Biomedical subjects

P Dean

Publications and source records attributed to P Dean.

At least 37 records · Page 2Linked to original sources

PubMed1999

Association of abnormal cerebellar activation with motor learning difficulties in dyslexic adults.

BACKGROUND: In addition to their impairments in literacy-related skills, dyslexic children show characteristic difficulties in phonological skill, motor skill, and balance. There is behavioural and biochemical evidence that these difficulties may be attributable to mild cerebellar dysfunction. We wanted to find out whether there was abnormal brain activation when dyslexic adults undertook tasks known normally to involve cerebellar activation. METHODS: Brain activation was monitored by positron emission tomography in matched groups of six dyslexic adults and six control adults as they carried out either a prelearned sequence or learned a novel sequence of finger movements. FINDINGS: Brain activation was significantly lower (p<0.01) for the dyslexic adults than for the controls in the right cerebellar cortex and the left cingulate gyrus when executing the prelearned sequence, and in the right cerebellar cortex when learning the new sequence. INTERPRETATION: The results provided direct evidence that, for this group of dyslexic adults, the behavioural signs of cerebellar abnormality reflect underlying abnormalities in cerebellar activation.

Adult↗

PubMed1999

Acute tryptophan depletion in healthy young women with a family history of major affective disorder.

BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin synthesis, lowers mood in normal males with a multi-generational family history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generational family history of MAD. In addition, the temporal stability of mood change following repeated trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the balanced condition, family history positive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD trials (N = 13) exhibited poor temporal stability. CONCLUSIONS: These results may indicate that serotonin responsiveness is not an important characteristic of vulnerability to depression in these women. Alternately, these negative results may be due to the exclusion of a large number of FH + women who had already experienced an episode of depression, resulting in the selection of a biased FH + sample who are resistant to the mood lowering effects of ATD.

Adolescent↗

PubMed1999

Optimality of position commands to horizontal eye muscles: A test of the minimum-norm rule.

Six muscles control the position of the eye, which has three degrees of freedom. Daunicht proposed an optimization rule for solving this redundancy problem, whereby small changes in eye position are maintained by the minimum possible change in motor commands to the eye (the minimum-norm rule). The present study sought to test this proposal for the simplified one-dimensional case of small changes in conjugate eye position in the horizontal plane. Assuming such changes involve only the horizontal recti, Daunicht's hypothesis predicts reciprocal innervation with the size of the change in command matched to the strength of the recipient muscle at every starting position of the eye. If the motor command to a muscle is interpreted as the summed firing rate of its oculomotor neuron (OMN) pool, the minimum-norm prediction can be tested by comparing OMN firing rates with forces in the horizontal recti. The comparison showed 1) for the OMN firing rates given by Van Gisbergen and Van Opstal and the muscle forces given by Robinson, there was good agreement between the minimum-norm prediction and experimental observation over about a +/-30 degrees range of eye positions. This fit was robust with respect to variations in muscle stiffness and in methods of calculating muscle innervation. 2) Other data sets gave different estimates for the range of eye-positions within which the minimum-norm prediction held. The main sources of variation appeared to be disagreement about the proportion of OMNs with very low firing-rate thresholds (i.e., less than approximately 35 degrees in the OFF direction) and uncertainty about eye-muscle behavior for extreme (>30 degrees ) positions of the eye. 3) For all data sets, the range of eye positions over which the minimum-norm rule applied was determined by the pattern of motor-unit recruitment inferred for those data. It corresponded to the range of eye positions over which the size principle of recruitment was obeyed by both agonist and antagonist muscles. It is argued that the current best estimate of the oculomotor range over which minimum-norm control could be used for conjugate horizontal eye position is approximately +/-30 degrees. The uncertainty associated with this estimate would be reduced by obtaining unbiased samples of OMN firing rates. Minimum-norm control may result from reduction of the image movement produced by noise in OMN firing rates.

Animals↗

PubMed1998

Bellini duct (collecting duct) carcinoma of the kidney.

Carcinoma of the collecting ducts, or Bellini carcinoma, is a rare renal tumour and, unlike most renal cell carcinomas, it derives from distal tubules. It displays highly aggressive behaviour and has a poor prognosis. In this study, the authors present three cases which they observed over the past three years.

Aged↗

PubMed1998

Epilepsy surgery in the first three years of life.

PURPOSE: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes. METHODS: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery. RESULTS: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment. CONCLUSIONS: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.

Adult↗

PubMed1997

Simulated recruitment of medial rectus motoneurons by abducens internuclear neurons: synaptic specificity vs. intrinsic motoneuron properties.

Ocular motoneuron firing rate is linearly related to conjugate eye position with slope K above recruitment threshold theta. Within the population of ocular motoneurons K increases as theta increases. These differences in firing rate between motoneurons might be determined either by the intrinsic properties of the motoneurons, or by differences in synaptic input to them, or by a combination of the two. This question was investigated by simulating the input signal to medial rectus motoneurons (MR-MNs) from internuclear neurons of the abducens nucleus (INNs). INNs were represented as input nodes in a two-layer neural net, each with weighted connections to every output node representing an MR-MN. Individual simulated MR-MNs were assigned parameters corresponding to an intrinsic current threshold I(R) and an intrinsic frequency-current (f-I) slope gamma. Their firing rates were calculated from these parameters, together with the effective synaptic current produced by their synaptically weighted INN inputs, with the use of assumptions employed in computer simulations of spinal motoneuron pools. The experimentally observed firing rates of MR-MNs served as training data for the net. The following two training conditions were used: 1) synaptic weights were fixed and the intrinsic parameters of the MR-MNs were allowed to vary, corresponding to the situation in which each MR-MN receives a common synaptic drive and 2) intrinsic MR-MN properties were fixed and synaptic weights were allowed to vary. In each case, the varying quantities were trained with a form of gradient descent error reduction. The simulations revealed the following three problems with the common-drive model: 1) the recruitment of INNs produced nonlinear responses in MR-MNs with low thetas; 2) the range of I(R)s required to reproduce the observed range of theta were generally larger than those measured experimentally for cat ocular motoneurons; and 3) the intrinsic f-I slope gamma increased with I(R). Experimental data from cat indicate that gamma decreases with I(R). When synaptic weights were allowed to vary, all three problems with the common-drive model were overcome. This required MR-MNs receiving selective input from INNs with similar firing rate thresholds. These results suggest that the differences in firing rate properties among MR-MNs in relation to steady-state eye position cannot be derived from their intrinsic properties alone but result at least partly from differences in their synaptic inputs. An MR-MN's individual set of synaptic inputs constitutes, in effect, a premotor receptive field.

Animals↗

PubMed1997

Results and complications after reoperation for failed epilepsy surgery in children.

The seizure outcome and neurological outcome in children who undergo reoperation for failed epilepsy surgery have not been well documented. This retrospective study evaluated 20 children who underwent a second resective surgery for recurrent seizures. Four categories of patients were identified: (1) extension of the initial resection was performed in 8 patients; (2) 5 patients underwent lobectomy or corticectomy in a region remote from the original surgical site; (3) multilobar resection which may have included further resection of the initial procedure was accomplished in 4 patients; (4) hemispherectomy was performed in 3 patients. Patients with reoperation in the same lobe as the first procedure (group 1) had a 62% seizure-free rate, while 44% of patients in groups 2 and 3 were free from seizures at follow-up evaluation. Patients undergoing hemispherectomy had a 67% seizure-free rate. Significant unexpected neurological deficits occurred in 3 patients who underwent multilobar resection at reoperation. Complications included motor and language deficits. Reoperation for intractable partial epilepsy is beneficial in selected children. Patients who require multilobar resections may have higher risk of postoperative neurological deficit than those patients with reoperation in one lobe. These factors may be useful in counseling parents of children considering reoperation for recurrent epilepsy.

Adolescent↗

PubMed1997

[Neuropathology of refractory epilepsy in children].

INTRODUCTION AND OBJECTIVES: The pathological findings in surgical material from children with refractory epilepsy has not offered yet a clear understanding of its role in this condition. The objective of this paper is to report our findings to further expand our knowledge about refractory epilepsy in children. MATERIAL AND METHODS: Results of microscopic examination of the surgical specimen obtained from 80 children, ages 12 or younger, who had surgery for intractable epilepsy at Miami Children's Hospital between 1990 and 1996 were reviewed. RESULTS: Examination was normal only in one. The rest revealed ectopic neurons (1), dysplastic cells with ectopic neurons (2), dyslamination with large neurons (7), dyslamination with ectopic neurons (18), dyslamination with dysplastic cells (10), pachygyria (2), encephalomalacia (9), gliosis with ectopic neurons (10), gliosis without ectopic neurons (3), developmental ectodermal tumor (6), ganglioglioma (2), tumors (3), and Rasmussen encephalitis (4). Lesions were located to the temporal lobe in 34 children. CONCLUSIONS. Extratemporal lesions are more frequent than temporal one, including hyppocampal sclerosis. Ectopic neurons, the most frequent pathological findings, rather than a cause of seizure may be a marker other highly epileptogenic cortical malformations.

Brain↗

PubMed1997

Clinical characteristics of peanut allergy.

BACKGROUND: Current clinical advice regarding peanut allergy is based on small series of patients. OBJECTIVE: To determine, in a large group of peanut allergic subjects, the patterns of clinical severity, symptom progression and availability and use of rescue medications. METHODS: Questionnaire study of 622 self-reported allergic subjects. RESULTS: A total of 406 patients (66%) reported symptoms on contact with peanut. Only 121 (19%) had been knowingly exposed to peanut before the first documented reaction, implying a high frequency of occult sensitization. Severe symptoms were more common in adults. Abdominal symptoms were significantly associated with collapse. Fifty per cent reported reactions in the previous year. Only 82 (13%) had been admitted to hospital because of a reaction. Adrenaline was carried in some form by 65% though only 78 subjects (12.5%) had ever received injected adrenaline. Only 18/43 subjects (41%) who collapsed were given adrenaline. Skin-prick test weal size correlated weakly with severity but there were large overlaps between the groups. Peanut-specific IgE peaked in the teenage group, but did not correlate with severity. CONCLUSIONS: Peanut allergy is characterized by more severe symptoms than other food allergies and by high rates of symptoms on minimal contact. Skin-prick testing and peanut-specific IgE levels do not predict clinical severity. Avoidance of peanut is difficult. Many people suffering severe relations are inadequately treated. Sufferers need education and training in the use of rescue medication.

Adolescent↗

PubMed1997

Alternative & complementary therapies: focus on epilepsy.

Many patients continue to search for ways to gain better control of their seizures and improve the quality of their lives. While nontraditional therapies are used by many, a clearer understanding of the benefits and risks of each therapeutic option is needed. Appropriately utilized, complementary therapies can play an integral part in patient-centered comprehensive epilepsy care.

Attitude to Health↗

PubMed1996

Language cortex representation: effects of developmental versus acquired pathology.

Relatively little is known about language cortex representation in patients with developmental pathology and epilepsy. We report the results of mapping language by electrical stimulation of chronically implanted subdural electrodes in 34 patients (mean age, 12.2 years) evaluated for epilepsy surgery, 28 of whom had magnetic resonance imaging or histological evidence of developmental tumors or cortical dysplasia. Language cortex was identified in the temporal or frontal lobe of 19 patients (left hemisphere in 17, right hemisphere in 2), and overlapped or bordered the epileptogenic region in 12. Language cortex was not found in the frontal or temporal lobe of 15 patients (left hemisphere in 4, right hemisphere in 11) and was presumed to be contralateral to grid placement. Three patients with left-hemisphere perinatal or postnatal cerebral insults before the age of 5 years had no language in the left hemisphere, while 3 patients with insults between the ages of 6 and 16 years had preserved left-hemisphere language. Developmental lesions and early-onset seizures do not displace language cortex from prenatally determined sites, whereas lesions acquired before the age of 5 years may cause language to relocate to the opposite hemisphere, but only when language cortex is destroyed.

Adolescent↗

PubMed1996

Differential expression of fos-like immunoreactivity in the descending projections of superior colliculus after electrical stimulation in the rat.

In rodent, there is evidence that the orienting behaviour elicited by direct stimulation of the superior colliculus (SC) is partly mediated by contralateral descending projections, while avoidance-type behaviour is associated with ipsilateral descending projections. However, the identity of target structures in the brainstem which mediate these different behavioural responses is unknown. The c-fos immediate early gene is expressed polysynaptically in neurons in response to a wide range of extracellular stimuli, and hence has been proposed as a technique for mapping functional pathways. The purpose of this study was, therefore, to use the c-fos technique to investigate the functional specificity of brainstem regions which are innervated by the two main descending projections of the SC. Patterns of fos-like immunoreactivity (FLI) were observed throughout the brainstem following electrical stimulation of the SC in Urethane-anaesthetized rats. Previously, the electrical stimulation had been shown to elicit either approach-like or avoidance-like movement. The main results of this experiment were; (i) animals in which the stimulation elicited defensive behaviour had elevated levels of immunostaining in specific terminal areas of the ipsilateral descending projections, e.g. the ventrolateral midbrain/pontine reticular formation, the cuneiform area and rostral periaqueductal grey; (ii) there was no FLI expression in any of the terminal areas of the crossed descending projection, even in animals where the electrical stimulation elicited approach. Control experiments showed that the lack of expression in the crossed descending pathway was not due to the restricted range of stimulation parameters used in the main study, or to the effects of the anaesthetic. In conclusion, this experiment was able to identify likely substrates for the mediation of defensive reactions elicited by tectal stimulation. However, given the total lack of expression in a pathway which is known to be activated, it also provides further evidence that c-fos cannot simply be used as a high resolution neuronal activity marker for mapping functional pathways.

Animals↗

PubMed1996

Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability.

We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.

Adolescent↗

PubMed1996

Regional distribution of the anticonvulsant and behavioural effects of muscimol injected into the substantia nigra of rats.

Previous anatomical investigations have reported a direct projection from substantia nigra pars lateralis to the dorsal midbrain anticonvulsant zone. The present study tested the hypothesis that the anticonvulsant properties of nigral inhibition previously attributed to substantia nigra pars reticulata were, in fact, due to the suppression of neural activity in the adjacent pars lateralis. Using the electroshock model of epilepsy, a systematic map of the anticonvulsant effects of bilateral injections of muscimol (60 ng/0.5 mu l per side) into different parts of substantia nigra was constructed. Electroshock (1 s of 40 mA 50 Hz AC) was administered via ear-clip electrodes 5 or 60 min following injections of muscimol, or 60 min after control injections of saline. To provide insight into the functional mechanisms whereby nigral inhibition might suppress tonic seizures the behavioural effects elicited by muscimol were also noted. No evidence supporting the experimental prediction was found. The most sensitive region of substantia nigra for suppressing tonic hindlimb extension was caudal pars reticulata. These data indicate a serious mismatch between the results of microinjection mapping studies and underlying patterns of anatomical connectivity. The behavioural reaction most closely associated with tonic seizure suppression was stereotyped locomotion; both were obtained maximally from caudal pars reticulata. Rostral substantia nigra was associated more with oral stereotypy, while a raised head position was observed at lateral injection sites and a lowered positioning of the head at medial locations. These data suggest that the rat substantia nigra may contain a functional organization based on a form of somatomotor topography. This organization may influence which part of the substantia nigra is most effective in suppressing seizures expressed by different muscle groups of the body.

Animals↗

PubMed1996

Motor unit recruitment in a distributed model of extraocular muscle.

1. Eye position commands frequently are treated as a lumped, single-valued variable that is related linearly to eye position. As a step toward investigating how system-level linearity might be achieved despite nonlinear components, a distributed model of motor units in the abducens nucleus and lateral rectus muscle was constructed. 2. Parameters in the model were estimated using data from three main sources: measurement of length-tension curves for eye muscle in people, electrophysiological recording of ocular motoneuron properties in monkeys, and investigations of oculomotor unit properties in cat. Units (n = 100) in the distributed model were assigned equal strengths and for a given fixation command, the force developed by each unit was calculated, and the sum of unit forces compared with the active force in the entire muscle as measured experimentally. 3. The properties of the active units then were adjusted to reduce the size of any resultant error in a manner related to gradient descent methods for neural-net training. Distributed models were "trained" in this fashion for a series of eye positions drawn at random from the oculomotor range until performance stabilized. The goal of the training procedure was to obtain a good match between the output of the model and the experimental data on muscle force as a function of eye position. 4. Plots of trained motor-unit strength against ocular motoneuron threshold revealed a U-shaped pattern with the strongest units being recruited at both extremes of the oculomotor range and the weakest units recruited in the middle. The pattern remained unaltered qualitatively over a range of assumptions about the distribution of ocular motoneuron parameters and the relation between motoneuron firing rate and unit force. 5. The right-hand limb of the U-shaped pattern is similar to that observed in spinal motoneurons, where stronger units tend to have higher recruitment thresholds. The left-hand limb may reflect the two specializations of eye muscle: the functional need for very precise control of eye position in the middle of the oculomotor range and the use of multiply innervated muscle fibers to provide ripple-free control of eye position at low firing frequencies.

Abducens Nerve↗

PubMed1996

Preoperative clinical, EEG, and imaging findings do not predict seizure outcome following temporal lobectomy in childhood.

Although certain clinical, electroencephalographic (EEG), magnetic resonance imaging (MRI), and pathologic findings in adults with intractable temporal lobe epilepsy predict seizure outcome following temporal lobectomy, predictors of seizure outcome have not been studied systematically in pediatric temporal lobectomy series. We retrospectively analyzed preoperative clinical, EEG, and neuroimaging findings with reference to seizure outcome (seizure free or non-seizure free) in 33 children (mean age, 9.3 years) who underwent tailored temporal lobe resections for intractable temporal lobe epilepsy. Trends were apparent with (1) younger age at seizure onset, younger age at surgery, shorter duration of epilepsy, localized unilateral temporal lesions on MRI, and right-sided surgery more frequently associated with a seizure-free outcome, and (2) significant prior history, daily preoperative seizures, generalized motor seizures, mental retardation, and localized unilateral temporal epileptiform EEG activity more frequently associated with a non-seizure-free outcome. However, none of these findings, alone or in combination, correlated with postoperative seizure status at a statistically significant level. Submitting the four variables generally considered to be most predictive of favorable outcome (ie, normal intelligence, unilateral ictal and interictal EEG discharges, and focal temporal MRI lesion) to a multiple-cutoff procedure did not predict seizure freedom. Our data indicate that predictors of outcome of temporal lobectomy in adults may not apply in children, perhaps due to inherent neurobiologic differences in the etiology and expression of temporal lobe epilepsy, and should therefore not be used as sole determinants of surgical candidacy in children.

Adolescent↗

PubMed1996

Adolescent psychosocial issues in epilepsy.

Adolescence is a period of profound biological, emotional, intellectual, and social transformation unmatched, perhaps, by any other period of life. Ideally, the individual emerges from this period with a positive self-image, a strong sense of identity, and the capacity for intimacy with peers and independence from the family (McAnarney, 1985). The adolescent with epilepsy is confronted with the additional task of adjusting to a chronic seizure condition. Epilepsy leads to problems when it interferes with the completion of developmental tasks at the proper time.

Activities of Daily Living↗

PubMed1995

Time estimation deficits in developmental dyslexia: evidence of cerebellar involvement.

In addition to their language-related difficulties, dyslexic children suffer problems in motor skill, balance, automatization and speeded performance. Given the recent evidence for cerebellar involvement in the acquisition of language fluency, these problems suggest cerebellar deficit. To test the hypothesis of cerebellar dysfunction in dyslexia, a time estimation task considered to be a sensitive index of cerebellar function was administered to matched groups of dyslexic and control children. The dyslexic children showed the predicted deficit on time estimation (among the most severe obtained in our research programme) but not on a control, loudness estimation, task. Cerebellar dysfunction, therefore, provides a parsimonious account of otherwise disparate data on deficits in dyslexia.

Acoustic Stimulation↗