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1.
Oncogene ; 33(20): 2665-73, 2014 May 15.
Article in English | MEDLINE | ID: mdl-23752194

ABSTRACT

Non-small-cell lung carcinoma (NSCLC) is among the deadliest of human cancers. The CDKN2A locus, which houses the INK4a and ARF tumor suppressor genes, is frequently altered in NSCLC. However, the specific role of ARF in pulmonary tumorigenesis remains unclear. KRAS and other oncogenes induce the expression of ARF, thus stabilizing p53 activity and arresting cell proliferation. To address the role of ARF in Kras-driven NSCLC, we compared the susceptibility of NIH/Ola strain wild-type and Arf-knockout mice to urethane-induced lung carcinogenesis. Lung tumor size, malignancy and associated morbidity were significantly increased in Arf(-/-) compared with Arf(+/+) animals at 25 weeks after induction. Pulmonary tumors from Arf-knockout mice exhibited increased cell proliferation and DNA damage compared with wild-type mice. A subgroup of tumors in Arf(-/-) animals presented as dedifferentiated and metastatic, with many characteristics of pulmonary sarcomatoid carcinoma, a neoplasm previously undocumented in mouse models. Our finding of a role for ARF in NSCLC is consistent with the observation that benign adenomas from Arf(+/+) mice robustly expressed ARF, while ARF expression was markedly reduced in malignant adenocarcinomas. ARF expression also frequently colocalized with the expression of p21(CIP1), a transcriptional target of p53, arguing that ARF induces the p53 checkpoint to arrest cell proliferation in vivo. Taken together, these findings demonstrate that induction of ARF is an early response in lung tumorigenesis that mounts a strong barrier against tumor growth and malignant progression.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Cyclin-Dependent Kinase Inhibitor p16/physiology , Lung Neoplasms/pathology , Animals , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Damage/physiology , Disease Progression , Genes, ras , Mice , Mice, Knockout , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Tumor Suppressor Protein p53/metabolism
2.
Oncogene ; 28(41): 3652-62, 2009 Oct 15.
Article in English | MEDLINE | ID: mdl-19648963

ABSTRACT

Reduced expression of the CDK inhibitor p27(Kip1) (p27) in human lung cancer correlates with tumor aggressiveness and poor prognosis. However, the regulation of p27 expression and the role of p27 during lung cancer are poorly understood. Urethane-induced lung tumors in mice frequently harbor mutations in the Kras oncogene, and in this study, we use this model to address the regulation of p27 during tumorigenesis. The Ras effector Akt is known to regulate p27 mRNA abundance by phosphorylating and inactivating the FOXO transcription factors. Phosphorylated Akt and FOXO proteins were both increased in lung tumors, correlating with a reduction in p27 mRNA transcript. Akt also directly phosphorylates p27 and regulates its nuclear/cytoplasmic localization. Tumors showed a reduced nuclear/cytoplasmic ratio of p27 protein, together with an increase in phosphorylated Thr197 p27 in the cytoplasmic pool. Treatment of lung tumor-bearing mice with the phosphoinositol-3 kinase inhibitor LY294002 induced a rapid decrease in phosphorylated Akt and phosphorylated p27, concomitant with an increase in nuclear p27. Germline p27 deficiency accelerated both the growth and malignant progression of urethane-induced lung tumors, and did so in a cell autonomous manner, confirming a causal role of p27 in tumor suppression. These results show that p27 is a potent barrier to the growth and malignant progression of Kras-initiated lung tumors. Further, the reduction of nuclear p27 in tumors is mediated by oncogene signaling pathways, which can be reversed by pharmacological agents.


Subject(s)
Cell Nucleus/drug effects , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/genetics , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins p21(ras)/metabolism , Animals , Carcinoma, Non-Small-Cell Lung/chemically induced , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Nucleus/genetics , Cell Nucleus/metabolism , Chromones/pharmacology , Cyclin-Dependent Kinase Inhibitor p27/deficiency , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Humans , Lung Neoplasms/chemically induced , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Mice , Morpholines/pharmacology , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Urethane/pharmacology
3.
Oncogene ; 27(22): 3145-55, 2008 May 15.
Article in English | MEDLINE | ID: mdl-18059331

ABSTRACT

The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cyclin-Dependent Kinase Inhibitor p16/physiology , Lymph Nodes/physiology , Lymphangiogenesis/genetics , Lymphatic Metastasis , Skin Neoplasms/pathology , Tumor Suppressor Protein p53/physiology , 9,10-Dimethyl-1,2-benzanthracene , Animals , B-Lymphocytes/pathology , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/genetics , Cell Proliferation , Chemotaxis, Leukocyte/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Macrophages/pathology , Mice , Mice, Transgenic , Neovascularization, Pathologic/genetics , Skin Neoplasms/blood supply , Skin Neoplasms/chemically induced , Skin Neoplasms/genetics , Tetradecanoylphorbol Acetate , Tumor Suppressor Protein p53/genetics , Vascular Endothelial Growth Factor A/metabolism
4.
J Bone Joint Surg Br ; 86(6): 876-86, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15330030

ABSTRACT

Untreated acetabular dysplasia following treatment for developmental dysplasia of the hip (DDH) leads to early degenerative joint disease. Clinicians must accurately and reliably recognise dysplasia in order to intervene appropriately with secondary acetabular or femoral procedures. This study sought early predictors of residual dysplasia in order to establish empirically-based indications for treatment. DDH treated by closed or open reduction alone was reviewed. Residual hip dysplasia was defined according to the Severin classification at skeletal maturity. Future hip replacement in a subset of these patients was compared with the Severin classification. Serial measurements of acetabular development and subluxation of the femoral head were collected, as were the age at reduction, type of reduction, and Tonnis grade prior to reduction. These variables were used to predict the Severin classification. The mean age at reduction in 72 hips was 16 months (1 to 46). On the final radiograph, 47 hips (65%) were classified as Severin I/II, and 25 as Severin III/IV (35%). At 40 years after reduction, five of 43 hips (21%) had had a total hip replacement (THR). The Severin grade was predictive for THR. Early measurements of the acetabular index (AI) were predictive for Severin grade. For example, an AI of 35 degrees or more at two years after reduction was associated with an 80% probability of becoming a Severin grade III/IV hip. This study links early acetabular remodelling, residual dysplasia at skeletal maturity and the long-term risk of THR. It presents evidence describing the diagnostic value of early predictors of residual dysplasia, and therefore, of the long-term risk of degenerative change.


Subject(s)
Acetabulum , Bone Diseases, Developmental/etiology , Hip Dislocation, Congenital/therapy , Adult , Arthroplasty, Replacement, Hip/statistics & numerical data , Bone Remodeling/physiology , Child, Preschool , Female , Follow-Up Studies , Hip Dislocation, Congenital/diagnostic imaging , Hip Dislocation, Congenital/physiopathology , Humans , Infant , Male , Radiography , Recurrence , Retreatment , Risk Factors
5.
Eur Spine J ; 13(1): 14-21, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14658061

ABSTRACT

This study was designed to develop predictive models for surgical outcome based on information available prior to lumbar stenosis surgery. Forty patients underwent decompressive laminarthrectomy. Preop and 1-year postop evaluation included Waddell's nonorganic signs, CT scan, Waddell disability index, Oswestry low back pain disability questionnaire, low back outcome score (LBOS), visual analog scale (VAS) for pain intensity, and trunk strength testing. Statistical comparisons of data used adjusted error rates within families of predictors. Mathematical models were developed to predict outcome success using stepwise logistic regression and decision-tree methodologies (chi-squared automatic interaction detection, or CHAID). Successful outcome was defined as improvement in at least three of four criteria: VAS, LBOS, and reductions in claudication and leg pain. Exact logistic regression analysis resulted in a three-predictor model. This model was more accurate in predicting unsuccessful outcome (negative predictive value 75.0%) than in successful outcome (positive predictive value 69.6%). A CHAID model correctly classified 90.1% of successful outcomes (positive predictive value 85.7%, negative predictive value 100%). The use of conservative surgical decompression for lumbar stenosis can be recommended, as it demonstrated a success rate similar to that of more invasive techniques. Given its physiologic and biomechanical advantages, it can be recommended as the surgical method of choice in this indication. Underlying subclinical vascular factors may be involved in the complaints of spinal stenosis patients. Those factors should be investigated more thoroughly, as they may account for some of the failures of surgical relief. The CHAID decision tree appears to be a novel and useful tool for predicting the results of spinal stenosis surgery


Subject(s)
Decompression, Surgical , Lumbar Vertebrae/surgery , Spinal Stenosis/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Biomechanical Phenomena , Chi-Square Distribution , Female , Follow-Up Studies , Humans , Laminectomy , Logistic Models , Low Back Pain/epidemiology , Low Back Pain/physiopathology , Low Back Pain/surgery , Male , Middle Aged , Patient Dropouts , Predictive Value of Tests , Risk Factors , Spinal Stenosis/epidemiology , Spinal Stenosis/physiopathology , Treatment Outcome
6.
Eur Respir J ; 22(4): 613-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14582913

ABSTRACT

Some asthma patients and physicians who treat asthma have reported that stress worsens their disease. It has also recently been shown that chronic stressful life events increase airway inflammation 6-24 h after inhalation of antigen in patients with allergic asthma. However, there is no data regarding the effect of an acute stressor on the airway constriction that occurs within minutes of antigen inhalation (early pulmonary response) in this same population. The aim of this study was to examine this effect in eight females with allergic asthma. Each subject was challenged with increasing concentrations of inhaled allergen on a control visit (no stress) and on a stress visit, when they were asked to verbally recount an emotionally stressful situation between each concentration. Systolic (SP) and diastolic (DP) blood pressure, cardiac frequency (fC) and forced expiratory volume in one second (FEV1) were measured on both visits. SP, DP and fC were statistically increased on the stress visit as compared to control. Per cent decrease in FEV1 at the same last dose of allergen was significantly less on the stress visit (11.2 +/- 7.0%) compared to control (15.0 +/- 8.7%). These findings suggest that the early pulmonary response to inhaled allergen is attenuated while verbally re-experiencing an acute emotional stressor in females with allergic asthma.


Subject(s)
Asthma/immunology , Asthma/psychology , Bronchial Hyperreactivity/immunology , Bronchial Hyperreactivity/psychology , Stress, Psychological/immunology , Acute Disease , Adult , Allergens , Bronchial Hyperreactivity/chemically induced , Bronchial Provocation Tests , Female , Forced Expiratory Volume , Humans , Time Factors
7.
J Spinal Disord Tech ; 16(3): 261-7, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12792340

ABSTRACT

This is a prospective study analyzing CT scan imaging outcomes after conservative decompression in patients with lumbar spinal stenosis. Forty patients (18 males and 22 females) initially underwent a laminarthrectomy surgical procedure to decompress the central canal as well as the neuroforamina and nerve root canals while respecting the integrity of the neural arches, facet joints, and most muscle attachments. Morphologic features of preoperative CT scan images were compared with postoperative CT scans of the operative levels, obtained for 36 patients (17 males and 19 females) after a minimum follow-up of 1 year (mean 1.7 years). Successful surgical outcome was defined as an improvement in at least three of the following four criteria: self-reported pain on a visual analog scale, self-reported functional status measured by LBOS, reduction of pain while walking, and reduction of leg pain. Fifty-five percent of patients met the successful surgical outcome criteria, including 14 subjects who met all four success criteria. Overall, there was a statistically significant increase in the interfacet bony canal diameter of the operated levels (3.9 mm, p < 001). However, patients categorized as successful surgical outcomes had a substantially, but not significantly, lower interfacet canal diameter increase postsurgically (mean 3.41 mm) in comparison with patients categorized as failures (mean postoperative increase 4.52 mm). Midsagittal canal diameters remained unchanged in the failure group but increased in the success group. The CT scan canal measures used in this study cannot be advocated for evaluation of outcome in conservative lumbar spinal canal decompression.


Subject(s)
Decompression, Surgical/methods , Risk Assessment/methods , Spinal Stenosis/diagnostic imaging , Spinal Stenosis/surgery , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Male , Middle Aged , Postoperative Care , Predictive Value of Tests , Preoperative Care , Treatment Failure , Treatment Outcome
8.
J Neurophysiol ; 90(4): 2548-59, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12801892

ABSTRACT

In the appendicular skeleton, substantial evidence demonstrates that somatosensory input from deep tissues including limb muscles and joints elicits somatosympathetic reflexes. Much less is known about the presence and organization of these reflexes from the axial skeleton. We determined if mechanical loading of the lumbar spine and lumbar paraspinal muscle irritation reflexively affects postganglionic sympathetic nerve discharge (SND) to the spleen and kidney. In 27 alpha-chloralose-anesthetized cats, the L2-4 multifidus muscles were injected with the inflammatory irritant mustard oil (20%, 60 microl total) and a vertebral load (100% body weight) was applied dorsal-ventral at the L3 spinous process. Mustard oil injection alone without vertebral loading (n = 7) increased mean splenic SND (60%), renal SND (30%), and heart rate (HR; 52 bpm). Mustard oil injection accompanied by the vertebral load (n = 7) increased mean splenic SND (55%), renal SND (16%), and HR (27 bpm). Blood pressure changes were biphasic and could not account for these changes. When the vertebral load accompanied mustard oil, the increases in splenic SND, renal SND, and HR remained elevated in a pattern significantly different from when the vertebral load was absent. Vehicle injection combined with the mechanical load (n = 3) did not change any of the autonomic responses. Similarly, mustard oil injection combined with a mechanical load did not change these responses when either the medial branches of the dorsal rami from T11-L5 had been cut (n = 4) or when the spinal cord had been transected between the second and third cervical vertebrae (n = 6). The results indicate that inflammatory stimulation of multifidus muscle in the low back evokes a somatosympathetic reflex integrated supraspinally in the upper cervical spinal cord or higher. The reflex's afferent arm travels in the medial branch of the dorsal ramus, and its efferent arm can affect sympathetic outflow to the spleen and the kidney as well as HR and BP. A static mechanical load applied to the lumbar spine accompanying the inflammatory stimulus appears to sustain the inflammatory-induced reflex activity.


Subject(s)
Anesthesia/methods , Reflex/physiology , Spinal Cord/physiology , Sympathetic Fibers, Postganglionic/physiology , Animals , Cats , Chemoreceptor Cells/drug effects , Chemoreceptor Cells/physiology , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiology , Lumbosacral Region/physiology , Mustard Plant , Plant Extracts/toxicity , Plant Oils , Reflex/drug effects , Spinal Cord/drug effects , Spinal Cord Injuries/physiopathology , Sympathetic Fibers, Postganglionic/drug effects , Weight-Bearing/physiology
9.
Eur Spine J ; 12(2): 197-204, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12709858

ABSTRACT

Less invasive decompressive surgery has emerged as a logical surgical treatment alternative to wide decompression of spinal stenosis. The clinical outcomes of such conservative surgical treatment, however, are not well known. The aim of the study was to evaluate short-term psychometric and functional outcomes after conservative decompressive surgery for lumbar canal stenosis. Forty patients had a lumbar laminectomy procedure, which preserved the integrity of the neural arches, facet joints and most muscle attachments. Pre-operative clinical evaluation of the patients included: Waddell's non-organic signs (NOS) performed by an independent surgeon observer; three self-report questionnaires--the Waddell Disability Index (WDI), the Oswestry Low Back Pain Disability Questionnaire (ODI), and the Low Back Outcome Score (LBOS); and a general questionnaire that included a visual analog pain intensity scale (VAS). Post-operative clinical evaluations and questionnaires were obtained in 36 subjects (mean age 59.8 years) after a 1.7-year follow-up (range 1-2.6 years). Pre-operative versus post-operative statistical comparisons of the data were performed using adjusted error rates within families of predictors. Successful surgical outcome was defined as an improvement in at least three of the following four criteria: self-reported pain on a VAS, self-reported functional status measured by LBOS, reduction of pain during walking and reduction of leg pain. At follow-up, there was a statistically significant improvement in VAS pain intensity, ODI, WDI, and LBOS. Patients classified as having mixed stenosis had a higher incidence of continuous pain symptoms in comparison with acquired stenosis, but there was no differential improvement with treatment depending upon stenosis classification and/or number of operative levels. Overall, 58% (21/36) of patients met the successful surgical outcome criteria, including 14 subjects who met all four success criteria. Based upon a stringent definition of successful surgical outcome, the results of a conservative laminectomy were as good as those of more aggressive decompressive procedures presented in the literature. Our findings indicate that, even in a highly organic disorder such as spinal stenosis, illness behavior plays an important role in predicting surgical outcome.


Subject(s)
Decompression, Surgical , Laminectomy , Spinal Stenosis/physiopathology , Spinal Stenosis/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Disability Evaluation , Female , Follow-Up Studies , Humans , Lumbosacral Region/surgery , Male , Middle Aged , Pain/etiology , Patient Satisfaction , Prospective Studies , Spinal Stenosis/complications , Treatment Outcome
11.
Clin Orthop Relat Res ; (390): 151-62, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11550861

ABSTRACT

Lumbar radiographs of 120 adolescent elite skiers were evaluated for radiologic abnormalities by two independent observers. All athletes had no symptoms before the study. Radiographs were taken before enrollment of the students in elite level training. To determine the clinical significance of these abnormalities, all athletes were observed prospectively during the subsequent 2-year period for development of low back pain under high performance training. Anterior end plate lesions, Schmorl's nodes, posterior end plate lesions, spondylolysis, scoliosis, and spina bifida occulta were found. The depth of anterior end plate lesions showed a two-peak distribution, with peaks at 11% and 22% and a valley at 18% vertebral body height. The overall low back pain incidence was 12.5%. Students with severe anterior lesions (greater than 18% vertebral body height, n = 25) had significantly more low back pain (incidence, 32%) than did students without severe anterior lesions (incidence, 7.4%). Accordingly, students with severe anterior lesions had a significantly higher risk of having low back pain develop. Moderate end plate lesions and other abnormalities were not related to an increased incidence of low back pain. Adolescent students of elite sports with severe lumbar anterior end plate lesions have an increased risk of having low back pain develop under high performance training.


Subject(s)
Low Back Pain/diagnostic imaging , Skiing/injuries , Adolescent , Adult , Female , Humans , Low Back Pain/epidemiology , Male , Prospective Studies , Radiography , Time Factors
12.
Int J Sports Med ; 22(6): 414-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11531033

ABSTRACT

Use of modified shoes and insole materials has been widely advocated to treat low back symptoms from running impacts, although considerable uncertainty remains regarding the effects of these devices on the rate of shock transmission to the spine. This study investigated the effects of shoes and insole materials on a) the rate of shock transmission to the spine, b) the temporal response of spinal musculature to impact loading, and c) the time interval between peak lumbar acceleration and peak lumbar muscle response. It was hypothesised that shoes and inserts a) decrease the rate of shock transmission, b) decrease the low back muscle response time, and c) shorten the time interval between peak lumbar acceleration and peak lumbar muscle response. Twelve healthy subjects were tested while jogging barefoot (unshod) or wearing identical athletic shoes (shod). Either no material, semi-rigid (34 Shore A), or soft (9.5 Shore A) insole material covered the force plate in the barefoot conditions and was placed as insole when running shod. Ground reaction forces, acceleration at the third lumbar level, and erector spinae myoelectric activity were recorded simultaneously. The rate of shock transmission to the spine was greater (p < 0.0003) unshod (acceleration rate: Means +/- SD 127.35 +/- 87.23 g/s) than shod (49.84 +/- 33.98 g/s). The temporal response of spinal musculature following heel strike was significantly shorter (p < 0.023) unshod (0.038 +/- 0.021 s) than shod (0.047 +/- 0.036 s). The latency between acceleration peak (maximal external force) and muscle response peak (maximal internal force) was significantly (p < 0.021) longer unshod (0.0137 +/- 0.022s) than shod (0.004 +/- 0.040 s). These results suggest that one of the benefits of running shoes and insoles is improved temporal synchronization between potentially destabilizing external forces and stabilizing internal forces around the lumbar spine.


Subject(s)
Jogging/physiology , Lumbosacral Region/physiology , Muscle, Skeletal/physiology , Shoes , Sports Equipment , Acceleration , Adult , Analysis of Variance , Biomechanical Phenomena , Female , Heel/physiology , Humans , Male , Reference Values
13.
Spine (Phila Pa 1976) ; 26(14): 1613-22, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11464157

ABSTRACT

STUDY DESIGN: The Boeing prospective study was reviewed. The Boeing prospective study, comprising two articles, was a large field study that explored why workers would or would not report occupational back pain problems. OBJECTIVES: The most immediate objective was to determine the extent to which conclusions drawn from the Boeing prospective study withstand critical examination. The ultimate purpose of this review was to develop guidelines for field studies of back pain in industry. SUMMARY OF BACKGROUND DATA: For more than a century, researchers have noted great variability among individuals in the reporting of back pain, but the explanations posed for this variability have been inconsistent. Because findings gain credibility roughly to the extent that they bear on the world outside the laboratory, field studies in particular hold great potential for clarifying the underlying explanation for individual variability in back pain reporting. The Boeing prospective study was a large and ambitious field study that examined this issue. METHODS: The Boeing prospective study was examined through the lens of research conducted since it was published. The review used both the methodological and substantive literature. RESULTS: The Boeing prospective study, based on a minority of workers originally solicited to participate in it (33-41%), accounted for 7% of the variation in why workers would or would not report a back pain problem. A number of issues that may have biased its results toward the null are examined. CONCLUSIONS: The highlighting of the Boeing prospective study's limitations may be instructive not so much to criticize this one particular study but, rather, to anticipate problems that in general may be encountered in field studies of back pain in industry. Looking beyond the Boeing prospective study, the following guidelines for the conduct of such studies may be proposed: 1) Study designs should be based on explanations from which testable hypotheses may be derived; 2) Subgroups within the more general category of "back pain" should be delineated; 3) Both occupational exposures and psychosocial factors should be entered into the analysis; 4) Factors not apparent at the workplace should be considered; 5. Abstracts of articles should be carefully crafted.


Subject(s)
Back Pain/psychology , Occupational Diseases/psychology , Patient Acceptance of Health Care/psychology , Guidelines as Topic , Humans , MEDLINE , Occupational Health , Prospective Studies
14.
Spine (Phila Pa 1976) ; 26(4): E38-49, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11224899

ABSTRACT

STUDY DESIGN: Immature Chacma baboon (Papio ursinus) spine specimens were used to determine load-displacement behavior as related to disc injury. This was accomplished through the application of A-P shear force until failure of FSUs with pars defects. Several finite element models (FEMs) of the FSU were developed to study the mechanism of slippage in immature baboon lumbar spines. OBJECTIVES: The purpose was to show that spondylolisthesis (olisthesis) always occurs through the growth plate using a model similar to immature human lumbar spines. Using FEMs, the roles of facet orientation, pars interarticularis thickness, and a weak growth-plate in producing slippage were examined. SUMMARY OF BACKGROUND DATA: Progression from spondylolysis (lysis) to olisthesis occurs, most often, during the adolescent growth spurt. The biomechanical literature dealing with the slippage mechanism in the immature lumbar spine does not provide a clear understanding and is sparse. METHODS: Several groups of FSUs were subjected to A-P shear force until failure. The results provided displacement at failure as a function of disc injury and flexion-extension fatigue. A bilateral pars defect was created in each specimen prior to application of A-P shear force using an MTS machine. Failure sites were assessed radiographically and histologically. A nonlinear 3-D FEM of the intact L4-L5 was created from CT scans. The model was modified to predict the effects of a pars fracture, a thin pars, a weak growth plate, and facet orientation on the shear load through the growth plate and stresses in the pars. RESULTS: Experimentally, failures always occurred through the growth-plate in the disc intact and disc-incised groups. In the intact FEM, the growth plate carried21% of the applied A-P shear force. The load increased when the facets were more sagittally oriented. The effect of thin pars and/or weaker growth plate was an increase in stresses in the pars. Changes in the load through the growth plate were minimal. CONCLUSIONS: The weakest link in immature baboon lumbar functional spinal units (FSUs) with lysis during an A-P shear load was the growth plate, between the cartilaginous and osseous end plates. Surgeons may assess this lesion on MRI views, thereby predicting the possible development and preventing progression of olisthesis. Finite element model results predict that more sagittally orientated facets and/or a pars fracture are prerequisites for olisthesis to occur.


Subject(s)
Intervertebral Disc Displacement/etiology , Intervertebral Disc/injuries , Lumbar Vertebrae/injuries , Papio/growth & development , Spondylolisthesis/etiology , Spondylolysis/complications , Age Factors , Animals , Disease Models, Animal , Female , Intervertebral Disc/growth & development , Intervertebral Disc/physiopathology , Intervertebral Disc Displacement/pathology , Intervertebral Disc Displacement/physiopathology , Lumbar Vertebrae/growth & development , Lumbar Vertebrae/physiopathology , Male , Papio/anatomy & histology , Papio/physiology , Spondylolisthesis/pathology , Spondylolisthesis/physiopathology , Spondylolysis/pathology , Spondylolysis/physiopathology , Weight-Bearing/physiology
15.
J Manipulative Physiol Ther ; 23(4): 252-7, 2000 May.
Article in English | MEDLINE | ID: mdl-10820298

ABSTRACT

INTRODUCTION: Many devices have been marketed claiming to increase the mobility of the articulations of the spine with active or passive distraction. In this study, the Rola Stretcher (Unique Relief, Inc, Davenport, Iowa) and an earlier version, the True Back II (True Back, Inc, Clearwater, Fla), were evaluated to see if they have a measurable biomechanic effect on the spine. METHODS: Two studies were conducted, each with 6 male participants and 6 female participants, using a stadiometer to accurately measure a person's sitting height. The increase in sitting height after using the True Back II or Rola Stretcher for 10 minutes was compared with that after lying supine for 10 minutes. A third intervention, a firm foam block cut to the same size and shape as the True Back II, was also used in this study. RESULTS: The Rola Stretcher had a significantly greater lengthening effect on the spine compared with supine rest (P <0050). The True Back II had a similar but lesser effect (P <.0509). Women demonstrated a greater height gain than men. CONCLUSION: The True Back II and the Rola Stretcher in particular appear to lengthen the spine after a single use of 10 minutes. The observed discrepancy between the effects in men and women may be an experimental artifact occurring as a result of less effective resetting of the posturing mechanisms in men compared with women. A trend showed the Rola Stretcher to be more effective than the foam block.


Subject(s)
Manipulation, Spinal/instrumentation , Motion Therapy, Continuous Passive/instrumentation , Spinal Diseases/rehabilitation , Adult , Biomechanical Phenomena , Equipment Design , Equipment Safety , Female , Humans , Male , Middle Aged , Probability , Reference Values , Treatment Outcome
16.
Spine (Phila Pa 1976) ; 24(21): 2206-13, 1999 Nov 01.
Article in English | MEDLINE | ID: mdl-10562985

ABSTRACT

STUDY DESIGN: An in vitro test of calf spine lumbar segments to compare biomechanical stabilization of a rigid versus a dynamic posterior fixation device. OBJECTIVES: To compare flexibility of a dynamic pedicle screw fixation device with an equivalent rigid device. SUMMARY OF BACKGROUND DATA: Dynamic pedicle screw device studies are not as prevalent in the literature as studies of rigid devices. These devices contain the potential to enhance load sharing and optimize fusion potential while maintaining stability similar to that of rigid systems. METHODS: Load-displacement tests were performed on intact and stabilized calf spines for the dynamic and rigid devices. Stability across a destabilized L3-L4 segment was restored by insertion of either a 6 mm x 40 mm dynamic or rigid pedicle screw fixation device across the L2-L4 segment. The screws then were removed, 7 mm x 45 mm pedicle screws of the opposite type were inserted, and the construct then was re-tested. Axial pull-out tests were performed to assess the likely effects of pedicle screw replacement on the load-displacement data. RESULTS: Results indicated a 65% reduction in motion in flexion-extension and a 90% reduction in lateral bending across the destabilized level for both devices, compared with intact spine values. Reduction in axial rotation motion was much smaller than in other modes. Axial pull-out tests showed no weakening of the bone-screw interface. CONCLUSIONS: Both devices provided significant stability of similar magnitudes in flexion, extension, and lateral bending. In axial rotation, the devices only could restore stability to levels similar to those in an intact spine. The dynamic device offers a design that may enhance load sharing without sacrificing construct stability.


Subject(s)
Bone Screws , Lumbar Vertebrae/surgery , Weight-Bearing , Animals , Cattle , Materials Testing , Torsion Abnormality/surgery
17.
J Bone Joint Surg Am ; 81(9): 1209-16, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10505517

ABSTRACT

BACKGROUND: Researchers and clinicians commonly use the classification system of Stulberg et al. as a basis for treatment decisions during the active phase of Legg-Calvé-Perthes disease because of its putative utility as a predictor of long-term outcome. It is generally assumed that this system has an acceptable degree of reliability. This assumption, however, is not convincingly supported by the literature. METHODS: The purpose of the present study was to assess the inter-rater and intra-rater reliability of the classification system of Stulberg et al. with use of a pre-test, post-test design. During the pre-test phase, nine raters independently used the system to evaluate the radiographs of skeletally mature patients who had been managed for Legg-Calvé-Perthes disease. The intervention between the pre-test and post-test phases consisted of a consensus-building session during which all raters jointly arrived at standardized definitions of the various joint structures that are assessed with use of the classification system. The effect of these definitions on reliability then was assessed by reevaluating the radiographs during the post-test phase. RESULTS: The pre-test intra-rater reliability coefficients ranged from 0.709 to 0.915, and the post-test coefficients ranged from 0.568 to 0.874. The pre-test inter-rater reliability coefficients ranged from 0.603 to 0.732, and the post-test coefficients ranged from 0.648 to 0.744. Contributing to the variance was a lack of agreement concerning the assessment of joint structures and the way in which the raters translated these evaluations into a classification according to the system of Stulberg et al. CONCLUSIONS: Although intra-rater reliability was marginally acceptable, the degree of variability between the classifications assigned by different raters even after the intervention - calls into question the reliability of the system of Stulberg et al.; consequently, the validity of any treatment decisions, outcome evaluations, or epidemiological studies based on this system is also in question.


Subject(s)
Legg-Calve-Perthes Disease/classification , Acetabulum/diagnostic imaging , Algorithms , Femur Head/diagnostic imaging , Femur Neck/diagnostic imaging , Humans , Internship and Residency , Legg-Calve-Perthes Disease/diagnostic imaging , Legg-Calve-Perthes Disease/surgery , Observer Variation , Orthopedics/education , Radiography , Reproducibility of Results
18.
Eur Spine J ; 8(3): 170-8, 1999.
Article in English | MEDLINE | ID: mdl-10413341

ABSTRACT

Lifting restrictions postoperatively are quite common, but there appears to be little scientific basis for them. Lifting restrictions are inhibitory in terms of return to work and may be a factor in chronicity. The mean functional spinal motion unit stiffness changes with in vitro or computer-simulated discectomies, facetectomies and laminectomies were reviewed from the literature. We modified the NIOSH lifting equation to include another multiplier related to stiffness change post surgery. The new recommended lifts were computed for different lifting conditions seen in industry. The reduction of rotational stiffness ranged from 21% to 41% for a discectomy, 1% to 59% for a facetectomy and 4% to 16% for a partial laminectomy. The recommended lifts based on our modified equation were adjusted accordingly. There is no rational basis for current lifting restrictions. The risk to the spine is a function of many other variables as well as weight (i.e., distance of weight from body). The adjusted NIOSH guidelines provide a reasonable way to estimate weight restrictions and accommodations such as lifting aids. Such restrictions should be as liberal as possible so as to facilitate, not prevent, return to work. Patients need more advice regarding lifting activities and clinicians should be more knowledgeable about the working conditions and constraints of a given workplace to effectively match the solution to the patient's condition.


Subject(s)
Lifting , Spine/surgery , Diskectomy , Humans , Laminectomy , Occupational Health , Postoperative Period , Surveys and Questionnaires
19.
Eur Spine J ; 8(3): 179-86, 1999.
Article in English | MEDLINE | ID: mdl-10413342

ABSTRACT

Lifting restrictions postoperatively are quite common but there appears to be little scientific basis for them. Lifting restricitions are inhibitory in terms of return to work and may be a factor in chronicity. The mean changes in functional spinal motion unit (FSU) stiffness with in vitro or computer-simulated discectomies, facetectomies and laminectomies were reviewed from the literature. We modified the NIOSH lifting equation to include another multiplier related to stiffness change post surgery. The new recommended lifts were computed for different lifting conditions seen in industry. The reduction of rotational stiffness ranged from 21% to 41% for a discectomy, 1% to 59% for a facetectomy and 4% to 16% for a partial laminectomy. The recommended lifts based on our modified equation were adjusted accordingly. There is no rational basis for current lifting resctrictions. The risk to the spine is a function of many other variables as well as weight (i.e., distance of weight from body). The adjusted NIOSH guidelines provide a reasonable way to estimate weight restrictions and accomodations such as lifting aids. Such resitrictions should be as liberal as possible so as to facilitate, not prevent, return to work. Patients need more advice regarding lifting activities and clinicians should be more knowledgeable about the working conditions and constraints of a given workplace to effectively match the solution to the patient's condition.


Subject(s)
Lifting , Diskectomy , Humans , Laminectomy , Low Back Pain/rehabilitation , Low Back Pain/surgery , Models, Theoretical , Postoperative Period , Prescriptions , Spine/surgery
20.
Eur Spine J ; 8(2): 118-25, 1999.
Article in English | MEDLINE | ID: mdl-10333150

ABSTRACT

Whiplash motion of the neck is characterized by having an extension-flexion motion of the neck. It has been previously assumed that muscles do not play a role in the injury. Eight healthy males were seated in a car seat mounted on a sled. The sled was accelerated by a spring mechanism. Muscle electromyographic (EMG) activity was measured by wire electrodes in semi-spinalis capitis, splenius capitis, and levator scapulae. Surface EMG activity was measured over trapezius and sternocleidomastoideus. Wavelet analysis was used to establish the onset of muscle activity with respect to sled movement. Shorter reaction times were found to be as low as 13.2 ms from head acceleration and 65.6 ms from sled acceleration. Thus the muscles could influence the injury pattern. It is of interest that clinical symptoms are often attributed to muscle tendon injuries.


Subject(s)
Muscle Contraction/physiology , Neck Muscles/physiology , Whiplash Injuries/etiology , Acceleration , Adult , Electromyography , Humans , Male , Reaction Time , Whiplash Injuries/physiopathology
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