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Disappointing Results (disappointing + result)

Distribution by Scientific Domains

Medical Sciences	42%
Business, Economics, Finance and Accounting	28%

Selected Abstracts

Allocating treatment options to patient profiles: clinical art or science?

ADDICTION, Issue 5 2006
Gerhard Bühringer
ABSTRACT Background For many researchers, the disappointing results of Project MATCH were the death blow for any further activities in the field of patient,treatment interactions. On the other hand, we have an increased knowledge of patient heterogeneity and a greater variety of treatment options than before, and allocation guidelines for an ongoing process of patient-placement decisions are of high practical relevance. Aims To analyse deficits in the current research and to provide suggestions for future action. Findings It is argued that (1) certain major design aspects of Project MATCH and other research studies,such as stringent patient exclusion criteria and low treatment ,dosage',minimize the chances of detecting possible patient,treatment interactions and (2) Project MATCH obscures our view of previous treatment-allocation research findings., Conclusions Several research strategies and specific research topics are suggested for (1) improving the theoretical and methodological basis for detecting possible patient,treatment interactions and (2) stimulating research on major treatment decision needs, such as site, setting, time in treatment (extensiveness and intensity), service components and specific treatment modules. More international research cooperation is needed to clarify the inconsistent findings. [source]

Transection of the sciatic nerve and reinnervation in adult rats: muscle and endplate morphology

EQUINE VETERINARY JOURNAL, Issue S33 2001
J. IJKEMA-PAASSEN
Summary The functional recovery after peripheral nerve lesions is generally poor. We studied whether changes in muscles after reinnervation might explain such disappointing results. The functional recovery after peripheral nerve lesions is generally poor. Changes in muscle morphology and neuromuscular innervation might partly explain this lack of compensation. In order to test this hypothesis, we studied muscular differentiation in the soleus, gastrocnemius and tibialis anterior muscles at 7, 15 and 21 weeks after a sciatic nerve lesion in adult rats. In the gastrocnemius and tibialis muscles the percentages of type II muscles fibres were decreased at 7 and 15 weeks but at 21 weeks they again approached normal values. The soleus muscle, however, was permanently decreased in size and this muscle, in contrast to the normal soleus muscle, contained mainly type II fibres. The morphology of the endplates showed distinct stages of degeneration and reinnervation. Two weeks after denervation, in rats in which reinnervation was prevented, all 3 muscles contained considerable numbers of morphologically abnormal endplates and, after 7 weeks, no endplates were detected. During reinnervation, endplates showing signs of acetylcholinesterase activity were observed in all 3 muscles from 7 weeks. At later ages a shift towards morphologically normal endplates occurred, but complete recovery was not observed. Endplates in all 3 muscles were polyneurally innervated at 7 weeks. Although these percentages decreased over age, polyneural innervation was still present at 21 weeks. We conclude that the changes in the distribution of fibre types, abnormal endplate morphology and polyneural innervation may in part explain the poor functional recovery after peripheral nerve lesions. [source]

Matrix metalloproteinase 11 (MMP-11; stromelysin-3) and synthetic inhibitors

MEDICINAL RESEARCH REVIEWS, Issue 4 2007
Magdalini Matziari
Abstract Matrix metalloproteinase (MMP)-11, or Stromelysin 3, is a particular member of MMP family, a group of zinc-dependent endopeptidases involved in matrix degradation and tissue remodeling. Despite intense efforts since its first characterization 15 years ago, its role and target substrates in different diseases remain largely unknown. While mice with MMP-11 deficiency display no particular phenotype, analysis of different tumorigenesis models with these mice lead to the conclusion that MMP-11 promotes tumor development. In contrast with other MMPs, MMP-11 is unable to degrade any major extracellular matrix component and unlike most of other MMPs that are secreted as inactive proenzymes and activated extracellularly, MMP-11 is secreted under active form. MMP-11 may thus play a unique role in tissue remodeling processes, including those associated with tumor progression. Although MMP-11 and other MMPs have been considered as promising targets to combat cancer, a first series of clinical trials using broad-spectrum MMP inhibitors have not led to significant therapeutic benefits. These disappointing results highlight the need for better understanding of the exact role played by each MMP during the different stages of tumor progression. Among the different strategies to fill this gap, highly specific MMP inhibitors would be of great value. This review provides an update on the selectivity profile of phosphinic MMP-11 synthetic inhibitors developed and discusses the opportunities and limitations to identify inhibitors able to fully discriminate MMP-11 from the other MMPs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 528,552, 2007 [source]

Anti-angiogenic drugs: from bench to clinical trials

MEDICINAL RESEARCH REVIEWS, Issue 4 2006
Ana R. Quesada
Abstract Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 483,530, 2006 [source]

POLITICAL ECONOMY OF THE DISAPPOINTING DOHA ROUND OF TRADE NEGOTIATIONS

PACIFIC ECONOMIC REVIEW, Issue 3 2007
Robert E. Baldwin
In particular, it is argued that economic factors of the type traditionally emphasized by economists in their classrooms are by themselves inadequate for analysing the negotiating process. A variety of political economy factors are discussed as explanations for the disappointing results of the Doha Round. [source]

HALT-C Is Huge Disappointment

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009
Article first published online: 26 MAR 200
This month, The AJT Report takes a look at developments in islet cell transplantation, and examines the disappointing results of the HALT-C trial. [source]

Co-Production and Health System Reform , From Re-Imagining To Re-Making

AUSTRALIAN JOURNAL OF PUBLIC ADMINISTRATION, Issue 1 2009
Roger Dunston
There is growing interest in the application of citizen participation within all areas of public sector service development, where it is increasingly promoted as a significant strand of post-neoliberal policy concerned with re-imagining citizenship and more participatory forms of citizen/consumer engagement. The application of such a perspective within health services, via co-production, has both beneficial, but also problematic implications for the organisation of such services, for professional practice and education. Given the disappointing results in increasing consumer involvement in health services via ,choice' and ,voice' participation strategies, the question of how the more challenging approach of co-production will fare needs to be addressed. The article discusses the possibilities and challenges of system-wide co-production for health. It identifies the discourse and practice contours of co-production, differentiating co-production from other health consumer-led approaches. Finally, it identifies issues critically related to the successful implementation of co-production where additional theorisation and research are required. [source]