PubMed · 3146118
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M Kinoshita. 1988. [Nitrate tolerance].. https://pubmed.ncbi.nlm.nih.gov/3146118/
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Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent, enduring, and progressively more robust behavioral response. This process serves as an important model of neural plasticity and has also been proposed as a model for a variety of psychiatric syndromes; however, there are no published controlled studies of behavioral sensitization in human subjects. The authors report results from a double-blind, placebo-controlled study of repeated d-amphetamine challenges in a sample of normal human volunteers. Eleven consecutively recruited normal volunteers participated in this 4-day protocol. Each subject received two daily doses of d-amphetamine (0.25 mg/kg) separated by 48 hours that alternated with two daily doses of matched placebo. Symptoms (activity/energy level, mood, rate, and amount of speech) and eye-blink rates were measured hourly for 5 hours following drug administration. All four measures demonstrated significantly enhanced increases following the second amphetamine dose as compared to the first amphetamine dose and both placebo conditions. These findings suggest that behavioral sensitization is measurable in human subjects.
BACKGROUND: Moderate anticoagulation may be proposed to reduce the risk of hemorrhage for certain patients with a mechanical prosthesis, but the consequences for risk of thromboembolism are debated. METHODS AND RESULTS: The purpose of the AREVA trial was to compare moderate oral anticoagulation (international normalized ratio [INR] of 2.0 to 3.0) with the usual regimen (INR of 3.0 to 4.5) after a single-valve replacement with a mechanical prosthesis, either Omnicarbon or St Jude. Patients included were between 18 and 75 years old, in sinus rhythm, and with a left atrial diameter < or = 50 mm on the time-motion echocardiogram. Patients were randomized for INR after surgery. From 1991 to 1994, 433 patients underwent valve replacement (aortic, 414; mitral, 19) with 353 St Jude and 80 Omnicarbon prostheses; 380 patients were randomized for INR: 188 for INR 2.0 to 3.0 and 192 for INR 3.0 to 4.5. Mean follow-up was 2.2 years (1 to 4 years). Analysis of 18001 INR samples showed that the mean of the median of INR was 2.74 +/- 0.35 in the 2.0 to 3.0 group and 3.21 +/- 0.33 in the 3.0 to 4.5 group (P < .0001). Thromboembolic events, as assessed from clinical data and CT brain scans, occurred in 10 patients in the 2.0 to 3.0 INR group and 9 patients in the 3.0 to 4.5 INR group (P = .78). Hemorrhagic events occurred in 34 patients in the 2.0 to 3.0 INR group and 56 patients in the 3.0 to 4.5 INR group (P < .01), with 13 and 19 major hemorrhagic events, respectively (P = .29). CONCLUSIONS: In selected patients with mechanical prostheses, moderate anticoagulation prevents thromboembolic events as effectively as conventional anticoagulation and reduces the incidence of hemorrhagic events.
BACKGROUND: There are no reported studies on the safety and efficacy of low-dose aspirin with low-intensity oral anticoagulation in patients with heart valve replacement. In this study, we compared the use of 100 mg/d aspirin with 650 mg/d aspirin in the prevention of systemic embolism and vascular death in patients with heart valve replacement who were being treated with oral anticoagulants with a target international normalized ratio (INR) of 2.0 to 3.0. METHODS AND RESULTS: Four hundred nine of 416 consecutive patients who had cardiac valve replacement were randomized in open allocation into one of two groups; both groups were treated with oral anticoagulant therapy with a target INR of 2.0 to 3.0. Two hundred seven patients who received 100 mg/d aspirin for an average of 24.1 months were compared with 202 patients who received 650 mg/d aspirin for an average of 21.7 months in a randomized-treatment, open-allocation study. There were no significant differences in systemic embolism, vascular death, or total death rates between the low- and high-dose aspirin treatment groups (0.5 and 1.1, 1.2 and 0.5, and 4.6 and 2.5 per 100 patients/y, respectively). The total number of hemorrhagic events was 13.4 per 100 patients/y in the high-dose aspirin group and 7.9 per 100 patients/y in the low-dose aspirin group (P = .035), but the rate of bleeding was influenced by dipyridamole in the 650-mg aspirin group. CONCLUSIONS: In patients with mechanical heart valve replacements, low-dose aspirin (100 mg/d) in conjunction with oral anticoagulants at an INR of 2.0 to 3.0 is as effective as the use of high-dose aspirin (650 mg/d) in the prevention of systemic embolism.