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While patients with Alzheimer's disease (AD)can be expected to exhibit multiple cognitive deficits, there is considerable variation in their manifestation of secondary behavioral symptoms. These symptoms have been characterized as positive (psychosis) or negative (apathy) depending upon whether their presence or absence 'results in aberrant behavior. Conventional antipsychotic medications have been effective in treating positive symptoms, but may exacerbate negative ones. The purpose of this study was to examine the overall efficacy of an atypical antipsychotic, olanzapine, in treating positive and negative secondary symptoms in AD. Thirteen subjects (Ss) were recruited from a university-based memory disorders program to participate in a 9-week treatment only, open label study with follow up at 24 weeks. All Ss met DSM-IV criteria for early or midstage AD (CDR= 1 or 2). Medication was monitored weekly and ranged from 2.5 to 12.5 mg/day. Outcome measures included standardized, assessment of S's neuropsychialric, cognitive, mood, and functional stares as well as adverse medication reaction and caregiver involvement/burden. A significant overall reduction in neuropsychiatric symptoms was observed (t=-3.16, p

Objectives The aim of this study was to map information literacy (IL) skill development in the Bachelor of Nursing (BN) content; identify educational practices in courses to asses students' information literacy (IL) skills; explore BN students' understandings of their IL skill development; and explore students' and academics' understandings of the link between IL skills and life long learning. Design The study used a qualitative exploratory triangulated design using document analysis, questionnaire and focus groups to evaluate BN students' and academics' understandings of IL; IL links to life long learning; and subsequent implications for high quality evidence based practice. Thematic analysis was used to review the individual and combined sources of data. Setting The setting for the study was one School of Nursing and Midwifery in a South Australian University. Subjects Participants included 394 Bachelor of Nursing students who responded to an anonymous questionnaire and 7 academics who participated in a focus group. Main outcomes Changes are required to increase BN students' and academics' understandings of IL and its links to life long learning, including staff development and collaboration between academics, librarians and study advisors on the design and implementation of a consistent and progressive curriculum approach to teaching IL skills. Results The themes resulting from the data were: students' and academics' understanding of the term information literacy and the links to lifelong learning; the role of the library; the role of the curriculum; and the roles of lecturers and student peers. Conclusions Study outcomes indicated there is a need for staff development and a progressive curriculum approach to ensure students understand IL and its links to life long learning. Such approaches require collaboration between librarians, study skills advisors and academics. [ABSTRACT FROM AUTHOR]

Ping-Hsiu Wu,1 Yasuhito Onodera,2 Yuki Ichikawa,3,4 Erinn B Rankin,5 Amato J Giaccia,5 Yuko Watanabe,3 Wei Qian,4 Takayuki Hashimoto,1 Hiroki Shirato,1,6,7 Jin-Min Nam1,6,7 1Department of Radiation Medicine, 2Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Hokkaido, 3Innovation Center, Aisin Seiki Co., Ltd., Aichi, Japan; 4IMRA America, Inc., Ann Arbor, MI, 5Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University Medical Center, Stanford, CA, USA; 6Research Center for Cooperative Projects, Graduate School of Medicine, 7Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Hokkaido, Japan Abstract: Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg–Gly–Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5- and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy. Keywords: gold nanoparticles, radiotherapy, breast cancer, invasion, integrin, fibronectin

In a retrospective study we have compared the toxic side effects related to the use of two antibiotic regimens in the treatment of febrile episodes in neutropenic, leukaemic patients undergoing first remission-induction. Nephrotoxicity was more severe in the gentamicin-mezlocillin (G/M) group: four patients developed oliguric renal failure and two others showed rises in the serum creatinine of more than 0.03 mmol/l. One of the two patients in the gentamicin-ticarcillin (G/T) group who showed nephrotoxicity developed renal failure. Ototoxicity and skin rashes were more commonly observed with G/M than with G/T, and the differences were statistically significant for both ototoxicity (P = 0.0004) and drug rashes (P = 0.02). The cause of the observed differences in toxicity has not been identified. [ABSTRACT FROM AUTHOR]

LL-D49194 alpha 1 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m2. One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D49194 alpha 1 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial. [ABSTRACT FROM AUTHOR]

A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy. [ABSTRACT FROM AUTHOR]

LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of "standard" side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m2. The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued. [ABSTRACT FROM AUTHOR]