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1.
BMJ Open Qual ; 12(2)2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37130695

RESUMEN

Hypocalcaemia following thyroid surgery can occur in up to 38% of patients. With over 7100 thyroid surgeries performed in 2018 in the UK, this is a common postoperative complication. Undertreated hypocalcaemia can result in cardiac arrhythmias and death. Preventing adverse events from hypocalcaemia requires preoperative identification and treatment of at-risk patients with vitamin D deficiency, timely recognition of postoperative hypocalcaemia and prompt appropriate treatment with calcium supplementation. This project aimed to design and implement a perioperative protocol for prevention, detection and management of post-thyroidectomy hypocalcaemia. A retrospective audit of thyroid surgeries (n=67; October 2017 to June 2018) was undertaken to establish baseline practice of (1) preoperative vitamin D levels assessment, (2) postoperative calcium checks and incidence of postoperative hypocalcaemia and (3) management of postoperative hypocalcaemia. A multidisciplinary team approach following quality improvement principles was then used to design a perioperative management protocol with all relevant stakeholders involved. After dissemination and implementation, the above measures were reassessed prospectively (n=23; April-July 2019). The percentage of patients having their preoperative vitamin D measured increased from 40.3% to 65.2%. Postoperative day-of-surgery calcium checks increased from 76.1% to 87.0%. Hypocalcaemia was detected in 26.8% of patients before and 30.43% of patients after protocol implementation. The postoperative component of the protocol was followed in 78.3% of patients. Limitations include low number of patients which precluded from analysis of the impact of the protocol on length of stay. Our protocol provides a foundation for preoperative risk stratification and prevention, early detection and subsequent management of hypocalcaemia in thyroidectomy patients. This aligns with enhanced recovery protocols. Moreover, we offer suggestions for others to build on this quality improvement project with the aim to further advance the perioperative care of thyroidectomy patients.


Asunto(s)
Hipocalcemia , Humanos , Hipocalcemia/etiología , Hipocalcemia/prevención & control , Hipocalcemia/diagnóstico , Calcio , Glándula Tiroides , Estudios Retrospectivos , Mejoramiento de la Calidad , Medicina Estatal , Vitamina D , Tiroidectomía/efectos adversos , Tiroidectomía/métodos
2.
Appl Biochem Biotechnol ; 195(12): 7176-7196, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36988845

RESUMEN

In Southeast Asia, the penaeid shrimp aquaculture production faces a new pandemic bacterial disease called acute hepatopancreatic necrosis disease (AHPND). The highly profitable pacific white shrimp, Litopenaeus vannamei, has become a challenging species due to severe lethal infections. Recent research has identified a critical pathogen, Vibrio parahaemolyticus, which caused significant loss in the shrimp industry. The disease pathway involves a virulence plasmid encoding binary protein toxins (PirA/B) that cause cell death. The protein toxins were inherited and conjugatively transferred to other Vibrio species through a post-segregational killing system. In this study, "in silico" (Glide, 2021) analysis identified four phytocompounds as myricetin (Myr), ( +)-taxifolin (TF), (-)-epigallocatechin gallate (EGCG), and strychnine (STN) which could be most effective against both the toxins concerning its docking score and affinity. The interactions of complexes and the critical amino acids involved in docking were analyzed using the Discovery Studio (version 2016). Molecular dynamic studies showed lower root mean square deviations (RMSD) and improved stabilization of ( +)-taxifolin (TF) and (-)-epigallocatechin-3-gallate (EGCG) against both the protein toxins. The antibacterial potential of all four selected compounds had tested against pathogenic strains of V. parahaemolyticus through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The best MBC results were observed at concentrations of 1 mg/mL for EGCG and 1.25 mg/mL for TF. Moreover, the complete reduction of viable cell counts in the in vitro bactericidal activity had recorded after 24 h of incubation.


Asunto(s)
Artemia , Toxinas Bacterianas , Fitoquímicos , Vibrio parahaemolyticus , Animales , Acuicultura , Artemia/microbiología , Toxinas Bacterianas/antagonistas & inhibidores , Toxinas Bacterianas/química , Catequina/química , Hepatopáncreas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Quercetina/química , Vibrio parahaemolyticus/fisiología , Fitoquímicos/química , Fitoquímicos/farmacología
3.
BMC Plant Biol ; 23(1): 137, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36907856

RESUMEN

Seed shattering is a critical challenge that significantly reduces sesame production by 50%. These shattering losses can be reduced by selecting shattering resistant genotypes or by incorporating modern agronomic management such as paclobutrazol, which can boost productivity and prevent seed shattering in sesame. Two-years of field trials were conducted to examine the effect of sesame genotypes, environment, and paclobutrazol (PBZ) concentrations. Twelve sesame genotypes were used in a four-way factorial RCBD with three replications and five PBZ concentrations (T0 = Control; T1 = 150; T2 = 300; T3 = 450; and T4 = 600 mg L- 1) under rainfed conditions of Pothwar. The findings revealed significant variations in the major effects of all examined variables (genotypes, locations, years, and PBZ levels). Sesame genotypes PI-154304 and PI-175907 had the highest plant height, number of capsule plant- 1, seed capsule- 1, 1000 seed weight, biological yield, and seed yield, while also having the lowest seed losses and shattering percentage. Regarding environments, NARC-Islamabad generated the highest plant height, number of capsule plant- 1, shattering percentage, and biological yield; however, the URF-Koont produced the highest seed yield with the lowest shattering percentage. Additionally, plant height, capsules plant- 1, and biological yield were higher in 2021, while seed capsule- 1, 1000 seed weight, seed losses, shattering percentage, and seed yield were higher in 2020. PBZ concentration affected all measured parameters; plant height and number of seed capsule- 1 decreased with increasing PBZ concentrations. 450 mg L- 1 PBZ concentration generated the highest biomass, number of capsules plant- 1, and seed yield. At the same time, PBZ concentration 600 mg L- 1 generated the smallest plant, the lowest seed capsules- 1, the greatest thousand seed weight, and the lowest shattering percentage. The study concluded that paclobutrazol could dramatically reduce shattering percentage and shattering losses while increasing economic returns through better productivity. Based on the findings, the genotypes PI-154304 and PI-175907 with paclobutrazol level 450 mgL- 1 may be suggested for cultivation in Pothwar farming community under rainfed conditions, as they showed promising shattering resistance as well as enhanced growth and yield.


Asunto(s)
Enfermedades de las Plantas , Sesamum , Triazoles , Cápsulas , Genotipo , Sesamum/genética , Sesamum/microbiología , Triazoles/farmacología , Enfermedades de las Plantas/microbiología
4.
Appl Biochem Biotechnol ; 195(11): 7110-7131, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36884191

RESUMEN

Feeds for aquaculture animals are designed to provide them with the greatest amount of nourishment they need to carry out their regular physiological activities, such as maintaining a potent natural immune system and boosting growth and reproduction. However, the problems that severely hamper this sector's ability to contribute to achieving global food security include disease prevalence, chemical pollution, environmental deterioration, and inadequate feed usage. The regulated release of active aquafeed components; limited water solubility, bioaccessibility, and bioavailability, as well as their potent odour and flavour, limit their utilisation. They are unstable under high temperatures, acidic pH, oxygen, or light. Recent advancements in nano-feed for aquaculture (fish/shrimp) have attract enormous attention due to its excellent nutritional value, defeating susceptibility and perishability. Encapsulation is a multifunctional smart system that could bring benefits of personalized medicine; minimize costs and resources in the preclinical and clinical study in pharmacology. It guarantees the coating of the active ingredient as well as its controlled release and targeted distribution to a particular area of the digestive tract. For instance, using nanotechnology to provide more effective fish/shrimps feed for aquaculture species. The review enables a perspective points on safety and awareness in aquafeeds that have been made by the advancements of nanosystem. Therefore, potential of nano-delivery system in aquafeed industry for aquaculture act as concluding remark on future directions.


Asunto(s)
Acuicultura , Explotaciones Pesqueras , Animales , Peces , Nanotecnología , Alimentación Animal/análisis
5.
Sci Rep ; 11(1): 11540, 2021 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-34079018

RESUMEN

Recently, there is an increasing trend of using metallic nanoparticles (NPs) in agriculture due to their potential role in remediating soil pollution and improving nutrient utilization from fertilizers. However, evidence suggested that these NPs were toxic to the soil life and their associated functions, and this toxicity depended on their dose, type, and size. Here, a dose-dependent (5, 50, and 100 mg kg-1 soil) toxicity of NiO NPs on poultry manure (PM: 136 kg N ha-1) decomposition, nutrient mineralization, and herbage N uptake were studied in a standard pot experiment. The NPs doses were mixed with PM and applied in soil-filled pots where then ryegrass was sown. Results revealed that the lowest dose significantly increased microbial biomass (C and N) and respiration from PM, whereas a high dose reduced these parameters. This decrease in such parameters by the highest NPs dose resulted in 13 and 41% lower soil mineral N and plant available K from PM, respectively. Moreover, such effects resulted in 32 and 35% lower herbage shoot and root N uptakes from PM in this treatment. Both intermediate and high doses decreased herbage shoot Ni uptake from PM by 33 and 34%, respectively. However, all NPs doses did not influence soil Ni content from PM. Hence, our results indicated that high NPs dose (100 mg kg-1) was toxic to decomposition, nutrient mineralization, and herbage N uptake from PM. Therefore, such NiONPs toxicity should be considered before recommending their use in agriculture for soil remediation or optimizing nutrient use efficiency of fertilizers.

6.
J Immunother Cancer ; 9(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33500259

RESUMEN

BACKGROUND: Pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved. METHODS: VVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer. RESULTS: VVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. CONCLUSIONS: Intravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Interleucina-12/genética , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/terapia , Inhibidores de Proteínas Quinasas/administración & dosificación , Virus Vaccinia/fisiología , Proteínas del Envoltorio Viral/metabolismo , Administración Intravenosa , Animales , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Terapia Combinada , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Interleucina-12/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Mesocricetus , Ratones , Viroterapia Oncolítica , Virus Oncolíticos/fisiología , Neoplasias Pancreáticas/inmunología , Inhibidores de Proteínas Quinasas/farmacología , Microambiente Tumoral , Proteínas del Envoltorio Viral/genética , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Oncogene ; 40(10): 1757-1774, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33479496

RESUMEN

Nasopharyngeal carcinoma (NPC) results from the aberrant and uncontrolled growth of the nasopharyngeal epithelium. It is highly associated with the Epstein-Barr virus, especially in regions where it is endemic. In the last decade, significant advances in genetic sequencing techniques have allowed the discovery of many new abnormal molecular processes that undoubtedly contribute to the establishment, growth and spread of this deadly disease. In this review, we consider NPC as EBV induced. We summarise the recent discoveries and how they add to our understanding of the pathophysiology of NPC in the context of genomics first in primary and then in recurrent disease. Overall, we find key early events lead to p16 inactivation and cyclin D1 expression, allowing latent viral infection. Host and viral factors work together to affect a variety of molecular pathways, the most fundamental being activation of NF-κB. Nonetheless, much still yearns to be discovered, especially in recurrent NPC.


Asunto(s)
Ciclina D1/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Carcinoma Nasofaríngeo/genética , Recurrencia Local de Neoplasia/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Genómica , Herpesvirus Humano 4/patogenicidad , Interacciones Huésped-Patógeno/genética , Humanos , Infección Latente/genética , Infección Latente/virología , FN-kappa B/genética , Carcinoma Nasofaríngeo/etiología , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/virología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología
8.
J Immunother Cancer ; 8(1)2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32217766

RESUMEN

BACKGROUND: Local recurrence and remote metastasis are major challenges to overcome in order to improve the survival of patients with cancer after surgery. Oncolytic viruses are a particularly attractive option for prevention of postsurgical disease as they offer a non-toxic treatment option that can directly target residual tumor deposits and beneficially modulate the systemic immune environment that is suppressed post surgery and allows residual disease escape from control. Here, we report that a novel Vaccinia virus (VV), VVΔTKΔN1L (with deletion of both thymidine kinase (TK) and N1L genes) armed with interleukin 12 (IL-12), can prolong postoperative survival when used as a neoadjuvant treatment in different murine and hamster surgical models of cancer. METHODS: A tumor-targeted replicating VV with deletion of TK gene and N1L gene (VVΔTKΔN1L) was created. This virus was armed rationally with IL-12. The effect of VVΔTKΔN1L and VVΔTKΔN1L-IL12 on modulation of the tumor microenvironment and induction of tumor-specific immunity as well the feasibility and safety as a neoadjuvant agent for preventing recurrence and metastasis after surgery were assessed in several clinically relevant models. RESULTS: VVΔTKΔN1L can significantly prolong postoperative survival when used as a neoadjuvant treatment in three different surgery-induced metastatic models of cancer. Efficacy was critically dependent on elevation of circulating natural killer cells that was achieved by virus-induced cytokine production from cells infected with N1L-deleted, but not N1L-intact VV. This effect was further enhanced by arming VVΔTKΔN1L with IL-12, a potent antitumor cytokine. Five daily treatments with VVΔTKΔN1L-IL12 before surgery dramatically improved postsurgical survival. VVΔTKΔN1L armed with human IL-12 completely prevented tumor recurrence in surgical models of head and neck cancer in Syrian hamsters. CONCLUSIONS: These data provide a proof of concept for translation of the regime into clinical trials. VVΔTKΔN1L-IL12 is a promising agent for use as an adjuvant to surgical treatment of solid tumors.


Asunto(s)
Inmunidad/inmunología , Neoplasias Pulmonares/prevención & control , Recurrencia Local de Neoplasia/prevención & control , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Neoplasias Pancreáticas/prevención & control , Virus Vaccinia/genética , Adyuvantes Inmunológicos/administración & dosificación , Animales , Apoptosis , Proliferación Celular , Femenino , Humanos , Interleucina-12/administración & dosificación , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Células Tumorales Cultivadas , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Int J Pediatr Otorhinolaryngol ; 105: 176-180, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29447810

RESUMEN

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited disorders that result in abnormal ciliary motion leading to mucous stasis. Clinical features include almost universally otitis media with effusion (OME), particularly in infants. PCD patients provide us with a cohort of patients with OME that is not treated with ventilatory tube (VT) insertion as these have been shown to result in frequent complications including chronic otorrhoea, early extrusion and persistent perforation without significant improvement to hearing in the long term. This cohort was used to investigate whether children with PCD and OME not treated with VT were predisposed to cholesteatoma formation in the setting of a paediatric quaternary referral centre. METHODS: A retrospective chart review was performed of all the children attending a multi-disciplinary PCD clinic at a national quaternary referral centre with a diagnosis of OME. We reviewed otoscopic findings, and audiometry and tympanometry results. We assessed the children in four groups: Watchful waiting, hearing aids, VT, and VT and hearing aids. RESULTS: One-hundred-and-one of 107 patients included in the study had a diagnosis of otitis media with effusion. No child with OME and PCD was diagnosed with a cholesteatoma during the follow up period. The only children who had insertion of a ventilatory tube were those who had the procedure prior to the formal diagnosis of PCD. We found a significant complication rate in the children with VT insertion. Hearing improved over time. The prevalence of retraction pockets in untreated OME was 1.72% (3 out of 174 ears). CONCLUSIONS: In children with PCD, OME is an almost universal finding in younger children, but not in adolescents. The study supports the current preference to avoid VT insertion in children with PCD as it confers a significantly higher rate of complications. No cases of cholesteatoma were found in this cohort of PCD children with OME managed without VTs.


Asunto(s)
Colesteatoma/etiología , Síndrome de Kartagener/complicaciones , Ventilación del Oído Medio/efectos adversos , Otitis Media con Derrame/cirugía , Pruebas de Impedancia Acústica , Adolescente , Audiometría , Niño , Preescolar , Colesteatoma/epidemiología , Femenino , Humanos , Lactante , Masculino , Ventilación del Oído Medio/métodos , Otitis Media con Derrame/complicaciones , Otoscopía , Estudios Retrospectivos
10.
J Photochem Photobiol B ; 174: 90-96, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28756157

RESUMEN

The work represents the potent catalytic activity of silver nanoparticles synthesized from Cicer arietinum (chickpea) leaf extract (CAL-AgNPs). Here, silver nano-catalysts were used against the anthropogenic pollutants mainly involving nitro-amines and azo dyes. These pollutants are extremely harmful to our environment and causes severe health issues. The CAL-AgNPs have the potential to degrade harmful toxins and their by-products, thereby decreasing the pollutants from the environment. The green synthesis of nano-catalyst includes a simple, cost effective and eco-friendly method using the leaf extract from the plant. A systematic study was conducted, including synthesis, optimization and characterization of the silver particles. The AgNPs were further assessed through DLS and TEM for size and morphological evaluation. The obtained particles have shown spherical morphology with the size range of 88.8nm. Further, FTIR were performed for compositional and functional group analysis of the particles. The antibacterial efficiency was also evaluated against E. coli and P. aeruginosa. For their catalytic evaluation, CAL-AgNPs were assessed for 4-nitrophenol, methylene blue and congo red. The results obtained through catalytic evaluation suggested that the CAL-AgNPs could be helpful to surmount the environmental pollution in a very effective manner.


Asunto(s)
Cicer/química , Colorantes/química , Contaminantes Ambientales/química , Nanopartículas del Metal , Hojas de la Planta/química , Plata/química , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Catálisis , Técnicas de Química Sintética , Colorantes/aislamiento & purificación , Contaminantes Ambientales/aislamiento & purificación , Escherichia coli/efectos de los fármacos , Tamaño de la Partícula , Extractos Vegetales/química , Pseudomonas aeruginosa/efectos de los fármacos , Plata/farmacología
11.
Mol Ther Methods Clin Dev ; 2: 15035, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26417609

RESUMEN

The current method for creation of vaccinia virus (VACV) vectors involves using a selection and purification marker, however inclusion of a gene without therapeutic value in the resulting vector is not desirable for clinical use. The Cre-LoxP system has been used to make marker-free Poxviruses, but the efficiency was very low. To obtain a marker-free VACV vector, we developed marker gene excision systems to modify the thymidine kinase (TK) region and N1L regions using Cre-Loxp and Flp-FRET systems respectively. CRISPR-Cas9 system significantly resulted in a high efficiency (~90%) in generation of marker gene-positive TK-mutant VACV vector. The marker gene (RFP) could be excised from the recombinant virus using Cre recombinase. To make a marker-free VV vector with double gene deletions targeting the TK and N1L gene, we constructed a donor repair vector targeting the N1L gene, which can carry a therapeutic gene and the marker (RFP) that could be excised from the recombinant virus using Flp recombinase. The marker-free system developed here can be used to efficiently construct VACV vectors armed with any therapeutic genes in the TK region or N1L region without marker genes. Our marker-free system platform has significant potential for development of new marker-free VACV vectors for clinical application.

12.
J Craniomaxillofac Surg ; 43(8): 1511-5, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26293186

RESUMEN

BACKGROUND: Patients with syndromic forms of craniosynostosis may experience functional problems such as raised intracranial pressure, proptosis, obstructive sleep apnoea and failure to thrive. The monobloc fronto-facial advancement with osteogenic distraction is increasingly used to correct these functional problems in one procedure as well as improve appearance. The authors report the phenomenon of post operative aberrant facial flushing - an unusual and previously unreported complication of the procedure. METHODS: The case notes of 80 consecutive patients undergoing fronto-facial advancement by distraction using the rigid external distraction device (RED) were reviewed for features of aberrant facial flushing. RESULTS: Four out of eighty individuals developed facial flushing after monobloc fronto-facial distraction using the rigid external distractor (RED) frame. All were female with Crouzon or Pfeiffer syndromes causing the severe functional problems for which they underwent the surgery. They were aged 6-8 years. Following removal of the frame, they developed intermittent but severe facial flushing. The flushing spontaneously settled in three patients after up to four years but persists in the other child seven years after her surgery. CONCLUSION: Aberrant facial flushing is a rare but significant complication of monobloc fronto-facial surgery. It occurred in 4 of our 80 (5%) patients. The skull base osteotomies essential for the procedure are made anterior to the pterygopalatine ganglion and it is our contention that damage from these was responsible for a neuropraxia of its efferent nerve branches. A review of the autonomic control of the facial vascular system suggests that the phenomenon is due to an unequal process of recovery that leaves the cutaneous vasodilating parasympathetic or beta-adrenergic innervation relatively unopposed - a situation that persists until with time a normal balance of autonomic input is achieved.


Asunto(s)
Huesos Faciales/cirugía , Rubor/etiología , Osteogénesis por Distracción/métodos , Complicaciones Posoperatorias , Acrocefalosindactilia/fisiopatología , Acrocefalosindactilia/cirugía , Obstrucción de las Vías Aéreas/cirugía , Niño , Disostosis Craneofacial/fisiopatología , Disostosis Craneofacial/cirugía , Exoftalmia/cirugía , Fijadores Externos , Femenino , Estudios de Seguimiento , Ganglios Parasimpáticos/lesiones , Humanos , Hipertensión Intracraneal/cirugía , Osteogénesis por Distracción/efectos adversos , Osteogénesis por Distracción/instrumentación , Osteotomía/efectos adversos , Osteotomía/métodos , Estudios Retrospectivos
13.
J Virol ; 89(9): 5176-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25741005

RESUMEN

Vaccinia virus (VACV) continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer since its use for the eradication of smallpox. However, the current method of editing the VACV genome is not efficient. Here, we demonstrate that the CRISPR-Cas9 system can be used to edit the VACV genome rapidly and efficiently. Additionally, a set of 8,964 computationally designed unique guide RNAs (gRNAs) targeting all VACV genes will be valuable for the study of VACV gene functions.


Asunto(s)
Sistemas CRISPR-Cas , Genoma Viral , Biología Molecular/métodos , Recombinación Genética , Virus Vaccinia/genética , Tecnología Farmacéutica/métodos
14.
Clin Cancer Res ; 21(2): 405-16, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25416195

RESUMEN

PURPOSE: Vaccinia virus has strong potential as a novel therapeutic agent for treatment of pancreatic cancer. We investigated whether arming vaccinia virus with interleukin-10 (IL10) could enhance the antitumor efficacy with the view that IL10 might dampen the host immunity to the virus, increasing viral persistence, thus maximizing the oncolytic effect and antitumor immunity associated with vaccinia virus. EXPERIMENTAL DESIGN: The antitumor efficacy of IL10-armed vaccinia virus (VVLΔTK-IL10) and control VVΔTK was assessed in pancreatic cancer cell lines, mice bearing subcutaneous pancreatic cancer tumors and a pancreatic cancer transgenic mouse model. Viral persistence within the tumors was examined and immune depletion experiments as well as immunophenotyping of splenocytes were carried out to dissect the functional mechanisms associated with the viral efficacy. RESULTS: Compared with unarmed VVLΔTK, VVLΔTK-IL10 had a similar level of cytotoxicity and replication in vitro in murine pancreatic cancer cell lines, but rendered a superior antitumor efficacy in the subcutaneous pancreatic cancer model and a K-ras-p53 mutant-transgenic pancreatic cancer model after systemic delivery, with induction of long-term antitumor immunity. The antitumor efficacy of VVLΔTK-IL10 was dependent on CD4(+) and CD8(+), but not NK cells. Clearance of VVLΔTK-IL10 was reduced at early time points compared with the control virus. Treatment with VVLΔTK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8(+) cells compared with VVLΔTK. CONCLUSIONS: These results suggest that VVLΔTK-IL10 has strong potential as an antitumor therapeutic for pancreatic cancer.


Asunto(s)
Interleucina-10/genética , Virus Oncolíticos/genética , Neoplasias Pancreáticas/terapia , Virus Vaccinia/genética , Animales , Línea Celular Tumoral , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Trasplante de Neoplasias , Viroterapia Oncolítica , Neoplasias Pancreáticas/inmunología , Replicación Viral
15.
Cochrane Database Syst Rev ; (7): CD008515, 2011 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-21735433

RESUMEN

BACKGROUND: Dilation of sinus ostia using a high-pressure balloon has been introduced as a treatment for chronic rhinosinusitis (CRS) refractory to medical treatment. The efficacy of this technology, however, has not been systematically reviewed. OBJECTIVES: To assess the effectiveness of balloon sinus ostial dilation as a treatment for patients suffering with CRS refractory to medical treatment. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 20 December 2010. SELECTION CRITERIA: Randomised controlled trials in patients of any age with rhinosinusitis lasting longer than 12 weeks who have failed a prolonged course of medical treatment. Studies compared either balloon sinus ostial dilation or a hybrid procedure (balloon dilation in conjunction with functional endoscopic sinus surgery (FESS)) versus conventional surgery (e.g. FESS) or a waiting list control. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and assessed risk of bias. MAIN RESULTS: One study (34 patients) met our inclusion criteria although it was not yet a peer reviewed publication. The study randomised patients with chronic frontal sinusitis who had failed a prolonged course of medical treatment into two groups: balloon dilatation of the frontal recess (plus conventional FESS of other involved sinuses) versus conventional FESS (Draf type 1/2a procedures on the frontal sinuses). At 12 months follow up there was no statistically significant difference in radiological resolution of frontal sinuses between the two groups. The percentages of directly observed patent frontal recesses at 12 months were 75% in the balloon dilation group versus 63% in the FESS-only group. The authors state that this was statistically significant but details of the analysis were not presented. Indeed the study as a whole suffers from a bias in the way its outcome measures were reported.No major complications were reported. Three patients in the FESS-only group required further revision frontal sinus surgery compared to one in the balloon dilation group, although synechiae were more common in the latter. AUTHORS' CONCLUSIONS: At present there is no convincing evidence supporting the use of endoscopic balloon sinus ostial dilation compared to conventional surgical modalities in the management of CRS refractory to medical treatment. With the escalating use of balloon sinuplasty, there is an urgent need for more randomised controlled trials to determine its efficacy over conventional surgical treatment modalities.


Asunto(s)
Cateterismo/métodos , Sinusitis Frontal/terapia , Rinitis/terapia , Endoscopía/métodos , Seno Frontal , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
J Craniofac Surg ; 22(1): 125-8, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21187762

RESUMEN

Obstructive sleep apnea in children with syndromic craniosynostosis is a well-documented entity, and airway management in these group of children is difficult, with well-documented cardiorespiratory and neurodevelopment consequences. Numerous well-documented techniques are available for airway management in this group of children. In our center, the nasopharyngeal airway (NPA) is the first-line treatment. This study aimed to evaluate the improvement in health-related quality of life in this group of children using the Glasgow Children's Benefit Inventory. We conducted a retrospective postal study of 24 patients with craniofacial disorders who had an NPA inserted as part of their airway management. A 79.2% (n = 19) response rate was obtained. Mean (SD) age was 5.8 (4.1) years. Patients were classified into 3 main groups: Crouzon (n = 11), Apert (n = 6), and Pfeiffer (n = 2) syndromes. There was improvement in 3 of the 4 domains, namely, learning (P = 0.006), vitality (P = 0.003), physical (range, -3 to 8; mean, 2; P = 0.005). There was significant improvement in the sleep study parameters; however, no correlation was found between this and the Glasgow Children's Benefit Inventory findings. Parents also preferred an NPA as opposed to a tracheostomy when given a choice. Our study shows that NPA confers significant improvement not only in health-related quality of life but also in severity of obstructive sleep apnea as judged by sleep study parameters. The NPA is also well tolerated by patients and is much preferred by parents for airway management for their children as opposed to having a tracheostomy. We think that this should be considered in other centers as first-line management in children with syndromic craniosynostosis.


Asunto(s)
Acrocefalosindactilia/complicaciones , Intubación Intratraqueal/instrumentación , Calidad de Vida , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/prevención & control , Acrocefalosindactilia/fisiopatología , Niño , Preescolar , Disostosis Craneofacial/complicaciones , Femenino , Humanos , Masculino , Estudios Retrospectivos , Apnea Obstructiva del Sueño/fisiopatología , Traqueostomía
17.
Otolaryngol Head Neck Surg ; 142(2): 164-8, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20115968

RESUMEN

OBJECTIVE: The chin is an important determinant of the lower third of the face, carrying much significance in an esthetically balanced facial appearance. It is, however, often neglected in patients undergoing rhinoplasty procedures in the UK National Health Service (NHS). The aim of this study was to establish the percentage of a cohort of rhinoplasty patients who may also have benefited from chin augmentation. STUDY DESIGN: A cross-sectional study. SUBJECTS AND METHODS: The digital preoperative pictures of the last 100 patients who underwent rhinoplasty at our institution were retrieved. Four popular methods of assessment were used to assess the chin, that is, those advocated by Silver, Legan, Merrifield, and Gonzales-Ulloa. All analyses were performed on Adobe Photoshop CS4 by two ENT registrars. Values were regarded as positive when there was interobserver agreement. Relevant angles were averaged. RESULTS: A total of 94 photographs were suitable for analysis. There were 58 males. Depending on the method of assessment, the percentage of males who fulfilled criteria for augmentation ranged from 17 to 62 percent and for females the range was 42 to 81 percent. Additionally, 21 percent of males were positive on three or more of the methods utilized. The respective figure was 58 percent for females. CONCLUSION: Surgeons who practice rhinoplasty should consider making an objective assessment of the need for possible chin augmentation. Our study shows that as many as 81 percent of patients may benefit, although this figure varies with the method of assessment. In this study, the necessity for further analysis with a view to chin augmentation was more likely in women.


Asunto(s)
Antropometría/métodos , Mentón/cirugía , Rinoplastia/métodos , Adulto , Estudios Transversales , Cara/anatomía & histología , Femenino , Humanos , Masculino , Satisfacción del Paciente , Procedimientos de Cirugía Plástica , Resultado del Tratamiento
18.
Eur Arch Otorhinolaryngol ; 267(4): 619-23, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19562361

RESUMEN

Various studies have shown that receiving a copy of the letter to the General Practitioner (GP) improves patient satisfaction with the consult. We aimed to establish whether dictating the letter to the GP in front of a listening patient does likewise. Follow-up patients have shorter allotted consultation times. This may contribute to dissatisfaction, hence the choice of our target group. One hundred consecutive follow-up patients who met the eligibility criteria were randomised to listen to the GP letter or not. Immediately after the consult, they were asked to fill in a questionnaire which, in addition to enquiring about various aspects of the consult asked them to quantify their overall satisfaction by means of a ten-point graded visual analogue score. Forty-nine patients received dictation. The mean age and sex distribution of the two groups were matched. The median overall satisfaction in the dictation and non-dictation groups were ten and eight, respectively, this was statistically significant. There was no significant difference between patients' rating of whether the consult had addressed their ailment adequately, explanation(s) given or the length of consult. Sixty-one percent of patients in the non-dictation group would like to have listened to the dictation, whilst all patients in the dictation group found it useful. This study is the first of its kind in the ENT population. Dictating a letter to the GP in front of a listening patient led to a statistically significant improvement in satisfaction independent of possible confounding aspects of the consult.


Asunto(s)
Comunicación , Satisfacción del Paciente , Atención Primaria de Salud , Derivación y Consulta , Estudios de Seguimiento , Humanos
19.
J Craniofac Surg ; 19(3): 659-63, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18520380

RESUMEN

Syndromic craniosynostosis is known to be associated with obstructive sleep apnea (OSA), which can often present in infancy. Although multifactorial, a predominant contributing factor is midface hypoplasia. Nasal continuous positive airway pressure has proven to be an effective treatment modality but may be poorly tolerated in certain cases. This study looks at the effectiveness of bypassing midface obstruction with a nasopharyngeal airway (NPA). Twenty-seven children with syndromic craniosynostosis with confirmed moderate to severe OSA were initially treated with an NPA. The mean age of NPA insertion was 12.3 months (range, 0.5-48 mo). Seventeen had severe OSA, and 10 had moderate OSA preinsertion. Post-NPA insertion, 26 of 27 children (96%) demonstrated an improvement in sleep severity scores, resulting in 3 with moderate OSA and 24 with mild OSA. There was a significant improvement in mean oxygen saturation, mean number of saturation dips greater than 4% per hour, percentage time spent less than 90% SpO2, and number of pulse rate rises per hour. There were no significant differences in mean pulse rate. The NPA was well tolerated by this patient group, with 24 of 26 children retaining it for at least 6 weeks. We believe that an NPA is therefore an effective first-line treatment modality in the management of OSA in children with syndromic craniosynostosis. It is well tolerated by the patient and may obviate the need for continuous positive airway pressure or tracheostomy.


Asunto(s)
Craneosinostosis/complicaciones , Intubación Intratraqueal/instrumentación , Nasofaringe/fisiopatología , Apnea Obstructiva del Sueño/prevención & control , Apnea Obstructiva del Sueño/fisiopatología , Preescolar , Femenino , Humanos , Lactante , Masculino , Apnea Obstructiva del Sueño/etiología
20.
Saudi J Kidney Dis Transpl ; 19(1): 47-53, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18087122

RESUMEN

This study was undertaken to assess potassium level and electrocardiographic (ECG) changes post hemodialysis and whether fall in potassium level during dialysis may potentiate cardiac arrythemia. We studied 21 chronic hemodialysis (HD) patients who had their serum electrolytes measured before and immediately after dialysis session, and ECG performed at the same time. The patients included 14 females and 7 males with a mean age of 53.1+/-15.6 years and range from 26 to 81 years; 9 (43%) patients were diabetics. All the patients had been on dialysis for a minimum of 6 months each Pre-HD serum potassium levels had no correlation with any ECG parameters except a negative correlation with the T wave amplitude r=-0.5, p=0.021. ECG parameters significantly changed post-HD; the T wave amplitude decreased, and the R wave amplitude increased. A comparatively higher R wave significantly decreased the T to R wave ratio post dialysis. The QRS duration and QTc interval also increased significantly. The patients with post-HD serum potassium of < or = 3.5 -in comparison to those with levels > 3.5 mmol/L -had a higher R wave amplitude and a significantly less T to R wave ratio (11.8+/-9.7 vs 6.4+/-5.1, p=0.045 and 0.4+/-0.38 vs 1.0+/-0.97, p=0.049, respectively. In patients with serum potassium decrement of > 2.0 mmol/L, the T to R wave ratio decreased significantly, 0.32+/-0.21 vs 0.85 +/-0.26, p=0.023; The T wave amplitude decreased more than the rise in R wave. Multiple regression analysis did not reveal any relationship of pre or post HD ECG changes and serum potassium, serum calcium or net change in serum potassium post-HD. We conclude that post-HD serum potassium decrement results in a decrease in T to R wave ratio on ECG; this change may have an arrhythmogenic potential.


Asunto(s)
Electrocardiografía , Fallo Renal Crónico/terapia , Potasio/sangre , Diálisis Renal , Calcio/sangre , Humanos , Hiperpotasemia/epidemiología , Hiperpotasemia/fisiopatología , Diálisis Renal/efectos adversos , Sodio/sangre , Factores de Tiempo
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