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[Development of an instrument for evaluating the moving and transfer of patients: an ergonomic approach].

Nursing personnel are at a high risk from work-related musculoskeletal disorders, especially back symptoms. Handling patients has been attributed as one of the factors playing an important role in the aetiology of occupational low back pain. The aim of the study was to construct an instrument to evaluate the ergonomic risks during patient-handling tasks. The instrument was developed with an ergonomic approach involving the equipment, the tasks, the environment and the personnel.

Back Injuries↗

Integrating psychosocial and behavioral interventions to achieve optimal rehabilitation outcomes.

INTRODUCTION: Psychosocial factors are important contributors to work disability associated with musculoskeletal conditions. The primary objectives of this paper were 1) to describe different psychosocial interventions that have been developed to prevent prolonged work disability, and 2) to identify future research directions that might enhance the impact of programs targeting psychosocial risk factors for work disability. METHODS: Selective review of scientific literature on psychosocial and behavioral interventions and work disability. RESULTS: Most prior interventions focused on psychosocial risk factors that exist primarily within the individual (e.g., pain catastrophizing, beliefs, expectancies). Successful disability prevention will require methods to assess and target psychosocial risk factors "outside" of the individual (e.g., interpersonal conflict in the workplace, job stress, etc.) using cost-effective, multipronged approaches. Research to explore interactions among different domains of psychosocial risk factors in relation to RTW outcomes is needed. Challenges to effective secondary prevention of work disability include developing competencies to enable a range of providers to deliver interventions, standardization of psychosocial interventions, and maximizing adherence to intervention protocols. CONCLUSION: Effective secondary prevention of work disability will require research to develop cost-effective, multipronged approaches that concurrently target both worker-related and workplace psychosocial risk factors.

Adaptation, Psychological↗

Neurofibromatosis update.

Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is one of the most common human single-gene disorders, affecting at least 1 million persons throughout the world. It encompasses a spectrum of multifacted disorders and may present with a wide range of clinical manifestations, including abnormalities of the skin, nervous tissue, bones, and soft tissues. The condition can be conclusively diagnosed when 2 of 7 criteria established by the National Institutes of Health Consensus Development Conference are met. Most children with NF-1 have no major orthopedic problems. For those with musculoskeletal involvement, the most important issue is early recognition. Spinal deformity, congenital tibial dysplasia (congenital bowing and pseudarthrosis), and disorders of excessive bone and soft-tissue growth are the three types of musculoskeletal manifestitations that require evaluation. Statistics gathered from the Cincinnati Children's Hospital Neurofibromatosis Center database of 588 patients show the incidence of spinal deformity in children with NF-1 to be 21%; pectus deformity, 4.3%; limb-length inequality, 7.1%; congenital tibial dysplasia, 5%; hemihypertrophy, 1.4%; and plexiform neurofibromas, 25%. The orthopedic complications can be managed, but only rarely are they cured. Current developments in molecular genetics are exciting and give hope to more positive outcomes.

Bone Diseases, Developmental↗

Occupational disease surveillance using disability insurance at an automotive stamping and assembly complex.

Sickness and accident-insurance (sick leave) claims at an automotive stamping and assembly complex were analyzed using Poisson regression over a 4-year period to identify occupational health problems. The incidence of lower-respiratory disability (excluding asthma) was higher in painting operations (rate ratio [RR] = 2.9, 95% confidence interval [CI] = 1.2 to 6.8), and final assembly and processing areas (RR = 2.7, 95% CI = 1.0 to 7.4) at the assembly plant, and in metal assembly (welding) areas (RR = 2.8, 95% CI = 1.4 to 5.7) at the stamping plant. Disability rates for upper-extremity musculoskeletal disorders were statistically significantly higher (RR = 3.1 to 3.8) in major assembly plant production areas, as were back disability rates (RR = 1.5). During the first 6 months of new work assignments in painting or final assembly, respiratory problem rates were four times higher than in other areas. Upper-extremity musculoskeletal rate ratios ranged from 4.4 to 5.7 for new assignments in body, hard trim, and chassis areas. Higher rates in new assignments appeared to result from assignment changes precipitated by developing health problems, or from routine assignments to new tasks, some of which conferred high risk and were tolerated for less than 6 months. Musculoskeletal disability was consistent with known ergonomic hazards and paralleled that reported on the Occupational Safety and Health Administration log. Work-related musculoskeletal and other problems can be readily identified from disability insurance claims without dependence on plant medical visits or workers' compensation records. Disability insurance appears to absorb considerable work-related medical and absence costs.

Accidents, Occupational↗

Molecular pathogenesis of staphylcoccal osteomyelitis.

Staphylococcus aureus is the most prominent musculoskeletal pathogen of man and animals. The persistent emergence of antibiotic-resistant strains has prompted renewed efforts to develop alternative protocols for the treatment and prevention of staphylococcal disease. These efforts have included attempts to develop an effective staphylococcal vaccine. Among the potential vaccine candidates are a group of surface proteins that act as adhesins by virtue of their ability to bind host proteins present in plasma and in the extracellular matrix. Because of our interest in the treatment and prevention of musculoskeletal infection, we have focused on adhesins that contribute to the colonization of bone and cartilage. Based on reports suggesting that colonization is a conserved characteristic of S. aureus strains that cause osteomyelitis and septic arthritis, we have paid particular attention to the factors that contribute to the ability to bind collagen. To date, only one collagen-binding adhesin (Cna) has been identified, and the gene encoding this adhesin (cna) is not present in most S. aureus strains. The possibility that a rare phenotype is conserved among isolates that cause a particular form of infection suggests a cause-and-effect relationship in which the phenotype contributes to the pathogenesis of the disease. To further evaluate that hypothesis, we attempted to determine whether Cna is the only collagen-binding adhesin produced by S. aureus and whether strains that encode cna share additional characteristics that distinguish them from other S. aureus strains. We also studied whether immunization with Cna induces a protective immune response. Our results confirm that Cna is the primary and probably the only collagen-binding adhesin and that the genetic element encoding cna does not encode any additional virulence factors. These results strongly suggest that the only consistent difference between cna-positive and cna-negative strains is the ability to bind collagen. We also demonstrated that vaccination with a recombinant fragment of Cna can protect animals against septic death and limit the ability to colonize bone.

Adhesins, Bacterial↗

Fever in rheumatic and autoimmune disease.

This article reviews the most common clinical conditions presenting with fever and musculoskeletal symptoms and attempts to categorize these disorders according to general etiologic categories as an aid to differential diagnosis. Although a substantial armamentarium of serologic, immunologic, and molecular laboratory studies have been developed and are available to the clinician, the most important data are obtained from a careful history and physical examination with emphasis on the musculoskeletal system.

Arthritis, Infectious↗

Mechanisms of central sensitization, neuroimmunology & injury biomechanics in persistent pain: implications for musculoskeletal disorders.

This review will offer an overview of the mechanistic pathways of chronic pain associated with musculoskeletal disorders (MSDs). Traditional electrophysiological pain pathways of these injuries will be reviewed. In addition, recent research efforts in persistent pain have characterized a cascade of neuroimmunologic events in the central nervous system that manifests in pain behaviors and neurochemical nociceptive responses. Physiologic changes in the central nervous system will be covered as they pertain to the interplay of these two areas, and also as they focus on MSDs and injuries. One such injury leading to persistent pain is radiculopathy, which results from nerve root compression or impingement and leads to low back pain. This painful syndrome will be used as an example to provide a context for presenting immune mechanisms of chronic pain and their relationship to injury. Measures of injury biomechanics are presented in the context of the resulting pain responses, including behavioral sensitivity, local structural changes, and cellular and molecular changes in the CNS. Lastly, based on these findings and others, a discussion is provided highlighting areas of future work to help elucidate methods of injury diagnosis and development of therapeutic treatments.

Biomechanical Phenomena↗

Unraveling 'F' factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging.

BACKGROUND: The rising co-occurrence of cardiometabolic diseases and musculoskeletal degeneration poses a critical challenge to healthy aging, yet the shared biological mechanisms underlying this multimorbidity remain poorly defined. This study aimed to establish an integrative clinical-genetic framework to elucidate the common frailty factor, the 'F' factor, that captures the systemic vulnerability linking cardiometabolic multimorbidity (CMM) and musculoskeletal aging. METHODS: Utilizing the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort, we developed and validated novel Frailty-Integrated Indices for CMM risk prediction, evaluated with machine learning models interpreted via SHapley Additive exPlanations (SHAP). Independently, we applied genomic structural equation modeling (Genomic-SEM) to integrate genome-wide association data from six traits-coronary artery disease, type 2 diabetes, hypertension, bone mineral density, frailty, and telomere length-to model a shared latent genetic factor ('F' factor). This was followed by multivariate GWAS, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, and functional annotation to prioritize causal genes, pathways, and cell types. RESULTS: Clinically, several Frailty-Integrated Indices significantly improved CMM risk prediction, with the optimal model achieving an AUC of 0.727. Genetically, we modeled a significant shared latent genetic factor ('F' factor), pinpointing novel risk loci and implicating key genes such as APOE and SLC22A3. These genes were enriched in pathways including cellular senescence and cholesterol metabolism and showed specific expression patterns in developmental brain stages and across multi-organ endothelial cells. CONCLUSION: Our findings provide converging evidence for Musculoskeletal‑Heart crosstalk of metabolic aging and inferred the 'F' factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities.

Humans↗

Mineral and nitrogen balance study observations: the second manned Skylab mission.

A metabolic study of the effects of space flight on various chemical elements, particularly those with special revelance to the musculoskeletal system, was carried out on the three astronauts of the SL-3 mission for 21 d preflight, during the 60 d flight phase, and for 17 d postflight. The study required of the cooperating crewmen quite constant dietary intake, continuous 24-hour urine collections and total fecal collections. Urinary calcium was significantly increased during flight in all three crewmen with man-to-man variation in pattern and amount; the degree of calcium loss was, in general, similar to that in the prior study of the 28-d Skylab flight (SL-2). The similarity to bedrest immobilization in the pattern of urinary calcium increases and of total calcium shifts suggested that calcium losses would continue for a very long time. Significant losses of nitrogen and phosphorus occurred that were associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens during flight. It was concluded that these studies give warning that capable musculoskeletal function may be significantly impaired during prolonged space flights lasting 1.5 to 3 years unless protective measures are developed.

Adult↗

Osseous disease in patients with pulmonary sarcoidosis and musculoskeletal symptoms.

Little is known about the clinical manifestations and correlates of osseous sarcoidosis and few data exist to guide pulmonologists in their evaluation of patients for possible osseous involvement. To determine the relationship between pulmonary and osseous sarcoidosis, and to develop an algorithm for use by pulmonologists in assessing patients with suspected osseous sarcoidosis, we conducted a retrospective, case control study of patients with pulmonary sarcoidosis and musculoskeletal complaints who were evaluated for osseous disease. All patients underwent a standard evaluation to include physical examination, chest radiograph (CXR), spirometry (PFTs), bone scintigraphy and plain radiographs of the hands and feet. Patients completed a health assessment questionnaire and serum angiotenisin converting enzyme, erythrocyte sedimentation rate, and C-reactive protein were measured. Patients eventually diagnosed with osseous sarcoidosis were compared to those lacking osseous involvement. Osseous involvement in patients with pulmonary sarcoidosis and musculoskeletal symptoms was common and seen in 38.9% of subjects. Patients with osseous sarcoidosis were more likely to concomitantly suffer from cutaneous sarcoidosis and to have elevated ACE levels and ESRs. No measure of pulmonary involvement (CXR stage, PFTs or symptoms) differentiated patients with osseous sarcoidosis from those without this condition. In cases of osseous sarcoidosis, bone scintigraphy identified a mean of four sites of osseous involvement, some of which would have been missed with the use of plain radiographs limited to the hands and feet. We conclude that in patients with pulmonary sarcoidosis who have significant musculoskeletal complaints, osseous involvement is frequent. Pulmonary features of sarcoidosis do not differ between patients with and without osseous disease. Bone scintigraphy aids in the evaluation of these patients.

Adult↗

Advantages of real-time spatial compound sonography of the musculoskeletal system versus conventional sonography.

OBJECTIVE: Spatial compound sonography is a method that obtains sonographic information from several different angles of insonation and combines them to produce a single image. By reducing speckle and improving definition of tissue planes, this method can potentially improve image quality in musculoskeletal sonography. The purpose of our study was to compare real-time spatial compound sonography with conventional high-resolution musculoskeletal sonography. MATERIALS AND METHODS: Thirty-four patients underwent sonography of the musculoskeletal system for a variety of indications. All patients were evaluated using conventional high-resolution sonography and real-time spatial compound sonography performed with a 12-5-MHz multifrequency linear array transducer. Conventional images and compound images depicting the same musculoskeletal structure were obtained in pairs. A total of 118 images (59 image pairs) were randomly assorted and reviewed on a computer monitor by three experienced sonologists working independently. The reviewers were unaware of the type of images they were evaluating. Image quality was rated using a 5-point scale. The image parameters evaluated were definition of tissue planes, speckle, other noise, and image detail. RESULTS: Analysis of variance revealed that real-time spatial compound sonography significantly improved definition of soft-tissue planes, reduced speckle and other noise, and improved image detail when compared with conventional high-resolution sonography (p < 0.0001 for all evaluated parameters). CONCLUSION: Real-time spatial compound sonography significantly improved sonographic image quality in the musculoskeletal system when compared with conventional high-resolution sonography. Because musculoskeletal sonography is highly dependent on image quality and tissue-plane definition, spatial compound sonography represents an important development.

Adolescent↗

Injectable gold for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included. DATA COLLECTION AND ANALYSIS: Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout. MAIN RESULTS: Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2). REVIEWER'S CONCLUSIONS: Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.

Antirheumatic Agents↗

Proteomic analysis of cartilage- and bone-associated samples.

The skeleton of the human body is built of cartilage and bone, which are tissues that contain extensive amounts of extracellular matrix (ECM). In bone, inorganic mineral hydroxyapatite forms 50-70% of the whole weight of the tissue. Although the organic matrix of bone consists of numerous proteins, 90% of it is composed of type I collagen. In cartilage, ECM forms a major fraction of the tissue, type II collagen and aggrecans being the most abundant macromolecules. It is obvious that the high content of ECM components causes analytical problems in the proteomic analysis of cartilage and bone, analogous to those in the analysis of low-abundance proteins present in serum. The massive contents of carbohydrates present in cartilage proteoglycans, and hydroxyapatite in bone, further complicate the situation. However, the development of proteomic tools makes them more and more tempting also for research of musculoskeletal tissues. Application of proteomic techniques to the research of chondrocytes, osteoblasts, osteocytes, and osteoclasts in cell cultures can immediately benefit from the present knowledge. Here we make an overview to previous proteomic research of cartilage- and bone-associated samples and evaluate the future prospects of applying proteomic techniques to investigate key events, such as cellular signal transduction, in cartilage- and bone-derived cells.

Amino Acid Sequence↗

Adenovirus-mediated BMP2 expression in human bone marrow stromal cells.

Recombinant adenoviral vectors have been shown to be potential new tools for a variety of musculoskeletal defects. Much emphasis in the field of orthopedic research has been placed on developing systems for the production of bone. This study aims to determine the necessary conditions for sustained production of high levels of active bone morphogenetic protein 2 (BMP2) using a recombinant adenovirus type 5 (Ad5BMP2) capable of eliciting BMP2 synthesis upon infection and to evaluate the consequences for osteoprogenitor cells. The results indicate that high levels (144 ng/ml) of BMP2 can be produced in non-osteoprogenitor cells (A549 cell line) by this method and the resultant protein appears to be three times more biologically active than the recombinant protein. Surprisingly, similar levels of BMP2 expression could not be achieved after transduction with Ad5BMP2 of either human bone marrow stromal cells or the mouse bone marrow stromal cell line W20-17. However, human bone marrow stromal cells cultured with 1 microM dexamethasone for four days, or further stimulated to become osteoblast-like cells with 50 microg/ml ascorbic acid, produced high levels of BMP2 upon Ad5BMP2 infection as compared to the undifferentiated cells. The increased production of BMP2 in adenovirus transduced cells following exposure to 1 microM dexamethasone was reduced if the cells were not given 50 microg/ml ascorbic acid. When bone marrow stromal cells were allowed to become confluent in culture prior to differentiation, BMP2 production in response to Ad5BMP2 infection was lost entirely. Furthermore, the increase in BMP2 synthesis seen during differentiation was greatly decreased when Ad5BMP2 was administered prior to dexamethasone treatment. In short, the efficiency of adenovirus mediated expression of BMP2 in bone marrow stromal cells appears to be dependent on the differentiation state of these cells.

Adenoviridae↗

The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease.

To determine the prevalence, clinical and radiological characteristics of spondyloarthropathy (SpA) in patients with inflammatory bowel disease (IBD), to assess the association between HLA B27 and B51 and the extraintestinal symptoms and to evaluate whether IBD is associated with Behçet's disease (BD). One hundred and sixty-two consecutive adult patients with established diagnosis of IBD as either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated. All the patients including those previously diagnosed with or without SpA had a complete rheumatologic examination and they were evaluated according to the European Spondyloarthropathy Study Group (ESSG) criteria for SpA and The International Study Group for Behçet's disease criteria for BD. The demographic and clinical data were recorded on a standardized form. The radiographies were obtained in all the patients and computed tomography (CT) was performed in the patients with suspected pelvic radiographies and/or low back pain in the physical examination. Radiological evaluation was made according to the Modified New York criteria. HLA B27, B51 and anti-neutrophile cytoplasmic antigen (ANCA) were searched in all the patients. Of the 162 patients with IBD (mean age 41.48+/-11.63 years, male 60, female 102), 78 were CD and 84 were UC. The mean of the IBD duration was 54.92+/-50.32 months and SpA duration was 20.63+/-34.37 months. The prevalence of SpA and AS in IBD was 45.7 and 9.9%, respectively. Frequencies of SpA and AS, the difference between UC and CD were not significant. Spondylitis, enthesitis, peripheral arthritis, oral ulcer and uveitis were not different between UC and CD, but erythema nodosum was found significantly more common in the CD patients compared with UC patients (P=0.005). The duration of IBD and SpA was similar in both groups. As the IBD duration increased, the prevalence of SpA development decreased (rr=0.991, P=0.009). Of the IBD patients, 13.6% were asymptomatic for musculoskeletal manifestations of SpA and their sacroiliac radiographies and CTs showed grade 2 sacroiliitis. HLA B27, B51 and ANCA positivities were not different between the patients with UC and CD. HLA B27 was significantly more common in the patients with sacroiliitis, spondylitis, enthesitis, peripheral arthritis, erythema nodosum, uveitis (P<0.001) and oral ulcer (P=0.025). BD was diagnosed in none of the patients. ANCA positivity was found to be related with the presence of erythema nodosum and uveitis (P=0.001 and P=0.005). The prevalence of SpA and AS is higher in the prospectively evaluated patients with radiological studies than those in the previously published studies. There is a high prevalence of asymptomatic sacroiliitis in IBD. An early diagnosis of inflammatory arthritis in IBD patients may prevent a disability due to SpA and AS.

Adolescent↗

Magnetic resonance diffusion-weighted imaging: extraneurological applications.

Diffusion-weighted (Dw) imaging has for a number of years been a diagnostic tool in the field of neuroradiology, yet only since the end of the 1990s, with the introduction of echoplanar imaging (EPI) and the use of sequences capable of performing diffusion studies during a single breath hold, has it found diagnostic applications at the level of the abdomen. The inherent sensitivity to motion and the magnetic susceptibility of Dw sequences nonetheless still create problems in the study of the abdomen due to artefacts caused by the heartbeat and intestinal peristalsis, as well as the presence of various parenchymal-gas interfaces. With regard to focal liver lesions, a review of the literature reveals that Dw imaging is able to differentiate lesions with high water content (cysts and angiomas) from solid lesions. With regard to the latter, although there are differences between benign forms [focal nodular hyperplasia (FNH), adenoma] and malignant forms [metastasis, hepatocellular carcinoma (HCC)] in their apparent diffusion coefficient (ADC) in the average values for histological type, there is a significant overlap in values when lesions are assessed individually, with the consequent problem of their correct identification. One promising aspect is the possibility of quantifying the degree of fibrosis in patients with chronic liver disease and cirrhosis given that the deposit of collagen fibres "restricts" the motion of water molecules and therefore reduces ADC values. However, even in this field, studies can only be considered preliminary and far from real clinical applications. The retroperitoneum is less affected by motion artefacts and similarly deserves the attention of Dw imaging. Here it is possible to differentiate mucin-producing tumours of the pancreas from pseudocystic forms on the basis of ADC values even though the limited spatial resolution of Dw imaging does not enable the identification of small lesions. Dw imaging may be applied to the study of the kidney to differentiate hydronephrosis from pyonephrosis and with regard to tumours, solid from pseudocystic forms. In addition, given that renal parenchyma has significantly variable ADC values on the basis of the anatomic section and physiological conditions, the possibility of assessing functional alterations is currently being studied. Indeed, a good correlation has been found between ADC values and glomerular filtration rate. With regard to musculoskeletal applications, the absence of motion artefacts in the regions studied has enabled the development of sequences less sensitive to magnetic susceptibility and with greater spatial resolution than EPI. Attempts have therefore been made to use Dw imaging in the characterization of soft-tissue tumours although the findings so far have been disputed. Greater agreement has been found regarding sensitivity of the technique in assessing response of these tumours to chemotherapy: tumour necrosis is thought to increase ADC whereas the persistence of vital neoplastic tissue tends to lower it. One of the most promising applications of Dw imaging is without doubt the assessment of vertebral collapse where a high ADC has been shown to be associated with an osteoporotic cause and a low ADC with a neoplastic cause. Nonetheless, even here, a moderate overlap between ADC values of the two types has been encountered. Dw imaging has also been used in the assessment of bone marrow cellularity: areas of tightly packed cells show a higher ADC value than hypocellular areas. In particular, no significant difference in ADC is noted between normal hypercellular bone marrow and hypercellular bone marrow secondary to lymphomatous infiltration whereas this difference is significant between hypocellular, normocellular and haematopoietic hypercellular bone marrow. With regard to the study of joints, the limited structure dimensions, particularly cartilage, creates technical difficulties related to spatial resolution and an adequate signal-to-noise ratio, problems that can only be solved by further technological developments. Lastly, a significant difference in ADC values between degenerative and inflammatory effusion has been found, a fact that may be explained as the result of the activity of hyaluronidase present in inflammatory forms, which causes a reduction in the concentration of hyaluronic acid with a consequent decrease in viscosity.

Abdomen↗

Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy.

This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another model of regeneration, but rather produces a unique environment which induces satellite cell migration and subsequent fiber formation in the interfascicular space. De novo fiber formation is apparently the principal mechanism for the hyperplasia reported to occur in the ALD muscle undergoing hypertrophy induced by wing-weighting.

Aging↗

Intramuscular injection of tumor necrosis factor-alpha induces muscle hyperalgesia in rats.

The role of proinflammatory cytokines in neuropathic and inflammatory pain is well established. Recent studies suggest that cytokines such as tumor necrosis factor-alpha (TNF) may also be involved in the development of muscle pain. To investigate the pathophysiology of intramuscular TNF, exogenous TNF (0.1-10 microg), formalin (9%) or vehicle was injected into the gastrocnemius or biceps brachii muscles of rats. To quantify muscle hyperalgesia, changes in forelimb grip force or withdrawal thresholds to increasing pressure applied to the gastrocnemius muscle were measured. TNF evoked a time- and dose-dependent muscle hyperalgesia within several hours after injection that was totally reversed by systemic treatment with the non-opioid analgesic metamizol. Paw withdrawal thresholds or latencies to mechanical and thermal stimuli, respectively, were unchanged after intramuscular injection of TNF or formalin. In contrast to formalin, which induced significant muscle tissue damage, macrophage infiltration, swelling and partial motor impairment demonstrated in rotarod tests, TNF induced neither histopathological tissue damage nor motor dysfunction. To investigate the effect of TNF and formalin on other potentially algesic mediators, muscles were analyzed for calcitonin-gene related peptide (CGRP), prostaglandin E2 (PGE2) and nerve growth factor (NGF) 1 day after injection. TNF and formalin evoked intramuscular upregulation of CGRP and NGF, whereas PGE2 was increased exclusively after TNF injection. These findings allow us to speculate that endogenous TNF may play a role in the development of muscle hyperalgesia. Targeting proinflammatory cytokines might be beneficial for the treatment of musculoskeletal pain syndromes.

Animals↗