PURPOSE: The purpose of this study was to demonstrate that surgically implanted, controlled-release, biodegradable polilactofate microspheres (Paclimer) can be used safely to bypass the blood-brain barrier and deliver paclitaxel to malignant brain tumors. EXPERIMENTAL DESIGN: The rate of paclitaxel release from Paclimer microspheres submerged in PBS was measured in vitro by high-performance liquid chromatography. In vivo studies of Paclimer were performed as intracranial implants in Fischer 344 rats in the presence or absence of 9L gliosarcoma. Mantel-Cox statistics were used to assess the efficacy of Paclimer at extending survival of tumor-bearing animals compared with control implants. Paclimer implants tagged with [(3)H]paclitaxel were used to measure biodistribution of paclitaxel from the Paclimer implant. RESULTS: Paclimer released paclitaxel at a constant rate for up to 3 months in vitro. In vivo, Paclimer implants placed intracranially in rats released active drug for up to 30 days after implantation and doubled the median survival of rats bearing established 9L gliosarcomas (median survival of paclitaxel-treated animals = 35 days; median survival of control-treated animal = 16 days; P < 0.0001). Active drug was distributed throughout the rat brain based on liquid scintillation counting and TLC. Rats implanted with Paclimer demonstrated no overt signs of neurotoxicity and exhibited local cytopathological changes consistent with exposure to an antimicrotubule agent. CONCLUSIONS: Paclimer extends survival in a rodent model of glioma with minimal morbidity and optimal pharmacokinetics. 相似文献
The Authors for the Live Organ Donor Consensus Group
JAMA. 2000;284:2919-2926.
Objective To recommend practice guidelines for transplantphysicians, primary care providers, health care planners, andall those who are concerned about the well-being of the liveorgan donor.
Participants An executive group representing the NationalKidney Foundation, and the American Societies of Transplantation,Transplant Surgeons, and Nephrology formed a steering committeeof 12 members to evaluate current practices of living donortransplantation of the kidney, pancreas, liver, intestine, andlung. The steering committee subsequently assembled more than100 representatives of the transplant community (physicians,nurses, ethicists, psychologists, lawyers, scientists, socialworkers, transplant recipients, and living donors) at a nationalconference held June 1-2, 2000, in Kansas City, Mo.
Consensus Process Attendees participated in 7 assignedwork groups. Three were organ specific (lung, liver, and kidney)and 4 were focused on social and ethical concerns (informedconsent, donor source, psychosocial issues, and live organ donorregistry). Work groups' deliberations were structured by a seriesof questions developed by the steering committee. Each workgroup presented its deliberations to an open plenary sessionof all attendees. This information was stored and shaped intoa statement circulated electronically to all attendees for theircomments, and finally approved by the steering committee forpublication. The term consensus is not meant to convey universalagreement of the participants. The statement identifies issuesof controversy; however, the wording of the entire statementis a consensus by approval of all attendees.
Conclusion The person who gives consent to be a live organdonor should be competent, willing to donate, free from coercion,medically and psychosocially suitable, fully informed of therisks and benefits as a donor, and fully informed of the risks,benefits, and alternative treatment available to the recipient.The benefits to both donor and recipient must outweigh the risksassociated with the donation and transplantation of the livingdonor organ.
The relationship between posterior capsule tightness and dysfunction has long been recognized clinically but has not been biometrically quantified. The purpose of this study was to quantify changes in range of motion and posterior capsule tightness in patients with dominant or nondominant shoulder impingement. Measurements of posterior capsule tightness and external and internal rotation range of motion were made in 31 patients with shoulder impingement and in 33 controls without shoulder abnormality. Patients with impingement in the nondominant arm had increased posterior capsule tightness and decreased internal and external rotation range of motion compared with controls. Patients with impingement in their dominant arm had increased posterior capsule tightness and reduced internal rotation range of motion but no significant loss of external rotation range of motion compared with controls. Posterior capsule tightness in impingement patients showed a significant correlation with loss of internal rotation range of motion. Patients with shoulder impingement in their nondominant arm had a more global loss of range of motion compared with patients having impingement in their dominant arm. We believe we have described a valid clinical measurement for identifying posterior capsule tightness in patients with shoulder impingement. 相似文献
Implementation models, such as the national Put Prevention Into Practice program, have produced small to moderate changes in the delivery of preventive services in primary care. More recently, researchers concluded that guides and tools, such as the PPIP toolkit, are helpful, but are not sufficient to facilitate substantive change in clinical preventive practice. Successful implementation of clinical preventive services, according to the Texas Department of Health-PPIP (TDH-PPIP) initiative, involves creating or altering systems to produce change in service delivery for a specific setting. This article describes the ways in which the guidelines and instruments that were developed and refined through the collaborative efforts among public and private health systems were used to implement systems change and improve clinical preventive services at one community primary health care clinic in Texas. The process and empirical results of using the TDH-PPIP Implementation Model in the field are also presented, as well as a discussion of one-year evaluation data. 相似文献
Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds syntaxin under physiological conditions. 相似文献
Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1β and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eμ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved. 相似文献
Microsatellite loci have been developed for three undescribed species discovered at hydrothermal vents on the East Scotia Ridge (ESR) in the Southern Ocean: a yeti crab, Kiwa sp. (Kiwaidae), a species of peltospiroid gastropod and a vent limpet, Lepetodrilus sp. (Lepetodrilidae). Nine, twelve and fourteen loci were developed for the three species respectively, with two loci deviating significantly from Hardy–Weinberg expectations. Observed heterozygosity ranged from 0.08 to 1 (means of 0.62, 0.44 and 0.63 for the three species respectively). These loci are being used to determine connectivity between vents at the northern and southern end of the ESR and between the ESR and the Kemp Caldera, a submerged part of the South Sandwich Island chain. These data will be crucial in understanding the ecology of the first hydrothermal vent communities discovered in the Southern Ocean. 相似文献