Biomedical subjects

J M Wild

Publications and source records attributed to J M Wild.

At least 55 records · Page 3Linked to original sources

PubMed1999

Characteristics of a unique visual field defect attributed to vigabatrin.

PURPOSE: Vigabatrin (VGB) therapy is associated with a loss of peripheral vision. The characteristics and prevalence of VGB-attributed visual field loss (V-AVFL) and associated risk factors were evaluated in patients with epilepsy. METHODS: The material comprised the visual fields and case notes of 88 patients with suspected V-AVFL (25 spontaneous reports and 63 cases from an open-label extension trial) and of 42 patients receiving alternative antiepileptic drugs (AEDs) from a cross-sectional study. RESULTS: Forty-two reliable cases of visual field loss could not be assigned to an alternative known cause and were therefore attributed to VGB (13 spontaneous reports and 29 from the open-label study). All cases except one were asymptomatic. Seven cases of field loss were present in the reference cohort of 42 patients; all cases could be attributed to a known aetiology. Thirty-six of the 42 confirmed cases of V-AVFL exhibited a bilateral defect that was most profound nasally, and three, a concentric constriction. The prevalence of V-AVFL was 29% (95% confidence interval, 21-39%). Male gender was associated with a 2.1-fold increased relative risk of V-AVFL (95% confidence interval, 1.20-4.6%). Age, body weight, duration of epilepsy, and daily dose of VGB, and concomitant AEDs did not predict the occurrence of V-AVFL. CONCLUSIONS: The unique visual field defect attributed to VGB is profound in terms of the frequency of occurrence and the location and severity of loss. The asymptomatic nature of the field loss indicates that V-AVFL can be elicited only by visual field examination.

Adult↗

PubMed1999

Adjustment of carbamazepine dose to offset the effects of the interaction with remacemide hydrochloride in a double-blind, multicentre, add-on drug trial (CR2237) in refractory epilepsy.

PURPOSE: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer. METHODS: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient. RESULTS: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced > or =50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L. CONCLUSIONS: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.

Acetamides↗

PubMed1999

Visual field defects associated with vigabatrin therapy.

OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.

Adolescent↗

PubMed1999

Between-algorithm, between-individual differences in normal perimetric sensitivity: full threshold, FASTPAC, and SITA. Swedish Interactive Threshold algorithm.

PURPOSE: To determine the between-algorithm differences in perimetric sensitivity for the Swedish Interactive Threshold algorithm (SITA) Standard, SITA Fast, FASTPAC, and Full Threshold algorithms; to determine the between-subject, between-algorithm differences in the magnitude of the normal variation in sensitivity. METHODS: The sample comprised 50 normal subjects (mean age, 52.9 +/- 18.5 years) experienced in automated perimetry. One randomly assigned eye was examined at three visits with Program 30-2 of the Humphrey Field Analyzer (HFA). The first visit was a familiarization session. A two-period crossover design with order randomization within visits was used over the second and third visits. SITA Standard, SITA Fast, and HFA 640 Full Threshold were administered during one visit. FASTPAC and HFA 750 Full Threshold were administered during the remaining visit. RESULTS: Group mean Mean Sensitivity was 0.8 dB higher for SITA Standard than for Full Threshold (P < 0.001) and 1.3 dB higher for SITA Fast than for Full Threshold (P < 0.001). A similar trend was found between SITA and FASTPAC. The group mean Mean Sensitivity for SITA Fast was 0.5 dB higher than for SITA Standard (P < 0.001). The pointwise between-algorithm difference in sensitivity was similar for all algorithms. The pointwise between-algorithm, between-subject variability was lower for SITA. The examination durations for SITA Fast and SITA Standard were half those for FASTPAC and Full Threshold; SITA Fast was 41% that of SITA Standard (P < 0.001). CONCLUSIONS: SITA produced marginally higher mean mean sensitivity compared with that of existing algorithms and markedly reduced examination duration. The reduced between-subject variability of SITA should result in narrower confidence limits for definition of normality.

Adult↗

PubMed1999

The SITA perimetric threshold algorithms in glaucoma.

PURPOSE: To determine the within-visit between-algorithm and the within-algorithm between-visit differences in sensitivity for the SITA Standard, SITA Fast, FASTPAC, and Full Threshold algorithms in stable primary open angle glaucoma. METHODS: One designated eye from each of 29 patients (age 67.3 +/- 10.2 years; mean +/- SD) experienced in automated perimetry was examined with the four algorithms on each of three visits, using the Humphrey Field Analyzer 750 and Program 30-2. RESULTS: The group mean Mean Sensitivity was 1.0 dB greater for SITA Standard than Full Threshold (P < 0.001), 0.7 dB greater for SITA Standard than FASTPAC (P < 0.001), 1.6 dB greater for SITA Fast than FASTPAC (P < 0.001), and 0.9 dB greater for SITA Fast than SITA Standard (P < 0.001). The higher pointwise sensitivity for SITA Fast compared to Full Threshold, FASTPAC, and SITA Standard increased with increase in defect depth. The examination duration for SITA Standard was 53% of that for Full Threshold and 50% shorter for SITA Fast compared to FASTPAC (P < 0.001), regardless of age (P = 0.932). The examination duration increased with increase in severity of field loss (P < 0.001), and this increase was proportionately greater for both SITA algorithms (P < 0.001), particularly SITA Fast. The Total and Pattern Deviation probability analyses of both SITA algorithms yielded a statistically greater defect than Full Threshold or FASTPAC (P < 0.001). The within-algorithm between-visit differences were similar between SITA Standard and Full Threshold and between SITA Fast and FASTPAC. CONCLUSIONS: Both SITA algorithms produce a marginally higher differential light sensitivity compared to existing algorithms but with a statistically deeper defect and a marked reduction in examination duration.

Adult↗

PubMed1998

Inspiratory muscle activity during bird song.

The apparently continuous flow of bird song is in reality punctuated by brief periods of silence during which there are short inspirations called minibreaths. To determine whether these minibreaths are accompanied, and thus perhaps caused, by activity in inspiratory muscles, electromyographic (EMG) activity was recorded in M. scalenus in zebra finches and in M. scalenus and Mm. levatores costarum in cowbirds, together with EMGs from the abdominal expiratory muscles, air sac pressure and tracheal airflow. EMG activity in Mm. scalenus and levatores costarum consistently preceded the onset of negative air sac pressure by approximately 11 ms during both quiet respiration and singing in both species. The electrical activity of these two muscles was very similar. Compared with during quiet respiration, the amplitude of inspiratory muscle EMG during singing was increased between five- and 12-fold and its duration was decreased from >200 ms to on average 41 ms during minibreaths, again for both species, but inspiratory muscle activity did not overlap with that of the expiratory muscles. Thus, there was no indication that the inspiratory muscles acted either to shorten the duration of expiration or to reduce the expiratory effort as might occur if both expiratory and inspiratory muscles were simultaneously active. Inspiratory and expiratory muscle activities were highly stereotyped during song to the extent that together, they defined the temporal pattern of the songs and song types of individual birds.

Abdominal Muscles↗

PubMed1998

Melanocortin-4 receptor mRNA expression in the developing autonomic and central nervous systems.

MC4-R mRNA expression was investigated in fetal rats (E14-E20) using in situ hybridisation. The autonomic nervous system showed the highest levels of MC4-R mRNA expression. In the spinal cord, dense signal was seen over the future intermediolateral cell column and dorsal horn. In the brain, MC4-R was expressed by E14 in diencephalon neuroepithelia, telencephalon, lamina terminalis and spinal trigeminal nucleus and was expressed by E19 throughout many regions of the brain.

Animals↗

PubMed1998

Organization of quinto-frontal structures in hatchling ring doves (Streptopelia risoria).

Transganglionic and retrograde tracing procedures were applied to peripheral and central trigeminal structures in hatchling ring doves. The organization of the trigeminal ganglion, its somatotopic projections upon the principal sensory nucleus (PrV), and the projections of PrV upon the telencephalon are similar in adult and hatchling Columbiformes. The results suggest that development of feeding patterns in these species involves experiential differentiation of trigeminal sensorimotor circuits present at hatching.

Animals↗

PubMed1998

Identification and connections of inspiratory premotor neurons in songbirds and budgerigar.

Recordings of extracellular unit activity in the ventrolateral medulla and of electromyographic activity in either the M. scalenus, a principal inspiratory muscle, or the abdominal expiratory muscles, were used to identify inspiratory related (IR) neurons. IR neurons extended from levels caudal to the obex through the caudal level of the descending vestibular nucleus. This distribution was found to correspond to that of a subset of cells retrogradely labeled from injections of neuronal tracers into the upper thoracic spinal cord, where motoneurons innervating the M. scalenus were located by retrograde transport. Injections of biotinylated dextran amine at the recording sites resulted in projections to the spinal cord and brainstem. Bulbospinal axons traveled in the lateral funiculus, predominantly contralaterally, and terminated in relation to the dendrites and cell bodies of motoneurons innervating the M. scalenus. Brainstem nuclei receiving projections from injections at IR loci included the retroambigualis, tracheosyringeal motor nucleus, ventrolateral nucleus of the rostral medulla, infraolivaris superior, ventrolateral parabrachial nucleus, and the dorsomedial nucleus of the intercollicular complex. In the finches, there were also bilateral projections to nucleus uvaeformis of the posterior thalamus. The spinal and brainstem projections are similar to those found in pigeon (Reinke and Wild, [1997] J. Comp. Neurol. 379:347-362), and probably mediate the intricate coordination of the vocal (syringeal) and respiratory systems for the control of vocalization. The distribution of IR neurons in birds is similar to that of the rostral ventral respiratory group (rVRG) in mammals.

Animals↗

PubMed1998

Statistical aspects of the normal visual field in short-wavelength automated perimetry.

PURPOSE: To determine the intraindividual and interindividual characteristics of normal sensitivity derived by short-wavelength automated perimetry (SWAP) as a function of threshold algorithm. To determine also the influence of ocular media absorption on the magnitude of the interindividual variation in normal sensitivity, and hence the confidence limits, derived by SWAP. METHODS: The sample comprised 51 normal subjects, stratified for age by decade (mean age, 55.5 years; range, 24-83 years) and experienced in white-on-white (W-W) perimetry and SWAP. One randomly assigned eye of each subject was examined on three occasions with Program 30-2 of the 640 Humphrey Field Analyzer using the Full Threshold and FASTPAC strategies for SWAP and W-W perimetries. Ocular media absorption (OMA) was assessed by the difference in scotopic sensitivity to stimuli of 410 and 560 nm. RESULTS: The group mean examination time (P < 0.001) was greater for SWAP than for W-W perimetry for both the Full Threshold (15.0% longer) and FASTPAC strategies (16.8% longer). The gradient of the age-decline in Mean Sensitivity for SWAP was approximately 25% less steep when corrected for OMA than when uncorrected. The interindividual normal variability, expressed as the coefficient of variation, for SWAP without correction for OMA was 2.7 times greater (range 2.0-3.9), and with correction 1.9 times greater (range 1.4-2.9), than that for W-W perimetry. CONCLUSIONS: The increased interindividual normal variability of SWAP, exacerbated by the lack of correction for OMA, currently limits the utility of SWAP in that the reduction in sensitivity required to indicate abnormality was proportionately greater than for W-W perimetry.

Absorption↗

PubMed1997

The avian somatosensory system: the pathway from wing to Wulst in a passerine (Chloris chloris).

The organization of the wing component of the dorsal column-medial lemniscal pathway, and somatosensory projections from the thalamus to the Wulst, are described for an oscine member of the major group of birds, the Passeriformes. Wing primary afferents terminate throughout the cervical spinal cord, but between the brachial enlargement and the spino-medullary junction, they are confined to medial lamina V. Within the medulla, terminations extend rostrally and laterally to occupy the cuneate (Cu) and external cuneate nuclei (CuE). Ascending projections from Cu and CuE form the contralateral medial lemniscus, which has extensive projections to the midbrain and to the thalamus. In the midbrain the projections surround the central auditory nucleus densely, and terminate more sparsely within it. In the thalamus, specific terminations were observed in nucleus uvaeformis and in the nucleus dorsalis intermedius ventralis anterior (DIVA). DIVA projects to the ipsilateral rostral Wulst where it terminates in the intercalated hyperstriatum accessorium, in a distinct, regular patchy fashion. The somatosensory projections to the telencephalon in green finch are similar to those in pigeon, but dissimilar to those in budgerigar.

Animals↗

PubMed1997

A non-thalamic pathway contributes to a whole body map in the brain of the budgerigar.

Nucleus basalis (Bas) of the budgerigar contains an ordered, but distorted, somatotopic representation of the whole body, as does the primary somatosensory cortex (SI) of mammals. Unlike SI, however, the beak and body regions of Bas receive their sensory input via disynaptic pathways relaying in the pons. That to the body parts originates in a previously undescribed nucleus that receives its inputs from primary afferents via a novel, ipsilateral somatosensory pathway.

Animals↗

PubMed1997

Distribution and connections of inspiratory premotor neurons in the brainstem of the pigeon (Columba livia).

We have recorded extracellular, inspiratory-related (IR) unit activity in the medulla at locations corresponding to those of neurons retrogradely labeled by injections of retrograde tracers in the lower brachial and upper thoracic spinal cord, injections that covered cell bodies and dendrites of motoneurons innervating inspiratory muscles. Bulbospinal neurons were distributed throughout the dorsomedial and ventrolateral medulla, from the spinomedullary junction through about 0.8 mm rostral to the obex. Almost all of the 104 IR units recorded were located in corresponding parts of the ventrolateral medulla, rostral to nucleus retroambigualis, where expiratory related units are found. Injections of biotinylated dextran amine at the recording sites labeled projections both to the spinal cord and to the brainstem. In the lower brachial and upper thoracic spinal cord, bulbospinal axons traveled predominantly in the contralateral dorsolateral funiculus and terminated in close relation to the dendrites of inspiratory motoneurons retrogradely labeled with cholera toxin B-chain. In the brainstem, there were predominantly ipsilateral projections to the nucleus retroambigualis, tracheosyringeal motor nucleus (XIIts), ventrolateral nucleus of the rostral medulla, infraolivary superior nucleus, ventrolateral parabrachial nucleus, and dorsomedial nucleus of the intercollicular complex. In all these nuclei, except XIIts, retrogradely labeled neurons were also found, indicating reciprocity of the connections. These results suggest the possibility of monosynaptic connections between inspiratory premotor neurons and inspiratory motoneurons, which, together with connections of IR neurons with other brainstem respiratory-vocal nuclei, seem likely to mediate the close coordination that exists in birds between the vocal and respiratory systems. The distribution of IR neurons in birds is similar to that of the rostral ventral respiratory group (rVRG) in mammals.

Animals↗

PubMed1997

Reciprocal connections between primary and secondary auditory pathways in the telencephalon of the budgerigar (Melopsittacus undulatus).

Among avian species that learn their vocalizations, budgerigars have been thought to be unusual in receiving auditory input to the vocal control circuitry of the telencephalon via an auditory component of nucleus basalis (NB), rather than via Field L2, the end station of the classical thalamofugal pathway. In the present study, however, the application of neural tracing techniques showed the two auditory pathways to be reciprocally connected within the telencephalon. The implication is, therefore, that auditory information essential for vocal learning and vocal production in the budgerigar is derived from the primary as well as the secondary auditory pathway.

Animals↗

PubMed1997

Projections of the dorsomedial nucleus of the intercollicular complex (DM) in relation to respiratory-vocal nuclei in the brainstem of pigeon (Columba livia) and zebra finch (Taeniopygia guttata).

Injections of neuronal tracers were made into the dorsomedial nucleus of the intercollicular complex (DM) of pigeons and zebra finches in order to investigate the projections of this nucleus which has long been implicated in respiratory-vocal control. Despite the fact that pigeons are nonsongbirds and zebra finches are songbirds, the projections were very similar in both species. Most descended throughout the brainstem, taking ventral and dorsal trajectories, which merged in the medulla. Those descending ventrally terminated upon the ventrolateral parabrachial nucleus (PBvl), the nucleus infraolivaris superior, a nucleus of the rostral ventrolateral medulla (RVL), and the nucleus retroambigualis (RAm). Those taking a dorsal trajectory via the occipitomesencephalic tract terminated in the tracheosyringeal part of the hypoglossal nucleus (XIIts), the suprahypoglossal region, and nucleus retroambigualis. There were also substantial projections throughout an arc extending between XIIts and RVL rostrally, and XIIts and RAm caudally. Neurons throughout this arc, which include inspiratory premotor neurons at levels straddling the obex and expiratory premotor neurons more caudally (in RAm), were retrogradely labeled from spinal injections. The DM projections were predominantly ipsilateral, but there were distinct contralateral projections to all the homologous nuclei in both species. All but the projections to PBvl and XIIts were reciprocal. In summary, the projections of DM suggest that it is able to influence all the key motor and premotor nuclei involved in patterned respiratory-vocal activity.

Animals↗

PubMed1997

Neural pathways for the control of birdsong production.

As in humans, song production in birds involves the intricate coordination of at least three major groups of muscles: namely, those of the syrinx, the respiratory apparatus, and the upper vocal tract, including the jaw. The pathway in songbirds that controls the syrinx originates in the telencephalon and projects via the occipitomesencephalic tract directly upon vocal motoneurons in the medulla. Activity in this pathway configures the syrinx into phonatory positions for the production of species typical vocalizations. Another component of this pathway mediates control of respiration during vocalization, since it projects upon both expiratory and inspiratory groups of premotor neurons in the ventrolateral medulla, as well as upon several other nuclei en route. This pathway appears to be primarily involved with the control of the temporal pattern of song, but is also importantly involved in the control of vocal intensity, mediated via air sac pressure. There are extensive interconnections between the vocal and respiratory pathways, especially at brain-stem levels, and it may be these that ensure the necessary temporal coordination of syringeal and respiratory activity. The pathway mediating control of the jaw appears to be different from those mediating control of the syrinx and respiratory muscles. It originates in a different part of the archistriatum and projects upon premotor neurons in the medulla that appear to be separate from those projecting upon the syringeal motor nucleus. The separateness of this pathway may reflect the imperfect correlation of jaw movements with the dynamic and acoustic features of song. The brainstem pathways mediating control of vocalization and respiration in songbirds have distinct similarities to those in mammals such as cats and monkeys. However, songbirds, like humans, but unlike most other non-songbirds, have developed a telencephalic vocal control system for the production of learned vocalizations.

Animals↗

PubMed1997

Calculations and experimental studies of the lineshape of the lactate doublet in PRESS-localized 1H MRS.

Accurate quantification of NMR metabolites by spectral modeling requires assumed lineshape functions. For singlet resonances, a combination of Lorentzian and Gaussian lineshapes is sufficient, but for weekly J-coupled resonances such as lactate, more complex lineshapes are necessary. In this work, the lactate lineshape is calculated for the PRESS sequence using standard RF pulses, and compared with experimental measurements. A similar comparison is made for PRESS-localized spectroscopic imaging, in which the lineshape varies from voxel to voxel across the field of view. These observations have important implications for the quantification of lactate in experimental and human studies.

Computer Simulation↗

PubMed1997

Pointwise univariate linear regression of perimetric sensitivity against follow-up time in glaucoma.

PURPOSE: The authors compared pointwise univariate linear regression (ULR) of sensitivity against follow-up as an indicator of visual field progression with that of the corresponding ULR of mean deviation (MD) and with the Glaucoma Change Probability (GCP) analysis. The authors determined the influence of the number and sequence of prior examinations on the slope of the pointwise function. METHODS: Univariate linear regression was undertaken at each stimulus location on the arbitrarily assigned left eyes of 38 patients with glaucoma examined with the Humphrey Field Analyzer Programs 30-2 or 24-2 (stimulus size III, Humphrey Instruments Inc, San Leandro, CA). The mean age was 59.0 years (standard deviation [SD] = 12.9), the mean number of fields per patients was 12.0 (SD = 2.8), and the mean duration of follow-up was 6.0 years (SD = 1.6). RESULTS: Four patients showed statistically significant MD slopes. Of the 34 patients exhibiting a nonsignificant MD slope, 15 exhibited clusters of at least two contiguous progressing locations. Less than half of these locations were designated as progressing by GCP. The GCP detected less than one third of the locations considered progressing by ULR for the last six fields in the series: this was attributed to the nonlinear nature of the decline in sensitivity. CONCLUSIONS: The degree of agreement between the outcomes of ULR and GCP was dependent on the quality of the collected data, the magnitude of the baseline sensitivity, the extent and type of the subsequent visual field progression, and the position of the fields within the examination series. Good agreement was illustrated at those locations where the deterioration fell outside the limits of expected variability in stable glaucoma.

Female↗