Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
1.
Br J Anaesth ; 131(3): 523-530, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37422414

RESUMEN

BACKGROUND: Sugammadex has been associated with increases in the bispectral index (BIS). We evaluated the effects of sugammadex administration on quantitative electroencephalographic (EEG) and electromyographic (EMG) measures. METHODS: We performed a prospective observational study of adult male patients undergoing robot-assisted radical prostatectomy. All patients received a sevoflurane-based general anaesthetic and a continuous infusion of rocuronium, which was reversed with 2 mg kg-1 of sugammadex i.v. BIS, EEG, and EMG measures were captured with the BIS Vista™ monitor. RESULTS: Twenty-five patients were included in this study. Compared with baseline, BIS increased at 4-6 min (ß coefficient: 3.63; 95% confidence interval [CI]: 2.22-5.04; P<0.001), spectral edge frequency 95 (SEF95) increased at 2-4 min (ß coefficient: 0.29; 95% CI: 0.05-0.52; P=0.016) and 4-6 min (ß coefficient: 0.71; 95% CI: 0.47-0.94; P<0.001), and EMG increased at 4-6 min (ß coefficient: 1.91; 95% CI: 1.00-2.81; P<0.001) after sugammadex administration. Compared with baseline, increased beta power was observed at 2-4 min (ß coefficient: 93; 95% CI: 1-185; P=0.046) and 4-6 min (ß coefficient: 208; 95% CI: 116-300; P<0.001), and decreased delta power was observed at 4-6 min (ß coefficient: -526.72; 95% CI: -778 to -276; P<0.001) after sugammadex administration. Neither SEF95 nor frequency band data analysis adjusted for EMG showed substantial differences. None of the patients showed clinical signs of awakening. CONCLUSIONS: After neuromuscular block reversal with 2 mg kg-1 sugammadex, BIS, SEF95, EMG, and beta power showed small but statistically significant increases over time, while delta power decreased.


Asunto(s)
Bloqueo Neuromuscular , Robótica , Adulto , Humanos , Masculino , Sugammadex/farmacología , Prostatectomía , Electroencefalografía , Androstanoles
2.
Life (Basel) ; 12(11)2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36362892

RESUMEN

Patients with obstructive sleep apnea (OSA) that do not tolerate/accept continuous positive airway pressure (CPAP) are candidates for surgical alternatives. Hypoglossal nerve stimulation (HNS) through the implantation of the Inspire® device constitutes a minimally invasive operative option. The main objective of this study is to estimate, under real-world clinical practice conditions, the 3-month impact on the quality of life (IQoL) of the HNS in patients with moderate/severe OSA who do not tolerate or accept CPAP, compared to patients who did not receive HNS. As a baseline, the unadjusted EuroQol utility index was 0.764 (SD:0.190) in the intervention group (IGr) and 0.733 (SD:0.205) in the control group (CGr); three months later, the indexes were 0.935 (SD: 0.101) and 0.727 (SD:0.200), respectively. The positive impact on quality of life was estimated to be +0.177 (95% CI: 0.044−0.310; p = 0.010). All dimensions in the IGr improved compared to CGr, especially for usual activities (p < 0.001) and anxiety/depression (p > 0.001). At the end of the follow-up, there was no significant difference in the quality of life between the general Spanish population and the IGr (difference: 0.012; CI95%: −0.03 to −0.057; p = 0.0578) for the same age range; however, there was a difference concerning the CGr (difference: −0.196; CI95%: −0.257 to −0.135; p < 0.001). In conclusion, patients with moderate/severe OSA implanted with the Inspire® device showed a positive IQoL.

3.
Artículo en Inglés | MEDLINE | ID: mdl-35682516

RESUMEN

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure­Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.


Asunto(s)
Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , Humanos , Polisomnografía/métodos , Procesamiento de Señales Asistido por Computador , Sueño , Apnea Obstructiva del Sueño/terapia
4.
Neuroreport ; 33(11): 487-494, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35767229

RESUMEN

There is a growing interest about the effects of static transcranial magnetic stimulation (tSMS) over different cortical areas, being the motor cortex the most widely studied region. Previous experiments have shown that noninvasive magnetic static stimulation of the human brain may change its excitability in a reversible way for a period that outlasts the time of application of the magnetic field. However, evidence about the effects over the auditory cortex are poor and this is the purpose of the present study. Twelve voluntary subjects were studied in two different sessions, immediately before and 20 min after the placement of a magnet or a sham over the left primary auditory cortex, for 30 min. No significant effects of the magnet were observed on auditory responses, including onset and offset potentials and oscillatory responses to stimulus frequency modulation. A reduction in the amplitude of the cortical onset and offset potentials was observed after the two sessions, both with the magnet and with the false magnet (sham). No effects of unilateral static magnetic stimulation on cortical auditory responses have been observed. However, we probe the feasibility and tolerability of the protocol performed and suggest the use of different stimulation protocols.


Asunto(s)
Corteza Auditiva , Estimulación Magnética Transcraneal , Corteza Auditiva/fisiología , Estudios de Factibilidad , Humanos , Campos Magnéticos , Estimulación Magnética Transcraneal/métodos
5.
Sci Transl Med ; 14(627): eabc0700, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-35020410

RESUMEN

Correction of enzymatic deficits in hepatocytes by systemic administration of a recombinant protein is a desired therapeutic goal for hepatic enzymopenic disorders such as acute intermittent porphyria (AIP), an inherited porphobilinogen deaminase (PBGD) deficiency. Apolipoprotein A-I (ApoAI) is internalized into hepatocytes during the centripetal transport of cholesterol. Here, we generated a recombinant protein formed by linking ApoAI to the amino terminus of human PBGD (rhApoAI-PBGD) in an attempt to transfer PBGD into liver cells. In vivo experiments showed that, after intravenous injection, rhApoAI-PBGD circulates in blood incorporated into high-density lipoprotein (HDL), penetrates into hepatocytes, and crosses the blood-brain barrier, increasing PBGD activity in both the liver and brain. Consistently, the intravenous administration of rhApoAI-PBGD or the hyperfunctional rApoAI-PBGD-I129M/N340S (rApoAI-PBGDms) variant efficiently prevented and abrogated phenobarbital-induced acute attacks in a mouse model of AIP. One month after a single intravenous dose of rApoAI-PBGDms, the protein was still detectable in the liver, and hepatic PBGD activity remained increased above control values. A long-lasting therapeutic effect of rApoAI-PBGDms was observed after either intravenous or subcutaneous administration. These data describe a method to deliver PBGD to hepatocytes with resulting enhanced hepatic enzymatic activity and protection against AIP attacks in rodent models, suggesting that the approach might be an effective therapy for AIP.


Asunto(s)
Hidroximetilbilano Sintasa , Porfiria Intermitente Aguda , Animales , Modelos Animales de Enfermedad , Terapia Genética/métodos , Hidroximetilbilano Sintasa/metabolismo , Hidroximetilbilano Sintasa/uso terapéutico , Ratones , Porfiria Intermitente Aguda/tratamiento farmacológico , Porfiria Intermitente Aguda/metabolismo
6.
Handb Clin Neurol ; 184: 259-271, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35034740

RESUMEN

Brain oscillations have been associated with Parkinson's disease (PD) for a long time mainly due to the fundamental oscillatory nature of parkinsonian rest tremor. Over the years, this association has been extended to frequencies well above that of tremor, largely owing to the opportunities offered by deep brain stimulation (DBS) to record electrical activity directly from the patients' basal ganglia. This chapter reviews the results of research on brain oscillations in PD focusing on theta (4-7Hz), beta (13-35Hz), gamma (70-80Hz) and high-frequency oscillations (200-400Hz). For each of these oscillations, we describe localization and interaction with brain structures and between frequencies, changes due to dopamine intake, task-related modulation, and clinical relevance. The study of brain oscillations will also help to dissect the mechanisms of action of DBS. Overall, the chapter tentatively depicts PD in terms of "oscillopathy."


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Ganglios Basales , Humanos , Enfermedad de Parkinson/terapia , Temblor/terapia
7.
Mol Ther Nucleic Acids ; 25: 207-219, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34458006

RESUMEN

Variegate porphyria (VP) results from haploinsufficiency of protoporphyrinogen oxidase (PPOX), the seventh enzyme in the heme synthesis pathway. There is no VP model that recapitulates the clinical manifestations of acute attacks. Combined administrations of 2-allyl-2-isopropylacetamide and rifampicin in rabbits halved hepatic PPOX activity, resulting in increased accumulation of a potentially neurotoxic heme precursor, lipid peroxidation, inflammation, and hepatocyte cytoplasmic stress. Rabbits also showed hypertension, motor impairment, reduced activity of critical mitochondrial hemoprotein functions, and altered glucose homeostasis. Hemin treatment only resulted in a slight drop in heme precursor accumulation but further increased hepatic heme catabolism, inflammation, and cytoplasmic stress. Hemin replenishment did protect against hypertension, but it failed to restore action potentials in the sciatic nerve or glucose homeostasis. Systemic porphobilinogen deaminase (PBGD) mRNA administration increased hepatic PBGD activity, the third enzyme of the pathway, and rapidly normalized serum and urine porphyrin precursor levels. All features studied were improved, including those related to critical hemoprotein functions. In conclusion, the VP model recapitulates the biochemical characteristics and some clinical manifestations associated with severe acute attacks in humans. Systemic PBGD mRNA provided successful protection against the acute attack, indicating that PBGD, and not PPOX, was the critical enzyme for hepatic heme synthesis in VP rabbits.

8.
Br J Anaesth ; 127(2): 245-253, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33896591

RESUMEN

BACKGROUND: Dexmedetomidine is frequently used for sedation during deep brain stimulator implantation in patients with Parkinson's disease, but its effect on subthalamic nucleus activity is not well known. The aim of this study was to quantify the effect of increasing doses of dexmedetomidine in this population. METHODS: Controlled clinical trial assessing changes in subthalamic activity with increasing doses of dexmedetomidine (from 0.2 to 0.6 µg kg-1 h-1) in a non-operating theatre setting. We recorded local field potentials in 12 patients with Parkinson's disease with bilateral deep brain stimulators (24 nuclei) and compared basal activity in the nuclei of each patient and activity recorded with different doses. Plasma levels of dexmedetomidine were obtained and correlated with the dose administered. RESULTS: With dexmedetomidine infusion, patients became clinically sedated, and at higher doses (0.5-0.6 µg kg-1 h-1) a significant decrease in the characteristic Parkinsonian subthalamic activity was observed (P<0.05 in beta activity). All subjects awoke to external stimulus over a median of 1 (range: 0-9) min, showing full restoration of subthalamic activity. Dexmedetomidine dose administered and plasma levels showed a positive correlation (repeated measures correlation coefficient=0.504; P<0.001). CONCLUSIONS: Patients needing some degree of sedation throughout subthalamic deep brain stimulator implantation for Parkinson's disease can probably receive dexmedetomidine up to 0.6 µg kg-1 h-1 without significant alteration of their characteristic subthalamic activity. If patients achieve a 'sedated' state, subthalamic activity decreases, but they can be easily awakened with a non-pharmacological external stimulus and recover baseline subthalamic activity patterns in less than 10 min. CLINICAL TRIAL REGISTRATION: EudraCT 2016-002680-34; NCT-02982512.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , España
9.
Hum Mol Genet ; 29(19): 3211-3223, 2020 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-32916704

RESUMEN

The morphological changes that occur in the central nervous system of patients with severe acute intermittent porphyria (AIP) have not yet been clearly established. The aim of this work was to analyze brain involvement in patients with severe AIP without epileptic seizures or clinical posterior reversible encephalopathy syndrome, as well as in a mouse model receiving or not liver-directed gene therapy aimed at correcting the metabolic disorder. We conducted neuroradiologic studies in 8 severely affected patients (6 women) and 16 gender- and age-matched controls. Seven patients showed significant enlargement of the cerebral ventricles and decreased brain perfusion was observed during the acute attack in two patients in whom perfusion imaging data were acquired. AIP mice exhibited reduced cerebral blood flow and developed chronic dilatation of the cerebral ventricles even in the presence of slightly increased porphyrin precursors. While repeated phenobarbital-induced attacks exacerbated ventricular dilation in AIP mice, correction of the metabolic defect using liver-directed gene therapy restored brain perfusion and afforded protection against ventricular enlargement. Histological studies revealed no signs of neuronal loss but a denser neurofilament pattern in the periventricular areas, suggesting compression probably caused by imbalance in cerebrospinal fluid dynamics. In conclusion, severely affected AIP patients exhibit cerebral ventricular enlargement. Liver-directed gene therapy protected against the morphological consequences of the disease seen in the brain of AIP mice. The observational study was registered at Clinicaltrial.gov as NCT02076763.


Asunto(s)
Encéfalo/patología , Ventrículos Cerebrales/patología , Modelos Animales de Enfermedad , Hidroximetilbilano Sintasa/genética , Porfiria Intermitente Aguda/fisiopatología , Adulto , Animales , Encéfalo/metabolismo , Estudios de Casos y Controles , Ventrículos Cerebrales/metabolismo , Ensayos Clínicos Fase I como Asunto , Femenino , Terapia Genética , Humanos , Masculino , Ratones , Persona de Mediana Edad , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/metabolismo , Estudios Prospectivos
10.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31937406

RESUMEN

INTRODUCTION: Cochlear implants have been able to treat some types of hearing loss, but those related to cochlear nerve impairment made it necessary to find new ways to manage these deficits; leading to auditory brainstem implants (ABI). AIM: Our objective is to present the clinical profile of patients treated through an ABI and the results obtained from 1997 to 2017. MATERIAL AND METHODS: On the one hand, patients with statoacoustic nerve tumours (VIIIcranial nerve) were selected, and on the other hand, patients withoutVIII tumours with congenital malformations of the inner ear. Before and after the placement of the ABI, hearing was assessed through tonal audiometry, from which the PTA (Pure Tone Average) and the CAP (Categories of Auditory Performance) scale were obtained. RESULTS: A total of 20 patients undergoing ABI surgery were included. Eight were of tumour cause (40%) and 12 non-tumour (60%). In 15 subjects (75%) a suboccipital approach was performed and in 5 (25%) translabyrinthine. The mean of active electrodes before the implantation of Cochlear® (Nucleus ABI24) was 13/21 (61.90%) versus 8.5/12 (70.83%) of the Med-el® (ABI Med-el). An improvement in the mean PTA of 118.49dB was found against 46.55dB at 2years. On the CAP scale, values of1 were obtained in the preimplantation and of 2.57 (1-5) in the 2-year revision. CONCLUSION: The ABI is a safe option, and with good hearing results when the indication is made correctly.


Asunto(s)
Implantes Auditivos de Tronco Encefálico , Nervio Coclear , Pérdida Auditiva/cirugía , Enfermedades del Nervio Vestibulococlear/cirugía , Adolescente , Niño , Preescolar , Femenino , Pérdida Auditiva/etiología , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades del Nervio Vestibulococlear/complicaciones
12.
Eur J Paediatr Neurol ; 24: 134-141, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31879226

RESUMEN

OBJECTIVE: To evaluate the capability of children with Dravet syndrome to generate brain γ-oscillatory activity in response to auditory steady-state stimulation. METHODS: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. RESULTS: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) γ-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. CONCLUSIONS: The ability to generate brain γ-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. SIGNIFICANCE: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions.


Asunto(s)
Encéfalo/fisiopatología , Epilepsias Mioclónicas/fisiopatología , Ritmo Gamma/fisiología , Estimulación Acústica , Adolescente , Animales , Niño , Preescolar , Epilepsias Mioclónicas/genética , Femenino , Humanos , Masculino , Ratones
13.
Nat Med ; 24(12): 1899-1909, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30297912

RESUMEN

Acute intermittent porphyria (AIP) results from haploinsufficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis pathway. Patients with AIP have neurovisceral attacks associated with increased hepatic heme demand. Phenobarbital-challenged mice with AIP recapitulate the biochemical and clinical characteristics of patients with AIP, including hepatic overproduction of the potentially neurotoxic porphyrin precursors. Here we show that intravenous administration of human PBGD (hPBGD) mRNA (encoded by the gene HMBS) encapsulated in lipid nanoparticles induces dose-dependent protein expression in mouse hepatocytes, rapidly normalizing urine porphyrin precursor excretion in ongoing attacks. Furthermore, hPBGD mRNA protected against mitochondrial dysfunction, hypertension, pain and motor impairment. Repeat dosing in AIP mice showed sustained efficacy and therapeutic improvement without evidence of hepatotoxicity. Finally, multiple administrations to nonhuman primates confirmed safety and translatability. These data provide proof-of-concept for systemic hPBGD mRNA as a potential therapy for AIP.


Asunto(s)
Terapia Genética , Hidroximetilbilano Sintasa/genética , Porfiria Intermitente Aguda/terapia , ARN Mensajero/administración & dosificación , Animales , Modelos Animales de Enfermedad , Femenino , Haploinsuficiencia/genética , Hemo/genética , Hemo/metabolismo , Hepatocitos/efectos de los fármacos , Humanos , Hidroximetilbilano Sintasa/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/patología , ARN Mensajero/genética
14.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28755767

RESUMEN

The objective of this communication is to describe our preliminary results in upper airway stimulation surgery via hypoglossal nerve stimulation implantation for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery were analysed using the Epworth scale, apnoea-hypopnoea index, minimal O2 Sat, average O2 Sat and snoring intensity. In all cases a significant reduction in Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The minimum and average oxygen saturation had better values after the surgery, however, there was no statistically significant difference. The snoring severity measured subjectively changed from «intense¼ to «absent¼ in all cases. The preliminary results obtained with the upper airway stimulation surgery via hypoglossal nerve stimulation showed objective and subjective improvement after the implant activation.


Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Nervio Hipogloso , Neuroestimuladores Implantables , Apnea Obstructiva del Sueño/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
15.
Brain Stimul ; 11(1): 231-238, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29051091

RESUMEN

BACKGROUND: High-frequency deep brain stimulation (DBS) has become a widespread therapy used in the treatment of Parkinson's Disease (PD) and other diseases. Although it has proved beneficial, much recent attention has been centered around the potential of new closed-loop DBS implementations. OBJECTIVE: Here we present a new closed-loop DBS scheme based on the phase of the theta activity recorded from the motor cortex. By testing the implementation on freely moving 6-OHDA lesioned and control rats, we assessed the behavioral and neurophysiologic effects of this implementation and compared it against the classical high-frequency DBS. RESULTS: Results show that both stimulation modalities produce significant and opposite changes on the movement and neurophysiological activity. Close-loop stimulation, far from improving the animals' behavior, exert contrary effects to those of high-frequency DBS which reverts the parkinsonian symptoms. Motor improvement during open-loop, high-frequency DBS was accompanied by a reduction in the amount of cortical beta oscillations while akinetic and disturbed behavior during close-loop stimulation coincided with an increase in the amplitude of beta activity. CONCLUSION: Cortical-phase-dependent close-loop stimulation of the STN exerts significant behavioral and oscillatory changes in the rat model of PD. Open-loop and close-loop stimulation outcomes differed dramatically, thus suggesting that the scheme of stimulation determines the output of the modulation even if the target structure is maintained. The current framework could be extended in future studies to identify the correct parameters that would provide a suitable control signal to the system. It may well be that with other stimulation parameters, this sort of DBS could be beneficial.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Locomoción/fisiología , Corteza Motora/fisiopatología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Animales , Modelos Animales de Enfermedad , Masculino , Destreza Motora/fisiología , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/terapia , Ratas , Ratas Wistar , Ritmo Teta
16.
Hum Gene Ther ; 29(4): 480-491, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28990424

RESUMEN

Porphobilinogen deaminase (PBGD) gene therapy represents a promising therapeutic option for acute intermittent porphyria (AIP) patients suffering recurrent acute attacks. A first-in-human Phase I clinical trial confirmed the safety and tolerability of adeno-associated virus (AAV)-AAT-PBGD gene therapy, but higher doses and/or more efficient vectors are needed to achieve therapeutic expression of the transgene. This study assayed the insertion into the promoter of a short enhancer element able to induce transgene expression during exposure to endogenous and exogenous stimuli related to the pathology of the disease. The inclusion in tandem of two elements of the minimal functional sequence of human δ-aminolevulinic acid synthase drug-responsive enhancing sequence (ADRES) positioned upstream of the promoter strongly induced transgene expression in the presence of estrogens, starvation, and certain drugs known to trigger attacks in porphyria patients. The inclusion of two ADRES motives in an AAV vector improved therapeutic efficacy, reducing 10-fold the effective dose in AIP mice. In conclusion, the inclusion of specific enhancer elements in the promoter of gene therapy vectors for AIP was able to overexpress the therapeutic transgene when it is most needed, at the time when porphyrinogenic factors increase the demand for hepatic heme and precipitate acute porphyria attacks.


Asunto(s)
Dependovirus/genética , Terapia Genética , Vectores Genéticos/administración & dosificación , Porfiria Intermitente Aguda/terapia , 5-Aminolevulinato Sintetasa/genética , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Vectores Genéticos/genética , Humanos , Hidroximetilbilano Sintasa/genética , Hígado/metabolismo , Hígado/patología , Ratones , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/patología , Regiones Promotoras Genéticas
17.
Med Clin (Barc) ; 149(11): 469-476, 2017 Dec 07.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28709670

RESUMEN

BACKGROUND AND OBJECTIVE: Arterial stiffness (AS) is a well-recognized target organ lesion. This study aims to determine: 1) the frequency of AS in community pharmacies; 2) if stiffened subjects identified by brachial oscillometry have more CV risk factors than normal subjects, and 3) the dependence of stiffness on using either age-adjusted values or a fixed threshold. PATIENTS AND METHOD: Observational, cross-sectional study in 32 community pharmacies of the Valencia Community, between November/2015 and April/2016. Stiffness was as pulse wave velocity (PWV) measured with a semi-automatic, validated device (Mobil-O-Graph®, IEM), followed by a 10-item questionnaire. RESULTS: Mean age of the 1,427 consecutive recruited patients was 56.6 years. Overall proportion of patients with AS was 17.4% with age-adjusted PWV (9.4% in normotensives, 28.3% in hypertensives). Multivariate logistic regression showed independent association of stiffness in normotensives with male gender, obesity, higher pulse pressure and heart rate, in hypertensives, with higher pulse pressure and lower age. AS was globally found in 20.5% of subjects, defining stiffness by PWV>10m/s (6.2% in normotensives, 40.2% in hypertensives). It was associated with higher age and pulse pressure in both groups. Concordance in classifying stiffness was 74.6%. CONCLUSIONS: Frequency of AS varied between 17.4-20.5%. Age-adjusted stiffness is associated in normotensives with male gender, pulse pressure, obesity and heart rate, in hypertensives with pulse pressure and inversely to age. Stiffness by 10m/s is determined by higher pulse pressure and higher age. Both definitions of PWV are not interchangeable.


Asunto(s)
Hipertensión/fisiopatología , Rigidez Vascular , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arteria Braquial/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oscilometría , Farmacias , Análisis de la Onda del Pulso
18.
Anesthesiology ; 126(6): 1033-1042, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28492384

RESUMEN

BACKGROUND: Deep brain stimulation electrodes can record oscillatory activity from deep brain structures, known as local field potentials. The authors' objective was to evaluate and quantify the effects of dexmedetomidine (0.2 µg·kg·h) on local field potentials in patients with Parkinson disease undergoing deep brain stimulation surgery compared with control recording (primary outcome), as well as the effect of propofol at different estimated peak effect site concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 µg/ml) from control recording. METHODS: A nonrandomized, nonblinded controlled clinical trial was carried out to assess the change in local field potentials activity over time in 10 patients with Parkinson disease who underwent deep brain stimulation placement surgery (18 subthalamic nuclei). The relationship was assessed between the activity in nuclei in the same patient at a given time and repeated measures from the same nucleus over time. RESULTS: No significant difference was observed between the relative beta power of local field potentials in dexmedetomidine and control recordings (-7.7; 95% CI, -18.9 to 7.6). By contrast, there was a significant decline of 12.7% (95% CI, -21.3 to -4.7) in the relative beta power of the local field potentials for each increment in the estimated peak propofol concentrations at the effect site relative to the control recordings. CONCLUSIONS: Dexmedetomidine (0.2 µg·kg·h) did not show effect on local field potentials compared with control recording. A significant deep brain activity decline from control recording was observed with incremental doses of propofol.


Asunto(s)
Ganglios Basales/efectos de los fármacos , Estimulación Encefálica Profunda , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Enfermedad de Parkinson/cirugía , Propofol/farmacología , Potenciales de Acción/efectos de los fármacos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
World Neurosurg ; 101: 114-121, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28179174

RESUMEN

BACKGROUND: The anesthetic management of patients requiring surgery for movement disorders needs to balance microrecording quality and patient cooperation with safety and comfort. Anesthetics can alter microrecording, although the effect on outcome is debatable. They also provide a rested and cooperative patient and minimize complications such as intracranial hemorrhage by providing better hemodynamic control. Most teams use local anesthesia with monitored anesthesia care or conscious sedation with propofol. Recently, dexmedetomidine has emerged as an alternative that, at low doses, does not affect microrecording, and that does not impair respiratory drive. METHODS: In the past 15 years, we have used in our institution local anesthesia, remifentanil, or dexmedetomidine sedation. We compared functional outcome and rate of complications in a group of 145 patients with similar characteristics. RESULTS: We found 5 (3.4%) intracranial hemorrhages. Two (1.4%) were symptomatic. The remifentanil group had the highest risk of having systolic blood pressure >160 mm Hg during surgery (odds ratio [OR], 2.8; 95% confidence interval [CI], 0.9-9.9), whereas the dexmedetomidine group had the lowest (OR, 0.7; 95% CI, 0.2-1.8), compared with the local anesthesia group. Surgical time was shortest with dexmedetomidine (mean, 283 minutes) and longest with local anesthesia only (mean, 328 minutes). Functional outcome (Unified Parkinson's Disease Rating Scale, Part III motor component scale) was similar among groups. The dexmedetomidine group had a statistically significant lower risk of perioperative neurologic events compared with the local anesthesia group (OR, 0.09; 95% CI, 0.002-0.68). CONCLUSIONS: Sedation can be used safely without affecting outcome, and dexmedetomidine provides better hemodynamic management. Clinical significance remains unclear and larger studies need to be undertaken.


Asunto(s)
Anestesia Local/métodos , Dexmedetomidina/uso terapéutico , Trastornos del Movimiento/cirugía , Enfermedades del Sistema Nervioso/etiología , Atención Perioperativa/métodos , Piperidinas/uso terapéutico , Anciano , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Remifentanilo , Estudios Retrospectivos , Estadísticas no Paramétricas
20.
Psychiatry Res ; 247: 214-221, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27918972

RESUMEN

The symptoms of schizophrenia might be mediated by a cortical network disconnection which may disrupt the cortical oscillatory activity. Steady-state responses are an easy and consistent way to explore cortical oscillatory activity. A chirp-modulated tone (increasing the frequency of the modulation in a linear manner) allows a fast measure of the steady-state response to different modulation rates. With this approach, we studied the auditory steady-state responses in two groups of patients with schizophrenia (drug-naive and treated with atypical antipsychotic drugs), in order to assess the differences in their responses with respect to healthy subjects, and study any potential effect of medication. Drug-naive patients had reduced amplitude and inter-trial phase coherence of the response in the 30-50Hz range, and reduced amplitude of the response in the 90-100Hz range, when compared to controls. In the treated patients group, the response in the 30-50Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90-100Hz range remained as in the drug-naive group. These results suggest that gamma activity impairment in schizophrenia is a complex phenomenon that affects a wide band of frequencies and may be influenced by antipsychotic treatment.


Asunto(s)
Antipsicóticos/farmacología , Potenciales Evocados Auditivos/efectos de los fármacos , Ritmo Gamma/efectos de los fármacos , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Estimulación Acústica/métodos , Adulto , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...