RESUMEN

PURPOSE: Non-tuberculous mycobacteria (NTM) are important pathogens in lung transplant recipients. This study describes the spectrum of NTM respiratory tract infections and examines the association of NTM infections with lung transplant complications. METHODS: Data from 208 recipients transplanted from November 1990 to November 2005 were analyzed. Follow-up data were available to November 2010. Lung infection was defined by bronchoalveolar lavage, sputum, or blood cultures in the appropriate clinical setting. All identified NTM respiratory tract infections were tabulated. The cohort of patients with NTM lung infections (NTM+) were compared to the cohort without infection (NTM-). Univariate and multivariate analysis was performed to determine characteristics associated with NTM infection. Survival analyses for overall survival and development of bronchiolitis obliterans syndrome (BOS) were also performed. RESULTS: In total, 52 isolates of NTM lung infection were identified in 30 patients. The isolates included Mycobacterium abscessus (46%), Mycobacterium avium complex (MAC) (36%), Mycobacterium gordonae (9%), Mycobacterium chelonae (7%), and Mycobacterium fortuitum (2%), with multiple NTM isolates seen on 3 different occasions. The overall incidence was 14%, whereas cumulative incidences at 1, 3, and 5 years after lung transplantation were 11%, 15%, and 20%, respectively. Comparisons between the NTM+ and NTM- cohorts revealed that NTM+ patients were more likely to be African-American and have cytomegalovirus mismatch. Although no difference was seen in survival, the NTM+ cohort was more likely to develop BOS (80% vs. 58%, P = 0.02). NTM+ infection, however, was not independently associated with development of BOS by multivariate analysis. CONCLUSION: With nearly 20 years of follow-up, 14% of lung recipients develop NTM respiratory tract infections, with M. abscessus and MAC more commonly identified. M. gordonae was considered responsible for nearly 10% of NTM infections. Although survival of patients with NTM infections is similar, a striking difference in BOS rates is present in the NTM+ and NTM- groups.

Asunto(s)

Bronquiolitis Obliterante/epidemiología , Trasplante de Pulmón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Adulto , Cultivo de Sangre , Bronquiolitis Obliterante/etiología , Lavado Broncoalveolar , Femenino , Estudios de Seguimiento , Rechazo de Injerto/complicaciones , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Prevalencia , Infecciones del Sistema Respiratorio/complicaciones , Estudios Retrospectivos , Esputo , Análisis de Supervivencia , Factores de Tiempo

RESUMEN

Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.

Asunto(s)

Circulación Sanguínea , Muerte Encefálica , Rechazo de Injerto/epidemiología , Trasplante de Pulmón/estadística & datos numéricos , Pulmón/fisiología , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adulto , California/epidemiología , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Incidencia , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Sistema de Registros , Factores de Riesgo , Donantes de Tejidos

RESUMEN

The production of carboxymethyl cellulase (CMCase) by Bacillus halodurans IND18 under solid substrate fermentation (SSF) using cow dung was optimized through two level full factorial design and second order response surface methodology (RSM). The central composite design (CCD) was employed to optimize the vital fermentation parameters, such as pH of the substrate, concentration of nitrogen source (peptone) and ion (sodium dihydrogen phosphate) sources in medium for achieving higher enzyme production. The optimum medium composition was found to be 1.46% (w/w) peptone, 0.095% (w/w) sodium dihydrogen phosphate and pH 8.0. The model prediction of 4210IU/g enzyme activity at optimum conditions was verified experimentally as 4140IU/g. The enzyme was active over a broad temperature range (40-60±1°C) and pH (7.0-9.0) with maximal activity at 60±1°C and pH 8.0. This study demonstrated the potential of cow dung as novel substrate for CMCase production.

Asunto(s)

Bacillus/enzimología , Celulasa/química , Estiércol , Agricultura/métodos , Animales , Bacillus cereus/enzimología , Bovinos , Contaminantes Ambientales/química , Fermentación , Residuos de Alimentos , Concentración de Iones de Hidrógeno , Microbiología Industrial/métodos , Modelos Estadísticos , Nitrógeno/química , Oryza , Peptonas/química , Pseudoalteromonas/enzimología , Eliminación de Residuos/métodos , Shewanella/enzimología , Temperatura , Xanthomonas/enzimología

RESUMEN

BACKGROUND: Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-AspergillusIMIs in this population have not been well documented. METHODS: LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis. RESULTS: During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03). CONCLUSIONS: There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality.

Asunto(s)

Aspergilosis/epidemiología , Fusariosis/epidemiología , Rechazo de Injerto/prevención & control , Trasplante de Corazón-Pulmón , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Trasplante de Pulmón , Mucormicosis/epidemiología , Adulto , Aspergilosis/etiología , Aspergilosis/inmunología , Estudios de Cohortes , Femenino , Fusariosis/etiología , Fusariosis/inmunología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mucormicosis/etiología , Mucormicosis/inmunología , Micosis/epidemiología , Micosis/etiología , Micosis/inmunología , Estudios Retrospectivos , Factores de Riesgo , Scedosporium

RESUMEN

Implementation of the lung allocation score (LAS) in 2005 led to transplantation of older and sicker patients without altering 1-year survival. However, long-term survival has not been assessed and emphasizing the 1-year survival metric may actually sustain 1-year survival while not reflecting worsening longer-term survival. Therefore, we assessed overall and conditional 1-year survival; and the effect of crossing the 1-year threshold on hazard of death in three temporal cohorts: historical (1995-2000), pre-LAS (2001-2005) and post-LAS (2005-2010). One-year survival post-LAS remained similar to pre-LAS (83.1% vs. 82.1%) and better than historical controls (75%). Overall survival in the pre- and post-LAS cohorts was also similar. However, long-term survival among patients surviving beyond 1 year was worse than pre-LAS and similar to historical controls. Also, the hazard of death increased significantly in months 13 (1.44, 95% CI 1.10-1.87) and 14 (1.43, 95% CI 1.09-1.87) post-LAS but not in the other cohorts. While implementation of the LAS has not reduced overall survival, decreased survival among patients surviving beyond 1 year in the post-LAS cohort and the increased mortality occurring immediately after 1 year suggest a potential negative long-term effect of the LAS and an unintended consequence of increased emphasis on the 1-year survival metric.

Asunto(s)

Asignación de Recursos para la Atención de Salud , Trasplante de Pulmón , Estudios de Cohortes , Humanos , Tasa de Supervivencia

RESUMEN

Studies were carried out for ß-glucosidase production using apple pomace (AP) in solid-state fermentation using 2(4) factorial design and response surface methodology. The influence of four independent variables including initial moisture level and inducers [veratryl alcohol (VA), lactose (LAC) and copper sulfate (CS)] was studied. The experimental design showed that initial moisture level had significant negative effect on the response. Higher ß-glucosidase activity of 64.18 IU/gram fermented substrate (gfs) was achieved in solid-state tray fermentation with optimum conditions having initial moisture level 55% (v/w), pH 4.5, 2 mM/kg VA, 2% (w/w) LAC and 1.5 mM/kg CS concentration, respectively,. The non-specific chitinase 70.28 ± 6.34 IU/gfs and chitosanase activities 60.18 ± 6.82 to 64.20 ± 7.12 IU/gfs were observed. The study demonstrated that AP can be potentially used for the ß-glucosidase production by Aspergillus niger. Moreover, ß-glucosidase can be used for the hydrolysis of chitin/chitosan to depolymerized products and in the formulation of biocontrol agents for enhanced entomotoxicity levels.

Asunto(s)

Aspergillus niger/enzimología , Quitina/metabolismo , Quitosano/metabolismo , Malus/enzimología , beta-Glucosidasa/biosíntesis , beta-Glucosidasa/metabolismo , Aspergillus niger/metabolismo , Alcoholes Bencílicos/química , Alcoholes Bencílicos/metabolismo , Agentes de Control Biológico , Quitinasas/biosíntesis , Quitinasas/metabolismo , Sulfato de Cobre/química , Sulfato de Cobre/metabolismo , Fermentación , Glicósido Hidrolasas/biosíntesis , Glicósido Hidrolasas/metabolismo , Concentración de Iones de Hidrógeno , Hidrólisis , Lactosa/química , Lactosa/metabolismo , Malus/metabolismo , Agua/química , Agua/metabolismo

RESUMEN

AIMS: To evaluate the potential of apple pomace (AP) supplemented with rice husk for hyper citric acid production through solid-state fermentation by Aspergillus niger NRRL-567. Optimization of two key parameters, such as moisture content and inducer (ethanol and methanol) concentration was carried out by response surface methodology. METHODS AND RESULTS: In this study, the effect of two crucial process parameters for solid-state citric acid fermentation by A. niger using AP waste supplemented with rice husk were thoroughly investigated in Erlenmeyer flasks through response surface methodology. Moisture and methanol had significant positive effect on citric acid production by A. niger grown on AP (P < 0·05). Higher values of citric acid on AP by A. niger (342·41gkg(-1) and 248·42gkg(-1) dry substrate) were obtained with 75% (v/w) moisture along with two inducers [3% (v/w) methanol and 3% (v/w) ethanol] with fermentation efficiency of 93·90% and 66·42%, respectively depending upon the total carbon utilized after 144h of incubation period. With the same optimized parameters, conventional tray fermentation was conducted. The citric acid concentration of 187·96gkg(-1) dry substrate with 3% (v/w) ethanol and 303·34gkg(-1) dry substrate with 3% (v/w) methanol were achieved representing fermentation efficiency of 50·80% and 82·89% in tray fermentation depending upon carbon utilization after 120h of incubation period. CONCLUSIONS: Apple pomace proved to be the promising substrate for the hyper production of citric acid through solid-state tray fermentation, which is an economical technique and does not require any sophisticated instrumentation. SIGNIFICANCE AND IMPACT OF THE STUDY: The study established that the utilization of agro-industrial wastes have positive repercussions on the economy and will help to meet the increasing demands of citric acid and moreover will help to alleviate the environmental problems resulting from the disposal of agro-industrial wastes.

Asunto(s)

Ácido Cítrico/metabolismo , Fermentación , Residuos Industriales , Malus , Aspergillus niger/metabolismo , Etanol/metabolismo , Industria de Procesamiento de Alimentos , Metanol/metabolismo

RESUMEN

Implemented in 2005, the lung allocation score (LAS) aims to distribute donor organs based on overall survival benefits for all potential recipients, rather than on waiting list time accrued. While prior work has shown that patients with scores greater than 46 are at increased risk of death, it is not known whether that risk is equivalent among such patients when stratified by LAS score and diagnosis. We retrospectively evaluated 5331 adult lung transplant recipients from May 2005 to February 2009 to determine the association of LAS (groups based on scores of < or =46, 47-59, 60-79 and > or =80) and posttransplant survival. When compared with patients with LAS < or = 46, only those with LAS > or = 60 had an increased risk of death (LAS 60-79: hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.21-1.90; LAS > or = 80: HR, 2.03; CI, 1.61-2.55; p < 0.001) despite shorter median waiting list times. This risk persisted after adjusting for age, diagnosis, transplant center volume and donor characteristics. By specific diagnosis, an increased hazard was observed in patients with COPD with LAS > or = 80, as well as those with IPF with LAS > or = 60.

Asunto(s)

Asignación de Recursos para la Atención de Salud , Trasplante de Pulmón , Sobrevida , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can cause significant morbidity and mortality in lung and heart-lung transplant recipients. We evaluated the utility of a multi-drug protocol for the treatment of RSV- and PIV-related infections. PATIENTS AND METHODS: RSV or PIV was identified in 25 patients with a total of 29 infectious episodes between January 2006 and December 2007. The study included 20 women and 5 men, mean age 42 +/- 13 years. Fifteen patients had received bilateral lung transplant and the remainder either received single lung or heart-lung transplant. Mean time from transplant to infection was 1192 days. RSV was identified in 23 cases, PIV in 7 cases. Patients underwent treatment with inhaled ribavirin, methylprednisolone, and intravenous immunoglobulin (IVIG). RSV-positive patients were also treated with palivizumab. We retrospectively evaluated their clinical status and pulmonary function for a 1-year interval before and after the date of infection. RESULTS: Average baseline forced expiratory volume in 1 s (FEV(1)) before infection was 2.14 +/- 0.68 L/min. Average decline in FEV(1) was 5.7% at the time of infection. Average FEV(1) during post-treatment follow-up was not significantly different than baseline (2.16 +/- 0.80 L/min). Among patients with bronchiolitis obliterans syndrome (BOS) stages 1, 2, or 3 at the time of infection, average FEV(1) declined by 14.8% and remained lower at 9.1% during follow-up when compared with patients with BOS stages 0 or 0p. No complications resulted from treatment. One patient died during follow-up as a result of pre-existing liver failure. CONCLUSIONS: This study of lung and heart-lung transplant recipients infected with RSV and PIV shows that a multi-drug regimen including inhaled ribavirin, corticosteroids, and IVIG (with or without palivizumab) is safe and effective. Prompt diagnosis and therapy for patients with RSV or PIV infections are critical for maintaining lung function.

Asunto(s)

Corticoesteroides , Trasplante de Corazón-Pulmón/efectos adversos , Factores Inmunológicos , Trasplante de Pulmón/efectos adversos , Infecciones por Paramyxoviridae/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Ribavirina , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Protocolos Clínicos , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Palivizumab , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Pruebas de Función Respiratoria , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Estudios Retrospectivos , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del Tratamiento

RESUMEN

PURPOSE: Gram-positive (GP) organisms are among the most common cause of infections in early postsurgical and immunocompromised populations. Patients recovering from lung transplantation (LT) are particularly susceptible owing to the physiologic stress imposed by surgery and induction with intense immunosuppression. Sites, types, and timing of GP infections following LT are not well documented. This report describes the clinical spectrum of GP infections and their effects on surgical airway complications (SAC) and bronchiolitis obliterans syndrome (BOS) following LT. METHODS AND MATERIALS: Data were collected from 202 patients undergoing 208 LT procedures at a single institution between November 1990 and November 2005. Data were retrospectively analyzed according to timing, location, and causative pathogen. RESULTS: In the median follow-up period of 2.7 years (range, 0-13.6 years), 137 GP infections were confirmed in 72 patients. Sites of infection included respiratory tract (42%), blood (27%), skin, wound and catheter (21%), and other (10%). GP pathogens identified were Staphylococcus species (77%), Enterococcus species (12%), Streptococcus species (6%), Pneumococcus (4%), and Eubacterium lentum (1%). The likelihood of SAC and BOS was increased in lung allograft recipients with GP pneumonia as compared with those without (hazard ratio 2.1; 95% confidence interval=1.5-3.1). CONCLUSIONS: GP organisms were responsible for infections in 40% of lung allograft recipients and most commonly isolated from the respiratory tract and blood stream. Staphylococcal species were most frequently identified, 42% of which were methicillin-resistant Staphylococcus aureus (MRSA). Given the strong association of respiratory tract infections with the development of SAC and BOS, empiric antimicrobial strategies after LT should include agents directed against GP organisms, especially MRSA.

Asunto(s)

Bronquiolitis Obliterante , Bacterias Grampositivas , Infecciones por Bacterias Grampositivas/fisiopatología , Trasplante de Pulmón/efectos adversos , Infección de la Herida Quirúrgica , Adolescente , Adulto , Anciano , Bacteriemia/microbiología , Bronquiolitis Obliterante/microbiología , Bronquiolitis Obliterante/fisiopatología , Niño , Femenino , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/aislamiento & purificación , Bacterias Grampositivas/patogenicidad , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/fisiopatología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/fisiopatología , Staphylococcus/clasificación , Staphylococcus/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/fisiopatología , Síndrome , Adulto Joven

RESUMEN

PURPOSE: Clostridium difficile colitis (CDC) is the most common nosocomial infection of the gastrointestinal tract in patients with recent antibiotic use or hospitalization. Lung transplant recipients receive aggressive antimicrobial therapy postoperatively for treatment and prophylaxis of respiratory infections. This report describes the epidemiology of CDC in lung recipients from a single center and explores possible associations with bronchiolitis obliterans syndrome (BOS), a surrogate marker of chronic rejection. METHODS: Patients were divided into those with confirmed disease (CDC+) and those without disease (CDC-) based on positive C. difficile toxin assay. Because of a bimodal distribution in the time to develop CDC, the early postoperative CDC+ group was analyzed separately from the late postoperative CDC+ cohort with respect to BOS development. RESULTS: Between 1990 and 2005, 202 consecutive patients underwent 208 lung transplantation procedures. Of these, 15 lung recipients developed 23 episodes of CDC with a median follow-up period of 2.7 years (range, 0-13.6). All patients with confirmed disease had at least 1 of the following 3 risk factors: recent antibiotic use, recent hospitalization, or augmentation of steroid dosage. Of the early CDC+ patients, 100% developed BOS, but only 52% of the late CDC+ patients developed BOS, either preceding or following infection. CONCLUSION: CDC developed in 7.4% of lung transplant patients with identified risk factors, yielding a cumulative incidence of 14.7%. The statistical association of BOS development in early CDC+ patients suggests a relationship between early infections and future chronic lung rejection.

Asunto(s)

Clostridioides difficile , Enterocolitis Seudomembranosa/epidemiología , Trasplante de Pulmón/efectos adversos , Adolescente , Adulto , Anciano , Bronquiolitis Obliterante/epidemiología , Bronquiolitis Obliterante/etiología , Niño , Enterocolitis Seudomembranosa/microbiología , Femenino , Rechazo de Injerto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

Much has been studied and written about plastic changes in the CNS of humans triggered by events such as limb amputation. However, little is known about the extent to which the original pathways retain residual function after peripheral amputation. Our earlier, acute study on long-term amputees indicated that central pathways associated with amputated peripheral nerves retain at least some sensory and motor function. The purpose of the present study was to determine if these functional connections would be strengthened or improved with experience and training over several days time. To do this, electrodes were implanted within fascicles of severed nerves of long-term human amputees to evaluate the changes in electrically evoked sensations and volitional motor neuron activity associated with attempted phantom limb movements. Nerve stimulation consistently resulted in discrete, unitary, graded sensations of touch/pressure and joint-position sense. There was no significant change in the values of stimulation parameters required to produce these sensations over time. Similarly, while the amputees were able to improve volitional control of motor neuron activity, the rate and pattern of change was similar to that seen with practice in normal individuals on motor tasks. We conclude that the central plasticity seen after amputation is most likely primarily due to unmasking, rather than replacement, of existing synaptic connections. These results also have implications for neural control of prosthetic limbs.

Asunto(s)

Amputación Quirúrgica , Movimiento/fisiología , Plasticidad Neuronal/fisiología , Miembro Fantasma/fisiopatología , Propiocepción/fisiología , Adulto , Vías Aferentes/fisiopatología , Amputados , Análisis de Varianza , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Electrodos , Potenciales Evocados/fisiología , Potenciales Evocados/efectos de la radiación , Humanos , Psicometría/métodos , Umbral Sensorial , Factores de Tiempo

RESUMEN

We examined the recording characteristics of two different types of polymer-based longitudinal intrafascicular electrodes (LIFEs) in peripheral nerve: single-stranded (s-polyLIFEs) and multistranded (m-polyLIFEs). Recordings were also made from Pt-Ir wire-based electrodes (PtIrLIFEs) as a control. The electrodes were implanted in either tibial or medial gastrocnemius branches of the rabbit sciatic nerve, and in the sciatic nerve of rats. Recorded neural activity induced by manually elicited afferent neural activity showed that both polyLIFE versions performed comparably to PtIrLIFEs.

Asunto(s)

Potenciales de Acción/fisiología , Electrodos Implantados , Nervio Ciático/fisiología , Animales , Análisis de Falla de Equipo , Femenino , Iridio , Masculino , Nervios Periféricos/fisiología , Platino (Metal) , Politetrafluoroetileno , Conejos , Ratas , Ratas Sprague-Dawley

RESUMEN

PURPOSE: To compare the results of the nonduplex ultrasonography (US) Stroke Prevention Trial in Sickle Cell Anemia (STOP) with those of transcranial duplex power Doppler US by using the STOP protocol and to correlate abnormal transcranial Doppler findings with magnetic resonance (MR) imaging and MR angiographic findings. MATERIALS AND METHODS: One hundred twenty-five asymptomatic patients aged 2-16 years with sickle cell anemia or sickle cell-beta thalassemia were examined by using transcranial duplex power Doppler US with a 2.5-MHz transducer and classified according to STOP criteria. The results were compared with those obtained in the nonduplex STOP study. Eight of 10 patients with abnormal results, as well as one who had normal results and a subsequent stroke, were examined with MR imaging and MR angiography. RESULTS: Ten (8.0%) patients were judged to have abnormal findings by using the duplex Doppler US and STOP criteria compared with 9.4% of patients in the nonduplex US STOP study. Of the eight patients with abnormal transcranial Doppler US results who underwent MR imaging and MR angiography, six had abnormal MR imaging findings and all eight had abnormal MR angiographic findings. CONCLUSION: The STOP protocol can be reproduced by using duplex power Doppler US. Abnormal results with the STOP criteria strongly suggest vascular abnormality.

Asunto(s)

Anemia de Células Falciformes/diagnóstico por imagen , Accidente Cerebrovascular/prevención & control , Ultrasonografía Doppler Dúplex , Ultrasonografía Doppler Transcraneal , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/patología , Velocidad del Flujo Sanguíneo , Arterias Cerebrales/patología , Infarto Cerebral/diagnóstico , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Circulación Cerebrovascular , Niño , Preescolar , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Factores de Riesgo , Accidente Cerebrovascular/etiología , Talasemia beta/complicaciones , Talasemia beta/diagnóstico por imagen , Talasemia beta/patología

RESUMEN

Surgical therapy currently allows for the correction of many pathologic conditions affecting the vasculature of the central nervous system. Recent advances in technology have given the cerebrovascular specialist further options in the minimally invasive sphere. Endovascular techniques, complimentary to surgery in some conditions, are poised to replace conventional open surgery in others. A review of current interventional radiological procedures for the treatment and prevention of ischemic and hemorrhagic stroke are herewith presented.

Asunto(s)

Angioplastia de Balón/métodos , Angiografía Cerebral/métodos , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/terapia , Stents , Trastornos Cerebrovasculares/prevención & control , Femenino , Humanos , Masculino , Pronóstico , Radiología Intervencionista/métodos , Sensibilidad y Especificidad

RESUMEN

Cyclic adenosine monophosphate (cAMP)-mediated signal transduction was evaluated in synaptosomes prepared from rat brain cortex. Adenylate cyclase was responsive to known adenylate cyclase stimulators including peptides (CRH and VIP), catecholamines (norepinephrine and isoproterenol) and ligands that directly stimulate adenylate cyclase (forskolin). Cyclic AMP accumulation also increased approximately 2 to 3-fold, but none of the agonists was able significantly to activate cyclic AMP-dependent protein kinase (A-kinase) in cortical synaptosomes. However, in parallel studies with slices prepared from rat brain cortex, adenylate cyclase activity, cAMP accumulation and A-kinase activity were all stimulated by CRH, VIP, norepinephrine, isoproterenol and forskolin. These data suggest that, in intact synaptosomes, either the cellular machinery which facilitates binding of cAMP to the regulatory subunit of A-kinase is missing or the cAMP produced by adenylate cyclase is not accessible to A-kinase.

Asunto(s)

Corteza Cerebral/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Sinaptosomas/metabolismo , Adenilil Ciclasas/metabolismo , Animales , Corteza Cerebral/enzimología , Hormona Liberadora de Corticotropina/fisiología , Activación Enzimática , Humanos , Isoproterenol/farmacología , Norepinefrina/fisiología , Inhibidores de Proteínas Quinasas , Ratas , Sinaptosomas/enzimología

RESUMEN

Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.

Asunto(s)

Adenilil Ciclasas/metabolismo , Glándulas Suprarrenales/fisiología , Hormona Adrenocorticotrópica/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Adenohipófisis/metabolismo , Proteínas Quinasas/metabolismo , Adrenalectomía , Animales , Regulación hacia Abajo , Femenino , Humanos , Masculino , Ratas , Ratas Endogámicas

RESUMEN

Rats sacrificed after 4 days in the activity-stress paradigm or after 4 days of food restriction had significantly elevated levels of plasma corticosterone as compared to control rats. The approximately 5 fold increase in corticosterone in the stressed treatment groups was consistently found in all experiments. ACTH levels were elevated in activity-stress and food-restricted groups in some experiments but these increases were not statistically significant. Prolactin levels were significantly elevated in food-restricted group rats as compared to controls or activity-stress group animals in one experiment but this finding was not repeated in further experiments. In a second series of experiments, rats from activity-stressed and food-restricted treatment groups and controls were exposed to an acute stressor for 15 min prior to sacrifice to assess the effects of prior sustained stress on hormonal responses to an acute stressor. Exposure to 15 min of immobilization or intermittent footshock immediately prior to sacrifice increased plasma levels of corticosterone, ACTH and prolactin in control, food-restricted and activity-stressed rats. Generally, hormonal responses to the acute stress were similar in all treatment groups. However, in two experiments where the resting levels of corticosterone were especially elevated in the activity-stress group, the acute stress-induced rise in corticosterone was less than that seen for the other two treatment groups. In another experiment, administration of dexamethasone suppressed acute stress-evoked levels of ACTH and corticosterone in control, activity-stressed and food-restricted rats. Thus, rats exposed to 4 days of sustained stress were found to have consistently elevated resting levels of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Hormona Adrenocorticotrópica/sangre , Corticosterona/sangre , Privación de Alimentos , Sistemas Neurosecretores/fisiopatología , Prolactina/sangre , Estrés Fisiológico/sangre , Animales , Dexametasona/farmacología , Masculino , Actividad Motora/fisiología , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/metabolismo , Ratas , Ratas Endogámicas

RESUMEN

With the use of -cAMP/+cAMP activity ratios of cAMP-dependent protein kinase (A-kinase) in fat cell extracts as an index of cellular cAMP concentrations, it is apparent from both the current literature and from data presented in this paper that classical cell isolation procedures yield cells whose behavior is unpredictable from day to day. Herein, procedures are described for isolating adipocytes, preparing cytosolic extracts, and assaying A-kinase that result in kinase activity ratios in isolated cells equal to those in the fat pad from which cells are derived, approximately 0.05. An important modification in the procedure is the inclusion of 200 nM exogenous Ado in all cell manipulation media, and the data indicate that variable removal of contaminating endogenous Ado accounts for unpredictable results with standard cell isolation techniques. A further benefit of Ado inclusion is greatly reduced cell lysis. Acute removal of Ado with adenosine deaminase results in rapid elevation of A-kinase activity ratios and lipolysis which, in fasted animals, equals that achieved with lipolytic hormones. Cells from fed animals exhibit poor predictability in behavior. Moreover, A-kinase activity ratios exhibit seasonal tendencies in response to Ado removal, with cells isolated in spring being more activated than cells isolated later in the year. The information and procedures in this paper form the basis for succeeding papers on the regulation of adipocyte metabolism by hormones.

Asunto(s)

Tejido Adiposo/enzimología , Lipólisis , Proteínas Quinasas/metabolismo , 1-Metil-3-Isobutilxantina/farmacología , Adenina/análogos & derivados , Adenina/farmacología , Adenosina/metabolismo , Adenosina/farmacología , Adenosina Desaminasa/metabolismo , Animales , Isoproterenol/farmacología , Cinética , Masculino , Fenilisopropiladenosina/farmacología , Ratas , Ratas Endogámicas , Estaciones del Año , Inanición/metabolismo