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1.
J Surg Res ; 234: 262-268, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30527483

RESUMEN

BACKGROUND: Mass casualty events are infrequent and create an abrupt surge of patients requiring emergency medical services within a brief period. We hypothesize that implementation of a controlled "traffic loop" pattern during a planned high-volume motorcycle rally could improve overall mortality and impact patient outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of all motorcycle-related injuries during the city's annual motorcycle rally over a 4-y period. Comparative analysis was completed between those injured during "nontraffic loop" hours versus the city's scheduled 23-mile, 3-d "traffic loop" pattern. The two groups were compared for age, gender, injuries, Injury Severity Score, Glasgow Coma Scale, length of stay, ventilator-free days, and mortality. The primary outcome was mortality. RESULTS: A total of 139 patients were included (120 nonloop and 19 loop). Mean (standard deviation) age was 36.1 (11.2) y and 72.1% were male. Both groups were equivalent in age, gender, Injury Severity Score, and Glasgow Coma Scale. Traffic loop patients required longer intensive care unit length of stay, (median = 9.0, range: 1-49 d), ventilator days (median = 29.5), (range: 1-49 d) and experienced abdominal trauma (P = 0.002). Emergency medical services transport times during loop hours had shorter response times than the nonloop injury group (7.79 ± 5.2 min and 13.22 ± 14.01 min (P = 0.049). No deaths occurred during the city's scheduled traffic loop (0 versus 22, P = 0.0447). CONCLUSIONS: Controlled traffic patterns during high-volume city gatherings can improve overall mortality and morbidity. Regional trauma system preparedness with field triage guidelines and coordinated trauma care is warranted to effectively care for the injured.


Asunto(s)
Accidentes de Tránsito , Planificación en Desastres/métodos , Incidentes con Víctimas en Masa , Motocicletas , Heridas y Lesiones/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciudades , Planificación en Desastres/organización & administración , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , South Carolina/epidemiología , Triaje , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/epidemiología , Heridas y Lesiones/terapia , Adulto Joven
2.
J Neuroimmune Pharmacol ; 16(3): 567-580, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-32808238

RESUMEN

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), the etiology of which is poorly understood. The most common laboratory abnormality associated with MS is increased intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands (OCBs) in the brain and cerebrospinal fluid (CSF). However, the major antigenic targets of these antibody responses are unknown. The risk of MS is increased after infectious mononucleosis (IM) due to EBV infection, and MS patients have higher serum titers of anti-EBV antibodies than control populations. Our goal was to identify disease-relevant epitopes of IgG antibodies in MS; to do so, we screened phage-displayed random peptide libraries (12-mer) with total IgG antibodies purified from the brain of a patient with acute MS. We identified and characterized the phage peptides for binding specificity to intrathecal IgG from patients with MS and from controls by ELISA, phage-mediated Immuno-PCR, and isoelectric focusing. We identified two phage peptides that share sequence homologies with EBV nuclear antigens 1 and 2 (EBNA1 and EBNA2), respectively. The specificity of the EBV epitopes found by panning with MS brain IgG was confirmed by ELISA and competitive inhibition assays. Using a highly sensitive phage-mediated immuno-PCR assay, we determined specific bindings of the two EBV epitopes to IgG from CSF from 46 MS and 5 inflammatory control (IC) patients. MS CSF IgG have significantly higher bindings to EBNA1 epitope than to EBNA2 epitope, whereas EBNA1 and EBNA2 did not significantly differ in binding to IC CSF IgG. Further, the EBNA1 epitope was recognized by OCBs from multiple MS CSF as shown in blotting assays with samples separated by isoelectric focusing. The EBNA1 epitope is reactive to MS intrathecal antibodies corresponding to oligoclonal bands. This reinforces the potential role of EBV in the etiology of MS. Graphical abstract Antibodies purified from an MS brain plaque were panned by phage display peptide libraries to discern potential antigens. Phage displaying peptide sequences resembling Epstein-Barr Virus Nuclear Antigens 1 & 2 (EBNA1 & 2) epitopes were identified. Antibodies from sera and CSF from other MS patients also reacted to those epitopes.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Anticuerpos Antivirales , Encéfalo , Epítopos , Antígenos Nucleares del Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Bandas Oligoclonales
3.
Ann Neurol ; 66(5): 617-29, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19938104

RESUMEN

OBJECTIVE: The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO-IgGs) directed against the aquaporin-4 (AQP4) water channel located on astrocyte foot processes in the perivessel and subpial areas of the brain. Our objectives were to determine the source of central nervous system (CNS) NMO-IgGs and their role in disease pathogenesis. METHODS: Fluorescence-activated cell sorting and single-cell reverse transcriptase polymerase chain reaction were used to identify overrepresented plasma cell immunoglobulin (Ig) sequences in the cerebrospinal fluid (CSF) of an NMO patient after a first clinical attack. Monoclonal recombinant antibodies (rAbs) were generated from the paired heavy and light chain sequences and tested for target specificity and Fc effector function. The effect of CSF rAbs on CNS immunopathology was investigated by delivering single rAbs to rats with experimental autoimmune encephalomyelitis (EAE). RESULTS: Repertoire analysis revealed a dynamic, clonally expanded plasma cell population with features of an antigen-targeted response. Using multiple independent assays, 6 of 11 rAbs generated from CSF plasma cell clones specifically bound to AQP4. AQP4-specific rAbs recognized conformational epitopes and mediated both AQP4-directed antibody-dependent cellular cytotoxicity and complement-mediated lysis. When administered to rats with EAE, an AQP4-specific NMO CSF rAb induced NMO immunopathology: perivascular astrocyte depletion, myelinolysis, and complement and Ig deposition. INTERPRETATION: Molecular characterization of the CSF plasma cell repertoire in an early NMO patient demonstrates that AQP4-specific Ig is synthesized intrathecally at disease onset and directly contributes to CNS pathology. AQP4 is now the first confirmed antigenic target in human demyelinating disease.


Asunto(s)
Acuaporina 4/líquido cefalorraquídeo , Acuaporina 4/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/diagnóstico , Secuencia de Aminoácidos , Animales , Acuaporina 4/genética , Biomarcadores/líquido cefalorraquídeo , Línea Celular , Células Cultivadas , Femenino , Feto , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Ratones , Persona de Mediana Edad , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas Lew , Punción Espinal , Factores de Tiempo
4.
Ann Neurol ; 65(6): 639-49, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19557869

RESUMEN

OBJECTIVE: Intrathecal IgG synthesis, persistence of bands of oligoclonal IgG, and memory B-cell clonal expansion are well-characterized features of the humoral response in multiple sclerosis (MS). Nevertheless, the target antigen of this response remains enigmatic. METHODS: We produced 53 different human IgG1 monoclonal recombinant antibodies (rAbs) by coexpressing paired heavy- and light-chain variable region sequences of 51 plasma cell clones and 2 B-lymphocyte clones from MS cerebrospinal fluid in human tissue culture cells. Chimeric control rAbs were generated from anti-myelin hybridomas in which murine variable region sequences were fused to human constant region sequences. Purified rAbs were exhaustively assayed for reactivity against myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein by immunostaining of transfected cells expressing individual myelin proteins, by protein immunoblotting, and by immunostaining of human brain tissue sections. RESULTS: Whereas humanized control rAbs derived from anti-myelin hybridomas and anti-myelin monoclonal antibodies readily detected myelin antigens in multiple immunoassays, none of the rAbs derived from MS cerebrospinal fluid displayed immunoreactivity to the three myelin antigens tested. Immunocytochemical analysis of tissue sections from MS and control brain demonstrated only weak staining with a few rAbs against nuclei or cytoplasmic granules in neurons, glia, and inflammatory cells. INTERPRETATION: The oligoclonal B-cell response in MS cerebrospinal fluid is not targeted to the well-characterized myelin antigens myelin basic protein, proteolipid protein, or myelin oligodendrocyte glycoprotein.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/líquido cefalorraquídeo , Proliferación Celular , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Animales , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Subgrupos de Linfocitos B/patología , Línea Celular , Células Clonales , Humanos , Ratones , Ratones Endogámicos BALB C , Esclerosis Múltiple/patología , Células Plasmáticas/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/líquido cefalorraquídeo
5.
JAMA Surg ; 149(4): 328-34, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24500799

RESUMEN

OBJECTIVES: To analyze the effect of laparoscopic sleeve gastrectomy (LSG) on patients with gastroesophageal reflux disease (GERD) and to compare the results of LSG vs gastric bypass (GB) among patients with known GERD. DESIGN, SETTING, AND PATIENTS: We performed a retrospective review of the Bariatric Outcomes Longitudinal Database from January 1, 2007, through December 31, 2010, including inpatient and all outpatient follow-up data. We compared patients undergoing LSG with a concurrent cohort undergoing GB. MAIN OUTCOMES AND MEASURES: Rates of improvement or worsening of GERD symptoms, development of new-onset GERD, and weight loss and complications. RESULTS: A total of 4832 patients underwent LSG and 33 867 underwent GB, with preexisting GERD present in 44.5% of the LSG cohort and 50.4% of the GB cohort. Most LSG patients (84.1%) continued to have GERD symptoms postoperatively, with only 15.9% demonstrating GERD resolution. Of LSG patients who did not demonstrate preoperative GERD, 8.6% developed GERD postoperatively. In comparison, GB resolved GERD in most patients (62.8%) within 6 months postoperatively (P < .001). Among the LSG cohort, the presence of preoperative GERD was associated with increased postoperative complications (15.1% vs 10.6%), gastrointestinal adverse events (6.9% vs 3.6%), and increased need for revisional surgery (0.6% vs 0.3%) (all P < .05). The presence of GERD had no effect on weight loss for the GB cohort but was associated with decreased weight loss in the LSG group. CONCLUSIONS AND RELEVANCE: Laparoscopic sleeve gastrectomy did not reliably relieve or improve GERD symptoms and induced GERD in some previously asymptomatic patients. Preoperative GERD was associated with worse outcomes and decreased weight loss with LSG and may represent a relative contraindication.


Asunto(s)
Gastrectomía/métodos , Reflujo Gastroesofágico/complicaciones , Gastroplastia/métodos , Laparoscopía/métodos , Obesidad Mórbida/cirugía , Vigilancia de la Población , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/cirugía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Washingtón/epidemiología , Pérdida de Peso/fisiología
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