bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ropivacaine in neonates and infants: a population pharmacokinetic evaluation following single caudal block
Authors: Rapp Hans‐Jürgen , Molnár Valeria , Austin Stephen , Krohn Stefan , Gädeke Veronika , Motsch Johann , Boos Karin , Williams D.G. , Gustafsson Urban , Huledal Gunilla , Larsson Lars E. 
Published: August 2004

SummaryBackground : The aims of this study were to evaluate pharmacokinetics, efficacy and safety of ropivacaine in infants aged 0–12 months following a single caudal injection.Methods : Term ASA I–III patients, scheduled for surgery, with a body weight of ≥2500 g received a caudal block with ropivacaine 2 mg·ml−1, 1.0 ml·kg−1. Plasma samples were collected at different time intervals up to 30 h, for analysis of total and unbound ropivacaine and alpha‐1‐acid glycoprotein (AAG). Pharmacokinetic data were characterized by population analysis. Unbound and total concentrations from 35 patients, median (min–max) postnatal age of 66 (4–351) days, were included in the nonlinear mixed effects modeling to provide estimates of pharmacokinetic parameters and the exploration of covariate relationships. Simulations were made to test the predictive performance of the final model and to describe the effect of significant covariates on systemic exposure.Results : The mean (min–max) peak plasma concentration of total ropivacaine was 0.83 (0.05–1.57) mg·l−1 at 0.5–5.7 h (median: 1.0 h) and the plasma concentration of unbound ropivacaine was 0.042 (0.012–0.081) mg·l−1 within 0.5–1 h. The observed unbound fraction in plasma was 6% (1%–14%). A one‐compartment open model with first‐order absorption and elimination, incorporating a linear‐binding model of ropivacaine to AAG best described the data. The only significant covariate relationship was that of age on Clu/F according to the following relationship Clu/F = 3.01 × e0.00474 × Age. This predicts a Clu/F of 3.5 l·h−1·kg−1 at 30 days and 10.8 l·h−1·kg−1 at 270 days with corresponding terminal half‐lives of 6.7 and 2.2 h. The interindividual variability (coefficient of variation, CV) in Clu/F was 39%. The population estimate (CV) of ka was 1.65 h−1 (30%), Vu/F was 33.6 (l·kg−1) (45%) and Ka was 1.78 l·mg−1 (14%). Thirty‐five infants received supplementary analgesics (mostly paracetamol). The median time to first supplementary analgesic (based on all 37 patients) was 3.9 h. No safety concerns or signs of systemic toxicity were observed.Conclusions : Following a caudal block with ropivacaine 2 mg·kg−1 plasma concentrations of unbound ropivacaine were well below threshold levels for toxicity in adults. Apparent volume of distribution is unchanged, apparent unbound clearance increases and the terminal half‐life decreases with age in 0–12‐month‐old neonates and infants. The postoperative pain management provided adequate analgesia and was well tolerated.
Mental Illness and Length of Inpatient Stay for Medicaid Recipients with AIDS
Authors: Hoover Donald R. , Sambamoorthi Usha , Walkup James T. , Crystal Stephen 
Published: August 2004

Objective. To examine the associations between comorbid mental illness and length of hospital stays (LOS) among Medicaid beneficiaries with AIDS.Data Source and Collection/Study Setting. Merged 1992–1998 Medicaid claims and AIDS surveillance data obtained from the State of New Jersey for adults with ≥1 inpatient stay after an AIDS diagnosis from 1992 to 1996.Study Design. Observational study of 6,247 AIDS patients with 24,975 inpatient visits. Severe mental illness (SMI) and other less severe mental illness (OMI) diagnoses at visits were ascertained from ICD–9 Codes. About 4 percent of visits had an SMI diagnosis; 5 percent had an OMI diagnosis; 43 percent did not have a mental illness diagnosis, but were patients who had been identified as having an SMI or OMI history; and 48 percent were from patients with no identified history of mental illness.Principal Findings. The overall mean hospital LOS was 12.7 days. After adjusting for measures of HIV disease severity and health care access in multivariate models, patients presenting with primary and secondary severe mental illness (SMI) diagnoses had ∼32 percent and ∼11 percent longer LOS, respectively, than did similar patients without a mental illness history (p<0.001 for each). But in these adjusted models of length of stay: (1) diagnosis of OMI was not related to LOS, and (2) in the absence of a mental illness diagnosed at the visit, an identified history of either SMI or OMI was also not related to LOS. In adjusted models of time to readmission for a new visit, current diagnosis of SMI or OMI and in the absences of a current diagnosis, history of SMI or OMI all tended to be associated with quicker readmission.Conclusions. This study finds greater (adjusted) LOS for AIDS patients diagnosed with severe mental illness (but not for those diagnosed with less severe mental comorbidity) at a visit. The effect of acute severe mental illness on hospitalization time may be comparable to that of an acute AIDS opportunistic illness. While previous research raises concerns that mental illness increases LOS by interfering with treatment of HIV conditions, the associations here may simply indicate that extra time is needed to treat severe mental illnesses or arrange for discharge of afflicted patients.
Cost Shifting to Jails after a Change to Managed Mental Health Care
Authors: Domino Marisa Elena , Norton Edward C. , Morrissey Joseph P. , Thakur Neil 
Published: August 2004

Objective. To determine whether managed mental health care for Medicaid enrollees in King County, Washington, has led to indirect cost‐shifting to substitute treatments, such as jails and state mental hospitals that are free goods to providers.Data Sources. Complete service records for 47,300 adults who used at least one of the following systems from 1993 to 1998: King County jail system, Medicaid, or the King County mental health system. Data were also obtained from the Washington State Hospital System.Study Design. A quasi‐experimental analysis that compares the difference in outcomes between the pre‐ and post‐managed care periods for Medicaid enrollees compared to non‐Medicaid enrollees. The outcomes—jail costs, state hospital costs, and county outpatient mental health costs—were estimated with two‐part difference‐in‐differences models. The regressions control for person‐level fixed effects on up to 66 months of data per person.Data Collection Methods. Administrative data were collected from the jail, Medicaid, and mental health systems, then merged and cleaned. Additional data on costs were obtained in interviews.Principal Findings. There is a striking increase in the probability of jail use for persons on Medicaid following the introduction of managed care. There was a significant decrease in expenditures in the county mental health system for outpatient care.Conclusions. Managed care led to indirect cost‐shifting, probably through poor access to services, which may have led to an increased probability of jail detention.
Communities and Hospitals: Social Capital, Community Accountability, and Service Provision in U.S. Community Hospitals
Authors: Lee Shoou‐Yih D. , Chen Wendy L. , Weiner Bryan J. 
Published: August 2004

Objectives.The study related community social capital to the level of community accountability and provision of community‐oriented services in U.S. community hospitals.Study Setting.The sample included 1,383 community hospitals that participated in the 1997 American Hospital Association's (AHA) Hospital Annual and Governance Surveys.Data Sources.(1) The 1997 AHA Annual Hospital Survey, (2) the 1997 AHA Hospital Governance Survey, (3) the DDB Needham Market Facts Survey, (4) the 1996 County Election Data File, and (5) the 1998 Area Resource File.Research Design.The study used a mix of longitudinal and cross‐sectional data.Key Findings.We identified two distinct indicators of social capital—community participation and voting participation. Community accountability in hospitals was unrelated to either indicator. Hospitals' provision of community‐oriented health services was negatively associated with community participation but unrelated with voting participation. The interaction between voting participation and community representation on hospital governance was positively associated with community accountability and provision of community‐oriented health services.Conclusion.Neither community participation nor voting participation was sufficient to influence hospital behavior. The positive finding associated with the interaction between voting participation and community representation on hospital governance underscored the importance of an active political culture in influencing hospital behavior, without which the installation of community representatives on hospital governance might be more symbolic than actually serving the health concerns of community residents.
Availability of Safety Net Providers and Access to Care of Uninsured Persons
Authors: Hadley Jack , Cunningham Peter 
Published: August 2004

Objective. To understand how proximity to safety net clinics and hospitals affects a variety of measures of access to care and service use by uninsured persons.Data Sources. The 1998–1999 Community Tracking Study household survey, administered primarily by telephone survey to households in 60 randomly selected communities, linked to data on community health centers, other free clinics, and safety net hospitals.Study Design. Instrumental variable estimation of multivariate regression models of several measures of access to care (having a usual source of care, unmet or delayed medical care needs, ambulatory service use, and overnight hospital stays) against endogenous measures of distances to the nearest community health center and safety net hospital, controlling for characteristics of uninsured persons and other area characteristics that are related to access to care. The models are estimated with data from a nationally representative sample of uninsured people.Principal Findings. Shorter distances to the nearest safety net providers increase access to care for uninsured persons. Failure to account for the endogeneity of distance to safety net providers on access to care generally leads to finding little or no safety net effects on access.Conclusions. Closer proximity to the safety net increases access to care for uninsured persons. However, the improvements in access to care are relatively small compared with similar measures of access to care for insured persons. Modest expansion of the safety net is unlikely to provide a full substitute for insurance coverage expansions.
The Alignment and Blending of Payment Incentives within Physician Organizations
Authors: Robinson James C. , Shortell Stephen M. , Li Rui , Casalino Lawrence P. , Rundall Thomas 
Published: August 2004

Objective.To analyze the blend of retrospective (fee‐for‐service, productivity‐based salary) and prospective (capitation, nonproductivity‐based salary) methods for compensating individual physicians within medical groups and independent practice associations (IPAs) and the influence of managed care on the compensation blend used by these physician organizations.Data Sources.Of the 1,587 medical groups and IPAs with 20 or more physicians in the United States, 1,104 responded to a one‐hour telephone survey, with 627 providing detailed information on physician payment methods.Study Design.We calculated the distribution of compensation methods for primary care and specialty physicians, separately, in both medical groups and IPAs. Multivariate regression methods were used to analyze the influence of market and organizational factors on the payment method developed by physician organizations for individual physicians.Principal Findings.Within physician organizations, approximately one‐quarter of physicians are paid on a purely retrospective (fee‐for‐service) basis, approximately one‐quarter are paid on a purely prospective (capitation, nonproductivity‐based salary) basis, and approximately one‐half on blends of retrospective and prospective methods. Medical groups and IPAs in heavily penetrated managed care markets are significantly less likely to pay their individual physicians based on fee‐for‐service than are organizations in less heavily penetrated markets.Conclusions.Physician organizations rely on a wide range of prospective, retrospective, and blended payment methods and seek to align the incentives faced by individual physicians with the market incentives faced by the physician organization.
Discrimination among Rhinovirus Serotypes for a Variant ICAM-1 Receptor Molecule
Authors: Xiao Chuan , Tuthill Tobias J. , Kelly Carol M. Bator , Challinor Lisa J. , Chipman Paul R. , Killington Richard A. , Rowlands David J. , Craig Alister , Rossmann Michael G. 
Published: August 2004

ABSTRACT

Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (HRV14) and HRV16. A naturally occurring variant of ICAM-1, ICAM-1
Kilifi
, has altered binding characteristics with respect to different HRV serotypes. HRV14 binds to ICAM-1 only transiently at physiological temperatures but forms a stable complex with ICAM-1
Kilifi
. Conversely, HRV16 forms a stable complex with ICAM-1 but does not bind to ICAM-1
Kilifi
. The three-dimensional structures of HRV14 and HRV16, complexed with ICAM-1, and the structure of HRV14, complexed with ICAM-1
Kilifi
, have been determined by cryoelectron microscopy (cryoEM) image reconstruction to a resolution of approximately 10 Å. Structures determined by X-ray crystallography of both viruses and of ICAM-1 were fitted into the cryoEM density maps. The interfaces between the viruses and receptors contain extensive ionic networks. However, the interactions between the viruses and ICAM-1
Kilifi
contain one less salt bridge than between the viruses and ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this charge interaction has a greater impact on the binding of ICAM-1
Kilifi
to HRV16 than to HRV14.
A Recombinant Newcastle Disease Virus (NDV) Expressing VP2 Protein of Infectious Bursal Disease Virus (IBDV) Protects against NDV and IBDV
Authors: Huang Zhuhui , Elankumaran Subbiah , Yunus Abdul S. , Samal Siba K. 
Published: August 2004

ABSTRACT
Infectious bursal disease virus (IBDV) causes a highly immunosuppressive disease in chickens. Currently available, live IBDV vaccines can lead to generation of variant viruses. We have developed an alternative vaccine that will not create variant IBDV. By using the reverse genetics approach, we devised a recombinant Newcastle disease virus (NDV) vector from a commonly used vaccine strain LaSota to express the host-protective immunogen VP2 of a variant IBDV strain GLS-5. The gene encoding the VP2 protein of the IBDV was inserted into the most 3′-proximal locus of a full-length NDV cDNA for high-level expression. We successfully recovered the recombinant virus, rLaSota/VP2. The rLaSota/VP2 was genetically stable, at least up to 12 serial passages in chicken embryos, and was shown to express the VP2 protein. The VP2 protein was not incorporated into the virions of recombinant virus. Recombinant rLaSota/VP2 replicated to a titer similar to that of parental NDV strain LaSota in chicken embryos and cell cultures. To assess protective efficacy of the rLaSota/VP2, 2-day-old specific-pathogen-free chickens were vaccinated with the recombinant virus and challenged with a highly virulent NDV strain Texas GB or IBDV variant strain GLS-5 at 3 weeks postvaccination. Vaccination with rLaSota/VP2 generated antibody responses against both NDV and IBDV and provided 90% protection against NDV and IBDV. Booster immunization induced higher levels of antibody responses against both NDV and IBDV and conferred complete protection against both viruses. These results indicate that the recombinant NDV can be used as a vaccine vector for other avian pathogens.
Cytoplasmic Dynein Mediates Adenovirus Binding to Microtubules
Authors: Kelkar Samir A. , Pfister K. Kevin , Crystal Ronald G. , Leopold Philip L. 
Published: August 2004

ABSTRACTDuring infection, adenovirus (Ad) capsids undergo microtubule-dependent retrograde transport as part of a program of vectorial transport of the viral genome to the nucleus. The microtubule-associated molecular motor, cytoplasmic dynein, has been implicated in the retrograde movement of Ad. We hypothesized that cytoplasmic dynein constituted the primary mode of association of Ad with microtubules. To evaluate this hypothesis, an Ad-microtubule binding assay was established in which microtubules were polymerized with taxol, combined with Ad in the presence or absence of microtubule-associated proteins (MAPs), and centrifuged through a glycerol cushion. The addition of purified bovine brain MAPs increased the fraction of Ad in the microtubule pellet from 17.3% ± 3.5% to 80.7% ± 3.8% (P< 0.01). In the absence of tubulin polymerization or in the presence of high salt, no Ad was found in the pellet. Ad binding to microtubules was not enhanced by bovine brain MAPs enriched for tau protein or by the addition of bovine serum albumin. Enhanced Ad-microtubule binding was also observed by using a fraction of MAPs purified from lung A549 epithelial cell lysate which contained cytoplasmic dynein. Ad-microtubule interaction was sensitive to the addition of ATP, a hallmark of cytoplasmic dynein-dependent microtubule interactions. Immunodepletion of cytoplasmic dynein from the A549 cell lysate abolished the MAP-enhanced Ad-microtubule binding. The interaction of Ad with both dynein and dynactin complexes was demonstrated by coimmunoprecipitation. Partially uncoated capsids isolated from cells 40 min after infection also exhibited microtubule binding. In summary, the primary mode of Ad attachment to microtubules occurs though cytoplasmic dynein-mediated binding.
Independent Evolution of Human Immunodeficiency Virus (HIV) Drug Resistance Mutations in Diverse Areas of the Brain in HIV-Infected Patients, with and without Dementia, on Antiretroviral Treatment
Authors: Smit Theresa K. , Brew Bruce J. , Tourtellotte Wallace , Morgello Susan , Gelman Benjamin B. , Saksena Nitin K. 
Published: August 2004

ABSTRACT
AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.
Role of Protein Kinase C δ in Reactivation of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Deutsch Einat , Cohen Adina , Kazimirsky Gila , Dovrat Sara , Rubinfeld Hadara , Brodie Chaya , Sarid Ronit 
Published: August 2004

ABSTRACT

TPA (12-
O
-tetradecanoylphorbol-13-acetate), a well-known activator of protein kinase C (PKC), can experimentally induce reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) in certain latently infected cells. We selectively blocked the activity of PKC isoforms by using GF 109203X or rottlerin and demonstrated that this inhibition largely decreased lytic KSHV reactivation by TPA. Translocation of the PKCδ isoform was evident shortly after TPA stimulation. Overexpression of the dominant-negative PKCδ mutant supported an essential role for the PKCδ isoform in virus reactivation, yet overexpression of PKCδ alone was not sufficient to induce lytic reactivation of KSHV, suggesting that additional signaling molecules participate in this pathway.
Full Resistance of Herpes Simplex Virus Type 1-Infected Primary Human Cells to Alpha Interferon Requires both the Us11 and γ
1
34.5 Gene Products
Authors: Mulvey Matthew , Camarena Vladimir , Mohr Ian 
Published: August 2004

ABSTRACT

The γ
1
34.5 gene product is important for the resistance of herpes simplex virus type 1 (HSV-1) to interferon. However, since the inhibition of protein synthesis observed in cells infected with a γ
1
34.5 mutant virus results from the combined loss of the γ
1
34.5 gene product and the failure to translate the late Us11 mRNA, we sought to characterize the relative interferon sensitivity of mutants unable to produce either the Us11 or the γ
1
34.5 polypeptide. We now demonstrate that primary human cells infected with a Us11 mutant virus are hypersensitive to alpha interferon, arresting translation upon entry into the late phase of the viral life cycle. Furthermore, immediate-early expression of Us11 by a γ
1
34.5 deletion mutant is sufficient to render translation resistant to alpha interferon. Finally, we establish that the Us11 gene product is required for wild-type levels of replication in alpha interferon-treated cells and, along with the γ
1
34.5 gene, is an HSV-1-encoded interferon resistance determinant.
Retroviral Capsid Determinants of
Fv1
NB and NR Tropism
Authors: Stevens Anthony , Bock Michael , Ellis Scott , LeTissier Paul , Bishop Kate N. , Yap Melvyn W. , Taylor Willie , Stoye Jonathan P. 
Published: August 2004

ABSTRACT

The specificity determinants for susceptibility to resistance by the
Fv1
n and b alleles map to amino acid 110 of the murine leukemia virus CA protein. To study the interaction between
Fv1
and CA, we examined changes in CA resulting in the loss of susceptibility to
Fv1
resistance in naturally occurring NB- and NR-tropic viruses. A variety of amino acid changes affecting Fv1 tropism were identified, at CA positions 82, 92 to 95, 105, 114, and 117, and they all were mapped to the apparent exterior of virion-associated CA. These amino acids may form a binding surface for Fv1.