Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation.

Previous studies have demonstrated that both mechanical perturbation and cell adhesion induced the expression of osteopontin (opn) by osteoblasts (Carvalho et al. [1998] J. Cell. Biochem. 70:376-390). The present study examined if these same stimuli on osteoblasts would induce the expression of other integrin binding proteins, specifically fibronectin (fn) and bone sialoprotein (bsp). All three genes showed three- to four-fold maximal induction in response to both cell adhesion and a single 2-h period of an applied spatially uniform, dynamic biaxial strain of 1.3% at 0.25 Hz. Each gene, however, responded with a different time course of induction to mechanical strain, with bsp, fn, and opn showing their maximal response at 1, 3, and 9 h, respectively, after the perturbation period. In contrast, peak induction to cell adhesion was observed at 24 h for bsp and opn, while fn levels peaked at 8 h. Interestingly, while both opn and fn mRNA expression returned to base line after cell adhesion, bsp mRNA levels remained elevated. Examination of collagen type I and osteocalcin mRNAs showed unaltered levels of expression in response to either type of perturbation. A common feature of the signal transduction pathways, which mediate the gene expression in response to both cell adhesion and mechanical perturbation, was the activation of specific tyrosine kinases based on the ablation of the induction of these genes by the tyrosine kinase inhibitor genistein. While cycloheximide blocked the induction of all three mRNAs in response cell adhesion, it failed to block the induction of any of these genes in response to mechanical perturbation. Such results suggest that the induction of these genes after mechanical perturbation was mediated by an immediate response to signal transduction, while cell adhesion mediated effects secondary to signal transduction. Depolymerization of microfilaments with cytochalasin D had no effect on the overall expression of any of these genes in response to cell adhesion and only blocked the induction of opn expression in response to mechanical perturbation. These results suggest that cytoskeletal integrity is only selectively important in the signal transduction of certain types of stimuli and for the regulation of certain genes. In summary, both mechanical perturbation and cell adhesion stimulated the expression of integrin binding proteins. Furthermore, while there are common features in the signal transduction processes that mediate the induction of these genes in response to both stimuli, specific genes are separately regulated by precise mechanisms that are unique to both forms of stimuli.

Effect of mechanical perturbation on the release of PGE(2) by macrophages in vitro.

Macrophages play numerous roles in both physiologic and pathologic processes. Along with fibroblasts, they comprise the synovial tissue that forms the lining of musculoskeletal joint capsules and bursae, and they often envelop implants. During the process of phagocytosing prosthesis-related particles, macrophages in peri-implant tissue release inflammatory mediators. Little is known, however, about the response of these cells to mechanical perturbation, which often is a component of the physical environment of the cell. Mouse peritoneal macrophages were grown on a flexible membrane in vitro and a dynamic 1-Hz spatially uniform sinusoidal strain pattern imparted to the elastomeric substrate. The effect of mechanical strain on prostaglandin (PG) E(2) release was evaluated using cells that were activated by lipopolysaccharide (LPS) as well as by those that were not. The results are compared with the levels of PGE(2) stimulated by metallic particles. Strain magnitudes of 4 and 8% applied for 1 h resulted in almost a twofold increase in the release of PGE(2) from LPS-stimulated cells (p < 0.05) and nonstimulated macrophages (p < 0.07), compared with nonperturbated controls. No release was elicited by a challenge of metal particles. These findings demonstrate for the first time an effect of mechanical force on the release of an inflammatory mediator by macrophages. This response may help to explain the macrophage-mediated processes underlying the osteolysis associated with loose prostheses in bone and suggests a mechanism for the inflammation of synovial tissues by excessive mechanical strain.

The rational clinical examination. Does this patient have a torn meniscus or ligament of the knee? Value of the physical examination.

CONTEXT: While most meniscal or ligamentous knee injuries heal with nonoperative treatments, a subset should be treated with arthroscopic or open surgery. OBJECTIVE: To analyze the accuracy of the clinical examination for meniscal or ligamentous knee injuries. DATA SOURCES: MEDLINE (1966-December 31, 2000) and HealthSTAR (1975-December 31, 2000) databases were searched for English-language articles describing the diagnostic accuracy of individual examination items for the knee and a combination of physical examination items (composite examination). Other data sources included reference lists from relevant articles. STUDY SELECTION: Studies selected for data extraction were those that compared the performance of the physical examination of the knee with a reference standard, such as arthroscopy, arthrotomy, or magnetic resonance imaging. Eighty-eight articles were identified, of which 23 (26%) met inclusion criteria. DATA EXTRACTION: A rheumatologist and an orthopedic surgeon independently reviewed each article using a standardized rating scale that scored the assembly of the study, the relevance of the patients enrolled, the appropriateness of the reference standard, and the blinding of the examiner. DATA SYNTHESIS: Summary likelihood ratios (LRs) were estimated from random effects models. The summary LRs for physical examination for tears of the anterior cruciate ligament, using the anterior drawer test, were 3.8 (95% confidence interval [CI], 0.7-22.0) for a positive examination and 0.30 (95% CI, 0.05-1.50) for a negative examination; the Lachman test, 25.0 (95% CI, 2.7-651.0) and 0.1 (95% CI, 0.0-0.4); and the composite assessment, 25.0 (95% CI, 2.1-306.0) and 0.04 (95% CI, 0.01-0.48), respectively. The LRs could not be generated for any specific examination maneuver for a posterior cruciate ligament tear, but the composite assessment had an LR of 21.0 (95% CI, 2.1-205.0) for a positive examination and 0.05 (95% CI, 0.01-0.50) for a negative examination. Determination of meniscal lesions, using McMurray test, had an LR of 1.3 (95% CI, 0.9-1.7) for a positive examination and 0.8 (95% CI, 0.6-1.1) for a negative examination; joint line tenderness, 0.9 (95% CI, 0.8-1.0) and 1.1 (95% CI, 1.0-1.3); and the composite assessment, 2.7 (95% CI, 1.4-5.1) and 0.4 (95% CI, 0.2-0.7), respectively. CONCLUSION: The composite examination for specific meniscal or ligamentous injuries of the knee performed much better than specific maneuvers, suggesting that synthesis of a group of examination maneuvers and historical items may be required for adequate diagnosis.

Referrals for musculoskeletal disorders: patterns, predictors, and outcomes.

OBJECTIVE: To examine factors associated with musculoskeletal referral and determine whether referral influences clinical outcomes. METHODS: Patients included in the study presented with knee or shoulder pain to primary care physicians affiliated with an academic teaching hospital. The primary clinical outcome was change in pain or function measured up to 12 months after initial presentation. Covariates included baseline pain and function, duration of complaint, initial diagnosis, insurance status, and several demographic factors. RESULTS: Forty-one percent (65 of 160 patients) were referred for knee or shoulder conditions, 47 (29%) patients were referred only to an orthopedic surgeon, and 12 (8%) only to a rheumatologist; 6 (4%) patients saw both specialists. For patients with knee pain, the only variable correlated with referral was an initial diagnosis of internal derangement (p = 0.02). No variable was significantly associated with referral for shoulder pain. Baseline pain, baseline function, duration of complaint, age, and insurance status were not associated with referral for either knee or shoulder pain (all p values > 0.05). The variables most associated with improvement in pain and function were more severe pain and function at baseline (all p values < 0.0001). In multivariate analyses controlling for clinical and demographic factors among patients with shoulder complaints, referral was associated with significantly less improvement in clinical outcomes than non-referral (p = 0.02). Referral was not associated with clinical outcomes for patients with knee pain. CONCLUSIONS: Referral was common for patients with knee or shoulder conditions. The only baseline variable correlated with referral was a diagnosis of knee internal derangement. Referral was not associated with improvement in pain or function and may actually be correlated with worse outcomes among patients with shoulder pain, although this is likely due to unmeasured factors contributing to the referral decision.

Outcomes of care and resource utilization among patients with knee or shoulder disorders treated by general internists, rheumatologists, or orthopedic surgeons.

PURPOSE: Previous studies have suggested that specialists may achieve better clinical outcomes for patients, albeit often at greater cost. We sought to compare outcomes of care and resource utilization among patients with shoulder or knee problems who were treated by general internists, rheumatologists, and orthopedic surgeons. SUBJECTS AND METHODS: Outpatients with knee or shoulder complaints who were seen by general internists, rheumatologists, or orthopedic surgeons at an academic medical center were administered questionnaires at enrollment in the study and again 3 months later. The questionnaires included validated measures of satisfaction, functional status, and pain severity, as well as resource utilization. We compared baseline clinical characteristics, satisfaction with care, resource utilization, and changes in function and symptoms during 3 months of follow-up among patients who were cared for by the three different types of providers. RESULTS: A total of 534 patients responded to the baseline survey and 436 (82%) to the 3-month follow-up survey. About 60% (n = 323) had knee pain. Orthopedists cared for 40% (n = 211) of the patients, with the remainder treated in approximately equal numbers by general internists or rheumatologists. At baseline, patients of internists had less severe pain (differences of 0.3 to 0.6 points on a 1 to 5 scale, P <0.05) and functional limitations (differences of 0.4 to 0.6 points on a 1 to 5 scale, P <0.0006) than patients of rheumatologists and orthopedic surgeons. Adjusting for baseline differences, there were no significant differences among provider groups in pain relief or functional improvement during follow-up. However, in adjusted analyses, patients with shoulder pain who were cared for by orthopedic surgeons were least satisfied with the office environment [adjusted mean (+/- SD) satisfaction score of 1.6 +/- 0.8 on a 1 to 4 scale for orthopedic surgeons vs 1.3 +/- 0.8 for rheumatologists and 1.4 +/- 0.8 for internists, P = 0.004]. Among patients with knee pain, those treated by rheumatologists and orthopedic surgeons were more satisfied with the doctor-patient interaction (adjusted mean satisfaction scores of 1.1 +/- 0.9 for rheumatologists and 1.2 +/- 0.7 for orthopedic surgeons on a 1 to 4 scale vs 1.4 +/- 0.8 for general internists, P = 0.003). Orthopedic surgeons obtained significantly more radiographs of the knee or shoulder and more magnetic resonance imaging scans of the knee. Rheumatologists performed significantly more aspirations or injection procedures. Among all patients, those treated by rheumatologists were most satisfied with the physician interaction, and those treated by orthopedic surgeons were most satisfied with treatment results. CONCLUSION: The relative benefits of specialist compared with generalist care for patients with knee or shoulder pain depend on the importance attached to resource utilization, patient satisfaction, and health outcomes.

Physical properties of hydrated tissue determined by surface interferometry of laser-induced thermoelastic deformation.

Knee meniscus is a hydrated tissue; it is a fibrocartilage of the knee joint composed primarily of water. We present results of interferometric surface monitoring by which we measure physical properties of human knee meniscal cartilage. The physical response of biological tissue to a short laser pulse is primarily thermomechanical. When the pulse is shorter than characteristic times (thermal diffusion time and acoustic relaxation time) stresses build and propagate as acoustic waves in the tissue. The tissue responds to the laser-induced stress by thermoelastic expansion. Solving the thermoelastic wave equation numerically predicts the correct laser-induced expansion. By comparing theory with experimental data, we can obtain the longitudinal speed of sound, the effective optical penetration depth and the Grüneisen coefficient. This study yields information about the laser tissue interaction and determines properties of the meniscus samples that could be used as diagnostic parameters.

Can history and physical examination be used as markers of quality? An analysis of the initial visit note in musculoskeletal care.

BACKGROUND: The medical record serves as an important source of information regarding the care process, but few studies have examined whether thoroughness of documentation is associated with outcomes. OBJECTIVE: The objectives of this study were to analyze the initial visit note for 513 patients presenting with acute musculoskeletal pain, compare thoroughness of documentation by physician specialty, and determine whether thoroughness of documentation was associated with clinical improvement or patient satisfaction. METHODS: A structured medical record abstraction was performed to examine whether treating physicians documented key historical and physical exam findings. Satisfaction with care, symptom relief, and functional improvement were assessed after 3 months with validated survey instruments. RESULTS: In the initial visit note, 43+/-16% of selected historical findings and 28+/-17% of physical examination findings were documented. Orthopedic surgeons documented 2 to 4 more historical and physical examination items (P <0.01) and assigned more specific diagnoses (P <0.01) than rheumatologists and general internists. Multivariate models showed a very weak association between all aspects of documentation and patient satisfaction with the provider-patient interaction (all partial R2 <0.016) and no association between documentation and 3-month pain relief or functional status. Patients' perception of physician communication was more highly associated with patient satisfaction (P = 0.0001) than was documentation. CONCLUSIONS: No provider types consistently documented many important historical items and physical examination findings. While thoroughness of documentation was not associated with clinical outcomes, there was a very weak relationship between documentation and patient satisfaction with provider-patient interactions.

Development and validation of a patient satisfaction scale for musculoskeletal care.

OBJECTIVE: To test the hypothesis that 3 distinct domains of patient satisfaction with musculoskeletal care--satisfaction with the office environment, provider-patient interaction, and treatment outcomes--can be measured reliably and, when considered separately, are more valid indicators of satisfaction than global measures. METHODS: Three hundred ninety-nine outpatients who presented with knee or shoulder pain were enrolled in a prospective cohort study. We measured patient satisfaction with musculoskeletal care by adapting a widely used generic satisfaction survey. RESULTS: Each domain of the scale was internally consistent, with Cronbach's alphas for satisfaction with the office environment, provider-patient interaction, and treatment outcome subscales of 0.68, 0.95, and 0.93, respectively. Validity correlations demonstrated the greater specificity of the subscales than global measures for particular aspects of musculoskeletal care. CONCLUSIONS: The musculoskeletal-specific satisfaction scale has excellent reliability and good discriminant validity. From a policy perspective, the distinct subscale structure is critical because problems within each domain may have different remedies.

Functional MRI of the lumbar spine in erect position in a superconducting open-configuration MR system: preliminary results.

The purpose of this study was to determine the feasibility of obtaining, and findings in, functional MRI of the lumbar spine in an erect position and with flexion and extension. Thirty subjects (including 5 volunteers) were imaged in a sitting position and while performing flexion and extension. The alternations in posterior disk margin, size of neural foramina, and central canal were evaluated. In addition, routine supine imaging was accomplished in 15 of these subjects. The foraminal size and posterior disk margins did not change appreciably from supine to upright position. With extension, there was an increased disk bulge in 27% of disks (40% of those with desiccation). Central canal size (50%) and foraminal size (27%) decreased with extension, especially at levels with disk desiccation. Images obtained with our open-configuration MR unit were diagnostically adequate, although of inferior quality compared with those obtained with a conventional unit. Our preliminary results show the feasibility of obtaining diagnostic images of the erect lumbar spine with flexion and extension. The results are in agreement with those obtained with cadaveric studies. The utility of this method in diagnostic imaging of patients with low back pain remains to be determined.

Chondrogenic potential of skeletal cell populations: selective growth of chondrocytes and their morphogenesis and development in vitro.

Most vertebrate embryonic and post-embryonic skeletal tissue formation occurs through the endochondral process in which cartilage serves a transitory role as the anlage for the bone structure. The differentiation of chondrocytes during this process in vivo is characterized by progressive morphological changes associated with the hypertrophy of these cells and is defined by biochemical changes that result in the mineralization of the extracellular matrix. The mechanisms, which, like those in vivo, promote both chondrogenesis in presumptive skeletal cell populations and endochondral progression of chondrogenic cells, may be examined in vitro. The work presented here describes mechanisms by which cells within presumptive skeletal cell populations become restricted to a chondrogenic lineage as studied within cell populations derived from 12-day-old chicken embryo calvarial tissue. It is found that a major factor associated with selection of chondrogenic cells is the elimination of growth within serum-containing medium. Chondrogenesis within these cell populations appears to be the result of permissive conditions which select for chondrogenic proliferation over osteogenic cell proliferation. Data suggest that chondrocyte cultures produce autocrine factors that promote their own survival or proliferation. The conditions for promoting cell growth, hypertrophy, and extracellular matrix mineralization of embryonic chicken chondrocytes in vitro include ascorbic acid supplementation and the presence of an organic phosphate source. The differentiation of hypertrophic chondrocytes in vitro is associated with a 10-15-fold increase in alkaline phosphatase enzyme activity and deposition of mineral within the extracellular matrix. Temporal studies of the biochemical changes coincident with development of hypertrophy in vitro demonstrate that proteoglycan synthesis decreases 4-fold whereas type X collagen synthesis increases 10-fold within the same period. Ultrastructural examination reveals cellular and extracellular morphology similar to that of hypertrophic cells in vivo with chondrocytes embedded in a well formed extracellular matrix of randomly distributed collagen fibrils and proteoglycan. Mineral deposition is seen in the interterritorial regions of the matrix between the cells and is apatitic in nature. These characteristics of chondrogenic growth and development are very similar in vivo and in vitro and they suggest that studies of chondrogenesis in vitro may provide a valuable model for the process in vivo.

Osteoblasts induce osteopontin expression in response to attachment on fibronectin: demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation.

Osteopontin is a predominant integrin binding protein of bone and its expression has been shown to be induced by mechanical stimuli within osteoblasts (Toma et al. [1997] J. Bone Miner. Res. 12:1626-1636). The present studies examined if the cell adhesion would mimic the mechano-transduction that stimulated opn mRNA expression and whether integrin receptors were involved in these processes. Osteopontin mRNA expression was induced three- to four-fold, 24 hours after embryonic chicken calvaria osteoblast attachment to fibronectin (FN), however no induction was observed if the cells were plated on tissue culture plastic alone. Osteopontin mRNA induction in response to cell attachment on FN was dependent on new protein synthesis and the activation of a tyrosine protein kinase(s) but unlike mechano-induction was independent of the maintenance of the cell's microfilament structure. Integrin receptor(s) were shown to be involved in mediating the signal transduction processes of both cell attachment and mechanical stimulation since incubation of osteoblasts with the integrin binding peptide RGDS partially blocked the induction of opn expression in response to both stimuli. Interestingly, incubation of the osteoblasts that were adherent on tissue culture plastic alone with the RGDS peptide lead to an induction in opn expression suggesting that integrin occupancy by itself was sufficient to initiate the signal transduction process that induced opn expression. In order to assess the role of integrin occupancy vs. focal adhesion complex formation that accompanies cell attachment, in the signal transduction process that induces opn expression, receptor clustering was stimulated pharmacologically with bombesin or lysophosphatidic acid in osteoblasts attached to tissue culture plastic. Neither compound in the absence of occupancy of the integrin receptors was capable of stimulating opn expression in attached cells, however if the cells were placed in suspension pharmacological mediation of receptor clustering and integrin occupancy were additive in their effect of inducing opn expression. These data demonstrate that induction of opn expression by mechanical stimuli and cell attachment are commonly mediated through integrin receptor(s). However, when cells are attached receptor clustering alone which accompanies focal adhesion formation was incapable of mediating signal transduction suggesting that receptor occupancy was a prerequisite to the signal transduction process that leads to the induction of opn mRNA expression.

Is cytoskeletal tension a major determinant of cell deformability in adherent endothelial cells?

We tested the hypothesis that mechanical tension in the cytoskeleton (CSK) is a major determinant of cell deformability. To confirm that tension was present in adherent endothelial cells, we either cut or detached them from their basal surface by a microneedle. After cutting or detachment, the cells rapidly retracted. This retraction was prevented, however, if the CSK actin lattice was disrupted by cytochalasin D (Cyto D). These results confirmed that there was preexisting CSK tension in these cells and that the actin lattice was a primary stress-bearing component of the CSK. Second, to determine the extent to which that preexisting CSK tension could alter cell deformability, we developed a stretchable cell culture membrane system to impose a rapid mechanical distension (and presumably a rapid increase in CSK tension) on adherent endothelial cells. Altered cell deformability was quantitated as the shear stiffness measured by magnetic twisting cytometry. When membrane strain increased 2.5 or 5%, the cell stiffness increased 15 and 30%, respectively. Disruption of actin lattice with Cyto D abolished this stretch-induced increase in stiffness, demonstrating that the increased stiffness depended on the integrity of the actin CSK. Permeabilizing the cells with saponin and washing away ATP and Ca2+ did not inhibit the stretch-induced stiffening of the cell. These results suggest that the stretch-induced stiffening was primarily due to the direct mechanical changes in the forces distending the CSK but not to ATP- or Ca(2+)-dependent processes. Taken together, these results suggest preexisting CSK tension is a major determinant of cell deformability in adherent endothelial cells.

Osteoblast cytoskeletal modulation in response to mechanical strain in vitro.

The structural integrity of microfilaments has been shown to be necessary for the signal transduction of mechanical stimuli within osteoblasts. Qualitative and quantitative changes within the cytoskeleton of osteoblasts may therefore be crucial components of the signal transduction processes of these cells in response to mechanical stimulation. Avian osteoblasts were strained with a device that deforms a flexible, cell-laden membrane at a defined frequency and intensity in a uniform biaxial manner. We examined the effects of mechanical strain on the accumulation of protein and the expression of the major cytoskeletal elements and specific integrin-binding (arginine-glycine-aspartic acid) proteins of these cells. Mechanical strain increased the level of total extracellular matrix-accumulated fibronectin by approximately 150% and decreased that of osteopontin by approximately 60% but had no quantifiable effect on the accumulation of beta1 integrin subunit or collagen type I. An examination of the major elements of the cytoskeleton demonstrated that neither the level of actin nor that of the intermediate filament protein vimentin changed; however, the amount of tubulin decreased by approximately 75% and the amount of vinculin, a major protein of focal adhesion complexes, increased by approximately 250%. An analysis of protein synthesis by two-dimensional gel electrophoresis of [35S]methionine-labeled cytoskeletal proteins demonstrated that the changes in the accumulation of vinculin and tubulin resulted from their altered synthesis. Messenger RNA analysis confirmed that the changes in accumulation and protein synthesis observed for vinculin, fibronectin, and osteopontin were controlled at a pretranslational level. Immunofluorescent microscopy demonstrated that mechanical strain led to increased formation and thickening of actin stress fibers, with a commensurate dissociation in microtubules and a clear increase in levels of vinculin at the peripheral edges of the cells. In conclusion, the elevated rate of synthesis and the increased accumulation of vinculin and fibronectin, as well as the increase in the number and size of stress fibers and focal adhesion complexes, suggest that mechanical strain leads to a coordinated change both in the cytoskeleton and in extracellular matrix proteins that will facilitate tighter adhesion of an osteoblast to its extracellular matrix.

Bipolar hemiarthroplasty for primary osteoarthritis of the hip: a review of 41 cases with 8 to 10 years of follow-up.

This article reports the results of 41 hips in 36 patients who underwent bipolar hemiarthroplasty for primary osteoarthritis of the hip. Surgical technique included a complete capsulectomy and light reaming of the acetabulum in all patients. The average follow-up was 8.9 years with a minimum of 8 years. Harris hip scores improved from 49 preoperatively to 93 at the latest follow-up, with 95% of the hips rated as excellent or good. Two patients had mild, intermittent groin pain, while a third developed recalcitrant pain necessitating revision. Migration of the bipolar cup was minimal with an average of 2.3 mm superior and 2.1 mm medial migration. Survivorship analysis demonstrated an 89.5% survival rate at 10 years.

Arthroscopic microdiscectomy and selective fragmentectomy.

A prospective outcome study to determine the efficacy and complications associated with posterolateral arthroscopic discectomy was initiated in April 1988. One hundred seventy-five patients with symptoms consistent with a lumbar disc herniation and correlative imaging studies were treated operatively, and 169 were available for followup evaluation. Fifty-nine patients with a central herniation or a nonmigrated sequestered fragment were treated using bilateral biportal posterolateral access, whereas 116 patients with radiographic evidence of a paramedial, foraminal, or extra-foraminal herniation were treated using the unilateral uniportal approach. The minimum duration of nonoperative management ranged from 3.5 to 28 months (average, 16 months), and all patients had a minimum of 24 months of postoperative followup. Outcome analysis indicated that 149 procedures were successful, whereas 20 (11.8%) procedures were failures because of persistent radicular symptoms that, in some cases, required open laminotomy. Complications associated with the procedures included one disc space infection, one transient peroneal neuropraxia, and four index extremity skin hypersensitivity. All of these complications resolved without sequelae, and there were no neurovascular complications directly related to the surgical approach.

Signal transduction of mechanical stimuli is dependent on microfilament integrity: identification of osteopontin as a mechanically induced gene in osteoblasts.

Mechanical perturbation has been shown to modulate a wide variety of changes in second message signals and patterns of gene expression in osteoblasts. Embryonic chick osteoblasts were subjected to a dynamic spatially uniform biaxial strain (1.3% applied strain) at 0.25 Hz for a single 2-h period, and osteopontin (OPN), an Arg-Gly-Asp (RGD)-containing protein, was shown to be a mechanoresponsive gene. Expression of opn mRNA reached a maximal 4-fold increase 9 h after the end of the mechanical perturbation that was not inhibited by cycloheximide, thus demonstrating that mechanoinduction of opn expression is a primary response through the activation of pre-existing transcriptional factors. The signal transduction pathways, which mediated the increased expression of opn in response to mechanical stimuli, were shown to be dependent on the activation of a tyrosine kinase(s) and protein kinase A (PKA) or a PKA-like kinase. Selective inhibition of protein kinase C (PKC) had no effect on the mechanoinduction of osteopontin even though opn has been demonstrated to be an early response gene to phorbol 12-myristate 13-acetate (PMA) stimulation. Mechanotransduction was dependent on microfilament integrity since cytochalasin-D blocked the up-regulation of the opn expression; however, microfilament disruption had no effect on the PMA induction of the gene. The microtubule component of the cytoskeleton was not related to the mechanism of signal transduction involved in controlling opn expression in response to mechanical stimulation since colchicine did not block opn expression. Mechanical stimulus was shown to activate focal adhesion kinase (FAK), which specifically became associated with the cytoskeleton after mechanical perturbation, and its association with the cytoskeleton was dependent on tyrosine kinase activity. In conclusion, these results demonstrate that the signal transduction pathway for mechanical activation of opn is uniquely dependent on the structural integrity of the microfilament component of the cytoskeleton. In contrast, the PKC pathway, which also activates this gene in osteoblasts, acts independently of the cytoskeleton in the transduction of its activity.

Assessment of postoperative pain management: patient satisfaction and perceived helpfulness.

OBJECTIVE: Increasing attention has been given to the assessment of patient satisfaction as a way to monitor quality of care in hospital settings. Postoperative patient satisfaction has been thought to be related to level of pain intensity, expectations of outcome, perceived concern by the staff, and helpfulness of treatments. The aim of this study is to develop a simple, reliable measure to assess pain and satisfaction in postsurgical patients and to examine factors related to patient satisfaction. DESIGN: A satisfaction questionnaire was developed for this study and administered to 119 patients who had undergone a major orthopedic surgical procedure. The majority of the patients were diagnosed with osteoarthritis and reported moderate to severe preoperative pain. The 13-item measure was found to be reliable (test-retest r = .86; interexaminer r = .98), valid (exploratory factor analyses; intercorrelations), and easy to administer. RESULTS: Results showed that the majority of the patients were satisfied with their care (91%), postoperative pain intensity (94%), and the way they were treated by the physicians and nurses (98%). Patients with low postoperative pain ratings who perceived that the physicians and nurses showed concern with how much pain they were feeling reported greatest satisfaction with their care (p < .001). In general, lower postoperative pain ratings were the best predictors of satisfaction and helpfulness of treatment. Preoperative pain status, expected level of postoperative pain, and time waiting for pain medication after a request was made were not significantly correlated with ratings of postoperative pain or satisfaction. CONCLUSIONS: These results highlight the important influence of adequate treatment of postoperative pain and perceived concern by the hospital staff on patient satisfaction.

The PartnerWeb Project: a component-based approach to enterprise-wide information integration and dissemination.

A component-based health information resource, delivered on an intranet and the Internet, utilizing World Wide Web (WWW) technology, has been built to meet the needs of a large integrated delivery network (IDN). Called PartnerWeb, this resource is intended to provide a variety of health care and reference information to both practitioners and consumers/patients. The initial target audience has been providers. Content management for the numerous departments, divisions, and other organizational entities within the IDN is accomplished by a distributed authoring and editing environment. Structured entry using a set of form tools into databases facilitates consistency of information presentation, while empowering designated authors and editors in the various entities to be responsible for their own materials, but not requiring them to be technically skilled. Each form tool manages an encapsulated component. The output of each component can be a dynamically generated display on WWW platforms, or an appropriate interface to other presentation environments. The PartnerWeb project lays the foundation for both an internal and external communication infrastructure for the enterprise that can facilitate information dissemination.

Developmental restriction of embryonic calvarial cell populations as characterized by their in vitro potential for chondrogenic differentiation.

The mechanism(s) by which the cells within the calvaria tissue are restricted into the osteogenic versus the chondrogenic lineage during intramembranous bone formation were examined. Cells were obtained from 12-day chicken embryo calvariae after tissue condensation, but before extensive osteogenic differentiation, and from 17-day embryo calvariae when osteogenesis is well progressed. Only cell populations from the younger embryos showed chondrogenic differentiation as characterized by the expression of collagen type II. The chondrocytes underwent a temporal progression of maturation and endochondral development, demonstrated by the expression of collagen type II B transcript and expression of collagen type X mRNA. Cell populations from both ages of embryos showed progressive osteogenic differentiation, based on the expression of osteopontin, bone sialoprotein, and osteocalcin mRNAs. Analysis using lineage markers for either chondrocytes or osteoblasts demonstrated that when the younger embryonic cultures were grown in conditions that were permissive for chondrogenesis, the number of chondrogenic cells increased from approximately 15 to approximately 50% of the population, while the number of osteogenic cells remained almost constant at approximately 35-40%. Pulse labeling of the cultures with BrdU showed selective labeling of the chondrogenic cells in comparison with the osteogenic cells. These data indicate that the developmental restriction of skeletal cells of the calvaria is not a result of positive selection for osteogenic differentiation but a negative selection against the progressive growth of chondrogenic cells in the absence of a permissive or inductive environment. These results further demonstrate that while extrinsic environmental factors can modulate the lineage progression of skeletal cells within the calvariae, there is a progressive restriction during embryogenesis in the number of cells within the calvaria with a chondrogenic potential. Finally, these data suggest that the loss of cells with chondrogenic potential from the calvaria may be related to the progressive limitation of the reparative capacity of the cranial bones.