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At least 199 records · Page 11Linked to original sources
PubMed1998

Glucosamine in osteoarthritis and gastrointestinal disorders: an exemplar of the need for a paradigm shift.

Glucosamine, after a latent period, is rapidly developing a position in the treatment of osteoarthritis, as well as a potential therapeutic place in wound healing and gastrointestinal disorders. Although recognized for a great many years, the association of gastrointestinal disorders and arthritis has been looked on as an unexplained oddity. Could this be indicative of a common etiology in the rate-limiting production of glucosamine? Could diverse presentations and pathology be due to a common-stem biochemical defect?

Animals↗
PubMed2002

Paradigm shifts in vaccine development: lessons learned about antigenicity, pathogenicity and virulence of Brucellae.

As part of a program to support the USDA Animal Plant Health Inspection Service Bovine Brucellosis Eradication Program, the Brucellosis Research Unit of the National Animal Disease Center (NADC) sought to develop a bovine brucellosis vaccine that would allow vaccinated animals to be distinguished from virulent field infected animals. In order to meet that goal, several avenues of research were undertaken to construct and test candidate vaccines, including Brucella abortus RB51. In early vaccine development studies, a subunit preparation obtained by extracting B. abortus with salts was studied as a candidate subunit vaccine. Later, molecular biological techniques were used both to clone genes encoding products found in the salt extract (BCSP31 and Cu-Zn SOD) and genes encoding proteins of B. abortus that were antigenic (HtrA) or possibly essential (two-component systems) for full virulence of B. abortus. In vitro systems using mammalian cells lines such as HeLa and macrophage-related were used along with the mouse model and host animal models. Results obtained at NADC and in other Brucellosis research laboratories, using survival in mammalian cell lines and the mouse model to access pathogenicity and virulence of genetically engineered strains, do not necessarily identify loci that are essential for full virulence or pathogenicity in the natural host, the bovine. Studies at NADC and other brucellosis laboratories showed that antigenicity was not a predictor of the effectiveness of a protein as a subunit vaccine.

Animals↗
PubMed2003

Shifting paradigms: biopharmaceuticals versus low molecular weight drugs.

Biopharmaceuticals are pharmaceutical products consisting of (glyco)proteins. Nowadays a substantial part of the FDA-approved drugs belong to this class of drugs. Biopharmaceuticals deserve special attention as they have a number of characteristics that set them aside from low molecular weight drugs. Their activity depends on their complicated shape based on secondary, tertiary and (sometimes) quaternary structures. These structures cannot be fully defined with our present set of analytical techniques and approaches for potency testing. They often are the same as (or closely resemble) endogenous proteins. This means that in safety testing and clinical test programs questions have to be addressed regarding species specific responses, selection of dosing schedules and route of administration, and the possible occurrence of immunogenicity. As the conformational structure of a protein is easily disturbed, formulation and handling of biopharmaceuticals needs special attention in order to optimize the therapeutic effect and minimize adverse reaction, among which immune responses. The issue of biogenerics is gaining more and more interest and different critical elements in the development of biogenerics are touched upon. In conclusion, biopharmaceuticals cannot be characterized fully in terms of their structure like low molecular weight drugs. The performance of biopharmaceuticals relies on strict production protocols and close monitoring of their activity in the clinical situation.

Animals↗
PubMed1995

A paradigm shift in providing care for the HIV/AIDS patient.

The authors report on a detailed cost study of HIV-infected patients receiving treatment at the McGill medical facilities. The results indicated that a home care setting is a cost-efficient site in which to care for an AIDS patient, with care provided in other settings when required. As the number of people with AIDS increases, efforts are needed to develop alternative care services for those infected with the virus. What is required would seem to be a service delivery system which would ensure cost-effective continuity of care across a continuum of services geared to varying levels of independence and illness severity.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Is the paradigm shifting?

Reduction in bone mass has long dominated the thinking about and approach to the problem of osteoporosis. A now large body of evidence indicates that bone mass is not adequate to explain satisfactorily either the skeletal fragility of osteoporosis or the effects of bone active agents. By contrast, bone remodeling activity seems to provide a better explanation of both. It is suggested that current syntheses in the field are shifting to this conclusion. In attempting to make sense out of how a process designed by evolution to sustain bone strength could instead be contributing to weakness, I suggest: (1) prevailing bone remodeling levels are substantially higher than are optimal for maintenance of bone strength; (2) this high level has discernible environmental causes; and (3) such high remodeling is a major source-perhaps the major source-of osteoporotic bony fragility. Within this context, reduced bone mass, rather than the primary cause of fracture, is seen as a factor that predisposes individuals to the harmful effects of excessive remodeling.

Bone Density↗
PubMed2003

Brain death: an important paradigm shift in the 20th century.

The description of death in medical or pathophysiological terms changed during the last century. The focus of attention shifted from the condition of the heart to the state of the brain. The current paper investigates the time period from 1866, when the effects of an increased intracranial pressure (ICP) were studied experimentally, to 1967, when the first heart transplantation was performed. Between 1894 and 1965 four neurosurgeons: Horsley in England, Cushing in USA, Wertheimer in France and Frykholm in Sweden made important contributions. Documented discussions, if ventilator treatment should be stopped in patients with a dead brain and a beating heart, began in 1959. However, already during the latter part of the 19th century it was shown that the heart could continue to beat if artificial ventilation was performed, when spontaneous respiration had ceased due to a high ICP. Furthermore, brain death was by chance implemented in clinical practice in heart surgery with cardiopulmonary bypass (CPB) some years before the expressions 'death of the nervous system' and 'brain death' were coined.

Brain Death↗