RESUMEN
BACKGROUND: Headache is a frequent symptom in coronavirus disease 2019 (COVID-19) patients, and idiopathic intracranial hypertension (pseudotumor cerebri) has been reported among patients who underwent lumbar puncture for persistent headaches. CASE PRESENTATION: A 45-year-old black man presented with dyspnea, cough, fever and headache for 05 days followed by blurring of vision associated with worsening of the headache. Physical examination was significant for tachypnea and oxygen desaturation and there were no abnormal neurologic findings. He tested positive for SARS-CoV-2 with nasopharyngeal swab PCR. His CSF opening pressure appeared high with normal CSF analysis and brain magnetic resonance imaging (MRI) revealed prominent subarachnoid space around the optic nerves and bilateral papilledema. He had significant improvement with medical therapy alone. CONCLUSION: Idiopathic intracranial hypertension (IIH) may occur in association with SARS-CoV-2 infection and should be considered when making a differential diagnosis for headache and blurring of vision. COVID-19 may play a role in the development of intracranial hypertension, even in the absence of known risk factors. Early diagnosis and treatment of IIH has paramount importance to prevent vision loss and other morbidities.
Asunto(s)
COVID-19 , Cefalea , Seudotumor Cerebral , SARS-CoV-2 , Humanos , Masculino , Persona de Mediana Edad , COVID-19/complicaciones , COVID-19/diagnóstico , Cefalea/etiología , Cefalea/virología , Imagen por Resonancia Magnética , Seudotumor Cerebral/diagnóstico , Seudotumor Cerebral/complicaciones , Negro o AfroamericanoRESUMEN
BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.
Asunto(s)
Anticoagulantes/uso terapéutico , Hemorragia Cerebral/complicaciones , Enoxaparina/uso terapéutico , Hematoma/etiología , Trombosis de la Vena/prevención & control , Anciano , Anticoagulantes/efectos adversos , Enoxaparina/efectos adversos , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Trombosis de la Vena/tratamiento farmacológicoRESUMEN
BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.
Asunto(s)
Productos Biológicos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Terapia PUVA , Psoriasis/terapia , Acitretina/uso terapéutico , Adalimumab/uso terapéutico , Austria , Terapia Combinada , Ciclosporina/uso terapéutico , República Checa , Quimioterapia Combinada , Etanercept/uso terapéutico , Femenino , Fumaratos/uso terapéutico , Humanos , Infliximab/uso terapéutico , Israel , Italia , Estimación de Kaplan-Meier , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Países Bajos , Sistema de Registros , Índice de Severidad de la Enfermedad , Ustekinumab/uso terapéuticoRESUMEN
BACKGROUND: Limited evidence is available on the impact of socioeconomic factors on drug prescriptions for psoriasis. OBJECTIVES: To investigate factors influencing prescription of conventional vs. biological treatment for patients with psoriasis, based on the Italian Psocare registry, with a special focus on socioeconomic factors. METHODS: This was a cross-sectional study evaluating the baseline data of patients included in the Psocare registry. All of the consecutive adult patients with a diagnosis of chronic plaque psoriasis or psoriatic arthritis who were prescribed a systemic treatment for psoriasis at participating centres were included in this study. Univariate and multivariate analyses of the baseline factors associated with a biologics prescription were performed. RESULTS: From September 2005 to September 2009, 12 838 patients were identified. A multivariate analysis revealed that, among other factors, completing a level of education higher than lower secondary school and being employed as a manager or a professional were independent factors associated with a biologics prescription at entry in the registry. Additional analyses on the association between these two variables and a severe psoriasis condition [Psoriasis Area Severity Index (PASI) score > 20] revealed a significantly increasing trend of severe disease towards lower educational attainment, while unemployed patients were more likely to have a more severe condition compared with the other categories of workers. CONCLUSIONS: We documented inequalities of drug prescriptions for psoriasis in Italy, with a trend towards a higher frequency of prescription for more expensive biologics in higher socioeconomic sectors of the population.
Asunto(s)
Productos Biológicos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Psoriasis/tratamiento farmacológico , Adolescente , Adulto , Distribución por Edad , Anciano , Productos Biológicos/provisión & distribución , Estudios Transversales , Fármacos Dermatológicos/provisión & distribución , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Medicamentos bajo Prescripción/provisión & distribución , Medicamentos bajo Prescripción/uso terapéutico , Sistema de Registros , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Therapeutic hypothermia (i.e., temperature management) is an effective option for improving survival and neurological outcome after cardiac arrest and is potentially useful for the care of the critically ill neurological patient. We analyzed the feasibility of a device to control the temperature of the brain by controlling the temperature of the blood flowing through the neck. METHODS: A lumped parameter dynamic model, with one-dimensional heat transfer, was used to predict cooling effects and to test experimental hypotheses. The cooling system consisted of a flexible collar and was tested on 4 adult sheep, in which brain and body temperatures were invasively monitored for the duration of the experiment. RESULTS: Model-based simulations predicted a lowering of the temperature of the brain and the body following the onset of cooling, with a rate of 0.4 °C/h for the brain and 0.2 °C/h for the body. The experimental findings showed comparable cooling rates in the two body compartments, with temperature reductions of 0.6 (0.2) °C/h for the brain and 0.6 (0.2) °C/h for the body. For a 70 kg adult human subject, we predict a temperature reduction of 0.64 °C/h for the brain and 0.43 °C/h for the body. CONCLUSIONS: This work demonstrates the feasibility of using a non-invasive method to induce brain hypothermia using a portable collar. This device demonstrated an optimal safety profile and represents a potentially useful method for the administration of mild hypothermia and temperature control (i.e., treatment of hyperpyrexia) in cardiac arrest and critically ill neurologic patients.
Asunto(s)
Temperatura Corporal/fisiología , Lesiones Traumáticas del Encéfalo/terapia , Encéfalo/irrigación sanguínea , Arterias Carótidas , Paro Cardíaco/terapia , Hipotermia Inducida/instrumentación , Cuello , Animales , Estudios de Factibilidad , Femenino , Hipotermia Inducida/métodos , Modelos Animales , OvinosRESUMEN
Among lifestyle factors, nutrition is one of the most important determinants of health, and represents a pivotal element of cancer risk. Nonetheless, epidemiological evidences of the relationship between several cancers and specific foods and nutrients is still inadequate, and solid conclusions are missing. Indeed, caloric restriction without malnutrition is associated to cancer prevention. Food may be also the primary route of exposure to contaminants such as metals, persistent organic pollutants, and pesticides. Exposuredisease associations and the interplay with genetic susceptibility requires further studies on genetic variation, environment, lifestyle, and chronic disease in order to eliminate and reduce associated health risks, thus contributing to improve health outcomes for the population. A primary nutritional approach for Active and Healthy Ageing (AHA) has been developed by the Nutrition group of the European Innovation Partnership (EIP) on AHA. The working group on lifestyles of the Italian Ministry of Health has developed a comprehensive approach to adequate nutrition using a consensus methodology to collect and integrate the available evidences from the literature and from the Italian experiences at the regional level, to raise the interest of other experts and relevant stakeholders to outline and scale-up joint strategies for a primary nutritional approach to cancer prevention.
RESUMEN
Objetivo Analizar la asociación del grado de conocimiento sobre Papillomavirus Humano y la aceptación de la auto-toma vaginal como prueba diagnóstica para la detección de cáncer cervical en mujeres mexicanas que ya han tenido la experiencia de una auto-toma vaginal en casa. Métodos Cuestionario estructurado de 22 preguntas a 690 mujeres del estado de Morelos que se realizaron la auto-toma vaginal en casa para explorar el nivel de conocimientos sobre transmisión del Papillomavirus Humano, identificación del virus como causa necesaria para cáncer cervicouterino, manifestaciones clínicas de la infección y tratamiento. Se construyó un índice de conocimientos identificando su asociación con la aceptación de la auto-toma y la confianza que las mujeres tienen en ella. El análisis estadístico incluyó regresión logística con estimación de medidas de asociación y sus respectivos intervalos de confianza al 95%. Resultados El nivel de conocimientos sobre Papillomavirus Humano presentó una asociación positiva con el grado de aceptación de la auto-toma vaginal (OR 2.9 IC 95% 1.0-5.01) y con el nivel de confianza de las mujeres (OR 2.9 IC 95% 1.8-4.67). El nivel de conocimientos se incrementa con el grado de escolaridad y es mayor en las mujeres más jóvenes. Conclusiones Para lograr una participación continuada de las mujeres con mayor riesgo de cáncer cervicouterino en la auto-toma vaginal es necesario informarlas ampliamente sobre los aspectos generales del virus, en especial a aquellas mujeres de edad avanzada, de nivel escolar y socioeconómico bajos.(AU)
Objective To analyze the relationship between the level of knowledge about human papilloma virus and the acceptance of vaginal self-sampling as a cervical cancer diagnostic test among Mexican women who have already experienced vaginal self-sampling at home. Methods A structured questionnaire consisting of 22 questions was applied to 690 women in the state of Morelos who had taken a vaginal self-sample at home. The aspects explored were the level of knowledge about transmission of the human papilloma virus, identification of the virus as a necessary cause of cervical cancer, and clinical manifestations of infection and treatment. A knowledge index was constructed, identifying the relationship between the index and the women's acceptance of self-sampling, and their degree of trust in the procedure. The statistical analysis included a logistic regression with estimates of measures of association and their respective 95% confidence intervals. Results The level of knowledge about human papillomavirus showed a positive association with the degree of acceptance of vaginal self-sampling (OR 2.9; 95% CI 1.0-5.01) and the women's level of confidence (OR 2.9; 95% CI 1.8-4.67). The level of knowledge increased with level of education and was higher in younger women. Conclusions In order for women with an increased risk of cervical cancer to continue participating in vaginal self-sampling, they must be well informed about the virus. This is especially true for older women, those with lower levels of education, and those in lower socioeconomic levels.(AU)
Asunto(s)
Humanos , Femenino , Papillomaviridae , Atención Primaria de Salud/métodos , Autocuidado/métodos , Neoplasias del Cuello Uterino/diagnóstico , Estudios Transversales/instrumentación , MéxicoRESUMEN
The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Asunto(s)
Trastornos Respiratorios/terapia , Envejecimiento , Asma/terapia , Toma de Decisiones , Europa (Continente) , Unión Europea , Guías como Asunto , Humanos , Cooperación Internacional , Área sin Atención Médica , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Rinitis/terapia , Factores de Riesgo , Organización Mundial de la SaludRESUMEN
OBJECTIVE: To analyze the relationship between the level of knowledge about human papilloma virus and the acceptance of vaginal self-sampling as a cervical cancer diagnostic test among Mexican women who have already experienced vaginal self-sampling at home. METHODS: A structured questionnaire consisting of 22 questions was applied to 690 women in the state of Morelos who had taken a vaginal self-sample at home. The aspects explored were the level of knowledge about transmission of the human papilloma virus, identification of the virus as a necessary cause of cervical cancer, and clinical manifestations of infection and treatment. A knowledge index was constructed, identifying the relationship between the index and the women's acceptance of self-sampling, and their degree of trust in the procedure. The statistical analysis included a logistic regression with estimates of measures of association and their respective 95% confidence intervals. RESULTS: The level of knowledge about human papillomavirus showed a positive association with the degree of acceptance of vaginal self-sampling (OR 2.9; 95% CI 1.0-5.01) and the women's level of confidence (OR 2.9; 95% CI 1.8-4.67). The level of knowledge increased with level of education and was higher in younger women. CONCLUSIONS: In order for women with an increased risk of cervical cancer to continue participating in vaginal self-sampling, they must be well informed about the virus. This is especially true for older women, those with lower levels of education, and those in lower socioeconomic levels.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Papillomaviridae , Infecciones por Papillomavirus/psicología , Aceptación de la Atención de Salud , Autocuidado/psicología , Frotis Vaginal/psicología , Adulto , Factores de Edad , Anciano , Estudios Transversales , Detección Precoz del Cáncer , Escolaridad , Femenino , Humanos , México , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Conducta Sexual , Parejas Sexuales , Clase Social , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virologíaRESUMEN
This study provides data on the genetic structuring of the pipefish Syngnathus abaster in the western Mediterranean and Adriatic Seas. A total of 109 specimens were collected in brackish-water biotopes. The control region and three other regions of the mitochondrial genome were analysed. The most relevant result was the high genetic structuring found by Bayesian inference (BI), maximum likelihood (ML) and network analyses, which were consistent in showing three well-separated clusters of S. abaster populations. Furthermore, BI and ML did not support the monophyly of the taxon S. abaster. These results suggest the occurrence of a species complex in the study area, whose differentiation may have occurred since the Pleistocene. The results also show a very high genetic variability at the inter-population level, with no shared haplotypes among sites. Evolutionary forces due to the fragmented nature of the brackish-water habitats may account for the high genetic divergence found among the groups and populations. Finally, although dispersal by rafting over long distances may occasionally occur, this study suggests linear stepping-stone model of colonization to be most likely. The complexity of the results obtained suggests that further studies are needed to elucidate the phylogeny of S. abaster.
Asunto(s)
ADN Mitocondrial/genética , Evolución Molecular , Variación Genética , Filogenia , Smegmamorpha/genética , Animales , Teorema de Bayes , Haplotipos , Funciones de Verosimilitud , Mar Mediterráneo , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: We sought to identify a causative mutation in a previously reported kindred with parental consanguinity and 5 of 10 siblings with adult-onset autoimmune myasthenia gravis. METHODS: We performed genome-wide homozygosity mapping, and sequenced all known genes in the one region of extended homozygosity. Quantitative and allele-specific reverse transcriptase PCR (RT-PCR) were performed on a candidate gene to determine the RNA expression level in affected siblings and controls and the relative abundance of the wild-type and mutant alleles in a heterozygote. RESULTS: A region of shared homozygosity at chromosome 13q13.3-13q14.11 was found in 4 affected siblings and 1 unaffected sibling. A homozygous single nucleotide variant was found in the 3'-untranslated region of the ecto-NADH oxidase 1 gene (ENOX1). No other variants likely to be pathogenic were found in genes in this region or elsewhere. The ENOX1 sequence variant was not found in 764 controls. Quantitative RT-PCR showed that expression of ENOX1 decreased to about 20% of normal levels in lymphoblastoid cells from individuals homozygous for the variant and to about 50% in 2 unaffected heterozygotes. Allele-specific RT-PCR showed a 55%-60% reduction in the level of the variant transcript in heterozygous cells due to reduced mRNA stability. CONCLUSION: These results indicate that this sequence variant in ENOX1 may contribute to the familial autoimmune myasthenia in these patients.
Asunto(s)
Enfermedades Autoinmunes/genética , Complejos Multienzimáticos/genética , Miastenia Gravis/genética , NADH NADPH Oxidorreductasas/genética , Anciano , Alelos , Mapeo Cromosómico , Consanguinidad , Ligamiento Genético , Humanos , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido SimpleRESUMEN
Adipose-derived stem cells (ASCs) may represent a novel and efficient tool to promote bone regeneration. In this study, rabbit ASCs were expanded in culture and used for the regeneration of full-thickness bone defects in the proximal epiphysis of tibia of 12 New Zealand rabbits. Defects were implanted with graft material as follows: untreated (control), empty hydroxyapatite (HA) disk, ASCs alone, and HA disk seeded with ASCs. Each isolated ASCs population was tested in vitro: they all showed a high proliferation rate, a marked clonogenic ability, and osteogenic differentiation potential. Eight weeks after implantation, macroscopic analyses of all the samples showed satisfactory filling of the lesions without any significant differences in term of stiffness between groups treated with or without cells (p > 0.05). In both the scaffold-treated groups, a good osteointegration was radiographically observed. Even if HA was not completely reabsorbed, ASCs-loaded HA displayed a higher scaffold resorption than the unloaded ones. Histological analyses showed that the osteogenic abilities of the scaffold-treated defects was greater than those of scaffold-free samples, and in particular new formed bone was more mature and more similar to native bone in presence of ASCs. These results demonstrated that autologous ASCs-HA constructs is a potential treatment for the regeneration of bone defects.
Asunto(s)
Tejido Adiposo/citología , Regeneración Ósea , Células Madre/fisiología , Tibia/cirugía , Animales , Densidad Ósea , Durapatita , Femenino , Conejos , Andamios del TejidoRESUMEN
Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant linkage to chromosome 12q24.11. We sequenced all genes in this region and identified two heterozygous missense mutations in the TRPV4 gene, C805T and G806A, resulting in the amino acid substitutions R269C and R269H. TRPV4 is a well-known member of the TRP superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations caused marked cellular toxicity and increased constitutive and activated channel currents. Mutations in TRPV4 were previously associated with skeletal dysplasias. Our findings indicate that TRPV4 mutations can also cause a degenerative disorder of the peripheral nerves. The CMT2C-associated mutations lie in a distinct region of the TRPV4 ankyrin repeats, suggesting that this phenotypic variability may be due to differential effects on regulatory protein-protein interactions.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Mutación/genética , Canales Catiónicos TRPV/genética , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Sustitución de Aminoácidos/genética , Repetición de Anquirina , Secuencia de Bases , Membrana Celular/metabolismo , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Análisis Mutacional de ADN , Femenino , Humanos , Activación del Canal Iónico , Masculino , Persona de Mediana Edad , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas Mutantes/metabolismo , Neurotoxinas , Linaje , Fenotipo , Canales Catiónicos TRPV/química , Adulto JovenAsunto(s)
Enfermedades de los Gatos/cirugía , Quistes/veterinaria , Hepatopatías/veterinaria , Enfermedades Vasculares/veterinaria , Animales , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Gatos , Quistes/diagnóstico , Quistes/cirugía , Diagnóstico Diferencial , Drenaje/veterinaria , Eutanasia Animal , Femenino , Hepatocitos/patología , Hepatopatías/patología , Hepatopatías/cirugía , Recurrencia , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/cirugíaRESUMEN
BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.
Asunto(s)
Ablación por Catéter/instrumentación , Criocirugía/instrumentación , Endoscopía/métodos , Hígado/diagnóstico por imagen , Hígado/cirugía , Bazo/diagnóstico por imagen , Bazo/cirugía , Animales , Diseño de Equipo , Estudios de Factibilidad , Hígado/patología , Modelos Animales , Bazo/patología , Porcinos , UltrasonografíaRESUMEN
Early treatment with the histone deacetylase inhibitor, trichostatin A, plus nutritional support extended median survival of spinal muscular atrophy mice by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after trichostatin A was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe spinal muscular atrophy. Early spinal muscular atrophy disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of histone deacetylase inhibitor treatment in human patients.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Atrofia Muscular Espinal/terapia , Apoyo Nutricional/métodos , Factores de Edad , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ratones , Ratones Transgénicos , Actividad Motora/efectos de los fármacos , Necrosis , Análisis de Supervivencia , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.
Asunto(s)
Ablación por Catéter/instrumentación , Criocirugía/instrumentación , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Animales , Proyectos Piloto , Complicaciones Posoperatorias , Análisis de Regresión , Estadísticas no Paramétricas , Porcinos , UltrasonografíaRESUMEN
BACKGROUND: Atrial fibrillation is the most common form of serious arrhythmia in humans. The therapeutic options offered are medical, surgical, and interventional. The surgical approach is justified in cases of atrial fibrillation already subjected to cardiac surgery for an associated organic heart disease such as a valvular or ischemic disease. A minimally invasive surgical approach is needed to extend the possibility of surgical treatment to patients with lone atrial fibrillation and those who cannot be treated by interventional procedures. This study aimed to use sheep as an experimental model in developing a minimally invasive surgical procedure for chronic atrial fibrillation therapy in humans. METHODS: The investigation was conducted with 20 animals using a video-assisted thoracoscopic approach, in which a flexible microwave energy ablating probe was positioned on the epicardial surface encircling the pulmonary veins. RESULTS: In 10 of the 20 animals, it was possible to encircle the pulmonary veins using the thoracoscopic approach in less than 3 h without major complications. CONCLUSION: The epicardial ablation procedure using the thoracoscopic approach is feasible, safe, and reproducible.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Cirugía Torácica Asistida por Video , Toracoscopía , Animales , Microondas , OvinosRESUMEN
The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by mutation of the telomeric survival motor neuron 1 (SMN1) gene with retention of the centromeric SMN2 gene. We sought to establish whether the potent and specific hydroxamic acid class of histone deacetylase (HDAC) inhibitors activates SMN2 gene expression in vivo and modulates the SMA disease phenotype when delivered after disease onset. Single intraperitoneal doses of 10 mg/kg trichostatin A (TSA) in nontransgenic and SMA model mice resulted in increased levels of acetylated H3 and H4 histones and modest increases in SMN gene expression. Repeated daily doses of TSA caused increases in both SMN2-derived transcript and SMN protein levels in neural tissues and muscle, which were associated with an improvement in small nuclear ribonucleoprotein (snRNP) assembly. When TSA was delivered daily beginning on P5, after the onset of weight loss and motor deficit, there was improved survival, attenuated weight loss, and enhanced motor behavior. Pathological analysis showed increased myofiber size and number and increased anterior horn cell size. These results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset.
Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Inhibidores Enzimáticos/farmacología , Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos/farmacología , Atrofia Muscular Espinal/tratamiento farmacológico , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN/genética , Animales , Células Cultivadas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/uso terapéutico , Humanos , Ácidos Hidroxámicos/uso terapéutico , Ratones , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN/análisis , Proteínas de Unión al ARN/metabolismo , Ribonucleoproteínas Nucleares Pequeñas , Proteínas del Complejo SMN , Proteína 1 para la Supervivencia de la Neurona Motora , Proteína 2 para la Supervivencia de la Neurona MotoraRESUMEN
Sequestration of the transcriptional coactivator CREB-binding protein (CBP), a histone acetyltransferase, has been implicated in the pathogenesis of polyglutamine expansion neurodegenerative disease. We used a Drosophila model to demonstrate that polyglutamine-induced neurodegeneration is accompanied by a defect in histone acetylation and a substantial alteration in the transcription profile. Furthermore, we demonstrate complete functional and morphological rescue by up-regulation of endogenous Drosophila CBP (dCBP). Rescue of the degenerative phenotype is associated with eradication of polyglutamine aggregates, recovery of histone acetylation, and normalization of the transcription profile. These findings suggest that histone acetylation is an early target of polyglutamine toxicity and indicate that transcriptional dysregulation is an important part of the pathogenesis of polyglutamine-induced neurodegeneration.