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71.
72.
L Zhang W Gorset C B Washington T F Blaschke D L Kroetz K M Giacomini 《Drug metabolism and disposition》2000,28(3):329-334
Recently, we cloned a human organic cation transporter, hOCT1, which is expressed primarily in the liver. hOCT1 plays an important role in the cellular uptake and elimination of various xenobiotics including therapeutically important drugs. HIV protease inhibitors are a new class of therapeutic agents. The purpose of this study was to elucidate the interactions of HIV protease inhibitors with hOCT1 and to determine whether hOCT1 is involved in the elimination of these compounds. We studied the interactions of HIV protease inhibitors with hOCT1 in a transiently transfected human cell line, HeLa. Uptake studies were carried out 40 h post-transfection using the radiolabeled model organic cation, [(14)C]tetraethylammonium (TEA), under different experimental conditions. In cis-inhibition studies, all of the HIV protease inhibitors tested, i.e., indinavir (IC(50) of 62 microM), nelfinavir (IC(50) of 22 microM), ritonavir (IC(50) of 5.2 microM), and saquinavir (IC(50) of 8.3 microM) inhibited TEA uptake in HeLa cells expressing hOCT1. However, none of the HIV protease inhibitors trans-stimulated [(14)C]TEA uptake, suggesting that they are poorly translocated by hOCT1. Nelfinavir, ritonavir, and saquinavir demonstrated an apparent "trans-inhibition" effect. No enhanced uptake of [(14)C]saquinavir was observed in hOCT1 DNA-transfected cells versus empty vector-transfected cells. These data suggest that HIV protease inhibitors are potent inhibitors, but poor substrates, of hOCT1. Some HIV protease inhibitors may potently inhibit the uptake and elimination of cationic drugs that are substrates for hOCT1, leading to potential drug-drug interactions. Other transporters, e.g., MDR1 and MRP1, in HIV-targeted cells may control the intracellular concentrations of HIV protease inhibitors. 相似文献
73.
A group of 99 babies born in hospital and subsequently transferred to the special care unit were examined for the presence of candidas orally. The rate of isolation rose from 6% neonatally to 53% on day 14 of life. Among infants who did not harbour the organisms when discharged from hospital, colonization rapidly took place so that 79% did so at 4 weeks of age, after which the rate fell to 50% at one year of age. The low incidence of clinical candidosis suggests that in these babies as in other groups C. albicans is normally a harmless commensal. 相似文献
74.
Eight cases of dermatomyositis in children admitted to Scottish hospitals between 1962 and 1972 have been reviewed. 6 of the 8 were currently in complete remission. In the other 2 cases the disease remained active in 1 and 1 had died of cardiac failure 6 years after the onset of disease. 5 had developed extensive soft tissue calcification for which 2 were treated with ethanehydroxydiphosphonate, one showing definite improvement and the other no change. All had been treated with corticosteroids and two in addition had had cytotoxic agents (methotrexate or cyclophosphamide). The overal prognosis had probably been improved by the use of corticosteroids but not by the cytotoxic drugs. Only one of the patients was incapacitated by residual contractures or calcinosis. 相似文献
75.
Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992 总被引:1,自引:1,他引:0 下载免费PDF全文
DB Langille MR Joffres KM MacPherson P Andreou SA Kirkland DR MacLean 《Canadian Medical Association journal》1999,161(8):S3-S9
BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification. 相似文献
76.
KM RAI KJ PHILIPOSE VSM P TAKKAR RR BHONDE KK MAUDAR NK PANICKER 《Medical Journal Armed Forces India》1999,55(2):119-122
Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono-layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.KEY WORDS: Endothelial cell seeding, Vascular grafts 相似文献
77.
Priyadarshini Arunakumar DM Anoop Ayyappan MD Deepa Sasikumar DM KM Krishnamoorthy DM 《Echocardiography (Mount Kisco, N.Y.)》2018,35(5):733-734
A 12‐year‐old child presented with recurrent respiratory infections and was diagnosed with Scimitar syndrome. Drainage of IVC and course of aberrant arterial supply from aorta were not clear by echocardiogram, and hence, additional imaging was planned. CT unraveled the presence of a rare combination of anomalous pulmonary venous connection (APVC) to IVC, with near‐atresia/severe stenosis of IVC, superior to the drainage of scimitar vein. There was a prominent azygos vein with preferential contrast opacification on lower limb injection. 相似文献
78.
Hasegawa BH; Naimuddin S; Dobbins JT d; Mistretta CA; Peppler WW; Hangiandreou NJ; Cusma JT; McDermott JC; Kudva BV; Melbye KM 《Radiology》1986,159(2):537-543
The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone. 相似文献
79.
The effect of probenecid on the renal elimination of cimetidine 总被引:1,自引:0,他引:1
L G Gisclon R A Boyd R L Williams K M Giacomini 《Clinical pharmacology and therapeutics》1989,45(4):444-452
It is generally assumed that the systems involved in the transport of organic cations and organic anions in the renal proximal tubule are substrate selective (i.e., organic anions do not inhibit organic cation transport and vice versa). However, recent data obtained in vitro have suggested that the organic anion probenecid inhibits the renal transport of the organic cation cimetidine. We addressed the question of whether this interaction is biologically relevant in human beings. The study involved a two-treatment, randomized crossover design. Six healthy male subjects were given an intravenous infusion of 300 mg cimetidine alone as one treatment and, as the other treatment, received multiple oral doses of probenecid before receiving the cimetidine infusion. The renal clearance of cimetidine and inulin was determined in each period. There were no significant differences between treatments in cimetidine plasma concentrations, apparent volume of distribution, systemic clearance, half-life, amount of drug excreted unchanged in the urine, or nonrenal clearance. Probenecid significantly decreased the renal clearance of cimetidine by decreasing both the filtration clearance and the net secretory clearance. These effects were most evident in the first 1/2 to 1 hour after cimetidine administration, when probenecid levels in plasma and renal tissue would have been the highest. Because there was no effect of probenecid on cimetidine plasma concentrations, this interaction is not clinically relevant to the therapeutic use of these two compounds. However, the study demonstrates that renal interactions between organic cations and organic anions can occur in human beings. The mechanism of this interaction and the implications to other drug combinations are being explored. 相似文献
80.
Mewissen MW; Erickson SJ; Foley WD; Lipchik EO; Olson DL; McCann KM; Schreiber ER 《Radiology》1989,173(1):155-157
Color Doppler flow imaging or compression ultrasound (US) was used to prospectively determine frequency of thrombosis at 54 venous insertion sites (47 in common femoral veins, seven in right internal jugular veins) after percutaneous placement of Greenfield filters for interruption of the inferior vena cava. Fifty-one filters were successfully placed in 51 patients with a dilator set or a balloon angioplasty catheter. Nine focal thrombi were detected in the common femoral vein (19%) and one in the right internal jugular vein (14%). Use of dilators induced eight thrombi (24%), compared with two (10%) from balloon catheters. The left common femoral vein had a high frequency of thrombosis, regardless of dilation technique (five of nine). Of nine patients with acute common femoral vein thrombosis, four became symptomatic within 10 days after the procedure. Patients may remain asymptomatic or have delayed symptoms; thus, US is valuable for determining patients at risk of thrombosis of the common femoral vein. 相似文献