ABSTRACT
BACKGROUND: Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid. METHODS: SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression). RESULTS: Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%. CONCLUSIONS: In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Dexamethasone/administration & dosage , Prednisone/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Aged, 80 and over , Androstenes/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Dexamethasone/therapeutic use , Disease Progression , Humans , Male , Middle Aged , Oncogene Proteins, Fusion/genetics , PTEN Phosphohydrolase/genetics , Pilot Projects , Prednisone/therapeutic use , Prospective Studies , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/genetics , Survival Analysis , Treatment OutcomeABSTRACT
Lymphatic malformations are congenital anomalies of the lymphatic system that can occur anywhere in the body and typically present in early childhood. They are often painless, slow-growing, and asymptomatic, but may lead to a wide range of symptoms depending on their size and location. Rarely, congenital malformations may not be diagnosed until later in childhood or adolescence, despite being present from birth. In some individuals, lymphatic malformations can expand quickly, especially in the setting of an inflammatory process. We present the case of an 8-year-old boy who had a rapidly enlarging, nonpainful mass on his right neck and a positive streptococcus throat swab. After evaluation by multiple specialists and imaging studies, he was diagnosed with a multilocular, multicystic lymphatic malformation. He was treated with fluoroscopy-guided doxycycline sclerotherapy, and has had near total resolution of neck swelling. This case report is significant because it highlights the potential benefits of a multidisciplinary approach to the diagnosis and management of lymphatic malformations. Additionally, it emphasizes the importance of considering congenital malformations in the differential diagnosis of neck masses, even in older children. Finally, it also adds to the growing body of evidence that hypothesizes that strep throat infections may trigger the sudden expansion of previously asymptomatic congenital lymphatic malformations.
ABSTRACT
Sigma-1 (σ1) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ1 receptor antagonist, has been found to produce a dose-dependent attenuation of locomotor activity induced by cocaine, and by itself, does not suppress basal locomotor activity in mice. Moreover, PD144418 decreases the motivational effort of a food-reinforced behavior in male rats, without altering appetite or food palatability. It remains unknown whether the PD144418 can alter the motivational effort of a food-reinforced behavior in response to altered energy homeostasis, as is the case under 24â¯-h food deprivation. Additionally, while the previous experiments indicate effects in male rats, there has been no research examining the effects of PD144418, or any other σ1 receptor antagonist, on motivational aspects of feeding in females. The present study examined the effects of PD144418 on motivational aspects of feeding in male and female rats using an operant task under sated or food deprived conditions. Results indicated that when animals are sated, at the highest dose (10⯵mol/kg), under a progressive ratio (PR) reinforcement schedule, PD144418 significantly attenuated the breakpoint and the number of active lever responses for sucrose pellets in both males and females. When animals are in a state of energy deficit, as is the case following 24-hr food deprivation, PD144418 does not alter motivationally driven operant responding as measured by the breakpoint in either sex but does alter the number of earned reinforcers responses in females.
Subject(s)
Feeding Behavior/physiology , Motivation/drug effects , Receptors, sigma/metabolism , Animals , Appetite/drug effects , Conditioning, Operant/drug effects , Energy Metabolism/drug effects , Feeding Behavior/drug effects , Female , Food , Food Deprivation/physiology , Isoxazoles/pharmacology , Male , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, sigma/antagonists & inhibitors , Reinforcement Schedule , Reinforcement, Psychology , Reward , Sex Factors , Sigma-1 ReceptorABSTRACT
1. INTRODUCCIÓN. La obesidad mórbida es una enfermedad crónica multifactorial asociada a complicaciones físicas y psicológicas que empeoran la calidad de vida de los pacientes y disminuyen su esperanza de vida; es un problema sanitario de primera magnitud debido al incremento de esta patología en Ecuador y a las dificultades que entraña su prevención y tratamiento. La cirugía de la obesidad es compleja, no exenta de complicaciones, cuyo objetivo es reducir de manera significativa las comorbilidades asociadas y mejorar el bienestar de los pacientes, cuya técnica quirúrgica sea fácil de reproducir, con porcentajes de revisión bajos y que constituya un tratamiento eficaz y seguro para la obesidad clínicamente grave, con evidencia que demuestra reducción de la mortalidad por todas las causas, mejoría en la expectativa y calidad de vida de los pacientes1.
1. INTRODUCTION. Morbid obesity is a multifactorial chronic disease associated with physical and psychological complications that worsen the quality of life of patients and decrease their life expectancy; it is a health problem of the first magnitude due to the increase of this pathology in Ecuador and the difficulties involved in its prevention and treatment. Obesity surgery is complex, not exempt of complications, whose objective is to significantly reduce associated comorbidities and improve the well-being of patients, whose surgical technique is easy to reproduce, with low revision percentages and that constitutes an effective and safe treatment for clinically severe obesity, with evidence that shows a reduction in all-cause mortality, improvement in life expectancy and quality of life of patients1.
Subject(s)
Humans , Male , Female , Bariatric Surgery , Obesity/surgery , Obesity/metabolism , Postoperative Complications/therapy , Obesity, Morbid/surgery , Obesity, Morbid/diagnosis , Obesity, Morbid/metabolism , Obesity, Morbid/epidemiology , Body Mass Index , Comorbidity , Obesity/diagnosis , Obesity/epidemiologyABSTRACT
Preventing vibriosis in juvenile cultured Turbot Scophthalmus maximus caused by Vibrio anguillarum frequently requires the use of feed supplemented with antibiotics in addition to vaccines. Whether the use of probiotics instead of antibiotics in juvenile Turbot is a safer strategy requires more study. The antibacterial potential of 148 Vibrio spp. strains (mostly isolated from cultures of healthy oysters, clams, and Turbot) was analyzed in vitro against V. anguillarum and other pathogens by means of an agar diffusion assay. A wide spectrum of inhibitory activity was shown by 9 strains. Based on their easy phenotypic differentiation from V. anguillarum, we selected two strains (S1 and S2, both isolated from the European flat oyster Ostrea edulis) for testing in juvenile Turbot (3 g). None of the strains were virulent by intraperitoneal or bath challenges, and all were susceptible to the antibiotics most frequently used in aquaculture. Three different stocks of Turbot, which were assayed separately, were significantly protected from infection with V. anguillarum. The final survival rates of fish treated in mixed challenges with S1 or S2 and V. anguillarum were 44% and 66%, respectively, whereas only 17% of the fish treated with only the pathogenic strain survived. The application of probiotic strains also increased the survival time of juvenile Turbot after infection with V. anguillarum. Both strains persisted in the epidermal mucus layer of the fish for 30 d, and they were not displaced by the pathogen. These data prove the efficacy of using bacteria well adapted to the dynamics of culture production as a way to provide juvenile Turbot immediate protection against infection by V. anguillarum. Moreover, the epidermal mucus sampling was useful for investigating the persistence of both probiotic strains when exposed to the pathogen.
Subject(s)
Flatfishes/microbiology , Ostreidae/microbiology , Vibrio Infections/veterinary , Vibrio/classification , Animals , Antibiosis , Aquaculture , Fish Diseases/microbiology , Fish Diseases/prevention & control , Time Factors , Vibrio/physiology , Vibrio Infections/prevention & controlABSTRACT
Introducción. Con el objeto de validar la medición del flujo espiratorio máximo como método para el control de la evolución de los pacientes asmáticos, se llevó a cabo una encuesta comparativa para determinar el grado de concordancia interobservador entre pacientes asmáticos y el médico neumólogo. Material y pacientes. De la clínica de Asma del departamento de Neumología del CMN La Raza, se tomaron 80 pacientes entre los 18 y 60 años con escolaridad de primaria completa y con agudeza visual de 20/20 ya fuera espontánea o corregida con lentes. Cada paciente se autorrealizó la medición del flujo espiratorio máximo con un medidor portátil, anotando en forma confidencial su lectura, al mismo tiempo, el médico neumólogo hizo la lectura del procedimiento y lo anotó en forma confidencial. Un segundo médico anotó ambas lecturas en una hoja de datos y un tercero llevó a cabo el análisis estadístico. Resultados. Los resultados mostraron un coeficiente de correlación de 0.99 entre la lectura de los pacientes y la del neumólogo. Conclusión. La lectura del medidor del flujo espiratorio es confiable y reproducible, debe emplearse en todos los pacientes asmáticos bajo control
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Asthma/diagnosis , Data Interpretation, Statistical , Maximal Expiratory Flow Rate , Rheology , Patients/statistics & numerical data , PhysiciansABSTRACT
Con el objetivo de analizar la morbilidad y mortalidad de los neonatos de bajo peso al nacer, se estudiaron 415 neonatos cuyos criterios de inclusión fueron el de peso menor a 2,500 g al nacer y de exclusión, la presencia de malformaciones congénitas mayores. La población se dividió para su estudio en tres grupos: menores de 1,000g, de 1,000-1,499 g y de 1,500-2,499 g y de cada grupo se dividió de acuerdo a su trofismo en adecuados (AEG) y pequeños (PEG) para la edad gestacional. Las tasas de mortalidad fueron más elevadas en el grupo de los menores de 1,000 g. Del total de la población el 33%correspondió a neonatos PEG y el 76%a neonatos AEG; la morbilidad intrahospitalaria presentada fué diferente en cada grupo de estudio, siendo los neonatos PEG los de menor morbilidad y menor número de días estancia hospitalaria presentaron, independientemente del peso al nacer. En nuestro estudio no hubo diferencias observados en relación al grado de asfixia al nacer y el trofismo, por lo que consideramos que la menor morbilidad de los PEG, se debió a que éstos nacieron en buenas condiciones