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1.
J Pediatr Hematol Oncol Nurs ; 41(1): 32-43, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37858932

RESUMEN

Objective: While medical advances are enabling more children with cancer to live into adulthood, a large majority of them suffer from the late effects of treatment and about 30% experience infertility. Infertility impacts both male and female survivors complicating typical development for emerging young adults (EYAs) who typically spend this developmental period actively constructing their identities related to family and gender roles, attaining professional skills, and establishing social views. As literature is limited on identity formation and coping with infertility in young survivors, this study aimed to understand the experiences of childhood cancer survivors who are faced with infertility as a late treatment effect while reconstructing their identity. Method: A qualitative descriptive approach was used to explore the experiences and effects of childhood cancer complications on the identity development of six emerging adults (ages 18-29). Guided by the theoretical framework of identity development data were collected using semistructured interviews. Results: Four distinct themes emerged after the data analyses: restricted exploration and uncertain future, challenges to intimacy and communication, restructuring identity through redefining roles, and coping through familial support. Conclusions: Findings indicate that developmental processes of identity formation are complicated by the challenges stemming from infertility and require specific efforts to reconstruct core identity and redefine desired parental roles. Experimentation and self-discovery may be restricted for EYA cancer survivors as they reevaluate their views on intimate relationships, communication, potential professional roles, and family composition. Practical recommendations for multidisciplinary team members to support this growing population are discussed.


Asunto(s)
Supervivientes de Cáncer , Infertilidad , Neoplasias , Humanos , Masculino , Niño , Femenino , Adulto Joven , Neoplasias/complicaciones , Infertilidad/terapia , Sobrevivientes , Conducta Sexual
2.
J Am Board Fam Med ; 36(4): 583-590, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37321654

RESUMEN

INTRODUCTION: Most family physicians do not provide abortion care, despite an apparent alignment between the defined values of family medicine and provision of abortion in primary care. This study seeks to understand how family physicians themselves perceive the relationship between their specialty's values and abortion provision. METHODS: We conducted in-depth interviews in 2019 with 56 family physicians who do not oppose abortion in the United States. We employed a deductive-inductive content analysis approach with memos to identify key themes. This analysis focuses on participants' beliefs in the core values of family medicine and how those values relate to abortion in family medicine. RESULTS: Participants identified and described six values of the specialty they prioritized, which included relationships, care across the lifespan, whole-person care, nonjudgmental care, meeting community needs, and social justice. Family physicians in the study overwhelmingly believed that abortion aligned with family medicine values, regardless of whether they themselves provided abortion care. CONCLUSIONS: Providing abortion care in primary care settings gives family physicians an opportunity to provide comprehensive care while improving access to meet community needs. As abortion care becomes increasingly restricted in the United States, family physicians can manifest the values of family medicine through integrating abortion care into their practices in states where abortion remains legal.


Asunto(s)
Aborto Inducido , Medicina Familiar y Comunitaria , Embarazo , Femenino , Humanos , Estados Unidos , Médicos de Familia
3.
J Cannabis Res ; 4(1): 26, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35619155

RESUMEN

OBJECTIVE: Cannabis is increasingly used for medical purposes, particularly in countries like Canada where cannabis was recently legalized for recreational use. We aimed to assess self-medication with cannabis post-cannabis legalization among adults in the Canadian province of Quebec. METHODS: This is a cross-sectional online survey of a self-selected convenience sample conducted in Quebec, Canada, from November 2020 to January 2021. Individuals aged ≥ 21 years who endorsed using cannabis bought in legal recreational cannabis stores to self-medicate a health condition were included. Data were analyzed using descriptive statistics and stratified according to sex, age, and the type of cannabis use (exclusively medical versus medical and recreational use). RESULTS: Four hundred eighty-nine participants were included. The median age was 34 years, and 48% were women. About 25% reported exclusive medical use of cannabis. Treated conditions included anxiety (70%), insomnia (56%), pain (53%), depression (37%), and many others. Reasons for not consulting in cannabis clinics included lack of information (52%), the complexity of the process (39%), accessibility of cannabis clinics (23%), and others. Tetrahydrocannabinol (THC) dosage > 20% was reported by 32%. Smoking was the main route of use (81%). Possession of prescribed drugs was reported by 56%. Professionals consulted for information on cannabis included recreational cannabis store agents (36%), physicians (29%), and others. Overall, significant differences were observed for many of the comparisons according to sex, age, and the type of cannabis use. CONCLUSIONS: Many conditions are self-medicated with cannabis. The use of high doses of cannabis, smoking as a preferred method of use, and concurrent use of other medications may pose some risks to individuals. Addressing the reported barriers to medical access to cannabis is urgently needed.

4.
J Am Board Fam Med ; 35(3): 579-587, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35641055

RESUMEN

PURPOSE: Medication abortion (MAB) provision by family physicians has the potential to expand abortion access. However, there are documented individual and structural barriers to provision. This study investigates how family physicians in the United States (US) navigate the barriers impeding abortion provision in primary care. METHODS: We conducted a qualitative study on the experiences of US family physicians with MAB in primary care. We recruited participants at national conferences and via professional networks. This analysis focuses on the experiences of the subset of participants who expressed interest in providing MAB. RESULTS: Forty-eight participants met inclusion criteria, with representation from all 4 regions of the US. Participants had diverse experiences related to abortion provision, training, and the environment in which they practice, with a third of participants working in states with hostile abortion policies. We categorized participants into 3 groups: (1) doctors who did not receive training and do not provide abortions (n = 11), (2) doctors who received training but do not provide abortions (n = 20), and (3) doctors who received training and currently provide abortions (n = 17). We found that training, administrative and community support, and internal motivation to overcome barriers help family physicians integrate MAB in primary care practices. Federal and state laws, absence of training, stigma around abortion provision, inaccurate or limited knowledge of institutional barriers, and administrative resistance all contributed to doctors excluding abortion provision from their scope of practice. CONCLUSION: Improving medication abortion provision by family physicians requires addressing the individual and system barriers family physicians encounter so they receive the education, training, and support to successfully integrate abortion care into clinical practice.


Asunto(s)
Aborto Inducido , Internado y Residencia , Femenino , Humanos , Médicos de Familia , Embarazo , Investigación Cualitativa , Estados Unidos
5.
Contraception ; 109: 19-24, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35131289

RESUMEN

OBJECTIVES: In 2000, the United States' Food and Drug Administration (FDA) approved mifepristone for medication abortion. In this article, we explore how the Risk Evaluation and Mitigation Strategy (REMS) criteria for mifepristone specifically impede family physicians' ability to provide medication abortion in primary care settings. STUDY DESIGN: We conducted 56 qualitative interviews with a national sample of family physicians across the US who were not opposed to abortion. We examined how the REMS criteria for mifepristone impact family physicians' ability to provide medication abortion. RESULTS: Of the 56 interviews conducted, 23 participants (41%) raised the REMS criteria as a barrier to providing medication abortion in primary care. These participants reported the REMS added a layer of bureaucratic complexity that made it difficult for family physicians to navigate, even when trained, to provide abortion care. These family physicians described 2 predominant ways the REMS impede their ability to provide medication abortion: (1) The REMS require substantial involvement of clinic administration, who can be unsupportive; (2) The complexity of navigating the REMS results in physicians and clinic administration in primary care viewing medication abortion as not worth the effort, since it is only a small component of services offered in primary care. CONCLUSION: Removing the REMS could simplify integration of medication abortion into primary care, which could meet patient preferences, improve access, and reduce abortion stigma. The FDA's revised REMS criteria may ease administrative burden but will likely maintain key barriers to integrating medication abortion into family physicians' practice. IMPLICATIONS: Our study highlights that the REMS criteria are barriers to family physicians' ability to integrate medication abortion into their primary care practices. The FDA's removal of in person dispensing criteria may provide some impetus for trained family physicians to integrate medication abortion into their scope of practice but the revised REMS criteria maintain key barriers to broader adoption.


Asunto(s)
Aborto Inducido , Aborto Espontáneo , Medicina Familiar y Comunitaria , Femenino , Humanos , Mifepristona , Embarazo , Atención Primaria de Salud , Evaluación y Mitigación de Riesgos , Estados Unidos
6.
Cell Metab ; 28(5): 793-800.e2, 2018 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-30146487

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is the most common form of human kidney cancer. Histological and molecular analyses suggest that ccRCCs have significantly altered metabolism. Recent human studies of lung cancer and intracranial malignancies demonstrated an unexpected preservation of carbohydrate oxidation in the tricarboxylic acid (TCA) cycle. To test the capacity of ccRCC to oxidize substrates in the TCA cycle, we infused 13C-labeled fuels in ccRCC patients and compared labeling patterns in tumors and adjacent kidney. After infusion with [U-13C]glucose, ccRCCs displayed enhanced glycolytic intermediate labeling, suppressed pyruvate dehydrogenase flow, and reduced TCA cycle labeling, consistent with the Warburg effect. Comparing 13C labeling among ccRCC, brain, and lung tumors revealed striking differences. Primary ccRCC tumors demonstrated the highest enrichment in glycolytic intermediates and lowest enrichment in TCA cycle intermediates. Among human tumors analyzed by intraoperative 13C infusions, ccRCC is the first to demonstrate a convincing shift toward glycolytic metabolism.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Glucosa/metabolismo , Neoplasias Renales/metabolismo , Adulto , Anciano , Isótopos de Carbono/metabolismo , Carcinoma de Células Renales/patología , Ciclo del Ácido Cítrico , Glucólisis , Humanos , Riñón/metabolismo , Riñón/patología , Neoplasias Renales/patología , Persona de Mediana Edad , Oxidación-Reducción
7.
Fam Med ; 49(9): 706-713, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29045988

RESUMEN

BACKGROUND AND OBJECTIVES: Family physicians are critical to reproductive health service provision including miscarriage management and abortion care, but many graduates report barriers in integrating these services into practice. We designed and implemented CREATE (Continuing Reproductive Education for Advanced Training Efficacy), an elective advanced training and leadership program for senior residents aimed to help new graduates integrate miscarriage and abortion care into practice. METHODS: We surveyed all 53 program graduates at graduation, and 47 completed a follow-up survey in March 2016. We describe program graduates' current reproductive health practices and differences by respondent characteristics. We report facilitators (or enabling factors) and barriers that graduates encountered in attempting to integrate reproductive health care into practice, as well as the perceived impact of the CREATE program. RESULTS: Forty-two percent of CREATE graduates were providing miscarriage management and 35% were providing abortion care at the time of the follow-up survey. Factors associated with abortion provision at follow-up include strength of intention to provide at graduation and higher volume of uterine aspirations performed during residency. Graduates reported a range of barriers, including internal factors such as strength of competing interests, and external barriers such as administrative and staff resistance. Graduates found the additional procedural training, networking opportunities, and the complication simulation to be the most helpful aspects of the CREATE program. CONCLUSIONS: The CREATE program model may provide a useful template for family medicine residencies working to incorporate advanced abortion training or other advanced procedural skills into their curricula. Future curricular interventions should consider providing additional postgraduate support, particularly in provider shortage areas.


Asunto(s)
Aborto Inducido/educación , Medicina Familiar y Comunitaria/educación , Internado y Residencia , Liderazgo , Salud Reproductiva/educación , Aborto Espontáneo , Curriculum , Femenino , Humanos , Masculino , Médicos de Familia/provisión & distribución , Servicios de Salud Reproductiva/estadística & datos numéricos , Encuestas y Cuestionarios
8.
Eur J Pharm Sci ; 108: 71-77, 2017 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-28619620

RESUMEN

Within this work, we develop vesicles incorporating sub-unit antigens as solid dosage forms suitable for the oral delivery of vaccines. Using a combination of trehalose, dextran and mannitol, freeze-dried oral disintegrating tablets were formed which upon rehydration release bilayer vesicles incorporating antigen. Initial studies focused on the optimisation of the freeze-dry cycle and subsequently excipient content was optimised by testing tablet hardness, disintegration time and moisture content. The use of 10% mannitol and 10% dextran produced durable tablets which offered strong resistance to mechanical damage yet appropriate disintegration times and dispersed to release niosomes-entrapping antigen. From these studies, we have formulated a bilayer vesicle vaccine delivery system as rapid disintegrating tablets and capsules.


Asunto(s)
Antígenos Virales/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Administración Oral , Antígenos Virales/inmunología , Química Farmacéutica , Dextranos/química , Sistemas de Liberación de Medicamentos , Estabilidad de Medicamentos , Excipientes/química , Liofilización , Dureza , Humanos , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/química , Liposomas/metabolismo , Manitol/química , Nanopartículas/química , Tamaño de la Partícula , Solubilidad , Comprimidos , Trehalosa/química
9.
Am J Med Genet A ; 173(3): 780-783, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28211988

RESUMEN

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre- and post-treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient.© 2017 Wiley Periodicals, Inc.


Asunto(s)
Disfunción Cognitiva/tratamiento farmacológico , Terapia de Reemplazo Enzimático , Iduronidasa/administración & dosificación , Mucopolisacaridosis I/tratamiento farmacológico , Mucopolisacaridosis I/psicología , Terapia de Reemplazo Enzimático/efectos adversos , Terapia de Reemplazo Enzimático/métodos , Humanos , Iduronidasa/efectos adversos , Inyecciones Espinales , Imagen por Resonancia Magnética , Masculino , Mucopolisacaridosis I/diagnóstico , Pruebas Neuropsicológicas , Fenotipo , Resultado del Tratamiento , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patología , Adulto Joven
10.
Magn Reson Med ; 77(3): 936-944, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-26991680

RESUMEN

PURPOSE: To test the efficacy of 7T MRS for in vivo detection of 2-hydroxyglutarate (2HG) in brain tumors. METHODS: The subecho times of point-resolved spectroscopy (PRESS) were optimized at 7T with density-matrix simulations and phantom validation to improve the 2HG signal selectivity with respect to the neighboring resonances of γ-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln). MRS data were acquired from 12 subjects with gliomas in vivo and analyzed with LCModel using calculated basis spectra. Metabolite levels were quantified using unsuppressed short echo time (TE) water as a reference. RESULTS: The PRESS TE was optimized as TE = 78 ms (TE1 = 58 ms and TE2 = 20 ms), at which the 2HG 2.25 ppm resonance appeared as a temporally maximum inverted narrow peak and the GABA, Glu, and Gln resonances between 2.2 and 2.5 ppm were all positive peaks. The PRESS TE = 78 ms method offered improved discrimination of 2HG from Glu, Gln, and GABA when compared with short-TE MRS. 2HG was detected in all patients enrolled in the study, the estimated 2HG concentrations ranging from 1.0 to 6.2 mM, with percentage standard deviation of 2%-7%. CONCLUSION: Data indicate that the optimized MRS provides good selectivity of 2HG from other metabolite signals and may confer reliable in vivo detection of 2HG at relatively low concentrations. Magn Reson Med 77:936-944, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Algoritmos , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Glutaratos/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Procesamiento de Señales Asistido por Computador , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/patología , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
Methods Mol Biol ; 1522: 131-143, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27837536

RESUMEN

The structural characteristics of liposomes have been widely investigated and there is certainly a strong understanding of their morphological characteristics. Imaging of these systems, using techniques such as freeze-fracturing methods, transmission electron microscopy, and cryo-electron imaging, has allowed us to appreciate their bilayer structures and factors which can influence this. However, there are few methods which all us to study these systems in their natural hydrated state; commonly the liposomes are visualized after drying, staining, and/or fixation of the vesicles. Environmental Scanning Electron Microscopy (ESEM) offers the ability to image a liposome in its hydrated state without the need for prior sample preparation. Within our studies we were the first to use ESEM to study liposomes and niosomes and we have been able to dynamically follow the hydration of lipid films and changes in liposome suspensions as water condenses on to, or evaporates from, the sample in real time. This provides insight into the resistance of liposomes to coalescence during dehydration, thereby providing an alternative assay of liposome formulation and stability.


Asunto(s)
Imagenología Tridimensional , Liposomas/ultraestructura , Microscopía Electrónica de Rastreo/métodos , Antígenos/metabolismo , Cationes , ADN/metabolismo , Membrana Dobles de Lípidos/química , Preparaciones Farmacéuticas/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química
12.
J Clin Oncol ; 34(33): 4030-4039, 2016 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-28248126

RESUMEN

Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.


Asunto(s)
Biomarcadores/análisis , Química Encefálica , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Glutaratos/análisis , Espectroscopía de Resonancia Magnética , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Femenino , Glioma/tratamiento farmacológico , Glioma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados
13.
AJR Am J Roentgenol ; 203(6): 1336-44, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25415713

RESUMEN

OBJECTIVE: The purpose of this study was to determine the range of effective doses associated with imaging techniques used during interventional radiology procedures on children. MATERIALS AND METHODS: A pediatric phantom set (1, 5, and 10 years) coupled with high-sensitivity metal oxide semiconductor field effect transistor (MOSFET) dosimeters was used to calculate effective doses. Twenty MOSFETs were inserted into each phantom at radiosensitive organ locations. The phantoms were exposed to mock head, chest, and abdominal interventional radiology procedures performed with different geometries and magnifications. Fluoroscopy, digital subtraction angiography (DSA), and spin angiography were simulated on each phantom. Road mapping was conducted only on the 5-year-old phantom. International Commission on Radiological Protection publication 103 tissue weights were applied to the organ doses recorded with the MOSFETs to determine effective dose. For easy application to clinical cases, doses were normalized per minute of fluoroscopy and per 10 frames of DSA or spin angiography. RESULTS: Effective doses from DSA, angiography, and fluoroscopy were higher for younger ages because of magnification use and were largest for abdominal procedures. DSA of the head, chest, and abdomen (normalized per 10 frames) imparted doses 2-3 times as high as corresponding doses per minute of fluoroscopy while all other factors remained unchanged (age, projection, collimation, magnification). Three to five frames of DSA imparted an effective dose equal to doses from 1 minute of fluoroscopy. Doses from spin angiography were almost one-half the doses received from an equivalent number of frames of DSA. CONCLUSION: Patient effective doses during interventional procedures vary substantially depending on procedure type but tend to be higher because of magnification use in younger children and higher in the abdomen.


Asunto(s)
Dosis de Radiación , Protección Radiológica/métodos , Radiografía Intervencional/métodos , Efectividad Biológica Relativa , Tomografía Computarizada por Rayos X/métodos , Recuento Corporal Total , Absorción de Radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Fantasmas de Imagen , Protección Radiológica/instrumentación , Radiografía Intervencional/instrumentación , Tomografía Computarizada por Rayos X/instrumentación
14.
Drug Deliv Transl Res ; 4(3): 233-45, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25786878

RESUMEN

The fundamentals of this research were to exploit non-ionic surfactant technology for delivery and administration of vaccine antigens across the oral route and to gain a better understanding of vaccine trafficking. Using a newly developed method for manufacture of non-ionic surfactant vesicles (niosomes and bilosomes) lower process temperatures were adopted thus reducing antigen exposure to potentially damaging conditions. Vesicles prepared by this method offered high protection to enzymatic degradation, with only ∼10 % antigen loss measured when vesicles incorporating antigen were exposed to enzyme digestion. Interestingly, when formulated using this new production method, the addition of bile salt to the vesicles offered no advantage in terms of stability within simulated gastro-intestinal conditions. Considering their ability to deliver antigen to their target site, results demonstrated that incorporation of antigen within vesicles enhanced delivery and targeting of the antigen to the Peyer's Patch, again with niosomes and bilosomes offering similar efficiency. Delivery to both the Peyer's patches and mesentery lymphatics was shown to be dose dependent at lower concentrations, with saturation kinetics applying at higher concentrations. This demonstrates that in the formulation of vaccine delivery systems, the lipid/antigen dose ratio is not only a key factor in production cost, but is equally a key factor in the kinetics of delivery and targeting of a vaccine system.

15.
Radiat Prot Dosimetry ; 157(3): 363-74, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23843426

RESUMEN

Modern-day interventional radiology (IR) procedures impart a wide range of occupational radiation doses to team members. Unlike thermoluminescent badges, digital dosemeters provide real-time dose readings, making them ideal for identifying different components during IR procedures, which influence staff radiation safety. This study focused solely on paediatric IR (PIR) cases. Digital dosemeters measured the impact of imaging modality, shielding, patient and operator specific factors, on the radiation dose received during various simulated and real live PIR procedures. They recorded potential dose reductions of 10- to 100-fold to each staff member with appropriate use of shielding, choice of imaging method, staff position in the room and complex interplay of other factors. The digital dosemeters were well tolerated by staff. Results highlight some unique radiation safety challenges in PIR that arise from dose increases with magnification use and close proximity of staff to the X-ray beam.


Asunto(s)
Exposición Profesional/prevención & control , Protección Radiológica/métodos , Radiografía Intervencional/métodos , Radiología Intervencionista/métodos , Radiometría/instrumentación , Administración de la Seguridad , Niño , Simulación por Computador , Humanos , Pediatría , Fantasmas de Imagen , Dosis de Radiación
16.
J Drug Target ; 21(3): 291-299, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30952177

RESUMEN

Oral vaccines offer significant benefits due to the ease of administration, better patient compliance and non-invasive, needle-free administration. However, this route is marred by the harsh gastro intestinal environment which is detrimental to many vaccine formats. To address this, a range of delivery systems have been considered including bilosomes; these are bilayer vesicles constructed from non-ionic surfactants combined with the inclusion of bile salts which can stabilize the vesicles in the gastro intestinal tract by preventing membrane destabilization. The aim of this study was to investigate the effect of formulation parameters on bilosome carriers using Design of Experiments to select an appropriate formulation to assess in vivo. Bilosomes were constructed from monopalmitoylglycerol, cholesterol, dicetyl phosphate and sodium deoxycholate at different blends ratios. The optimized bilosome formulation was identified and the potential of this formulation as an oral vaccine delivery system were assessed in biodistribution and vaccine efficacy studies. Results showed that the larger bilosomes vesicles (~6 µm versus 2 µm in diameter) increased uptake within the Peyer's patches and were able to reduce median temperature differential change and promote a reduction in viral cell load in an influenza challenge study.

17.
J Pharm Sci ; 100(5): 1856-65, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21374619

RESUMEN

The adjuvanticity of liposomes can be directed through formulation to develop a safe yet potent vaccine candidate. With the addition of the cationic lipid dimethyldioctadecylammonium bromide (DDA) to stable neutral distearoylphosphatidylcholine (DSPC):cholesterol (Chol) liposomes, vesicle size reduces while protein entrapment increases. The addition of the immunomodulator, trehalose 6,6-dibehenate (TDB) to either the neutral or cationic liposomes did not affect the physiochemical characteristics of these liposome vesicles. However, the protective immune response, as indicated by the amount of IFN-γ production, increases considerably when TDB is present. High levels of IFN-γ were observed for cationic liposomes; however, there was a marked reduction in IFN-γ release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-γ was slightly lower than the cationic equivalent, the overall protective immune responses of these neutral liposomes were effectively maintained over time, generating good levels of protection. To that end, although the addition of DSPC and Chol reduced the protective immunity of DDA:TDB liposomes, relatively high protection was observed for the neutral counterpart, DSPC:Chol:TDB, which may offer an effective neutral alternative to the DDA:TDB cationic system, especially for the delivery of either zwitterionic (neutral) or cationic molecules or antigens.


Asunto(s)
Liposomas/química , Fosfatidilcolinas/química , Proteínas Recombinantes de Fusión/administración & dosificación , Vacunas contra la Tuberculosis/administración & dosificación , Tuberculosis/prevención & control , Vacunas de Subunidad/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Femenino , Glucolípidos/administración & dosificación , Glucolípidos/inmunología , Humanos , Interferón gamma/inmunología , Ratones , Ratones Endogámicos C57BL , Compuestos de Amonio Cuaternario/química , Proteínas Recombinantes de Fusión/inmunología , Vacunas contra la Tuberculosis/inmunología , Vacunas de Subunidad/inmunología
18.
Curr Drug Deliv ; 8(4): 448-55, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21235468

RESUMEN

Poly(ε-caprolactone) (PCL) is biocompatible, non-immunogenic and non-toxic, and slowly degrades, allowing sufficient time for tissue regeneration. PCL has the potential for application in bone and cartilage repair as it may provide the essential structure required for bone regeneration, however, an ideal scaffold system is still undeveloped. PCL fibres were prepared using the gravity spinning technique, in which collagen was either incorporated into or coated onto the 'as-spun' fibres, in order to develop novel biodegradable polymer fibres which will effectively deliver collagen and support the attachment and proliferation of human osteoblast (HOB) cells for bone regeneration. The physical and mechanical characteristics and cell fibre interactions were analysed. The PCL fibres were found to be highly flexible and inclusion of collagen did not alter the mechanical properties of PCL fibres. Overall, HOB cells were shown to effectively adhere and proliferate on all fibre platforms tested, although proliferation rates were enhanced by surface coating PCL fibres with collagen compared to PCL fibres incorporating collagen and PCL-only fibres. These findings highlight the potential of using gravity spun PCL fibres as a delivery platform for extracellular matrix proteins, such as collagen, in order to enhance cell adherence and proliferation for tissue repair.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Colágeno/administración & dosificación , Colágeno/química , Poliésteres/administración & dosificación , Poliésteres/química , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Sistemas de Liberación de Medicamentos/métodos , Humanos , Microscopía Electrónica de Rastreo/métodos , Osteoblastos/efectos de los fármacos
19.
Int J Pharm ; 417(1-2): 138-50, 2011 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-21182914

RESUMEN

A plethora of techniques for the imaging of liposomes and other bilayer vesicles are available. However, sample preparation and the technique chosen should be carefully considered in conjunction with the information required. For example, larger vesicles such as multilamellar and giant unilamellar vesicles can be viewed using light microscopy and whilst vesicle confirmation and size prior to additional physical characterisations or more detailed microscopy can be undertaken, the technique is limited in terms of resolution. To consider the options available for visualising liposome-based systems, a wide range of microscopy techniques are described and discussed here: these include light, fluorescence and confocal microscopy and various electron microscopy techniques such as transmission, cryo, freeze fracture and environmental scanning electron microscopy. Their application, advantages and disadvantages are reviewed with regard to their use in analysis of lipid vesicles.


Asunto(s)
Lípidos/química , Liposomas/química , Liposomas/ultraestructura , Microscopía Electrónica de Rastreo/métodos
20.
Pharmaceutics ; 3(4): 848-64, 2011 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-24309311

RESUMEN

Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH2O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent.

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