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1.
J Mech Behav Biomed Mater ; 100: 103398, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31450100

RESUMEN

In a study of spine injuries in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) from 2001-09, spinal fractures sustained by mounted soldiers accounted for 26% of all injuries, and of that, 43% were caused by explosions [1]. The thoracolumbar region is the most vulnerable area of the spine [2], and injuries are often incapacitating, making egress from vehicles difficult. Injury prediction from such events continues to remain a challenge due to the limited availability of studies specifically focused on underbody blasts (UBB) and criteria on related injuries. This study focuses on developing and validating the spine response of an updated 50th percentile male Global Human Body Models Consortium (GHBMC) Finite Element (FE) model using instrumented post-mortem human subject (PMHS) laboratory tests under two unique conditions. The model was validated against response corridors created using scaled thoracic (T12, T8, T5, T1) and sacrum (S1) spine Z-axis accelerations obtained from WSU whole-body PMHS tests. The scores for the updated spine model ranged from 0.557 - 0.756 for condition 1 (Seat- 4 m/s in 10 ms; Floor- 6 m/s in 5 ms) and 0.639-0.849 for condition 2 (Seat- 4 m/s in 55 ms; Floor- 8 m/s in 2 ms). The PMHS tests sustained spinal injuries in the thoracolumbar region. The validated model indicates high stress and strain concentrations at the same locations, providing an explanation for the fractures sustained in the PMHS tests.


Asunto(s)
Traumatismos por Explosión/fisiopatología , Explosiones , Sacro/fisiopatología , Vértebras Torácicas/fisiopatología , Aceleración , Accidentes de Tránsito , Fenómenos Biomecánicos , Cadáver , Fuerza Compresiva , Simulación por Computador , Análisis de Elementos Finitos , Cuerpo Humano , Humanos , Masculino , Ensayo de Materiales , Reproducibilidad de los Resultados , Estrés Mecánico , Tomografía Computarizada por Rayos X
2.
Traffic Inj Prev ; 19(sup2): S14-S19, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30570338

RESUMEN

OBJECTIVES: With regard to the pediatric population involved in vehicle side impact collisions, epidemiologic data can be used to identify specific injury-producing conditions and offer possible safety technology effectiveness through population-based estimates. The objective of the current study was to perform a field data analysis to investigate injury patterns and sources of injury to 4- to 10-year-olds in side and oblique impacts to determine the potential effect of updated side impact regulations and airbag safety countermeasures. METHODS: The NASS-CDS, years 1991 to 2014, was analyzed in the current study. The Abbreviated Injury Scale (AIS) 2005-Update 2008 was used to determine specific injuries and injury severities. Injury distributions were examined by body region as specified in the AIS dictionary and the Maximum AIS (MAIS). Children ages 4 to 10 were examined in this study. All occupant seating locations were investigated. Seating positions were designated by row and as either near side, middle, or far side. Side impacts with a principal direction of force (PDOF) between 2:00 and 4:00 as well as between 8:00 and 10:00 were included. Restraint use was documented only as restrained or unrestrained and not whether the restraint was being used properly. Injury distribution by MAIS, body region, and source of injury were documented. Analysis regarding occupant injury severity, body region injured, and injury source was performed by vehicle model year to determine the effect of updated side impact testing regulation and safety countermeasures. Because the aim of the study was to identify the most common injury patterns and sources, only unweighted data were analyzed. RESULTS: Main results obtained from the current study with respect to 4- to 10-year-old child occupants in side impact were that a decrease was observed in frequency of MAIS 1-3 injuries; injuries to the head, face, and extremities; as well as injuries caused by child occupant interaction with the vehicle interior and seatback support structures in 1998 model year passenger cars and newer. CONCLUSIONS: Results from this study could be useful in design advances of pediatric anthropomorphic test devices, child restraints, as well as vehicles and their safety countermeasure systems.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Escala Resumida de Traumatismos , Niño , Preescolar , Análisis de Datos , Humanos , Prevalencia , Estados Unidos , Heridas y Lesiones/etiología
3.
Traffic Inj Prev ; 17(5): 535-43, 2016 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-26507576

RESUMEN

OBJECTIVES: The objective of this study was to assess and compare the current lateral impact biofidelity of the shoulder, thorax, abdomen, and pelvis of the Q6, Q6s, and Hybrid III (HIII) 6-year-old anthropomorphic test devices (ATDs) through lateral impact testing. METHODS: A series of lateral impact pendulum tests, vertical drop tests, and Wayne State University (WSU) sled tests was performed, based on the procedures detailed in ISO/TR 9790 (1999) and scaling to the 6-year-old using Irwin et al. ( 2002 ). The HIII used in this study was tested with the Ford-designed abdomen described in Rouhana ( 2006 ) and Elhagediab et al. ( 2006 ). The data collected from the 3 different ATDs were filtered using SAE J211 (SAE International 2003 ), aligned using the methodology described by Donnelly and Moorhouse ( 2012 ), and compared for each body region tested (shoulder, thorax, abdomen, and pelvis). The biofidelity performance in lateral impact for the 3 ATDs was assessed against the scaled biofidelity targets published in Irwin et al. ( 2002 ), the abdominal biofidelity target suggested in van Ratingen et al. ( 1997 ), and the biofidelity targets published in Rhule et al. ( 2013 ). Regional and overall biofidelity rankings for each of the 3 ATDs were performed using both the ISO 9790 biofidelity rating system (ISO/TR 9790 1999) and the NHTSA's external biofidelity ranking system (BRS; Rhule et al. 2013 ). RESULTS: All 3 6-year-old ATD's pelvises were rated as least biofidelic of the 4 body regions tested, based on both the ISO and BRS biofidelity rating systems, followed by the shoulder and abdomen, respectively. The thorax of all 3 ATDs was rated as the most biofidelic body region using the aforementioned biofidelity rating systems. The HIII 6-year-old ATD was rated last in overall biofidelity of the 3 tested ATDs, based on both rating systems. The Q6s ATD was rated as having the best overall biofidelity using both rating systems. CONCLUSIONS: All 3 ATDs are more biofidelic in the thorax and abdomen than the shoulder and pelvis, with the pelvis being the least biofidelic of all 4 tested body regions. None of the 3 tested 6-year-old ATDs had an overall ranking of 2.0 or less, based on the BRS ranking. Therefore, it is expected that none of the 3 ATDs would mechanically respond like a postmortem human subject (PMHS) in a lateral impact crash test based on this ranking system. With respect to the ISO biofidelity rating, the HIII dummy would be considered unsuitable and the Q-series dummies would be considered marginal for assessing side impact occupant protection.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Maniquíes , Abdomen/fisiología , Fenómenos Biomecánicos , Niño , Humanos , Pelvis/fisiología , Hombro/fisiología , Tórax/fisiología
4.
Osteoarthritis Cartilage ; 23(12): 2242-2251, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26117175

RESUMEN

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.


Asunto(s)
Degeneración del Disco Intervertebral/genética , Cápsula Articular/metabolismo , Dolor de la Región Lumbar/genética , Vértebras Lumbares , Osteoartritis de la Columna Vertebral/genética , ARN Mensajero/metabolismo , Escoliosis/genética , Espondilolistesis/genética , Articulación Cigapofisaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Western Blotting , Cadáver , Técnicas de Cocultivo , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Ganglios Espinales , Humanos , Inmunohistoquímica , Degeneración del Disco Intervertebral/inmunología , Degeneración del Disco Intervertebral/metabolismo , Cápsula Articular/inmunología , Dolor de la Región Lumbar/inmunología , Dolor de la Región Lumbar/metabolismo , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/metabolismo , Osteoartritis de la Columna Vertebral/inmunología , Osteoartritis de la Columna Vertebral/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor trkA/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Escoliosis/inmunología , Escoliosis/metabolismo , Espondilolistesis/inmunología , Espondilolistesis/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven , Articulación Cigapofisaria/inmunología
5.
J Bone Joint Surg Br ; 88(4): 554-7, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16567796

RESUMEN

To clarify the pathomechanisms of discogenic low back pain, the sympathetic afferent discharge originating from the L5-L6 disc via the L2 root were investigated neurophysiologically in 31 Lewis rats. Sympathetic afferent units were recorded from the L2 root connected to the lumbar sympathetic trunk by rami communicantes. The L5-L6 discs were mechanically probed, stimulated electrically to evoke action potentials and, finally, treated with chemicals to produce an inflammatory reaction. We could not obtain a response from any units in the L5-L6 discs using mechanical stimulation, but with electrical stimulation we identified 42 units consisting mostly of A-delta fibres. In some experiments a response to mechanical probing of the L5-L6 disc was recognised after producing an inflammatory reaction. This study suggests that mechanical stimulation of the lumbar discs may not always produce pain, whereas inflammatory changes may cause the disc to become sensitive to mechanical stimuli, resulting in nociceptive information being transmitted as discogenic low back pain to the spinal cord through the lumbar sympathetic trunk. This may partly explain the variation in human symptoms of degenerate discs.


Asunto(s)
Disco Intervertebral/fisiopatología , Dolor de la Región Lumbar/fisiopatología , Neuronas Aferentes/fisiología , Sistema Nervioso Simpático/fisiopatología , Animales , Carragenina/farmacología , Discitis/fisiopatología , Estimulación Eléctrica , Potenciales Evocados/fisiología , Disco Intervertebral/efectos de los fármacos , Vértebras Lumbares , Masculino , Fibras Nerviosas/fisiología , Estimulación Física/métodos , Ratas , Ratas Endogámicas Lew , Raíces Nerviosas Espinales/fisiopatología , Estimulación Química
6.
Spine (Phila Pa 1976) ; 26(17): E395-8, 2001 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-11568716

RESUMEN

STUDY DESIGN: The case of patient with scoliosis based on a rare hamartomatous, Proteus syndrome, is reported. OBJECTIVES: To present the characteristics of scoliosis associated with Proteus syndrome, and to investigate the mechanisms that cause it. SUMMARY OF BACKGROUND DATA: Proteus syndrome, a rare hamartomatous disorder first coined by Wiedemann, manifests many clinical morphologic abnormalities including scoliosis. The characteristics and cause of scoliosis in this syndrome are fully unknown. METHODS: A patient with Proteus syndrome was followed from the age of 3 months to the age of 21 years. This patient received spinal corrective surgery for severe scoliosis. Detailed investigations of the scoliosis as well as the physical and imaging examinations were performed to characterize the scoliosis. RESULTS: Computed tomography showed exclusive asymmetric appearance of lumbar spine, hypertrophy of the only right facet joints, and pedicles at L1-L4, which accorded with the right-side hemihypertrophy of the patient's extremities. CONCLUSIONS: Scoliosis with Proteus syndrome seems to be based on hemihypertrophy, with no influence of mechanical stress.


Asunto(s)
Síndrome de Proteo/patología , Escoliosis/patología , Humanos , Hipertrofia , Lactante , Vértebras Lumbares/anomalías , Vértebras Lumbares/diagnóstico por imagen , Masculino , Síndrome de Proteo/complicaciones , Escoliosis/complicaciones , Escoliosis/cirugía , Tomografía Computarizada por Rayos X
7.
Spine (Phila Pa 1976) ; 26(8): 940-5, 2001 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-11317117

RESUMEN

STUDY DESIGN: This study was designed to investigate, using neurophysiologic techniques in an in vivo rat model, the effect of application of nucleus pulposus to the nerve root on the neural activity of the dorsal root ganglion and the corresponding receptive fields. OBJECTIVES: To assess a further role of the dorsal root ganglion in mechanisms of radicular pain in lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been suggested that the epidural application of autologous nucleus pulposus without mechanical compression causes nerve root inflammation and related radicular pain in lumbar disc herniation. Concerning the dorsal root ganglion, its mechanical hypersensitivity and potential for generating ectopic discharges have been reported. However, the effect of autologous nucleus pulposus on the dorsal root ganglion is uncertain. METHODS: In adult Sprague-Dawley rats spontaneous neural activity was recorded from the surgically exposed L5 dorsal root using electrophysiologic techniques, and the mechanosensitivity of L5 dorsal root ganglia and corresponding receptive fields on the hind paw were measured using calibrated nylon filaments. Autologous nucleus pulposus from the tail or fat was implanted at the L5 nerve root. Neural activity was monitored for 6 hours. RESULTS: Spontaneous neural activity in the nucleus pulposus group gradually increased and showed significant differences compared with the fat group from 2.5 to 6 hours after exposure. The mechanosensitivity of the dorsal root ganglia showed significant increases compared with the fat group. CONCLUSIONS: After application of nucleus pulposus to the nerve root, the dorsal root ganglion demonstrated increased excitability and mechanical hypersensitivity. These results suggest that nucleus pulposus causes excitatory changes in the dorsal root ganglion.


Asunto(s)
Ganglios Espinales/fisiopatología , Desplazamiento del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/fisiopatología , Disco Intervertebral/patología , Radiculopatía/fisiopatología , Animales , Electrofisiología , Ganglios Espinales/patología , Vértebras Lumbares , Masculino , Neuralgia/patología , Neuralgia/fisiopatología , Neuronas/fisiología , Radiculopatía/patología , Ratas , Ratas Sprague-Dawley , Umbral Sensorial
8.
Stapp Car Crash J ; 45: 101-42, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17458742

RESUMEN

The biomechanical response and injury tolerance of the shoulder in lateral impacts is not well understood. These data are needed to better understand human injury tolerance, validate finite element models and develop biofidelic shoulders in side impact dummies. Seventeen side impact sled tests were performed with unembalmed human cadavers. Data analyzed for this study include T1-Y acceleration, shoulder and thoracic load plate forces, upper sternum x and y accelerations, and struck side acromion x, y and z accelerations. One dimensional deflection at the shoulder level was determined from high-speed film by measuring the distance between a target on T1 and the impacted wall. Force-time response corridors were obtained for tests with 9 m/s pelvic offset, 10.5 m/s pelvic offset, 9 m/s unpadded flat wall, 6.7 m/s unpadded flat wall, 9 m/s soft padding and 9 m/s stiff padding. Maximum shoulder plate forces in unpadded 9 m/s tests (5.5 kN) were larger than in 6.7 m/s tests (3.3 kN). The peak force at the shoulder was larger than at the thorax plate in unpadded and soft padded tests. T1-Y accelerations were larger in unpadded 9 m/s flat wall tests and unpadded pelvic offset 10.5 m/s tests (peak values of 130 and 145 g's) than in other test conditions. Deflections between T1 and the struck wall ranged from 88 to 154 mm in unpadded tests and 95 to 128 mm in stiff and soft padded tests. Eighteen AIS 2 level shoulder injuries occurred in 11 test subjects. These injuries included left acromion fracture in five subjects, left acromioclavicular separation in ten subjects and left clavicle fracture in three subjects. Average MAIS to the shoulder was 0.86 in seven subjects which impacted 4 to 6 inches (101.6 to 152.4 mm) of soft or stiff padding and 1.6 in ten subjects which impacted no padding or 3 inches (76.2 mm) of stiff padding. Previous findings from this test series were reported by Irwin et al. (1993) for seven tests and focused on detailed analysis of shoulder deflection (T5 to shoulder edge). The current study is expanded to 17 tests and includes force, acceleration response and analysis of shoulder deflection (T1 to shoulder edge). Padding of 4 to 6 inches (101.6 mm to 152.4 mm) reduced shoulder injury approximately one AIS level. A combination of ASA10 and deflection was the best shoulder injury predictor. Shoulder deflection of 106 mm predicts 50% probability of MAIS 2.

9.
Spine (Phila Pa 1976) ; 23(12): 1297-306, 1998 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-9654618

RESUMEN

STUDY DESIGN: This study was designed to characterize the effects of phospholipase A2 on the neural response of dorsal root and dorsal root ganglion in the anesthetized New Zealand White rabbit. OBJECTIVES: To examine the effects of phospholipase A2 on the neural response of somatosensory neurons at the dorsal root ganglion level. SUMMARY OF BACKGROUND DATA: Phospholipase A2 may be an irritating component of disc tissue that is present in high concentration in painful herniated discs, in synovial fluids, and in sera of rheumatoid arthritis patients. Phospholipase A2 is inflammatory; however, its effects on dorsal roots and dorsal root ganglion response have never been demonstrated. METHODS: Surgically isolated dorsal roots and dorsal root ganglia from New Zealand White rabbits were investigated by electrophysiologic techniques. Phospholipase A2 doses ranging from 100 to 400 U were applied on the mechanically sensitive segments of the dorsal root ganglia, and responses to varying doses were evaluated in relation to elapsed time. RESULTS: The application of phospholipase A2 on the dorsal root ganglion resulted in possible neurotoxicity at doses more than 375 U, with no significant effect at lower doses except for recruitment of "silent units" at doses ranging from 200 to 340 U. CONCLUSIONS: Phospholipase A2 doses comparable to serum concentrations in human rheumatoid arthritis appeared to be neurotoxic when applied to dorsal root ganglia. At lower doses, silent units become activated that were not active before the phospholipase A2 application. These results suggest that dorsal roots and dorsal root ganglion may be impaired by phospholipase A2, leading to sciatica and low back pain.


Asunto(s)
Fosfolipasas A/toxicidad , Raíces Nerviosas Espinales/efectos de los fármacos , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Electrofisiología , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/fisiopatología , Masculino , Fosfolipasas A/administración & dosificación , Fosfolipasas A/farmacología , Fosfolipasas A2 , Conejos , Procesamiento de Señales Asistido por Computador , Raíces Nerviosas Espinales/fisiopatología
10.
Spine (Phila Pa 1976) ; 23(4): 403-11, 1998 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-9516694

RESUMEN

STUDY DESIGN: An immunocytochemical study of nerve fibers in lumbar spinal dura and longitudinal ligaments was conducted in New Zealand white rabbits. OBJECTIVES: To demonstrate the presence of nerve fibers and to establish the presence of nociceptive and sympathetic nerve fibers in lumbar dura and longitudinal ligaments. SUMMARY OF BACKGROUND DATA: The role of dura as a source of low back pain is still unclear, and the data present a somewhat conflicting picture of the nature of nociceptive innervation in this tissue. METHODS: An immunocytochemical method was used to study dura and longitudinal ligaments from New Zealand White rabbits. RESULTS: Numerous fine nerve fibers and some small bundles were demonstrated in both the dura and the longitudinal ligaments. In dorsal dura, the fibers were seen at lateral margins running toward midline. In ventral dura and longitudinal ligaments, the fibers were seen throughout the substance of these tissues. A population of substance P, calcitonin gene-related peptide, and tyrosine hydroxylase-reactive nerve fibers were observed in all the tissues. In addition, fibers exhibiting nicotinamide adenine dinucleotide phosphate diaphorase activity were also observed, indicating the presence of nitric oxide in dura. CONCLUSIONS: The results clearly demonstrate an extensive distribution of nerve fibers in dura and longitudinal ligaments. The presence of a significant number of putative nociceptive fibers supports a possible role for these structures as a source of low back pain and radicular pain.


Asunto(s)
Duramadre/metabolismo , Ligamentos/inervación , Médula Espinal/metabolismo , Columna Vertebral/inervación , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Femenino , Inmunohistoquímica , Región Lumbosacra , Masculino , NADPH Deshidrogenasa/metabolismo , Fibras Nerviosas/metabolismo , Conejos , Sustancia P/metabolismo , Tioléster Hidrolasas/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Ubiquitina Tiolesterasa
11.
Spine (Phila Pa 1976) ; 22(10): 1057-64, 1997 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-9160462

RESUMEN

STUDY DESIGN: To investigate the effects of phospholipase A2 on the neurophysiology and histology of rat lumbar spinal nerves and the corresponding behavioral changes. OBJECTIVES: To study possible mechanisms of sciatica. SUMMARY OF BACKGROUND DATA: The pathophysiology of sciatica is uncertain, although mechanical, chemical, and ischemic factors have been proposed. METHODS: Phospholipase A2 was injected into the rat L4-L5 epidural space, and the rats were observed for 3 or 21 days. Behavioral studies were conducted daily during the survival period. On the 3rd or 21st day, extracellular nerve recordings were made from dorsal roots, to determine discharge properties and mechanical sensitivity. The nerve roots were then sectioned for a light-microscopic examination. RESULTS: Motor weakness of hind limbs and altered sensation were observed. In the 3-day phospholipase A2 groups, squeezing the dorsal roots at the L4-L5 disc level (force = 0.8 g) evoked sustained ectopic discharge that lasted approximately 8 minutes. Squeezing the roots distal to the L4-L5 area did not result in sustained discharges. In sham, control, and 21-day phospholipase A2 groups, squeezing the dorsal roots elicited only a transient firing that lasted approximately 0.1 second. Loss of myelin was seen in the nerve root cross sections in the 3-day group, and remyelination was observed in the 21-day group. No abnormality was found in the control groups. CONCLUSIONS: Based on these studies, it is hypothesized that phospholipase A2 causes demyelination that results in hypersensitive regions where ectopic discharge may be elicited by mechanical stimulation. These ectopic discharges may be a source of sciatica. We believe that, as long as these irritating factors are present, the hypersensitive nerve root nerve will continue to fire, and sciatic pain will persist.


Asunto(s)
Fosfolipasas A/toxicidad , Ciática/inducido químicamente , Raíces Nerviosas Espinales/efectos de los fármacos , Animales , Enfermedades Desmielinizantes/inducido químicamente , Miembro Posterior/inervación , Desplazamiento del Disco Intervertebral/complicaciones , Masculino , Fosfolipasas A/farmacología , Fosfolipasas A2 , Ratas , Ratas Sprague-Dawley , Ciática/etiología , Ciática/fisiopatología , Raíces Nerviosas Espinales/fisiopatología
12.
Clin Pharmacol Ther ; 61(4): 450-8, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9129562

RESUMEN

The pharmacokinetics of lansoprazole, a new benzimidazole proton pump inhibitor, was evaluated after multiple-dose oral administration to 20 subjects with various degrees of kidney function. Multiple blood samples were obtained after doses 1 and 7 of the once-daily seven-dose regimen, and plasma concentrations of lansoprazole and five metabolites were quantitated with use of HPLC. The free fraction of lansoprazole increased as kidney function declined. A significant, although weak, relationship existed between creatinine clearance (CLCR) and area under the plasma concentration versus time curve (AUC) and terminal disposition half-life (t1/2), calculated with total concentration data. Those individuals with lower CLCR values also had lower total AUC and t1/2 values. However, there was no statistically significant relationship between CLCR and peak plasma concentration or AUC, calculated with unbound concentration data. No adjustment of lansoprazole dose is recommended on the basis of impaired kidney function.


Asunto(s)
Enfermedades Renales/fisiopatología , Riñón/fisiología , Omeprazol/análogos & derivados , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Anciano , Área Bajo la Curva , Estudios de Casos y Controles , Semivida , Humanos , Riñón/fisiopatología , Enfermedades Renales/sangre , Lansoprazol , Persona de Mediana Edad , Omeprazol/sangre , Omeprazol/farmacocinética , Unión Proteica , Índice de Severidad de la Enfermedad
13.
Clin Orthop Relat Res ; (335): 166-80, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9020216

RESUMEN

Idiopathic low back pain has confounded health care practitioners for decades. The cellular and neural mechanisms that lead to facet pain, discogenic pain, and sciatica are not well understood. To help elucidate these mechanisms, anesthetized New Zealand white rabbits were used in a series of neurophysiologic and neuroanatomic studies. These studies showed the following evidence in support of facet pain: an extensive distribution of small nerve fibers and endings in the lumbar facet joint, nerves containing substance P, high threshold mechanoreceptors in the facet joint capsule, and sensitization and excitation of nerves in facet joint and surrounding muscle when the nerves were exposed to inflammatory or algesic chemicals. Evidence for pain of disc origin included an extensive distribution of small nerve fibers and free nerve endings in the superficial annulus of the disc and small fibers and free nerve endings in adjacent longitudinal ligaments. Possible mechanisms of sciatica included vigorous and long lasting excitatory discharges when dorsal root ganglia were subjected to moderate pressure, excitation of dorsal root fibers when the ganglia were exposed to autologous nucleus pulposus, and excitation and loss of nerve function in nerve roots exposed to phospholipase A2.


Asunto(s)
Dolor de la Región Lumbar/fisiopatología , Animales , Disco Intervertebral/inervación , Articulaciones/inervación , Vértebras Lumbares , Masculino , Mecanorreceptores/fisiología , Terminaciones Nerviosas/fisiología , Conducción Nerviosa , Neuroanatomía/métodos , Neurofisiología/métodos , Conejos , Raíces Nerviosas Espinales/efectos de los fármacos , Raíces Nerviosas Espinales/fisiología , Sustancia P/fisiología
14.
J Biomech ; 29(9): 1117-29, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8872268

RESUMEN

Idiopathic low back pain has confounded health care practitioners for decades. Although there has been much advance in the understanding of the biomechanics of the lumbar spine over the past 25 years, the cellular and neural mechanisms that lead to facet pain are not well understood. An extensive series of experiments was undertaken to help elucidate these mechanisms and gain a better understanding of lumbar facet pain. Biomechanic and neuroanatomic studies were performed in human cadaveric facet joints and neurophysiologic studies were performed in New Zealand White rabbits. These studies provide the following evidence to help explain the mechanisms of lumbar facet pain: (1) The facet joint can carry a significant amount of the total compressive load on the spine when the human spine is hyperextended. (2) Extensive stretch of the human facet joint capsule occurs when the spine is in the physiologic range of extreme extension. (3) An extensive distribution of small nerve fibers and free and encapsulated nerve endings exists in the lumbar facet joint capsule, including nerves containing substance P, a putative neuromodulator of pain. (4) Low and high threshold mechanoreceptors fire when the facet joint capsule is stretched or is subject to localized compressive forces. (5) Sensitization and excitation of nerves in facet joint and surrounding muscle occur when the joint is inflamed or exposed to certain chemicals that are released during injury and inflammation. (6) Marked reduction in nerve activity occurs in facet tissue injected with hydrocortisone and lidocaine. Thus, the facet joint is a heavily innervated area that is subject to high stress and strain. The resulting tissue damage or inflammation is likely to cause release of chemicals irritating to the nerve endings in these joints, resulting in low back pain.


Asunto(s)
Vértebras Lumbares/patología , Vértebras Lumbares/fisiopatología , Sistema Nervioso/patología , Sistema Nervioso/fisiopatología , Dolor/fisiopatología , Analgésicos/farmacología , Animales , Antiinflamatorios/farmacología , Fenómenos Biomecánicos , Humanos , Inflamación/fisiopatología , Vértebras Lumbares/inervación , Masculino , Músculos/fisiología , Fibras Nerviosas Mielínicas/efectos de los fármacos , Fibras Nerviosas Mielínicas/fisiología , Sistema Nervioso/efectos de los fármacos , Fosfolipasas A/farmacología , Estimulación Física , Conejos , Sustancia P/farmacología , Soporte de Peso
15.
Spine (Phila Pa 1976) ; 21(5): 538-43, 1996 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-8852306

RESUMEN

STUDY DESIGN: Macroscopic and microscopic investigations of the human lumbar facet joint capsule were undertaken. OBJECTIVE: To describe the morphologic characteristics of the fibrous capsule of the lumbar facet joints. SUMMARY OF BACKGROUND DATA: Previous biomechanical and neurophysiologic studies by the authors have shown that the lumbar facet joint capsule may be a source of low back pain. METHODS: Macroscopic investigation was performed on the facet joint capsules dissected from five fresh adult cadavers. For microscopic studies, facet joint capsules obtained from cadaver dissection and spinal surgeries were stained by the hematoxylin and eosin method and the Elastica-Van Gieson method. RESULTS: The outer layer of the fibrous capsule is a dense regular connective tissue that is composed of parallel bundles of collagenous fibers. The inner layer of the fibrous capsule consists of bundles of elastic fibers, similar to the ligamentum flavum. In the superior and middle part of the joint, the fibers run in the medial to lateral direction, crossing over the joint gap. In the inferior part of the joint, the fibers are relatively long and run in a superior-medial to inferior-lateral direction, covering the inferior articular recess. They are thicker than the layer in the superior and middle parts of the joint. CONCLUSIONS: Anatomical and histologic features of the lumbar facet joint capsule are different between its outer layer and inner layer. This complex of morphologic factors can affect the biomechanics and neurophysiology of the lumbar facet joint.


Asunto(s)
Tejido Conectivo/anatomía & histología , Cápsula Articular/anatomía & histología , Vértebras Lumbares/anatomía & histología , Adulto , Cadáver , Colágeno/análisis , Tejido Elástico/anatomía & histología , Fibroblastos/citología , Humanos , Persona de Mediana Edad
16.
Spine (Phila Pa 1976) ; 20(24): 2659-68, 1995 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-8747244

RESUMEN

STUDY DESIGN: The present study was designed to characterize the effect of phospholipase A2 on the discharge of perispinal sensory nerves in the anesthetized New Zealand white rabbit. OBJECTIVES: To examine the effects of phospholipase A2 on the neural response of somatosensory neurons innervating the lumbar facet joint and surrounding tissues. SUMMARY OF BACKGROUND DATA: An irritating component of disc tissue may be phospholipase A2, which has been found at extraordinary high levels in herniated and painful discs. Phospholipase A2 has been shown to be inflammatory, but its effect on nerve response has never been shown. METHODS: Surgically isolated facet joint capsules from rabbits were investigated by means of electrophysiologic and histologic techniques. Phospholipase A2 was injected into the characterized nerve receptive field, and responses were evaluated over time with varying doses. RESULTS: The injection of phospholipase A2 into the nerve receptive fields produced neurotoxicity with a 1500-U dose, sensitization of the nerves and recruitment of "silent units" with a 750-U dose, and no electrophysiologic effect with a 400-U dose. The tissues injected with phospholipase A2 and control solutions were examined histologically using a hematoxylin and eosin staining technique. In all three doses, the inflammatory changes were observed as soon as 2 hours after the injections. In control subjects, no changes were observed. CONCLUSIONS: After phospholipase A2 injection, the discharge rate of the units showed dose and time dependent patterns. Regardless of the different doses, histologic changes were observed as soon as 2 hours after the phospholipase A2 injections.


Asunto(s)
Vértebras Lumbares/fisiología , Fosfolipasas A/farmacología , Nervios Espinales/enzimología , Anestésicos Locales/farmacología , Animales , Electrofisiología , Articulaciones/inervación , Articulaciones/fisiología , Lidocaína/farmacología , Vértebras Lumbares/química , Vértebras Lumbares/inervación , Masculino , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Neuronas/fisiología , Fosfolipasas A/metabolismo , Fosfolipasas A2 , Conejos , Nervios Espinales/efectos de los fármacos
17.
Spine (Phila Pa 1976) ; 20(19): 2080-5, 1995 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-8588162

RESUMEN

STUDY DESIGN: The present study sought to determine to what extent the lumbar intervertebral disc and posterior longitudinal ligament are innervated in the New Zealand white rabbit. The intent is to use this disc model in future neurophysiology studies. OBJECTIVE: To characterize the distribution of nerve fibers and endings in the lumbar intervertebral disc and posterior longitudinal ligament in an animal model. SUMMARY OF BACKGROUND DATA: The results of previous disc innervation reports are somewhat conflicting regarding the density and depth of innervation into the anulus. METHODS: A silver impregnation technique was used to analyze sections from lumbar intervertebral disc and posterior longitudinal ligament of the New Zealand white rabbit. RESULTS: Numerous fine profiles of nerve fibers were demonstrated in the lumbar disc anulus and posterior longitudinal ligament. In the disc, the nerves were limited to the superficial anulus and anular surface. The nerve axons typically were 1 to 3 microns in diameter and were found around the entire periphery of the disc. No encapsulated endings were seen within the anulus, while occasional encapsulated endings were seen on the anular surface and posterior longitudinal ligament. CONCLUSION: This study demonstrates an extensive distribution of small nerve fibers in the size range of C and A-delta fibers throughout the peripheral anulus and provides an illustration of this distribution. These findings support a role for the disc as a source of low back pain.


Asunto(s)
Disco Intervertebral/inervación , Ligamentos Longitudinales/inervación , Vértebras Lumbares/inervación , Conejos/anatomía & histología , Animales , Masculino , Terminaciones Nerviosas/ultraestructura , Fibras Nerviosas/ultraestructura , Fibras Nerviosas Mielínicas/ultraestructura
18.
Spine (Phila Pa 1976) ; 20(16): 1804-9, 1995 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-7502138

RESUMEN

This article discusses neuroanatomic and neurophysiologic bases for low back pain. Evidence for the existence of pain generators in facet, disc, muscle, nerve roots, and dorsal root ganglia are discussed. Mechanisms that may explain the persistence of pain, including neurogenic and non-neurogenic inflammation and central sensitization, are also presented.


Asunto(s)
Dolor de la Región Lumbar/etiología , Vértebras Lumbares/inervación , Terminaciones Nerviosas/fisiopatología , Animales , Humanos , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/fisiopatología , Vértebras Lumbares/patología , Terminaciones Nerviosas/patología
19.
J Clin Pharmacol ; 35(8): 815-20, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8522639

RESUMEN

The pharmacokinetics of the new benzimidazole proton pump inhibitor lansoprazole and five of its metabolites were assessed after single oral dose administration to five hemodialysis patients. Patients were studied on dialysis and nondialysis days. Multiple blood and dialysate samples were collected after dosing and were assayed for lansoprazole and metabolite content via high-performance liquid chromatography. The degree of lansoprazole plasma protein binding was lower in hemodialysis patients than in subjects with normal renal function or patients with renal impairment not requiring dialytic therapy, although this tended to moderate when assessed immediately after dialysis. Examination of venous plasma concentration, paired arterial-venous concentration, and dialysate data revealed that lansoprazole and its metabolites were poorly dialyzable. No dosage adjustment of lansoprazole is necessary in hemodialysis patients nor is supplementation after hemodialysis sessions necessary.


Asunto(s)
Antiulcerosos/farmacocinética , Omeprazol/análogos & derivados , Inhibidores de la Bomba de Protones , Diálisis Renal , 2-Piridinilmetilsulfinilbencimidazoles , Administración Oral , Adulto , Antiulcerosos/administración & dosificación , Antiulcerosos/sangre , Cromatografía Líquida de Alta Presión , Soluciones para Diálisis/análisis , Esquema de Medicación , ATPasa Intercambiadora de Hidrógeno-Potásio/sangre , Humanos , Lansoprazol , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/sangre , Omeprazol/farmacocinética , Unión Proteica
20.
Neurosci Res ; 20(4): 355-64, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7870388

RESUMEN

The effects of experimentally induced inflammation of the lumbar facet joint capsule and adjacent tissues were investigated electrophysiologically and histologically. Type II carrageenan was injected into the receptive fields innervated by identified mechanosensitive afferent units. The multi-unit spontaneous background discharge rate showed increases that consisted of two phases over a time period of 150 min: the first phase (0-30 min) and the second phase (45-150 min). The time course of single units, identified as groups II, III and IV, and silent units, was also investigated. The silent unit discharge rates displayed a gradual increase in the first 15 min and persisted beyond 75 min. Histological examination revealed inflammatory changes in carrageenan injected tissues. In contrast, in isotonic saline injected control experiments there were no changes observed in the electrophysiological or histological studies. This study shows the effects of inflammation in rabbit lumbar facet joint capsule and adjacent tissues. The electrophysiological results show that inflammation of the facet joint and deep back muscles causes (1) increases in multi-unit discharge rate, (2) sensitization to mechanical stimuli and (3) recruitment of previously silent units. Inflammatory changes were also demonstrated histologically.


Asunto(s)
Artritis/inducido químicamente , Carragenina , Cápsula Articular/fisiopatología , Enfermedades de la Columna Vertebral/inducido químicamente , Animales , Artritis/complicaciones , Artritis/fisiopatología , Dolor de Espalda/etiología , Umbral Diferencial , Electrofisiología , Cápsula Articular/inervación , Cápsula Articular/patología , Región Lumbosacra , Masculino , Mecanorreceptores/fisiopatología , Conducción Nerviosa , Neuronas Aferentes/fisiología , Conejos , Enfermedades de la Columna Vertebral/patología , Enfermedades de la Columna Vertebral/fisiopatología , Columna Vertebral/inervación , Factores de Tiempo
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