domicilio/normas , Enfermería/normas , Alta del Paciente , Estudios Transversales , Humanos , EspañaRESUMEN
We aimed to study the complexity and time asymmetry of short-term heart rate variability (HRV) as an index of complex neurocardiac control in response to stress using symbolic dynamics and time irreversibility methods. ECG was recorded at rest and during and after two stressors (Stroop, arithmetic test) in 70 healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%), and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV magnitude was quantified by linear parameters: spectral powers in low (LF) and high frequency (HF) bands. Our results showed a reduction of HRV complexity in stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern classification analysis revealed significantly higher 0V% and lower 2LV% with both stressors, indicating a shift in sympathovagal balance, and significantly higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time irreversibility: significantly lower G% and E with both stressors, P% index significantly declined only with arithmetic test. Linear HRV analysis confirmed vagal withdrawal (lower HF) with both stressors; LF significantly increased with Stroop and decreased with arithmetic test. Correlation analysis revealed no significant associations between symbolic dynamics and time irreversibility. Concluding, symbolic dynamics and time irreversibility could provide independent information related to alterations of neurocardiac control integrity in stress-related disease.
Asunto(s)
Frecuencia Cardíaca , Estrés Psicológico/fisiopatología , Pensamiento/fisiología , Femenino , Humanos , Modelos Lineales , Masculino , Conceptos Matemáticos , Dinámicas no Lineales , Solución de Problemas , Descanso/fisiología , Test de Stroop , Tiempo , Adulto JovenRESUMEN
BACKGROUND: The urokinase plasminogen activator receptor (u-PAR) focuses the proteolytic activity of the urokinase plasminogen activator (u-PA) on the endothelial cell surface, thus promoting angiogenesis in a protease-dependent manner. The u-PAR may exist in a glycophosphatidylinositol-anchored and in a soluble form (soluble u-PAR [Su-PAR]), both including the chemotactic Ser88 -Arg-Ser-Arg-Tyr9² internal sequence. OBJECTIVE: To investigate whether Su-PAR may trigger endothelial cell signaling leading to new vessel formation through its chemotactic Ser88 -Arg-Ser-Arg-Tyr9² sequence. METHODS AND RESULTS: In this study, the formation of vascular-like structures by human umbilical vein endothelial cells was assessed by using a matrigel basement membrane preparation. First, we found that Su-PAR protein promotes the formation of cord-like structures, and that this ability is retained by the isolated Ser(88) -Arg-Ser-Arg-Tyr9² chemotactic sequence, the maximal effect being reached at 10 nmol L⻹ SRSRY peptide (SRSRY). This effect is mediated by the α(v) ß3 vitronectin receptor, is independent of u-PA proteolytic activity, and involves the internalization of the G-protein-coupled formyl-peptide receptor in endothelial cells. Furthermore, exposure of human saphenous vein rings to Su-PAR or SRSRY leads to a remarkable degree of sprouting. Finally, we show that Su-PAR and SRSRY promote a marked response in angioreactors implanted into the dorsal flank of nude mice, retaining 91% and 66%, respectively, of the angiogenic response generated by a mixture of vascular endothelial growth factor and fibroblast growth factor type 2. CONCLUSIONS: Our results show a new protease-independent activity of Su-PAR that stimulates in vivo angiogenesis through its Ser88 -Arg-Ser-Arg-Tyr9² chemotactic sequence.
Asunto(s)
Quimiotaxis , Neovascularización Fisiológica/fisiología , Receptores del Activador de Plasminógeno Tipo Uroquinasa/fisiología , Secuencia de Aminoácidos , Animales , Células Cultivadas , Técnicas de Cocultivo , Humanos , Ratones , Ratones Desnudos , Microscopía Fluorescente , Receptores del Activador de Plasminógeno Tipo Uroquinasa/química , Transducción de Señal , SolubilidadRESUMEN
OBJECTIVE: To evaluate the diagnostic role of bronchoalveolar lavage (BAL) in mechanically ventilated patients with suspected pneumonia and to describe the clinical outcome in the different kinds of pneumonia in critically ill patients. DESIGN: Descriptive study. SETTING: A 17-bed medical and surgical intensive care unit. PATIENTS: Mechanically ventilated patients admitted to the ICU from November 2003 to March 2006 with suspected pneumonia who underwent bronchoscopy with BAL. INTERVENTIONS: BAL was performed by fiberoptic bronchoscopy with three aliquots of 50 ml sterile normal saline. Recovered BAL fluid was pro-cessed for microbiologic analysis. MAIN VARIABLES OF INTEREST: Age, APACHE II score within the first 24 hours of admission, time on mechanical ventilation, ICU length of stay, mortality, and isolated bacteria were analyzed. RESULTS: A total of 96 cases of suspected pneumonia with BAL were recruited, including 4 groups: community associated pneumonia (CAP), 12 cases, early-onset ventilator-associated pneumonia (VAP), 26 cases, late-onset ventilator-associated pneumonia, 43 cases, and immunocompromised patients, 15 cases. BAL was positive (> 10000 ufc/ml) in 40 (41.7%) patients (2, 16, 17 and 5 patients with CAP, early-onset VAP, late-onset VAP and immunocompromised, respectively). Mortality was 33.3%, 26.9%, 25.6% and 73.3% in CAP, early-onset VAP, late-onset VAP and immunocompromised patients respectively. CONCLUSIONS: The low incidence of positive BAL in the CAP group supports using BAL only for particularly severe, selected cases. Mortality was very high in the immunocompromised patients. In the light of our personal experience, BAL is most useful in the diagnosis of pneumonia in the group of patients with VAP.
Asunto(s)
Líquido del Lavado Bronquioalveolar , Neumonía Asociada al Ventilador/diagnóstico , Humanos , Persona de Mediana EdadRESUMEN
Experience with a colonoscope with a distal segment that allows for the incorporation of dilating olives of the Eder Puestow type is presented. 15 patients with the diagnosis of benign stenosis of the colon or rectum who suffered of abdominal pain and constipation were treated. In 13 patients it was possible to eliminate the patients symptoms. There where no complications. The dilating colonoscope is a valid, alternative in the management of stenosis of the colon and rectum.
Asunto(s)
Enfermedades del Colon/terapia , Colonoscopios , Enfermedades del Recto/terapia , Colonoscopía/métodos , Constricción Patológica , Dilatación/instrumentación , Endoscopios Gastrointestinales , Endoscopía Gastrointestinal/métodos , HumanosRESUMEN
A 33-year old farmer ingested approximately 300 ml of a 20% solution of diquat along with about 80 mg flunitrazepam. The patient presented neurological (coma grade I), digestive (oro-pharyngeal erosions, ileus), hepatic (cytolysis), hematological (thrombopenia) and renal (tubular dysfunction) signs. Plasma creatinine did not exceed 1.22 mg/dl (upper normal value), but retinol binding protein level in urine (a marker of renal tubular dysfunction) reached a value of 337 mg/d (normal values less than 300 micrograms/d). Its level returned to normal value 18 days after the ingestion. Four hours after the poisoning, diquat level in blood amounted to 10.4 mg/l, but its level was below the detection limit (0.2 mg/l) 6 hours later. In urine, however, diquat was detected until day 13. The following therapy was applied: ventilation (FiO2:0.21), gastro-intestinal lavage, hemoperfusion, anti-oxidants and prolonged forced diuresis. The patient made an uneventful recovery. intestinal washout must be applied with caution since an ileus is a classical complication of diquat poisoning. Hemoperfusion was found to be of little value. The interest of prolonged application of forced diuresis is suggested by the detection of diquat in urine for about 2 weeks along with the presence of biological signs of renal tubular dysfunction.
Asunto(s)
Diquat/envenenamiento , Enfermedades Renales/inducido químicamente , Compuestos de Piridinio/envenenamiento , Adulto , Diquat/orina , Diuresis/efectos de los fármacos , Flunitrazepam/toxicidad , Humanos , Enfermedades Renales/metabolismo , Túbulos Renales Proximales/metabolismo , Masculino , Proteinuria/inducido químicamente , Proteinuria/metabolismoRESUMEN
Objetivo. Evaluar la utilidad diagnóstica del lavado broncoalveolar (LBA) en enfermos en ventilación mecánica con sospecha de neumonía y describir los resultados clínicos de los diferentes tipos de neumonía en enfermos críticos. Diseño. Estudio descriptivo. Ámbito. Unidad de cuidados intensivos (UCI) médico-quirúrgica de 17 camas. Pacientes. Enfermos ingresados en UCI desde noviembre de 2003 a marzo de 2006 con ventilación mecánica y sospecha clínica de neumonía a quienes se realizó LBA. Intervenciones. Se realizó LBA a través de tubo orotraqueal con 150 ml de suero salino fisiológico, repartidos en tres alícuotas de 50 ml; la muestra se procesó para estudio microbiológico. Principales variables de interés. Edad, APACHE II al ingreso, días en ventilación mecánica, estancia en UCI, mortalidad y agentes etiológicos aislados en el LBA. Resultados. Se incluyó a 96 pacientes a quienes se realizó LBA; se distinguieron 4 grupos: neumonía adquirida en la comunidad (NAC), 12 casos; neumonía asociada a ventilación mecánica (NAVM) precoz, 26 casos. NAVM tardía, 43 casos, y neumonía en enfermos inmunodeficientes, 15 casos. El LBA fue positivo (> 10.000 ufc/ml) en 40 (41,7%) pacientes (2 con NAC, 16 con NAVM precoz, 17 con NAVM tardía, 5 con neumonía e inmunodeficiencia). La mortalidad fue del 33,3, el 26,9, el 25,6 y el 73,3% en NAC, NAVM precoz, NAVM tardía e inmunodeficientes, respectivamente. Conclusiones. La escasa sensibilidad del LBA en la NAC corrobora la actitud de limitar su indicación sólo a casos seleccionados. En el grupo de enfermos inmunodeficientes la mortalidad fue muy elevada. El LBA, según nuestra limitada experiencia, tiene su mayor utilidad en el diagnóstico de NAVM
Objective. To evaluate the diagnostic role ofbronchoalveolar lavage (BAL) in mechanicallyventilated patients with suspected pneumoniaand to describe the clinical outcome in the differentkinds of pneumonia in critically ill patients.Design. Descriptive study.Setting. A 17-bed medical and surgical intensivecare unit.Patients. Mechanically ventilated patients admittedto the ICU from November 2003 to March2006 with suspected pneumonia who underwentbronchoscopy with BAL.Interventions. BAL was performed by fiberopticbronchoscopy with three aliquots of 50 ml sterilenormal saline. Recovered BAL fluid was processedfor microbiologic analysis.Main variables of interest. Age, APACHE IIscore within the first 24 hours of admission, timeon mechanical ventilation, ICU length of stay,mortality, and isolated bacteria were analyzed.Results. A total of 96 cases of suspected pneumoniawith BAL were recruited, including 4 groups: community associated pneumonia (CAP), 12 cases, early-onset ventilator-associated pneumonia (VAP), 26 cases, late-onset ventilator-associated pneumonia, 43 cases, and immunocompromised patients, 15 cases. BAL was positive (>10000 ufc/ml) in 40 (41.7%) patients (2, 16, 17 and5 patients with CAP, early-onset VAP, late-onset VAP and immunocompromised, respectively).Mortality was 33.3%, 26.9%, 25.6% and 73.3% inCAP, early-onset VAP, late-onset VAP and immunocompromised patients respectively.Conclusions. The low incidence of positive BALin the CAP group supports using BAL only for particularlysevere, selected cases. Mortality wasvery high in the immunocompromised patients. Inthe light of our personal experience, BAL is mostuseful in the diagnosis of pneumonia in the groupof patients with VAP