Citations

Background— Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET A ) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and Results— Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET A receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10 −6 to 10 −4 mol/L) in the left anterior descending coronary artery. N G -monomethyl- l -arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus −2.22%, 95% confidence interval −27.37% to 15.28%; P <0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N G -monomethyl- l -arginine were similar between the groups at baseline and at 6 months. Conclusions— This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.

Background— Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. Methods and Results— The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004–2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 am and 3 pm ( P <0.001). Time of onset was associated with prehospital delay and timeliness of reperfusion. Patients with onset from 12 am to 5:59 am had median prehospital delays of 121 minutes versus 70 minutes from 12 pm to 5:59 pm ( P <0.001). Patients with onset time from 12 am to 5:59 am had median door-to-balloon times of 75 minutes versus 60 minutes from 6 am to 11:59 am ( P <0.001). Using multivariable modeling to control for baseline patient characteristics, prehospital delay, and timeliness of reperfusion, there was no significant association between time of symptom onset with in-hospital death. Conclusions— Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 am to 5:59 am present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death.

Object Second-generation antiepileptic drugs (AEDs) are increasingly used in the care of patients with glioma. There is little data on how this practice compares with the use of traditional AEDs in this population. This noninferiority analysis compares seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy. Methods The authors retrospectively reviewed the records of 500 consecutive patients with glioma who were treated in clinical trials from 2001 to 2008 at 3 Mayo Clinic campuses. To be eligible for the study, these patients had to have had at least 1 clinical seizure and to have undergone follow-up for at least 6 months. Seizure outcomes, defined by the occurrence of a second seizure, time to second seizure, and seizure frequency, along with AED side effects, were compared between cohorts treated with phenytoin or levetiracetam Results Seventy-six patients were identified, 25 treated with phenytoin and 51 with levetiracetam. Sixty-four percent of the patients had a Grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p = 0.584), second seizure rates (p = 0.561), and average seizures per month (p = 0.776). When adjusting for age, sex, type of seizure, type of glioma, and dosage using univariate and multivariate models, there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values > 0.05). The incidence of side effects in the levetiracetam group was 6% versus 20% in the phenytoin group (p = 0.106). Additionally, 36% of the patients in the phenytoin group had dose adjustments unrelated to breakthrough seizures compared with only 10% in the levetiracetam group (p = 0.010) Conclusions In this study, patients with glioma treated with levetiracetam and phenytoin had similar seizure control. Patients treated with levetiracetam experienced fewer side effects and required fewer nonseizure-related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma.

Background There are sparse data available regarding outcome of meniscal repair performed at the time of ACL reconstruction in the pediatric and adolescent population. Purpose To review the results of meniscal repair performed at the time of ACL reconstruction in pediatric and adolescent patients. Study Design Case series; Level of evidence, 4. Methods The records of all patients age 18 years or younger who underwent meniscal repair at the time of ACL reconstruction between 1990 and 2005 were reviewed. Ninety-nine patients (56 female, 43 male) with an average age of 16 years (range, 13-18) were included. Average injury to surgery interval was 107 days (range, 2-1109). Clinical outcomes were assessed at a mean of 8 years postoperatively (range, 2-19). A multivariate model was used to compare this cohort with a previously published cohort of patients with isolated meniscal tears. Results The clinical success rate of meniscal repair was 84% for simple tears, 59% for displaced bucket-handle tears, and 57% for complex tears (74% overall). Twenty-six menisci (26% overall) failed repair and 25 patients underwent repeat arthroscopic surgery (19 partial meniscectomies, 6 re-repairs). The average Tegner and International Knee Documentation Committee scores were 6.2 (range, 2-10) and 90.3 (range, 52-100), respectively. Risk factors for failure included complex and bucket-handle tear (P = .01), medial meniscal tears (P = .03), and skeletal immaturity (P = .01). Compared with isolated meniscal repairs in a similar pediatric and adolescent population, complex tears repaired in combination with ACL reconstruction did significantly better (57% vs 13%; P = .004). Conclusion Clinically successful repair of meniscal tears treated at the time of ACL reconstruction in patients 18 years or younger depends on tear type, with complex and bucket-handle tears being negative prognostic factors. Complex tears have a higher rate of clinical success when repaired at the time of ACL reconstruction versus when repaired in isolation.