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At least 937 records · Page 52Linked to original sources
PubMed2005

Evaluation of HMG-CoA reductase inhibitors for multiple sclerosis: opportunities and obstacles.

The disease-modifying agents currently used in the treatment of multiple sclerosis (MS) are not completely effective and are associated with adverse effects and high costs. Thus, alternative treatment options are highly desirable. HMG-CoA reductase inhibitors (statins), widely prescribed as cholesterol-lowering agents, may be a future treatment option for MS--either in an add-on therapy regimen or alone--as they have been shown to exhibit potent immunomodulatory effects. Several recent reports have demonstrated that HMG-CoA reductase inhibitors prevent and reverse chronic and relapsing experimental autoimmune encephalomyelitis, an animal model of MS. Furthermore, in vitro experiments with human immune cells have shown an immunomodulatory mode of action of HMG-CoA reductase inhibitors that is comparable to that of interferon-beta, an established treatment for MS. An open-label clinical trial assessing simvastatin treatment in patients with MS revealed a significant decrease in the number and volume of new lesions, as assessed using magnetic resonance imaging, and a favourable safety profile. A large multicentre, placebo-controlled phase II clinical trial assessing atorvastatin in patients with a clinically isolated syndrome (i.e. a single clinical event that is indicative of demyelination, and that predisposes to the development MS) has recently been initiated. However, prospective placebo-controlled trials of HMG-CoA reductase inhibitors in definite MS are difficult to perform because of ethical and financial issues. Furthermore, overly optimistic reports in the popular media, as well as the often uncontrolled access to HMG-CoA reductase inhibitors by patients with MS, complicate the evaluation of HMG-CoA reductase inhibitors as a realistic future treatment option for MS.

Animals↗
PubMed2005

Mining the probiotic genome: advanced strategies, enhanced benefits, perceived obstacles.

Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availability of annotated genome sequence will be important in defining the capabilities of the individual strains of probiotic bacteria. It will also form the platform for microarray and proteomic technologies that allow real-time analysis of RNA and protein expression in the bacterial cell. Investigation of probiotic organisms with these new and potentially powerful tools will facilitate the development of the bacteria as therapeutic agents, and provide the mechanisms to produce advanced probiotic strains. This paper addresses the core technologies in the rapidly growing area of genomics, and their application to the molecular characterisation of probiotic bacteria and host-microbe interactions.

Databases, Genetic↗
PubMed2005

Overcoming obstacles to work-changing technology such as PACS and voice recognition.

OBJECTIVE: When implementing picture archival communication systems (PACS) and voice recognition (VR) technology in radiology, management attention generally has focused on justifying the system financially, investigating potential vendors, developing timelines for hardware delivery, installing the software, developing interfaces, and tracking and measuring results. These are critical components in implementing PACS and VR technology, but not sufficient for success. CONCLUSION: This article argues that the ability to view organizational issues related to changing how people do their work from multiple organizational perspectives is equally important in determining the success of PACS and VR projects.

Adaptation, Psychological↗
PubMed1987

Low antigen density tumor cells: an obstacle to effective autologous bone marrow purging?

Autologous bone marrow transplantation is a potentially curative approach to the treatment of various tumors that are refractory to conventional therapies. A major problem associated with the procedure is the possibility of tumor cell contamination in the autologous graft used to reconstitute the patient's immune system after supralethal chemoradiotherapy. A variety of different approaches to eliminating tumor cells from bone marrow have been proposed and tested. These include destruction of tumor cells with antibody and complement, use of antibody conjugated to drugs or toxins, and the physical separation of antibody-coated tumor cells by attachment to magnetic microspheres. Each of these approaches has different limitations and technical problems. One problem common to all, however, is that the tumor cells most likely to avoid removal are those demonstrating a low level of surface antigen. In this paper we have offered a practical approach to amplifying the unique surface antigen expression in order to enable this elusive tumor cell population to be eliminated. The approach proposed is adaptable to all the techniques currently being studied, since it is designed to add additional antigens to tumor cells which can then be used as targets at which to direct the various purging strategies.

Antibodies, Monoclonal↗
PubMed1995

Poor cellular uptake of antisense oligodeoxynucleotides: an obstacle to their use in chronic myeloid leukaemia.

The molecular effect of the Philadelphia translocation typical of over 90% of chronic myeloid leukaemia (CML) patients is to create a novel hybrid gene, bcr-abl. The mRNA transcript of this CML-specific gene has only 2 alternative sequences, designated b3a2 and b2a2. Short oligodeoxynucleotide (ODN) sequences complementary (or antisense) to the bcr-abl junction may have potential as leukaemia-specific therapy. However, the studies on ODN targeting bcr-abl reported so far have used ODN linked by either phosphodiester or phosphorothionate linkages. Both of these ODN structures have drawbacks as potential therapeutic agents (nuclease sensitivity, non-specific effects). In contrast, ODN linked by a mixture of methylphosphonate and conventional linkages can mediate cleavage of bcr-abl mRNA target in a sequence-specific fashion, unlike conventionally linked ODN. Poor ODN uptake into intact cells remains a central difficulty for all ODN structures. Several strategies to improve cellular uptake of ODN are under current investigation.

Base Sequence↗
PubMed1997

Abstinence fear in methadone maintenance withdrawal: a possible obstacle for getting off methadone.

The present study attempts to shed light on methadone maintenance patients expectations regarding withdrawal symptoms during voluntary methadone detoxification. The study includes two groups of subjects; one group who have tried on their own initiative to terminate their methadone maintenance treatment (Group 1) and one group that contains rehabilitated patients who have not tried to quit using methadone (Group 2). Two main results have emerged. Group 1 has negative expectations beforehand about the intensity of withdrawal which significantly exceed the later, actual experience. Group 2 has negative expectations about the intensity of withdrawal that significantly exceed the negative expectations of Group 1. The clinical implications of these results are discussed.

Adult↗
PubMed1999

Presenting psychology research on the Internet: obstacles and opportunities.

The Internet presents a potentially revolutionary tool in the dissemination of scientific information, offering many advantages to authors and audiences. However, this resource has been underutilized in psychological research because of several factors: unfamiliarity with required technology, lack of peer review, absence of an efficient centralized accessibility resource, concerns about copyright issues, and financial considerations. The present article describes the advantages of on-line presentation of research, as well as discusses various concerns about on-line publishing and the developing solutions to deal with those concerns.

Evaluation Studies as Topic↗
PubMed1989

Obstacle perception by congenitally blind children.

The ability to perceive objects from a distance and navigate without vision depends principally on auditory information. Two experiments were conducted in order to assess this ability in congenitally blind children aged 4 to 12 years who had negligible amounts of visual experience or formal mobility training. In Experiment 1, children walked along a sidewalk toward a target location to get some candy. A box was placed along the path on some trials, and the children were instructed to avoid the box if it was present. The children spent more time in the region just in front of the box than in the region just behind it, indicating that they perceived the box and acted so as to navigate around it. In Experiment 2, children attempted to discriminate whether a nearby disk was on their left or on their right. The children performed at above-chance levels, again indicating distal perception of objects. The results of both experiments suggest that blind children with little or no visual experience or formal training utilize nonvisual information, presumably auditory, to perceive objects. The specific nature of this auditory information requires further investigation, but these findings imply that the underlying perceptual ability does not require experience in spatial vision or deliberate training and intervention.

Auditory Perception↗
PubMed2002

Barriers to blood pressure control in African Americans. Overcoming obstacles is challenging, but target goals can be attained.

Outdated and biased attitudes and care standards impede optimal care of hypertension in African Americans. The negative expectations that blood pressure targets cannot be reached must be overcome by systematic and appropriate education and treatment. However, physicians should expect that (1) African American patients with elevated blood pressure benefit from early and intensive management, (2) blood pressure can be maintained at goal with appropriate therapeutic lifestyle changes and medications, and (3) complications related to high blood pressure can be avoided. To bring blood pressure down to the target goal, combination pharmacologic therapy is often required. When extensive efforts to achieve blood pressure control prove unattainable in the primary care setting, consultation with a hypertension specialist should be considered.

Black or African American↗
PubMed1989

Obstacles to research analysis.

1. The homeless population is composed of subgroups with varying mental health status and needs. 2. Different research designs and data collection methods require differing psychosocial abilities and skills on the part of the respondent. 3. As a result of the psychosocial abilities required and method of sampling, studies are likely to either underrepresent or overrepresent the severely mentally ill homeless. 4. Caution must be exercised in drawing conclusions from any one study.

Data Collection↗