阿霉素磁性明胶微球的研究

报告了阿霉素磁性明胶微球（Ａｄｒ－ＭＧ－ｍｓ）的制备与性质，研究了超细氧化铁粒子的合成和磁性明胶微球（ＭＧ－ｍｓ）在狗体内的栓塞效果。阿霉素磁性明胶微球由２％阿霉素（Ａｄｒ）、６８％明胶和３０％的磁铁粒子组成，微球的平均粒径为２２μｍ。在体外实验中，药物释放速度证明微球有缓释的性质。磁铁粒子的平均粒径约为１０ｎｍ，磁性明胶微球与￣（９９ｍ）Ｔｃ标记磁性明胶微球通过导管分别输入狗的肝动脉内进行栓塞，照相和血管造影显示在未加外磁场时磁性明胶微球在左右肝叶分布几乎相等，而在１２００高斯的外磁场作用下，靶部位肝左叶的微球分布是肝右叶的２．２５倍，而甲状腺、脑、心脏的微球很微量，结果表明磁性明胶微球在外磁场作用下是一个很好的治疗肝癌的栓塞剂。     

Cellular drug action profile paradigm applied to XK469

The cellular paradigm presented here defines the cellular action profile of new anticancer agents that complements our discovery and development paradigm. The main elements of this profile include a concentration clonogenicity response relationship on proliferating and plateau phase cells, flow cytometry studies assessing progression delay and apoptosis, macromolecular synthesis inhibition, and DNA damage assessment by the comet assay; other specific assessments then derive from these findings such as topoisomerase assays. XK469 is a new anticancer agent derived from the herbicide Assure that is the inactive parent compound of a family of quinoxaline analogs found to have anticancer activity in vivo. We have applied the described cellular action profile paradigm to XK469 to define a novel action at the cellular level. XK469 is a G2M phase-specific, antiproliferative agent whose activity is related to the 7-position of the chlorine ion in the benzene ring and expressed through a unique cellular action profile resulting in the irreversible increase in cyclin B1 (possibly by specific inhibition of its ubiquitination) and leading, in the absence of apoptosis, to the final mitotic arrest of HCT-116 cells in prophase with subsequent loss of clonogenicity.     

Absent otoacoustic emissions predict otitis media in young Aboriginal children: A birth cohort study in Aboriginal and non-Aboriginal children in an arid zone of Western Australia

Background  

Otitis media (OM) is the most common paediatric illness for which antibiotics are prescribed. In Australian Aboriginal children OM is frequently asymptomatic and starts at a younger age, is more common and more likely to result in hearing loss than in non-Aboriginal children. Absent transient evoked otoacoustic emissions (TEOAEs) may predict subsequent risk of OM.     

Otitis media with effusion

The clinical practice guideline on otitis media with effusion (OME) provides evidence-based recommendations on diagnosing and managing OME in children. This is an update of the 1994 clinical practice guideline "Otitis Media With Effusion in Young Children," which was developed by the Agency for Healthcare Policy and Research (now the Agency for Healthcare Research and Quality). In contrast to the earlier guideline, which was limited to children 1 to 3 years old with no craniofacial or neurologic abnormalities or sensory deficits, the updated guideline applies to children aged 2 months through 12 years with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The American Academy of Pediatrics, American Academy of Family Physicians, and American Academy of Otolaryngology-Head and Neck Surgery selected a subcommittee composed of experts in the fields of primary care, otolaryngology, infectious diseases, epidemiology, hearing, speech and language, and advanced-practice nursing to revise the OME guideline. The subcommittee made a strong recommendation that clinicians use pneumatic otoscopy as the primary diagnostic method and distinguish OME from acute otitis media. The subcommittee made recommendations that clinicians should 1) document the laterality, duration of effusion, and presence and severity of associated symptoms at each assessment of the child with OME, 2) distinguish the child with OME who is at risk for speech, language, or learning problems from other children with OME and more promptly evaluate hearing, speech, language, and need for intervention in children at risk, and 3) manage the child with OME who is not at risk with watchful waiting for 3 months from the date of effusion onset (if known) or diagnosis (if onset is unknown). The subcommittee also made recommendations that 4) hearing testing be conducted when OME persists for 3 months or longer or at any time that language delay, learning problems, or a significant hearing loss is suspected in a child with OME, 5) children with persistent OME who are not at risk should be reexamined at 3- to 6-month intervals until the effusion is no longer present, significant hearing loss is identified, or structural abnormalities of the eardrum or middle ear are suspected, and 6) when a child becomes a surgical candidate (tympanostomy tube insertion is the preferred initial procedure). Adenoidectomy should not be performed unless a distinct indication exists (nasal obstruction, chronic adenoiditis); repeat surgery consists of adenoidectomy plus myringotomy with or without tube insertion. Tonsillectomy alone or myringotomy alone should not be used to treat OME. The subcommittee made negative recommendations that 1) population-based screening programs for OME not be performed in healthy, asymptomatic children, and 2) because antihistamines and decongestants are ineffective for OME, they should not be used for treatment; antimicrobials and corticosteroids do not have long-term efficacy and should not be used for routine management. The subcommittee gave as options that 1) tympanometry can be used to confirm the diagnosis of OME and 2) when children with OME are referred by the primary clinician for evaluation by an otolaryngologist, audiologist, or speech-language pathologist, the referring clinician should document the effusion duration and specific reason for referral (evaluation, surgery) and provide additional relevant information such as history of acute otitis media and developmental status of the child. The subcommittee made no recommendations for 1) complementary and alternative medicine as a treatment for OME, based on a lack of scientific evidence documenting efficacy, or 2) allergy management as a treatment for OME, based on insufficient evidence of therapeutic efficacy or a causal relationship between allergy and OME. Last, the panel compiled a list of research needs based on limitations of the evidence reviewed. The purpose of this guideline is to inform clinicians of evidence-based methods to identify, monitor, and manage OME in children aged 2 months through 12 years. The guideline may not apply to children more than 12 years old, because OME is uncommon and the natural history is likely to differ from younger children who experience rapid developmental change. The target population includes children with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The guideline is intended for use by providers of health care to children, including primary care and specialist physicians, nurses and nurse practitioners, physician assistants, audiologists, speech-language pathologists, and child-development specialists. The guideline is applicable to any setting in which children with OME would be identified, monitored, or managed. This guideline is not intended as a sole source of guidance in evaluating children with OME. Rather, it is designed to assist primary care and other clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all children with this condition and may not provide the only appropriate approach to diagnosing and managing this problem.     

Management of acute adverse reactions to contrast media

When anaphylactoid and other severe adverse reactions to contrast media occur, prompt recognition and immediate treatment are essential. Simple guidelines for treatment have been requested by many radiologists, and therefore the Contrast Media Safety Committee has produced guidelines for treatment of acute adverse reactions to contrast media. The committee made an extensive review of the literature on treatment of adverse reactions to contrast media. Based on this, a report and guidelines were prepared. The resulting report was discussed at the 10th European Symposium on Urogenital Radiology in Uppsala. Sweden, September 2003. Guidelines for treatment of acute adverse reactions and a list of first-line drugs and equipment that should be available in the room where contrast medium is given are provided.The members of the Contrast Media Safety Committee of ESUR are H.S. Thomsen (Chairman, Denmark), S.K. Morcos (Secretary, United Kingdom), T. Almén (Sweden), P. Aspelin (Sweden), M.F. Bellin (France), H. Flaten (Amersham Health, Norway), J.Å. Jakobsen (Norway), G.P. Krestin (The Netherlands), A. Löwe (Schering, Germany), R. Oyen (Belgium), F. Stacul (Italy) and J.A.W. Webb (UK).     

Late adverse reactions to intravascular iodinated contrast media

Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after non-ionic dimers. The majority of late skin reactions after contrast medium exposure are probably T-cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interleukin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions. Electronic Publication     

Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects

trans-Resveratrol is a dietary polyphenolic compound present in grapes, which has been shown to exhibit strong anti-inflammatory, antioxidant, and chemopreventive activities. In this study we have compared the in vitro and in vivo effects of resveratrol on the development of various cell-mediated immune responses, including mitogen/antigen-induced T cell proliferation, induction of cytotoxic T lymphocytes (CTLs), interleukin-2 (IL-2) induced lymphokine activated killer cells, and cytokine production. We found significant suppression (>90%) of the mitogen/antigen-induced T cell proliferation and development of allo-antigen specific CTLs in vitro with resveratrol at a concentration of 25 microM. Intragastric administration of resveratrol (2 mg daily) to mice for 4 weeks showed no effect on age-related gain in body weight, peripheral blood cell counts (WBC, RBC, or platelets), or the cellularity of bone marrow or spleen. The CD4(+) and CD8(+) T cells in spleen or colony-forming units-total in the marrow also remained unaffected by treatment with resveratrol. Spleen cells, which were stimulated in vitro after being removed from mice which had been administered resveratrol for 2 or 4 weeks, showed no significant change in IL-2 or concanavalin A induced proliferation of T cells or production of IL-2 induced lymphokine activated killer cells. Further, the production of in interferon-gamma and IL-12 was not affected by administration of resveratrol, but production of tumor necrosis factor-alpha was reduced. Even when conducted entirely in vivo, treatment with resveratrol was found to only marginally reduce allo-antigen induced T cell proliferation and the generation of CTLs in the draining lymph nodes. Thus, even though resveratrol strongly inhibits T cell proliferation and production of cytolytic cells in vitro, oral administration of resveratrol for 4 weeks does not induce hematologic or hematopoietic toxicity, and only marginally reduces the T cell-mediated immune responses.     

SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions

Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on proliferation, morphology, and cell density of glioma cells grown in vitro, in the absence and presence of ECM proteins under standard (10% fetal bovine serum [FBSI) and reduced (0.1% FBS) serum stress conditions. Under standard conditions, MTT (3-(4,5-cimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) growth curves, morphology, and Western blot analyses demonstrated that SPARC had a suppressive and biphasic effect on growth that was not grossly modulated by the ECMs. The SPARC-induced changes in morphology observed at 24 h were not altered by the presence of ECMs. Under reduced-serum stress conditions, Western blot, morphological, and flow cytometric analyses indicated that the SPARC-induced suppressive growth effects were eliminated when the cells were grown on plastic. However, ECM-specific changes in growth were observed, some of which correlated with secreted SPARC levels. These results indicate that the differential effects of SPARC and ECMs on proliferation are dependent on culture conditions. Since the results obtained under standard conditions agree with our in vivo observations, we conclude that the ability of SPARC to suppress proliferation is regulated to a greater degree by the level of SPARC and that this suppressive effect is not influenced by the presence of any of the ECMs examined.