Biomedical subjects
Publications and source records attributed to Bruce Rothschild.
Calcium pyrophosphate deposition (CPPD) disease is confirmed as equally common in rheumatoid arthritis by synovial fluid and macroscopic skeletal examination. Furthermore, differential frequencies in rheumatoid arthritis and spondyloarthropathy provide additional insights to the "lumper-splitter" question.
Actinomycosis, originally classified as a fungus, is now considered a branching bacteria. Although jaw involvement often presents with classic pathognomonic signs, postcranial disease has not been so characterized. Affected bones from individuals diagnosed in life with actinomycosis were macroscopically and radiologically examined for their macroscopic character. The bones were riddled with spheroid, occasionally coalescing defects associated with periosteal reaction. Erosion penetrated cortical bone as readily as through cortical bone or subchondral bone. X-ray revealed circular lesions with a slight sclerotic margin. Actinomycosis apparently has unique features, which should allow it to be distinguished from multiple myeloma (because of presence of reactive new bone formation) and from fungal disease (because of lack of "fronts of resorption" and penetrating spicules). Similarity to fungal infection is especially of interest because of the earlier phylogenetic classification question.
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STUDY DESIGN: Thoracolumbar facet and interfacet linear dimensions were measured and analyzed. OBJECTIVE: To characterize and analyze the thoracolumbar facet and interfacet size and shape in relation to gender, ethnic group, and age and to detect the extent of normal facet tropism along the thoracolumbar spine. SUMMARY OF BACKGROUND DATA: Knowledge on facet tropism and interfacet shape is limited in the literature as most data are based on 2-dimensional measurements, small samples, or isolated vertebrae. METHODS: Facet shape as represented by width, length, width/length ratio and interfacet distances was obtained directly from dry vertebrae of 240 adult human spines. The specimen's osteologic material is part of the Hamann-Todd Osteological Collection housed at the Cleveland Museum of Natural History, Cleveland, OH. A total of 4080 vertebrae (T1-L5) from the vertebral columns of individuals 20 to 80 years of age were measured, using a Microscribe 3-dimensional apparatus (Immersion Co., San Jose, CA). Data were recorded directly on computer software. Statistical analysis included paired t tests and ANOVA. RESULTS: A significant correlation was found between all thoracolumbar facet dimensions and an individual's height and weight. Facet tropism is a major characteristic of the thoracolumbar spine, the left being longer in the thorax while the right is longer in the lumbar. In general, facet size is age-independent and greater in males compared with females with a significant ethnic component. Facet length is similar for all thoracic vertebrae, whereas it sharply and continuously increases in the lumbar vertebrae. Facet dimension manifests a bipolar distribution along the thoracolumbar vertebrae. Width/length ratio indicates that facets are longer than wider for most verte-brae. The interarticular area manifests a marked inverted trapezoidal shape at T1-T2, a rectangular shape at T3-L3, and an ordinary trapezoidal shape at L4-L5. CONCLUSIONS: Facet tropism is a normal characteristic in humans, yet it varies along the thoracolumbar spine.
STUDY DESIGN: Thoracolumbar facet orientations were measured and analyzed. OBJECTIVES: To establish a comprehensive database for facet orientation in the thoracolumbar vertebrae and to determine the normal human condition. SUMMARY OF BACKGROUND DATA: Most studies on facet orientation have based their conclusions on two-dimensional measurements, in small samples or isolated vertebrae. The amount of normal asymmetry in facet orientation is poorly addressed. METHODS: Transverse and longitudinal facet angles were measured directly from 240 human vertebral columns (males/females, blacks/whites). The specimens' osteologic material is part of the Hamann-Todd Osteological Collection housed at the Cleveland Museum of Natural History (Cleveland, OH). A total of 4,080 vertebrae (T1-L5) from the vertebral columns of individuals 20 to 80 years of age were measured, using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA). Data were recorded directly on computer software. Statistical analysis included paired t tests and analysis of variance. RESULTS.: Facet orientation is independent of gender, age, and ethnic group. Asymmetry in facet orientation is found in the thorax. All thoracolumbar facets are positioned in an oblique plane. In the transverse plane, all facets from T1 to T11 are positioned with an anterior inclination of approximately 25 degrees to 30 degrees from the frontal plane. The facets of T12-L2 are oriented closer to the midsagittal plane of the vertebral body (mean range, 25.89 degrees-33.87 degrees), while the facets of L3-L5 are oriented away from that plane (mean range, 40.40 degrees-56.30 degrees). Facet transverse orientation at the thoracolumbar junction is highly variable (approximately 80% with approximately 101 degrees and approximately 20% with 35 degrees). All facets are oriented more vertically from T1 (approximately 150 degrees) to L5 (approximately 170 degrees). The facet sagittal orientations of the lumbar zygoapophyseal joints are not equivalent. CONCLUSIONS.: Asymmetry in facet orientation is a normal characteristic in the thorax.
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Finding the interacting pairs of proteins between two different protein families whose members are known to interact is an important problem in molecular biology. We developed and tested an algorithm that finds optimal matches between two families of proteins by comparing their distance matrices. A distance matrix provides a measure of the sequence similarity of proteins within a family. Since the protein sets of interest may have dozens of proteins each, the use of an efficient approximate solution is necessary. Therefore the approach we have developed consists of a Metropolis Monte Carlo optimization algorithm which explores the search space of possible matches between two distance matrices. We demonstrate that by using this algorithm we are able to accurately match chemokines and chemokine-receptors as well as the tgfbeta family of ligands and their receptors.
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OBJECTIVE: A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug. METHODS: Patients with active RA (n = 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using high-performance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis. RESULTS: The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination half-lives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P = 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P = 0.001-0.021) during weeks 1, 2, and 3. CONCLUSION: There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.
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