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51.
52.
Julie C. Oki Pharm. D. 《Pharmacotherapy》1995,15(3):317-337
To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reductase inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs. 相似文献
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Petra Mullner Simon E.F. Spencer Daniel J. Wilson Geoff Jones Alasdair D. Noble Anne C. Midwinter Julie M. Collins-Emerson Philip Carter Steve Hathaway Nigel P. French 《Infection, genetics and evolution》2009,9(6):1311-1319
Integrated surveillance of infectious multi-source diseases using a combination of epidemiology, ecology, genetics and evolution can provide a valuable risk-based approach for the control of important human pathogens. This includes a better understanding of transmission routes and the impact of human activities on the emergence of zoonoses. Until recently New Zealand had extraordinarily high and increasing rates of notified human campylobacteriosis, and our limited understanding of the source of these infections was hindering efforts to control this disease. Genetic and epidemiological modeling of a 3-year dataset comprising multilocus sequence typed isolates from human clinical cases, coupled with concurrent data on food and environmental sources, enabled us to estimate the relative importance of different sources of human disease. Our studies provided evidence that poultry was the leading cause of human campylobacteriosis in New Zealand, causing an estimated 58–76% of cases with widely varying contributions by individual poultry suppliers. These findings influenced national policy and, after the implementation of poultry industry-specific interventions, a dramatic decline in human notified cases was observed in 2008. The comparative-modeling and molecular sentinel surveillance approach proposed in this study provides new opportunities for the management of zoonotic diseases. 相似文献
55.
Gerald L DeNardo Arutselvan Natarajan Saphon Hok Julie Perkins Monique Cosman Sally J DeNardo Felice C Lightstone Gary R Mirick Laird A Miers Rodney L Balhorn 《Journal of nuclear medicine》2007,48(8):1338-1347
Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting. 相似文献
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Julie N Hook Bruno Giordani David E Schteingart Kenneth Guire Jodie Giles Kelley Ryan Stephen S Gebarski Scott A Langenecker Monica N Starkman 《Journal of the International Neuropsychological Society》2007,13(1):21-29
Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment. 相似文献
58.
Holly K Craig Connie A Thompson Julie A Washington Stephanie L Potter 《J. Speech Lang. Hear. Res.》2003,46(3):623-635
The production of phonological features of African American English (AAE) was examined for 64 typically developing African American children in the 2nd through the 5th grade. Students read aloud passages written in Standard American English. Sixty of the students read the passages using AAE, and 8 different phonological features were represented in their readings. Phonological features were more frequent than morphosyntactic features. The findings as a whole support use of the taxonomy developed for this investigation in characterizing the phonological features of child AAE. 相似文献
59.
Marlon Normandin Joel Gagn Julie Bernard Robert lie Dom Miceli Michel Baudry Guy Massicotte 《Brain research》1996,730(1-2):40-46
Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A2 (PLA2) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA2 inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA2 and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD. 相似文献