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Biomedical subjects

J French

Publications and source records attributed to J French.

At least 37 records · Page 2Linked to original sources
PubMed2001

Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation.

PURPOSE: the choices available for patients whose partial seizures are poorly controlled include seven new antiepileptic drugs (AEDs) or vagal nerve stimulation (VNS) as add-on therapy. Comparisons are needed to help physicians and patients select among the options for treatment. METHODS: we compared efficacy and adverse events of new treatments from controlled clinical trials of patients with uncontrolled partial seizures. Response rates (> or =50% decrease in partial seizures) at doses recommended in product labeling for adjunct therapy were tabulated for overall success (placebo response rate subtracted from AED response rate). Adverse events listed in product labeling were tabulated as complaint rates (placebo events subtracted from AED events). VNS trials used low dose stimulation as a pseudo-placebo. RESULTS: overall success rates fell into two general groups with ranges of 12-20% for gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), zonisamide and 27-29% for levetiracetam, oxcarbazepine, and topiramate (TPM). Summary Complaint Scores also fell into two general groups with ranges of -27 to -82 for GBP, levetiracetam, TGB, zonisamide and -113 to -205 for LTG, oxcarbazepine and TPM. VNS scores were in the lower or higher success and summary complaint categories depending on whether scores from the pseudo-placebo group were subtracted from the high dose group. CONCLUSIONS: these data allow comparisons among AEDs and VNS using similar data from standard types of clinical trials.

Anticonvulsants↗
PubMed2001

A systematic review of the safety profile of levetiracetam: a new antiepileptic drug.

PURPOSE: This report provides detailed review of safety information on levetiracetam (LEV) (Keppra), a new antiepileptic drug. METHODS: The integrated summary of safety report submitted for regulatory review was examined to collate information about abnormal laboratory tests values and adverse event reports collected during the overall LEV development program. Analyses included 3347 patients exposed to LEV in clinical trials for epilepsy, cognition, and anxiety disorders. RESULTS: Safety data from all studies depict a similar pattern of adverse effects, predominantly somnolence, asthenia, and dizziness that occurred most frequently during the first month of LEV treatment. Changes in laboratory test values from placebo-controlled trials that were statistically significant remained in the normal range (red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils). Reports of the coding term 'infection' (common cold, upper respiratory infection) were not preceded by low neutrophil counts that might suggest impaired immunological status. Selection of adverse event coding terms probably contributed to the high rate of adverse effects termed 'infection.' Higher incidences of adverse effects, particularly behavioral effects, were found among epilepsy patients than in elderly patients with cognitive disorders or patients with anxiety disorders given lower doses. CONCLUSIONS: This review of patients evaluated during the clinical development program suggests that LEV was well tolerated and safe for patients with seizure, cognitive and anxiety disorders. Overall incidence of adverse effects in the LEV groups was little higher than reports from the placebo groups. Of course, this data was derived from clinical trials that are of relatively short duration, and provide data on only several thousand patients. Therefore, long-term side effects, and/or rare side effects cannot be ruled out on the basis of this analysis.

Anticonvulsants↗
PubMed2001

Quantitative assessment of seizure severity for clinical trials: a review of approaches to seizure components.

Quantitative assessment of seizure severity has been approached using a variety of systems. This review describes currently available methods and possible new approaches to seizure assessment for clinical trials. A review of the literature on methods of seizure assessments resulted in tabulation of the seizure rating scales known as VA, Chalfont-National Hospital, Liverpool, Hague, and the Occupational Hazard Scale. Seizures have been evaluated by simply counting all events, counting events by type, by clinician ratings, patient ratings, and combinations. Each of the scales has advantages and disadvantages. Most scales share core components: seizure frequency, seizure type, seizure duration, postictal events, postictal duration, automatisms, seizure clusters, known patterns, warnings, tongue biting, incontinence, injuries, and functional impairment. This review revealed a partial consensus about aspects of seizures that are important markers for severity. However, usefulness of the existing scales is limited by lack of data on responsiveness. New approaches are needed to assess changes in seizure severity as a result of an intervention in a clinical trial.

Clinical Trials as Topic↗
PubMed2001

The nature of the heterozygous Trp53 knockout model for identification of mutagenic carcinogens.

The heterozygous Trp53 null allele C57BL/6 (N5) mouse is susceptible to the rapid development of neoplasia by mutagenic carcinogens relative to control strains. This mouse model of chemical carcinogenesis demonstrates 1) dose-related rapid induction of tumors (26 wks), 2) multiple sites of carcinogen-specific tissue susceptibility, and 3) carcinogen-induced loss of heterozygosity involving the Trp53 wild-type allele or a p53 haploinsufficiency permitting mutation of other critical protooncogenes and/or inactivation of tumor suppressor genes driving tumorigenesis. Demonstration of mutation or loss of heterozygosity involving the Trp53 locus is consistent with a common finding in human cancers and supports extrapolation between rodents and humans. Using diverse experimental protocols, almost all mutagenic rodent carcinogens (including all mutagens that are carcinogenic to humans), but not nonmutagenic rodent carcinogens, induce tumors within 26 weeks of continuous exposure. These characteristics and results indicate that the mouse heterozygous for the Trp53 null allele may be of significant use for the prospective identification of mutagenic carcinogens of potential risk to human health.

Animals↗
PubMed2001

Evaluation of pharmacological aids on physical performance after a transmeridian flight.

PURPOSE: The purpose of this study was to evaluate physical performance (static and dynamic) of U.S. Air Force reservists after an eastbound air travel across seven time zones and to estimate the pharmacological aids slow-release caffeine and melatonin versus placebo in attempt to overcome the decline in performance. METHODS: 27 American volunteers were randomly divided into three groups: caffeine 300 mg, melatonin 5 mg, and placebo (lactose capsules). Two days before the flight and 10 d after, three tests were performed: hand grip strength test (static performance), squat jump test (maximal height), and multiple jump test (power and endurance). All measures were repeated twice a day: morning and afternoon. RESULTS: In placebo conditions, the static performance of the dominant hand decreased significantly during the first three mornings and tended to decrease the fourth morning. Simultaneously, the caffeine group's static performance increased significantly, whereas the melatonin group maintained its levels. No significant differences were observed the afternoons. No statistical differences appeared for the nondominant hand in the mornings or afternoons. Dynamic capacities presented no significant degradation after the travel. In the placebo group, for the squat jump test, performance increased from the fourth day. No real explanation can be given about this result. CONCLUSIONS: We demonstrated that slow-release caffeine and melatonin might be used to compensate for jet-lag troubles and particularly for the static physical performance decrease. The slow-release caffeine seems to be the best treatment, but its effects are only demonstrated on previously damaged performance. These preliminary results need further investigation, but we are the first to report a beneficial effect of slow-release caffeine and melatonin on physical performances after jet-lag.

Adult↗
PubMed2001

Buprenorphine: "field trials" of a new drug.

Buprenorphine is being introduced as a new treatment drug for narcotics addiction in the United States. The authors were asked by the National Institute on Drug Abuse to conduct a field trial to determine if buprenorphine might play a role in street markets. Because no street use of the drug existed in the United States, the authors used three sources of information: (a) "street readings" of clinical studies, (b) Internet discussion lists, and (c) research in other countries. By using an emergent style of analysis that relies on replication of patterns across disparate data sources, it was determined that buprenorphine has desirable characteristics from a street addict point of view. An evaluation of the field trial 5 years later evaluates its accuracy.

Bibliometrics↗
PubMed2001

Use of levetiracetam in special populations.

A subset of the 27 safety and pharmacokinetic studies of levetiracetam has been conducted in selected special populations: children, the elderly, and people with renal or hepatic impairment. The results of these studies indicate that higher doses need to be used for children (on a per-weight basis), and individuals with renal dysfunction require dosage modifications related to creatinine clearance. Individuals with hepatic impairment do not require modifications from standard doses. Little information is available on the effect of levetiracetam on the developing fetus, so cautious use during pregnancy is recommended until more information is available. Additional studies will refine the recommendations for use of levetiracetam in these special populations.

Adult↗
PubMed2001

Psychophysiological effects of a brief nocturnal light exposure.

This study compared the effects of a brief pulse (60-minute) of three full spectrum light intensities (1000, 500 and 30 lux) and two green light intensities (1000 and 500 lux) administered between 0200 and 0300 hrs. Ten participants were involved in this repeated measures study. Each participant experienced one condition every week for five weekends. Sessions began at 1800 hours and ended at 0600 hours the following day. Outside of the 60-minute exposure period, each session was spent in 30 lux white light. Oral temperature, salivary melatonin, cognitive performance and subjective mood were sampled throughout the sessions. Analysis revealed that all of the experimental light conditions significantly reduced salivary melatonin concentrations immediately following the pulse. This effect was not maintained beyond the duration of the light pulse. There was no significant effect on oral temperature. There were also no significant effects on cognitive performance and subjective mood, though some positive trends were observed. These results argue that brief, moderate intensity, pulses of either green or full spectrum light are sufficient to suppress the normal nocturnal rise in melatonin. However, the level of suppression obtained does not translate into significant improvement in cognitive performance or subjective mood.

Adolescent↗
PubMed2000

SSCP is not so difficult: the application and utility of single-stranded conformation polymorphism in evolutionary biology and molecular ecology.

All genetic markers are estimators of DNA nucleotide sequence variation. Rather than obtaining DNA sequence data, it is cheaper and faster to use techniques that estimate sequence variation, although this usually results in the loss of some information. SSCP (single-stranded conformation polymorphism) offers a sensitive but inexpensive, rapid, and convenient method for determining which DNA samples in a set differ in sequence, so that only an informative subset need be sequenced. In short, most DNA sequence variation can be detected with relatively little sequencing. SSCP has been widely applied in medical diagnosis, yet few studies have been published in population genetics. The utility and convenience of SSCP is far from fully appreciated by molecular population biologists. We hope to help redress this by illustrating the application of a single simple SSCP protocol to mitochondrial genes, nuclear introns, microsatellites, and anonymous nuclear sequences, in a range of vertebrates and invertebrates.

Animals↗
PubMed2000

Cortical reorganization in linear nevus sebaceous syndrome: a multimodality neuroimaging study.

The authors report the findings of multimodal structural, functional, and metabolic imaging in a patient with linear nevus sebaceous syndrome, intractable seizures, and right megalencephaly. Despite nearly continuous paroxysmal electrical activity from the megalencephalic region, imaging studies suggested nonfunctional tissue in this region with reorganization of cortical function to the unaffected ipsilateral hemisphere. Hemispherectomy has been successfully performed in previous patients; however, it could have led to marked left hemiparesis with significant functional morbidity in this patient because of ipsilateral reorganization of the primary motor cortex.

Adult↗
PubMed1999

Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord.

Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component of many persistent pain states. Here we report that the neurotrophin, brain-derived neurotrophic factor (BDNF), is a modulator of excitability within the spinal cord and contributes to the mechanism of central sensitization. BDNF, localized in primary sensory neuron cell bodies and central terminals, potentiates nociceptive spinal reflex responses in an in vitro spinal cord preparation and induces c-fos expression in dorsal horn neurons. NMDA receptor-mediated responses, known as a major contributor to central sensitization, were significantly enhanced by exogenous BDNF. Systemic NGF treatment, a procedure that mimics peripheral inflammatory states, raises BDNF levels in sensory neurons and increases nociceptive spinal reflex excitability. This increased central excitability is reduced by trkB-IgG, a BDNF "antagonist." We also show directly that inflammatory pain-related behavior depends on BDNF release in vivo. Thus behavioral nociceptive responses induced by intraplantar formalin and by intraplantar carageenan are significantly attenuated by trkB-IgG. Hence BDNF is appropriately localized and regulated in inflammatory states and is sufficient and necessary for the expression of central sensitization in the spinal cord. We propose that BDNF may function as a modulator of central sensitization in pathological states, and our results suggest that pharmacological antagonism of BDNF may prove an effective and novel analgesic strategy for the treatment of persistent inflammatory pain states.

Animals↗
PubMed1999

Adding lamotrigine to valproate: incidence of rash and other adverse effects. Postmarketing Antiepileptic Drug Survey (PADS) Group.

PURPOSE: Valproate (VPA) triples the half-life of lamotrigine (LTG), and combined use may be difficult. The adverse effect (AE) profile of this combination needs clarification. METHODS: We prospectively recorded our experience in adding LTG to VPA-containing regimens in 108 patients. Data collected included medications, seizure types and syndromes, and AEs. Patients were followed up to 27 months, until a stable dose was reached, or until LTG was discontinued. Patient management was not altered by this study. There were 60 patients with partial-onset seizures, 30 with generalized onset, and 12 with the Lennox-Gastaut syndrome. In 37, LTG was added to VPA monotherapy, and in 71, to VPA and other drugs. The median starting dose of LTG in our adult patients was 20.8 mg/day. RESULTS: LTG was added successfully in 86 (80%) patients. It was discontinued in 22 (20%): seven because of rash, seven for other AEs, and nine for other reasons. Rash occurred in 14 (13%) but caused discontinuation of LTG in only seven. We found a rash rate of 14.2% and a discontinuation rate because of rash of 8.7% among 310 patients in whom LTG was added to drug regimens not including VPA. Other AEs included fatigue (12%), gastrointestinal (GI) symptoms (9%), dizziness, headache, and insomnia (3% each). Serious AEs were hallucinations (two patients), hepatic enzyme elevations (two patients), irritability (one patient), and low white blood cell count (one patient). Whether LTG was added to VPA monotherapy or polytherapy made no difference in overall AE rate. CONCLUSIONS: LTG can be added to VPA with an acceptable incidence of side effects. LTG-induced rashes are no more common with VPA than with other drugs when LTG is added at very low initial dosages. Rashes are potentially serious and should be evaluated promptly.

Adolescent↗
PubMed1999

New antiepileptic drugs: comparison of key clinical trials.

PURPOSE: Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated. METHODS: A review of double-blind, placebo-controlled clinical trials of a new AED or placebo added to a standard AED provided data on reduction of complex partial seizures (CPSs). Success is > or =50% fewer CPSs with a new AED or placebo; Overall Improvement is the success rate with drug minus the success rate with placebo. Adverse events were tabulated from product-labeling lists of COSTART items (incidence, > or =5%). The Summary Complaint score is the total number of reports of individual events for each AED. RESULTS: Efficacy data demonstrate differences in Overall Improvement rates among five new AEDs and placebos (p = 0.001). However, rates of response to placebo also differed significantly among trials (p = 0.01). Adverse events predominantly affect central nervous system, psychiatric, and general body systems. However, patients in the placebo control groups did not consistently report adverse effects. Summary Complaint scores differ among the five new AEDs, but variability in use of COSTART terms nullifies comparisons. CONCLUSIONS: Comparisons of data for five new AEDs provide information for selection among treatments when a second drug is needed to improve control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects.

Acetates↗