Gene/Protein Disease Symptom Drug Enzyme Compound
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This paper is a summary of several papers published in different journals and conference proceedings. The contents deal with the incidence of load related musculoskeletal illness of female workers exposed to various workloads. Furthermore, the changes in workload due to improved workplace design and the effect on the incidence of musculoskeletal illness was evaluated. The sick-leave due to musculoskeletal illness was reduced from 5.3% to 3.1% and the reduction in turn-over from 30.1% to 7.6%. The cost and the benefits of this ergonomic intervention were analysed, and showed that an investment of NOK. 350,000 produced total savings of NOK. 3,200,000. Postural load was assessed by recording electromyography (EMG) on the upper part of musculus trapezius, postural angles of the upper arm and flexion/extension of the head and back. A quantitative relationship was found between the static trapezius load and the development of musculoskeletal sick-leave, related to the length of employment. Indications were found that certain factors were associated with reduced incidence of musculoskeletal illness. These were: increasing the number and total duration of trapezius load below 1% to 2% MVC (Maximum Voluntary Contraction); reducing the magnitude of flexion angle of the upper arm in the sagittal plane and distributing the work between flexors and extensors; and a more dynamic work pattern of the upper arm. The relationship between postural load and musculoskeletal injury was studied in comparable groups of female workers with respect to age, working hours per day and time of employment. Psychosocial problems, spare time activities and living habits of the workers did not show any significant differences across the groups. The results from this study indicate that: the static trapezius load must be kept at a minimum; a median arm flexion should be less than 15 degrees and a median arm abduction less than 10 degrees. These values seem roughly to approach an acceptable arm position; and a forward median flexion of the back of less than 20 degrees seems not to lead to a higher rate of low back pain for workers with long periods of employment.
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PMID:The impact of ergonomic intervention on individual health and corporate prosperity in a telecommunications environment. 795 20

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.
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PMID:Glucocorticoid receptors, fibromyalgia and low back pain. 948 5

Via a multicentre study coordinated by the EPM research group carried out in 216 wards in a total of 56 hospitals, old peoples homes and geriatric departments, it was possible to quantify exposure to patient handling (classified in 4 classes: 0-1.5 negligible, 1.51-5 slight to average, 5.01-10 average to high, > 10 elevated), and at the same time identify the damage to the lumbosacral spine thus caused. Both assessment of exposure and identification of health impairment were carried out using homogeneous methods. Subjects with work seniority in the job of less than 6 months and subjects who had been transferred because of back trouble were excluded from the study. It was therefore possible to carry out two types of study to assess the association between exposure and impairment. In study A, covering 3021 subjects, an analysis was performed of the association between exposure index, positive response to the anamnestic threshold for lumbosacral disorders and acute low back pain using the method of logistic analysis to obtain the prevalence odds ratios. In study B, covering 418 subjects, the analysis of association was performed on the incidence rates of episodes of acute low back pain and pharmacologically controlled acute low back pain, assuming that exposure in the wards had remained constant. The technique used was Poisson regression, thereby calculating the relative incidence rate ratios. Both for PORs and IRRs the reference group consisted of the exposure class judged as negligible (exposure index 0-1.5). The results showed that the PORs calculated for positive lumbar threshold were significant for increasing exposure classes with a positive trend for the second and third exposure class but not for the last, presumably due to a healthy worker selection effect. Neither in Study A nor in Study B were any associations observed between exposure and acute low back pain occurring in the previous 12 months: this may be due to the fact that the impairment indicator does not appear to be appropriate in terms of latency period. A different result was obtained in Study B which showed a good association between exposure and incidence rates of episodes of acute low back pain and pharmacologically controlled acute low back pain according to department. The IRRs showed a positive trend both for acute episodes (IRR: 1.932, 2.439, 2.847) and for acute plus pharmacologically controlled acute episodes (1.798, 1.830, 4.523). On the basis of these results, even with the caution required for the reasons explained in the text, it seems to be possible to identify three grades of exposure which correspond to increasing probability of impairment of the lumbosacral region of the spine: the first where risk seems negligible corresponds to an exposure level between 0 and 1.5. The second, where the episodes of low back pain may occur with an incidence 3.8 times greater, corresponds to an exposure level between 1.51 and 5, and the third corresponds to exposure levels exceeding 5, where the episodes of low back pain may occur with an incidence up to 5.6 times greater than expected.
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PMID:[The application of a synthetic index of exposure in the manual lifting of patients: the initial validation experiences]. 1037 18

Pathological features and genomic basis of a rare case of ALK(+), CD30(-), CD20(-) large B-cell lymphoma were analyzed. A 36-year-old Japanese female was admitted because of lumbago and constitutional symptoms. Physical examination and laboratory tests showed anemia (hemoglobin, 7.5 g/dL), mild hepatosplenomegaly, and immunoglobin G (IgG) lambda-type monoclonal gammopathy (IgG, 2782 mg/dL). The lymphoma spread exclusively in extranodal sites such as bone marrow, liver, spleen, ovary, and muscle. Biopsy specimens obtained from the ovary showed monomorphic proliferation of large immunoblastic cells with basophilic cytoplasm, round-shaped nuclei with a high nuclear to cytoplasmic ratio, and prominent single nucleolus. Immunostaining with anti-anaplastic lymphoma kinase (ALK) antibody, ALK1, showed finely granular cytoplasmic staining pattern. These cells were also positive for epithelial membrane antigen, CD4, CD19, CD38, CD138, cytoplasmic IgG, and lambda chain, but negative for CD30 (Ber-H2), CD56, CD57, and other T- and B-cell markers. Southern blot analyses revealed that Ig heavy and lambda light chain genes, but not T-cell receptor (TCR) beta gene, were clonally rearranged. Chromosomal analyses by conventional G-banding, spectral karyotyping, and fluorescence in situ hybridization showed complex abnormality involving 2p23, and chromosome 2 was translocated to chromosome 17. As 2;17 translocation resulting in the fusion of clathrin heavy chain (CLTC) gene with ALK was previously reported in inflammatory myofibroblastic tumor, we performed reverse transcriptase-polymerase chain reaction and demonstrated that the lymphoma cells contained CLTC-ALK fusion transcript. Under the diagnosis of ALK(+), CD30(-), CD20(-) large B-cell lymphoma, she was treated with conventional combination chemotherapies. However, the lymphoma was primarily chemotherapy resistant, and the patient died 11 months after admission. We consider that this case confirms the existence of ALK(+), CD30(-), CD20(-) large B-cell lymphomas proposed by Delsol et al. (16) and further provides relevant information regarding their clinicopathological features and cytogenetics.
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PMID:ALK+, CD30-, CD20- large B-cell lymphoma containing anaplastic lymphoma kinase (ALK) fused to clathrin heavy chain gene (CLTC). 1292 Feb 29

Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic approach.
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PMID:Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc. 1627 6

The cognitive-behavioral, fear-avoidance (FA) model of chronic pain (Vlaeyen JWS, Kole-Snijders AMJ, Boeren RGB, van Eek H. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain 1995a;62:363-72) has found broad empirical support, but its multivariate, predictive relationships have not been uniformly validated. Applicability of the model across age groups of chronic pain patients has also not been tested. Goals of this study were to validate the predictive relationships of the multivariate FA model using structural equation modeling and to evaluate the factor structure of the Tampa Scale of Kinesiophobia (TSK), levels of pain-related fear, and fit of the FA model across three age groups: young (< or =40), middle-aged (41-54), and older (> or =55) adults. A heterogeneous sample of 469 chronic pain patients provided ratings of catastrophizing, pain-related fear, depression, perceived disability, and pain severity. Using a confirmatory approach, a 2-factor, 13-item structure of the TSK provided the best fit and was invariant across age groups. Older participants were found to have lower TSK fear scores than middle-aged participants for both factors (FA, Harm). A modified version of the Vlaeyen JWS, Kole-Snijders AMJ, Boeren RGB, van Eek H (Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain 1995a;62:363-72.) FA model provided a close fit to the data (chi(2)(29)=42.0, p>0.05, GFI=0.98, AGFI=0.97, CFI=0.99, RMSEA=0.031 (90% CI 0.000-0.050), p close fit=0.95). Multigroup analyses revealed significant differences in structural weights for older vs. middle-aged participants. For older chronic pain patients, a stronger mediating role for pain-related fear was supported. Results are consistent with a FA model of chronic pain, while indicating some important age group differences in this model and in levels of pain-related fear. Longitudinal testing of the multivariate model is recommended.
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PMID:The fear-avoidance model of chronic pain: validation and age analysis using structural equation modeling. 1651 74

Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain, spinal mobility, disability, psychological state, and aerobic capacity. Sixty patients with chronic low back pain were randomized to three groups: group 1, aerobic exercise + home exercise; group 2, physical therapy (hot pack, ultrasound, TENS) + home exercise; group 3, home exercise only. Spinal mobility, pain severity, disability, and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up. Aerobic capacities of the patients were measured before and after treatment. All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up, and there was no significant difference between the groups. In group 2, a significant decrease in Beck Depression Inventory scores was observed with treatment. At 1-month follow-up, group 1 and 2 showed significant decreases in General Health Assessment Questionnaire scores. In group 2, there was also a significant improvement in Roland Morris Disability scores. There were similar improvements in exercise test duration and the MET levels in all the three groups. All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain. On the other hand, physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance.
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PMID:Comparison of three different approaches in the treatment of chronic low back pain. 1818 60

The spino-thalamic tract consists of two systems; the lateral system terminates in the somato-sensory cortex, and participates in the sensory discrimination of pain, and the medial system terminates in the anterior cingulated cortex (ACC) and insular cortex (IC) to mediate affective components of pain. Persistent pain induces plastic changes in cortical neurons, especially in the ACC and IC. Activation of these neurons is transmitted to the periaqueductal gray and rostroventromedial medulla (RVM) (descending pain control system). This system has long been considered to exert descending inhibition, but recent studies revealed that it also causes facilitation in certain pathological conditions. A variety of stressful stimuli have been shown to affect pain sensitivity. We demonstrated that chronic restraint stress induced thermal hyperalgesia in rats, in which phosphorylated ERK and levels of tryptophan hydroxylase, a key enzyme of 5-HT production, were increased in the RVM. 5HT released from the bulbospinal neurons may exert facilitatory effects on spinal nociceptive processing probably through 5HT3 receptors. Patients suffering chronic pain originating from deep tissues, such as temporo-mandibular disorder, fibromyalgia, or low back pain, often complain of pain and tenderness in various parts of the body. We injected complete Freund's adjuvant into a temporo-mandibular joint of rats unilaterally, and then injected 5% formalin into the ipsilateral or contralateral masseter muscle 2 weeks later. Pain-related behavior and neuronal activation in the spinal trigeminal nucleus were enhanced on both sides compared to those in non-inflammatory controls. Systemic enhancement of pain and hyperalgesia induced by unilateral joint inflammation may have been caused by the central sensitization and descending facilitation.
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PMID:[Descending facilitation in chronic stress and chronic pain state]. 1841 7

The aim of this work was to study whether fear of movement, and pain catastrophizing predict pain related-disability and depression in sub-acute whiplash patients. Moreover, we wanted to test if fear of movement is a mediator in the relation between catastrophizing and pain-related disability/depression as has been suggested by the fear-avoidance model [Vlaeyen JWS, Kole-Snijders AMJ, Boeren RGB, van Eek H. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain 1995;62:363-72]. The convenience sample used was of 147 sub-acute whiplash patients (pain duration less than 3 months). Two stepwise regression analyses were performed using fear of movement and catastrophizing as the independent variables, and disability and depression as the dependent variables. After controlling for descriptive variables and pain characteristics, catastrophizing and fear of movement were found to be predictors of disability and depression. Pain intensity was a predictor of disability but not of depression. The mediation effect of fear of movement in the relationships between catastrophizing and disability, and between catastrophizing and depression was also supported. The results of this study are in accordance with the fear-avoidance model, and support a biopsychosocial perspective for whiplash disorders.
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PMID:The fear-avoidance model in whiplash injuries. 1864 Aug 60

Functional pain syndromes usually are characterized by a local or generalized increase in pain sensitivity, spontaneous ongoing pain, and a variety of other common symptoms. Classification or definition of a syndrome is usually somewhat arbitrarily based on the predominantly affected body region or a main symptom, resulting in significant overlap between conditions. Support for the involvement of the central nervous system (CNS) comes from the frequent comorbidity of affective disorders and symptomatology, disturbances in cognitive function, changes in neuroendocrine function, and dysregulation of the autonomic nervous system, although only subgroups of patients are affected. Findings of neuroimaging studies in functional pain syndromes typically reveal plausible correlates for the patients' subjective complaints and indicate a central augmentation in pain processing but also in other sensory systems including a postulated interoceptive system. The pathophysiology of this augmentation is not clear, and the importance of peripheral input remains unresolved, as well as the contribution of spinal and supraspinal mechanisms. Affective and cognitive factors clearly influence pain processing in these syndromes, but do not fully explain the observed augmentation. For FMS, chronic low back pain, and irritable bowel syndrome a dysfunction of the descending inhibitory systems is supported by these findings. However, longitudinal studies are needed to confirm the causality of the reported associations and to establish a primary role of the CNS in these syndromes. Current techniques like VBM and H-MRS have revealed potential yet highly variable structural abnormalities of the CNS in several of the syndromes, but clinical relevance and conclusions from these studies remain far from clear. New theoretical concepts should drive prospective and interdisciplinary research based on well-defined hypotheses to use the full potential of the current neuroimaging techniques.
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PMID:[CNS processing of pain in functional somatic syndromes]. 2037 3


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