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51.
Kieren J. Mather 《Reviews in endocrine & metabolic disorders》2013,14(1):87-99
Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin’s actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits. 相似文献
52.
Eman Hamad Dr Paul J. Mather Siva Srinivasan Sharon Rubin David J. Whellan Arthur M. Feldman 《Am J Cardiovasc Drugs》2007,7(4):235-248
Over the past 2 decades, investigators have learned more about the pathophysiologic changes that occur in systolic and diastolic dysfunction. Ironically, in some cases, the biologic pathways that have protected the heart during acute dysfunction are the same pathways that cause progressive deleterious effects with chronic activation. In particular, it is the activation of the neurohormonal system that has a significant impact on disease progression. As a result, the neurohormonal system has provided a key target for pharmacologic therapy in patients with heart failure secondary to systolic dysfunction. These targets include the renin-angiotensin-aldosterone system as well as the sympathetic nervous system. Neurohormonal manipulation, however, is often ineffective in the pharmacologic therapy of patients with endstage heart failure, therefore other treatment strategies - including the use of inotropic agents to improve pump function and diuretics to control fluid balance are needed. 相似文献
53.
Schaffer MA Mather S Gustafson V 《Journal of health care for the poor and underserved》2000,11(4):385-399
An agency providing health care services for homeless persons and a nursing department at a liberal arts college established a service-learning partnership to complete a health needs assessment of homeless persons. Under the guidance of agency staff and a nursing faculty member, seven nursing students surveyed shelter residents (n = 101) in four urban shelters and conducted a focus group to identify residents' perceptions of health, health care needs, and health care service delivery. The service-learning partnership expanded the agency's services by providing research consultation and data collection that resulted in recommendations to improve health care services for the homeless. The agency contributed to the education of health professionals by providing students with a meaningful community service experience. 相似文献
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56.
Mather KJ Norman EG Prior JC Elliott TG 《The Journal of clinical endocrinology and metabolism》2000,85(12):4644-4649
Regularly menstruating women are relatively protected from cardiovascular disease. Epidemiological and endothelial function studies attribute this protection to estradiol (E(2)), but both progesterone (P) and E(2) are normally present. A range of vascular effects of added progestins have been described, from neutral to detrimental, but the effects of P per se on endothelial function in humans have not been reported. We therefore investigated the acute effects of E(2), P, and E(2) combined with P, on endothelium-dependent and -independent forearm blood flow responses. Using venous occlusion plethysmography, forearm blood flow (FBF) was measured during acute brachial artery infusions, achieving physiologic levels of 17-beta-E(2), P, and 17-beta-E(2) with P in healthy menopausal women with no cardiovascular disease risk factors. Vehicle or hormones were infused, in random order, on 4 days, 1 week apart. Flow responses were measured during coinfusions of hormone with the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside. Twenty-seven healthy menopausal women were studied, and all had normal baseline endothelial responses. Small ( approximately 15%), statistically nonsignificant increases in endothelium-dependent flow responses were seen after all acute hormone treatments. No impairment in response was seen with P alone or in combination with 17-beta-E(2). In healthy menopausal women without cardiovascular disease risk factors and without baseline defects in endothelial function, acute exposure to physiologic levels of 17-beta-E(2), P, and 17-beta-E(2) with P produced equivalent endothelium-dependent responses. These data suggest that P does not have detrimental vascular effects in humans. 相似文献
57.
J Bomanji S Mather J Moyes D Ellison A Grossman K E Britton G M Besser 《Journal of nuclear medicine》1992,33(6):1121-1124
A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors. 相似文献
58.
Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery 总被引:4,自引:1,他引:3
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Laurence E. Mather Annie Woodhouse M. Elizabeth Ward Stephen J. Farr Reid A. Rubsamen & Lorne G. Eltherington 《British journal of clinical pharmacology》1998,46(1):37-43
Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMistTM , Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain.
Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMistTM and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects.
Results Plasma concentrations from SmartMistTM were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes.
Conclusions Fentanyl delivery using SmartMistTM can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. 相似文献
Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist
Results Plasma concentrations from SmartMist
Conclusions Fentanyl delivery using SmartMist
59.
L E Scheving C D Enna F Halberg R R Jacobson A Mather J E Pauly 《International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association》1975,43(4):364-377
We have herewith examined the characteristics of circadian rhythms in patients with lepromatous leprosy, active or inactive, allowing a comparison with corresponding properties of rhythms in healthy subjects mapped earlier. Group results were illustrated by cosinor plots, produced directly on microfilm by computer. Eventually such reference standards in the form of cosinors, among other displays, notably of waveform, may be individualized and carried on a person's health record. Such a quantitative assessment of an individual's rhythms in health may serve for rigorous comparison with any changes accompanying increased susceptibility or occult or overt disease. 相似文献
60.
L. E. Mather Ph.D G. T. Tucker T. M. Murphy M. d'A. Stanton-Hicks J. J. Bonica 《Acta anaesthesiologica Scandinavica》1976,20(3):207-210
Hypotension following peridural anesthesia with lidocaine was treated by intravenous injection of ephedrine. The ephedrine relieved the cardiovascular depression, but was associated with a concomitant increase in plasma lidocaine concentrations. This increase may push the plasma lidocaine concentration into the toxic region. 相似文献