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Biomedical subjects

J Ives

Publications and source records attributed to J Ives.

At least 19 recordsLinked to original sources
PubMed2003

Differential effects of low-frequency rTMS at the occipital pole on visual-induced alpha desynchronization and visual-evoked potentials.

Visual-induced alpha desynchronization (VID) and visual-evoked potentials (VEPs) characterize occipital activation in response to visual stimulation but their exact relationship is unclear. Here, we tested the hypothesis that VID and VEPs reflect different aspects of cortical activation. For this purpose, we determined whether VID and VEPs are differentially modulated by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the occipital pole. Scalp EEG responses to visual stimuli (flashed either to the left or to the right visual field) were recorded for 8 min in six healthy subjects (1) before, (2) immediately following, and (3) 20 min after left occipital rTMS (1 Hz, 10 min). The parameters aimed to reduce cortical excitability beyond the end of the TMS train. In addition, simple reaction times to visual stimulation were recorded (left or right hand in separate blocks). In all subjects, VID was significantly and prominently reduced by rTMS (P = 0.0001). In contrast, rTMS failed to modulate early VEP components (P1/N1). A moderate effect was found on a late VEP component close to manual response onset (P = 0.014) but this effect was in the opposite direction to the VID change. All changes were restricted to the targeted left occipital cortex. The effects were present only after right visual field stimulation when a right hand response was required, were associated with a behavioral effect, and had washed out 20 min after rTMS. We conclude that VID and early VEPs represent different aspects of cortical activation. The findings that rTMS did not change early VEPs and selectively affected VID and late VEPs in conditions where the visual input must be transferred intrahemispherically for visuomotor integration (right visual field/right hand) are suggestive of rTMS interference with higher-order visual functions beyond visual input. This is consistent with the idea that alpha desynchronization serves an integrative role through a corticocortical "gating function."

Adult↗
PubMed2002

Influenza virus carrying an R292K mutation in the neuraminidase gene is not transmitted in ferrets.

A model of influenza transmission has been established in ferrets in which wild-type influenza infection in a donor ferret can be transmitted sequentially to other ferrets. We have studied the transmission in ferrets of a clinical isolate of A/Sydney/5/97 (H3N2) carrying the neuraminidase 292K mutation compared with the corresponding wild-type virus from the same subject. Donor ferrets (n=four per group) were inoculated intranasally with mutant or wild-type virus and each housed with three naïve contact ferrets. All donor ferrets inoculated with wildtype virus were productively infected and transmitted virus to all 12 contacts, who in turn had high viral titres in their nasal washes. In contrast, only two of the donor ferrets inoculated with mutant virus were productively infected. There was little or no evidence that the two infected donor animals transmitted mutant virus to their contact animals. This ferret model has demonstrated that the mutant influenza virus with lysine at position 292 of the neuraminidase is of reduced infectivity and does not transmit under conditions in which the wild-type virus with arginine at position 292 readily transmits.

Animals↗
PubMed2002

Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo.

Oseltamivir phosphate (Tamiflu, Ro 64-0796) is the first orally administered neuraminidase (NA) inhibitor approved for use in treatment and prevention of influenza virus infection in man. Oseltamivir phosphate is the pro-drug of the active metabolite oseltamivir carboxylate (Ro 64-0802). Extensive monitoring throughout the oseltamivir development programme has identified a very low incidence of patients who have carried drug-resistant virus. The predominant mutation seen is the substitution of arginine for lysine at position 292 of the viral NA. The fitness of clinically isolated influenza virus A/Sydney/5/97 (H3N2) carrying this mutation was markedly reduced in animal models of influenza virus infection. The infectivity and replicative abilities of R292K mutant virus were reduced by at least 2 logs in a mouse model of influenza infection and by 2 and 4 logs, respectively, in the ferret model. Pathogenicity of R292K influenza virus A/Sydney/5/97 was reduced in ferrets as measured by inflammatory and febrile responses at least in parallel to the decrease in replicative ability. The data indicate that the R292K NA mutation compromises viral fitness such that virus carrying this mutation is unlikely to be of significant clinical consequence in man.

Acetamides↗
PubMed2000

EEG-Linked functional magnetic resonance imaging in epilepsy and cognitive neurophysiology.

The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of EEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e.g. focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions.

Artifacts↗
PubMed1999

Silent functional magnetic resonance imaging demonstrates focal activation in rapid eye movement sleep.

Functional imaging of human sleep has been performed with nuclear medicine methods, but MRI has been difficult to implement, in part because of the noise associated with echo-planar imaging as well as the difficulty in reading physiologic signals in the MRI environment. We describe a silent MR sequence that can record brain activation over many hours with simultaneous acquisition of an EEG. This shows activation of occipital cortex and deactivation of frontal cortex during REM sleep, in agreement with previous studies using other techniques. MRI-Sleep-REM sleep.

Adult↗
PubMed1999

Visual evoked potential (VEP) measured by simultaneous 64-channel EEG and 3T fMRI.

We present the first simultaneous measurements of evoked potentials (EPs) and fMRI hemodynamic responses to visual stimulation. Visual evoked potentials (VEPs) were recorded both inside and outside the static 3T magnetic field, and during fMRI examination. We designed, constructed, and tested a non-magnetic 64-channel EEG recording cap. By using a large number of EEG channels it is possible to design a spatial filter capable of removing the artifact noise present when recording EEG/EPs within a strong magnetic field. We show that the designed spatial filter is capable of recovering the ballistocardiogram-contaminated original EEG signal. Isopotential plots of the electrode array recordings at the peak of the VEP response (approximately 100ms) correspond well with simultaneous fMRI observed activated areas of primary and secondary visual cortices.

Artifacts↗
PubMed1998

Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography.

We present a new approach for non-invasive localization of focal epileptogenic discharges in patients considered for surgical treatment. EEG-triggered functional MR imaging (fMRI) and 3D EEG source localization were combined to map the primary electrical source with high spatial resolution. The method is illustrated by the case of a patient with medically intractable frontal lobe epilepsy. EEG obtained in the MRI system allowed triggering of the fMRI acquisition by the patient's habitual epileptogenic discharges. fMRI revealed multiple areas of signal enhancement. Three-dimensional EEG source localization identified the same active areas and provided evidence of onset in the left frontal lobe. Subsequent electrocorticography from subdural electrodes confirmed spike and seizure onset over this region. This approach, i.e. the combination of EEG-triggered fMRI and 3D EEG source analysis, represents a promising additional tool for presurgical epilepsy evaluation allowing precise non-invasive identification of the epileptic foci.

Adolescent↗
PubMed1998

Incidence of spikes and paroxysmal rhythmic events in overnight ambulatory computer-assisted EEGs of normal subjects: a multicenter study.

The incidences of spikes and paroxysmal rhythmic events (PREs) in 10-h overnight EEGs of normal adult volunteers (n=135) were studied at 11 sites with a computer-assisted ambulatory EEG monitoring system with automatic spike and PRE detection. Spikes were evident in the overnight EEG of 1 subject (0.7%), and PREs were apparent in the overnight EEG of the same subject (0.7%). The incidences of spikes of 24 other subjects with a history of migraine and/or a family history of epilepsy were 12.5 and 13.3%, respectively. The overnight EEGs of these subjects were significantly more likely to show spikes than the overnight EEGs of subjects without migraine or a family history of epilepsy.

Adolescent↗
PubMed1997

Evidence for rapid face recognition from human scalp and intracranial electrodes.

It is still generally believed that complex visual analysis is not carried out within the first 100 ms. Here we show that intra- and extracranial visual evoked potentials (VEPs) differentiate previously seen faces from novel faces as early as 50 ms after stimulus onset. EEG was recorded from scalp electrodes in 12 male healthy volunteers (group I) and intracranially from implanted depth electrodes in the temporal and frontal cortex of seven epilepsy patients (group II). Both groups were engaged in a face recognition task. All subjects showed significant differential responses which occurred very early (50-90 ms) and later (190-600 ms). In group II, the early responses were recorded more frequently in the right hemisphere, whereas the late differential VEPs were found in both hemispheres. Both types of VEPs were more frequent in the temporal neocortex, underlining its role as a major contributor to these fast recognition processes.

Adult↗
PubMed1996

An integrated map with cosmid/PAC contigs of a 4-Mb Down syndrome critical region.

The major phenotypic features of Down syndrome have been correlated with partial trisomies of chromosome 21, allowing us to define the candidate gene region to a 4-Mb segment on the 21q22.2 band. We present here a high-resolution physical map with megabase-sized cosmid/PAC contigs. This ordered clone library has provided unique material for the integration of a variety of mappable objects, including exons, cDNAs, restriction sites, etc. Furthermore, our results have exemplified a strategy for the completion of the chromosome 21 map to sequencing.

Bacteriophage P1↗
PubMed1995

Systems analysis of adverse drug events. ADE Prevention Study Group.

OBJECTIVE: To identify and evaluate the systems failures that underlie errors causing adverse drug events (ADEs) and potential ADEs. DESIGN: Systems analysis of events from a prospective cohort study. PARTICIPANTS: All admissions to 11 medical and surgical units in two tertiary care hospitals over a 6-month period. MAIN OUTCOME MEASURES: Errors, proximal causes, and systems failures. METHODS: Errors were detected by interviews of those involved. Errors were classified according to proximal cause and underlying systems failure by multidisciplinary teams of physicians, nurses, pharmacists, and systems analysts. RESULTS: During this period, 334 errors were detected as the causes of 264 preventable ADEs and potential ADEs. Sixteen major systems failures were identified as the underlying causes of the errors. The most common systems failure was in the dissemination of drug knowledge, particularly to physicians, accounting for 29% of the 334 errors. Inadequate availability of patient information, such as the results of laboratory tests, was associated with 18% of errors. Seven systems failures accounted for 78% of the errors; all could be improved by better information systems. CONCLUSIONS: Hospital personnel willingly participated in the detection and investigation of drug use errors and were able to identify underlying systems failures. The most common defects were in systems to disseminate knowledge about drugs and to make drug and patient information readily accessible at the time it is needed. Systems changes to improve dissemination and display of drug and patient data should make errors in the use of drugs less likely.

Boston↗
PubMed1995

Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain.

Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task-related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding. In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set.

Adult↗
PubMed1994

Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates.

The synthesis of a series of alkylcarbamates of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-7-ol is reported. Many of these compounds are potent acetylcholinesterase (AChE) inhibitors. The in vitro AChE inhibition, cholinergic effects, acute toxicity, and elevation of brain acetylcholine levels in vivo of this series of compounds are described. A representative compound, 1d (5.6 mg/kg, po), was able to reverse hemicolinium-3-induced amnesia in the mouse passive avoidance assay.

Administration, Oral↗
PubMed1994

Altered pulsatile secretion of luteinizing hormone in women with epilepsy.

Menstrual disorders and infertility are common among women with epilepsy of temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause. Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic hypogonadism, HH), in particular, are significantly overrepresented and attributable to hypothalamic dysfunction. We therefore compared the hypothalamic function of 14 women with clinically and electrographically documented TLE with that of eight age-matched normal controls by determining the interictal pulse frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse frequency values were significantly more variable (p < 0.05) and lower (p < 0.05) among women with TLE than among controls. Women with left temporal EEG foci showed a trend toward higher pulse frequencies compared to women with right foci (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the three with PCO had left-sided foci and average LH pulse frequency two times higher than that of the two women with HH, who had right-sided foci. Eight reproductively normal, medically treated women with TLE had significantly lower LH pulse frequencies than did the one reproductively normal, untreated woman with TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest that LH pulse frequencies in women with TLE may be influenced by the laterality of the epileptic focus, the reproductive endocrine status, and the use of antiseizure medications.

Adult↗
PubMed1993

Differential neural activity in the human temporal lobe evoked by faces of family members and friends.

In 6 patients, depth electrodes revealed differential evoked responses to familiar versus novel faces. These differential responses were obtained in the amygdala, hippocampus, and temporal neocortex but not in the dorsolateral frontal or cingulate cortex. The limbic and temporal structures that differentiated novel from familiar faces did not respond differentially to variations in luminance. Limbic structures and temporal cortex thus appear to participate in face recognition and in encoding the familiarity of visual experiences.

Adult↗
PubMed1992

Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues.

The synthesis of a series of 1,2,3,3a,8,8a-hexahydroindeno[2,1-b]pyrrole 5-alkylcarbamates and their resolution are reported. These compounds are structurally related to physostigmine with substitution of a methylene group in place of the NMe group at position 8 of physostigmine. Many of these 8-carbaphysostigmine analogues are more potent acetylcholinesterase inhibitors in vitro and less toxic in vivo than physostigmine. The (-)-enantiomer (e.g., 1d and 1g) possessing the same absolute configuration at C3a and C8a as that of physostigmine, is about 6 to 12-fold more potent at inhibiting acetylcholinesterase than the corresponding (+)-enantiomer (e.g., 1e and 1h).

Animals↗