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1.
Cell ; 184(13): 3426-3437.e8, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-33991487

RESUMEN

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , COVID-19/transmisión , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Mutación/genética , Secuenciación Completa del Genoma/métodos
2.
medRxiv ; 2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33758899

RESUMEN

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

3.
Neuromodulation ; 24(4): 672-684, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33471409

RESUMEN

BACKGROUND/OBJECTIVES: The physiological mechanisms underlying the pain-modulatory effects of clinical neurostimulation therapies, such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS), are only partially understood. In this pilot prospective study, we used patient-reported outcomes (PROs) and quantitative sensory testing (QST) to investigate the physiological effects and possible mechanisms of action of SCS and DRGS therapies. MATERIALS AND METHODS: We tested 16 chronic pain patients selected for SCS and DRGS therapy, before and after treatment. PROs included pain intensity, pain-related symptoms (e.g., pain interference, pain coping, sleep interference) and disability, and general health status. QST included assessments of vibration detection theshold (VDT), pressure pain threshold (PPT) and tolerance (PPToL), temporal summation (TS), and conditioned pain modulation (CPM), at the most painful site. RESULTS: Following treatment, all participants reported significant improvements in PROs (e.g., reduced pain intensity [p < 0.001], pain-related functional impairment [or pain interference] and disability [p = 0.001 for both]; better pain coping [p = 0.03], sleep [p = 0.002]), and overall health [p = 0.005]). QST showed a significant treatment-induced increase in PPT (p = 0.002) and PPToL (p = 0.011), and a significant reduction in TS (p = 0.033) at the most painful site, but showed no effects on VDT and CPM. We detected possible associations between a few QST measures and a few PROs. Notably, higher TS was associated with increased pain interference scores at pre-treatment (r = 0.772, p = 0.009), and a reduction in TS was associated with the reduction in pain interference (r = 0.669, p = 0.034) and pain disability (r = 0.690, p = 0.027) scores with treatment. CONCLUSIONS: Our preliminary findings suggest significant clinical and therapeutic benefits associated with SCS and DRGS therapies, and the possible ability of these therapies to modulate pain processing within the central nervous system. Replication of our pilot findings in future, larger studies is necessary to characterize the physiological mechanisms of SCS and DRGS therapies.


Asunto(s)
Dolor Crónico , Estimulación de la Médula Espinal , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Ganglios Espinales , Humanos , Estudios Prospectivos , Médula Espinal
4.
J Women Aging ; 33(6): 569-582, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32070239

RESUMEN

Physical activity is a priority to improve health. However, a sedentary lifestyle is increasingly becoming the norm. For example, in Mexico, sedentarism has increased, especially among older women. This study evaluated the effects of aquafitness on the health of older women in Mexico. Healthy older women performed aquafitness exercise and were compared to a control group of comparable women. Outcome assessments performed at baseline and after 17-weeks included psychological and physical/anthropometric measures. Participants in aquafitness became more optimistic, lost more weight, body fat, and a subsequent decrease in BMI, compared to controls. The results suggest important avenues for future research.


Asunto(s)
Ejercicio Físico , Salud Mental , Anciano , Femenino , Humanos , México , Proyectos Piloto , Conducta Sedentaria
5.
J Neural Eng ; 17(3): 036019, 2020 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-32365340

RESUMEN

OBJECTIVE: Spinal cord stimulation (SCS) is a common neurostimulation therapy to treat chronic pain. Computational models represent a valuable tool to study the potential mechanisms of action of SCS and to optimize the design and implementation of SCS technologies. However, it is imperative that these computational models include the appropriate level of detail to accurately predict the neural response to SCS and to correlate model predictions with clinical outcomes. Therefore, the goal of this study was to investigate several anatomic and technical factors that may affect model-based predictions of neural activation during thoracic SCS. APPROACH: We developed computational models that consisted of detailed finite element models of the lower thoracic spinal cord, surrounding tissues, and implanted SCS electrode arrays. We positioned multicompartment models of sensory axons within the spinal cord to calculate the activation threshold for each sensory axon. We then investigated how activation thresholds changed as a function of several anatomical variables (e.g. spine geometry, dorsal rootlet anatomy), stimulation type (i.e. voltage-controlled vs. current-controlled), electrode impedance, lead position, lead type, and electrical properties of surrounding tissues (e.g. dura conductivity, frequency-dependent conductivity). MAIN RESULTS: Several anatomic and modeling factors produced significant percent differences or errors in activation thresholds. Rostrocaudal positioning of the cathode with respect to the vertebrae had a large effect (up to 32%) on activation thresholds. Variability in electrode impedance produced significant changes in activation thresholds for voltage-controlled stimulation (38% to 51%), but had little effect on activation thresholds for current-controlled stimulation (less than 13%). Changing the dura conductivity also produced significant differences in activation thresholds. SIGNIFICANCE: This study demonstrates several anatomic and technical factors that can affect the neural response to SCS. These factors should be considered in clinical implementation and in future computational modeling studies of thoracic SCS.


Asunto(s)
Estimulación de la Médula Espinal , Axones , Electrodos Implantados , Espacio Epidural , Médula Espinal
6.
JAMA ; 323(12): 1141-1150, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32207797

RESUMEN

Importance: Treating biliary atresia in newborns earlier can delay or prevent the need for liver transplant; however, treatment typically occurs later because biliary atresia is difficult to detect during its early stages. Objective: To determine the diagnostic yield of newborn screening for biliary atresia with direct or conjugated bilirubin measurements and to evaluate the association of screening implementation with clinical outcomes. Design, Setting, and Participants: A cross-sectional screening study of 124 385 infants born at 14 Texas hospitals between January 2015 and June 2018; and a pre-post study of 43 infants who underwent the Kasai portoenterostomy as treatment for biliary atresia at the region's largest pediatric hepatology center before (January 2008-June 2011) or after (January 2015-June 2018) screening implementation. Final follow-up occurred on July 15, 2019. Exposures: Two-stage screening with direct or conjugated bilirubin measurements. In stage 1, all newborns were tested within the first 60 hours of life, with a positive screening result defined as bilirubin levels exceeding derived 95th percentile reference intervals. In stage 2, infants who had a positive screening result in stage 1 were retested at or before the 2-week well-child visit, with a positive screening result defined as bilirubin levels greater than the stage 1 result or greater than 1 mg/dL. Main Outcomes and Measures: The primary outcomes of the screening study were sensitivity, specificity, positive predictive value, and negative predictive value based on infants testing positive in both stages. The reference standard was biliary atresia diagnosed at the region's pediatric hepatology centers. The primary outcome of the pre-post study was the age infants underwent the Kasai portoenterostomy for treatment of biliary atresia. Results: Of 124 385 newborns in the screening study, 49.2% were female, 87.6% were of term gestational age, 70.0% were white, and 48.1% were Hispanic. Screening identified the 7 known infants with biliary atresia with a sensitivity of 100% (95% CI, 56.1%-100.0%), a specificity of 99.9% (95% CI, 99.9%-99.9%), a positive predictive value of 5.9% (95% CI, 2.6%-12.2%), and a negative predictive value of 100.0% (95% CI, 100.0%-100.0%). In the pre-post study, 24 infants were treated before screening implementation and 19 infants were treated after screening implementation (including 6 of 7 from the screening study, 7 from screening at nonstudy hospitals, and 6 from referrals because of clinical symptoms). The age infants underwent the Kasai portoenterostomy was significantly younger after screening was implemented (mean age, 56 days [SD, 19 days] before screening implementation vs 36 days [SD, 22 days] after screening implementation; between-group difference, 19 days [95% CI, 7-32 days]; P = .004). Conclusions and Relevance: Newborn screening with direct or conjugated bilirubin measurements detected all known infants with biliary atresia in the study population, although the 95% CI around the sensitivity estimate was wide and the study design did not ensure complete ascertainment of false-negative results. Research is needed in larger populations to obtain more precise estimates of diagnostic yield and to better understand the clinical outcomes and cost-effectiveness of this screening approach.


Asunto(s)
Atresia Biliar/diagnóstico , Bilirrubina/sangre , Tamizaje Neonatal/métodos , Portoenterostomía Hepática/estadística & datos numéricos , Factores de Edad , Atresia Biliar/sangre , Atresia Biliar/cirugía , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Trasplante de Hígado , Masculino , Valor Predictivo de las Pruebas , Valores de Referencia , Sensibilidad y Especificidad , Tiempo de Tratamiento
7.
Med. crít. (Col. Mex. Med. Crít.) ; 34(1): 68-72, Jan.-Feb. 2020. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1386255

RESUMEN

Resumen: Durante la pandemia de SARS-CoV-2 se presenta el caso clínico de un hombre joven de 43 años, sin comorbilidades, quien asiste a un concierto en la Ciudad de México y seis días después inicia con un cuadro infeccioso de vías respiratorias altas que evoluciona en seis días a una neumonía con síndrome de insuficiencia respiratoria progresiva aguda (SIRPA) grave. Se confirma infección por SARS-CoV-2 y sobreinfección bacteriana por Staphylococcus aureus meticilino resistente, requiriendo asistencia ventilatoria invasiva y cuidados en la Unidad de Terapia Intensiva del Hospital Bité Medica de la Ciudad de México por un grupo interdisciplinario. El paciente evoluciona favorablemente con hidroxicloroquina y lopinavir/ritonavir, esteroide sistémico, linezolid, estrategias ventilatorias de protección pulmonar y cuidados críticos generales sin desarrollar falla de otros órganos o sistemas.


Abstract: During the SARS-CoV-2 Pandemic, a clinical case of a 43-year-old young man is presented, who after six days of attending a concert in Mexico City developed an infectious of the upper respiratory tract that evolved to a pneumonia with severe acute respiratory distress syndrome (ARDS), confirming SARS CoV2 infection and bacterial superinfection with resistant methicillin Staphylococcus aureus, requiring invasive ventilatory assistance and care in the Intensive Care Unit of the Hospital Bité Medica, Mexico City by an interdisciplinary group. The patient improved with hydroxychloroquine and lopinavir/ritonavir, systemic steroid, linezolid, ventilatory strategies for pulmonary protection, and general critical care without developing failure of other organs or systems.


Resumo: Durante a pandemia de SARS CoV 2, é apresentado o caso clínico de um jovem de 43 anos que assiste a um concerto na Cidade do México e seis dias depois começa com um quadro infeccioso do trato respiratório superior que evolui em seis dias para pneumonia com síndrome do desconforto respiratório agudo grave, confirmando infecção por SARS CoV2 e superinfecção bacteriana com meticilina resistente Staphylococcus aureus, exigindo assistência ventilatória invasiva e cuidados na Unidade de Terapia Intensiva do Hospital Bitémedica, Cidade do México por um grupo interdisciplinar. O paciente progride para melhora com hidroxicloroquina e lopinavir/ritonavir, esteróide sistêmico, linezolida, estratégias ventilatórias para proteção pulmonar e cuidados críticos em geral, sem desenvolver falha de outros órgãos ou sistemas.

8.
Neuromodulation ; 23(5): 572-581, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31464040

RESUMEN

OBJECTIVE: Despite the widespread use of spinal cord stimulation (SCS) for chronic pain management, its neuromodulatory effects remain poorly understood. Computational models provide a valuable tool to study SCS and its effects on axonal pathways within the spinal cord. However, these models must include sufficient detail to correlate model predictions with clinical effects, including patient-specific data. Therefore, the goal of this study was to investigate axonal activation at clinically relevant SCS parameters using a computer model that incorporated patient-specific anatomy and electrode locations. METHODS: We developed a patient-specific computer model for a patient undergoing SCS to treat chronic pain. This computer model consisted of two main components: 1) finite element model of the extracellular voltages generated by SCS and 2) multicompartment cable models of axons in the spinal cord. To determine the potential significance of a patient-specific approach, we also performed simulations with standard canonical models of SCS. We used the computer models to estimate axonal activation at clinically measured sensory, comfort, and discomfort thresholds. RESULTS: The patient-specific and canonical models predicted significantly different axonal activation. Relative to the canonical models, the patient-specific model predicted sensory threshold estimates that were more consistent with the corresponding clinical measurements. These results suggest that it is important to account for sources of interpatient variability (e.g., anatomy, electrode locations) in model-based analysis of SCS. CONCLUSIONS: This study demonstrates the potential for patient-specific computer models to quantitatively describe the axonal response to SCS and to address scientific questions related to clinical SCS.


Asunto(s)
Axones/fisiología , Dolor Crónico , Estimulación de la Médula Espinal , Médula Espinal/fisiología , Dolor Crónico/terapia , Simulación por Computador , Humanos , Modelos Neurológicos , Dimensión del Dolor
9.
Neuromodulation ; 23(1): 64-73, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31215720

RESUMEN

OBJECTIVES: Spinal cord stimulation (SCS) for pain is typically implemented in an open-loop manner using parameters that remain largely unchanged. To improve the overall efficacy and consistency of SCS, one closed-loop approach proposes to use evoked compound action potentials (ECAPs) recorded from the SCS lead(s) as a feedback control signal to guide parameter selection. The goal of this study was to use a computational modeling approach to investigate the source of these ECAP recordings and technical and physiological factors that affect their composition. METHODS: We developed a computational model that coupled a finite element model of lower thoracic SCS with multicompartment models of sensory axons within the spinal cord. We used a reciprocity-based approach to calculate SCS-induced ECAPs recorded from the SCS lead. RESULTS: Our model ECAPs contained a triphasic, P1, N1, P2 morphology. The model P2-N1 amplitudes and conduction velocities agreed with previous experimental data from human subjects. Model results suggested that the ECAPs are dominated by the activation of axons with diameters 8.7-10.0 µm located in the dorsal aspect of the spinal cord. We also observed changes in the ECAP amplitude and shape due to the electrode location relative to the vertebrae and spinal cord. CONCLUSION: Our modeling results suggest that clinically effective SCS relies on the activation of numerous axons within a narrow fiber diameter range and that several factors affect the composition of the ECAP recordings. These results can improve how we interpret and implement these recordings in a potential closed-loop approach to SCS.


Asunto(s)
Simulación por Computador , Potenciales Evocados/fisiología , Modelos Anatómicos , Manejo del Dolor/métodos , Estimulación de la Médula Espinal/métodos , Médula Espinal/fisiología , Humanos
10.
Diabetes ; 68(11): 2143-2154, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31492662

RESUMEN

While peripheral neuropathy is the most common complication of long-term diabetes, cognitive deficits associated with encephalopathy and myelopathy also occur. Diabetes is a risk factor for Alzheimer disease (AD) and increases the risk of progression from mild cognitive impairment to AD. The only current recommendation for preventing or slowing the progression of peripheral neuropathy is to maintain close glycemic control, while there is no recommendation for central nervous system disorders. NSI-189 is a new chemical entity that when orally administered promotes neurogenesis in the adult hippocampus, increases hippocampal volume, enhances synaptic plasticity, and reduces cognitive dysfunction. To establish the potential for impact on peripheral neuropathy, we first showed that NSI-189 enhances neurite outgrowth and mitochondrial functions in cultured adult rat primary sensory neurons. Oral delivery of NSI-189 to murine models of type 1 (female) and type 2 (male) diabetes prevented multiple functional and structural indices of small and large fiber peripheral neuropathy, increased hippocampal neurogenesis, synaptic markers and volume, and protected long-term memory. NSI-189 also halted progression of established peripheral and central neuropathy. NSI-189, which is currently in clinical trials for treatment of major depressive disorder, offers the opportunity for the development of a single therapeutic agent against multiple indices of central and peripheral neuropathy.


Asunto(s)
Aminopiridinas/uso terapéutico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Piperazinas/uso terapéutico , Células Receptoras Sensoriales/efectos de los fármacos , Aminopiridinas/farmacología , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/fisiopatología , Femenino , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Proyección Neuronal/efectos de los fármacos , Piperazinas/farmacología , Ratas , Sinapsis/efectos de los fármacos
11.
Rev chil anest ; 48(1): 36-43, 2019. tab
Artículo en Español | LILACS | ID: biblio-1451522

RESUMEN

OBJECTIVE: To describe and evaluate the postoperative analgesic effectiveness of the combination of morphine, dexamethasone and local anesthetic in ultrasound-guided brachial plexus block. MATERIALS AND METHODS: A prospective, observational and analytical cohort study was conducted. The cohort was composed of 106 patients divided into three groups: 1. Local anesthetic (AL), 2. Local anesthetic plus dexamethasone (ALD) and 3. Local anesthetic plus dexamethasone and morphine (ALDM). The outcome variable was acute postoperative pain (DAP) and the need for analgesic rescue. The DAP was evaluated at 3, 6, 9, 12, 18 and 24 postoperative hours using an analogous verbal scale (VAS) and was additionally recorded if it required analgesic rescue. Additionally, latency time, duration of sensory and motor block were recorded. Analysis was done with stata14 software. RESULTS: The overall incidence of postoperative pain was higher in the AL group (89%) than in the ALD group (58.3%) and ALDM (60%). At 3,6 and 9 hours postoperatively, no differences were found between the three groups. At 12 and 18 hours postoperatively, the incidence of pain in the ALD and ALDM groups was lower and significant (p < 0.05) with respect to the AL group. There were no statistically significant differences between the ALD and ALDM groups. At 24 post-operative time no statistically, significant differences were found between the three groups, however at that time the incidence of pain in the AL group was 38% vs 25% of the ALDM group vs 23% of the ALD group. At the end of the study, the intervention in the ALDM group and the ALD group presented Relative Risks (RR) of 0.68 and 0.65 respectively to the LA group. CONCLUSIONS: The addition of morphine and dexamethasone or morphine alone to the local anesthetic reduces the postoperative acute pain between 12 and 18 hours and prolongs the time of peripheral ultrasound-guided brachial plexus block. To evaluate differences between these coadjutant's, a study with more power and controlled clinical trial type is required.


Objetivo: Describir y evaluar la efectividad analgésica postoperatoria de la combinación de morfina y dexametasona como coadyuvantes a anestésicos locales en bloqueo ecodirigido del plexo braquial. Materiales y Métodos: Se realizó un estudio tipo cohorte prospectivo, observacional y analítico. La cohorte quedó conformada por 106 pacientes divididos en tres grupos: grupo anestésico local sin coadyuvantes (ALSC), grupo anestésico local más dexametasona (ALD) y grupo anestésico local más dexametasona y morfina (ALDM). La variable resultado fue dolor agudo posoperatorio (DAP) moderado a severo y necesidad de rescate analgésico. EL DAP se evaluó a las 3, 6, 9, 12, 18 y 24 horas posoperatorias (POP) utilizando escala verbal análoga (EVA) y, adicionalmente, se registró si se requirió rescate analgésico. Igualmente, se registró tiempo de latencia, duración del bloqueo sensitivo y motor. El análisis se realizó con software stata14. Resultados: La incidencia global de DAP moderado a severo fue mayor en el grupo ALSC (89%) con respecto al grupo ALD (58,3%) y grupo ALDM (60%). A las 3, 6 y 9 horas posoperatorias no se evidenció diferencias entre los tres grupos. A las 12 y 18 horas posoperatorias la incidencia de dolor en los grupos con coadyuvantes fue menor y significativo (p < 0,05) con respecto al grupo control. Entre los grupos ALD y ALDM no hubo diferencias estadísticamente significativas. A las 24 horas POP no se encontraron diferencias estadísticamente significativas entre los tres grupos, sin embargo, en ese momento la incidencia de DAP moderado a severo en los tres grupos fue 38%, 25% y 23% respectivamente. Al final del estudio la intervención en los grupos ALD y ALDM presentaron riesgos relativos (RR) de 0,68 y 0,65 respecto al grupo ALSC. Conclusiones: La adición de morfina y dexametasona o de morfina sola al anestésico local parece disminuir el DAP moderado a severo entre las 12 y 18 horas y prolongar la duración de bloqueos periféricos ecoguiados del plexo braquial. Para evaluar diferencias entre estos coadyuvantes se requieren un estudio con más poder y de tipo ensayo clínico controlado.


Asunto(s)
Dolor Postoperatorio/prevención & control , Dexametasona/administración & dosificación , Bloqueo del Plexo Braquial/métodos , Morfina/administración & dosificación , Estudios Prospectivos , Ultrasonografía , Resultado del Tratamiento , Adyuvantes Anestésicos/administración & dosificación , Anestésicos Locales/administración & dosificación
12.
Neuroscience ; 354: 136-145, 2017 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-28476321

RESUMEN

Diabetes mellitus represents a group of metabolic diseases that are characterized by hyperglycemia caused by either lack of insulin production or a reduced ability to respond to insulin. It is estimated that there were 347 million people worldwide who suffered from diabetes in 2008 and incidence is predicted to double by 2050. Neuropathy is the most common complication of long-term diabetes and approximately 30% of these subjects develop chronic neuropathic pain. A distinct acute, severe form of neuropathic pain, called insulin neuritis or treatment-induced painful neuropathy of diabetes (TIND), may also occur shortly after initiation of intensive glycemic control, with an incidence rate of up to 10.9%. The pathological mechanisms leading to TIND, which is mostly unresponsive to analgesics, are not yet understood, impeding the development of therapies. Studies to date have been clinical and with limited cohorts of patients. In the current study, we developed chronic and acute insulin-induced neuropathic pain in mice with type 2 insulin-resistant diabetes. Furthermore, we determined that insulin-induced acute allodynia is independent of glycemia levels, can also be induced with Insulin-like Growth Factor 1 (IGF1) and be prevented by inhibition of AKT, providing evidence of an insulin/IGF1 signaling pathway-based mechanism for TIND. This mouse model is useful for the elucidation of mechanisms contributing to TIND and for the testing of new therapeutic approaches to treat TIND.


Asunto(s)
Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/terapia , Modelos Animales de Enfermedad , Hipoglucemiantes/toxicidad , Insulina/toxicidad , Neuralgia/complicaciones , Neuralgia/terapia , Aminas/uso terapéutico , Animales , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Neuropatías Diabéticas/genética , Inhibidores Enzimáticos/farmacología , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Femenino , Proteínas Activadoras de GTPasa , Gabapentina , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Hiperalgesia/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Conducción Nerviosa/genética , Conducción Nerviosa/fisiología , Neuralgia/genética , Umbral del Dolor/fisiología , Tiempo de Reacción/fisiología , Receptor de Insulina/deficiencia , Receptor de Insulina/genética , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Ácido gamma-Aminobutírico/uso terapéutico
13.
Rev. colomb. obstet. ginecol ; 68(1): 35-48, Jan.-Mar. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-900738

RESUMEN

ABSTRACT Objective: There is insufficient evidence about the impact of cesarean delivery on maternal request (CDMR). This study was designed to evaluate different maternal and neonatal outcomes comparing CDMR with vaginal deliveries in low-risk pregnancies. Materials and methods: Prospective observational study including women aged 18 to 45 with a low-risk, term pregnancy, who delivered between June 2008 and April 2012 at a University Hospital in Bogota Colombia. The occurrence of any of 5 pre-specified adverse maternal events (maternal outcome) and of any of 17 pre-specified adverse neonatal events (neonatal outcome) was compared between CDMR and vaginal deliveries. Induced vaginal deliveries were analyzed separately. All women received the same standard of care. The effect of confounders was adjusted using multivariate logistic regression. Results: The study included 214 women with CDMR, 341 with spontaneous vaginal delivery (SVD) and 376 with induced vaginal delivery (IVD). Relative to the SVD group, the multivariate-adjusted odds ratios for adverse maternal outcomes were 0.21 (95% CI: 0.05-0.97) in the CDMR group and 0.93 (95% CI: 0.42-2.06) in the IVD group. The multivariate ORs for adverse neonatal outcomes were 0.59 (95% CI: 0.36-0.93) for CDMR and 0.84 (95% CI: 0.59-1.21) for IVD. The frequency of hospitalization of the newborn was lowest in the cesarean delivery group (10.3% versus 15.8% for spontaneous deliveries, 16.2% for induced vaginal deliveries). Conclusions: Among low-risk pregnancy women who entered a standardized obstetric care protocol, CDMR was associated with a lower rate of adverse perinatal outcomes when compared to spontaneous vaginal delivery. Further studies are needed to assess long-term the safety of CDMR.


RESUMEN Objetivo: Existe evidencia insuficiente sobre el impacto de la cesárea por solicitud materna (CSM); este estudio evalúa el efecto de la CSM en los múltiples desenlaces maternos y neonatales comparando CSM con parto vaginal entre embarazos de bajo riesgo. Materiales y métodos: Estudio observacional prospectivo que incluyó mujeres entre 18 y 45 años de edad, con un embarazo a término y de bajo riesgo, que tuvieron parto entre junio de 2008 y abril de 2012 en un hospital universitario en Bogotá, Colombia. Se comparó la ocurrencia de cualquiera de 5 eventos adversos maternos preespecificados, y de cualquiera de 17 eventos neonatales preespecificados, entre CSM y partos vaginales. Los partos vaginales inducidos fueron analizados separadamente. Todas las mujeres recibieron el mismo cuidado estandarizado. El efecto de variables confusoras se ajustó mediante regresión logística múltiple. Resultados: Se incluyeron 214 mujeres con CSM, 341 con parto vaginal espontáneo (PVE) y 376 con parto vaginal inducido (PVI). Respecto al grupo PVE, el OR ajustado del desenlace materno fue 0,21 (IC 95 %: 0,05-0,97) en el grupo CSM y 0,93 (IC 95%: 0,42-2,06) en el grupo PVI. El OR de presentar un mal desenlace neonatal fue: 0,59 (95% CI: 0,36-0,93) para CSM y 0,84 (95% CI: 0,59-1,21) para PVI. La frecuencia de hospitalización del neonato más baja fue en el grupo de CSM (10,3 % frente a 15,8 % para PVE, 16,2 % para PVI). Conclusiones: En pacientes con embarazo de bajo riesgo que ingresaron a un protocolo estándar de cuidado obstétrico, CSM se acompañó de una menor tasa de eventos adversos perinatales respecto al parto vaginal espontáneo. Sin embargo, se requieren estudios que evalúen la seguridad de CSM en el largo plazo.


Asunto(s)
Femenino , Adulto , Histerectomía , Histerectomía Vaginal , Calidad de Vida
14.
Rev. cuba. cir ; 55(2): 0-0, abr.-jun. 2016. tab
Artículo en Español | LILACS | ID: lil-791489

RESUMEN

Introducción: el cáncer de esófago es la neoplasia del tubo digestivo de peor pronóstico. Su tratamiento constituye un desafío al tratarse de pacientes con deterioro nutricional con incapacidad de ingerir alimentos. La mayoría son tributarios de tratamiento paliativo. Objetivo: describir la experiencia en la atención nutricional de los pacientes con cáncer de esófago y cardias con la introducción del grupo de apoyo nutricional en el Hospital Universitario Comandante Manuel Fajardo. Método: se presentan 126 enfermos con cáncer de esófago y cardias, 51 de ellos con lesiones resecables a los que se realizó esofagectomía y 75 enfermos con cáncer avanzado e intervenciones paliativas, atendidos desde 2006 hasta 2015, según los protocolos de actuación del grupo de apoyo nutricional. Resultados: todos los pacientes se encontraban entre 46 y 76 años, 69 por ciento mayor de 60 años, 87,3 port ciento del sexo masculino, 90 por ciento con antecedentes de tabaquismo y 80 por ciento de alcoholismo. La localización del tumor predominó en el un tercio inferior del esófago y cardias, seguido por tercio medio y el tercio superior. Presentaron desnutrición leve 4,1 por ciento, 53,9 por ciento moderada y 42 por ciento grave. Todos presentaron disminución de la albúmina y 57,9 por ciento, la capacidad funcional disminuida. Todos recibieron consejería dietética y dietoterapia orientada. Se incrementó la supervivencia en 14 meses en los casos paliativos y a 39 meses en los resectivos, comparado con un periodo anterior sin la presencia del grupo de apoyo nutricional. Conclusiones: la valoración nutricional debe ser parte de la evaluación clínica de los pacientes con cáncer de esófago desde el momento del diagnóstico y durante la enfermedad, para identificar y corregir el déficit nutricional, mantener y preservar el peso. Esto mejora la respuesta a los distintos tratamientos oncológicos, aumenta la supervivencia y mejora la calidad de vida(AU)


Introduction: esophageal cancer is a malignancy of the digestive tract with the worst prognosis. Its treatment constitutes a challenge in the case of patients with nutritional deterioration and inability to ingest food. Most of them are candidates for palliative treatment. Objective: to describe the experience regarding the nutritional care of patients with esophageal cancer and cardias, with the introduction of the nutritional support group at Comandante Manuel Fajardo University Hospital. Method: 126 patients with esophageal cancer and cardia presented: 51 of them with resectable lesions and who underwent esophagectomy, and 75 with advanced cancer and palliative interventions, treated from 2006 to 2015, according to the performance protocols of the nutritional support group. Results: all patients were at age 46-76 years (69 percent over 60 years), 87.3 percent were male, 90 percent had a history of smoking and 80 percent of alcohol. The predominant location of the tumor was the third-lower esophagus and the cardia, followed by the middle and upper thirds. They had mild malnutrition (4,1 percent), 53,9 percent had moderate and 42 percent, severe malnutrition. All of them showed decreased albumin and 57,9 percent showed decreased functional capacity. All of them received dietary counseling and oriented diet therapy. Survival after 14 months was increased in the palliative cases and after 39 months in respective cases, compared with a previous period without the presence of the nutritional support group. Conclusions: nutritional assessment should be part of the clinical evaluation of patients with esophageal cancer from the time of diagnosis and during illness, in order to identify and correct nutritional deficit, maintain and preserve the weight, thus improving response to cancer treatments, and increasing survival, which improves quality of life(AU)


Asunto(s)
Humanos , Masculino , Adulto , Anciano , Neoplasias Esofágicas/terapia , Esofagectomía , Calidad de Vida , Neoplasias Gástricas/terapia
15.
Rev. cuba. cir ; 54(3): 0-0, jul.-set. 2015.
Artículo en Español | LILACS | ID: lil-765758

RESUMEN

El cáncer de mama es la primera causa de muerte por tumores malignos entre las mujeres. Una dieta no saludable, el sedentarismo y la obesidad son factores de riesgo importantes para padecer cáncer de mama, sobre todo en mujeres posmenopáusicas. El objetivo del presente trabajo es revisar los estudios epidemiológicos más relevantes sobre dieta, obesidad y cáncer de mama en las mujeres. Se estableció una estrategia de información, educación y comunicación social como apoyo a las acciones del Programa Nacional de Control de Cáncer Mamario. Para la prevención y tratamiento de la obesidad e incidencia de cáncer de mama es necesario actividades de educación nutricional, para producir cambios en los patrones y hábitos alimentarios y por consiguiente de estilos de vida, que promuevan una dieta más variada y el aumento del ejercicio físico, entre otros aspectos(AU)


Breast cancer is the first cause of death from malignant tumors in women. Unhealthy diet, sedentary lifestyle and obesity are important risk factors to suffer breast cancer, mainly in post-menopausal women. The objective of this article was to check the most relevant epidemiological studies on diet, obesity and breast cancer in women. Information, education and social communication strategy has been set as a support to the National Program of Breast Cancer Control. For the prevention and treatment of obesity and of the breast cancer incidence, it is necessary to implement nutritional education activities in order to bring about changes in feeding patters and habits and consequently in lifestyles that may promote more varied diet and increase of exercising, among other things(AU)


Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/prevención & control , Obesidad/prevención & control , Factores de Riesgo , Conducta Sedentaria , Conducta Alimentaria , Educación Alimentaria y Nutricional , Estilo de Vida
16.
Semin Ultrasound CT MR ; 30(3): 205-14, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19537053

RESUMEN

Blunt cerebrovascular injuries (BCVI) can cause ischemic stroke and are associated with high mortality rates. These injuries may have an initial silent course and if recognized in a timely fashion can be treated before neurologic deficit occurs. This has led to the growing implementation of aggressive screening programs to detect and thereby treat BCVI early, before onset of symptoms. Digital subtraction angiography is the diagnostic reference standard for diagnosing BCVI. However, in recent years, there has been a renewed interest in the use of noninvasive techniques, such as multidetector computed tomography angiography (MDCTA) for the evaluation of these patients. The accuracy of MDCTA with respect to digital subtraction angiography is not completely elucidated; however, MDCTA shows a level of accuracy sufficient to serve as an initial screening examination for blunt cerebrovascular injuries.


Asunto(s)
Traumatismos del Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Heridas no Penetrantes/diagnóstico por imagen , Angiografía/métodos , Angiografía de Substracción Digital , Traumatismos de las Arterias Carótidas/diagnóstico por imagen , Traumatismos de las Arterias Carótidas/terapia , Circulación Cerebrovascular/fisiología , Medicina Basada en la Evidencia , Humanos , Ultrasonografía , Arteria Vertebral/lesiones
17.
Rev. cuba. cir ; 47(3)sept.-dic. 2008.
Artículo en Español | LILACS, CUMED | ID: lil-515548

RESUMEN

Se realizó un estudio descriptivo, retrospectivo y longitudinal, de tipo serie de casos, con 69 pacientes atendidos en el Hospital Universitario Manuel Fajardo entre 1995 y 2007, que requirieron decorticación pulmonar como tratamiento de un empiema pleural. Se seleccionaron los expedientes clínicos de 29 pacientes, a los cuales fue necesario realizar una decorticación pulmonar como tratamiento quirúrgico y estos constituyeron la muestra de la investigación. Diez de los 29 pacientes estaban en fase fibrinopurulenta y 19, en la organizada (hubo 13 pacientes en la fase organizada temprana, la cual coincide con el período subagudo de la enfermedad, y 6, en la tardía, que corresponde con el período de conicidad de la enfermedad). El sexo más afectado fue el masculino (relación de 8:1). Hubo fuga aérea en todos los pacientes, con diferente duración según el tipo de decorticación (más duradera en la clásica y la tardía). Las complicaciones fueron escasas en la decorticación temprana. En las decorticaciones clásica y tardía se presentaron 4 complicaciones sépticas respiratorias y falleció un paciente en fase organizada tardía. A este se practicó una decorticación tardía, paquipleurectomía y resección pulmonar. La decorticación temprana es una opción terapéutica segura, de poca morbilidad, que evita las complicaciones presentes en las decorticaciones clásicas y tardías(AU)


A case series descriptive, retrospective and longitudinal study that included 69 patients attended at Manuel Fajardo University Hospital from 1995 to 2007 was undertaken. These patients required pulmonary decortication to treat a pleural empyema. The clinical histories of 29 patients who underwent pulmonary decortication and were taken as a sample for the investigation were selected. Ten of the 29 patients were in fibrinopurulent stage and 19 in the organized (13 patients were in the early organized stage, which coincided with the subacute period of the disease, and 6 were in the late that corresponded to the conicity period of the disease). Males were the most affected (ratio 8:1). There was air leak in all patients with different duration according to the time of decortication (it lasted more in the classic and in the late). A few complications were observed in early decortication. In the classic and late decortications, there were 4 septic respiratory complications and a patient in late organized stage that had undergone late decortication, pachypleurectomy and lung resection died. Early decortication is a safe therapeutical option with low morbidity that prevents the complications appearing in the classic and late decortications(AU)


Asunto(s)
Humanos , Masculino , Adulto , Empiema Pleural/terapia , Pulmón/cirugía , Epidemiología Descriptiva , Estudios Retrospectivos , Estudios Longitudinales
18.
Rev. cuba. cir ; 47(1)ene.-mar. 2008. tab
Artículo en Español | LILACS, CUMED | ID: lil-507052

RESUMEN

INTRODUCCIÓN. El neumotórax espontáneo simple es causado, en general, por la rotura de una pequeña zona debilitada del pulmón. Un neumotórax recidivante puede causar una incapacidad considerable. MÉTODOS. Se realizó un estudio descriptivo, prospectivo, de corte transversal de los pacientes con neumotórax persistente y recidivante, atendidos en el Hospital Universitario «Comandante Manuel Fajardo¼ en el período de 1988 a 2006. Se analizaron las causas del neumotórax y los resultados de su tratamiento. El universo de estudio fueron todos los pacientes con diagnóstico de neumotórax (225 pacientes), entre los cuales se seleccionó a los diagnosticados de neumotórax persistente o recidivante (42 en total). Todos los pacientes fueron atendidos siguiendo un algoritmo de trabajo del servicio de cirugía del hospital. RESULTADOS. Las bullas fueron la causa fundamental en el neumotórax recidivante y las vesículas subpleurales, en los persistentes. En los neumotórax persistentes se mantuvo la sonda de aspiración hasta el quinto día en el 71 por ciento de los casos, hasta 5 a 7 días en el 23 por ciento y por más de 7 días en el 6 por ciento. Se utilizó la vía axilar para la incisión y se realizó resección atípica o reglada con pleurectomía parietal o abrasión, que tuvo un 100 por ciento de efectividad. La mortalidad quirúrgica fue nula. CONCLUSIONES. Los cuidados de la sonda de pleurotomía y la aspiración continua controlada son pilares en el tratamiento primario del neumotórax. Después de 5 días sin lograr la reexpansión pulmonar y si existe un segundo neumotórax, debe siempre valorarse el tratamiento definitivo por toracotomía. Debe considerarse la pleurectomía parietal como el proceder de elección en los pacientes con reserva cardiorrespiratoria adecuada. Un buen sistema de aspiración de drenaje hace que no sea necesaria una segunda intervención y disminuye las posibilidades de complicaciones(AU)


INTRODUCTION. The simple spontaneous pneumothorax is generally caused by the rupture of a small weakened zone of the lung. A recurrent pneumothorax may cause considerable disability. METHODS. A descriptive, prospective and cross-sectional study was conducted among the patients with persistent and recurrent pneumothorax that received attention at "Comandante Manuel Fajardo" University Hospital from 1998 to 2006. The causes of the pneumothorax and the results of its treatment were analyzed. The study group was composed of all the patients with pneumothorax diagnosis (225 patients), of whom those diagnosed with persistent or recurrent pneumothorax (42 in all) were selected. All the patients were attended by following a working algorithm of surgery service of the hospital. RESULTS. The bullae were the main cause of the recurrent pneumothorax, and the subpleural vesicles of the persistent. In the persistent pneumothorax, the aspiration probe was maintained until the fifth day in 71 percent of the cases, from 5 to 7 in 23 percent, and for more than 7 days in 6 percent. The axillary route was used for the incision, and atypical or regulated resection was performed with parietal pleurotomy or abrasion, which had 100 percent of effectivity. No surgical mortality was reported. CONCLUSIONS. The care of the pleurotomy catheter and the continual controlled aspiration are milestones in the primary treatment of pneumothorax. After 5 days without attaining the pulmonary reexpansion, and if there is a second pneumothorax, the definitive treatment by thoracotomy should always be assessed. Parietal pleurotomy should be considered as an elective procedure in the patients with an adequate respiratory reserve. A good drainage aspiration system prevents a second intervention and reduces the possibilities of complications(AU)


Asunto(s)
Humanos , Masculino , Adulto , Neumotórax/diagnóstico , Neumotórax/terapia , Epidemiología Descriptiva , Estudios Transversales , Estudios Prospectivos
19.
Oecologia ; 150(4): 602-10, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17024378

RESUMEN

N cycling in tropical dry forests is driven by rainfall seasonality but the mechanisms involved are not well understood. We studied the seasonal variation in N dynamics and microbial biomass in the surface litter of a tropical dry forest ecosystem in Mexico over a 2-year period. Litter was collected at 4 different times of the year to determine changes in total, soluble, and microbial C and N concentrations. Additionally, litter from each sampling date was incubated under laboratory conditions to determine potential C mineralization rate, net N mineralization, net C and N microbial immobilization, and net nitrification. Litter C concentrations were highest in the early-dry season and lowest in the rainy season, while the seasonal changes in N concentrations varied between years. Litter P was higher in the rainy than in the early-dry season. Water-soluble organic C (WSOC) and water-soluble N concentrations were highest during the early- and late-dry seasons and represented up to 4.1 and 5.9% of the total C and N, respectively. NH (4) (+) and NO (3) (-) showed different seasonal and annual variations. They represented an average 23% of soluble N. Microbial C was generally higher in the dry than in the wet seasons, while microbial N was lowest in the late-dry and highest in the early-rainy seasons. Incubations showed that lowest potential C mineralization rates and C and N microbial immobilization occurred in rainy season litter, and were positively correlated to WSOC. Net nitrification was highest in rainy season litter. Our results showed that the seasonal pattern in N dynamics was influenced by rainfall seasonality and labile C availability, and not by microbial biomass. We propose a conceptual model to hypothesize how N dynamics in the litter layer of the Chamela tropical dry forest respond to the seasonal variation in rainfall.


Asunto(s)
Carbono/análisis , Nitrógeno/análisis , Lluvia , Microbiología del Suelo , Árboles , México , Fósforo/análisis , Estaciones del Año , Clima Tropical
20.
Rev. Fac. Med. (Bogotá) ; 54(4): 269-282, oct.-dic. 2006. ilus
Artículo en Español | LILACS | ID: lil-440756

RESUMEN

La necesidad de alcanzar un tratamiento óptimo para el tabaquismo, la obesidad y sus comorbilidades, conocidos factores de riesgo cardiovascular, ha fomentado la búsqueda de objetivos terapéuticos novedosos. Es el caso del sistema endocanabinoide, involucrado en diversos fenómenos fisiológicos entre los que se encuentran el refuerzo de ciertos comportamientos y la regulación del apetito. La sobreactivación de este sistema altera la homeostasis corporal predisponiendo a dependencias o a un aumento en la ingesta alimentaria, lo que puede traducirse en tabaquismo u obesidad. La intervención farmacológica sobre el sistema endocanabinoide puede contribuir al manejo de estos factores de riesgo cardiovascular, teniendo en cuenta que a tales beneficios se suman otros independientes de la suspensión del tabaquismo o la reducción de peso, como el aumento del colesterol de alta densidad, la disminución de triglicéridos y la mejoría del control glucémico en pacientes con diabetes. Ensayos clínicos controlados aleatorizados adelantados en poblaciones con diferentes características, han evaluado la utilidad de la regulación farmacológica del sistema endocanabinoide; confirmando su eficacia en personas con factores de riesgo cardiovascular establecidos...


Asunto(s)
Humanos , Obesidad/metabolismo , Receptores de Cannabinoides/metabolismo , Tabaquismo , Factores de Riesgo
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