ABSTRACT
INTRODUCTION: The management of patients with BRAF-mutated advanced melanoma who are undergoing targeted therapy with MEK inhibitors can be complicated by the co-administration of multiple medications, which can give rise to drug-drug interactions of clinical significance. COVERED AREAS: Our review presents a comprehensive analysis of the pharmacokinetic and pharmacodynamic interactions of the three approved for advanced melanoma MEK inhibitor drugs - binimetinib, cobimetinib, and trametinib. MEDLINE (PubMed) was utilized for the literature search, comprising clinical studies, observational studies, and preclinical research. The review discusses the impact of these interactions on efficacy and safety of the treatments and differentiates between interactions supported by pharmacokinetic or pharmacodynamic mechanisms, those encountered in clinical practice, and those observed in preclinical studies. EXPERT OPINION: Physicians should be aware about potential benefits, but also increased toxicity caused by drug interactions between MEK inhibitors and other drugs in the management of patients with metastatic melanoma.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Mitogen-Activated Protein Kinases , Melanoma/drug therapy , Melanoma/pathology , Protein Kinase Inhibitors/adverse effects , Mitogen-Activated Protein Kinase Kinases/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Mutation , Skin Neoplasms/drug therapy , Skin Neoplasms/pathologySubject(s)
Dermatology , Cross-Sectional Studies , Feedback , Humans , Internet , Motivation , OutpatientsSubject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Dermatologists , Pneumonia, Viral/complications , COVID-19 , Cohort Studies , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2ABSTRACT
Estudou-se o efeito da fertilizaçäo com sulfato de cálcio (gesso agrícola) e com fosfato (termofosfato) em pastagem de capim-braquiária (Brachiaria decumbens Stapf) estabelecida em latossolo vermelho sobre a capacidade de suporte e sobre o rendimento de peso vivo por hectare e por ano da pastagem. As forragens que receberam sulfato de cálcio e fosfato apresentaram níveis mais elevados de proteína bruta, cálcio e fósforo. Verificou-se também maior taxa de lotaçäo e maior rendimento em peso vivo por hectare nas pastagens que receberam fertilizaçäo
Subject(s)
Animals , Animal Nutritional Physiological Phenomena , Calcium Sulfate , PhosphatesABSTRACT
Se describen los métodos clásicos electrofisiológicos para evaluar la disfunción sexual masculina (reflejo bulbocarvenoso (RBC) y potencial evocado somatosensitivo (PESS) practicados en el nervio pudendo y las técnicas recientes de exploración del nervio eringente desarrollada por los autores, en sujetos normales y en pacientes con impotencia y antecedentes de diabetes, prostatectomía, eyaculación precoz, ingesta alcohólica y tratamiento de HTA (hipertensión arterial) y depresión. En todos ellos se efectuó un estudio comparativo tanto de las respuestas de ambos nervios, como de la sensibilidad de ambos exámenes; los resultados fueron evaluados estadísticamente (Test de Mc Nemar), demostrando que el PESS practicado en el nervio eringente es el único examen estadísticamente significativo para evaluar la impotencia de origen neuropático. Por otra parte, debido a la constitución anatómica simpática (D12 a L4) del nervio eringente y su control preponderante neurovascular de la irrigación de los cuerpos cavernosos, la evaluación electrofisiológica precoz de este nervio tiene una relación muy estrecha con el comportamiento simpático de los cuerpos cavernosos en la función eréctil (neuropatía autonómica)
Subject(s)
Humans , Male , Sexual Dysfunction, Physiological/physiopathology , Sexual Dysfunction, Physiological/diagnosis , Neural Conduction , ElectrophysiologyABSTRACT
A quasi-free-field technique was used to assess the effects of extra-high-frequency-band masking on detection threshold of middle and high (1-7 kHz) frequencies. At an SPL of 60 dB, the 10- to 20-kHz masker produced a slight amount of masking. Increasing the masking level by another 5 dB produced a disproportionate increase of the detection thresholds. This increase was greatest in response to 4- and 5-kHz stimuli, and was detected with both constant and pulsed tones. Decreasing the bandwidth of the masker reduced the magnitude of the effect, but not the frequency-specific pattern of the remote masking. Extra-high-frequency masking also increased the amount of temporal integration at middle and high frequencies. The data are discussed in reference to peripheral and central neural changes associated with sensorineural hearing loss.
Subject(s)
Auditory Threshold , Noise , Perceptual Masking , Adult , Cochlea/physiopathology , Female , Hearing Loss, Sensorineural/physiopathology , Humans , Male , Sound Spectrography , Time FactorsABSTRACT
Three trained subjects were repeatedly tested for detection of auditory thresholds at 27 frequencies, from 2 to 18 kHz. A double-blind procedure was used with the method of adjustment, and the quasi-free-field delivery system of Osterhammel et al. [Scand. Audiol. 6:91-95, 1977] was used to monaurally stimulate the ear. A very reliable series of high- and low-threshold changes, termed the fine structure of the extra-high-frequency audiogram, was observed from 8 to 16 kHz. All 6 ears had a major low-threshold region at or near 13.5 kHz, and up to 3 other replicable sensitive frequencies along this one octave range. Thresholds were invariant over 3 conditions of stimulus presentation (constant tone; 500 ms duration, 25 ms rise and decay, 1 s interstimulus interval; and 100 ms duration, 1.5 ms rise and decay, 200 ms interstimulus interval). As the duration of the tone was decreased from 100 to 5 ms, temporal integration (an average of approximately 2.5 dB threshold increase as the duration was halved) was noted. Although temporal integration was slightly less at higher frequencies, the shape of the audiograms remained essentially unchanged as the stimulus duration was decreased to 5 ms. There was no consistent relationship between the maximally sensitive high frequencies and the amount of temporal integration. But there was a general association between the maximally sensitive high frequencies and the resonant frequency characteristics of that particular ear.
Subject(s)
Auditory Threshold , Adult , Audiometry/methods , Auditory Threshold/physiology , Ear, External/physiology , Female , Humans , Male , Reference ValuesABSTRACT
El objetivo del presente trabajo fue llevar a cabo una experiencia previa de musicoterapia con pacientes inválidos ambulatorios, del Servicio de Medicina Física y Rehabilitación, Sección Terapia Ocupacional, Hospital José Joaquín Aguirre, de la Universidad de Chile, con el propósito de obtener experiencia para elaborar un programa de este tipo de actividades para pacientes afectados por diversas invalideces. Este trabajo se realizó en conjunto con la unidad de Patología de Lenguaje del Servicio de Neurología de este Hospital, y se contó, además, con la valiosa colaboración ad-honorem del profesor de baile, señor Sergio Valero. (AU)
