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At least 397 records · Page 22Linked to original sources
PubMed2002

Helicobacter: a paradigm shift in peptic ulcer disease and more?

There are many diseases where the cause is unknown and this makes a specific treatment difficult. In many cases all that can be achieved is amelioration of the illness. Peptic ulcer disease was one such condition no more that 20 years ago. The management was drastic--either an operation or life-long medication in order to reduce the acid secreted by the stomach. However, the cause of this condition was discovered in 1983. Although initially sceptical, the medical fraternity now almost universally endorse Helicobacter pylori as the cause of the majority of stomach ulcers. Peptic ulcers can now be cured by antibiotics. This is a major shift in medical practice. Continued investigations on Helicobacter pylori are bringing to light other possible associations with disease as well as delineating plausible biological mechanisms for disease pathogenesis.

Autoantibodies↗
PubMed2004

Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurologic disorders.

Alzheimer's disease (AD) is the most common form of dementia, as least in western countries. It has been estimated that the cost to society for caring for AD patients will consume the entire gross national product of the U.S.A. by the middle of this century if left unabated. Until recently, the only available drugs for this condition were cholinergic treatments, which symptomatically enhance cognitive state to some degree, but they were not neuroprotective. In fact, many potential neuroprotective drugs tested in clinical trials failed because they were poorly tolerated. However, after our discovery of its clinically-tolerated mechanism of action, one neuroprotective drug, memantine, was recently approved by the European Union and the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease. Recent phase 3 clinical trials have shown that memantine is effective in the treatment of moderate-to-severe Alzheimer's disease and possibly vascular dementia (multi-infarct dementia). Here we review the molecular mechanism of memantine's action and also the basis for the drug's use in these neurological diseases, which are mediated at least in part by excitotoxicity. Excitotoxicity is defined as excessive exposure to the neurotransmitter glutamate or overstimulation of its membrane receptors, leading to neuronal injury or death. Excitotoxic neuronal cell death is mediated in part by overactivation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, which results in excessive Ca(2+) influx through the receptor's associated ion channel. Physiological NMDA receptor activity, however, is also essential for normal neuronal function. This means that potential neuroprotective agents that block virtually all NMDA receptor activity will very likely have unacceptable clinical side effects. For this reason many previous NMDA receptor antagonists have disappointingly failed advanced clinical trials for a number of neurodegenerative disorders. In contrast, studies in our laboratory have shown that the adamantane derivative, memantine, preferentially blocks excessive NMDA receptor activity without disrupting normal activity. Memantine does this through its action as an uncompetitive, low-affinity, open-channel blocker; it enters the receptor-associated ion channel preferentially when it is excessively open, and, most importantly, its off-rate is relatively fast so that it does not substantially accumulate in the channel to interfere with normal synaptic transmission. Clinical use has corroborated the prediction that memantine is thus well tolerated. Besides Alzheimer's disease, memantine is currently in trials for additional neurological disorders, including other forms of dementia, depression, glaucoma, and severe neuropathic pain. A series of second-generation memantine derivatives are currently in development and may prove to have even greater neuroprotective properties than memantine. These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention.

Alzheimer Disease↗
PubMed2004

Unconscious perception: the need for a paradigm shift.

According to Snodgrass, Bernat, and Shevrin (2004), unconscious perception can be demonstrated convincingly only at the objective detection threshold, provided that the conditions of their objective detection/strategic model are met, whereas both the subjective threshold model of Cheesman and Merikle (1984, 1986) and the objective threshold/rapid decay model of Greenwald, Draine, and Abrams (1996) are inconclusive. We argue on theoretical, metatheoretical, and empirical grounds that all three dual-process models, which are based on both conscious and unconscious perception, should be rejected in favor of the single-process conscious perception model.

Humans↗
PubMed2004

Shifting paradigms. Teaching gerontological nursing from a new perspective.

Gerontological health care is undergoing a revolution, much like that of the feminist movement of the 1960s. Fundamental changes in health care require revisions in nursing education to ensure appropriate care of older adults in the least restrictive environment. The purpose of this study is to promote the preparation of future nurses who have the knowledge and the skills necessary to provide nursing care for the growing cohorts of older adults. A theoretical rationale for a new perspective in nursing education is discussed. An experiential clinical learning activity based on the functional model of gerontological health care is examined. This home visit clinical learning activity provides nursing students with the opportunity to practice nursing reflective of the health care needs of older adults. Strategies for replication of this clinical learning activity are provided.

Aged↗
PubMed2006

Mixed behaviors in dementia: the need for a paradigm shift.

This research was an examination of two specific types of behaviors, apathy and agitation, that commonly occur in older adults with dementia. In a retrospective analysis of existing data from two intervention projects, the authors explored the times and the types of behaviors occurring in 141 older adults living in the community, assisted living, and nursing home settings. The occurrence of apathetic and agitated behaviors was monitored throughout the day for a 2-week period. The result of the analysis suggests that in all stages and settings, a combination of apathy and agitation is the most common phenomenon, and that the predominant behavior actually fluctuates during the course of the day. The use of individualized interventions based on carefully monitored behavior patterns may provide a more sensitive approach to the overall treatment needs of individuals with dementia in the future.

Activities of Daily Living↗
PubMed1999

Diagnosing polycythemia vera: a paradigm shift.

The primary objective during the evaluation of erythrocytosis is to ascertain the presence or absence of polycythemia vera (PV). Because of prognostic and treatment differences, PV must be distinguished from relative polycythemia and secondary erythrocytosis. This distinction is currently accomplished through the laboratory measurement of red blood cell mass, plasma volume, and arterial oxygen saturation and determination of oxygen pressure at 50% hemoglobin saturation (P50). Furthermore, according to the Polycythemia Vera Study Group guidelines, the demonstration of an increased red blood cell mass is an absolute criterion for the diagnosis of PV. This article discusses the use of the serum erythropoietin level and endogenous erythroid colony assay as a potential alternative in the diagnosis of PV.

Decision Trees↗
PubMed2004

Shifting paradigms in hormonal therapy for breast cancer.

BACKGROUND: Tamoxifen has been the mainstay of endocrine treatment for postmenopausal patients with early and advanced breast cancer for many years. However, as an anti-estrogen with partial estrogenic effects, tamoxifen also has some serious safety and tolerability issues. Following tamoxifen treatment failure there were initially limited options for subsequent therapy. Therefore, new agents, including new anti-estrogens and aromatase inhibitors (AIs) were developed. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles. Abstracts were included only when the relevant information had not been published in full elsewhere. Only papers published in English were included. RESULTS: The AIs have been shown to be effective treatments for hormone-sensitive metastatic breast cancer. CONCLUSIONS: Current clinical trial data in early breast cancer show longer disease-free survival and time to recurrence with anastrozole than that demonstrated with tamoxifen and very good general tolerability, although longer follow-up is warranted. Clinical trials of the use of AIs in breast cancer prevention and preliminary data for the combination of anastrozole with a gonadotrophin-releasing hormone for the treatment of premenopausal women with early stage breast cancer are also discussed here.

Antineoplastic Agents, Hormonal↗
PubMed2006

Shifting paradigms: a social-determinants approach to solving problems in men's health policy and practice.

The lack of an evidence base for formulating men's health policies means existing programs and practices for men are influenced by prevailing cultural norms concerning men or habitual health service attitudes towards them. Factors impeding the development of an effective health policy for men include a preoccupation with limited clinical perspectives (an emphasis on the prostate and erectile dysfunction) and a common assumption that all health problems in men are a result of "masculinity" and "men behaving badly". Viewing men's health in terms of gender and health and the socially constructed differences between men and women is important, but does not provide all the perspectives required for meeting men's health needs. A "social determinants of health" approach to men's health would help Australia and Australian medical practitioners move away from policies and practices that perpetuate negative views of men and ignore the complexity of their health problems. The result would be a more evidence-based approach to men's health policy, and the likelihood of improved health outcomes.

Australia↗
PubMedDate not supplied

Medicine in resource-poor settings: time for a paradigm shift?

The current global health system, which concentrates on a few and neglects billions of people who live in resource-poor settings and carry the largest burden of global diseases, is unacceptable. The weight of medical practice patterns ought to shift from the therapeutic phase of medical care to prevention. Achieving better health for the majority of humanity requires innovation, improved resources, new cooperation between the rich and the poor, and a clear ethical vision, consolidated by goal-oriented and system-focused strategic health planning. Development assistance from wealthier nations to developing countries must shift from the current donor-driven agendas to country-driven sector-wide approaches for health development with adequate accountability and sustainability. There must be a fundamental departure from classical universalism to new universalism, reoriented by a new public health, and reinforced by a new solidarity, using holistic approaches to ensure better health for the whole of humanity.

Developing Countries↗