bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Prices and Emergency Department Mentions for Cocaine and Heroin
Authors: Caulkins Jonathan P. 
Published: November 2008

Objectives. In this report, the author illustrates the historic relation between retail drug prices and emergency department mentions for cocaine and heroin. Methods. Price series based on the Drug Enforcement Administration's System to Retrieve Information From Drug Evidence database were correlated with data on emergency department mentions from the Drug Abuse Warning Network for cocaine (1978–1996) and heroin (1981–1996). Results. A simple model in which emergency department mentions are driven by only prices explains more than 95% of the variation in emergency department mentions. Conclusions. Fluctuations in prices are an important determinant of adverse health outcomes associated with drugs.
Eligibility Under State Children's Health Insurance Programs
Authors: Ullman Frank , Hill Ian 
Published: November 2008

Objectives. This study analyzed associations between income eligibility criteria under the State Children's Health Insurance Program (SCHIP) and state characteristics. Methods. We used multivariate methods to explore relations between eligibility expansions under SCHIP and percentages of uninsured children from low-income families, per capita income, and political characteristics. Results. Proportions of uninsured children, per capita income, and states' preexisting eligibility thresholds were statistically associated with changes in eligibility thresholds, whereas only per capita income was associated with overall SCHIP eligibility thresholds. Political dynamics were not statistically related to SCHIP expansions. Conclusions. State demographic characteristics were associated with changes in eligibility from preexisting levels but rarely were associated with SCHIP eligibility thresholds.
Health and Federal Budgetary Effects of Increasing Access to Antiretroviral Medications for HIV by Expanding Medicaid
Authors: Kahn James G. , Haile Brain , Kates Jennifer , Chang Sophia 
Published: November 2008

Objectives. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. Methods. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10 000, absent or inadequate medication insurance, and annual income less than $10 000. Two benefits were modeled, “full” and “limited” (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. Results. An estimated 38 000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13 000 AIDS diagnoses and 2600 deaths and add 5816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Conclusions. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.
Use of Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors Among Medicaid Beneficiaries With AIDS
Authors: Sambamoorthi Usha , Moynihan Patrick J. , McSpiritt Elizabeth , Crystal Stephen 
Published: November 2008

Objectives. This study compared the use of new antiretroviral treatments across sociodemographic subgroups during the 3 years after the introduction of these treatments and examined diffusion of the therapies over time. Methods. Merged surveillance and claims data were used to examine use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors (PI/NNRTIs) among New Jersey Medicaid beneficiaries with AIDS. Results. In 1996, there were sharp disparities in use of PI/NNRTI therapy among racial minorities and injection drug users, even after control for other patient characteristics. These gaps had decreased by 1998. Higher PI/NNRTI treatment rates were also observed among beneficiaries enrolled in a statewide HIV/AIDS-specific home- and community-based Medicaid waiver program. Conclusions. Even within a population of individuals similar in regard to health coverage, there were substantial sociodemographic differences in use of PI/NNRTIs during the early years after their introduction. These differences narrowed as new treatments became standard. Participation in a case-managed Medicaid waiver program seems to be associated with a more appropriate pattern of use. These results suggest a need to address nonfinancial barriers to care.
The Quality Improvement–Research Divide and the Need for External Oversight
Authors: Bellin Eran , Dubler Nancy Neveloff 
Published: November 2008

Historically, quality assurance studies have received scant ethical attention. The advent of information systems capable of supporting research-grade continuous quality improvement projects demands that we clearly define how these projects differ from research and when they require external review. The ethical obligation for the performance of quality assurance projects, with its emphasis on identifiable immediate action for a served population, is a critical distinction. The obligation to perform continuous quality improvement is a deliverable of the social contract entered into implicitly by patients and health care providers and systems. In this article, the authors review the ethical framework that requires these studies, evaluate the differences between quality assurance studies and classic research, and propose criteria for requiring external review.
Surgical treatment of a rostral mandibular complex odontoma in a 3‐year‐old horse
Authors: Snyder C. , Dubielzig R. R. , Gengler W. , Livesey M. A. 
Published: November 2008

SummaryComplex odontomas are rare odontogenic tumours in horses comprised of a combination of mesenchymal and epithelial tissues. Examination, radiographic and histopathological findings in this patient all represent the typical behaviour of a complex odontoma. Oral tumours in horses may have treatment limitations due to tumour size and location. Similar to treatment in other species, surgical enucleation was curative for this type of tumour.
Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone–related protein in mice
Authors: Chen Xuesong , Macica Carolyn M. , Nasiri Ali , Broadus Arthur E. 
Published: November 2008

AbstractObjectiveChondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (IHH)–parathyroid hormone–related protein (PTHrP) axis. In weight‐bearing joints, this growth zone comes to be subdivided by the secondary ossification center into distinct articular and growth cartilage structures. The purpose of this study was to explore the cells of origin, localization, regulation of expression, and putative functions of IHH and PTHrP in articular cartilage in the mouse.MethodsWe assessed IHH and PTHrP expression in an allelic PTHrP‐LacZ–knockin mouse and several versions of PTHrP‐null mice. Selected joints were unloaded surgically to examine load‐induction of PTHrP and IHH.ResultsThe embryonic growth zone appears to serve as the source of PTHrP‐expressing proliferative chondrocytes that populate both the forming articular cartilage and growth plate structures. In articular cartilage, these cells take the form of articular chondrocytes in the midzone. In PTHrP‐knockout mice, mineralizing chondrocytes encroach upon developing articular cartilage but appear to be prevented from mineralizing the joint space by IHH‐driven surface chondrocyte proliferation. In growing and adult mice, PTHrP expression in articular chondrocytes is load‐induced, and unloading is associated with rapid changes in PTHrP expression and articular chondrocyte differentiation.ConclusionWe conclude that the IHH–PTHrP axis participates in the maintenance of articular cartilage. Dysregulation of this system might contribute to the pathogenesis of arthritis.
Disease activity–guided rituximab therapy in rheumatoid arthritis: The effects of re‐treatment in initial nonresponders versus initial responders
Authors: Thurlings Rogier M. , Vos Koen , Gerlag Daniëlle M. , Tak Paul P. 
Published: November 2008

AbstractObjectiveTo explore the efficacy of re‐treatment with rituximab in patients with rheumatoid arthritis (RA) who were initial nonresponders to treatment, and to evaluate the effects of rituximab in RA when re‐treatment is given in a standardized way based on the Disease Activity Score in 28 joints (DAS28), according to the international consensus statement.MethodsPatients with RA who had a DAS28 of ≥3.2 received up to 3 courses of rituximab at intervals of at least 6 months, regardless of whether the patient had responded to the first course of treatment with rituximab.ResultsOf the 30 patients with RA who were included in the study, 26 could be evaluated for the efficacy of treatment after 6 months. Eighteen patients qualified for re‐treatment at 6 months, 6 patients were re‐treated at a later time point because of a disease relapse, and 2 other patients were not re‐treated because they had low disease activity. Seven of the 24 patients who qualified for re‐treatment had not exhibited clinical improvement after the first treatment course. These patients typically did not respond to subsequent courses of rituximab. Of interest, in the 17 patients who had exhibited a clinical response to the first course of rituximab, the second and third treatment courses resulted in European League Against Rheumatism responses similar to those observed after the first course, and no major relapses occurred before re‐treatment.ConclusionRituximab re‐treatment is not effective in patients who do not exhibit clinical improvement after the first treatment course, which is consistent with the notion that such patients represent a different pathogenetic subset of RA. Patients who initially responded to rituximab treatment experienced sustained benefit from DAS28‐based systematic re‐treatment according to the international consensus statement.
Zonal gene expression of chondrocytes in osteoarthritic cartilage
Authors: Fukui Naoshi , Miyamoto Yoshinari , Nakajima Masahiro , Ikeda Yasuko , Hikita Atsuhiko , Furukawa Hiroshi , Mitomi Hiroyuki , Tanaka Nobuho , Katsuragawa Yozo , Yamamoto Seizo , Sawabe Motoji , Juji Takuo , Mori Toshihito , Suzuki Ryuji , Ikegawa Shiro 
Published: November 2008

AbstractObjectiveTo determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage.MethodsOA cartilage was obtained from macroscopically intact areas of 4 knee joints with end‐stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom‐designed microarray that focused on chondrocyte‐related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real‐time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones.ResultsA total of 198 genes (∼40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real‐time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone‐related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression.ConclusionIn OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.
Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophages
Authors: Reiss Allison B. , Carsons Steven E. , Anwar Kamran , Rao Soumya , Edelman Sari D. , Zhang Hongwei , Fernandez Patricia , Cronstein Bruce N. , Chan Edwin S. L. 
Published: November 2008

AbstractObjectiveTo determine whether methotrexate (MTX) can overcome the atherogenic effects of cyclooxygenase 2 (COX‐2) inhibitors and interferon‐γ (IFNγ), both of which suppress cholesterol efflux protein and promote foam cell transformation in human THP‐1 monocyte/macrophages.MethodsMessage and protein levels of the reverse cholesterol transport proteins cholesterol 27‐hydroxylase and ATP‐binding cassette transporter A1 (ABCA1) in THP‐1 cells were evaluated by real‐time polymerase chain reaction and immunoblot, respectively. Expression was evaluated in cells incubated in the presence or absence of the COX‐2 inhibitor NS398 or IFNγ, with and without MTX. Foam cell transformation of lipid‐laden THP‐1 macrophages was detected with oil red O staining and light microscopy.ResultsMTX increased 27‐hydroxylase message and completely blocked NS398‐induced down‐regulation of 27‐hydroxylase (mean ± SEM 112.8 ± 13.1% for NS398 plus MTX versus 71.1 ± 4.3% for NS398 alone; P < 0.01). MTX also negated COX‐2 inhibitor–mediated down‐regulation of ABCA1. The ability of MTX to reverse inhibitory effects on 27‐hydroxylase and ABCA1 was blocked by the adenosine A2A receptor–specific antagonist ZM241385. MTX also prevented NS398 and IFNγ from increasing transformation of lipid‐laden THP‐1 macrophages into foam cells.ConclusionThis study provides evidence supporting the notion of an atheroprotective effect of MTX. Through adenosine A2A receptor activation, MTX promotes reverse cholesterol transport and limits foam cell formation in THP‐1 macrophages. This is the first reported evidence that any commonly used medication can increase expression of antiatherogenic reverse cholesterol transport proteins and can counteract the effects of COX‐2 inhibition. Our results suggest that one mechanism by which MTX protects against cardiovascular disease in rheumatoid arthritis patients is through facilitation of cholesterol outflow from cells of the artery wall.
Disparate folding and stability of the ankylosing spondylitis–associated HLA–B*1403 and B*2705 proteins
Authors: Merino Elena , Galocha Begoña , Vázquez Miriam N. , López De Castro José A. 
Published: November 2008

AbstractObjectiveTo investigate the folding, assembly, maturation, and stability of HLA–B*1402 and B*1403, which differ by 1 amino acid change and are differentially associated with ankylosing spondylitis (AS), and to compare these features with those of B*2705.MethodsStable transfectants expressing B*1402, B*1403, and B*2705 were used. Folding rates were estimated from the ratio of unfolded heavy chains to folded heavy chains that had been immunoprecipitated with specific antibodies in pulse–chase experiments. Heavy chain misfolding was measured as the half‐life of endoglycosidase H (Endo H)–sensitive β2‐microglobulin–free heavy chains. Maturation/export rates were measured by acquisition of Endo H resistance. Association with calnexin or tapasin was analyzed by coprecipitation with chaperone‐specific antibodies, and surface expression was estimated by flow cytometry. Thermostability of HLA–peptide complexes was assessed by immunoprecipitation after incubation at various temperatures. Heavy chain expression was quantified by Western blotting.ResultsThe folding rates of B*1402 and B*1403 were similar, and both were faster and more efficient than B*2705, but some unfolded heavy chains from both B14 subtypes remained in the endoplasmic reticulum (ER) with a long half‐life. The export rates of B*1402 and B*1403 were slow, and the heterodimers partially dissociated after exiting the ER, as revealed by significant amounts of Endo H–resistant and surface‐expressed free heavy chains. Both interaction with tapasin and thermostability were higher for B*2705 than for B*1402 and higher for B*1402 than for B*1403, suggesting that the repertoires of the B*1402‐bound peptide and especially the B*1403‐bound peptide were less optimized than that of B*2705.ConclusionOur results indicate that the folding, maturation, and stability of B*1403 differ more from B*2705 than from B*1402. Thus, these features cannot account for the fact that only the 2 former allotypes are associated with AS.
Increased hydraulic conductance of human articular cartilage and subchondral bone plate with progression of osteoarthritis
Authors: Hwang Jennifer , Bae Won C. , Shieu Wendy , Lewis Chad W. , Bugbee William D. , Sah Robert L. 
Published: November 2008

AbstractObjectiveOsteoarthritis (OA) is characterized by progressive degeneration of articular cartilage and remodeling of the subchondral bone plate, comprising calcified cartilage and underlying subchondral bone. Calcified cartilage remodeling due to upward invasion by vascular canals or to calcified cartilage erosion may contribute to biomechanical alteration of the osteochondral tissue and its subchondral bone plate component. The study hypothesis was that hydraulic conductance of osteochondral tissue and subchondral bone plate increases with structural changes indicative of increasing stages of OA.MethodsOsteochondral cores were harvested from the knees of cadaveric tissue donors and from discarded fragments from patients with OA undergoing knee surgery. The osteochondral cores from tissue donors were macroscopically normal, and the cores from patients with OA had partial‐thickness or full‐thickness erosion to bone. The cores were perfusion‐tested to determine the hydraulic conductance, or ease of fluid flow, in their native state and after enzymatic removal of cartilage. Adjacent portions were analyzed by 3‐dimensional histology for calcified cartilage, subchondral bone, and subchondral bone plate thickness and vascular canal density.ResultsHydraulic conductance of native osteochondral tissue and subchondral bone plate was higher (2,700‐fold and 3‐fold, respectively) in fully eroded samples than in normal samples. The calcified cartilage layer was thicker (1.5‐fold) in partially eroded samples than in normal samples but thinner and incomplete in fully eroded samples. Subchondral bone plate vascularity was altered with increasing stages of OA.ConclusionDuring joint loading, increased hydraulic conductance of the osteochondral tissue and subchondral bone plate could have deleterious biomechanical consequences for cartilage. Increased fluid exudation from overlying and opposing cartilage, increased fluid depressurization, and increased cartilage tissue strains could lead to chondrocyte death and cartilage damage.
White and gray matter abnormalities in the brain of patients with fibromyalgia: A diffusion‐tensor and volumetric imaging study
Authors: Lutz Jürgen , Jäger Lorenz , de Quervain Dominique , Krauseneck Till , Padberg Frank , Wichnalek Martina , Beyer Antje , Stahl Robert , Zirngibl Ben , Morhard Dominik , Reiser Maximilian , Schelling Gustav 
Published: November 2008

AbstractObjectiveTo use a combination of magnetic resonance diffusion‐tensor imaging (MR‐DTI) and MR imaging of voxel‐based morphometry (MR‐VBM) in patients with fibromyalgia syndrome (FMS) to determine microstructural and volume changes in the central neuronal networks involved in the sensory‐discriminative and affective‐motivational characteristics of pain, anxiety, memory, and regulation of the stress response.MethodsThirty female patients with FMS and 30 healthy female control subjects were studied. Predefined areas of the brain were measured for volume of gray matter by MR‐VBM and for diffusivity and fractional anisotropy (FA) by MR‐DTI. Higher FA values and reduced diffusivity are thought to reflect increased complexity of brain‐tissue microstructure.ResultsMR‐VBM and MR‐DTI demonstrated a striking pattern of changes in brain morphology in patients with FMS. Both thalami, the thalamocortical tracts, and both insular regions showed significant decreases in FA. In contrast, increases in FA and decreases in gray matter volume were seen in the postcentral gyri, amygdalae, hippocampi, superior frontal gyri, and anterior cingulate gyri. Increased pain intensity scores were correlated with changes in MR‐DTI measurements in the right superior frontal gyrus. Increased fatigue was correlated with changes in the left superior frontal and left anterior cingulate gyrus, and self‐perceived physical impairment was correlated with changes in the left postcentral gyrus. Higher intensity scores for stress symptoms were correlated negatively with diffusivity in the thalamus and FA in the left insular cortex. No relationship was found between MR‐VBM measurements and symptom intensity scores.ConclusionMR‐DTI allows the visualization of microstructural changes in the brain of patients with FMS, appears to be more sensitive than MR‐VBM, and may serve as an additional diagnostic technique in FMS and probably other dysfunctional pain syndromes.
Cited2 modulates hypoxia‐inducible factor–dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc
Authors: Agrawal Amit , Gajghate Sachin , Smith Harvey , Anderson D. Greg , Albert Todd J. , Shapiro Irving M. , Risbud Makarand V. 
Published: November 2008

AbstractObjectiveTo determine whether nucleus pulposus cells of the intervertebral disc express hypoxia‐inducible factor 2α (HIF‐2α), and to assess the role of HIF‐1 and HIF‐2 in controlling cited2 and vascular endothelial growth factor (VEGF) expression.MethodsRat cells were cultured under normoxic (21% O2) or hypoxic (2% O2) conditions, and expression and promoter activity of HIF‐2 target genes were evaluated. Gain‐ or loss‐of‐function experiments were performed to investigate the contribution of HIF isoforms to cited2 activity as well as the role of cited2 in regulating VEGF expression.ResultsWe found that HIF‐2α protein was expressed in vivo and that protein and messenger RNA expression were similar under both normoxic and hypoxic conditions. However, there was a significant increase in HIF‐2α transactivation under hypoxic conditions. With respect to functional activity, unlike the case in most other tissues, HIF‐2 failed to increase the transcriptional activities of superoxide dismutase 2 and frataxin, 2 common target genes involved in radical dismutation. However, under hypoxic conditions, HIF‐2 preferentially regulated the expression and promoter activity of cited2, a p300 binding protein. When HIF‐2α or HIF‐1α was suppressed, cited2 promoter activity was inhibited. Finally, we showed that forced expression or suppression of cited2 resulted in corresponding changes in expression of VEGF, a common target gene for HIF‐1 and HIF‐2 in the nucleus pulposus cells.ConclusionResults of this study indicate that in nucleus pulposus cells, HIF‐2 and HIF‐1 modulate their own transcriptional activity through cited2. We suggest that the 2 arms of the regulatory circuit serve to maintain survival activities and inhibit angiogenesis in the healthy disc.