Evaluation ofin vitro drug screening leads using experimental models of human ovarian cancer

Summary Five compounds which were identified as potential new anticancer drugs inin vitro screening with the human tumor colony forming assay were selected for further evaluation usingin vitro andin vivo models of human ovarian cancer. Three of five compounds were found to inhibitin vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.     

Diverse implications of a national health crisis: A qualitative exploration of community nurses' SARS experiences.

The purpose of this study was to enhance our understanding of the influence of the SARS crisis on the work and personal lives of community nurses.A total of 941 community nurses employed in a range of health-care settings in the province of Ontario, Canada, provided qualitative information about their perceptions of the impact of SARS in their workplace and in their personal lives. Themes and subthemes from the data were organized into 2 categories: The Experience (operational, organizational, and personal narratives), and Learning from the Experience (opportunities for personal learning, professional and policy development, and insight into policy and administrative implications). The findings are discussed within a framework of the learning opportunity presented by the crisis at the local, national, and international levels. The roles of effective communication, emergency response coordination, and education are considered with respect to policy development and administrative responses to infectious disease protocol. The findings are particularly relevant at this time of heightened fear of global epidemics.     

Xenopus Tadpole Melanophores Are Controlled by Dark and Light and Melatonin Without Influence of Time of Day

Melanophores were studied in tadpoles of the South African clawed toad, Xenopus laevis , during the first week after hatching (stages 46–49) at 25°C. The tadpoles had melanophores with dispersed melanosomes in the light and punctate melanophores in the dark in LD12:12. The melanophores remained punctate in constant dark and the melanosomes remained dispersed in constant light. Lights-out (in the light-time of LD12:12) caused the melanophores to become punctate, which occurred more quickly than the dispersion of melanosomes, which commenced when the lights were turned on (in the dark-time of LD12:12). Melanophores with dispersed melanosomes in tadpoles (in constant light) became punctate in response to a series of melatonin concentrations (0.2–5 ng/ml) in their bathing water irrespective of the time of day melatonin was administered. An image-analysis technique for assessing melanophore responses was tested.     

Tau immunoreactivity and SDS solubility of two populations of paired helical filaments that differ in morphology

To further understand the processes that lead to the formation of neurofibrillary tangles from paired helical filaments (PHF) in Alzheimer brains, we studied two morphologically distinct fractions of PHF separated on sucrose density gradient. In a fraction with mostly short and non-aggregated PHF, the majority of filaments could be solubilized in SDS. In a fraction containing primarily PHF aggregated into clusters or bundles, sometimes resembling neurofibrillary tangles, filaments were less soluble in SDS. Immunogold labelling with a panel of tau-immunoreactive antibodies demonstrated that N-terminal epitopes of tau were preserved in the short filaments, but were reduced or absent in aggregated filaments. In contrast, C-terminal epitopes were present in both fractions. Furthermore, the accessibility of the microtubule-binding domain to immunolabelling was markedly impaired in short and non-aggregated filaments compared to aggregated filaments. These results are consistent with proteolytic degradation of the N-terminal epitopes and preservation of the C-terminal epitopes and the microtubule-binding domain of tau in the aggregated filaments. Partial proteolysis may be involved in the generation of aggregated PHF in neurofibrillary tangles.     

The clinical nurse leader: a response from practice.

In October 2003, over 200 nurse leaders from education and practice met at the invitation of the American Association of Colleges of Nursing. A newly released white paper, describing the role of the clinical nurse leader, was discussed at the conference. This article outlines a response to that white paper from one practice setting. The article shares information about another role, that of team coordinator, that is similar to clinical nurse leader and has been implemented at an integrated not-for-profit health care system in 5 hospitals. The comparison of the team coordinator role to the clinical nurse leader role might assist in visualizing such a role in practice. Although the roles are not identical, many of the driving forces for change were similar; these included the need to meet the changing demands for improved patient outcomes and nurse retention. The team coordinator role has 4 domains of practice that are crosswalked against the clinical nurse leader 15 core competencies. An evaluation of the team coordinator role showed changes that need to be made, such as placing more emphasis on clinical progression of patients. Lessons learned are shared, including keeping the scope of the role manageable, providing documentation standards for new roles, and the leadership required of the nursing executive to implement change.     

Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.