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Biomedical subjects

J A Lynch

Publications and source records attributed to J A Lynch.

At least 19 recordsLinked to original sources

Improved daily precipitation nitrate and ammonium concentration models for the Chesapeake Bay Watershed.

Daily precipitation nitrate and ammonium concentration models were developed for the Chesapeake Bay Watershed (USA) using a linear least-squares regression approach and precipitation chemistry data from 29 National Atmospheric Deposition Program/National Trends Network (NADP/NTN) sites. Only weekly samples that comprised a single precipitation event were used in model development. The most significant variables in both ammonium and nitrate models included: precipitation volume, the number of days since the last event, a measure of seasonality, latitude, and the proportion of land within 8km covered by forest or devoted to industry and transportation. Additional variables included in the nitrate model were the proportion of land within 0.8km covered by water and/or forest. Local and regional ammonia and nitrogen oxide emissions were not as well correlated as land cover. Modeled concentrations compared very well with event chemistry data collected at six NADP/AirMoN sites within the Chesapeake Bay Watershed. Wet deposition estimates were also consistent with observed deposition at selected sites. Accurately describing the spatial distribution of precipitation volume throughout the watershed is important in providing critical estimates of wet-fall deposition of ammonium and nitrate.

Air Pollutants↗

Value of micro-CT as an investigative tool for osteochondritis dissecans.

PURPOSE: To evaluate micro computed tomography (micro-CT) for the assessment of osteochondritis dissecans in comparison with histology. MATERIAL AND METHODS: Osteochondritis dissecans lesions of 3 patients were evaluated using micro-CT (0.125 mA, 40 keV, 60 microm slice thickness, 60 microm isotropic resolution, entire sample) and light microscopy (toluidine blue, 3-5 microm slice thickness). The methods were compared regarding preparation time, detectability of tissue types and morphologic features of bone and cartilage. RESULTS: Non-destructive micro-CT imaging of the entire sample was faster than histologic preparation of a single slice for light microscopy. Morphologic features of bone and cartilage could be imaged in a comparable way to histology. It was not possible to image cells or different tissue types of bone and cartilage with micro-CT. CONCLUSION: Micro-CT is a fast, non-destructive tool that may be a supplement or, if detailed histologic information is not necessary, an alternative to light microscopy for the investigation of osteochondritis dissecans.

Adult↗

Digital tomosynthesis of hand joints for arthritis assessment.

The two principal forms of hand arthritis, rheumatoid arthritis (RA) and osteoarthritis (OA) have large clinical and economic costs. Radiography has been shown to be a useful tool to assess the condition of the disease. A hand radiograph, however, is a two-dimensional projection of a three-dimensional object. In this report we present the results of a study that applied digital tomosynthesis to hand radiography in order to extract three-dimensional outcome measures that should be more sensitive to arthritis progression. The study was performed using simulated projection radiographs created using micro computed tomography (microCT) and a set of five dry-bone hand skeletons. These simulated projection images were then reconstructed into tomographic slices using the matrix inversion tomosynthesis (MITS) algorithm. The accuracy of the tomosynthesis reconstruction was evaluated by comparing the reconstructed images to a gold standard created using the microCT data. A parameter from image registration science, normalized mutual information, provided a quantifiable figure of merit. This study examined the effects of source displacement, number of reconstructed planes, number of acquisitions, noise added to the gray scale images, and errors in the location of a fiducial marker. We also optimized the reconstruction as a function of two variables k and alpha, that controlled the mixing of MITS with conventional shift-and-add tomosynthesis. A study using hand delineated joint margins demonstrated that MITS images provided a better measurement of average joint space width. We found good agreement between the MITS slices and the true planes. Both joint margins and trabecular structure were visible and the reconstructed slices showed additional structures not visible with the standard projection image. Using hand-delineated joint margins we compared the average joint space width of the gold standard slices to the MITS and projection images. A root-mean square deviation (RMSD), calculated for this comparison, gave RMSDproj = 0.18 mm and RMSDMITS = 0.14 mm for the projection and MITS images, respectively. We have demonstrated the potential of digital tomosynthesis for imaging of the hand to assess arthritic changes. We have also developed a methodology that can be used to optimize the technique and have studied the issues that will control the feasibility of clinical implementation.

Arthritis↗

A comparison of two nickel-titanium instrumentation techniques in teeth using microcomputed tomography.

AIM: The aim of the study was to compare the shaping of root canals by two nickel-titanium instrumentation techniques using microcomputed tomography (MCT). METHODOLOGY: Ten mandibular first molar teeth (30 canals) that had intact crowns and fully formed roots were scanned using MCT. Fifteen canals were instrumented using NiTiFlex hand files (Maillefer) using balanced force. The remainder were instrumented using prototype ProFile 0.04 Taper instruments (Dentsply) in a crown-down manner to an apical size ISO 25. The teeth were scanned again following instrumentation. The two instrumentation techniques were compared in a total of 27 canals. The area of dentine removed at predetermined levels (2.0, 3.0, 4.5, 6.0, 7.5 mm) from the apex was measured. Transportation and centring were recorded. Images constructed at these levels were compared with video images of equivalent physical sections created after the second scan. The volume of dentine removed in the apical 7.5 mm of the root canals of each tooth was calculated and the different techniques compared. Rendered three-dimensional images were used to assess the preparations qualitatively. The time taken for preparation was recorded. RESULTS: There was no significant difference between hand instrumentation with NitiFlex files and machine instrumentation with prototype ProFile 0.04 Taper instruments for any of the variables tested. CONCLUSIONS: Both techniques produced well centred and tapered preparations.

Dental High-Speed Technique↗

Early radiographic features in patients with anterior cruciate ligament rupture.

OBJECTIVE: To determine, in a preliminary cross sectional study of patients with anterior cruciate ligament (ACL) ruptured knees, which of the radiographic features-subchondral cortical plate thickness, trabecular sclerosis, and osteophytosis-appears before or in association with changes in joint space width (JSW) as a surrogate for articular cartilage thickness in patients with ruptured knees. METHODS: 19 patients (14 men), mean (95% CI) age 28.7 (23.6 to 33.8) years, had ACL rupture in one knee only, confirmed by arthroscopy. Anterior draw, Lachman's test, and pivot shift tests were performed and x5 posteroanterior macroradiographs of both knees in a standing semiflexed view were taken at a mean (95% CI) time from injury of 34. 3 (26.9 to 41.7) months. In each radiograph, computerised methods were used to measure minimum JSW and fractal signature analysis (FSA) to quantify the vertical and horizontal trabecular organisation, osteophyte area, and the subchondral cortical plate thickness, in the medial and lateral tibial compartments of all knees. RESULTS: Physical examination confirmed the presence of joint laxity in the injured knees. No statistical difference in either medial or lateral JSW and subchondral cortical plate thickness was detected between ACL ruptured and uninjured knees. FSA showed a significant decrease in fractal dimension for the horizontal trabeculae (size 0.42 mm) in the medial compartment of the ACL ruptured knees compared with the uninjured knees (p<0.01, multivariate analysis of variance). There was an inverse correlation (R -0.74) between the time since knee injury and the difference in FSA values for ACL ruptured and uninjured knees in medial compartment horizontal trabeculae (size 0.4 mm). No significant changes were detected in the lateral compartment. Osteophytes were detected in the medial compartment of nine ACL injured knees. CONCLUSION: Compared with the uninjured knee, ACL rupture leads to thickening of subchondral horizontal trabeculae (decreased FSA) in the medial tibial compartment of all knees, reaching significance at about four years after injury. Osteophytes were present in the same compartment in 9/19 knees. No changes in JSW and subchondral cortical plate thickness were detected. Whether the bony changes detected in these ACL ruptured knees presage those of early osteoarthritis requires further study.

Adult↗

Micro-computed tomography: a new tool for experimental endodontology.

AIM: Micro-computed tomography (MCT) using conebeam geometry is a method of producing true 3D images of the structure of small samples. A prototype MCT unit was adapted for imaging teeth to examine whether it could be used to quantify the instrumentation of root canals. METHODOLOGY: Ten mandibular first molar teeth that had intact crowns and fully formed roots were scanned using MCT at a resolution of 0.081 mm and 3D-rendered images created; root canals were segmented from this. Reproducibility of MCT was verified for root canal shape and size. Access cavities were prepared into the pulp space and root canals enlarged to a continously tapering preparation using a crowndown technique. Each tooth was scanned again to allow comparison of pre- and post-instrumentation images. The roots were then sectioned at five predetermined horizontal levels for video-digitized measurement of dimensions of roots and root canals. The video images had a resolution of 0.025 mm. Video-digitized images of the physical cut surfaces were compared with equivalent MCT reconstructed images. The total area of the root canals (internal) and root (external) at each level were calculated from both MCT reconstructions and video-digitized images, and compared. RESULTS: There was a highly significant correlation between MCT and video images for both external and internal areas (r = 0.94). Rendered 3D images were constructed to show the root canal systems of teeth. The total volumes of the apical 7.5 mm of root canals were calculated from rendered images of nine teeth before and after instrumentation. The mean amount of dentine removed by instrumentation was 3.725 mm3, which was 28% of the original canal volume. CONCLUSIONS: Micro-computed tomography was shown to be accurate for experimental endodontology.

Anatomy, Cross-Sectional↗

Field test of the reproducibility of automated measurements of medial tibiofemoral joint space width derived from standardized knee radiographs.

OBJECTIVE: To estimate the reproducibility of computerized measurements of minimum joint space width (JSW) in the medial tibiofemoral compartment in knee radiographs (semiflexed AP view) obtained from clinical radiology units. METHODS: Technologists from 5 clinical radiology units were trained in the performance of the fluoroscopically assisted semiflexed AP knee examination. Each of 44 subjects (34 with knee osteoarthritis, OA, 10 with bilaterally normal knees) were examined within 7 days in 2 of the 5 units. The examination in each unit was repeated 1 week later. Minimum JSW was measured on digitized radiographic images with computer software that corrected for radiographic magnification. RESULTS: Despite ongoing quality control by technologists, 11% of radiographs were flawed with respect to the protocol standard for knee rotation and 36% with respect to the standard for knee flexion. The standard error of measurement (SEm) of JSW in 174 knees that were examined twice in the same unit was 0.32 mm (SEm = 0.25 mm for the subset of 76 paired radiographs with uniformly high quality). The overall between-unit SEm was 0.45 mm. Within-unit, but not between-unit, precision was related to the technical quality of the radiographs. Precision was unrelated to subject age, sex, race, weight, and radiographic severity of knee OA. CONCLUSION: The within-unit precision of JSW measurements from all pairs of semiflexed views (irrespective of technical quality) represented a notable improvement over that observed in radiographs with flawed knee rotation or flexion (as would be the case in conventional extended knee views). In future applications of this technique, assurance of technical quality by an independent observer should result in a level of measurement precision that will permit the design of clinical trials of disease modifying OA drugs with fewer subjects and/or shorter duration of treatment than is possible with conventional knee radiography.

Female↗

Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais.

A globally effective vaccine will need to elicit cytotoxic T lymphocytes (CTL) capable of recognizing diverse human immunodeficiency virus type 1 (HIV-1) clades. Study of the cellular immune responses of HIV-1-infected persons may allow predictions to be made regarding useful vaccine antigen components. The frequency and magnitude of CTL responses to clade E and B Gag, Pol-RT, Env, and Nef proteins were compared in 12 HLA-characterized, clade E-infected Thais and in 10 clade B-infected North Americans using vaccinia recombinant constructs for protein expression. While responses were detected against all proteins, they were most frequent and cross-reactive to Gag in both groups. Pol-RT was recognized less frequently in Thais than North Americans. Cross-clade protein recognition was common but not uniformly present among these HLA-disparate individuals. Population-specific CTL data are needed to adequately prepare for vaccine trials outside of North America and Europe.

Asian People↗

Novel fluorescent indicator proteins for monitoring free intracellular Ca2+.

We have recently described a fluorescent indicator protein in which red- and blue-shifted variants of green fluorescent protein are joined by the calmodulin-binding sequence from smooth muscle myosin light chain kinase [Romoser V.A., Hinkle P.M., Persechini A. Detection in living cells of Ca(2+)-dependent changes in the fluorescence of an indicator composed of two green fluorescent protein variants linked by a calmodulin-binding sequence. A new class of fluorescent indicators. J Biol Chem 1997; 272: 13270-13274]. The fluorescence emission of this protein at 505 nm (380 nm excitation) is reduced by approximately 65% when (Ca2+)4-calmodulin is bound, with a proportional increase in fluorescence emission at 440 nm. We have found that fusion of an engineered calmodulin, in which the C- and N-terminal EF hand pairs have been exchanged, to the C-terminus of this protein results in a novel indicator that responds directly to changes in the Ca2+ ion concentration, with an apparent Kd value of 100 nM for Ca2+ in the presence of 0.5 mM Mg2+. The affinity of the indicator for Ca2+ can be decreased by altering the amino acid sequence of the calmodulin-binding sequence to weaken its interaction with the intrinsic calmodulin domain. The fluorescence emission of this indicator can be used to monitor physiological changes in the free Ca2+ ion concentration in living cells.

Artificial Gene Fusion↗

Microfocal techniques in quantitative radiography: measurement of cancellous bone organization.

Microfocal radiography records, with unusually good resolution, the detailed structural organization of cancellous bone. A textural imaging method, fractal signature analysis (FSA), was used to quantify the horizontal and vertical trabecular organization recorded within macroradiographic images of the spine of post-menopausal women and the tibia in osteoarthritic knees, and the analysis of variance method was applied to the wrist and hand of rheumatoid patients. Changes in trabecular structure were found to correlate with (i) body weight, age and bone mineral density in the lumbar spine of post-menopausal women; (ii) the degree of cartilage loss and age in the tibia of patients with knee OA; and (iii) analysis of variance quantified the extent of 'normal', osteopaenic and eroded bone in rheumatoid joints. Quantitation of cancellous bone organization can add significantly to our understanding of disease processes and effect of therapy in diseased joints.

Aged↗

Fractal signature analysis measures cancellous bone organisation in macroradiographs of patients with knee osteoarthritis.

OBJECTIVE: To determine whether fractal signature analysis (FSA) of digitised macroradiographs of knees quantifies alterations in trabecular structure in the tibial cancellous bone of osteoarthritic patients with either early or definite joint space narrowing compared with non-arthritic subjects. METHODS: 90 osteoarthritic knees had macroradiographs at x5 magnification. Joint space width and FSA of horizontal and vertical trabecular organisation in the tibial subarticular cancellous bone were measured in the medial and lateral tibio-femoral compartments and compared to reference values obtained from the knees of 14 healthy non-arthritic volunteers, and to the subject's age and weight. RESULTS: Compared to the non-arthritic joints, FSA of the trabecular structure of the medial diseased compartment of the tibia was significantly different and correlated with the degree of joint space narrowing (P < 0.003); FSA of horizontal trabecular structures decreased (P < 0.001) in knees with early osteoarthritis (joint space > 3 mm) and vertical trabecular FSA increased in knees with marked joint space narrowing (joint space < 3 mm). In the lateral compartment of the tibia, FSA did not show a difference between any of the categories. With increasing age of all subjects, the changes in FSA indicated a significant increase in the number of fine horizontal and vertical trabeculae. No correlation was found between the subjects' body weight and changes in the subarticular cancellous bone organisation. CONCLUSIONS: FSA quantifies changes in cancellous bone organisation in knee osteoarthritis. In the diseased compartment, increased horizontal trabecular thickness occurred early and preceded the later changes in the vertical structures.

Age Factors↗

Joint space width measures cartilage thickness in osteoarthritis of the knee: high resolution plain film and double contrast macroradiographic investigation.

OBJECTIVE: To test reliability of joint space width (JSW) measurements as a predictor of cartilage thickness in knees of patients with osteoarthritis (OA), using high definition microfocal radiography. METHOD: JSW was measured from weight bearing plain film macroradiographs taken in the tunnel view and compared with the sum of femoral and tibial cartilage thicknesses measured from double contrast macroarthrograms of the same regions of the same knees obtained in the non-weight bearing lateral position. RESULTS: All knees had medial compartment OA. Comparison of the JSW with the sum of the tibial and femoral cartilage thicknesses revealed a highly significant correlation (p < 0.0001) between the two measurements in the medial but not the lateral compartment. In the middle region of both compartments, JSW was smaller than the cartilage thickness, indicating that, on standing, the curvature of the femoral condyles compressed the cartilage in this region. CONCLUSIONS: JSW reliably measured cartilage thickness in the medial but not the lateral compartment of knees with medial compartment OA. Depending upon the stage of OA disease, JSW reliably reflects cartilage thinning and compression.

Adult↗

Sensitivity of radiographic features and specificity of scintigraphic imaging in hand osteoarthritis.

We undertook to determine which of the radiographic features most reliably detected the presence and disease progression in osteoarthritis in the hand; and which of the radiographic features corresponded with the radionuclide bone scan images. 32 patients with osteoarthritis had X 5 macroradiographs taken of their wrists and hands at 6 monthly intervals over an 18 month period. The high magnification and resolution of microfocal radiography permitted quantitative detection of the extent and change in joint space width, subchondral sclerosis, osteophytosis and juxtaarticular radiolucencies. 4-hour technetium 99m methylene bisphosphonate bone scans were taken at 0 and 12 months and the activity of the tracer uptake at each joint scored. The latter was compared with the radiographic features at each visit and the changes between visits analysed. In hand OA the most sensitive radiographic parameters for detecting disease were osteophytes, subchondral sclerosis and juxtaarticular radiolucencies, with radionuclide imaging demonstrating the increased activity in bone formation associated with the growth and remodelling of osteophytes. Changes in the number and size of osteophytes and joint space narrowing were the only reliable and sensitive parameters for assessing disease progression. We conclude that in osteoarthritis, the bony changes progress significantly before the occurrence of radiographically evident joint space narrowing indicative of cartilage thinning.

Adult↗

Quantitative microfocal radiography detects changes in OA knee joint space width in patients in placebo controlled trial of NSAID therapy.

OBJECTIVE: To assess the usefulness of, and define the time course of changes in the features of osteoarthritic (OA) knees measurable using microfocal radiography, and to determine whether it differs in patients taking a nonsteroidal antiinflammatory drug (NSAID). METHODS: Forty-five patients with knee OA were randomly allocated to receive either diclofenac sodium or placebo for 18 months; 33 (17 NSAID, 16 placebo) completed the study. Clinical and 5 x high definition macroradiographic assessments of both knees in standing semiflexed views were carried out at 6-monthly intervals. Precise measurements were taken of the tibial and femoral subchondral thickness and osteophyte size, and of joint space width (JSW) across the narrowest part of the medial and lateral tibiofemoral compartments. RESULTS: In all knees as a group, there was no statistically significant difference in JSW between treatment groups. However, changes in JSW were significantly different (p < 0.04, multivariate analysis of variance) between treatments in 51 knees with early disease, i.e., those with initially > 50% JSW (22 active, 29 placebo), but not in 15 knees with severe disease, i.e., initially < 50% JSW (10 active, 5 placebo). During the study, osteophyte size in all knees and in those with > 50% JSW increased significantly (p < 0.016; p < 0.008) in the placebo group but remained unchanged in the treatment group. No significant changes were detected in subchondral cortical thickness. CONCLUSION: Using microfocal radiography the time course of changes in JSW and osteophyte size of knees with early, but not late OA, was found to differ in both pattern and magnitude in patients receiving NSAID: In knees with late stage OA the JSW progressively decreased irrespective of treatment. The observations may prove useful for the design of future therapeutic trials.

Adult↗

Fractal signature analysis of macroradiographs measures trabecular organization in lumbar vertebrae of postmenopausal women.

High definition macroradiography was used to provide an image of the detailed structural organization of the cancellous bone in human lumbar vertebrae. The fractal signature analysis (FSA) method was used to quantify the horizontal and vertical trabecular organization recorded within the image. Comparison of the FSA of the postero-anterior and lateral macroradiographs in postmortem lumbar vertebrae showed that neither the superimposition of the neural arch nor the radiographic angle affected the trabecular measurement within the vertebral body. FSA analysis of the trabecular structure measured from the macroradiographs of lumbar vertebrae in two groups of postmenopausal women, with high and low bone mineral density (BMD), showed that the large vertical trabecular structures correlated with the women's body weight (P < 0.01-0.03) and body mass index (P < 0.005-0.05), the fine horizontal structures correlated with the women's age (P < 0.005-0.05), and fine vertical trabecular structures were significantly greater (P < 0.005-0.05) in the low compared with the high BMD group.

Adult↗

Quantitative microfocal radiographic assessment of osteoarthritis of the knee from weight bearing tunnel and semiflexed standing views.

OBJECTIVE: Joint space width (JSW) in osteoarthritis (OA) knee radiography is reported to be optimally assessed from semiflexed standing and tunnel views although no detailed assessment of tunnel view radiography of OA knees has been done. The primary objective of our study was to determine the incidence of joint space narrowing (JSN) in semiflexed standing vs weight bearing tunnel views. The data were also analyzed to examined the degree and relationship of JSN and bony features of OA in the 2 views. METHODS: Ninety OA knees had macroradiographs at 5 times magnification taken in weight bearing standing semiflexed and weight bearing tunnel views. JSW and OA related bony features were measured and compared with reference values obtained from the knees of 14 healthy volunteers without arthritis. RESULTS: Comparison of JSW between the 2 radiographic views identified 3 locations of cartilage loss: JSN recorded in the tunnel only (22%), that in standing view only (8%), and that in both the views (30%). Subchondral sclerosis and osteophytes were significantly larger in 40% of OA knees despite a normal JSW. The tunnel view also enabled better visualization and measurement of osteophytes. CONCLUSION: Standing semiflexed view radiography alone failed to detect JSN in 22% of OA knees. Combined standing and tunnel radiographic views detected JSN more frequently than either view alone. Bony changes were radiographically evident without the presence of JSN indicative of cartilage thinning in as many as 40% of the patients with OA studied.

Aged↗

Precision of joint space width measurement in knee osteoarthritis from digital image analysis of high definition macroradiographs.

The precision of joint space width (JSW) measurements from plain film radiographs of the knee is limited by poor radio-anatomical positioning of the joint and/or insensitive methods of measurement. These limitations were overcome by establishing a precise radio-anatomical position for standing loaded and weight-bearing tunnel views of the knee, using the advantages of high definition macroradiography and a new computerized method for automatic JSW measurement from digitized macroradiographs of the knee. Reproducibility of JSW measurements was obtained from macroradiographs of knees of five post-mortem subjects and 12 patients with osteoarthritis (OA). JSW measurements were altered more by vertical than by horizontal misalignment of the X-ray beam relative to the joint space. In OA knees with medial compartment involvement, JSW measurements were more reproducible in the medial than lateral compartments in both radiographic views. In the medial compartment, the coefficient of variation for joint repositioning was 1% for minimum and 2% for average JSW, and for inter- and intraobserver errors, it was < 1% for both JSW measurements. The precision of this method will permit quantification of changes in JSW associated with disease progression and the treatment of OA.

Aged↗