Intrathoracic meningocele associated with neurofibromatosis: case report

The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy.     

Motor map expansion following repeated cortical and limbic seizures is related to synaptic potentiation.

The effect of experimentally induced seizure activity on the functional reorganization of motor maps has not previously been investigated. Furthermore, while the functional reorganization of motor maps has been thought to involve increases in synaptic communication, there has yet to be a test of this hypothesis. Here we show that repeated seizure activity (kindling), that is accompanied by increased synaptic strength within adult rat motor cortex, results in a doubling of the caudal forelimb motor area. We measured neo-cortical evoked potentials in the right hemisphere prior to 25 days of electrical kindling of the medial frontal corpus callosum or amygdala and re-measured them either 1 or 21 days following the last kindling session. Then, using high resolution intracortical microstimulation (ICMS), the caudal forelimb area in the left hemisphere was mapped. This is the first report of any procedure causing a motor representation to double in size. Furthermore, this expansion was related to the enhanced area of a neocortical polysynaptic field potential and not the motor convulsions per se. Moreover, both the motor map and field potential enhancements were persistent in nature and could be driven from either cortical or limbic sites. The data have implications for human populations with epilepsy.     

Conventional anticonvulsant drugs in the guinea pig kindling model of partial seizures: effects of acute phenobarbital,valproate, and ethosuximide

This study addressed the anticonvulsant effects of phenobarbital, valproate, and ethosuximide in the amygdala of kindled guinea pigs to further validate this model for the screening of anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using quantitative locomotor tests, as well as scores on a sedation and muscle relaxation rating index. The anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioral seizure severity (SS) during early and late phases of kindling acquisition, and in kindled guinea pigs. ADD and SS were also measured in response to both threshold and suprathreshold kindling stimulation. All drugs exerted slight to moderate sedative effects in guinea pigs on both the behavioral tests and rating index. We found that phenobarbital exhibited effective anticonvulsant properties in guinea pigs by consistently reducing ADD and SS in response to both threshold and suprathreshold kindling stimulation. Valproate exhibited effective anticonvulsant properties at threshold stimulation and less effective properties at suprathreshold stimulation. Lastly, we found that ethosuximide lacked effective anticonvulsant action at either threshold or suprathreshold kindling stimulation. Our results indicate that the guinea pig kindling model correctly predicted the actions of phenobarbital, valproate, and ethosuximide in the treatment of partial seizures. Guinea pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.     

Sensory stimulation reduces seizure severity but not afterdischarge duration of partial seizures kindled in the hippocampus at threshold intensities

Epilepsy is a family of neurological disorders that result in seizure activity that is characterized by transient hypersynchronous activation of a large population of neurons. In animal models, focal tetanic electrical stimulation of sufficient duration and intensity, can elicit epileptiform activity, that if repeated results in progressive intensification of seizure activity known as kindling. Kindling serves as a model of partial as well as secondarily generalized temporal lobe epilepsy. We utilized hippocampal kindling to provide a means of evaluating the effect of sensory stimulation on the duration and severity of the induced seizure activity. Sensory stimuli targeted either the olfactory, auditory or somatosensory systems in an attempt to retard or suppress seizure activity. To that end, rats were chronically implanted with electrodes in the CA1 region of dorsal hippocampus and kindled once daily until the seizure behaviour was fully generalized. Kindling stimulation consisted of daily application of 1-s trains of biphasic square wave pulses applied at a frequency of 60Hz, at the afterdischarge (AD) threshold. Sensory stimulation was applied 6-8s after the kindling stimulation every third day. One group of rats received a different sensory stimulus (novel) every third day, while another group was presented with the same sensory stimulus (repeated) every third day. Kindling stimulation applied to the dorsal hippocampus resulted in progression of the AD characteristics and seizure behavior, which typically developed very slowly in the early stages. The application of both the novel and repeated sensory stimulation during partial seizures (stages 1 and 2) resulted in a reduction in the seizure severity but not in the afterdischarge duration. Sensory stimulation delivered during secondarily generalized seizures (stages 4 and 5) failed to affect either parameter.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Modifications of social conflict-induced analgesic and activity responses in male mice receiving chronic opioid agonist and antagonist treatments.

This study examined the effects of chronic (7 day) administrations of opioid agonists, via osmotic minipumps (20 micrograms/microliters/h, or 2 mg/kg/h for each agent) on: 1) nociception and activity, and 2) the analgesic and locomotor responses of subordinate male mice experiencing social conflict (aggression without defeat) and defeat in a "resident-intruder" paradigm. Chronic infusion of the mu opioid antagonist, naltrexone, resulted in a hypoanalgesic response and a decrease in basal locomotor activity on days 3-7 postimplantation which returned to the basal levels of saline-implanted control mice after termination of the infusions on day 9. Naltrexone reduced defeat-induced analgesia on the second day after implantation, but had no consistent effects on analgesia on test days 6 and 9 or on the aggression-induced (nondefeat) analgesia and increases in activity. The delta opioid antagonist ICI-154, 129, while having no significant effects on basal nociception or locomotor activity, augmented nondefeat-induced analgesia (day 2) and reduced the defeat-induced increases in activity (days 2 and 6). The mu agonist, levorphanol, resulted in a significant analgesia on the first two days after infusion, followed by the development of tolerance to the analgesic effects over days 3-7. On day 9, a hypoanalgesic response indicative of withdrawal was evident. Levorphanol also induced a marked decrease in locomotor activity over days 3-7 postimplantation, with no evidence of the development of tolerance or withdrawal following termination of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Mossy fiber sprouting is dissociated from kindling of generalized seizures in the guinea-pig

Controversy surrounds whether aberrant mossy fiber sprouting in the hippocampus is necessary for the establishment of seizure states. We investigated the association between mossy fiber sprouting and kindling in guinea-pigs, using either single-site or alternate-site stimulation. Kindling with single-site amygdaloid stimulation did not induce significant sprouting, despite the development of partial seizures. In contrast, single-site septal and alternating amygdaloid-septal stimulation produced moderate but significant sprouting in about 60% of animals that failed to develop stage 5 generalized seizures. Since the magnitude of sprouting was similar despite striking differences in the intensity of seizures that developed, we conclude that mossy sprouting is not causally associated with seizure development.