Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study

CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. OBJECTIVE: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING: Intramural National Institute of Mental Health; approved by the institutional review board.Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD.     

Risk factors for adverse outcomes in spontaneous versus assisted conception twin pregnancies

OBJECTIVE: To evaluate risk factors for adverse outcomes in spontaneous vs. assisted conception twin pregnancies. DESIGN: Historical cohort study. SETTING: Four academic tertiary medical centers. PATIENT(S): Women with twin pregnancies, including 2,143 spontaneous and 424 assisted conception; 2,492 nonreduced and 75 reduced. INTERVENTION(S): None (observational). MAIN OUTCOME MEASURE(S): Preeclampsia, preterm premature rupture of membranes, birth <32 weeks and <30 weeks, low birth weight, very low birth weight, and slowed midgestation fetal growth (<10th percentile between 20 and 28 weeks). RESULT(S): Among nonreduced pregnancies, assisted conception was not significantly associated with any adverse outcomes; among nulliparas, the risk for preeclampsia was increased regardless of method of conception; among spontaneous conceptions, the risks for preterm premature rupture of membranes, low birth weight, very low birth weight, and slowed midgestation fetal growth were increased. Among all pregnancies, fetal reduction increased risks for birth <32 weeks and <30 weeks, low birth weight, very low birth weight, and slowed midgestation fetal growth. Among nulliparas with assisted conceptions, fetal reduction increased the risks for birth <30 weeks, very low birth weight, and slowed midgestation fetal growth. CONCLUSION(S): These findings indicate that in twin pregnancies, assisted conception is not a risk factor for adverse outcomes, but rather specific factors that are more common among these pregnancies, such as nulliparity and fetal reduction, increase risks.     

Survival in patients with peripheral vascular disease after percutaneous coronary intervention and coronary artery bypass graft surgery

Background

Patients with peripheral vascular disease (PVD) undergoing coronary revascularization have high rates of adverse outcomes. Whether there are important differences in outcomes for surgical versus percutaneous coronary revascularization is unknown. The objective of this study was to compare survival in patients with PVD who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) surgery for multivessel coronary artery disease.

Methods

In-hospital data were collected on 1,305 consecutive patients undergoing coronary revascularization (PCI, n = 341; CABG, n = 964) in northern New England from 1994 to 1996. Patient records were linked to the National Death Index to assess survival out to 3 years (mean 1.2 years). Logistic and Cox proportional hazards regression were used to calculate risk-adjusted odds ratios and hazard ratios.

Results

Compared with CABG patients, those undergoing PCI were more often women, had more renal failure, more prior coronary revascularizations, were more likely to have two-vessel coronary artery disease and were more likely to undergo the procedure emergently. They were less likely to have a history of heart failure. After adjusting for differences in baseline characteristics, patients undergoing CABG had better intermediate survival than did PCI patients (hazard ratio 0.68; 95% confidence interval, 0.46 to 1.00; p = 0.05).

Conclusions

Patients with multivessel coronary artery disease and PVD undergoing CABG surgery have better intermediate survival out to 3 years than similar patients undergoing PCI. This information may be useful in counseling patients with PVD requiring coronary revascularization.     

Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.     

Shifting paradigms. Teaching gerontological nursing from a new perspective

Gerontological health care is undergoing a revolution, much like that of the feminist movement of the 1960s. Fundamental changes in health care require revisions in nursing education to ensure appropriate care of older adults in the least restrictive environment. The purpose of this study is to promote the preparation of future nurses who have the knowledge and the skills necessary to provide nursing care for the growing cohorts of older adults. A theoretical rationale for a new perspective in nursing education is discussed. An experiential clinical learning activity based on the functional model of gerontological health care is examined. This home visit clinical learning activity provides nursing students with the opportunity to practice nursing reflective of the health care needs of older adults. Strategies for replication of this clinical learning activity are provided.     

The use of discriminant function analysis to predict student success on the NCLEX-RN

Predicting whether a student will be successful on the National Council Licensure Examination for Registered Nurses (NCLEX-RN) has been an important endeavor for faculty in schools of nursing for the past 2 decades. Extensive documentation exists in the literature concerning research aimed at exploring the academic and nonacademic predictors of success on the NCLEX-RN. Reviews of the findings of these studies indicate that various factors emerge as academic predictors of success. The results of this study suggest that first-time success on the NCLEX-RN can be predicted with a high level of accuracy using existing student data. The findings also support the belief that it is possible to identify students who may be at risk for unsuccessful first time performance on the NCLEX-RN. Early identification of at-risk students will promote timely intervention strategies to optimize the students' potential for success.     

Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls

CONTEXT: An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. OBJECTIVE: To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD. DESIGN: Randomized double-blind crossover study. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years). INTERVENTIONS: We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale. RESULTS: Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls. CONCLUSION: The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.     

Contour integration in peripheral vision reduces gradually with eccentricity

Hess and Dakin reported that normally-sighted subjects using peripheral vision (beyond 10 degrees ) were unable to detect paths of alternating-phase Gabors embedded within randomly positioned Gabors, but could detect same-phase paths. This result led them to propose a "fundamental difference" between central and peripheral visual processing. While we were able to replicate many of their results, our normally-sighted observers could detect alternating-phase paths beyond 10 degrees. We found that path detection decreased monotonically as a function of eccentricity (0 degrees -30 degrees ) for both alternating-phase and same-phase stimuli. As with most visual functions the more difficult path detection condition (alternating-phase) declined slightly faster. The results for the normally-sighted observers could not be explained by poor fixation. Three people with substantial central vision loss (i.e. they can only use peripheral vision) could see both same- and alternating-phase stimuli with eccentric viewing of 13 degrees -17 degrees. Therefore central and peripheral vision appear to use similar visual mechanisms to perform the task, there being no fundamental difference.