Predictors of decline in verbal fluency after frontal lobe epilepsy surgery.

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome.

Dense arrays of micro-needles for recording and electrical stimulation of neural activity in acute brain slices.

OBJECTIVE: This paper describes the design, microfabrication, electrical characterization and biological evaluation of a high-density micro-needle array. The array records from and electrically stimulates individual neurons simultaneously in acute slices of brain tissue. APPROACH: Acute slices, arguably the closest in-vitro model of the brain, have a damaged surface layer. Since electrophysiological recording methods rely heavily on electrode-cell proximity, this layer significantly attenuates the signal amplitude making the use of traditional planar electrodes unsuitable. To penetrate into the tissue, bypassing the tissue surface, and to record and stimulate neural activity in the healthy interior volume of the slice, an array of 61 micro-needles was fabricated. MAIN RESULTS: This device is shown to record extracellular action potentials from individual neurons in acute cortical slices with a signal to noise ratio of up to ∼15:1. Electrical stimulation of individual neurons is achieved with stimulation thresholds of 1.1-2.9 µA. SIGNIFICANCE: The novelty of this system is the combination of close needle spacing (60 µm), needle heights of up to 250 µm and small (5-10 µm diameter) electrodes allowing the recording of single unit activity. The array is coupled to a custom-designed readout system forming a powerful electrophysiological tool that permits two-way electrode-cell communication with populations of neurons in acute brain slices.

Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease.

OBJECTIVE: To evaluate the efficacy and tolerability of lubiprostone (Amitiza) for constipation in Parkinson disease (PD) in a double-blind, randomized, controlled study. METHODS: Patients with PD and clinically meaningful constipation (constipation rating scale score > 10 [range: 0-28]) were recruited from 2 academic movement disorder centers to participate in the study. After enrollment, patients were initially followed for 2 weeks and then were randomly assigned 1:1 to lubiprostone, and the dose was titrated up to 48 µg/day. They returned 4 weeks later for a final assessment. Data included stool diaries and global impressions (co-primary endpoints), demographics, Unified Parkinson's Disease Rating Scale scores, constipation scale scores, visual analog scale (VAS) scores, a stool diary, and adverse events. RESULTS: Fifty-four subjects (39 male, mean age 67.0 ± 10.1 years, and mean duration of PD 8.3 ± 5.4 years) were randomly assigned to lubiprostone or placebo. One patient in the drug group discontinued the study because of logistics, and one patient in the placebo group discontinued the study because of lack of efficacy. A marked or very marked clinical global improvement was reported by 16 of 25 (64.0%) subjects receiving drug vs 5 of 27 (18.5%) subjects receiving placebo (p = 0.001). The constipation rating scale (p < 0.05), VAS (p = 0.001), and stools per day in the diary (p < 0.001) all improved with drug compared with placebo. Adverse events with drug were mild, most commonly intermittent loose stools. CONCLUSION: In this randomized controlled trial, lubiprostone seemed to be well tolerated and effective for the short-term treatment of constipation in PD.

Magnetic resonance angiography of the circle of Willis in patients with symptomatic intracranial neuropathology: medicare LCD L25367(R4).

Patients with symptomatic intracranial neuropathology such as atherosclerotic occlusive disease or unruptured aneurysms face high risks for morbidity and mortality. Magnetic resonance angiography of the circle of Willis is an important tool used to detect and diagnose intracranial neuropathology; however, recent changes to the Medicare local coverage determinations for this procedure threaten to compromise the physician's ability to deliver this current standard of care. Physicians can assume an important role in advocating for this lifesaving procedure on behalf of this vulnerable patient population.

Guidance of magnetic resonance imaging and placement of skin-marker localization devices.

AIM: A variety of magnetic resonance imaging (MRI)-compatible skin-marker localization devices are available on the market. MRI protocols call for the liberal use of the skin markers over the specific site of symptoms or over any palpable mass. This study investigates the usefulness of patient-assisted placement of 1 000-mg fish oil capsules as skin markers over the area of maximum localized pain, signs, or symptoms and correlates this placement with any potential underlying neuropathology or potential pain generator. METHODS: One-hundred symptomatic patients undergoing MRI were assessed for focal or localized signs or symptoms. Under the direction of a physician and with guidance from the patient, the MRI technician placed a 1 000-mg fish-oil capsule over the area of maximum pain or signs and symptoms. Patients with poorly localized, diffuse symptoms or an area of maximal signs and symptoms outside the field of view of the MRI were not included in this study. All MRI exams were reviewed by clinical physicians and radiologists or neuroimaging physicians. RESULTS: In all 100 cases, the images show clearly visible MRI-compatible skin-surface markers that correlate with potential underlying neuropathology. CONCLUSION: Our results show that 1 000-mg fish-oil capsules can be used as MRI localization devices as a cost-effective alternative to more expensive commercially available devices.

Urine drug testing in the treatment of chronic noncancer pain in a Kentucky private neuroscience practice: the potential effect of Medicare benefit changes in Kentucky.

BACKGROUND: Because the symptoms of drug misuse are nonspecific and difficult to detect, pain physicians have relied heavily on the results of urine drug tests to diagnose and treat chronic noncancer pain in patients who are prescribed controlled substances. However, changes in Medicare local carrier determinations for Medicare Part B providers in Connecticut, Indiana, Kentucky, and New York went into effect on July 1, 2009, whereby qualitative drug screening was no longer recognized as medically reasonable and necessary in the treatment of patients with chronic noncancer pain unless the patient presents with suspected drug overdose. STUDY DESIGN: A retrospective review of urine drug testing services. OBJECTIVE: To determine the extent of urine drug testing in patients with chronic noncancer pain in a large, Kentucky neuroscience practice offering pain management services combined with neurologic and neurosurgical services to better understand the potential effects of recent changes to Medicare benefits. METHODS: An audit of services provided during 2007 was conducted using computer software. OUTCOME MEASURES: Outcome measures included the number of practice services, number of urine drug tests by payor, and the number of noncompliant patients by payor who self-released from care. RESULTS: Urine drug tests represented approximately 18.2% of professional medical services rendered in 2007 to patients with a diagnosis of chronic noncancer pain. Of these, UDTs represented approximately 22.2% of services provided to Medicare patients and 24.6% of services provided to Medicaid patients. In 2007, 2,081 patients with noncompliant UDTs self released from the practice against medical advice. Of these, 23.1% were enrolled in Medicare and 47.5% were enrolled in Medicaid. Approximately 40% of patients were referred to the CARE Clinic on the basis of noncompliance as indicated by UDT and/or behavioral health issues. Of these, approximately 50% remained in treatment. Urine drug tests were also instrumental in revealing that 19.6% of patients showed signs of drug abuse or addiction. Of these patients, approximately 60% were government insured. LIMITATIONS: Not a prospective, double-blinded study. We approximated the proportion of patients potentially affected by drug abuse or addiction as the percentage of patients self releasing from medical care. CONCLUSION: In 2007, UDTs were used as an effective tool in adherence monitoring in a private neuroscience practice in Kentucky that offers pain management services combined with neurologic and neurosurgical services. UDTs were instrumental in referring 40% of patients for evaluation and treatment by behavioral health and addiction medicine specialists. UDTs were also instrumental in discovering signs of drug abuse or addiction in 19.6% of patients. Of these patients, approximately 60% were government insured. Should the objective and reliable sign offered by UDTs be eliminated from the physician's toolbox, the physician's ability to accurately diagnose and treat these patients could be impaired.

Importance of urine drug testing in the treatment of chronic noncancer pain: implications of recent medicare policy changes in kentucky.

BACKGROUND: Urine drug testing has become a widely used tool in American society for deterring illicit drug use. In the practice of medicine, urine drug testing is commonly used to help diagnose substance misuse, abuse, or addiction. OBJECTIVE: This narrative review provides an informed perspective on the importance of urine drug testing in the medical treatment of chronic noncancer pain. The history and current uses of urine drug tests in the United States are reviewed, the prevalence and nature of prescription drug misuse is described as is related to chronic noncancer pain, and implications and considerations for practitioners are presented related to the noncancer pain diagnosis and treatment. DISCUSSION: Practitioners are confronted with the ethical and legal dilemma of being called to adequately treat chronic pain in a culture with a high prevalence of prescription drug abuse. Yet the symptoms of drug abuse are nonspecific and therefore of limited value to the practitioner in determining patient compliance to drug treatment regimens. In contrast, urine drug testing has a reliable history, both in and out of medicine, as an independent sign of drug misuse. This sign can be used to aid in the diagnosis and treatment of drug misuse and underlying addictions to improve patient outcomes. CONCLUSION: Regular urine drug testing should be a part of acute and chronic pain management whether or not the patient has any signs or symptoms of drug misuse.

Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse.

Estrogen, acting via estrogen receptor (ER)alpha, regulates serum gonadotropin levels and pituitary gonadotropin subunit expression. However, the cellular pathways mediating this regulation are unknown. ERalpha signals through classical estrogen response element (ERE)-dependent genomic as well as nonclassical ERE-independent genomic and nongenomic pathways. Using targeted mutagenesis in mice to disrupt ERalpha DNA binding activity, we previously demonstrated that ERE-independent signaling is sufficient to suppress serum LH levels. In this study, we examined the relative roles of ERE-dependent and -independent estrogen signaling in estrogen regulation of LH, FSH, prolactin, and activin/inhibin subunit gene expression, pituitary LH and FSH protein content, and serum FSH levels. ERE-independent signaling was not sufficient for estrogen to induce pituitary prolactin mRNA or suppress pituitary LHbeta mRNA, LH content, or serum FSH in estrogen-treated ovariectomized mice. However, ERE-independent signaling was sufficient to reduce pituitary glycoprotein hormone alpha-subunit, FSHbeta, and activin-betaB mRNA expression. Together with previous serum LH results, these findings suggest ERE-independent ERalpha signaling suppresses serum LH via reduced secretion, not synthesis. Additionally, ERE-dependent and ERE-independent ERalpha pathways may distinctly regulate steps involved in the synthesis and secretion of FSH.

Botulinum toxin in the treatment of blepharospasm and hemifacial spasm.

Blepharospasm and hemifacial spasm are the two most common craniofacial movement disorders. Blepharospasm is a syndrome characterized by excessive or continuous eye closure related to overactivity of the orbicularis oculi and adjacent muscles bilaterally. Hemifacial spasm is a peripherally-induced movement disorder typically caused by vascular compression of cranial nerve VII (CN VII) leading to involuntary unilateral contractions of muscles used in facial expression. Treatment options for both conditions include medications, botulinum toxin, and various surgical interventions. This article summarizes the existing medical literature which indicates that botulinum toxin is the treatment of choice for blepharospasm and hemifacial spasm.

Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis.

Ovarian estrogen exerts both positive and negative feedback control over luteinizing hormone (LH) secretion during the ovulatory cycle. Estrogen receptor (ER) alpha but not ERbeta knockout mice lack estrogen feedback. Thus, estrogen feedback appears to be primarily mediated by ERalpha. However, it is now recognized that, in addition to binding to estrogen response elements (EREs) in DNA to alter target gene transcription, ERalpha signals through ERE-independent or nonclassical pathways, and the relative contributions of these pathways in conveying estrogen feedback remain unknown. Previously we created a knockin mouse model expressing a mutant form of ERalpha (AA) with ablated ERE-dependent but intact ERE-independent activity. Breeding this allele onto the ERalpha-null (-/-) background, we examine the ability of ERE-independent ERalpha signaling pathways to convey estrogen feedback regulation of the female hypothalamic-pituitary axis in vivo. ERalpha-/AA exhibited 69.9% lower serum LH levels compared with ERalpha-/- mice. Additionally, like wild type, ERalpha-/AA mice exhibited elevated LH after ovariectomy (OVX). Furthermore, the post-OVX rise in serum LH was significantly suppressed by estrogen treatment in OVX ERalpha-/AA mice. However, unlike wild type, both ERalpha-/AA and ERalpha-/- mice failed to exhibit estrous cyclicity, spontaneous ovulation, or an afternoon LH surge response to estrogen. These results indicate that ERE-independent ERalpha signaling is sufficient to convey a major portion of estrogen's negative feedback actions, whereas positive feedback and spontaneous ovulatory cyclicity require ERE-dependent ERalpha signaling.

Active-edge planar radiation sensors.

Many systems in medicine, biology, high-energy physics, and astrophysics require large area radiation sensors. In most of these applications, minimizing the amount of dead area or dead material is crucial. We have developed a new type of silicon radiation sensor in which the device is active to within a few microns of the mechanical edge. Their perimeter is made by a plasma etcher rather than a diamond saw. Their edges can be defined and also passivated by growing, in an intermediate step, a field oxide on the side surfaces. In this paper, the basic architecture and results from a synchrotron beam test are presented.

Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke.

One hundred seventy-six consecutive patients treated with IV tissue plasminogen activator (tPA) for acute ischemic stroke were examined prospectively, and orolingual angioedema was found in nine (5.1%; 95% CI 2.3 to 9.5). The reaction was typically mild, transient, and contralateral to the ischemic hemisphere. Risk of angioedema was associated with angiotensin-converting enzyme inhibitors (relative risk [RR] 13.6; 95% CI 3.0 to 62.7) and signs on initial CT of ischemia in the insular and frontal cortex (RR 9.1; 95% CI 1.4 to 30.0).

Effect of treatment with the selective oestrogen receptor modulator LY117018-HCl on pituitary sensitivity to GnRH and subsequent ovulation.

The effects of LY117018-HCl (LY; a benzothiophene similar to raloxifene) were examined on various reproductive parameters in female rats. Four-day cyclic rats were treated (10:00 h on dioestrus) with LY (0.01, 0.1, 0.5, 1, 2, 4 or 16 mg kg(-1) p.o.) and assessed for ovulation at oestrus. LY inhibited ovulation at doses as low as 0.5 mg kg(-1), and ovulation did not occur at doses of 4 and 16 mg kg(-1). LY (16 mg kg(-1)) reduced wet uterine mass and LH concentrations at the time of the expected ovulatory surge. Ovulation induced by hCG in pentobarbital-treated rats was not altered by LY treatment, indicating normal ovarian sensitivity to gonadotrophins. LY, however, completely blocked the effects of oestradiol (under either negative or positive feedback modes) on LH secretion in ovariectomized rats. GnRH secretion into hypophyseal portal blood during pro-oestrus was not affected by treatment with LY, whereas the concentrations of serum LH remained reduced. Finally, treatment with LY markedly reduced pituitary sensitivity to GnRH during pro-oestrus, as it completely blocked GnRH-induced LH secretion. These results demonstrate that LY inhibits oestradiol action in the uterus and prevents ovulation in normal cyclic rats. LY-induced inhibition of ovulation is not caused by an alteration of the ovarian response to gonadotrophins or an impairment of GnRH secretion at the hypothalamus, but by a reduction in the sensitivity of gonadotrophs to the stimulatory effects of GnRH during pro-oestrus.

Androgen responsiveness of the pituitary gonadotrope cell line LbetaT2.

Androgens have a profound effect on the hypothalamic-pituitary axis by reducing the synthesis and release of the pituitary gonadotropin LH. The effect on LH is partly a consequence of a direct, steroid-dependent action on pituitary function. Although androgen action has been well studied in vivo, in vitro cell models of androgen action on pituitary gonadotropes have been scarce. Recently, an LH-expressing cell line, LbetaT2, was generated by tumorigenesis targeted to the LH-producing cells of the mouse pituitary. The purpose of these studies was to determine the presence of androgen receptor (AR) and establish its function in this cell line. RT-PCR analysis indicated that the LbetaT2 cell line expresses AR mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV) promoter, showed that a functional AR is also present. Testosterone (TEST), dihydrotestosterone (DHT), 7alpha-methyl-19-nortestosterone (MENT), and fluoxymesterone (FLUOXY) increased reporter gene activity in the rank order of potencies MENT>DHT> TEST>FLUOXY. Additionally, activation of MMTV promoter activity by DHT in LbetaT2 cells was diminished by the AR antagonists casodex and 2-hydroxy-flutamide, indicating that the effects of DHT are mediated through AR. In summary, these studies showed that the LbetaT2 cell line is a useful model for the evaluation and molecular characterization of androgen action in pituitary gonadotropes.

An efficient color representation for image retrieval.

A compact color descriptor and an efficient indexing method for this descriptor are presented. The target application is similarity retrieval in large image databases using color. Colors in a given region are clustered into a small number of representative colors. The feature descriptor consists of the representative colors and their percentages in the region. A similarity measure similar to the quadratic color histogram distance measure is defined for this descriptor. The representative colors can be indexed in the three-dimensional (3-D) color space thus avoiding the high-dimensional indexing problems associated with the traditional color histogram. For similarity retrieval, each representative color in the query image or region is used independently to find regions containing that color. The matches from all of the query colors are then combined to obtain the final retrievals. An efficient indexing scheme for fast retrieval is presented. Experimental results show that this compact descriptor is effective and compares favorably with the traditional color histogram in terms of overall computational complexity.

Peer group image enhancement.

Peer group image processing identifies a "peer group" for each pixel and then replaces the pixel intensity with the average over the peer group. Two parameters provide direct control over which image features are selectively enhanced: area (number of pixels in the feature) and window diameter (window size needed to enclose the feature). A discussion is given of how these parameters determine which features in the image are smoothed or preserved. We show that the Fisher discriminant can be used to automatically adjust the peer group averaging (PGA) parameters at each point in the image. This local parameter selection allows smoothing over uniform regions while preserving features like corners and edges. This adaptive procedure extends to multilevel and color forms of PGA. Comparisons are made with a variety of standard filtering techniques and an analysis is given of computational complexity and convergence issues.

Phase II double-blind, dose-ranging clinical evaluation of gadobenate dimeglumine in focal liver lesions: with analysis of liver and kidney signal change on early and delayed imaging.

To evaluate the effect of contrast dose using gadobenate dimeglumine, 30 patients with focal liver lesions documented by computed tomography or ultrasound were studied by magnetic resonance imaging at 1.5 T. Patients received one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, or 0.2 mmol/kg) or saline. The order of dosage was randomized, with both the physician and patient blinded to the administered dose. Scans were obtained before, immediately following injection, and after 80 minutes of delay. Enhancement effects were quantified by region of interest measurements. Films were also reviewed in a randomized prospective fashion by an abdominal radiologist blinded to contrast dose and diagnosis. Higher doses led to a statistically significant improvement in enhancement of normal liver, both on immediate (P = 0.01 for the comparison of 0.1 and 0.2 mmol/kg immediately post-contrast) and delayed scans (P = 0.003 for the same comparison). Liver-lesion contrast-to-noise ratio also increased with dose, although results for most comparisons by dose were not statistically significant. Scans following gadobenate dimeglumine injection were judged to provide additional diagnostic confidence sufficient to affect patient management in 10 of 24 cases. In seven cases this information was provided by dynamic scans, in one case by delayed scans, and in two cases by both dynamic and delayed scans. In 2 of the 10 cases the dose was 0.025 mmol/kg, in 2 cases 0.05 mmol/kg, in 3 cases 0.1 mmol/kg, and in 3 cases 0.2 mmol/kg. Gadobenate dimeglumine is effective for imaging of focal liver lesions at a range of doses, with trends toward improved diagnostic information at higher doses.

What five clinical pastoral education residents discovered from a JCAHO review.

Discusses the process one pastoral care department and its five residents used to prepare for a JCAHO review and reports the experience, detailing questions asked and chaplains' responses when they sat in on twenty unit reviews.

Study to validate the outcome goal, competencies and educational objectives for use in intensive care orientation programs.

Intensive care orientation programs have become an accepted component of intensive care education. To date, however, there have been no Australian-based standards defining the appropriate level of competence to be attained upon completion of orientation. The aim of this study was to validate a set of aims, competencies and educational objectives that could form the basis of intensive care orientation and which would ensure an outcome standard of safe and effective practice. An initial document containing a statement of the desired outcome goal, six competency statements and 182 educational objectives was developed through a review of the orientation programs developed by the investigators. The Delphi technique was used to gain consensus among 13 nurses recognised for their expertise in intensive care education. The expert group rated the acceptability of each of the study items and provided suggestions for objectives to be included. An approval rating of 80 per cent was required to retain each of the study items, with the document refined through three Delphi rounds. The final document contains a validated statement of outcome goal, competencies and educational objectives for intensive care orientation programs.