We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery.
This was a multicenter, ...randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization.
Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients (
P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group.
Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.
This study quantifies excess annual costs associated with schizophrenia patients in the United States in 2002 from a societal perspective.
Annual direct medical costs associated with schizophrenia ...were estimated separately for privately (N = 1090) and publicly (Medicaid; N = 14,074) insured patients based on administrative claims data, including a large private claims database and the California Medicaid program (MediCal) database, and compared separately to demographically/geographically matched control samples (1 case:3 controls). Medicare costs of patients over age 65 years were imputed using the Medicare/MediCal dual-eligible patients (N = 1491) and published statistics. Excess annual direct non-health care costs were estimated for law enforcement, homeless shelters, and research/training related to schizophrenia. Excess annual indirect costs were estimated for 4 components of productivity loss: unemployment, reduced workplace productivity, premature mortality from suicide, and family caregiving using a human capital approach based on market wages. All costs were adjusted to 2002 dollars using the Medical Care Consumer Price Index and were based on the reported prevalence in the National Comorbidity Survey Replication.
The overall U.S. 2002 cost of schizophrenia was estimated to be $62.7 billion, with $22.7 billion excess direct health care cost ($7.0 billion outpatient, $5.0 billion drugs, $2.8 billion inpatient, $8.0 billion long-term care). The total direct non-health care excess costs, including living cost offsets, were estimated to be $7.6 billion. The total indirect excess costs were estimated to be $32.4 billion.
Schizophrenia is a debilitating illness resulting in significant costs. The indirect excess cost due to unemployment is the largest component of overall schizophrenia excess annual costs.
The benefits of diagnostic imaging are immense and have revolutionized the practice of medicine. The increased sophistication and clinical efficacy of imaging have resulted in its dramatic growth ...over the past quarter century. Although data derived from the atomic bomb survivors in Japan and other events suggest that the expanding use of imaging modalities using ionizing radiation may eventually result in an increased incidence of cancer in the exposed population, this problem can likely be minimized by preventing the inappropriate use of such imaging and by optimizing studies that are performed to obtain the best image quality with the lowest radiation dose. The ACR, which has been an advocate for radiation safety since its inception in 1924, convened the ACR Blue Ribbon Panel on Radiation Dose in Medicine to address these issues. This white paper details a proposed action plan for the college derived from the deliberations of that panel.
The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an ...important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-related pathways. However, the regulatory role and targets of Auts2 are not well known. Here, by using ChIP-seq (chromatin immunoprecipitation followed by deep sequencing) and RNA-seq on mouse embryonic day 16.5 forebrains, we elucidated the gene regulatory networks of Auts2. We find that the majority of promoters bound by Auts2 belong to genes highly expressed in the developing forebrain, suggesting that Auts2 is involved in transcriptional activation. Auts2 non-promoter-bound regions significantly overlap developing brain-associated enhancer marks and are located near genes involved in neurodevelopment. Auts2-marked sequences are enriched for binding site motifs of neurodevelopmental transcription factors, including Pitx3 and TCF3. In addition, we characterized two functional brain enhancers marked by Auts2 near NRXN1 and ATP2B2, both ASD-implicated genes. Our results implicate Auts2 as an active regulator of important neurodevelopmental genes and pathways and identify novel genomic regions that could be associated with ASD and other neurodevelopmental diseases.
A Gene Expression Map of the Arabidopsis Root Birnbaum, Kenneth; Shasha, Dennis E.; Wang, Jean Y. ...
Science (American Association for the Advancement of Science),
12/2003, Letnik:
302, Številka:
5652
Journal Article
Recenzirano
A global map of gene expression within an organ can identify genes with coordinated expression in localized domains, thereby relating gene activity to cell fate and tissue specialization. Here, we ...present localization of expression of more than 22,000 genes in the Arabidopsis root. Gene expression was mapped to 15 different zones of the root that correspond to cell types and tissues at progressive developmental stages. Patterns of gene expression traverse traditional anatomical boundaries and show cassettes of hormonal response. Chromosomal clustering defined some coregulated genes. This expression map correlates groups of genes to specific cell fates and should serve to guide reverse genetics.
Background: Recent studies report an important—and previously underestimated—role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a ...large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. Method: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. Results: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). Conclusions: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.
Aroclor 1254 is a widely studied commercial polychlorinated biphenyl (PCB) mixture which, by definition, contains 54% chlorine by weight. Recent reports indicate substantial differences in the ...congener composition among Aroclor lots and hence their biologic effects. We designed the current study to compare the effects of two lots of Aroclor 1254 (lots 6024 and 124-191). We analyzed these two lots for PCB congeners, polychlorinated dibenzofurans (PCDFs), polychlorinated naphthalenes (PCNs), and polychlorinated dibenzodioxins (PCDDs). We used previously established techniques for analyzing intracellular Ca2+buffering and protein kinase C (PKC) translocation to test their biologic activity in neuronal preparations. PCB congener-specific analysis indicated that ortho and non-ortho congeners in these two lots varied in their percent contribution. Among all congeners, the percentages of non-ortho congeners (PCBs 77, 81, 126, and 169) were higher in lot 6024 (2.9% of total) than in lot 124-191 (0.02% of total). We detected no dioxins in these two lots (< 2 ppb). Although there are some differences in the congener composition, total PCNs were similar in both lots: 171 ppm in lot 6024 and 155 ppm in lot 124-191. However, total PCDFs were higher in lot 6024 (38.7 ppm) than in lot 124-191 (11.3 ppm). When we tested these two Aroclors on Ca2+buffering and PKC translocation in brain preparations, the effects were significantly different. Although lot 124-191 was more potent on PKC translocation than lot 6024, lot 6024 was slightly more active on Ca2+buffering than lot 124-191. These effects could not be attributed to the differences in the percentage of non-ortho congeners or PCDFs because they were inactive on these two parameters. The effects could not be attributed to PCNs because the levels were almost similar. The effects seen with two lots of Aroclor 1254 in neuronal cells were also not predicted based on the TCDD toxic equivalents (TEQs), although TEQs predicted the effects on ethoxyresorufin-O-deethylase (EROD) or methoxyresorufin-O-deethylase (MROD) activities. It is possible that the differential effects seen in neuronal cells could be caused by differences in the composition of ortho-congeners in these two mixtures, because PCBs with ortho-lateral substitutions can exhibit different activities on the selected neurochemical end points. Because of these differential effects with different lot numbers, the composition of Aroclor mixtures used in investigations should be disclosed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Isotope Production Facility (IPF) at Los Alamos National Laboratory (LANL) is used to produce an array of isotopes for medical, global security, and research applications with an intense beam of ...protons supplied by the linear accelerator at the Los Alamos Neutron Science Center (LANSCE). An Accelerator Improvement Project (AIP) was recently conducted at IPF to improve facility reliability and reduce programmatic risk while increasing general isotope production capacity and flexibility. This was accomplished through the installation of an improved beam window assembly, more robust beam diagnostics, an active and adjustable collimator, and a new beam rastering system. This paper will highlight the four exciting innovations and how they were designed, validated, and installed in parallel as well as the significant operational advantages they provide to IPF. Key experiments and the increased currents achieved in routine production runs demonstrating the enhanced capability from the AIP will be presented. The most notable capability enhancements include irradiations with beam currents ranging from 100 nA experimental runs up to 300 μA on routine production targets and utilization of a range of cylindrical target diameters.
1 Institut fuer Pharmakologie und Toxikologie, Medizinische
Fakultaet der RWTH Aachen, 52057 Aachen, Germany;
2 University of Chicago, Howard Hughes Medical Institute,
Chicago, Illinois 60637; 3 ... St. Vincent's Hospital, Department
of Medicine, Melbourne 3065; and 8 University of
Queensland, Institute for Molecular Bioscience, St. Lucia, Queensland
4072, Australia; 4 University of Pennsylvania School of
Medicine, Howard Hughes Medical Institute, Philadelphia,
Pennsylvania 19104; 5 Department of Biochemistry, Albert
Einstein College of Medicine, Bronx, New York 10461;
6 Department of Pediatrics, Duke University School of Medicine,
Durham, North Carolina 27710; 7 Division of Chemical Biology,
Molecular Pharmacology, Stanford University Medical Center, Stanford,
California 94305; 9 Massachusetts Institute of Technology,
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts
02142; Departments of 10 Obstetrics and Gynecology,
11 Surgery, and 12 Cell Biology and Physiology,
Washington University School of Medicine, St. Louis, Missouri 63110;
15 Department of Cellular and Molecular Medicine, Chiba
University Graduate School of Medicine, Chiba 260-8670, Japan; and
16 Institute of Pharmacology and Toxicology, CH1005 Lausanne,
Switzerland
The recent identification of several
additional members of the family of sugar transport facilitators (gene
symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in
part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A
and GLUT symbols.
membrane transport; glucose transporters; glucose transporter genes
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