Fibromyalgia and disability.
Explore the source record for details and available documents.
Disability Evaluation↗
Biomedical subjects
M D Smith
Publications and source records attributed to M D Smith.
Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.
OBJECTIVE: To establish the presence of inflammation in and cytokine production by synovial membranes from patients with various stages of early osteoarthritis (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of chondral damage. METHODS: Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables including thickness of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled ribo-probes and immunohistochemistry. RESULTS: There was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA, with the most marked changes seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovial membranes from all patients with OA, irrespective of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA. CONCLUSION: Chronic inflammatory changes with production of proinflammatory cytokines are a feature of synovial membranes from patients with early OA, with the most severe changes seen in patients at the time of joint replacement surgery resembling those seen in rheumatoid arthritis. This low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.
Adolescent↗
Pediatric seat belt injuries.
Two cases are reported that reiterate the significance of pediatric seat belt usage. Detection of associated injuries is difficult and often delayed. The presence of intra-abdominal free fluid on CT without solid organ injury should indicate the need for surgical intervention. Diagnostic peritoneal lavage usage in pediatric seat belt trauma may need to be re-evaluated. These cases emphasize the above as well as important postinjury clinical changes necessary for earlier diagnosis. A newly designed youth seat belt is presented to help prevent these injuries.
Child↗
Synovial membrane cytokine profiles in reactive arthritis secondary to intravesical bacillus Calmette-Guérin therapy.
We describe the cellular infiltrate and cytokine profile in sequential synovial membrane biopsies from a patient with acute followed by chronic synovitis after intravesical bacillus Calmette-Guérin (BCG) therapy for an in situ transitional cell carcinoma of the bladder. Histological and immunohistochemical analysis of 3 synovial biopsies were done sequentially over a 9 month period. The patient was HLA-B27 positive, but HLA-DR4 negative, and did not have the "shared epitope." Unlike other cases, this patient's arthritis did not respond initially to nonsteroidal antiinflammatory drugs and was exacerbated by corticosteroid therapy. The synovitis took a neutrophilic form, with marked synovial membrane content of interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). It subsequently developed into chronic lymphoplasmacytoid synovitis, similar to rheumatoid arthritis (RA), with decreased IL-8 but continuing IL-1 and TNF-alpha production in the synovial membrane. The synovitis resolved to a fibrotic synovium with residual thickening of the synovial lining layer and continued production of TNF-alpha. Thus, during the evolution of this arthritis, the synovial layer and continued production of TNF-alpha. Thus, during the evolution of this arthritis, the synovial membrane yielded a cellular infiltrate and cytokine content that had marked similarities with that seen in RA; however, the arthritis eventually remitted spontaneously.
Aged↗
An in vivo analysis of the dimensional changes of the neuroforamen after anterior cervical diskectomy and fusion: a radiologic investigation.
Eighteen patients (11 men, 7 women; average age, 45.5 years) who underwent anterior cervical diskectomy and fusion (ACDF) for the treatment of radiculopathy had preoperative and immediate postoperative computed tomography (CT) scans to measure pre- and postoperative foraminal heights and foraminal areas, preoperative disk space height, and postoperative graft height. The mean foraminal height preoperatively was 0.851 cm; postoperatively, it was 1.01 cm, with a mean percentage increase of 20% (-8.8 to 56.8%). Mean preoperative foraminal area was 37.53 mm2, increasing to a mean of 49.04 mm2 postoperatively with a mean percentage increase of 33% (range, -1.5 to 76.9%). No significant correlations between graft height and change in maximal foraminal height or foraminal area or between changes in foraminal height or area and postoperative symptom relief were found. Although significant increases in foraminal dimensions were seen radiographically after ACDF, these increases were variable and not strongly related to graft height. In addition, the increases in foraminal dimensions were not related to the short-term clinical results of ACDF. This study fails to support the hypothesis that the reliable results of ACDF can be ascribed primarily to indirect decompression of the uncovertebral foramen by disk-space distraction.
Adult↗
Variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biopsies: quantification using color video image analysis.
OBJECTIVE: To investigate the variability in immunostaining for cytokines and cell adhesion molecules using multiple arthroscopically directed synovial biopsies from within a rheumatoid knee joint, quantitated by color video image analysis. METHODS: Needle arthroscopic biopsies were taken from multiple sites (4-7 sites) around a knee joint in 8 patients with rheumatoid arthritis (RA). In 5 patients, immunoperoxidase staining for the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and IL-1beta as well as the IL-1 receptor antagonist protein (IL-1ra) was performed. In 3 patients, immunoperoxidase staining for the cell adhesion molecules E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1, CD54), and platelet endothelial cell adhesion molecule (PECAM, CD31) was performed. Immunostaining was quantified using color video image analysis. RESULTS: The overall probability of paired biopsies from the same RA knee joint being significantly different from each other due to sampling variation was at most 22% for cytokine staining (usually less than 10%). There were no significant differences between intrabiopsy and interbiopsy variability for cell adhesion molecule staining of the sublining and vessels. CONCLUSION: The variability in cytokine and cell adhesion molecule staining within any single biopsy usually reflects the variability between biopsies taken from different sites in the same rheumatoid joint when the immunostaining is quantified using color video image analysis. Therefore, only a small number of synovial biopsies are required to accurately determine the cytokine and cell adhesion molecule expression in a single joint.
Aged↗
The functionally antagonistic POU family transcription factors Brn-3a and Brn-3b show opposite changes in expression during the growth arrest and differentiation of human neuroblastoma cells.
The Brn-3a and Brn-3b POU family transcription factors have previously been shown to have functionally antagonistic effects, with Brn-3a activating specific gene promoters which are repressed by Brn-3b. We show here that proliferating cell lines of human neuroblastoma origin have a high ratio of Brn-3b to Brn-3a compared with other cell lines derived from related tumours. Moreover, the level of Brn-3a rises and that of Brn-3b falls when neuroblastoma cell lines are exposed to treatments which induce a cessation of proliferation. Such treatments also result in the activation of a test promoter which is normally stimulated by Brn-3a and repressed by Brn-3b. Our findings suggest that these antagonistic factors may play a key role in regulation of gene expression during human neuroblastoma differentiation and could thus represent a potential therapeutic target for treatments designed to induce such differentiation.
Base Sequence↗
Is a clinical application of hybrid liver support systems limited by an initial disorder in cellular amino acid and alpha-keto acid metabolism, rather than by later gradual loss of primary hepatocyte function?
The in-vitro amino acid (AA) and alpha-keto acid (KA) metabolism of bioreactors initially seeded with 2.5 x 10(9) pig hepatocytes was investigated with a perfusion technique. Considerable changes in the culture medium concentrations of AA and KA were measured during the first days in culture. This is indicative of dynamic cellular metabolism in the initial phase. While the concentration of pyruvate decreased starting on the first day, alpha-ketoglutarate, alpha-ketoisocaproate, alpha-ketoisovalerate, and alpha-keto-beta-methyl-n-valerate were synthesized. The long term use of hepatocyte cultures in bioreactors and thus a desirable clinical hybrid liver support therapy appears to be possible since the hepatocytes switched, after 15 days in culture, to steady-state conditions with a stable amino acid turnover featuring general AA uptake accompanied by KA release. The release of branched chain KA, in particular that of alpha-ketoisocaproate, reflects an effective transamination activity in the bioreactor system. Primary pig hepatocytes cultivated in hybrid liver support systems for therapy of acute liver failure or as devices for bridging to liver transplantation can sustain amino acid metabolism for at least 30 days in vitro. However, an initial disorder following the cell isolation that is demonstrated may limit immediate utilization of the systems prior to the reorganisation of the cells to tissue-like structures in bioreactors.
Amino Acids↗
Cervical discogenic pain. Prospective correlation of magnetic resonance imaging and discography in asymptomatic subjects and pain sufferers.
STUDY DESIGN: Asymptomatic subjects and chronic head/neck pain sufferers were studied with high-field magnetic resonance imaging and cervical discography to compare and correlate both tests. OBJECTIVES: To assess the accuracy of magnetic resonance imaging and discography in identifying the source(s) of cervical discogenic pain. SUMMARY OF BACKGROUND DATA: Previous retrospective studies describe a generally poor correlation between magnetic resonance imaging and provocative discography in the cervical spine. METHODS: Ten lifelong asymptomatic subjects and 10 nonlitigious chronic neck/head pain patients underwent discography at C3-C4 through C6-C7 after magnetic resonance imaging. Disc morphology and provoked responses were recorded at each level studied. RESULTS: Of 20 normal discs by magnetic resonance from the asymptomatic volunteers, 17 proved to have painless anular tears discographically. The average response per disc (N = 40) for this group was 2.42, compared to 5.2 (N = 40) for the neck pain group. In the pain patients, 11 discs appeared normal at magnetic resonance imaging, whereas 10 of these proved to have anular tears discographically. Two of these 10 proved concordantly painful with intensity ratings of at least 7/10. Discographically normal discs (N = 8) were never painful (both groups), whereas intensely painful discs all exhibited tears of both the inner and outer aspects of the anulus. CONCLUSIONS: Significant cervical disc anular tears often escape magnetic resonance imaging detection, and magnetic resonance imaging cannot reliably identify the source(s) of cervical discogenic pain.
Adult↗
Pharmacoeconomic analysis of smoking-cessation interventions.
A model for evaluating the costs and benefits of smoking-cessation interventions is proposed and published data on the subject are analyzed. Decision-tree analysis was used to determine the costs and benefits, from an employer's perspective, of several smoking-cessation options. The probability that a smoker would stop smoking was based on two published meta-analyses of smoking-cessation interventions and a national study of nicotine patch users who received a smoking-cessation consultation from a pharmacist. The costs were determined by telephone interviews and market research information. A sensitivity analysis of treatment costs was conducted to determine the optimal treatment from the standpoint of costs versus benefits. The smoking-cessation intervention from which an employer would receive the greatest net benefit is the nicotine patch with smoking-cessation consultation from a pharmacist and patient participation in a formal smoking-cessation program. Pharmacists included in this analysis could charge a smoking-cessation consultation fee of up to $109 per patient. Pharmacoeconomic analysis suggested that smoking-cessation therapy consisting of treatment with nicotine patches, consultations with pharmacists, and participation in a comprehensive behavioral program would be the most cost-beneficial to employers.
Behavior Therapy↗
Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone.
OBJECTIVE: To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP). METHODS: Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. RESULTS: Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P<0.05), tender joints (P<0.005), VAS for pain (p<0.005), and generalized stiffness (P<0.005), as well as a decrease in the C-reactive protein level (P<0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. CONCLUSION: Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.
Aged↗
Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E-selectin and intercellular adhesion molecule 1 expression.
OBJECTIVE: To investigate the effects of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP) on cell adhesion molecule expression on the synovial vascular endothelium in patients with rheumatoid arthritis (RA). METHODS: Sequential arthroscopic biopsy samples were taken before and 24 hours after MP administration (10 patients) and at the time of RA flare (2 patients) and after retreatment with MP (1 patient). Immunoperoxidase staining for E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1; CD54) and platelet-endothelial cell adhesion molecule (PECAM; CD31) was performed, and the staining was quantified by color video image analysis. RESULTS: MP caused a rapid (within 24 hours) and substantial decrease in the expression of E-selectin on the synovial vascular endothelium, with a smaller reduction in ICAM-1 expression on synovial vascular endothelium and the synovial lining. There were no similar effects on synovial membrane P-selectin or PECAM expression. CONCLUSION: A potential mechanism by which MP impairs neutrophil trafficking into inflamed RA joints might be by reducing E-selectin, and possibly, ICAM-1, expression in the synovial membrane.
Aged↗
Systemic liberation of interleukin-1 beta and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation.
We measured systemic serum levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) during the preoperative, anhepatic, and postreperfusional phases up to the 7th postoperative day in 60 patients undergoing orthotopic liver transplantation (LTx). In contrast to IL-1 beta, IL-1ra, TNF-alpha, and IL-6 showed a significant elevation in relation to the early phase after reperfusion, while TNF-alpha displayed a high grade of scatter. In addition, IL-1ra levels were significantly elevated during the anhepatic phase. Maximum serum levels were found at 15 min after reperfusion, 120 min after reperfusion, and on the 1st postoperative day, respectively. Serum levels decreased considerably at 24 h and 7 days after reperfusion. The comparative monitoring of systemic cytokine and cytokine antagonist levels, in particular the liberation of IL-1ra and IL-6 may provide useful parameters for the development of new liver preservation theories for LTx.
Adult↗
Antibody production in plants.
Production of heterologous proteins in plants has become increasingly efficient due to recent advances in plant biotechnology. Heterologous proteins that have specifically attracted a great deal of attention are plant-produced monoclonal antibodies. A variety of applications for these so-called plantibodies have been explored since they were first expressed in tobacco seven years ago. Both full length antibodies and antibody fragments produced in transgenic plants offer many intriguing possibilities to plant molecular biologists and plant breeders. However, questions such as how cellular targeting influences the expression and accumulation of these proteins in plants still need to be answered before the technology can be used commercially, on a large-scale.
Journal Article↗
Validation of three-dimensional echocardiography for quantifying the extent of dyssynergy in canine acute myocardial infarction: comparison with two-dimensional echocardiography.
OBJECTIVES: This study was designed to compare the accuracy of three- and two-dimensional echocardiography for quantifying the extent of abnormal wall motion in experimental acute myocardial infarction, as correlated with the pathologic determination of infarct size. BACKGROUND: Two-dimensional echocardiographic estimations of the fraction of myocardium showing abnormal wall motion are often used as an index of infarct size even though they rely on image plane positioning and geometric assumptions that may not be valid. Three-dimensional echocardiographic reconstruction of the endocardial surface eliminates the need for these assumptions and may improve echocardiographic estimates of infarct size. METHODS: Coronary ligation was performed in 14 open chest dogs, and echocardiographic imaging of the ventricle was performed 6 h later. Three-dimensional echocardiography used seven or eight spatially registered short-axis images to measure percent of endocardial surface and mass showing abnormal wall motion. Three two-dimensional echocardiographic methods using multiple, nonpatially registered images were evaluated. One method used seven or eight-axis slices and a summation of discs algorithm for computing surface area. The second method used the same images and a conical model for the left ventricle. The third used basal, middle and apical short-axis plus apical four- and two-chamber views comparing summed endocardial lengths showing abnormal wall motion with the total of the endocardial dimensions, expressed as percent. The percent of left ventricular mass and surface area infarcted was determined by staining with triphenyltetrazolium chloride. RESULTS: Three-dimensional echocardiographic measurements of endocardial surface and correlated more closely with infarct mass (r = 0.94, SEE +/- 3.6%) than did the two-dimensional method using the summation of discs algorithm (r = 0.85, SEE +/- 6.6%), he summation of conical sections algorithm (r = 0.82, SEE +/- 5.4%) or the method using summed endocardial lengths (r = 0.79, SEE +/- 7.4%). Limits of agreement analysis comparing mass showing abnormal wall motion with anatomic infarct mass surface area showing abnormal wall motion with anatomic infarct surface area showed the smallest limits for three-dimensional echocardiography. CONCLUSIONS: Three-dimensional echocardiography is a more accurate means of noninvasively estimating myocardial infarct size in this canine model than two-dimensional echocardiography.
Animals↗
Three-dimensional echocardiography compared to two-dimensional echocardiography for measurement of left ventricular mass anatomic validation in an open chest canine model.
A three-dimensional echocardiographic system has been developed that can accurately compute left ventricular mass in vitro. This study was designed to validate the new echocardiographic system for the measurement of left ventricular mass in vivo and to compare the accuracy of three-dimensional echocardiography to the accuracy of conventional two-dimensional echocardiography for measuring left ventricular mass. Echocardiographic imaging was performed 6 h following coronary ligation in 20 open chest dogs, at which time the heart was excised and the left ventricle weighed. Three-dimensional echocardiography used multiple short axis sections and polyhedral surface reconstruction to compute myocardial volume. The two dimensional methods employed the truncated ellipsoid model and the area-length model. Myocardial volume was multiplied by 1.05 g/cc and echocardiographic mass estimates were compared to the true left ventricular weight. Three-dimensional echocardiography provided the best correlation (r = 0.96, upsilon r = 0.88 and r = 0.83 for the truncated-ellipsoid and area-length methods, respectively), and the lowest standard error of the estimate for the regression equation (+/- 5.5 g upsilon +/- 11.0 and +/- 14.6 g, respectively). Three dimensional echocardiography also had the lowest standard deviation for the echo-true mass differences (+/- 5.8 g upsilon +/- 10.7 g and +/- 14.2 g) and a lower root mean square percent error (6.8%) upsilon 12.6% and 12.7%). In this open chest canine model, three-dimensional echocardiography is more accurate than standard two-dimensional echocardiographic methods for measuring left ventricular mass.
Animals↗
Relation of Doppler transmitral flow patterns to functional status in congestive heart failure.
We analyzed the relation of Doppler transmitral flow patterns and New York Heart Association (NYHA) classification in 60 consecutive patients with heart failure (44 men and 16 women; mean age 58 +/- 13 years) with left ventricular ejection fraction of < 40 percent. Of the study population, 40 patients with mild to moderate heart failure underwent symptom-limited exercise testing. The relation of transmitral flow pattern and exercise tolerance was also analyzed. Doppler echocardiography was performed in all patients. The patients were subdivided into nonrestrictive and restrictive groups according to the pattern. The univariate analysis showed a relation for left ventricular ejection fraction (p = 0.01 by analysis of variance testing) and transmitral flow pattern (p = 0.0003 by chi-squared test) with NYHA classification. When the multivariate regression analysis was performed, only the restrictive pattern by Doppler emerged as an independent determinant of the advanced NYHA class (p = 0.005). In mild to moderate congestive heart failure, patients with nonrestrictive pattern exercised significantly longer than those with the restrictive pattern by an average of 133 seconds (p = 0.003) despite comparable reductions in ejection fraction. Thus the restrictive transmitral flow pattern by Doppler is a noninvasive marker for severe symptoms and diminished exercise tolerance in heart failure patients.
Aged↗
In-vitro activity of carbapenem antibiotics against beta-lactam susceptible and resistant strains of Burkholderia pseudomallei.
Four carbapenem antibiotics were tested for their in-vitro activities (MICs, MBCs and time-kill studies) against Burkholderia pseudomallei. The carbapenems were all more active than either ceftazidime or co-amoxiclav against strains of B. pseudomallei with a normal susceptibility pattern. Biapenem was the most active antibiotic tested. All four carbapenems retained bactericidal activity against 24 strains of B. pseudomallei with reduced susceptibility to ceftazidime and/or co-amoxiclav.
Anti-Bacterial Agents↗