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Biomedical subjects

W J Peacock

Publications and source records attributed to W J Peacock.

At least 19 recordsLinked to original sources
PubMed1992

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy.

Despite the use of hemispherectomy in the treatment of medically refractory seizures since the early 1950's, few studies published have documented neuropathologic findings in the resected specimens. This report describes the neuropathologic findings in 38 children who underwent either hemispherectomy or multilobar cortical resection as treatment for medically intractable epilepsy between 1986 and 1990. Examination of the resected specimens revealed a variety of abnormalities which fell into four broad categories. Malformations or hamartomatous lesions were the dominant finding in 15 patients, whereas encephalomalacic lesions were the most prominent abnormality in 16; chronic pathogen-free encephalitits (Rasmussen's encephalitis) was present in 3 and an additional 3 children had Sturge-Weber-Dimitri syndrome. There were no gross or microscopic abnormalities in 1 patient. This report provides the first comprehensive description of the pathologic findings in a series of children with refractory epilepsy of varying types treated by hemispherectomy-multilobar resection.

Brain Ischemia↗
PubMed1992

Morphological substrates of infantile spasms: studies based on surgically resected cerebral tissue.

Extensive surgical resections of neocortical cerebral tissue (including hemispherectomies) from 13 infants and children with infantile spasms showed that 12 of 13 specimens contained either malformative and dysplastic lesions of the cortex and white matter (sometimes with associated hamartomatous proliferation of globular cells), or destructive lesions possibly acquired as a result of anoxic-ischemic injury, or a combination of the two. In brain tissue from 4 patients, coarse neuronal cytoplasmic fibrils resembling neurofibrillary tangles were seen in areas of dysplastic brain on silver-stained (Bielschowsky technique) sections. Immunohistochemical (immunoperoxidase) study of cortical lesions containing globular cells employing primary antibodies to glial fibrillary acidic protein and synaptophysin as markers of astrocytic and neuronal differentiation, respectively, revealed that many cells showed astrocytic and/or neuronal features, suggesting the local proliferation of primitive or multipotential neuroectodermal cells as one substrate for this seizure disorder. Morphological abnormalities of a severe degree and wide extent in the resected tissue (e.g., in one patient with hemimegalencephaly) often showed features to suggest that they may represent variants of tuberous sclerosis. These most likely result from abnormal movement and/or local proliferation of neuroectodermal precursors that have migrated from the germinal matrix to the cortical mantle. Cellular, molecular and neurophysiological study of these abnormalities is likely to yield information about basic molecular mechanisms of brain malformation and injury important in the pathogenesis of infantile spasms and other forms of focal or generalized epilepsy.

Cerebral Cortex↗
PubMed1992

Non-verbal communication skills of surgically treated children with infantile spasms.

The authors present preliminary findings on the effects of surgery on the development of early non-verbal social communication skills in eight children with intractable infantile spasms. After a mean follow-up of 15.2 months, there was no statistically significant change in the post-surgical non-verbal communication behavior of these children beyond the expected developmental change. Implications of these findings for the developmental impairment associated with infantile spasms are discussed.

Cerebral Cortex↗
PubMed1992

Treatment of infantile spasms: medical or surgical?

Although infantile spasms were initially described in 1841, remarkably little progress has been made in understanding the pathophysiology of this "peculiar form of infantile convulsions." Consequently, our ability to treat infantile spasms is limited. Infantile spasms are classified as a "generalized" seizure disorder in the international classification system, which suggests that the underlying brain abnormality causing the seizures also must be diffuse or generalized. As the classification suggests, there are many diffuse, or multifocal, brain disorders related to infantile spasms, e.g., inborn errors of metabolism, hypoxic-ischemic brain injury, and developmental brain defects such as tuberous sclerosis or Aicardi's syndrome. On the other hand, infantile spasms have been reported in which a localized brain abnormality was present, e.g., tumor, stroke, and trauma. On rare occasions, removal of a tumor has resulted in cessation of the generalized infantile spasms. This finding suggests that focal cortical abnormalities can cause infantile spasms and that removing the abnormality can stop the seizures. At University of California, Los Angeles, the Pediatric Epilepsy Surgery Program has developed new approaches to the treatment of infantile spasms. The principal underlying concepts are (a) children with medically refractory infantile spasms may have an area of cortical defect (called the zone of cortical abnormality) that causes the seizures and (b) infantile spasms are usually generalized seizures. Thus, the goal of the surgical assessment is not the identification of the focus of seizure onset but rather the identification of the zone of cortical abnormality.

Adrenocorticotropic Hormone↗
PubMed1992

Single-electrode voltage-clamp analysis of the N-methyl-D-aspartate component of synaptic responses in neocortical slices from children with intractable epilepsy.

1. Synaptic transmission mediated by the N-methyl-D-aspartate (NMDA)-receptor type was studied in neocortex from children undergoing surgical treatment for intractable epilepsy. Intracellular recordings from pyramidal cells were obtained in slices of neocortical tissue by use of microelectrodes. Synaptic responses were induced by electrical stimulation and studied with current-clamp and single-electrode voltage-clamp techniques. The NMDA-receptor-mediated component of the synaptic responses was isolated by addition of 10 microM bicuculline and 30 microM 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) in the perfusion solution. 2. In the presence of bicuculline and CNQX, electrical stimulation evoked an excitatory postsynaptic potential (EPSP) in every recorded cell. The amplitude of this EPSP increased when membrane potential was depolarized with injected current. 3. All cells studied in voltage clamp were recorded with microelectrodes containing Cs+ and QX 314. To avoid contamination of the responses from voltage-dependent Ca2+ conductances, membrane potential was held at depolarized potentials until Ca2+ spiking inactivated completely. The evoked excitatory postsynaptic currents (EPSCs) measured at resting membrane potential ranged from 100 to 400 pA. The NMDA receptor-selective antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5) reversibly decreased the current amplitude by 60% for 10 microM and 80% for 30 microM. 4. The current-voltage (I-V) relation showed a region of negative slope conductance between -100 and -20 mV. The largest currents (-250 to -900 pA) were recorded in the range of -45 to -20 mV and reversed between -10 and +10 mV. Removing Mg2+ from the perfusion solution decreased the negativity of the slope, which is consistent with a reduction in the voltage-dependent Mg2+ block of the NMDA-receptor channel. 5. The I-V plots obtained from cells recorded in the most abnormal tissue were averaged and compared with those from the least abnormal tissue. No significant difference was found between these two groups. The averaged plots from the youngest patients (8 and 10 mo old) and those from the oldest (5-15 yr old) patients were also compared, and the results from these two groups were not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Local synaptic circuits and epileptiform activity in slices of neocortex from children with intractable epilepsy.

1. Single and dual intracellular recordings were performed in neocortical slices obtained from tissue samples surgically removed from children (8 mo to 15 yr) for the treatment of intractable epilepsy. Electrical stimulation and glutamate microapplication were used to study local synaptic inputs to pyramidal cells. 2. In recordings with potassium-acetate electrodes, activation of presynaptic neocortical neurons with glutamate microdrops did not elicit a clear increase in postsynaptic potentials (PSPs) but did suppress current-evoked repetitive spike firing in recorded neurons. Bicuculline (10 microM) blocked this effect, suggesting it was caused by the activation of presynaptic gamma-aminobutyric acid (GABA) cells. In recordings with KCl electrodes, glutamate microdrops elicited an increase in the frequency and amplitude of depolarizing PSPs. Bicuculline (5-10 microM) blocked the glutamate-evoked PSPs, suggesting they were reversed GABAA-receptor-mediated inhibitory postsynaptic potentials (IPSPs). In one cell recorded with a KCl electrode (total n = 8), current-evoked spike trains elicited afterdischarges of reversed IPSPs, thus revealing a recurrent inhibitory circuit. Therefore local inhibitory synaptic circuits were robust and could be observed in tissue from patients as young as 11 mo. 3. In addition to short-latency (10-25 ms), monosynaptic excitatory postsynaptic potentials (EPSPs), electrical stimulation at low intensities sometimes elicited delayed EPSPs (20-60 ms). When GABAA-receptor-mediated synaptic inhibition was partially reduced in bicuculline (5-10 microM), electrical stimulation evoked large EPSPs at long and variable latencies (100-300 ms). Glutamate microapplication caused an increase in the frequency and amplitude of EPSPs; preliminary results suggest that glutamate microdrops were less likely to evoke EPSPs in tissue from younger patients (8-12 mo) than in slices from patients greater than 4 yr. Evidence for local excitatory synaptic circuits was thus found when synaptic inhibition was partially reduced. 4. After further reduction of inhibition in bicuculline (5-50 microM), electrical stimulation elicited epileptiform bursts. In pairs of simultaneously recorded neurons, bursts were generated synchronously from long-latency EPSPs (100-300 ms) in slices from patients as young as 8 mo. Reflected EPSPs at very long and variable latencies (500-1,100 ms) and repetitive epileptiform bursts could be evoked synchronously in pairs of cells. Glutamate activation of local presynaptic neurons elicited robust epileptiform events in recorded cells. This was seen in slices from patients as young as 16 mo. 5. These data provide physiological evidence for the presence of local inhibitory and excitatory synaptic circuits in human neocortex at least as early as 11 and 8 mo, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Temporal and extended temporal resections for the treatment of intractable seizures in early childhood.

In our series of 33 children who underwent temporal and extended temporal lobe resections because of seizures, the average age at surgery was 7 years, 11 months. Sixteen cases (48%) were diagnosed as having tumors: low-grade astrocytoma (6), hamartoma (5), and ganglioglioma/neuroma (5). Other pathologic diagnoses included one or more cytoarchitectural abnormalities and/or reactive changes. Due to a more aggressive and early radiologic and electrophysiologic investigation of children with seizures, a resectable focus, e.g. neoplasm or structural abnormality, was found in a much younger age group of patients than previously reported. In children who had intractable seizures but normal radiologic studies, positron emission tomography was of great value in localizing the seizure focus. In a group of children with infantile spasms, seizures were controlled following the identification and resection of a focal lesion. Prompt detection and precise localization of lesions in the temporal lobe in the pediatric population may lead to surgical management and seizure control.

Adolescent↗
PubMed1992

Intractable seizures, compulsions, and coprolalia: a pediatric case study.

A 10-year-old girl with intractable complex partial seizures developed aphasia, coprolalia, and repetitive motor behaviors involving touching, sexual touching, and aggressive acts. Her symptoms subsided following surgical resection of a left anterior temporal lobe ganglioglioma and control of seizures. Possible neurobehavioral implications of the reversibility of this patient's symptoms are discussed.

Brain Neoplasms↗
PubMed1991

Advancement-onlay: an improved technique of fronto-orbital remodeling in craniosynostosis.

Eighteen patients with nonsyndromic craniosynostosis underwent fronto-orbital remodeling with an advancement-onlay technique. The mean age of the infants was 5 months (range = 2-11 months) when the procedure was performed for the following indications: unilateral coronal synostosis (n = 10); bilateral coronal synostosis (n = 3); metopic synostosis (n = 2); and multiple craniosynostoses (n = 3). The technique consists of (1) unilateral or bifrontal craniotomy, (2) superior orbital rim recontouring and advancement, and (3) frontal bone graft rotation and onlay. Posteriorly, the frontal bone graft is left "floating," while anteriorly, rigid fixation with microplates and screws has supplanted wire osteosynthesis. The use of rigid fixation prevents uncontrolled "float" of the forehead and eliminates the need for temporal struts. Follow-up time ranged from 6 to 60 months (mean = 2.6 years). There were no serious postoperative complications. Surgical results were good to excellent in 94% of cases and poor to fair in 6%. Only 1 patient with a Kleeblattschädel deformity required major revision, while another patient with trigonocephaly underwent a minor, extracranial recontouring procedure. Supraorbital rim and/or forehead recession suggestive of relapse or initial inadequacy of anterior projection occurred in 3 patients (17%). Residual, mild contour abnormalities of the forehead and/or temporal regions were found in 5 cases. To date, no gross disturbances in craniofacial growth related to our method of rigid fixation have been observed and no clinically detectable resynostosis has occurred.

Craniosynostoses↗
PubMed1991

The anaerobic responsive element contains two GC-rich sequences essential for binding a nuclear protein and hypoxic activation of the maize Adh1 promoter.

We have identified a protein (GCBP-1) in nuclear extracts from maize suspension cell cultures that binds to specific sequences within the Anaerobic Responsive Element (ARE) of the maize Adh1 promoter. Competition analyses show that the GCBP-1 binding activity distinguishes ARE sequence motifs from other enhancer elements or pUC19 sequences. The binding activities of several mutant ARE sequences define two regions of the ARE important for GCBP-1 binding in vitro, between nucleotides -135 to -131 and nucleotides -120 to -112 of the maize Adh1 promoter. Both regions are required for efficient GCBP-1 binding to occur in vitro. The minimum consensus binding site for GCBP-1 is 5'-GC(G/C)CC-3'. This sequence is similar to a part of the binding site of the human transcription factor Sp1 (1). We demonstrate that maize GCBP-1 and human Sp1 have similar recognition properties. Using ARE mutants in a transient assay in maize protoplasts we have shown that mutation of the GCBP-1 binding sites prevents significant hypoxic activation of the maize Adh1 promoter. These results suggest a direct role for GCBP-1 in the hypoxic activation of Adh1 gene expression. GCBP-1 is present in both uninduced and induced nuclei, indicating that inducible gene expression is not dependent upon synthesis of GCBP-1 and suggesting that post-translational modification of bound GCBP-1 may be important for enhanced transcription to occur.

Alcohol Dehydrogenase↗
PubMed1991

Cerebral palsy and rhizotomy. A 3-year follow-up evaluation with gait analysis.

A recent increase in the popularity of selective rhizotomy for reduction of spasticity in cerebral palsy has led to a demand for more objective studies of outcome and long-term follow-up results. The authors present the results of gait analysis on 14 children with spastic cerebral palsy, who underwent selective posterior rhizotomy in 1985. Sagittal plane gait patterns were studied before surgery and at 1 and 3 years after surgery using a digital camera system. The parameters measured included the range of motion at the knee and thigh, stride length, speed of walking, and cadence. The range of motion at the knee was significantly increased at 1 year after surgery and further improved to a nearly normal range at 3 years after surgery. In contrast, postoperative measurements of thigh range exceeded normal values at 1 year, but decreased toward normal range at 3 years. While improvements in range of motion continued between Years 1 and 3, the children developed a more extended thigh and knee position, which indicated a more upright walking posture. Stride length and speed of walking also improved, while cadence remained essentially unchanged. This 3-year follow-up study, the first to examine rhizotomy using an objective approach, has provided some encouraging results regarding early functional outcome.

Adolescent↗
PubMed1991

Functional outcomes following selective posterior rhizotomy in children with cerebral palsy.

The recent increase in popularity of selective posterior rhizotomy demands objective documentation of surgical outcome. For this reason, the authors have analyzed the status of 25 children with spastic cerebral palsy before and after rhizotomy to determine the effects of this therapy on muscle tone, range of movement, and motor function. Postoperative tests showed a reduction in muscle tone compared with preoperative assessments. Range of motion in the lower extremities was significantly increased and improvements in functional gross motor skills were noted. An increase in range of motion in the knees and thighs during gait was detected in 18 ambulatory patients studied with computerized two-dimensional motion analysis. Preliminary findings indicate that selective posterior rhizotomy reduced spasticity, thereby increasing range of motion and contributing to improvements in active functional mobility.

Cerebral Palsy↗
PubMed1990

Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment.

Positron emission tomography (PET) of local cerebral glucose metabolism in 13 children with infantile spasms of undetermined cause (cryptogenic spasms) revealed unilateral hypometabolism involving the parieto-occipito-temporal region in 5 female infants. Cranial computed tomography showed normal findings in all infants. Magnetic resonance imaging (MRI) demonstrated a normal appearance in 4 of the 5 infants; in 1 infant, MRI revealed a subtle abnormality consisting of poor demarcation between occipital gray and white matter. Surface electroencephalography (EEG) in 4 showed hypsarrythmia at some time in the patients' courses, but at other times showed localized or lateralized abnormalities corresponding to areas of PET-detected hypometabolism. Because of poor seizure control, 4 infants underwent surgical removal of the cortical focus guided by intraoperative electrocorticography and were seizure free postoperatively. Neuropathological examination of resected tissue in each showed microscopic cortical dysplasia. Our findings indicate that in infants with cryptogenic spasms, PET can effectively identify those due to unsuspected focal cortical dysplasia, for which resective surgery offers improved prognosis.

Cerebral Cortex↗
PubMed1990

Synaptic transmission in human neocortex removed for treatment of intractable epilepsy in children.

Synaptic transmission to pyramidal cells was studied in slices of neocortex resected from infants and children (n = 10, age 8 months to 13 years) undergoing surgical treatment for intractable epilepsy. Most specimens were from the least abnormal area of the resection. Stable intracellular recordings could be obtained for up to 8 hours. Most of the recorded neurons had electrophysiological characteristics similar to those of regular-firing pyramidal cells and were in layers III to V, which was confirmed by intracellular staining with Lucifer yellow. Local extracellular stimulation evoked a sequence of excitatory and inhibitory postsynaptic potentials. After application of the gamma-aminobutyric acid antagonist, bicuculline (10-30 microM), extracellular stimulation induced large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous bursts occasionally occurred in bicuculline. This effect of bicuculline was observed in all the tissue samples, even those from infant patients (n = 4, age 8-16 months). Kynurenic acid depressed or abolished both spontaneous and stimulation-induced bursts. The competitive antagonist for N-methyl-D-aspartate receptors, DL-2-amino-5-phosphonopentanoic acid decreased the duration of bicuculline-induced bursts. These data provide evidence that, similar to rat and cat neocortex, excitatory and inhibitory amino acids are important transmitters to pyramidal cells in immature human neocortex.

2-Amino-5-phosphonovalerate↗
PubMed1990

Functional properties of the anaerobic responsive element of the maize Adh1 gene.

The functional properties of the anaerobic responsive element (ARE) of the maize Adh1 gene have been analysed using a transient expression assay in electroporated maize protoplasts. The ARE functions in both orientations although inversion of the ARE sequence relative to the TATA box element produces slightly weaker promoter activity under anaerobic conditions and elevated expression under aerobic conditions. Promoter activity under anaerobic conditions is proportional to the number of complete ARE sequences in the Adh1 promoter. The ARE contains two sub-regions and dimers of sub-region II are as efficient as the wild-type sequence in activating gene expression under anaerobic conditions. However, sub-region I dimers do not appear capable of inducing gene expression in response to anaerobic stress. We conclude that sub-region II is essential for anaerobic induction of gene expression. Reporter gene expression remains constant when the spacing between sub-regions of the ARE is increased up to at least 64 bp, but increased spacing of 136 bp or greater abolishes expression in both aerobic and anaerobic conditions, indicating that a close association of the two sub-regions is required both for anaerobic responsiveness and for maximal levels of aerobic gene expression. When the ARE is placed upstream of position -90 of the CaMV 35S promoter, the ARE produces a high level of expression in both aerobic and anaerobic conditions. The general enhancement of gene expression driven by the hybrid ARE/35S promoter in aerobic conditions requires an intact sub-region II motif since mutation or deletion of sub-region II from the hybrid promoter reduces the level of expression to that observed for the truncated 35S promoter alone. In addition, mutation of the sub-region I sequences in the ARE/35S hybrid promoter does not significantly reduce expression in aerobic conditions, relative to pARE/delta 35S(-90), suggesting that sub-region I does not contribute to this general enhancer function.

Alcohol Dehydrogenase↗
PubMed1990

Incidence of spinal deformity in children after multiple level laminectomy for selective posterior rhizotomy.

Fifty-five children with cerebral palsy had multiple-level laminectomies for selective posterior rhizotomies for the relief of spasticity. They were followed up clinically and radiologically to assess their spinal stability and the possible development of post-laminectomy deformity of the spine. The majority of the deformities found were related to cerebral palsy and did not appear to be due to the laminectomy: 16% had scoliosis, 5% kyphosis, 7% lordosis, and 9% spondylolysis/spondylolisthesis. Spondylolysis is the only abnormality that appeared to be more common in this group than in children with cerebral palsy.

Adolescent↗
PubMed1990

A DNA-binding protein factor recognizes two binding domains within the octopine synthase enhancer element.

A protein that binds to the enhancing element of the octopine synthase gene has been identified in nuclear extracts from maize cell suspension cultures. Two protein-DNA complexes are distinguishable by electrophoretic mobility in gel retardation assays. Footprint analyses of these low and high molecular weight complexes show, respectively, half and complete protection of the ocs-element DNA from cleavage by methidiumpropyl-EDTA.FE(II). Two lines of evidence indicate that the element has two recognition sites, each of which can bind identical protein units. Elements that are mutated in one or the other half and form only the low molecular weight complex interfere with the formation of both the low and high molecular weight complexes by the wild-type element. Protein isolated from a complex with only one binding site occupied can bind to the wild-type ocs-element and generate complexes with protein occupying one or both binding sites. Occupation of both sites of the ocs-element is a prerequisite for transcriptional enhancement.

Amino Acid Oxidoreductases↗