RESUMEN

PURPOSE: The aim of PRISTINE was to evaluate the 6 and 12 months safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon for treatment of complex lower limb occlusive lesions (TASC II C & D) in patients with chronic limb threatening ischemia (CLTI) from Singapore. METHODS: PRISTINE was a prospective, non-randomized, single arm, observational, multi-investigator, single-center clinical study. Complication-free survival at 30 days was the safety clinical endpoint. Immediate technical success (ability to cross and dilate the lesion and achieve residual angiographic stenosis < 30%), 6-month primary vessel patency, limb salvage, clinically driven target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. RESULTS: Seventy five patients were included. There were 50 (68.0%) males; mean age, 69.0 ± 10.7 years. CLTI severity was based on the Rutherford Scale (R5 = 51; R6 = 17). Significant co-morbidities included diabetes mellitus (n = 68; 91.0%) and end-stage renal failure (n = 28; 37.0%). 112 atherosclerotic lesions were treated (TASC II D = 58 (52%); 76 (67%) de novo). There was 100% technical success. Mean lesion length treated was 22.4 ± 13.9 cm. Primary vessel patencies at 6 and 12 months were 64/86 (74%) and 43/74 (58%) and freedom from clinically driven TLR were 72/86 (84%) and 55/74 (74%) respectively. AFS was 61/73 (84.0%; five deaths and seven major lower extremity amputation) at 6-months. Mean Rutherford score improved from 5.1 ± 0.55 at baseline to 1.1 ± 2.05 (p < 0.05) at one year and there was a wound healing rate of 38/48 (79%) at the same timepoint. CONCLUSIONS: The Selution SLR™ drug eluting balloon is safe and efficacious in treating highly complex infra-inguinal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients with a high incidence of diabetes and end-stage renal failure. It is associated with highly satisfactory acute technical and clinical success, 12-month target lesion patency and AFS. LEVEL OF EVIDENCE: Level 2b, Individual Cohort Study.

Asunto(s)

Sistema de Registros , Sirolimus , Humanos , Masculino , Femenino , Anciano , Singapur , Estudios Prospectivos , Sirolimus/administración & dosificación , Resultado del Tratamiento , Angioplastia de Balón/métodos , Persona de Mediana Edad , Recuperación del Miembro/métodos , Isquemia Crónica que Amenaza las Extremidades , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea

RESUMEN

BACKGROUND: The rate of post-operative urinary retention (POUR) in inguinal hernia repairs (IHR) is estimated to be approximately 5.9% to 38% worldwide. Currently, there are minimal studies on the prophylaxis of POUR after IHR. Pre-operative administration of alpha-blockers such as (but not limited to) Tamsulosin, Prazosin and Alfuzosin has shown promising results in the prevention of POUR in patients undergoing IHR. This study aims to determine the effectiveness of prophylactic alpha-blockade in the prevention of POUR after IHR. METHODS: This study reports the findings of a systematic review and meta-analysis. Randomised controlled trials (RCTs) using prophylactic alpha-blockade for the prevention of POUR after open and/or laparoscopic IHR in patients aged more than 18 years in all sex groups were included. Multiple databases were searched from inception to October 2021 using the PRISMA flow diagram. Data were extracted and analysed to include eligibility criteria, comparator, intervention, study and participant characteristics. Studies excluded were non-RCT studies and patients with known urinary tract disorders such as benign prostate hypertrophy, urinary incontinence and cancer of the bladder or prostate. Subgroup analyses were also conducted. All effect measures of each data were odds ratio with 95% confidence interval. All studies were pooled using the dichotomous random effects Mantel-Haenszel statistical mode and I2 was used to assess heterogeneity. Publication bias was detected using the Cochrane risk-of-bias tool for randomised trials (RoB-2) involving two independent reviewers. RESULTS: A total of eight RCTs were identified which provided adequate numeric data for incorporation into the meta-analysis. Overall, administration of pre-operative alpha-blocker prior to IHR did not prevent POUR (95% CI 1.20 (0.96-1.49), I2: 34%). Subgroup analysis comparing pre-operative use of prophylactic alpha-blocker in open versus laparoscopic IHR has shown statistically significant reduction of POUR prevention in the laparoscopic group (95% CI 0.66 (0.47-0.92)), I2: 43%). The older age group benefited from pre-operative alpha-blocker use with reduced incidence of POUR post-IHR (95% CI 0.14 (0.08, 0.23), I2: 0%)). Gender did not affect the difference of incidence of POUR post-IHR despite pre-operative alpha-blockers (95% CI 0.62 (0.27, 1.44)), I2: 53%)). CONCLUSION: Overall, this meta-analysis has shown that administration of prophylactic alpha-blockers did not prevent POUR. However, there was statistically significant reduction of POUR in patients undergoing laparoscopic IHR as compared to open, as well as in older patients (age more than 60 years) after administration of pre-operative alpha-blocker. Hence, the use of pre-operative alpha-blocker especially in older patients should be considered and more RCTs should be undertaken.

Asunto(s)

Hernia Inguinal , Retención Urinaria , Masculino , Humanos , Anciano , Retención Urinaria/etiología , Retención Urinaria/prevención & control , Retención Urinaria/epidemiología , Hernia Inguinal/cirugía , Hernia Inguinal/complicaciones , Herniorrafia/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Tamsulosina

RESUMEN

PURPOSE: This study aims to examine outcomes of immature arteriovenous fistula salvage using balloon angioplasty (PTA) without and with accessory vein obliteration (PTA + VO). MATERIALS AND METHODS: PubMed and Embase were accessed on 21 September 2020 to retrieve cohort studies on adult patients with end-stage renal failure (ESRF) requiring dialysis. Risk of bias was assessed using Newcastle-Ottawa Scale. Studies were pooled into PTA or PTA + VO arms, with outcomes (technical/clinical success, primary/secondary post-intervention patency until 12 months) reported as event rates with 95% confidence intervals. Random-effects model and maximum likelihood meta-regression were used for meta-analysis. RESULTS: Fourteen studies (1030 participants) were included. The between-subgroup difference in outcomes was largely non-significant (p > 0.050). CONCLUSION: The evidence does not support balloon angioplasty with concomitant accessory vein obliteration for immature fistula salvage.

Asunto(s)

Angioplastia de Balón , Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Adulto , Angioplastia de Balón/efectos adversos , Fístula Arteriovenosa/etiología , Derivación Arteriovenosa Quirúrgica/efectos adversos , Oclusión de Injerto Vascular/cirugía , Humanos , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Grado de Desobstrucción Vascular

RESUMEN

PURPOSE: To asses the occurrence of discrepancies between the Doppler waveforms of the left and right umbilical arteries in their paravesical part in fetuses with absent or reversed end-diastolic flow in the free-floating umbilical cord. METHODS: This prospective observational study included pregnant women with fetal growth restriction or twin-to-twin transfusion syndrome. Umbilical arterial Doppler waveforms were obtained from both umbilical arteries in their intra-abdominal paravesical part. Doppler findings were recorded as present end-diastolic flow (PEDF)/absent end-diastolic flow (AEDF); AEDF/AEDF; AEDF/reversed end-diastolic flow (REDF); or REDF/REDF pattern. RESULTS: There were 49 fetuses with AEDF or REDF at the free-floating umbilical cord. Of these, 20 (40.8%) had a discrepancy in Doppler waveforms between the two umbilical arteries, with 14 (28.6%) showing PEDF/AEDF, 17 (34.7%) AEDF/AEDF, 6 (12.2%) AEDF/REDF, and 12 (24.5%) REDF/REDF pattern. CONCLUSION: Doppler waveforms showed discrepancies between the two umbilical arteries in 40.8% of pregnant women with AEDF or REDF in the free-floating umbilical cord. The presence of end-diastolic flow in one umbilical artery cannot exclude the possibility of AEDF in the other.

Asunto(s)

Retardo del Crecimiento Fetal/fisiopatología , Transfusión Feto-Fetal/fisiopatología , Ultrasonografía Doppler/métodos , Ultrasonografía Prenatal/métodos , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/fisiopatología , Adulto , Velocidad del Flujo Sanguíneo , Diástole , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/diagnóstico por imagen , Humanos , Embarazo , Estudios Prospectivos , Arterias Umbilicales/embriología

Asunto(s)

Anilidas/administración & dosificación , Carcinoma Basocelular/terapia , Cirugía de Mohs , Terapia Neoadyuvante/métodos , Piridinas/administración & dosificación , Neoplasias Cutáneas/terapia , Anilidas/efectos adversos , Biopsia , Carcinoma Basocelular/patología , Femenino , Humanos , Masculino , Márgenes de Escisión , Prueba de Estudio Conceptual , Piridinas/efectos adversos , Piel/efectos de los fármacos , Piel/patología , Neoplasias Cutáneas/patología , Resultado del Tratamiento

RESUMEN

Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry. 90 patients undergoing open lobectomy were randomly assigned to have phrenic nerve infiltration (n = 46) or not (n = 44). The phrenic nerve infiltration group received 10 mL of 0.25% bupivacaine into the periphrenic fat pad. Preoperative assessments of spirometry and pain scores were recorded (at rest and with movement). Postoperative assessments included peak flow and pain measurements at intervals up to 72 hours. Less shoulder pain was experienced with phrenic nerve infiltration up to 6 hours postsurgery at rest (P = 0.005) and up to 12 hours with movement (P < 0.001). Reduced back pain was reported in the phrenic nerve infiltration group up to 6 hours after surgery both at rest (P = 0.001) and with movement (P = 0.00). Phrenic nerve infiltration reduced pain at the incision site for up to 3 hours both at rest (P < 0.001) and with movement (P = 0.001). Spirometry readings dropped in both groups with consistently lower readings at baseline and follow-up in the PNI group (P = 0.007). Lower analgesic usage of patient controlled analgesia morphine (P < 0.0001), epipleural bupivacaine (P = 0.001), and oramorph/zomorph (P = 0.0002) were recorded. Our findings indicate that the use of phrenic nerve infiltration significantly reduced patient pain scores during the early postoperative period, particularly during movement. We believe that each technique has advantages and disadvantages; however, further studies with large sample size are warranted.

Asunto(s)

Anestésicos Locales/administración & dosificación , Dolor de Espalda/prevención & control , Bupivacaína/administración & dosificación , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Nervio Frénico , Neumonectomía , Dolor de Hombro/prevención & control , Toracotomía , Anciano , Anciano de 80 o más Años , Anestésicos Locales/efectos adversos , Dolor de Espalda/diagnóstico , Dolor de Espalda/epidemiología , Bupivacaína/efectos adversos , Inglaterra , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Neumonectomía/efectos adversos , Dolor de Hombro/diagnóstico , Dolor de Hombro/epidemiología , Espirometría , Toracotomía/efectos adversos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma. It is commonly reported in the younger population with no underlying chronic liver disease and free of viral Hepatitis B and C. Local recurrence and distant metastasis are common despite better prognosis compared to conventional hepatocellular carcinoma. Complete surgical resection is associated with higher median survival and is the mainstay treatment option for localized FL-HCC. Multi-modality therapies such as TACE can be used to downstage upfront unresectable FL-HCC. Complete response with GEMOX chemotherapy has been reported in advanced metastatic FL-HCC and should be considered in upfront unresectable or metastatic disease. We present a case of biopsied proven relapse FL-HCC with oligo- left lung metastasis who successfully underwent a left lung lobectomy after neo-adjuvant GEMOX chemotherapy, and is disease free at 24 months follow up.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/terapia , Desoxicitidina/análogos & derivados , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundario , Carcinoma Hepatocelular/patología , Terapia Combinada , Desoxicitidina/uso terapéutico , Femenino , Humanos , Neoplasias Hepáticas/patología , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Compuestos Organoplatinos/uso terapéutico , Tomografía Computarizada por Rayos X

RESUMEN

BACKGROUND AND OBJECTIVE: The Glasgow prognostic score (GPS) reflects the host systemic inflammatory response and is a validated independent prognostic factor in lung cancer. We investigated GPS as a potential predictive factor of clinical outcomes in idiopathic pulmonary fibrosis (IPF) patients with acute exacerbation (AE). METHODS: This was a retrospective study performed between January 2006 and March 2016 in Bucheon St. Mary's Hospital, The Catholic University of Korea. Overall, 327 admitted IPF patients were registered in the study. Patients with definite pneumonia at the time of admission, those with left-sided heart failure, pulmonary embolism and an identifiable cause of acute lung injury, and those whose albumin or C-reactive protein levels were not measured were excluded. RESULTS: A total of 66 patients hospitalized with IPF-AE were finally included. Median survival was 20.7 days and 29 (43.9%) patients died during hospitalization. The median length of overall survival (OS) was 26.0, 20.0 and 15.0 days for GPS-0, GPS-1 and GPS-2, respectively. There were significant differences in OS between GPS-0 and GPS-2 (P = 0.002). In a multivariate analysis performed using a Cox regression model, eosinopenia (P = 0.007), lower partial pressure of oxygen/fraction of inspired oxygen ratio (P = 0.014), and higher GPS (P = 0.006) were independent predictors of mortality. CONCLUSION: GPS can be helpful in predicting mortality in IPF patients with AE.

Asunto(s)

Proteína C-Reactiva/metabolismo , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico , Albúmina Sérica/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia

RESUMEN

OBJECTIVES: Body fat content, fat distribution, and adiponectin level are important variables in the development of obesity related complications. Anthropometric indices may provide an economic and faster method in measuring the risk for complications through their predictive effect of fat distribution and adiponectin concentration. We aimed to determine, which of the waist circumference (WC), waist-to-hip ratio (WHR), and body mass index (BMI) may be the best predictor for the total fat percentage (WF), visceral fat level (VF), and subcutaneous whole-body fat (SCWBF). We aimed also to investigate the potential use of the anthropometric measures and fat distribution as predictors for the salivary adiponectin level in the healthy adult males. SUBJECTS: A total of 88 adult males aged between 18-25 years with a wide range of BMI were studied. Anthropometric indices were measured using standardized methods and salivary adiponectin level was assessed using an enzyme-linked immunosorbent assay. RESULTS: In path analysis of the Structural Equation Model (SEM) using IBM@SPSS AMOS, version22, BMI and WC, but not WHR, were strong predictors for WF and SCWBF (p<0.05). BMI but not WC was a strong predictor for VF (p<0.001). WF was strong predictor for SCWBF (p<0.001), but not for VF. BMI, WC, WHR, WF, VF, and SCWBF were poor predictors of the salivary adiponectin level. CONCLUSION: BMI is the best predictor for the total body fat and fat distribution. However, WHR seems to be of a little value and the salivary adiponectin level independent of BMI and body fat in healthy adult Malay males.

Asunto(s)

Adiponectina/análisis , Adiposidad/fisiología , Índice de Masa Corporal , Saliva/química , Circunferencia de la Cintura/fisiología , Adolescente , Adulto , Antropometría , Humanos , Malasia , Masculino , Adulto Joven

RESUMEN

Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.

Asunto(s)

Carcinoma de Células de Merkel/cirugía , Carcinoma de Células Escamosas/cirugía , Melanoma/cirugía , Trasplante de Órganos , Guías de Práctica Clínica como Asunto , Neoplasias Cutáneas/cirugía , Humanos , Agencias Internacionales , Pronóstico , Melanoma Cutáneo Maligno

RESUMEN

Necrotic enteritis (NE) is a poultry disease caused by Clostridium perfringens and characterized by severe intestinal necrosis. The incidence of avian NE has been progressively increasing following the removal of antibiotics from poultry feed. We evaluated the effect of diets supplemented with the thermally-processed clays, calcium montmorillonite (CaMM) on clinical signs, immunopathology, and cytokine responses in broiler chickens using an experimental model of NE consisting of co-infection with Eimeria maxima and C. perfringens. In Trial 1, Ross/Ross chickens were fed from hatch with a normal basal diet or a CaMM-supplemented diet with or without a fermentable fiber, an organic acid, and/or a plant extract, and co-infected with E. maxima and C. perfringens under conditions simulating clinical infection in the field. Chickens fed a diet supplemented with CaMM plus a fermentable fiber and an organic acid had increased body weight gain, reduced gut lesions, and increased serum antibody levels to C. perfringens α-toxin and NetB toxin compared with chickens fed the basal diet alone. Levels of transcripts for interleukin-1ß (IL-1ß), IL-6, inducible nitric oxide synthase, and tumor necrosis factor-α superfamily-15 were significantly altered in the intestine and spleen of CaMM-supplemented chickens compared with unsupplemented controls (p<0.05). In Trial 2, Cobb/Cobb chickens were fed an unsupplemented diet or a diet supplemented with CaMM or Varium®, each with a fermentable fiber and an organic acid, and co-infected with E. maxima and C. perfringens under subclinical infection conditions. Compared with unsupplemented controls, broilers fed with CaMM plus a fermentable fiber and an organic acid had increased body weight gain, and reduced feed conversion ratio, mortality, and intestinal lesions, compared with chickens fed an unsupplemented diet (p<0.05). Dietary supplementation of broiler chickens with CaMM plus a fermentable fiber and an organic acid might be useful to control avian NE in the field.

RESUMEN

BACKGROUND: Hepatitis B is an important disease of ethnic disparity which affects Asian Americans and other minority populations disproportionately. Despite the high prevalence of hepatitis B in Asian Americans, many of them remain unscreened and untreated. A majority of the individuals chronically infected with hepatitis B virus (HBV) are not linked to care, for instance, due to a lack of culturally competent programs. There are many serious barriers preventing linkage to care (LTC), including personal, socio-cultural, and economic issues. The purpose of this study was to evaluate various barriers affecting LTC and to investigate the role and efficacy of a community-based Patient Navigator (PN) program in expediting LTC and in improving health outcomes for hepatitis B patients in a high risk population. METHODS: A total of 45 individuals chronically infected with HBV were identified through community screening events and were subsequently linked to patient navigators (PN), who then arranged for the patients to have a medical evaluation with a provider of their choice in their communities. The navigators kept detailed records of the patients' progress towards goal, and planned follow up visits for each patient. A self-report questionnaire was employed to assess patients' demographics, history of HBV infection, and barriers in accessing health care. Specifically, the levels of importance of the barriers due to language, culture, financial reasons were assessed. RESULTS: The study revealed that 38 of the 45 HBV infected individuals knew about their infection status from previous screening. Forty two out of 45 HBV infected individuals were linked to care within a 12 month period, demonstrating a high linkage rate. Most significant barriers identified were language and finance, followed by cultural barrier and others. CONCLUSION: There are specific barriers to accessing adequate care for the patients affected by chronic hepatitis B (CHB) in Korean American community. The implementation of a PN program in conjunction with the community network of health care providers may help to overcome the barriers and facilitate LTC in hepatitis B.

RESUMEN

Pulmonary vein deceleration injury is rare and patients can be deceptively stable for a period after injury. Quick diagnosis and transfer to the operating theatre is the only way to treat this potentially lethal injury successfully. Techniques of repair are a useful addition to the cardiovascular surgeon's repertoire.

Asunto(s)

Venas Pulmonares/lesiones , Traumatismos Torácicos/cirugía , Toracotomía/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Lesiones del Sistema Vascular/cirugía , Heridas no Penetrantes/cirugía , Humanos , Masculino , Venas Pulmonares/cirugía , Traumatismos Torácicos/diagnóstico , Tomografía Computarizada por Rayos X , Índices de Gravedad del Trauma , Lesiones del Sistema Vascular/diagnóstico , Heridas no Penetrantes/diagnóstico , Adulto Joven

RESUMEN

This paper presents a method to improve the contrast of digital X-ray image using CUDA program on a GPU. The histogram is commonly used to get the statistical distribution of the contrast in image processing. To increase the visibility of the image in real time, we use the histogram stretching function. It is difficult to implement the function on a GPU because the CUDA program is due to handle the complex process to transfer the source data and the processed results between the memory of GPU and the host system. As a result, we show to operate the histogram stretching function quickly on GPU by the CUDA program.

Asunto(s)

Algoritmos , Interpretación Estadística de Datos , Intensificación de Imagen Radiográfica/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Procesamiento de Señales Asistido por Computador , Programas Informáticos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Diseño de Software

RESUMEN

All but 11 of the 323 known actin sequences have Tyr at position 53, and the 11 exceptions have the conservative substitution Phe, which raises the following questions. What is the critical role(s) of Tyr-53, and, if it can be replaced by Phe, why has this happened so infrequently? We compared the properties of purified endogenous Dictyostelium actin and mutant constructs with Tyr-53 replaced by Phe, Ala, Glu, Trp, and Leu. The Y53F mutant did not differ significantly from endogenous actin in any of the properties assayed, but the Y53A and Y53E mutants differed substantially; affinity for DNase I was reduced, the rate of nucleotide exchange was increased, the critical concentration for polymerization was increased, filament elongation was inhibited, and polymerized actin was in the form of small oligomers and imperfect filaments. Growth and/or development of cells expressing these actin mutants were also inhibited. The Trp and Leu mutations had lesser but still significant effects on cell phenotype and the biochemical properties of the purified actins. We conclude that either Tyr or Phe is required to maintain the functional conformations of the DNase I-binding loop (D-loop) in both G- and F-actin, and that the conformation of the D-loop affects not only the properties that directly involve the D-loop (binding to DNase I and polymerization) but also allosterically modifies the conformation of the nucleotide-binding cleft, thus increasing the rate of nucleotide exchange. The apparent evolutionary "preference" for Tyr at position 53 may be the result of Tyr allowing dynamic modification of the D-loop conformation by phosphorylation (Baek, K., Liu, X., Ferron, F., Shu, S., Korn, E. D., and Dominguez, R. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 11748-11753) with effects similar, but not identical, to those of the Ala and Glu mutations.

Asunto(s)

Actinas/genética , Desoxirribonucleasa I/genética , Mutación , Tirosina/genética , Actinas/química , Animales , ADN Complementario/metabolismo , Dictyostelium , Miosina Tipo II/química , Nucleótidos/química , Nucleótidos/genética , Fenotipo , Fosforilación , Unión Proteica , Conformación Proteica , Estructura Terciaria de Proteína , Subtilisina/metabolismo

RESUMEN

INTRODUCTION: Sphenoid sinus mucoceles represent only 1-2 per cent of all paranasal sinus mucoceles. Patients may present with a myriad of symptoms. Pre-operative investigations include nasoendoscopy, computed tomography and/or magnetic resonance imaging. Treatment is by endoscopic sinus surgery. METHODOLOGY: A retrospective review of the archives of the Singapore General Hospital otolaryngology department (1999-2006) identified 10 cases of sphenoid sinus mucocele. Patient demographics, presenting symptoms, investigations and treatment were evaluated. RESULTS: The 10 patients identified (three women and seven men) had a mean age of 54.5 years (range 24-70 years). Thirty per cent of patients had a history of nasopharyngeal carcinoma treated with radiotherapy. Presenting symptoms, in order of decreasing frequency, were: ocular symptoms (50 per cent), headaches (30 per cent), nasal discharge (30 per cent) and facial pain (10 per cent). All patients underwent pre-operative computed tomography or magnetic resonance imaging. Twenty per cent of patients had evidence of intracranial involvement on imaging. All patients underwent uncomplicated transnasal sphenoidotomy and drainage of the mucocele. There was no clinical or radiological evidence of recurrence at a mean follow up of 29 months (range 4-90 months). CONCLUSION: Sphenoid sinus mucocele is a rare condition. In this study, radiation to the head and neck appeared to be a predisposing factor, and eye symptoms were the commonest presentation. Endoscopic sinus surgery is a safe and effective treatment modality.

Asunto(s)

Mucocele , Enfermedades de los Senos Paranasales , Seno Esfenoidal , Adulto , Anciano , Endoscopía/métodos , Dolor Facial/etiología , Femenino , Cefalea/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mucocele/diagnóstico , Mucocele/cirugía , Enfermedades de los Senos Paranasales/diagnóstico , Enfermedades de los Senos Paranasales/cirugía , Estudios Retrospectivos , Seno Esfenoidal/cirugía , Tomografía Computarizada por Rayos X , Trastornos de la Visión/etiología , Adulto Joven

RESUMEN

The incidence of necrotic enteritis (NE) due to Clostridium perfringens (CP) infection in commercial poultry has been increasing at an alarming rate. Although pre-exposure of chickens to coccidia infections is believed to be one of the major risk factors leading to NE, the underlying mechanisms of CP virulence remain undefined. The objectives of this study were to utilize an experimental model of NE produced by Eimeria maxima (EM) and CP coinfection to investigate the pathologic and immunologic parameters of the disease. Broilers coinfected with EM plus CP exhibited more severe gut pathology compared with animals given EM or CP alone. Additionally, EM/CP coinfection increased the numbers of intestinal CP bacteria compared with chickens exposed to an identical challenge of CP alone. Coinfection with EM and CP repressed nitric oxide synthase gene expression that was induced by EM alone, leading to lower plasma NO levels. Intestinal expression of a panel of cytokine and chemokine genes following EM/CP coinfection showed a mixed response depending on the transcript analyzed and the time following infection. In general, IFN-alpha, IFN-gamma, IL-1beta, IL-2, IL-12, IL-13, IL-17, and TGF-beta4 were repressed, whereas IL-8, IL-10, IL-15, and LITAF were increased during coinfection compared with challenge by EM or CP alone. These results are discussed in the context of EM and CP to act synergistically to create a more severe disease phenotype leading to an altered cytokine/chemokine response than that produced by infection with the individual pathogens.

Asunto(s)

Pollos , Infecciones por Clostridium/veterinaria , Clostridium perfringens , Coccidiosis/veterinaria , Eimeria , Enfermedades de las Aves de Corral , Animales , Pollos/microbiología , Pollos/parasitología , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/inmunología , Infecciones por Clostridium/patología , Coccidiosis/complicaciones , Coccidiosis/inmunología , Coccidiosis/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/parasitología , Enterocolitis Necrotizante/veterinaria , Femenino , Regulación de la Expresión Génica , Intestinos/microbiología , Intestinos/patología , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/patología

RESUMEN

A key challenge in Parkinson's disease research is to understand mechanisms underlying selective degeneration of dopaminergic neurons mediated by genetic factors such as alpha-synuclein (alpha-Syn). The present study examined whether dopamine (DA)-dependent oxidative stress underlies alpha-Syn-mediated neurodegeneration using Drosophila primary neuronal cultures. Green fluorescent protein (GFP) was used to identify live dopaminergic neurons in primary cultures prepared on a marked photoetched coverslip, which allowed us to repeatedly access preidentified dopaminergic neurons at different time points in a non-invasive manner. This live tracking of GFP-marked dopaminergic neurons revealed age-dependent neurodegeneration mediated by a mutant human alpha-Syn (A30P). Degeneration was rescued when alpha-Syn neuronal cultures were incubated with 1 mm glutathione from Day 3 after culturing. Furthermore, depletion of cytoplasmic DA by 100 microm alpha-methyl-p-tyrosine completely rescued the early stage of alpha-Syn-mediated dopaminergic cell loss, demonstrating that DA plays a major role in oxidative stress-dependent neurodegeneration mediated by alpha-Syn. In contrast, overexpression of a Drosophila tyrosine hydroxylase gene (dTH1) alone caused DA neurodegeneration by enhanced DA synthesis in the cytoplasm. Age-dependent dopaminergic cell loss was comparable in alpha-Syn vs dTH1-overexpressed neuronal cultures, indicating that increased DA levels in the cytoplasm is a critical change downstream of mutant alpha-Syn function. Finally, overexpression of a Drosophila vesicular monoamine transporter rescued alpha-Syn-mediated neurodegeneration through enhanced sequestration of cytoplasmic DA into synaptic vesicles, further indicating that a main cause of selective neurodegeneration is alpha-Syn-induced disruption of DA homeostasis. All of these results demonstrate that elevated cytoplasmic DA is a main factor underlying the early stage of alpha-Syn-mediated neurodegeneration.

Asunto(s)

Dopamina/metabolismo , Homeostasis/fisiología , Degeneración Nerviosa/metabolismo , Receptores de Dopamina D1/metabolismo , alfa-Sinucleína/metabolismo , Alanina/genética , Animales , Animales Modificados Genéticamente , Células Cultivadas , Drosophila , Embrión no Mamífero , Inhibidores Enzimáticos/farmacología , Glutatión/farmacología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Homeostasis/efectos de los fármacos , Humanos , Indoles , Mutación/fisiología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/tratamiento farmacológico , Prolina/genética , Receptores de Dopamina D1/genética , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismo , Proteínas de Transporte Vesicular de Monoaminas/metabolismo , alfa-Metiltirosina/farmacología , alfa-Sinucleína/genética

RESUMEN

The yeast Saccharomyces cerevisiae uses two class V myosins to transport cellular material into the bud: Myo2p moves secretory vesicles and organelles, whereas Myo4p transports mRNA. To understand how Myo2p and Myo4p are adapted to transport physically distinct cargos, we characterize Myo2p and Myo4p in yeast extracts, purify active Myo2p and Myo4p from yeast lysates, and analyze their motility. We find several striking differences between Myo2p and Myo4p. First, Myo2p forms a dimer, whereas Myo4p is a monomer. Second, Myo4p generates higher actin filament velocity at lower motor density. Third, single molecules of Myo2p are weakly processive, whereas individual Myo4p motors are nonprocessive. Finally, Myo4p self-assembles into multi-motor complexes capable of processive motility. We show that the unique motility of Myo4p is not due to its motor domain and that the motor domain of Myo2p can transport ASH1 mRNA in vivo. Our results suggest that the oligomeric state of Myo4p is important for its motility and ability to transport mRNA.

Asunto(s)

Cadenas Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , Miosinas/metabolismo , Transporte de ARN , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Reactivos de Enlaces Cruzados/farmacología , Etildimetilaminopropil Carbodiimida/farmacología , Proteínas Fluorescentes Verdes/metabolismo , Microscopía Electrónica , Proteínas Motoras Moleculares/metabolismo , Cadenas Pesadas de Miosina/química , Cadenas Pesadas de Miosina/aislamiento & purificación , Cadenas Pesadas de Miosina/ultraestructura , Miosina Tipo V/química , Miosina Tipo V/aislamiento & purificación , Miosina Tipo V/ultraestructura , Miosinas/química , Miosinas/aislamiento & purificación , Miosinas/ultraestructura , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Transporte de Proteínas/efectos de los fármacos , Transporte de ARN/efectos de los fármacos , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/efectos de los fármacos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/aislamiento & purificación , Proteínas de Saccharomyces cerevisiae/ultraestructura

RESUMEN

Using double-resonance conditions, in which the Larmor frequency of a spin-1/2 nucleus is matched to one of the nuclear quadrupole resonance frequencies of a spin-1 nucleus, the authors demonstrate increased cross relaxation between the two nuclear spin species. They calculate the cross-relaxation rate using the motionally averaged heterogeneous dipole Hamiltonian as a perturbation to the combined quadrupole and Zeeman Hamiltonians. Using this cross-relaxation rate, in addition to hydrogen and nitrogen autorelaxation rates, expressions governing spin-1/2 and spin-1 spin-lattice relaxation are determined. With ammonium nitrate, containing nitrogen (spin-1) and hydrogen (spin-1/2), increased nitrogen signal and spin-lattice relaxation are demonstrated, using fields less than 120 G. The cross-relaxation rate is also measured and an overall signal/noise improvement by a factor of 2.3+/-0.1 is attained.