RESUMEN
BACKGROUND: Following traumatic brain injury (TBI), individuals may experience chronic problems with irritability or aggression, which may need treatment to minimize the negative impact on their relationships, home life, social interactions, community participation, and employment OBJECTIVE: : To test the a priori hypothesis that amantadine reduces irritability (primary hypothesis) and aggression (secondary hypothesis) among individuals greater than 6 months post-TBI METHODS:: A total of 76 individuals greater than 6 months post-TBI referred for irritability management were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine (n = 38) versus placebo (n = 38). Study participants were randomly assigned to receive amantadine hydrochloride 100 mg twice daily versus equivalent placebo for 28 days. Symptoms of irritability and aggression were measured before and after treatment using the Neuropsychiatric Inventory Irritability (NPI-I) and Aggression (NPI-A) domains, as well as the NPI-Distress for these domains RESULTS: : In the amantadine group, 80.56% improved at least 3 points on the NPI-I, compared with 44.44% in the group that received placebo (P = .0016). Mean change in NPI-I was -4.3 in the amantadine group and -2.6 in the placebo group (P = .0085). When excluding individuals with minimal to no baseline aggression, mean change in NPI-A was -4.56 in the amantadine group and -2.46 in the placebo group (P = .046). Mean changes in NPI-I and NPI-A Distress were not statistically significant between the amantadine and placebo groups. Adverse event occurrence did not differ between the 2 groups CONCLUSIONS: : Amantadine 100 mg every morning and at noon appears an effective and safe means of reducing frequency and severity of irritability and aggression among individuals with TBI and sufficient creatinine clearance.
Asunto(s)
Agresión , Amantadina/uso terapéutico , Lesiones Encefálicas/psicología , Dopaminérgicos/uso terapéutico , Genio Irritable , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Estudios Prospectivos , Escalas de Valoración PsiquiátricaRESUMEN
Mutations in fukutin-related protein (FKRP) cause a common subset of muscular dystrophies characterized by aberrant glycosylation of alpha-dystroglycan (α-DG), collectively known as dystroglycanopathies. The clinical variations associated with FKRP mutations range from mild limb-girdle muscular dystrophy type 2I with predominantly muscle phenotypes to severe Walker-Warburg syndrome and muscle-eye-brain disease with striking structural brain and eye defects. In the present study, we have generated animal models and demonstrated that ablation of FKRP functions is embryonic lethal and that the homozygous-null embryos die before reaching E12.5. The homozygous knock-in mouse carrying the missense P448L mutation almost completely lacks functional glycosylation of α-DG in muscles and brain, validating the essential role of FKRP in the functional glycosylation of α-DG. However, the knock-in mouse survives and develops a wide range of structural abnormalities in the central nervous system, characteristics of neuronal migration defects. The brain and eye defects are highly reminiscent of the phenotypes seen in severe dystroglycanopathy patients. In addition, skeletal muscles develop progressive muscular dystrophy. Our results confirm that post-translational modifications of α-DG are essential for normal development of the brain and eyes. In addition, both the mutation itself and the levels of FKRP expression are equally critical for the survival of the animals. The exceptionally wide clinical spectrums recapitulated in the P448L mice also suggest the involvement of other factors in the disease progression. The mutant mouse represents a valuable model to further elucidate the functions of FKRP and develop therapies for FKRP-related muscular dystrophies.
Asunto(s)
Encéfalo/embriología , Distroglicanos/metabolismo , Ojo/embriología , Desarrollo de Músculos , Músculo Esquelético/embriología , Distrofia Muscular Animal , Proteínas/metabolismo , Animales , Southern Blotting , Western Blotting , Encéfalo/fisiología , Ojo/metabolismo , Técnica del Anticuerpo Fluorescente , Eliminación de Gen , Expresión Génica , Técnicas de Sustitución del Gen , Glicosilación , Malformaciones del Desarrollo Cortical del Grupo II , Ratones , Ratones Noqueados , Modelos Animales , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Mutación Missense , Pentosiltransferasa , Reacción en Cadena de la Polimerasa , Procesamiento Proteico-Postraduccional , Proteínas/genética , TransferasasRESUMEN
BACKGROUND: Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells. METHODS: Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR. RESULTS: The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and prostaglandin E synthase (PTGES), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific. CONCLUSION: Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA.
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Expresión Génica/genética , Predisposición Genética a la Enfermedad/genética , Articulación de la Rodilla/patología , Meniscos Tibiales/patología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/patología , Adulto , Anciano , Células Cultivadas , Niño , Condrocitos/metabolismo , Condrocitos/patología , Proteínas de la Matriz Extracelular/genética , Femenino , Perfilación de la Expresión Génica , Marcadores Genéticos/genética , Humanos , Mediadores de Inflamación/análisis , Mediadores de Inflamación/metabolismo , Articulación de la Rodilla/fisiopatología , Masculino , Meniscos Tibiales/metabolismo , Meniscos Tibiales/fisiopatología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteoartritis de la Rodilla/fisiopatología , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Laparoscopic ventral hernia repair requires an intraperitoneal prosthetic; however, these materials are not without consequences. We evaluated host reaction to intraperitoneal placement of various prosthetics and the functional outcomes in an animal model. Mesh (n = 15 per mesh type) was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included ePTFE (DualMesh), ePTFE and polypropylene (Composix), polypropylene and oxidized regenerated cellulose (Proceed), and polypropylene (Marlex). Adhesion formation was evaluated at 1, 4, 8, and 16 weeks using 2-mm mini-laparoscopy. Adhesion area, adhesion tenacity, prosthetic shrinkage, and compliance were evaluated after mesh explantation at 16 weeks. DualMesh had significantly less adhesions than Proceed, Composix, or Marlex at 1, 4, 8, and 16 weeks (P < 0.0001). Marlex had significantly more adhesions than other meshes at each time point (P < 0.0001). There were no statistically significant differences in adhesions between Proceed and Composix meshes. After mesh explantation, the mean area of adhesions for Proceed (4.6%) was less than for Marlex (21.7%; P = 0.001). The adhesions to Marlex were statistically more tenacious than the DualMesh and Composix groups. Overall prosthetic shrinkage was statistically greater for DualMesh (34.7%) than for the remaining mesh types (P < 0.01). Mesh compliance was similar between the groups. Prosthetic materials demonstrate a wide variety of characteristics when placed inside the abdomen. Marlex formed more adhesions with greater tenacity than the other mesh types. DualMesh resulted in minimal adhesions, but it shrank more than the other mesh types. Each prosthetic generates a varied host reaction. Better understanding of these reactions can allow a suitable prosthetic to be chosen for a given patient in clinical practice.
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Materiales Biocompatibles/efectos adversos , Hernia Ventral/cirugía , Prótesis e Implantes/efectos adversos , Mallas Quirúrgicas/efectos adversos , Adherencias Tisulares/etiología , Animales , Modelos Animales de Enfermedad , Polímeros de Fluorocarbono/efectos adversos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Polipropilenos/efectos adversos , Estudios Prospectivos , ConejosRESUMEN
OBJECTIVE: To determine the optimal approach to prevent adhesions comparing leuprolide acetate (GnRH-a), Interceed (oxidized regenerated cellulose; Johnson & Johnson Medical, Inc., New Brunswick, NJ), and a combination of leuprolide with Interceed in a rabbit uterine horn adhesion model. DESIGN: Prospective, randomized, blinded study. SETTING: Certified animal care facility. ANIMAL(S): Twenty-eight sexually mature, female New Zealand White rabbits. INTERVENTION(S): Animals were prospectively randomized (by number generator) to receive GnRH-a or saline. After 6 weeks, standard surgical manipulations were performed at three sites in each uterine horn by [1]. suture, [2]. unipolar cautery, and [3]. superficial abrasion. Interceed was applied over one randomly assigned uterine horn only. Six weeks after surgery, uterine adhesions were assessed visually, and tissue fibrosis was assessed by histology. MAIN OUTCOME MEASURE(S): Presence or absence of adhesions and microscopic tissue fibrosis. RESULT(S): Gonadotropin-releasing hormone agonist significantly decreased adhesions, whereas Interceed alone did not reduce adhesions. However, GnRH agonist plus Interceed was the most effective measure to reduce tissue fibrosis. CONCLUSION(S): Preoperative GnRH-a is more effective than Interceed in preventing surgical adhesions in the rabbit uterine horn. However, preoperative GnRH-a plus Interceed may provide optimal results in this animal model, because microscopic tissue fibrosis is minimized with this combination.
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Celulosa Oxidada/uso terapéutico , Leuprolida/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Útero/cirugía , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Fibrosis/prevención & control , Hormona Liberadora de Gonadotropina/agonistas , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Conejos , Distribución Aleatoria , Análisis de Regresión , Adherencias Tisulares , Útero/patologíaRESUMEN
OBJECTIVE: The purpose of this study was to gather descriptive information from residency program directors regarding characteristics of the education and experiences of resident physicians in oncology rehabilitation. DESIGN: The program directors responded to a 28-question survey. Information collected included general descriptors of residency programs, oncology rehabilitation services lines within the institution, educational and clinical opportunities for trainees, and perceptions of quality for oncology experiences. RESULTS: Thirty-eight responses, with a response rate of 48%, were recorded. Thirty-two percent of the programs did not have any dedicated faculty for cancer rehabilitation. A majority of the respondents felt that cancer rehabilitation should be an important component of the curriculum. Sixty-six percent of the programs admitted only one to two cancer diagnoses to their inpatient units per week, and 26% had outpatient clinics that focused specifically on rehabilitation needs for oncology patients. A majority of the programs felt that experiences were only average and that residents do not receive adequate exposure to cancer rehabilitation during their training. CONCLUSIONS: Although cancer rehabilitation is considered an important area of education, quality and quantity of experiences may be improved. Several opportunities may exist to improve such exposure in anticipation of serving the functional needs for a growing population of cancer survivors.
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Competencia Clínica , Oncología Médica/educación , Neoplasias/rehabilitación , Medicina Física y Rehabilitación/educación , Estudios Transversales , Curriculum , Educación de Postgrado en Medicina/organización & administración , Femenino , Humanos , Internado y Residencia/organización & administración , Masculino , Evaluación de Necesidades , Encuestas y Cuestionarios , Estados UnidosRESUMEN
BACKGROUND: Ultrasound (US) vascular guidance is traditionally performed in transverse (T) and longitudinal (L) axes, each with drawbacks. We hypothesized that the introduction of a novel oblique (O) approach would improve the success of US-guided peripheral venous access. We examined emergency physician (EP) performance using the O approach in a gel US phantom. METHODS: In a prospective, case control study, EPs were enrolled from four levels of physician experience including postgraduate years one to three (PGY1, PGY2, PGY3) and attending physicians. After a brief training session, each participant attempted vessel aspiration using a linear probe in T, L, and O axes on a gel US phantom. Time to aspiration and number of attempts to aspiration were recorded. The approach order was randomized, and descriptive statistics were used. RESULTS: Twenty-four physicians participated. The first-attempt success rate was lower for O, 45.83%, versus 70.83% for T (p = 0.03) and 83.33% for L (p = 0.01). The average time to aspiration was 12.5 s (O) compared with 9.47 s (T) and 9.74 s (L), respectively. There were no significant differences between all four groups in regard to total amount of time and number of aspiration attempts; however, a trend appeared revealing that PGY3 and attending physicians tended to aspirate in less time and by fewer attempts in all three orientations when compared with the PGY2 and PGY1 physicians. CONCLUSION: In this pilot study, US-guided simulated peripheral venous access using a phantom gel model in a mixed user group showed that the novel oblique approach was not initially more successful versus T and L techniques.