46 research outputs found
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Background
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens â aspirin plus extendedrelease
dipyridamole (ASAâERDP) versus clopidogrel.
Methods
In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive
25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive
75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke.
The secondary outcome was a composite of stroke, myocardial infarction, or death
from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075),
followed by superiority testing, was planned.
Results
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke
occurred in 916 patients (9.0%) receiving ASAâERDP and in 898 patients (8.8%) receiving
clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The
secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for
ASAâERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events
among ASAâERDP recipients (419 [4.1%]) than among clopidogrel recipients (365
[3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage
(hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major
hemorrhagic event was similar in the two groups (1194 ASAâERDP recipients [11.7%],
vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions
The trial did not meet the predefined criteria for noninferiority but showed similar rates
of recurrent stroke with ASAâERDP and with clopidogrel. There is no evidence that either
of the two treatments was superior to the other in the prevention of recurrent
stroke. (ClinicalTrials.gov number, NCT00153062.
Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors
Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects
Opportunistic illnesses in Brazilian children with AIDS: results from two national cohort studies, 1983-2007
<p>Abstract</p> <p>Background</p> <p>HAART has significantly reduced AIDS-related morbidity in children. However, limited evidence is available from developing countries regarding patterns of opportunistic illnesses. We describe these events and their associated factors in children with AIDS in Brazil.</p> <p>Methods</p> <p>This study is based on two representative retrospective multi-center cohorts including a total 1,859 children with AIDS, infected via mother-to-child transmission (MTCT), between 1983-2002. Opportunistic illnesses were described and analyzed over time. The association of demographic, clinical and operational data with the occurrence of opportunistic diseases was assessed.</p> <p>Results</p> <p>In total, 1,218 (65.5%) had at least one event of an opportunistic disease. Variables significantly associated with occurrence of these events included: region of residence (OR 2.68-11.33, as compared to the Northern region), age < 1 year at diagnosis (OR 2.56, 95% CI 1.81-3.61, p < 0.001), and non-performance of MTCT prevention measures (OR 1.58, 95% CI 1.21-2.07, p < 0.001). Protective factors included year of HIV diagnosis in the HAART era (OR 0.34, 95% CI 0.15-0.76, p = 0.009) and ART use (OR 0.58, 95% CI 0.44-0.77, p < 0.001). In both periods bacterial infections represented the most common opportunistic events (58.6 vs. 34.7%; p < 0.001), followed by <it>Pneumocystis jirovecii </it>pneumonia (21.9 vs. 13.2%; p < 0.001), and bacterial meningitis/sepsis (16.8 vs. 7.4%; p < 0.001).</p> <p>Conclusions</p> <p>Despite the significant reduction in recent years, opportunistic illnesses are still common in Brazilian children with AIDS in the HAART era, especially bacterial diseases. The data reinforce the need for scaling up prevention of MTCT, early diagnosis of infection, and improvement of comprehensive pediatric care.</p
Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications
The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are α-[11C]methyltryptophan ([11C]AMT) and 5-hydroxy-L-[ÎČ-11C]tryptophan ([11C]5-HTP). Both tracers have advantages and disadvantages. [11C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [11C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain
Behavioral correlates of the activity of serotonergic and non-serotonergic neurons in caudal raphe nuclei
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Background
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens â aspirin plus extendedrelease
dipyridamole (ASAâERDP) versus clopidogrel.
Methods
In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive
25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive
75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke.
The secondary outcome was a composite of stroke, myocardial infarction, or death
from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075),
followed by superiority testing, was planned.
Results
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke
occurred in 916 patients (9.0%) receiving ASAâERDP and in 898 patients (8.8%) receiving
clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The
secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for
ASAâERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events
among ASAâERDP recipients (419 [4.1%]) than among clopidogrel recipients (365
[3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage
(hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major
hemorrhagic event was similar in the two groups (1194 ASAâERDP recipients [11.7%],
vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions
The trial did not meet the predefined criteria for noninferiority but showed similar rates
of recurrent stroke with ASAâERDP and with clopidogrel. There is no evidence that either
of the two treatments was superior to the other in the prevention of recurrent
stroke. (ClinicalTrials.gov number, NCT00153062.
Telmisartan to prevent recurrent stroke and cardiovascular events
Background
Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent
stroke. In addition, inhibition of the reninâangiotensin system in high-risk patients
reduces the rate of subsequent cardiovascular events, including stroke. However, the
effect of lowering of blood pressure with a reninâangiotensin system inhibitor soon
after a stroke has not been clearly established. We evaluated the effects of therapy
with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.
Methods
In a multicenter trial involving 20,332 patients who recently had an ischemic stroke,
we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive
placebo. The primary outcome was recurrent stroke. Secondary outcomes were
major cardiovascular events (death from cardiovascular causes, recurrent stroke,
myocardial infarction, or new or worsening heart failure) and new-onset diabetes.
Results
The median interval from stroke to randomization was 15 days. During a mean followup
of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan
group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group
and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in
the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P = 0.23). Major
cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and
1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01;
P = 0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the
placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10).
Conclusions
Therapy with telmisartan initiated soon after an ischemic stroke and continued for
2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular
events, or diabetes. (ClinicalTrials.gov number, NCT00153062.