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1.
Surg Endosc ; 38(7): 3494-3502, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38872020

RESUMEN

BACKGROUND: Burnout is a crisis in medicine, and especially in surgery it has serious implications not only for physician well-being but also for patient outcomes. This study builds on previous SAGES Reimagining the Practice of Surgery Task Force work to better understand how organizations might intervene to increase the "joy in surgery." METHODS: This was a cross-sectional, descriptive study utilizing a REDCap survey with closed-ended questions for data collection across 5 domains: facilitators of joy, support for best work, time for work tasks, barriers to joy, and what they would do with more time. We calculated average scores and "percentage of respondents giving a high score" for each item. RESULTS: There were 307 individuals who started the survey; 223 completed it and were surgeons who met the inclusion criteria. The majority (85.7%) were trained in general surgery, regardless of sub-specialty. Surgeons found joy in operating and its technical skills, curing disease, patient relationships, and working with a good team. They reported usually having what they needed to deliver care. A majority felt valued and respected. Most were dissatisfied with reimbursement, perceiving it as unfair. The most commonly worked range of hours was 51-70 per week. They reported having little time for paperwork and documentation, and if they had more time, they would spend it with friends and family. CONCLUSION: Organizations should consider interventions to address the operative environment, provide appropriate staff support, and foster good teamwork. They can also consider interventions that alleviate time pressures and administrative burden while at the same time promoting sustainable workloads.


Asunto(s)
Agotamiento Profesional , Satisfacción en el Trabajo , Cirujanos , Humanos , Estudios Transversales , Cirujanos/psicología , Femenino , Agotamiento Profesional/psicología , Masculino , Adulto , Persona de Mediana Edad , Carga de Trabajo/psicología , Encuestas y Cuestionarios , Felicidad , Actitud del Personal de Salud
2.
Surg Endosc ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902408

RESUMEN

INTRODUCTION: Burnout in medicine is an epidemic, and surgeons are not immune. Studies often focus on negative factors leading to burnout, with less emphasis on optimizing joy. The purpose of this study, conducted by the SAGES Reimagining the Practice of Surgery Task Force, was to explore how gender may influence surgeon well-being to better inform organizational change. METHODS: The study team developed a survey with the domains: facilitators of joy, support for best work, time for work tasks, barriers to joy, and what they would do with more time. The survey was emailed to 5777 addresses on the SAGES distribution list. Results were analyzed by calculating summary statistics. RESULTS: 223 surgeons completed the survey; 62.3% identified as men, 32.3% as women, and 5.4% did not indicate gender. Female compared to male respondents were younger (41.6 vs 52.5 years) and had practiced for fewer years (8.4 vs 19.4 years). The three greatest differences in facilitators of joy were being a leader in the field, leading clinical teams, and teaching, with a > 10 percentage point difference between men/women rating these highly (score of ≥ 8). Women generally perceived less support from their institutions than men. The greatest gender difference was in support for teaching, with 52.8% of men rating this highly compared to 30.2% of women. Only 52% of women felt respected by coworkers most of the time compared to 68.3% of men. Most (96.0%) respondents (men 95.7% and women 98.6%) reported wanting more time with family and friends. CONCLUSION: This study demonstrates the complexity of the personal and professional factors that influence joy in surgery, highlight gender differences that impact joy and suggests opportunities for improved gender-based support. These results can inform potential organization-level changes and further research to better understand emerging differences in joy across gender identities.

3.
Surg Endosc ; 37(8): 6464-6475, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37221414

RESUMEN

BACKGROUND: There has been considerable research into burnout but much less into how surgeons thrive and find joy. This study, conducted by the SAGES Reimagining the Practice of Surgery Task Force, explored factors influencing surgeon well-being, the eventual goal being translating findings into tangible changes to help restore the joy in surgery. METHODS: This was a qualitative, descriptive study. Purposive sampling ensured representation across ages, genders, ethnicities, practice types, and geographies. Semi-structured interviews were recorded and transcribed. We coded inductively, finalized the codebook by consensus, and then constructed a thematic network. Global themes formed our conclusions; organizing themes gave additional detail. Analysis was facilitated by NVivo. RESULTS: We interviewed 17 surgeons from the US and Canada. Total interview time was 15 hours. Our global and organizing themes were: Stressors (Work-life Integration, Administration-related Concerns, Time and Productivity Pressures, Operating Room Factors, and Lack of Respect). Satisfaction (Service, Challenge, Autonomy, Leadership, and Respect and Recognition). Support (Team, Personal Life, Leaders, and Institutions). Values (Professional and Personal). Suggestions (Individual, Practice, and System level). Values, stressors, and satisfaction influenced perspectives on support. Experiences of support shaped suggestions. All participants reported stressors and satisfiers. Surgeons at all stages enjoyed operating and being of service. Supports and suggestions included compensation and infrastructure, but human resources were most critical. To experience joy, surgeons needed high-functioning clinical teams, good leaders/mentors, and supportive family/social networks. CONCLUSIONS: Our results indicated organizations could (1) better understand surgeons' values, like autonomy; (2) provide more time for satisfiers, like patient relationship building; (3) minimize stressors, like time and financial pressures; and (4) at all levels focus on (4a) building teams and leaders and (4b) giving surgeons time and space for healthy family/social lives. Next steps include developing an assessment tool for individual institutions to build "joy improvement plans" and to inform surgical associations' advocacy efforts.


Asunto(s)
Agotamiento Profesional , Cirujanos , Humanos , Masculino , Femenino , Canadá , Agotamiento Profesional/prevención & control
4.
Surg Endosc ; 36(11): 7938-7948, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35556166

RESUMEN

BACKGROUND: Efforts to improve surgical safety and outcomes have traditionally placed little emphasis on intraoperative performance, partly due to difficulties in measurement. Video-based assessment (VBA) provides an opportunity for blinded and unbiased appraisal of surgeon performance. Therefore, we aimed to systematically review the existing literature on the association between intraoperative technical performance, measured using VBA, and patient outcomes. METHODS: Major databases (Medline, Embase, Cochrane Database, and Web of Science) were systematically searched for studies assessing the association of intraoperative technical performance measured by tools supported by validity evidence with short-term (≤ 30 days) and/or long-term postoperative outcomes. Study quality was assessed using the Newcastle-Ottawa Scale. Results were appraised descriptively as study heterogeneity precluded meta-analysis. RESULTS: A total of 11 observational studies were identified involving 8 different procedures in foregut/bariatric (n = 4), colorectal (n = 4), urologic (n = 2), and hepatobiliary surgery (n = 1). The number of surgeons assessed ranged from 1 to 34; patient sample size ranged from 47 to 10,242. High risk of bias was present in 5 of 8 studies assessing short-term outcomes and 2 of 6 studies assessing long-term outcomes. Short-term outcomes were reported in 8 studies (i.e., morbidity, mortality, and readmission), while 6 reported long-term outcomes (i.e., cancer outcomes, weight loss, and urinary continence). Better intraoperative performance was associated with fewer postoperative complications (6 of 7 studies), reoperations (3 of 4 studies), and readmissions (1 of 4 studies). Long-term outcomes were less commonly investigated, with mixed results. CONCLUSION: Current evidence supports an association between superior intraoperative technical performance measured using surgical videos and improved short-term postoperative outcomes. Intraoperative performance analysis using video-based assessment represents a promising approach to surgical quality-improvement.


Asunto(s)
Complicaciones Posoperatorias , Cirujanos , Humanos , Complicaciones Posoperatorias/etiología , Pérdida de Peso
5.
J Reconstr Microsurg ; 38(2): 89-95, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34187060

RESUMEN

BACKGROUND: Pelvic reconstruction with a muscle flap significantly improves postoperative outcomes following abdominoperineal resection (APR). Despite it being the gold standard, significant surgeon-selection bias remains with respect to the necessity of pelvic obliteration, flap choice, and ostomy placement. The objective of the study was to characterize management practices among colorectal surgeons (CSs) and plastic surgeons (PSs). METHODS: Specialty-specific surveys were distributed electronically to CSs and PSs via surgical societies. Surveys were designed to illustrate geographic and specialty-specific differences in management. RESULTS: Of 106 (54 CSs and 52 PSs) respondents (58% Canada, 21% Europe, 14% the United States, and 6% Asia/Africa), significant interdisciplinary differences in practices were observed. Most respondents indicated that multidisciplinary meetings were not performed (74% of CSs and 78% of PSs). For a nonradiated pelvic dead space with small perineal defect, 91% of CSs and 56% of PSs indicated that flap reconstruction was not required. For a radiated pelvic dead space with small perineal defect, only 54% of CSs and 6% of PSs indicated that there was no need for flap reconstruction. With respect to ostomy placement, 87% of CSs and 21% of PSs indicated that stoma placement through the rectus was superior. When two ostomies were required, most CSs preferred exteriorizing ostomies through bilateral recti and requesting thigh-based reconstruction. PSs favored the vertical rectus abdominis muscle (VRAM; 52%) over the gracilis (23%) and inferior gluteal artery perforator (IGAP; 23%) flaps. Among PSs, North Americans favor abdominally based flaps (VRAM 60%), while Europeans favor gluteal-based flaps (IGAP 78%). CONCLUSION: A lack of standardization continues to exist with respect to the reconstruction of pelvic defects following APR and pelvic exenteration. Geographic and interdisciplinary biases with respect to ostomy placement, flap choice, and role for pelvic obliteration continues to influence reconstructive practices. These cases should continue to be approached on a case by case basis, driven by pathology, presence of radiation, comorbidities, and the size of the pelvic and perineal defect.


Asunto(s)
Neoplasias Colorrectales , Exenteración Pélvica , Procedimientos de Cirugía Plástica , Proctectomía , Cirujanos , Humanos , Perineo/cirugía , Colgajos Quirúrgicos
6.
Vet Pathol ; 59(1): 143-151, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34794345

RESUMEN

Xanthogranulomatosis is an inflammatory lesion characterized by lipid-containing macrophages, extracellular lipid, hemorrhage, and necrosis. We describe disseminated intracoelomic xanthogranulomatosis in 5 eclectus parrots (Eclectus roratus) and 2 budgerigars (Melopsittacus undulatus). Postmortem, clinicopathologic, and historical case material was reviewed. Ages ranged from 3 to 24 years; there were 5 males and 2 females. Table food was included in the diet of 3/5 cases, and animal products were included in 2/3 cases. Common clinicopathologic abnormalities included leukocytosis (4/5 cases) and elevated concentrations of bile acids (3/4 cases) and cholesterol within 6 months prior to death (2/4 cases). At postmortem examination, all 7 birds had grossly visible, irregular, soft, tan to yellow, amorphous plaques distributed on the surfaces of the viscera and body wall. Histologic evaluation and oil red O stain revealed xanthogranulomatous inflammation with phagocytized and extracellular lipid, necrosis, cholesterol clefts, fibrosis, and mineralization. Infectious agents were not identified with special stains in all cases. Concurrent hepatobiliary disease was present in 6/7 cases, and 6/7 had lipid accumulation within the parenchyma of various visceral organs. Five cases had atherosclerosis of great vessels. We describe a unique form of disseminated coelomic xanthogranulomatosis in 2 psittacine species. This condition should be recognized as a differential diagnosis in cases of disseminated coelomic mass formation and coelomic distension in psittacine birds, particularly in eclectus parrots and budgerigars.


Asunto(s)
Enfermedades de las Aves , Melopsittacus , Loros , Animales , Enfermedades de las Aves/diagnóstico , Diagnóstico Diferencial , Femenino , Masculino
7.
Vet Radiol Ultrasound ; 61(4): 409-416, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32436257

RESUMEN

Xanthogranulomatous disease is a rare condition, which can be caused by infection, inflammation, hemorrhage, immunologic disease, or inherited lysosomal disorders. It is characterized by non-intracellular lipid and cholesterol deposits among an inflammatory infiltrate of vacuolated macrophages and giant cells. The diagnosis of xanthogranulomatous disease is challenging, with nonspecific imaging findings often misinterpreted as aggressive neoplastic processes in humans. In this retrospective case series study, we describe the diagnostic imaging characteristics of a disseminated xanthogranulomatous condition identified in five eclectus parrots (Eclectus roratus). Decreased serosal detail and celomic distension were present in all three birds radiographed, with multifocal variably sized celomic mineralization (3/3 birds), and extracelomic mineralized masses (1/3 birds). Celomic effusion with foci of celomic mineralization and hepatomegaly were identified in all birds (3/3) imaged with ultrasound. Finally, a mineralized mural ventricular mass was present in one of three patients imaged with CT, multifocal celomic mineralization with moderate to severe celomic effusion in two of three patients, diffuse severe proventricular and intestinal dilation in all three patients, and atherosclerosis of the major arterial trunks in all three patients. Veterinary radiologists should be aware of this inflammatory condition in birds, especially in eclectus parrots, and should be able to recognize the imaging features of xanthogranulomatous inflammation.


Asunto(s)
Enfermedades de las Aves/diagnóstico por imagen , Granuloma/veterinaria , Loros , Xantomatosis/veterinaria , Animales , Femenino , Granuloma/diagnóstico por imagen , Inflamación/veterinaria , Estudios Retrospectivos , Xantomatosis/diagnóstico por imagen
8.
Can J Surg ; 60(1): 69-70, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28234594

RESUMEN

SUMMARY: Informed consent for surgery has become a critical component of surgical practice. There are specific legal requirements for what has to be disclosed to patients and for the accompanying documentation. The hospital consent for surgery form with the patient's signature is a small part of the process. A quality assurance review of the documentation of informed consent by our surgical group indicated major deficiencies and prompted this article (and its Appendix containing further information). Our intent was to inform surgeons about modern standards and to discuss particular challenges. Informed consent for surgery entails what surgeons communicate to their patients about the proposed surgery and is a key element in the trust patients have in surgeons. It is of increasing importance, and we must keep up to date with patient and legal expectations.


Asunto(s)
Consentimiento Informado/normas , Procedimientos Quirúrgicos Operativos/legislación & jurisprudencia , Humanos , Consentimiento Informado/ética , Consentimiento Informado/legislación & jurisprudencia
9.
J Virol ; 90(19): 8875-90, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27466419

RESUMEN

UNLABELLED: An effective preventive vaccine is highly sought after in order to stem the current HIV-1 pandemic. Both conservation of contiguous gp41 membrane-proximal external region (MPER) amino acid sequences across HIV-1 clades and the ability of anti-MPER broadly neutralizing antibodies (BNAbs) to block viral hemifusion/fusion establish the MPER as a prime vaccination target. In earlier studies, we described the development of an MPER vaccine formulation that takes advantage of liposomes to array the MPER on a lipid bilayer surface, paralleling its native configuration on the virus membrane while also incorporating molecular adjuvant and CD4 T cell epitope cargo. Here we demonstrate that several immunizations with MPER/liposomes induce high levels of bone marrow long-lived plasma cell (LLPC) antibody production. Single-cell immunoglobulin gene retrieval analysis shows that these plasma cells are derived from a germ line repertoire of B cells with a diverse representation of immunoglobulin genes, exhibiting antigen-driven positive selection. Characterization of LLPC recombinant monoclonal antibodies (rMAbs) indicates that antigen recognition is achieved through convergence on a common epitopic focus by utilizing various complementarity-determining region H3 (CDRH3) lengths. Importantly, the vast majority of rMAbs produced from these cells lack polyreactivity yet manifest antigen specificity in the context of lipids, shaping MPER-specific paratopes through selective pressure. Taken together, these findings demonstrate that the MPER is a vaccine target with minimal risk of generating off-target autoimmunity. IMPORTANCE: A useful vaccine must generate desired long-term, antigen-specific antibody responses devoid of polyreactivity or autoreactivity. The common polyreactive features of some HIV-1 BNAbs have raised concern about elicitation of anti-MPER antibodies. Utilizing single-LLPC repertoire analysis and biophysical characterization of anti-MPER rMAbs, we show that their fine specificities require a structural fitness of the antibody combining site involving heavy and light chain variable domains shaped by somatic hypermutation and affinity maturation of B cells in the germinal center. Perhaps more importantly, our results demonstrate that the majority of MPER-specific antibodies are not inherently polyspecific and/or autoreactive, suggesting that polyreactivity of MPER-specific antibodies is separable from their antigen specificity.


Asunto(s)
Anticuerpos Anti-VIH/inmunología , Anticuerpos Anti-VIH/metabolismo , Antígenos VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , Células Plasmáticas/inmunología , Anticuerpos Monoclonales/inmunología , Epítopos de Linfocito B/inmunología , Lípidos de la Membrana/metabolismo
10.
J Vet Cardiol ; 18(1): 79-87, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26777393

RESUMEN

An 11 month old spayed, female dog presented with exercise intolerance and cyanosis upon exertion. Echocardiography revealed an imperforate cor triatriatum dexter with mild tricuspid valve dysplasia, an underfilled right ventricle and significant right to left shunting across a presumptive patent foramen ovale. Balloon dilation of the abnormal atrial membrane was initially successful in creating a communication between the right atrial chambers, but stenosis of the original perforation and persistent clinical signs prompted a second intervention. A balloon expandable biliary stent was placed across the abnormal partition, improving caudal venous return to the right ventricle and reducing the right to left shunt. Three months after stent placement, resting oxygen saturation had normalized. Six months after stent placement, exercise tolerance had improved and exertional cyanosis had resolved. Long term follow up will be necessary to assess for remodeling of the right ventricle with improved venous return. Stent placement can be considered as a palliative treatment option for cor triatriatum dexter, especially for stenosis post-balloon dilation.


Asunto(s)
Corazón Triatrial/veterinaria , Enfermedades de los Perros/terapia , Foramen Oval Permeable/veterinaria , Stents/veterinaria , Animales , Corazón Triatrial/terapia , Perros , Cuidados Paliativos
11.
J Clin Invest ; 125(6): 2532-46, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25938786

RESUMEN

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.


Asunto(s)
Adyuvantes Inmunológicos , GMP Cíclico/análogos & derivados , Sistemas de Liberación de Medicamentos , Lípido A/análogos & derivados , Ganglios Linfáticos/inmunología , Proteínas de la Membrana/agonistas , Nanopartículas/química , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/farmacología , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Animales , GMP Cíclico/química , GMP Cíclico/farmacología , Proteína gp41 de Envoltorio del VIH/inmunología , Proteína gp41 de Envoltorio del VIH/farmacología , VIH-1/inmunología , Lípido A/química , Lípido A/farmacología , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Polietilenglicoles/química , Polietilenglicoles/farmacología
12.
Can J Surg ; 58(3): 209-11, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26011854

RESUMEN

Pilonidal disease is a chronic, acquired inflammatory process of the skin due to entrapped hair at the natal cleft. Reported recurrence rates are as high as 30%, and recurrence has been attributed to persistent hair near the surgical site. Although conservative measures, such as meticulous hair control and improved perineal hygiene, have been shown to be effective, these techniques typically require much effort on behalf of the patient. Laser hair epilation (LE) might solve this issue of poor patient compliance while helping patients to avoid surgical excision. In this article, we discuss recurrence rates of pilonidal disease in children treated with LE versus surgical excision in relation to findings from our institution between 2005 and 2013 as well as patient satisfaction with the treatment method.


Asunto(s)
Remoción del Cabello , Terapia por Láser , Seno Pilonidal/cirugía , Niño , Femenino , Estudios de Seguimiento , Remoción del Cabello/métodos , Humanos , Masculino , Satisfacción del Paciente , Recurrencia , Resultado del Tratamiento
13.
J Biol Chem ; 288(44): 31888-901, 2013 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24047898

RESUMEN

Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membrane-proximal external region (MPER) of HIV-1 glycoprotein 41 as a model antigen, we investigated the influence of physicochemical properties on immunogenicity in relation to structural modifications of MPER/liposome vaccines. Anchoring the MPER to the membrane via an alkyl tail or transmembrane domain retained the MPER on liposomes in vivo, while preserving MPER secondary structure. However, structural modifications that affected MPER membrane orientation and antigenic residue accessibility strongly impacted induced antibody responses. The solvent-exposed MPER tryptophan residue (Trp-680) was immunodominant, focusing immune responses, despite sequence variability elsewhere. Nonetheless, immunogenicity could be readily manipulated using site-directed mutagenesis or structural constraints to modulate amino acid surface display. These studies provide fundamental insights for immunogen design aimed at targeting B cell antibody responses.


Asunto(s)
Vacunas contra el SIDA/inmunología , Antígenos Virales/inmunología , Epítopos de Linfocito B/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Péptidos/inmunología , Vacunas contra el SIDA/química , Vacunas contra el SIDA/genética , Animales , Antígenos Virales/química , Antígenos Virales/genética , Linfocitos B/inmunología , Epítopos de Linfocito B/química , Epítopos de Linfocito B/genética , Proteína gp41 de Envoltorio del VIH/química , Proteína gp41 de Envoltorio del VIH/genética , VIH-1/química , VIH-1/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Mutagénesis Sitio-Dirigida , Péptidos/química , Péptidos/genética
14.
J Vet Cardiol ; 15(3): 211-6, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23932425

RESUMEN

Unilateral absence of the left or right pulmonary artery with concurrent contralateral pulmonary arterial branch stenoses is an exceptionally rare disorder. We describe this anomaly in a cat with severe exercise intolerance and respiratory distress. Transthoracic echocardiography and angiography demonstrated the absence of the left pulmonary artery with concurrent right pulmonary branch stenosis. Palliative balloon angioplasty of the right pulmonary artery substantially reduced right ventricular systolic pressure load and alleviated the patient's clinical signs.


Asunto(s)
Angioplastia Coronaria con Balón/veterinaria , Enfermedades de los Gatos/cirugía , Cuidados Paliativos , Arteria Pulmonar/patología , Animales , Gatos , Constricción Patológica/cirugía , Constricción Patológica/veterinaria , Masculino , Cuidados Paliativos/métodos
15.
Biotechnol Bioeng ; 98(1): 141-54, 2007 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-17657776

RESUMEN

This case study focuses on the scale-up of a Sp2/0 mouse myeloma cell line based fed-batch bioreactor process, from the initial 3-L bench scale to the 2,500-L scale. A stepwise scale-up strategy that involved several intermediate steps in increasing the bioreactor volume was adopted to minimize the risks associated with scale-up processes. Careful selection of several available mixing models from literature, and appropriately applying the calculated results to our settings, resulted in successful scale-up of agitation speed for the large bioreactors. Consideration was also given to scale-up of the nutrient feeding, inoculation, and the set-points of operational parameters such as temperature, pH, dissolved oxygen, dissolved carbon dioxide, and aeration in an integrated manner. It has been demonstrated through the qualitative and the quantitative side-by-side comparison of bioreactor performance as well as through a panel of biochemical characterization tests that the comparability of the process and the product was well controlled and maintained during the process scale-up. The 2,500-L process is currently in use for the routine clinical production of Epratuzumab in support of two global Phase III clinical trials in patients with lupus. Today, the 2,500 L, fed-batch production process for Epratuzumab has met all scheduled batch releases, and the quality of the antibody is consistent and reproducible, meeting all specifications, thus confirming the robustness of the process.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Reactores Biológicos/microbiología , Técnicas de Cultivo de Célula/instrumentación , Modelos Biológicos , Mieloma Múltiple/metabolismo , Ingeniería de Proteínas/instrumentación , Animales , Anticuerpos Monoclonales Humanizados , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Ratones , Mieloma Múltiple/genética , Proyectos Piloto , Ingeniería de Proteínas/métodos
16.
Ann Neurol ; 54(2): 271-4, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12891685

RESUMEN

Mutations in DJ-1 have been linked to an autosomal recessive form of early-onset parkinsonism. To identify mutations causing Parkinson's disease (PD), we sequenced exons 1 through 7 of DJ-1 in 107 early-onset (age at diagnosis up to 50 years) PD subjects. One subject had a frameshift mutation in the first coding exon and an exon 7 splice mutation both predicted to result in a loss of functional protein. This subject was diagnosed with probable PD at age 24 years with asymmetric onset and an excellent response to levodopa therapy. Our observations suggest that sequence alterations in DJ-1 are a rare cause of early-onset PD.


Asunto(s)
Antígenos de Neoplasias/genética , Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , Anciano , ADN/genética , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Genet Test ; 6(3): 217-20, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12490063

RESUMEN

Spinocerebellar ataxia, type 2 (SCA2), results from an expansion of a stretch of polyglutamine repeats within the coding sequence of the ataxin-2 gene (ATX2), localized to chromosome 12q23-24. Recent studies have widened the clinical phenotype, notably for individuals with repeats of intermediate size, from 32 to 35 glutamine residues. This narrow range necessitates precise determination of repeat size. Diagnostic laboratories most often perform direct genotyping of ATX2 from polymerase chain-amplified patient DNA with subsequent sizing utilizing slab gel polyacrylamide gel electrophoresis (PAGE) or capillary electrophoresis. Using cloning and sequencing methods, we have constructed a ladder of ATX2 alleles of known size and sequence composition. This freely available size ladder will facilitate future quantification of expansions of the ATX2 locus.


Asunto(s)
Péptidos/genética , Proteínas/genética , Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido , Ataxinas , Análisis Mutacional de ADN/métodos , Proteínas del Tejido Nervioso , Reacción en Cadena de la Polimerasa
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