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Biomedical subjects

Robert S Fisher

Publications and source records attributed to Robert S Fisher.

At least 19 recordsLinked to original sources
PubMed2007

Gender and age differences in expression of GABAA receptor subunits in rat somatosensory thalamus and cortex in an absence epilepsy model.

Absence epilepsy is more prevalent in females, but reasons for this gender asymmetry are unknown. We reported previously that perinatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 causes a life-long increase in EEG spike-wave discharges (SWDs), correlated with decreased expression of GABA(A) receptor subunit gamma2 protein levels in thalamic reticular and ventrobasal nuclei (SS thalamus) [Li, H., Kraus, A., Wu, J., Huguenard, J.R., Fisher, R.S., 2006. Selective changes in thalamic and cortical GABA(A) receptor subunits in a model of acquired absence epilepsy in the rat. Neuropharmacology 51, 121-128]. In this study, we explored time course and gender different effects of perinatal AY9944 treatment on expression of GABA(A) receptor alpha1 and gamma2 subunits in SS thalamus and SS cortex. Perinatal AY9944 treatment-induced decreases in GABA(A) gamma2 receptor subunits in rat SS thalamus and increases in SS cortex are gender and age specific. The findings suggest a mechanism for the higher prevalence of absence epilepsy in female patients.

Age Factors↗
PubMed2006

Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat.

Neonatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 has been shown to increase occurrence of spike-waves in EEG recordings and decrease benzodiazepines sensitivity of GABA(A) receptor-mediated responses in neurons from the thalamic reticular nuclei (nRt, Wu et al., 2004). The present experiments were designed to investigate the changes in the gamma2 and alpha1 subunits of the GABA(A) receptor in CSI model rats as possible mechanisms of these changes. Western blot, immunohistochemistry and real-time PCR techniques were performed to measure the levels of GABA(A) receptor gamma2 and alpha1 subunit transcripts and protein in the nRt and ventrobasal (VB) relay nuclei of thalamus and in somatosensory cortex. In CSI model animals, Western blot results showed that gamma2 subunit expression significantly decreased in thalamus (control, n=6: 0.17+/-0.02 relative to actin vs. CSI model, n=6: 0.11+/-0.01, P<0.05) but neither in cortex nor in hippocampal tissues. Conversely, alpha1 subunit expression decreased in CSI model somatosensory cortex, but not in nRt and VB. The present results demonstrate that neonatal block of cholesterol synthesis produces region- and subunit-specific decreases in GABA(A) receptor subunits in thalamus and cortex. Selective reductions in GABA(A) receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.

Animals↗
PubMed2006

Measuring the effects of antiepileptic medications on balance in older people.

BACKGROUND: Dizziness and ataxia are among the most common adverse events associated with antiepileptic medications. Despite this, few studies have attempted to quantitatively assess the effects of antiepileptic therapies on equilibrium. This study was undertaken to prospectively compare quantitative measures of balance in older people taking carbamazepine, gabapentin and lamotrigine. METHODS: Thirty patients on monotherapy for idiopathic partial or generalized epilepsy were enrolled after giving informed consent. Patients had to be at least 50 years old, able to give consent, and on a stable dose of carbamazepine, gabapentin or lamotrigine for at least 30 days. Since this was a study of asymptomatic patients, all patients had to be without complaint of dizziness or imbalance. Patients with a history of alcohol or drug abuse or any medical or neurological condition expected to adversely affect equilibrium were excluded. Each patient underwent a history and examination, computerized dynamic posturography, the activities-specific balance confidence (ABC) scale, Fregly ataxia battery, and the Berg balance scale. Serum drug levels of carbamazepine were obtained to eliminate patients with toxic levels upon enrollment. Two-tailed paired t-tests were used to determined statistical significance among those on each antiepileptic medication. RESULTS: Thirty patients were enrolled: 10 on gabapentin, 10 on lamotrigine and 10 on carbamazepine monotherapy for epilepsy. There were no differences in age or sex among those in each treatment group. The average dosages were 1,120 mg/day for those on gabapentin, 335 mg for lamotrigine, and 640 mg for carbamazepine. There were no differences in the activities-specific balance confidence (ABC) or the Berg balance scale scores. All patients had normal vestibular function by quantitative testing. Posturography showed no statistically significant differences. The Fregly ataxia battery includes the sum of timed trials in the sharpened Romberg (SR) position, standing on one leg with eyes closed (SOLEC), and when walking in tandem with eyes closed (WITEC). The patients on lamotrigine exhibited ability to maintain balance in these positions significantly longer than did those on carbamazepine: SR (P<0.05), SOLEC (P<0.05) and WITEC (P<0.05). CONCLUSIONS: The effects of antiepileptic medications on equilibrium in asymptomatic older people may require more dynamic and challenging measures of equilibrium than are commonly employed in physical therapy to monitor risk of falls. Although the sample size is small, this study suggests that lamotrigine may induce less disequilibrium than does carbamazepine in older people on monotherapy for epilepsy. Further study in this area is needed, particularly given the risks of falling from imbalance in the elderly.

Aged↗
PubMed2006

Downstream effects of esophageal distention.

This review focuses on primary peristalsis and the normal swallow and secondary peristalsis as it relates to esophageal distention. In addition, high-pressure zones in the esophageal sphincters and innervation in the esophageal body are discussed. Distention-induced protective reflexes for the pharynx and airway are described, as are extraesophageal effects of esophageal distention. Experimental and clinical research in these areas is summarized, along with its possible clinical applications.

Deglutition↗
PubMed2006

New routes for delivery of anti-epileptic medications.

Use of novel drug delivery methods might enhance efficacy and reduce toxicity, in comparison with currently existing oral anti-epileptic drugs (AEDs). Novel methods aim to deliver optimal drug concentration more specifically to the seizure focus or foci. In this review, we first consider unconventional routes of drug delivery to the peripheral system, then potential new methods of targeted CNS drug delivery. Intrathecal or intraventricular AEDs might circumvent systemic toxicity. Drug-eluting wafers could be surgically positioned over an epileptogenic region of brain. Drug can be delivered to a seizure focus by an implanted catheter and subcutaneous pump. Inactive prodrugs, given systemically, can be made active only at the seizure focus, by interaction with locally-released substances. Liposomes and polysomes are engineered slow-release storage vehicles for drugs. Targeting components can hold liposomes near a region of interest, provided that they can penetrate the blood brain barrier. Lastly, we discuss future prospects for the use of transplanted cells and genes as potential vehicles for local delivery of renewable anti-epileptic regimen.

Anticonvulsants↗
PubMed2005

Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis. METHODS: The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate. RESULTS: Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic-clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic-clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test-induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures. RECOMMENDATIONS: Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic-clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

Diagnosis, Differential↗
PubMed2005

Measurement of gastrointestinal transit.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

Breath Tests↗
PubMed2005

Increased Barrett's esophagus for the decade between 1991 and 2000 at a single university medical center.

Barrett's esophagus is being diagnosed increasingly in the United States. The aim of this study was to determine whether the increased diagnosis of Barrett's esophagus is due to endoscopic reporting and/or a truly increasing rate. This retrospective study reviewed 18,183 endoscopy reports at Temple University Hospital from January 1991 through December 2000. Annual rates of new cases of endoscopically suspected Barrett's esophagus were determined. Biopsy results were reviewed for the diagnosis of Barrett's esophagus (i.e., specialized intestinal metaplasia). Rates of Barrett's esophagus increased from 3.22 to 8.28 per 100 endoscopies (257%; P < 0.01) on endoscopy and from 0.67 to 2.76 per 100 endoscopies (412%; P < 0.01) on histology from 1991 to 2000. Twenty-four and seven-tenths percent (252/1020) of patients suspected at endoscopy to have Barrett's esophagus were confirmed by histology. This study demonstrates an increasing rate of new cases of suspected Barrett's esophagus on endoscopy and confirmed Barrett's esophagus on histology over the last decade. The endoscopic impression of Barrett's esophagus was about four times higher than the confirmed diagnosis of Barrett's esophagus (intestinal metaplasia) on histology.

Academic Medical Centers↗
PubMed2005

Regional postprandial differences in pH within the stomach and gastroesophageal junction.

Our objective was to determine regional differences in intragastric pH after different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat dinner, and a typical bland breakfast. The fatty dinner had the highest postprandial buffering effect, elevating proximal and mid/distal gastric pH to 4.9 +/- 0.4 and 4.0 +/- 0.4, respectively, significantly (P < 0.05) higher compared to 4.2 +/- 0.3 and 3.0 +/- 0.4 for the spicy lunch and 3.0 +/- 0.3 and 2.5 +/- 0.8 for the breakfast. The buffering effect of the high-volume fatty meal to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min) and the bland breakfast, which did not increase gastric pH to > 4 at any time. Proximal gastric acid pockets were seen between 15 and 90 min postprandially. These were located 3.4 +/- 0.8 cm below the proximal LES border, extending for a length of 2.3 +/- 0.8 cm, with a drop in mean pH from 4.7 +/- 0.4 to 1.5 +/- 0.9. Acid pockets were seen equally after the spicy lunch and fatty dinner but less frequently after the bland breakfast. We conclude that a high-volume fatty meal has the highest buffering effect on gastric pH compared to a spicy lunch or a bland breakfast. Buffering effects of meals are significantly higher in the proximal than in the mid/distal stomach. Despite the intragastric buffering effect of meals, focal areas of acidity were observed in the region of the cardia-gastroesophageal junction during the postprandial period.

Adult↗
PubMed2005

Experimental Electrical Stimulation Therapy for Epilepsy.

Electrical stimulation of the nervous system is an attractive possible therapy for intractable epilepsy, but only stimulation of the vagus nerve has been subjected to large, controlled, and completed clinical trials. Controlled trials are in progress for intermittent cycling stimulation of the anterior nuclei of the thalamus, and for cortical stimulation at a seizure focus, responsive to detection of seizure onset. Anecdotal experience has been gathered with stimulation of cerebellum, centromedian thalamus, subthalamus, caudate, hippocampus, and brainstem. All stimulation of the central nervous system for epilepsy must be considered experimental.

Journal Article↗
PubMed2005

A blinded pilot study of artwork in a comprehensive epilepsy center population.

The production of artwork is a complex neurological task. A controlled study of artwork produced by people with epilepsy has not previously been performed. The present report details the results of a three-part study involving 60 subjects from a comprehensive epilepsy center population. Subjects were grouped by the following diagnoses: seizures, partial seizures, complex partial seizures with temporal focus, and nonepileptic events. Data were collected in a blinded fashion. The Formal Elements Art Therapy Scale task showed significant effects in patients with epileptic seizures. The Free Drawing was most sensitive to complex partial seizures with temporal focus, while the Outline was most predictive of nonepileptic events. In addition to giving some insight into the neurological functioning of these subjects, this pilot study provides a basis for the future development of diagnostic tests to be used within this patient group.

Adolescent↗
PubMed2005

Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis.

BACKGROUND: Botulinum toxin A injected into the pyloric sphincter has been reported in small case series to treat gastroparesis. This study reviews the use of this treatment in a large number of patients with gastroparesis. METHODS: Patients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patient's major symptom and/or two minor symptoms for 4 weeks. RESULTS: Of 115 patients treated, 63 patients met the study criteria. There were 53 women, 10 men, mean age 42 years. Most patients (56%) had idiopathic gastroparesis. Twenty-seven of 63 (43%) patients experienced a symptomatic response to treatment. By stepwise logistic regression, male gender was associated with response to treatment (OR 3.27: 95% CI[1.31, 8.13], p = 0.01). Vomiting as a major symptom was associated with a lack of response (OR 0.16: 95% CI[0.04, 0.67], p = 0.01). Despite the association of male gender with response, the mean duration of response for those patients responding, with a minimum of 3 months' follow-up was 4.9 months (+/-2.7 months) for women and 3.5 months (+/-0.71 months) for men (p = 0.59). The corresponding medians and interquartile ranges (IQR) were 5 (IQR 3-6) for females and 3.5 (IQR 3-4) for males. CONCLUSIONS: Of the patients, 43% had a response to botulinum toxin treatment that lasted a mean of approximately 5 months. Male gender was associated with a response to this therapy; however, durability of response was unrelated to gender. Vomiting as a major symptom predicted no response.

Abdominal Pain↗
PubMed2005

Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Brain↗
PubMed2005

Photic- and pattern-induced seizures: expert consensus of the Epilepsy Foundation of America Working Group.

PURPOSE: In August, 2004, the Epilepsy Foundation of America convened a workshop to begin to develop an expert consensus on photosensitive seizures. METHODS: Literature and data were reviewed, and consensus was derived from discussion. RESULTS: A flash is a potential hazard if it has luminance >or=20 cd/m2, occurs at a frequency of >or=3 Hz, and occupies a solid visual angle of >or=0.006 steradians (approximately 10% of the central visual field or 25% of screen area at typical viewing distances). A transition to or from saturated red also is considered a risk. A pattern with the potential for provoking seizures contains clearly discernible stripes, numbering more than five light-dark pairs of stripes in any orientation. When the light-dark stripes of any pattern collectively subtend at the eye from the minimal-expected viewing distance a solid angle of >0.006 steradians, the luminance of the lightest stripe is >50 cd/m2, and the pattern is presented for >or=0.5 s, then the pattern should display no more than five light-dark pairs of stripes, if the stripes change direction, oscillate, flash, or reverse in contrast; if the pattern is unchanging or smoothly drifting in one direction, no more than eight stripes. These principles are easier to apply in the case of fixed media, for example, a prerecorded TV show, which can be analyzed frame-by-frame, as compared with interactive media. CONCLUSIONS: A consensus view of stimuli likely to provoke visually evoked seizures can be developed.

Computer Terminals↗
PubMed2005

Photic- and pattern-induced seizures: a review for the Epilepsy Foundation of America Working Group.

PURPOSE: This report summarizes background material presented to a consensus conference on visually provoked seizures, convened by the Epilepsy Foundation of America. METHODS: A comprehensive review of literature was performed. RESULTS: Photosensitivity, an abnormal EEG response to light or pattern stimulation, occurs in approximately 0.3-3% of the population. The estimated prevalence of seizures from light stimuli is approximately 1 per 10,000, or 1 per 4,000 individuals age 5-24 years. People with epilepsy have a 2-14% chance of having seizures precipitated by light or pattern. In the Pokemon cartoon incident in Japan, 685 children visited a hospital in reaction to red-blue flashes on broadcast television (TV). Only 24% who had a seizure during the cartoon had previously experienced a seizure. Photic or pattern stimulation can provoke seizures in predisposed individuals, but such stimulation is not known to increase the chance of subsequent epilepsy. Intensities of 0.2-1.5 million candlepower are in the range to trigger seizures. Frequencies of 15-25 Hz are most provocative, but the range is 1-65 Hz. Light-dark borders can induce pattern-sensitive seizures, and red color also is a factor. Seizures can be provoked by certain TV shows, movie screen images, video games, natural stimuli (e.g, sun on water), public displays, and many other sources. CONCLUSIONS: Recommendations on reducing risk of seizures have been developed by agencies in the United Kingdom, Japan, and the International Telecommunications Union, affiliated with the United Nations. The Epilepsy Foundation of America has developed a consensus of medical experts and scientists on this subject, reported in an accompanying work.

Cartoons as Topic↗
PubMed2004

Abnormal benzodiazepine and zinc modulation of GABAA receptors in an acquired absence epilepsy model.

Brain cholesterol synthesis inhibition (CSI) at a young age in rats has been shown to be a faithful model of acquired absence epilepsy, a devastating condition for which few therapies or models exist. We employed the CSI model to study cellular mechanisms of acquired absence epilepsy in Long-Evans Hooded rats. Patch-clamp, whole-cell recordings were compared from neurons acutely dissociated from the nucleus reticularis of thalamus (nRt) treated and untreated with a cholesterol synthesis inhibitor, U18666A. In U18666A-treated animals, 91% of rats developed EEG spike-waves (SWs). Patchclamp results revealed that although there was no remarkable change in GABAA receptor affinity, both a loss of ability of benzodiazepines to enhance GABAA-receptor responses and an increase of Zn2+ inhibition of GABAA-receptor responses of nRt neurons occurred in Long-Evans Hooded rats previously administered U18666A. This change was specific, since no significant changes were found in neurons exposed to the GABA allosteric modulator, pentobarbital. Taken collectively, these findings provide evidence for abnormalities in benzodiazepine and Zn2+ modulation of GABAA receptors in the CSI model, and suggest that decreased gamma2 subunit expression may underlie important aspects of generation of thalamocortical SWs in atypical absence seizures. The present results are also consistent with recent findings that mutation of the gamma2 subunit of the GABAA receptor changes benzodiazepine modulation in families with generalized epilepsy syndromes.

Androstenes↗