Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa

PURPOSE: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose-range effect of the treatment was also investigated. METHODS: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated. The eyes were processed for histologic evaluation. RESULTS: In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye. No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout. CONCLUSIONS: CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B-deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.     

Qualitative findings on the experience of end-of-life care for hematological malignancies

There is a loud silence in the literature on the issues related to palliative care for hematological malignancies. This article presents information that begins to address that silence. The limited research that is available indicates that, to date, patients with a hematological malignancy and their families received scant attention with regards to the provision of palliative care. The findings presented in this article demonstrates that families are enduring considerable hardship and are left with much emotional pain and many unresolved issues when such care is not offered. It is hoped that the findings presented in this article will be used for developing effective strategies to ensure that patients with hematological malignancies and their families, no less than any others, can be afforded the dignity and respect that the appropriate provision of palliative services ensures.     

Synthesis of ketone analogues of prolyl and pipecolyl ester FKBP12 ligands

The recently discovered small-molecule ligands for the peptidyl and prolyl isomerases (PPIase) of FKBP12 have been shown to possess powerful neuroprotective and neuroregenerative effects. Ketone analogues of the prolyl and pipecolyl esters, which mimic only the FKBP binding domain portion of FK506, are proposed and an efficient synthetic strategy is presented in this report, along with the preliminary results of in vitro and in vivo biological studies.     

Amodiaquine treatment of uncomplicated malaria in children, in an area of chloroquine-resistant Plasmodium falciparum in north-central Nigeria

The efficacy of amodiaquine against Plasmodium falciparum malaria was assessed in an area of confirmed chloroquine resistance in the cool, north-central plateau of Nigeria, using a 14-day protocol. The patients were all children aged <5 years of age. The drug proved highly efficacious, giving a cure 'rate' of 100% on day 14 and mean fever- and parasite-clearance times of 1.11 and 3.11 days, respectively. It was also well tolerated. Following treatment, packed-cell volumes (PCV) generally increased (65% of patients) but remained constant (12%) or even decreased (23%) in some patients; the overall improvement in PCV was not statistically significant (P >0.05). The results justify the use of amodiaquine to treat P. falciparum malaria in those who have failed treatment with chloroquine and the second-line drugs (e.g. sulfadoxine-pyrimethamine) currently used in Nigeria. As the amodiaquine would be better employed as one part of a combination than on its own, there is a need to identify suitable partner compounds.     

Practical aspects of performance improvement in pediatric trauma

Pediatric trauma performance improvement programs may share some of the criteria tracked by their counterparts in the adult trauma world. However, some of the criteria must be specific to the unique diagnostic and therapeutic needs of children. Nine criteria are defined in terms of the critical issues, what information is required to evaluate the appropriateness of the care provided in regards to those issues, and acceptable thresholds for review. In addition, practical aspects of multi-disciplinary peer review in the performance improvement process is presented.     

The impact of a worker health study on working conditions

A research partnership of representatives from labor, academia, and public health enabled unionized San Francisco hotel workers to achieve important policy changes in workplace health and safety. Known as the "Housekeeping Study," the project took sixteen months to complete. A unique aspect of the project was that it utilized participatory action research methods, involving workers themselves as full participants in the study. A core group of 25 hotel room cleaners was involved in each phase of the project. The study developed health data which enabled room cleaners and their union to formulate and justify a contract proposal calling for a significant reduction in housekeeping workloads. The employer association agreed to a contract which reduced the maximum required room assignment from 15 rooms to 14 rooms per day in 14 San Francisco hotels. By lowering the maximum work assignment, these workers set a new standard which can potentially protect the health of room cleaners across the country. The project can serve as a model for worker and union participation in academic research, as well as for the application of research to improving working conditions, particularly for low-wage immigrant workers.     

Professional development for general practitioners through fellowship by assessment

BACKGROUND AND STUDY AIMS: The Royal College of General Practitioners has designed its Fellowship by Assessment (FBA) programme with the twin goals of promoting higher standards of care and offering GPs a professional challenge. By November 2000, 223 eligible doctors (2%) had opted to take FBA. This number is increasing annually. There is, however, little research to account for why GPs undertake it, or what the barriers might be. The aim of our study was to investigate GPs' experience and thinking on this issue. METHODS: A total of 13 GPs who had attained Fellowship by Assessment in the Tamar and Severn Faculties were invited to participate in a qualitative study. They were identified from the list of RCGP Fellows in the Institute of General Practice, University of Exeter, and purposefully selected to include trainers and non-trainers, men and women, rural and urban practitioners, and single-handed and large practices. Analysis of in-depth interviews was informed by grounded theory. FINDINGS: FBA served to acknowledge high standards of care. There was some variation in views about FBA, however, ranging from a perspective which prized the professional award, to the view that endorsed it as a pragmatic and useful way of structuring and monitoring improvements. Fellowship by Assessment improves the care of patients and empowers the doctors by improving their confidence. It is, however, hugely time-consuming and while our findings suggest it should be encouraged, there is a need for ways to be found whereby doctors may be supported in this form of professional development.