bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Memory Decline Following Epilepsy Surgery: A Multivariate Approach
Authors: Baxendale Sallie , Thompson Pamela , Harkness William , Duncan John 
Published: October 2006

Summary:  Background: While some patients experience a decline in memory function following an anterior temporal lobe resection, there is considerable individual variation in the extent, nature, and direction of postoperative memory change. Patients with surgically remediable temporal lobe epilepsy differ in etiology, the extent and type of underlying pathology, and on demographic and epilepsy‐related variables, all of which may have an impact on their pre‐ and postoperative neuropsychological functioning. This study examined the relationship between these variables and postoperative memory decline. Methods: Logistic regression was used to examine the effects of age, laterality of surgery, age of onset of epilepsy, underlying pathology and preoperative level of memory function on postoperative verbal learning in 288 patients who had undergone an anterior temporal lobe resection. One hundred twenty‐five patients underwent a right temporal lobe resection (RTL), 163 patients underwent a left temporal lobe resection (LTL). Results: In the group as a whole, 25% of the patients demonstrated a significant postoperative deterioration in verbal learning. Postoperative deterioration in verbal learning was significantly associated with higher levels of preoperative function in both the RTL and LTL groups. Older age at the time of the operation and a lower verbal IQ were additional significant predictors for the RTL group. The presence of cortical dysgenesis was a significant predictor of postoperative decline in the LTL group. The logistic regression models accurately identified 3/4 of those who experienced a postoperative decline in memory, using a cutoff of 0.25 or above to identify high risk. Conclusions: Our analyses suggest that the majority of patients with a high risk of significant postoperative memory decline can be reliably identified preoperatively. These models are valuable tools helping patients make an informed decision regarding surgery.
Memory, Emotional and Vocational Impairments before and after Anterior Temporal Lobectomy for Complex Partial Seizures
Authors: Dulay Mario F. , York Michele K. , Soety Elizabeth M. , Hamilton Winifred J. , Mizrahi Eli M. , Goldsmith Ian L. , Verma Amit , Grossman Robert G. , Yoshor Daniel , Armstrong Dawna D. , Levin Harvey S. 
Published: October 2006

Summary:  Purpose: To assess the pre‐ and postsurgical frequency of memory, emotional, and vocational impairments in patients who underwent anterior temporal lobectomy (ATL), and to assess the relationship between emotional disturbance and memory abilities after ATL. Methods: Retrospective analysis of data was performed on 90 patients with medically intractable complex partial seizures who underwent ATL between 1981 and 2003. Patients were evaluated an average of 5 months before surgery and 11.3 months after surgery. Results: A moderate to high frequency of memory impairment (44.4%; verbal or nonverbal), emotional disturbance (38.9%) and unemployment (27.8%) existed in the same individuals both before and after surgery. There were small to moderate rates of new onset memory (18.9%), emotional (11.1%), and vocational (7.8%) difficulties after surgery often regardless of seizure control outcome. Patients who underwent left‐ATL and had emotional disturbance after surgery had the lowest verbal memory test scores. Conclusions: Results highlight the importance of taking into account emotional status when assessing memory abilities after ATL. Results replicate the finding of moderate to high frequencies of memory impairment, emotional disturbance, and unemployment both before and after ATL. Results provide support for the rationale that cognitive, psychiatric and vocational interventions are indicated to mitigate the problems that exist before and persist after ATL.
Pharmacokinetics of the New Antiepileptic and CNS Drug RWJ‐333369 Following Single and Multiple Dosing to Humans
Authors: Yao Caiping , Doose Dennis R. , Novak Gerald , Bialer Meir 
Published: October 2006

Summary:  Purpose: To characterize the pharmacokinetics of the new antiepileptic and CNS drug RWJ‐333369 following single and multiple oral doses to healthy subjects, including the effect of food on bioavailability. Method: Two studies were conducted. The first study had a randomized, double‐blind, placebo‐controlled, sequential, ascending‐dose crossover design. Subjects were divided into four dose groups (100, 250, 500, and 750 mg) of 10 to 11 subjects each. RWJ‐333369 or placebo was administered for two 7‐day periods, separated by a 14‐day washout. In the second study RWJ‐333369 (750 mg) was administered to 12 healthy subjects under fasted and fed conditions. Plasma and urine samples were analyzed for RWJ‐333369 by liquid chromatography‐mass spectroscopy. Safety was assessed throughout the studies. Results: Mean (range) pharmacokinetic parameters in the above studies were: oral clearance (CL/F) 3.4–4.2 L/h, half‐life (t1/2) 10.6–12.8 h, and renal clearance (CLr) 0.042–0.094 L/h, indicating that RWJ‐333369 is eliminated primarily by metabolism. These parameters were not significantly different (p > 0.05) for the four dose groups and for single and multiple dosing. Cmax and AUC increased proportionally with dose and decreased with food by 11% and 5%, respectively. Conclusions: Following single and repetitive (q12h) doses of 100–750 mg, RWJ‐333369 had linear pharmacokinetics; food did not alter pharmacokinetics to a clinically relevant extent. RWJ‐333369 is extensively metabolized and has a low CL/F that equals < 5% of the liver blood flow. Thus, orally administered RWJ‐333369 has no hepatic first‐pass effect. The 12‐h half‐life will enable bid dosing with an immediate‐release oral formulation.
Effects of the Novel Antiepileptic Drug Lacosamide on the Development of Amygdala Kindling in Rats
Authors: Brandt Claudia , Heile Anna , Potschka Heidrun , Stoehr Thomas , Löscher Wolfgang 
Published: October 2006

Summary: Purpose:The current treatment of epilepsy focuses exclusively on the prophylaxis or suppression of seizures and thus provides merely a symptomatic treatment, without clear influence on the course of the disease. There is a need for new drugs that act at different molecular targets than currently available antiepileptic drugs (AEDs) and for new therapies designed to block the process of epileptogenesis. In recent years, different research lines have examined the epileptogenic process in order to understand the different stages in this process, and with the hope that early recognition and intervention could prevent the development or progression of epilepsy. In animals, acquired epilepsy is studied most commonly with the kindling model and status epilepticus models. In the present study, we used the kindling model to evaluate whether the novel AED lacosamide affects kindling‐induced epileptogenesis. This drug does not seem to act by any of the mechanisms of currently available AEDs, but the exact molecular mechanisms of action of lacosamide have not yet been clarified.Methods:Groups of 9–10 rats were treated with either vehicle or different doses of lacosamide (3, 10, or 30 mg/kg/day) over 22–23 days during amygdala kindling.Results:Daily administration of lacosamide during kindling acquisition produced a dose‐dependent effect on kindling development. While the drug was inactive at 3 mg/kg/day, significant retardation of kindling was observed at 10 mg/kg/day, by which the average number of stimulations to reach kindling criterion was increased by >90%. A significant inhibitory effect on kindling acquisition was also observed with 30 mg/kg/day, but this dose of lacosamide was associated with adverse effects.Conclusions:The present data demonstrate that lacosamide, in addition to exerting anticonvulsant activity, has the potential to retard kindling‐induced epileptogenesis. Whether this indicates that lacosamide possesses antiepileptogenic or disease‐modifying potential needs to be further evaluated, including studies in other models of acquired epilepsy.
In Situ Metabolism of Levetiracetam in Blood of Patients with Epilepsy
Authors: Patsalos Philip N. , Ghattaura Sandirup , Ratnaraj Neville , Sander Josemir W. 
Published: October 2006

Summary: Purpose:Although levetiracetam undergoes minimum metabolism, B‐esterases have been identified in whole blood that are capable of metabolising levetiracetam. The present study was designed to ascertain any variability in levetiracetam blood concentrations that could be attributed to in situ metabolism and which could impact on the utility of such concentration measurements in guiding therapeutic management.Methods:Blood samples were collected from 40 patients that were prescribed levetiracetam. Sera (Groups 1 and 2) or whole blood (Groups 3 and 4) were compared. Paraoxan, an inhibitor of B‐esterase activity, was added to samples assigned to Groups 2 and 4. Samples within each group were assigned to Time 0 (frozen within 30 min of sample collection), Time 2 days and Time 7 days (samples kept at ambient temperature for 2 and 7 days).Results:For serum samples, mean levetiracetam concentrations at Time 2 days and Time 7 days were indistinguishable from Time 0, regardless of whether B‐esterase activity was inhibited on not. In contrast, for whole blood, in the absence of B‐esterase inhibition, mean levetiracetam concentrations declined over time (11% and 29%; 2 and 7 days) compared to baseline values. In the presence of B‐esterase inhibitor, mean levetiracetam concentrations at 2 days were indistinguishable from baseline values, although at 7 days values declined by 4%.Conclusions:If therapeutic monitoring of levetiracetam is to be undertaken, serum should be the matrix of choice and that whole blood should be separated as soon as possible after patient sampling so as to minimize in situ levetiracetam metabolism which could result in spuriously low concentrations and substantial intrapatient variability.
Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells
Authors: Chen Cui Ping , Boyadjieva Nadka I. , Advis Juan P. , Sarkar Dipak K. 
Published: October 2006

Background: Immune signals activate a network of cytokines in the central nervous system (CNS) that in turn causes release of neurotransmitters and hormones to modulate immune cell functions. We have recently shown that hypothalamic β‐endorphin neurons, via inhibition of the sympathetic neuronal activity, activate natural killer (NK) cell function in the spleen, and this communication is disrupted following chronic ethanol administration. β‐Endorphin neuronal function is known to be regulated by various proinflammatory and anti‐inflammatory cytokines. The effects of ethanol on the proinflammatory and anti‐inflammatory cytokines known to control β‐endorphin neuronal and NK cell functions during immune challenges have not been determined.Methods: In the present study, we evaluated the effects of chronic ethanol consumption on the basal and lipopolysaccharide (LPS)‐activated NK cells' functions in the spleen, the β‐endorphin peptide precursor proopiomelanocortin (POMC) gene expression in the arcuate nucleus (ARC) of the hypothalamus, and mRNA levels of proinflammatory cytokines interleukin‐1β (IL‐1β), tumor necrosis factor α (TNF‐α), and anti‐inflammatory cytokines IL‐6 and IL‐10 in the spleen and in the ARC. Male rats were ad libitum fed rat chow (ad lib‐fed), pair‐fed an isocaloric liquid diet, or fed an ethanol‐containing liquid diet, and each was treated with LPS (100 μg/kg body weight). After 2 hours, splenocytes and ARC tissues were isolated and used for this study. Splenocytes were used to determine mRNA levels of IL‐1β, TNF‐α, IL‐6, IL‐10, granzyme B, and perforin using the real‐time RT‐PCR assays. Splenocytes were also used to determine the cytolytic activity using a standard 4‐hour 51Cr release assay against YAC‐1 lymphoma target cells. Arcuate nuclei were used to determine IL‐1β, TNF‐α, IL‐6, IL‐10, and POMC mRNA levels using real‐time RT‐PCR assays.Results: The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS‐stimulated NK cell cytolytic functions and the levels of cytotoxicity‐regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS‐stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS‐induced levels of IL‐1β and TNF‐α mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS‐stimulated expression of IL‐6 and IL‐10 mRNAs in the spleen and of IL‐6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.
The Bolger Conference on PDE-5 Inhibition and HIV Risk: Implications for Health Policy and Prevention
Authors: Rosen Raymond C. , Catania Joseph A. , Ehrhardt Anke A. , Burnett Arthur L. , Lue Tom F. , McKenna Kevin , Heiman Julia R. , Schwarcz Sandy , Ostrow David G. , Hirshfield Sabina , Purcell David W. , Fisher William A. , Stall Ron , Halkitis Perry N. , Latini David M. , Elford Jonathan , Laumann Edward O. , Sonenstein Freya L. , Greenblatt David J. , Kloner Robert A. , Lee Jay , Malebranche David , Janssen Erick , Diaz Rafael , Klausner Jeffrey D. , Caplan Arthur L. , Jackson Graham , Shabsigh Ridwan , Khalsa Jag H. , Stoff David M. 
Published: October 2006

ABSTRACT

Introduction
Recent reports have linked the use of phosphodiesterase type 5 (PDE-5) inhibitors with increased rates of high-risk sexual behavior and HIV transmission in some individuals.

Aim
A National Institute of Mental Health (NIMH)-funded, multidisciplinary conference was convened to evaluate scientific research, clinical and ethical considerations, and public policy implications of this topic.

Main Outcome Measures
Published and unpublished findings on effects of PDE-5 inhibitors on sexual behavior; published guidelines and management recommendations.

Methods
Leading investigators in relevant disciplines (e.g., public health, epidemiology, medical ethics, urology, psychology) participated in a 2-day meeting, including representatives of government, scientific, and regulatory agencies (the Centers for Disease Control, Food and Drug Administration, NIMH, and the National Institute on Drug Abuse). Panelists provided critical reviews of substantive areas of research, followed by question and answer sessions on each topic. On the second day, working groups were convened to identify critical gaps and priorities in three major areas: (i) research and evaluation needs; (ii) prevention strategies and clinical management issues; and (iii) policy and prevention implications.

Results
Research needs and priorities were categorized into four specific areas: (i) basic and clinical/laboratory research; (ii) epidemiology and risk factors; (iii) social-behavioral processes and interventions; and (iv) prevention/policy and educational needs. Identified gaps in the available data include populations at risk (e.g., risk among heterosexuals, risk profiles among subpopulations of men who have sex with men) and the specific role of PDE-5 inhibitors in HIV seroconversion. Specific areas of emphasis were the need for safer sex counseling, comprehensive sexually transmitted infection (STI) screening and follow-up when indicated, avoidance of potentially dangerous drug interactions, and potential benefits of testosterone replacement for HIV-positive men with decreased androgen and other symptoms of hypogonadism.

Conclusions
A conference was convened on the topic of PDE-5 inhibition and HIV risk. This “white paper” summarizes the findings of the conference and recommendations for future research.
Feasibility of the Use of Phosphodiesterase Type 5 Inhibitors in a Pharmacologic Prevention Program for Recurrent Priapism
Authors: Burnett Arthur L. , Bivalacqua Trinity J. , Champion Hunter C. , Musicki Biljana 
Published: October 2006

ABSTRACT

Introduction
Recurrent ischemic priapism is an enigmatic erectile disorder in need of improved clinical interventions to avert its known, potentially serious complications.

Aim
To evaluate the use of a long-term, continuous phosphodiesterase type 5 (PDE5) inhibitor therapeutic regimen in controlling recurrent ischemic priapism and its feasibility in a clinical management program for the disorder.

Main Outcome Measures
The main outcome measure was reduction in frequency or duration of priapism episodes. A secondary outcome measure was preservation of erectile ability.

Methods
We retrospectively evaluated the clinical progress of seven patients (age 22–37 years) with sickle cell disease-associated “stuttering” priapism (N = 4) and idiopathic recurrent priapism (N = 3), who were counseled and consented to the “off-label” use of the PDE5 inhibitors sildenafil citrate and tadalafil. The medications were administered according to a specified therapeutic regimen based on scientific evidence that chronic PDE5 inhibitor administration in priapism contexts effectively reconditions PDE5 regulatory function in the penis. The duration of clinical follow-up extended through 2 years.

Results
All seven patients were confirmed to have recurrent ischemic priapism without identifiable pharmacologic, traumatic, or neoplastic disease associations based on clinical history, physical examination, laboratory testing, and penile diagnostics. PDE5 inhibitor treatment was successful in alleviating or resolving priapism recurrences in six of the seven patients. Erectile function was unchanged in six patients and improved in one patient at last follow-up compared with baseline status. All the patients reported that PDE5 inhibitor therapy was well tolerated and did not cause any adverse effects limiting their continued use of the medication.

Conclusions
Because of their efficacy, safety, and tolerability as shown in this case series, PDE5 inhibitors would appear to have a possible role in a rigorously implemented clinical management program to control recurrent priapism. However, completion of a controlled clinical trial is necessary to confirm the utility of this treatment.
Wide Variability in Laboratory Reference Values for Serum Testosterone
Authors: Lazarou Stephen , Reyes-Vallejo Luis , Morgentaler Abraham 
Published: October 2006

ABSTRACT

Introduction
The laboratory determination of testosterone levels consistent with a diagnosis of hypogonadism is complicated by the availability of multiple testosterone assays and varying reference ranges.

Aim
To assess current laboratory practices regarding availability of testosterone assays and use of reference values.

Methods
A telephone survey of 12 academic, 12 community medical laboratories, and one national laboratory.

Main Outcome Measures
Types of androgen assays offered and determination of reference values.

Results
All of the academic and eight of the community centers performed total testosterone testing. Free testosterone was performed in-house by six of the 12 academic and one community center. Testing for bioavailable testosterone, free androgen index, and percent free testosterone was performed in-house by no more than two centers. There were eight and four different assays used for total and free testosterone, respectively. One national laboratory offered equilibrium dialysis measurement of free testosterone. Of the 25 labs, there were 17 and 13 different sets of reference values for total and free testosterone, respectively. The low reference value for total testosterone ranged from 130 to 450 ng/dL (350% difference), and the upper value ranged from 486 to 1,593 ng/dL (325% difference). Age-adjusted reference values were applied in four centers for total testosterone and in seven labs for free testosterone. All reference values were based on a standard statistical model without regard for clinical aspects of hypogonadism. Twenty-three of the 25 lab directors responded that clinically relevant testosterone reference ranges would be preferable to current standards.

Conclusions
Laboratory reference values for testosterone vary widely, and are established without clinical considerations.
Nurse practitioner’s characteristics and job satisfaction
Authors: Wild Priscilla , Parsons Virgil , Dietz Elizabeth 
Published: October 2006

AbstractPurpose: To identify the demographics and job satisfaction levels of currently working nurse practitioners (NPs) in California.Data sources: The Mueller McCloskey Satisfaction Scale (MMSS) was mailed to a random sample of 200 California NPs with active licensure. Descriptive analysis was employed.Conclusions: The NPs reported high levels of job satisfaction according to the MMSS. Aspects of the job that showed significant levels of satisfaction were schedules, flexibility of hours, and interprofessional relationships. NPs were least satisfied with not having professional opportunities such as participation in nursing research, writing/publishing, and belonging to a department/nursing committee.Implications for practice: The findings may be used to guide NP recruitment and retention strategies, influence practice issues, and facilitate job satisfaction for NPs by employing agencies.
Association of spinal cord compression seen on magnetic resonance imaging with clinical outcome in 67 dogs with thoracolumbar intervertebral disc extrusion
Authors: Penning V. , Platt S. R. , Dennis R. , Cappello R. , Adams V 
Published: October 2006

Objectives:To determine whether there is an association between the degree of transverse spinal cord compression detected by magnetic resonance imaging following thoracolumbar Hansen type 1 intervertebral disc disease in dogs and their presenting and postsurgical neurological status.Methods:Medical records of 67 dogs with surgically confirmed Hansen type 1 intervertebral disc disease (2000 to 2004) were reviewed to obtain the rate of onset of disease, duration of clinical signs and presurgical and postsurgical neurological grade. Percentage of spinal cord compression was determined on transverse T2‐weighted magnetic resonance images. Linear regression was used to examine the association between spinal cord compression and each of the above variables. Chi‐squared tests were used to examine associations among postsurgical outcome and presurgical variables.Results:Eighty‐five per cent (57 of 67) of dogs were chondrodystrophoid. Mean spinal cord compression was 53 per cent (sd=219·7, range 14·3 to 84·9 per cent). There was no association between the degree of spinal cord compression and the neurological grade at presentation, rate of onset of disease, duration of clinical signs or postsurgical outcome, with no difference between chondrodystrophoid and non‐chondrodystrophoid dogs.ClinicalSignificance:The degree of spinal cord compression documented with magnetic resonance imaging in dogs with thoracolumbar Hansen type 1 intervertebral disc disease was not associated with the severity of neurological signs and was not a prognostic indicator in this study.