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2.
Scand J Med Sci Sports ; 22(5): 653-61, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21410545

RESUMEN

Previous authors have reported that chronic eccentric cycling facilitates greater changes in multi-joint leg function (hopping frequency, maximum jumping height) compared with concentric cycling. Our purpose was to evaluate changes in leg spring stiffness and maximum power following eccentric and concentric cycling training. Twelve individuals performed either eccentric (n=6) or concentric (n=6) cycling for 7 weeks (3 sessions/week) while training duration progressively increased. Participants performed trials of submaximal hopping, maximal counter movement jumps, and maximal concentric cycling to evaluate leg spring stiffness, maximum jumping power, and maximum concentric cycling power respectively, before and 1 week following training. Total work during training did not differ between eccentric and concentric cycling (126 ± 15-728 ± 91 kJ vs 125 ± 10-787 ± 76 kJ). Following training, eccentric cycling exhibited greater changes in k(leg) and jumping P(max) compared with CON(cyc) (10 ± 3% vs -2 ± 4% and 7 ± 2% vs -2 ± 3%, respectively, P=0.05). Alterations in CON(cyc) P(max) did not differ between ECC(cyc) (1035 ± 142 vs 1030 ± 133 W) and CON(cyc) (1072 ± 98 vs 1081 ± 85 W). These data demonstrate that eccentric cycling is an effective method for improving leg spring stiffness and maximum power during multi-joint tasks that include stretch-shortening cycles. Improvements in leg spring stiffness and maximum power would be beneficial for both aging and athletic populations.


Asunto(s)
Ciclismo/fisiología , Tolerancia al Ejercicio/fisiología , Ejercicio Físico/fisiología , Pierna/fisiología , Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Adaptación Fisiológica , Adulto , Análisis de Varianza , Ergometría , Terapia por Ejercicio , Femenino , Humanos , Contracción Isométrica/fisiología , Masculino , Factores de Tiempo
3.
J R Army Med Corps ; 156(2): 97-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20648945

RESUMEN

OBJECTIVE: To measure the perception of military mental health clients of the impact of wearing military uniform on the therapeutic relationship between client and clinician and to ascertain if uniform and rank is perceived as a barrier. METHOD: A brief questionnaire was distributed to Departments of Community Mental Health to be disseminated to their mental health clients to measure their responses. RESULTS: 282 responses from mental health clients were collected over a 30 day period regarding the impact that military uniform makes to the therapeutic relationship with the clinician. 63% (n = 178) regarded uniform as negatively influencing their relationship with the clinician, 37% (n = 104) responded that it did not. 39% (n = 111) believed rank to be a barrier, whereas 61% (n = 171) did not believe it affected the relationship. CONCLUSION: The majority of military mental health clients regard the wearing of uniform as negative to the therapeutic relationship and a significant minority have similar feelings about rank. Military mental health practitioners should consider the impact of these results on the therapeutic relationship with military patients.


Asunto(s)
Servicios de Salud Mental , Personal Militar/psicología , Relaciones Profesional-Paciente , Humanos , Personal Militar/clasificación , Percepción Social
4.
J R Army Med Corps ; 156(1): 41-3, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20433105

RESUMEN

We describe the case of a 32-year-old soldier who presented with acute organic psychosis during an operational tour to Iraq. This was precipitated by excessive consumption of caffeine coupled with additional use of oral nutritional stimulants. Her biochemical profile was compounded by the additional use of exogenous creatine. We present a brief overview of the issue of exercise supplementation and highlight some of the potential problems and clinical issues surrounding their use. This has important implications for both serving soldiers and the wider medical community.


Asunto(s)
Cafeína/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Creatina/efectos adversos , Suplementos Dietéticos/efectos adversos , Guerra de Irak 2003-2011 , Psicosis Inducidas por Sustancias/etiología , Adulto , Delirio/inducido químicamente , Delirio/diagnóstico , Suplementos Dietéticos/estadística & datos numéricos , Femenino , Humanos , Irak , Psicosis Inducidas por Sustancias/diagnóstico , Reino Unido
5.
J Fish Dis ; 32(2): 173-81, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19261044

RESUMEN

Rainbow trout, Oncorhynchus mykiss (Walbaum), were exposed continuously to infectious pancreatic necrosis virus (IPNV) at 0, 10(1), 10(3) or 10(5) plaque forming units (pfu) L(-1) of water to estimate the effects of chronic IPNV exposure on early life stages. Fish density averaged 35 fish L(-1) (low density) or 140 fish L(-1) (high density), and the tank flow rate was 250 mL(-1) min. Virus exposure began at 6 days before hatch and continued until fish were 44 days old. Cumulative per cent mortality, analysis of survival and hazard functions, and discrete-time event analysis were used to explore the patterns of survival and mortality. In eggs and fish exposed to IPNV, mortality significantly greater than in the 0 pfu L(-1) exposure did not occur until IPNV concentration was 10(5) pfu L(-1) at low fish density and 10(3) pfu IPNV L(-1) at high fish density. These results suggest that in the natural aquatic environment, where rainbow trout densities are likely to be considerably lower than in this study, mortality resulting from infection with IPNV will very likely not occur when ambient concentrations of virus are < or =10(3) pfu IPNV L(-1). In aquaculture rearing units, trout density is likely to be as high or higher than the densities used in this study. Therefore, continuous inputs of virus at concentrations greater than 10(1) pfu L(-1) may result in IPN epidemics in aquaculture facilities.


Asunto(s)
Infecciones por Birnaviridae/veterinaria , Exposición a Riesgos Ambientales , Enfermedades de los Peces/virología , Virus de la Necrosis Pancreática Infecciosa/fisiología , Oncorhynchus mykiss/virología , Animales , Infecciones por Birnaviridae/mortalidad , Infecciones por Birnaviridae/virología , Enfermedades de los Peces/mortalidad , Densidad de Población , Análisis de Regresión , Análisis de Supervivencia , Factores de Tiempo
6.
Br J Oral Maxillofac Surg ; 57(7): 694-696, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31239228

RESUMEN

Unilateral soft palate paralysis is rare. No cases of unilateral soft palate paralysis with associated velopharyngeal insufficiency (VPI) secondary to minor blunt neck trauma have been reported to date. This case details the presentation of a man with isolated unilateral soft palate paralysis and associated velopharyngeal insufficiency following a collision with an opponent when playing soccer.


Asunto(s)
Traumatismos del Cuello , Paladar Blando/fisiopatología , Parálisis/complicaciones , Insuficiencia Velofaríngea/etiología , Heridas no Penetrantes , Adolescente , Fisura del Paladar , Humanos , Masculino , Cuello
7.
J R Army Med Corps ; 154(2): 107-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19043989

RESUMEN

The three most common clinical sequelae of trauma have been outlined above. However, the vast majority of cases will produce a normal reaction, which would not fulfil any of the diagnostic criteria. Overall, therefore, clinically significant traumatic responses are rare in the military environment, and for the most part short lived. For the conditions that are not self-limited, there are effective treatment options available which will be outlined later in this series.


Asunto(s)
Trastornos por Estrés Postraumático/diagnóstico , Trastornos de Adaptación/diagnóstico , Trastornos de Adaptación/psicología , Humanos , Clasificación Internacional de Enfermedades , Personal Militar/psicología , Trastornos por Estrés Postraumático/psicología
8.
J R Army Med Corps ; 154(2): 102-6, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19043988

RESUMEN

UK Forces are currently engaged in high tempo, high intensity operations in both Iraq and Afghanistan. Concern has been raised about the impact of current operations upon the mental health of Service personnel. Using data gathered from deployed Field Mental Health Teams, a random sample of UK based non-deployed Community Mental Health Teams and services dedicated to mobilising, de-mobilising and to de-mobilised Reserve Forces, this paper explores the current mental health burden for UK Forces. At present, operationally related psychological disorders do not appear to be a substantial concern for Regular Forces, although for the minority that suffer such problems they are both distressing and of occupational relevance. Proportionately there are more mobilised Reserve Forces seeking help for mental health problems than Regular Forces on operations, but the overall burden that they currently place upon the Defence Mental Health Services is small. There is at present no evidence of an epidemic of mental health problems amongst either Regular or Reserve Forces veterans of the Op TELIC deployment, however, this may change in the future given the evolving nature and fluctuating intensity of operational activity.


Asunto(s)
Trastornos Mentales/epidemiología , Personal Militar/psicología , Humanos , Guerra de Irak 2003-2011 , Trastornos Mentales/diagnóstico , Salud Mental , Servicios de Salud Mental , Reino Unido/epidemiología
9.
J R Army Med Corps ; 153(3): 170-1, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18200911

RESUMEN

OBJECTIVE: to measure the perceptions of military staff of the impact of wearing military uniform on the therapeutic relationship with mental health clients. METHOD: a brief questionnaire was distributed to all military clinicians in Departments of Community Mental Health to measure their attitudes. RESULTS: there was a 67.9% (n=70) response rate regarding the impact of uniform on the therapeutic relationship. 20% of responses were positive, 31% negative, 37% mixed and 12% gave no answer. CONCLUSION: there was no clear pre-existing literature on this issue. Overall, the wearing of uniform appeared to be perceived positively positive. There is a need to assess clients' points of view in future studies.


Asunto(s)
Jerarquia Social , Trastornos Mentales/terapia , Servicios de Salud Mental/organización & administración , Personal Militar/psicología , Psiquiatría Militar/organización & administración , Relaciones Médico-Paciente , Clase Social , Encuestas de Atención de la Salud , Humanos , Percepción , Pruebas Psicológicas , Psicometría , Encuestas y Cuestionarios , Reino Unido
10.
Dev Biol (Basel) ; 121: 165-74, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15962479

RESUMEN

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also coexpressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56%) than in the control fish (77%), showing a dose-response pattern.


Asunto(s)
Infecciones por Birnaviridae/veterinaria , Enfermedades de los Peces/prevención & control , Expresión Génica , Genes Virales/genética , Virus de la Necrosis Pancreática Infecciosa/genética , Salmonidae , Vacunación/veterinaria , Proteínas Estructurales Virales/genética , Vacunas Virales/genética , Animales , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Baculoviridae , Infecciones por Birnaviridae/prevención & control , Células Cultivadas , ADN Complementario/genética , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Enfermedades de los Peces/virología , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Proteínas Fluorescentes Verdes/metabolismo , Inmunohistoquímica , Spodoptera , Transfección , Vacunación/métodos , Vacunas de Subunidad/genética , Virión/inmunología , Virión/metabolismo
11.
Mech Ageing Dev ; 13(2): 105-9, 1980 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7431999

RESUMEN

Muscle satellite cells from old (> 30 months) female Long-Evans rats were isolated and grown in cell culture. Satellite cells differentiated in culture to form multinucleated myotubes that had the ability to accumulate muscle-specific proteins. Therefore, satellite cells exist in muscle through senescence and retain their myogenic potential.


Asunto(s)
Músculos/citología , Envejecimiento , Animales , Células Cultivadas , Femenino , Proteínas Musculares/biosíntesis , Músculos/metabolismo , Ratas
12.
Mech Ageing Dev ; 18(1): 89-95, 1982 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7062790

RESUMEN

Because muscle satellite cells have been implicated in the process of muscle growth and mass regulation, as well as regeneration, alterations in the capacity of satellite cells to differentiate and accumulate muscle specific proteins during aging could play a role in the process of senile muscle atrophy. Skeletal muscle satellite cells were cultured from male rats from the following four age groups: neonatal rats (less than 5 days of age), growing rats (1--3 months of age, adult rats (9--12 months of age) and old rats (more than 24 months of age). A series of experiments was conducted in which cultures were harvested at daily intervals following fusion, and the amount of alpha-actin per myotube nucleus was determined. Analysis of maximum actin accumulation in myotubes from each experiment within each age group revealed no significant differences among cells derived from growing, adult or old rats; however, myotubes differentiating from neonatal muscle cells were able to accumulate more than three times as much alpha-actin per myotube nuclei as cells from the other three age groups. This result may reflect fundamental differences between authentic satellite cells and myogenic cells of prenatal origin. Aside from differences between neonatal cells and satellite cells, satellite cells from old muscle do not appear to have a diminished capacity to accumulate muscle-specific proteins following differentiation into muscle fibers.


Asunto(s)
Actinas/metabolismo , Músculos/citología , Factores de Edad , Animales , Fusión Celular , Núcleo Celular/metabolismo , Fibroblastos/metabolismo , Técnicas In Vitro , Masculino , Ratas
13.
J Med Chem ; 23(8): 862-5, 1980 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7401115

RESUMEN

A new series of phosphonium salts was examined for effects on the cholinergic nervous system of Schistosoma mansoni. Studies were conducted using both an activity-monitoring and fluorescent-labeling technique. The activity method gave more definitive results, indicating that some poly(methylene)bis(triphenylphosphonium) salts and some [3-(alkylamino)propyl]triphenylphosphonium salts have strong anticholinergic effects. Hexyltriphenylphosphonium bromide has very marked effects both in the motility and the fluorescence test, but these effects cannot immediately be ascribed to cholinergic actions.


Asunto(s)
Schistosoma mansoni/efectos de los fármacos , Acetilcolina/metabolismo , Animales , Compuestos de Dansilo , Masculino , Microscopía Fluorescente , Movimiento/efectos de los fármacos , Compuestos Onio/síntesis química , Compuestos Onio/farmacología , Receptores Colinérgicos/efectos de los fármacos , Schistosoma mansoni/metabolismo
14.
Hum Pathol ; 10(3): 347-9, 1979 May.
Artículo en Inglés | MEDLINE | ID: mdl-468218

RESUMEN

Juxtaposition of the atrial appendages is a rare congenital cardiac anomaly almost universally associated with severe conotruncal abnormalities, especially transposition of the aorta. This presentation describes a case of right sided juxtaposition of the atrial appendages without concomitant conotruncal malformations. This finding contradicts previous hypotheses concerning the genesis of juxtaposition.


Asunto(s)
Atrios Cardíacos/anomalías , Cardiopatías Congénitas/patología , Defectos del Tabique Interventricular/patología , Conducto Arterioso Permeable/complicaciones , Conducto Arterioso Permeable/cirugía , Eclampsia/complicaciones , Femenino , Atrios Cardíacos/patología , Defectos del Tabique Interventricular/complicaciones , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Masculino , Meningitis/complicaciones , Embarazo
15.
J Appl Physiol (1985) ; 76(1): 333-8, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8175526

RESUMEN

Viral bronchiolitis is a common disease that may result in persistent airway abnormalities. Previous studies of neonatal bronchiolitis in rats revealed chronic sequelae, including airway obstruction, airway hyperresponsiveness, increased production of airway eicosanoids, and increased numbers of bronchiolar mast cells. To address the hypothesis that postbronchiolitis airway obstruction is caused in part by reversible processes, we tested whether obstruction could be reversed by a brief course of high-dose corticosteroids. Neonatal Brown Norway rats (5 days of age) were inoculated with parainfluenza type 1 virus or sterile vehicle. At 8 wk of age, rats were treated with dexamethasone (1.4 mg.kg-1 x day-1 sc) or saline for 3 days and were evaluated for lung mechanics, gas exchange, and lung inflammatory cells 1 day after the last injection. Dexamethasone normalized the chronic virus-induced airway obstruction and reduced the numbers of bronchiolar mast cells and other inflammatory cells. Resistance and dynamic compliance correlated significantly with bronchiolar mast cells but not with other airway inflammatory cell infiltrates. We conclude that the airway abnormalities that persist in rats after recovery from neonatal bronchiolitis are associated with increased numbers of bronchiolar mast cells and are largely due to corticosteroid-sensitive mechanisms.


Asunto(s)
Bronquiolitis Viral/tratamiento farmacológico , Dexametasona/uso terapéutico , Resistencia de las Vías Respiratorias/fisiología , Animales , Animales Recién Nacidos , Bronquiolitis Viral/patología , Bronquiolitis Viral/fisiopatología , Femenino , Histamina/sangre , Pulmón/patología , Masculino , Mastocitos/fisiología , Oxígeno/sangre , Virus de la Parainfluenza 1 Humana , Infecciones por Paramyxoviridae/patología , Embarazo , Intercambio Gaseoso Pulmonar/fisiología , Ratas , Ratas Endogámicas BN
16.
Neurosurgery ; 33(5): 898-900; discussion 900-1, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8264890

RESUMEN

The incidence of intracerebral hematomas after myocardial infarction increases after thrombolysis. As noted in the case described, clots formed after the administration of thrombolytic agents may remain liquid, and this blood can be drained by a catheter. However, in this case, the patient continued to bleed locally. This problem requires the development of methods to stop such ongoing local bleeding. It may be prevented in the future by improved thrombolytic drugs.


Asunto(s)
Hemorragia Cerebral/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/efectos adversos , Anciano , Hemorragia Cerebral/cirugía , Drenaje , Quimioterapia Combinada , Resultado Fatal , Femenino , Heparina/efectos adversos , Heparina/uso terapéutico , Humanos , Examen Neurológico/efectos de los fármacos , Recurrencia , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía Computarizada por Rayos X
17.
Neurosurgery ; 38(4): 741-5, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8692394

RESUMEN

Within recent years, the technologies of radiological imaging and spinal instrumentation have exponentially increased. New methods of preoperative imaging, that is, magnetic resonance imaging (MRI) and computed tomography, have allowed for a better understanding of surgical pathology. Such an understanding is likely to lead to a more successful surgical experience, which certainly is the case with spine surgery with instrumentation. However, after implantation of most instrumentation, imaging is greatly impaired. Metallurgic advancements in titanium were sought to reduce postoperative imaging problems. The purpose of this study is to assess the presence and extent of artifacts seen on postoperative MRI scans in patients with titanium spinal implants. Six patients, four with degenerative spine disease and two with neoplasms, had thoracic and/or lumbar spinal fixation performed with titanium instrumentation. All patients underwent postoperative conventional MRI with the use of T1-weighted, T2-weighted, and gradient-echo sequences. The scans and individual sequences were then analyzed for image quality. A progressive and significant increase in imaging artifact related to the titanium spinal instrumentation was observed on the T1-weighted, T2-weighted, and gradient-echo sequences. Titanium spinal instruments do not allow optimal postoperative imaging on conventional MRI scanners.


Asunto(s)
Imagen por Resonancia Magnética , Complicaciones Posoperatorias/diagnóstico , Prótesis e Implantes , Enfermedades de la Columna Vertebral/cirugía , Fusión Vertebral/instrumentación , Neoplasias de la Columna Vertebral/cirugía , Titanio , Adulto , Anciano , Artefactos , Diagnóstico Diferencial , Femenino , Humanos , Vértebras Lumbares/patología , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Enfermedades de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/diagnóstico , Vértebras Torácicas/patología , Vértebras Torácicas/cirugía
18.
J Neurosurg ; 82(6): 1011-4, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7760174

RESUMEN

Knowledge of the relevant anatomy is important when developing a strategy for introducing screws into the lateral masses to secure internal fixation devices. This paper defines key bony landmarks and their relationship to critical neurovascular structures and identifies a location for safe placement of cervical articular pillar (lateral mass) screws. Measurements of anatomical landmarks in 10 spines from human cadavers aged 61 to 85 years were made by caliper and a metric ruler. Landmarks were the lateral facet line, rostrocaudal line, medial facet line, intrafacet line, and medial facet line-vertebral artery line. The average distances and ranges were recorded. Such great variance existed in measurements from spine to spine and within the same spine as to render averages clinically unreliable. Dissection revealed that division of the articular pillar into four quadrants leaves one, the superior lateral quadrant, under which there are no neurovascular structures; this may be considered the "safe quadrant" for placement of posterior screws and plates.


Asunto(s)
Vértebras Cervicales/anatomía & histología , Anciano , Anciano de 80 o más Años , Cadáver , Humanos , Ilustración Médica , Persona de Mediana Edad , Raíces Nerviosas Espinales/anatomía & histología , Arteria Vertebral/anatomía & histología
19.
J Chromatogr A ; 917(1-2): 23-7, 2001 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-11403474

RESUMEN

For pharmaceutical products, one approach developed to assure that different chromatographic systems are capable of generating valid results is the system suitability test. Typically, a system suitability test involves numerical limits for predefined chromatographic parameters such as theoretical plates, tailing factor, injector reproducibility, etc. An estimation of the ratio of signal compared to baseline is one way to measure system performance, according to a valid method, independent of the instrument. However, since this comparison relates the height of the signal to the height of the noise, it is difficult to relate to the peak area measurements that are typically used for quantification of samples. Additionally, although peak area and peak height may be highly correlated over a wide region, peak area at very low concentrations can be more sensitive to all components of noise due to peak shape. To establish a system suitability criterion, one can use the ratio of the area signal to the baseline noise for replicate injections for samples prepared at concentration equal to the limit of quantitation during the validation studies. A lower limit for this ratio can be derived using statistical tolerance intervals. This lower limit can be applied as a system suitability criterion to measure that any system is performing adequately for measuring low level components in the sample for all future use of the method.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
J Bone Joint Surg Am ; 81(7): 905-17, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10428121

RESUMEN

BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) can induce bone formation, but the inability to identify an ideal delivery system limits their clinical application. We used ex vivo adenoviral gene transfer to create BMP-2-producing bone-marrow cells, which allow delivery of the BMP-2 to a specific anatomical site. The autologous BMP-2-producing bone-marrow cells then were used to heal a critical-sized femoral segmental defect in syngeneic rats. METHODS: Femoral defects in five groups of rats were filled with 5 x 10(6) BMP-2-producing bone-marrow cells, created through adenoviral gene transfer (twenty-four femora, Group I); twenty micrograms of rhBMP-2 (sixteen femora, Group II); 5 x 10(6) beta-galactosidase-producing rat-bone-marrow cells, created through adenoviral gene transfer of the lacZ gene (twelve femora, Group III); 5 x 10(6) uninfected rat-bone-marrow cells (ten femora, Group IV); or guanidine hydrochloride-extracted demineralized bone matrix only (ten femora, Group V). Guanidine hydrochloride-extracted demineralized bone matrix served as a substrate in all experimental groups. Specimens that were removed two months postoperatively underwent histological and histomorphometric analysis as well as biomechanical testing. RESULTS: Twenty-two of the twenty-four defects in Group I (BMP-2-producing bone-marrow cells) and all sixteen defects in Group II (rhBMP-2) had healed radiographically at two months postoperatively compared with only one of the thirty-two defects in the three control groups (beta-galactosidase-producing rat-bone-marrow cells, uninfected rat-bone-marrow cells, and guanidine hydrochloride-extracted demineralized bone matrix alone). Histological analysis of the specimens revealed that defects that had received BMP-2-producing bone-marrow cells (Group I) were filled with coarse trabecular bone at two months postoperatively, whereas in those that had received rhBMP-2 (Group II) the bone was thin and lace-like. Defects that had been treated with bone-marrow cells producing beta-galactosidase (Group III), uninfected bone-marrow cells (Group IV), or guanidine hydrochloride-extracted demineralized bone matrix only (Group V) demonstrated little or no bone formation. Histomorphometric analysis revealed a significantly greater total area of bone formation in the defects treated with the BMP-2-producing bone-marrow cells than in those treated with the rhBMP-2 (p = 0.036). Biomechanical testing demonstrated no significant differences, with the numbers available, between the healed femora that had received BMP-2-producing bone-marrow cells and the untreated (control) femora with respect to ultimate torque to failure or energy to failure. CONCLUSIONS: This study demonstrated that BMP-2-producing bone-marrow cells created by means of adenoviral gene transfer produce sufficient protein to heal a segmental femoral defect. We also established the feasibility of ex vivo gene transfer with the use of biologically acute autologous short-term cultures of bone-marrow cells.


Asunto(s)
Proteínas Morfogenéticas Óseas/genética , Técnicas de Transferencia de Gen , Terapia Genética , Factor de Crecimiento Transformador beta , Animales , Trasplante de Médula Ósea , Proteína Morfogenética Ósea 2 , Regeneración Ósea/genética , Fémur/patología , Humanos , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes
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