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121.
Identification and use of biomarkers in Gaucher disease and other lysosomal storage diseases 总被引:1,自引:0,他引:1
J M F G Aerts C E M Hollak M van Breemen M Maas J E M Groener RG Boot 《Acta paediatrica (Oslo, Norway : 1992)》2005,94(S447):43-46
The value of biomarkers in the clinical management of lysosomal storage diseases is best illustrated by the present use of plasma chitotriosidase levels in the diagnosis and monitoring of Gaucher disease. The enzyme chitotriosidase is specifically produced and secreted by the pathological storage macrophages (Gaucher cells). Plasma chitotriosidase levels are elevated on average 1000-fold in symptomatic patients with Gaucher disease and reflect the body burden on storage cells. Changes in plasma chitotriosidase reflect changes in clinical symptoms. Monitoring of plasma chitotriosidase levels is nowadays commonly used in decision making regarding initiation and optimization of costly therapeutic interventions (enzyme replacement therapy or substrate reduction therapy). A novel substrate has been developed that further facilitates the measurement of chitotriosidase in plasma samples. Moreover, an alternative Gaucher-cell marker, CCL18, has been very recently identified and can also be employed to monitor the disease, particularly in those patients lacking chitotriosidase due to a genetic mutation. There is a need for comparable surrogate markers for other lysosomal storage diseases and the search for such molecules is an area of intense investigation.
Conclusion: The use of biomarkers can provide valuable insight into the molecular pathogenesis of LSDs, such as Gaucher disease and Fabry disease. 相似文献
Conclusion: The use of biomarkers can provide valuable insight into the molecular pathogenesis of LSDs, such as Gaucher disease and Fabry disease. 相似文献
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Deep brain stimulation in the treatment of Parkinson's disease: a cost-effectiveness analysis 总被引:4,自引:0,他引:4
BACKGROUND: In treating PD, deep brain stimulation (DBS) has shown great promise in a series of uncontrolled studies. OBJECTIVE: To estimate the incremental cost effectiveness of DBS compared with the best medical management in late-stage PD. METHODS: The authors constructed a decision model to determine the lifetime incremental cost effectiveness between two options in patients with PD aged 50 years and older: 1) best medical management and 2) DBS. As the long-term efficacy of DBS (>3 years) is not known, key assumptions regarding the procedure's long-term durability were made. Costs were in US 2000 dollars, and quality-adjusted life year (QALY) was the effectiveness measure. Base assumptions were that quality of life (QOL) in patients with late-stage PD is 0.55 (0-to-1 scale, 1 is perfect health) and that DBS benefits are constant for 4 years, eroding gradually over the next 5 years until at parity with those produced by best medical management. Incremental cost-effectiveness and sensitivity analyses were performed. RESULTS: Under base-case assumptions, DBS provides an additional 0.72 QALY at an additional cost of $35,000 compared with best medical management that results in an incremental cost-effectiveness ratio (C/E) of $49,000. QOL increases of between 18 and 30% resulted in questionable cost effectiveness. QOL increases of between 6 and 18% resulted in incremental C/E ratios not usually considered cost effective (>100,000/QALY). CONCLUSIONS: The results suggest that DBS may be cost effective in treating PD if QOL improves 18% or more compared with those receiving best medical management. This underscores the need for randomized, controlled, prospective DBS experiments including QOL and economic components. 相似文献
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Antibodies to tumor necrosis factor alpha prevent increases in cell replication in liver due to the potent peroxisome proliferator, WY- 14,643 总被引:7,自引:6,他引:7
Bojes HK; Germolec DR; Simeonova P; Bruccoleri A; Schoonhoven R; Luster MI; Thurman RG 《Carcinogenesis》1997,18(4):669-674
Several structurally dissimilar hypolipidemic drugs, plasticizers and
halogenated hydrocarbons induce peroxisomes in hepatocytes, and cause
hepatocellular adenoma and carcinoma in rats and mice. The mechanism by
which these agents act is unknown, although recent studies have suggested a
link between increased cell proliferation and hepatic cancer caused by
peroxisome proliferators. Here, we demonstrate that neutralizing antibodies
to tumor necrosis factor alpha (TNF alpha) block increases in protein
kinase C and cell proliferation due to [4-
chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643), a
hypolipidemic drug and potent peroxisome proliferator that causes tumors.
WY-14,643 moderately elevated the level of TNF alpha mRNA in the liver. TNF
alpha was detected immunohistochemically exclusively in Kupffer cells.
These results demonstrate that WY-14,643 acts as an indirect mitogen on
hepatocytes via TNF alpha. We propose that the Kupffer cell, a major source
of TNF alpha in the liver, is involved in the mechanism of the mitogenic
effect of WY-14,643.
相似文献
127.
Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care 总被引:1,自引:0,他引:1
Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants. 相似文献
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An 18-year-old air traffic controller fainted while running; an asymptomatic accelerated idioventricular rhythm was discovered in the ensuing aeromedical workup. The clinical presentation, ECG diagnosis, and aeromedical disposition of accelerated idioventricular rhythm are discussed. 相似文献