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

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

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

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

Oxatomide for stable asthma in adults and children.

BACKGROUND: Oxatomide is a histamine H1-receptor antagonist. As an oral agent, oxatomide may be useful in managing asthma. Some guidelines recommend oxatomide for long-term prophylaxis of asthma in children. There is no clear evidence whether children or adults with asthma benefit from oxatomide. OBJECTIVES: To determine whether oxatomide alone, or in combination with other interventions, results in better disease control in people with asthma. SEARCH STRATEGY: The Collaborative Airway Group register and Collaborations trial register CENTRAL were searched using terms: oxatomide* OR Celtect OR Pinset OR KW-4354 OR Tincet. Reference lists of all relevant trials or review articles were checked. Enquiries were made of authors of included studies and relevant pharmaceutical companies. A search of 'Igaku Chuo Zasshi' and 'J-Medicine' were made using the following terms: oxatomide (also in Japanese) or Celtect (also in Japanese) or KW-4354. SELECTION CRITERIA: Studies were randomised, placebo-controlled trials and the interventions were oxatomide or matched placebo given alone or in combination with other asthma-medication for at least 4 weeks. DATA COLLECTION AND ANALYSIS: Four independent reviewers performed assessments of methodological quality and extracted relevant data. MAIN RESULTS: Six studies are included in this review. Three studies were mainly conducted in adults, two were conducted in older children (5-16 years) and one in infants (18-25 months). Trial duration was 4 to 52 weeks. Doses of oxatomide varied between studies, ranging from 1 mg/kg/day for infants to 180 mg/day for adults. Only data on adverse events was suitable for meta-analysis. Although PEF did not change significantly in any of the studies, the FVC and FEV1 improved significantly in two. There was no uniform change in symptom scores. There was no significant difference between oxatomide and placebo treatment in use of inhaled corticosteroid or bronchodilator. Two studies showed significant improvement with oxatomide as judged subjectively by physicians. Adverse events, analysed using data from 4 parallel and one cross over study, showed oxatomide to be associated with a significantly higher risk of any adverse event (OR: 2.97, 95%CI: 1.69 to 5.22) and drowsiness (OR: 5.22,95%CI: 2.53 to 10.74). REVIEWER'S CONCLUSIONS: There is no evidence to show that oxatomide has a significant effect on the control of stable asthma. Some studies reported significant benefits in subjective parameters. There was improvement in some lung function outcomes reported, but this were not consistent across measures or studies and may represent reporting bias. Adverse events, including drowsiness, were significantly greater with oxatomide than placebo.

Asymmetrical blood flow in the temporal lobe in the Charles Bonnet syndrome: serial neuroimaging study.

Clinical features and results of neuroimagings of an 86 year old woman with the Charles Bonnet syndrome are reported. She had become completely blind bilaterally due to cataracts and glaucoma. Shortly after an operation for cataracts, she developed visual hallucinations which lasted for 22 years. She had no deterioration of intelligence. Computed tomography (CT) and magnetic resonance imaging (MRI) showed moderate generalized atrophy, particularly of the temporal lobes. A serial single photon emission computed tomography (SPECT) study during visual hallucinations demonstrated hyperperfusion in the left temporal region and the basal ganglia and hypoperfusion in the right temporal region. These findings suggest that asymmetrical blood flow, particularly in the temporal regions, may be correlated with visual hallucination in the Charles Bonnet syndrome.

[Partial status epilepticus developed 41 years after psychosurgery--an electroencephalographic and neuropathological study].

The authors report an 85-year-old man with schizophrenia, who had undergone bilateral frontal gyrectomy at the age of 44 and had a single series of convulsions 6 months after the psychosurgery. Forty-one years later, he had developed partial seizures with secondary generalized seizures, and died of partial status epilepticus. Ictal EEG showed generalized high-amplitude spikes or sharp waves spreading from the left frontal region. Interictal EEG showed slowing of background activity and high-amplitude paroxysmal discharges on the left frontal and central regions. Postmortem examination of the brain revealed tissue defects in the superior and middle frontal gyri caused by resection at the time of gyrectory and old cysts in the deep frontal white matter as late sequelae of the psychosurgery. There was fibrillary gliosis in the surrounding cerebral convolutions and the deep white matter. We considered that the glial scar in the frontal lobes, on the left side in particular, had developed the epileptogenic focus. The pathophysiological mechanism by which the intractable epileptic seizures appeared 41 years after psychosurgery is discussed.

[Studies of childhood non-Hodgkin's lymphoma--treatment results with the CCLSG NHL 960 protocol. Children's Cancer and Leukemia Study Group (CCLSG)].

We report here on the preliminary treatment findings of a CCLSG NHL 960 study that was initiated in March 1996. In this study, 37 patients with non-Hodgkin's lymphoma were assigned to 4 different treatment groups according to disease stage and histology: (1) localized disease; (2) advanced disease, lymphoblastic type; (3) advanced disease, large cell type; and (4) advanced disease, Burkitt type. The first three groups received the modified protocols of the NHL 890 study. Groups 1 and 3 received COPADM induction therapy (CPM, VCR, PRD, ADR, and MTX). After achieving remission, Group 1 received only maintenance therapy consisting of alternate administration of 7 drugs, while Group 3 received additional intensification therapy with combination chemotherapy consisting of MTX and Ara-C, followed by a maintenance phase involving the administration of 9 drugs. Group 2 received COPADL induction therapy (CPM, VCR, PRD, ADR, and LASP) and consolidation/intensification therapies followed by a maintenance phase. Group 4 received short-term intensive COPADM polychemotherapy. Twelve patients with localized with localized disease (stage I-II) and 25 patients with advanced disease (stage III-IV) were enrolled in this study. Except for 2 patients in the advanced disease stages who died earlier in the course of the study, all patients remained in remission.

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

[Treatment and prognosis of children with relapsed non-Hodgkin's lymphoma--a report from CCLSG-NHL 890 Study. Children's Cancer and Leukemia Study Group (CCLSG)].

To address the issue of salvageability in relapsed children with NHL who had all received the same frontline therapy, we retrospectively studied the treatment response and the outcome of 27 children who relapsed following the CCLSG-NHL890 protocol. The reinduction rates and 3-year survival rates (mean +/- SD) were as follows: lymphoblastic lymphoma (LB, n = 9), 44% & 17 +/- 14%; leukemia lymphoma syndrome (LLS, n = 8), 25% & 0%; large cell lymphoma (LC, n = 3) 100% & 67 +/- 27%; Burkitt's lymphoma (B, n = 7) 0% & 0%. Thus, the salvageability of LC lymphoma was good, but the outcome of Burkitt's lymphoma was very poor. CCLSG-NHL960 protocol for LB lymphomas and intensive multiagent regimens for LC lymphomas produced favorable response rates, but the effect of the high-dose Ara-C regimen for Burkitt's lymphoma was not determined. The initial stages of the disease seemed to be associated with the patient outcome: the outcome of the patients in stage IV was inferior to that of patients in stages II or III. Other clinical variables, such as relapse sites, relapse time and BM rescue did not affect the patients' outcome.

Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.

We examined, for the first time, the possible association between schizophrenia and the anaplastic lymphoma kinase (ALK) gene which plays an important role in neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and Glu1529Asp) were examined, there were significant differences in genotype and allele distributions between patients and controls. Individuals homozygous for the minor allele (1491Lys-1529Asp) were more common in patients than in controls (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic variations of the ALK gene might confer susceptibility to schizophrenia.

The analgesic activity of imidazopyridine derivatives.

Analgesic and antipyretic activities of 2-(4-(2-imidazo-[1,2-a]pyridylphenyl)propionic acid (Y-9213) were studied with various experimental models. The analgesic activity of Y-9213 was found to be more potent than that of indometacin and morphine in the silver nitrate, Randall-Selitto, and phenylquinone writhing tests. Y-9213 also showed an analgesia in the tail pinch and electric stimulation test. On the warm water induced foot withdrawal reflex, Y-9213 was more effective in spinal-sectioned mice than in intact mice similarly to mephenesin and diazepam. Y-9213 was also proved to possess antipyretic activity as potent as indometacin and to be devoid of morphine-like property. Y-9213 exhibited little effect on the respiration and cardiovascular system in dogs. Y-9213 was found to be rapidly absorbed and eliminated from the blood with a half-life of about 2.5 h in rats. These findings indicate that Y-9213 may be an effective and well tolerated antipyretic and analgesic agent.

[Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice].

Effects of Y-8894 on learning and memory were studied using a radial maze task in intact and scopolamine-induced amnesic mice. The following results were obtained: 1) Repeated administration of Y-8894 (1, 2.5 and 5 mg/kg, i.p.) significantly increased the number of initial correct responses (ICR) in the training session in intact mice, facilitating the learning of the maze task. Dihydroergotoxine (5 mg/kg, i.p.) significantly facilitated the learning of this task in the initial stage of the training session, but non-specifically inhibited the performance in the late stage of training. Ca-hopantenate did not modify the learning of this task. 2) A single administration of Y-8894 (2.5 or 5 mg/kg, i.p.) showed an antagonistic effect on scopolamine (1 mg/kg, s.c.)-induced amnesic mice. Dihydroergotoxine (5 mg/kg, i.p.) and Ca-hopantenate (500 mg/kg, i.p.) also significantly antagonized the ICR-decreasing effect of scopolamine. These results suggest that Y-8894 has an ameliorative and/or facilitative effect on learning and memory in the radial maze task, and Y-8894 is more potent than dihydroergotoxine and Ca-hopantenate.

[Pharmacological studies on sufoxazine (Y-8894). (I) Effects on experimental amnesia in mice].

The effects of sufoxazine on various experimental amnesia models were studied using passive avoidance behavior in mice. Sufoxazine had no influence on learning and memory in intact mice. Sufoxazine, administered either immediately after CO2 exposure or 30 min prior to the acquisition trial, improved CO2 induced amnesia. It also improved both electroconvulsive shock (ECS) induced amnesia (administered immediately after the amnestic treatment) and scopolamine induced amnesia (administered immediately after the acquisition trial). The anti-depressant drugs, imipramine and desipramine had no ameliorative activity in any of these experimental amnesia models. These results suggest that sufoxazine improves amnesia experimentally induced by various methods.

[Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats].

The effects of Y-8894 on learning and memory were studied using the pole climbing avoidance (PCA) response in intact and experimentally induced amnesic rats. The following results were obtained: A single administration of Y-8894 (2.5 mg/kg, i.p.) to experimentally induced amnesic rats significantly antagonized the decrease in the mean number of PCA responses induced by an electroconvulsive shock (ECS). At a higher dose (10 mg/kg, i.p.), however, this effect was reduced. Repeated administration of Y-8894 (5 mg/kg, i.p.) significantly antagonized the facilitation of the extinction of the PCA response induced by exposure to CO2. Repeated administration of Y-8894 (2.5 mg/kg, i.p.) significantly facilitated the learning of the PCA response in intact rats. At a higher dose (5 mg/kg, i.p.), however, this effect was reduced. A single administration of Y-8894 (5 mg/kg, i.p. and 25 mg/kg, p.o.) significantly delayed the extinction of the PCA response in intact rats. These results suggest that Y-8894 has an ameliorative and facilitative effect on learning and memory in experimentally induced amnesic and intact rats.

[Pharmacological studies of 2-(5H-(1)benzopyrano(2,3-b)pyridin-7-yl)propionic acid (Y-8004). (I) Anti-inflammatory, analgesic and antipyretic actions].

A newly synthesized anti-inflammatory agent, Y-8004 demonstrated a greater inhibition than did indomethacin (IM). on inflammatory response such as ultraviolet erythema in guinea pigs, carrageenin edema, evans blue and carrageenin-induced pleuritis and acetic acid-induced peritonitis in rats. On the other hand, the inhibition of Y-8004 was to the same extent as IM regarding granuloma formation around cotton pellet and the development of adjuvant arthritis in rats, however, Y-8004 was only half as effective as IM regarding exudation in granuloma pouch. In addition, the agent was effective in alleviating established adjuvant arthritis, the anti-inflammatory activity was not mediated by stimulation of the adrenals, and glucocorticoid-like activity could not be demonstrated. Furthermore, analgesic and antipyretic activities were to the degree as seen with IM, and the analgesic property of Y-8004 was considered to be peripheral as is the case with IM. The ulcerogenic activity of Y-8004 was observed to be mainly in the jejunum and ileum of the rat, but compared to IM, there were considerable differences between the ulcerogenic and the effective doses. As Y-8004 has a wider therapeutic margin than IM, this non-steroidal anti-inflammatory agent should be quite applicable for clinical purposes.

[Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats].

The effects of Y-8894 on experimental amnesia in rats induced by transient cerebral ischemia (600 sec) according to the method of Pulsinelli and Brierley were studied using the one trial passive avoidance response and the pole climbing discrete avoidance response. All drugs were administered to the rats immediately after recirculation. The following results were obtained: 1) In the one trial passive avoidance response test, Y-8894 (2.5, 5 and 10 mg/kg, i.p.) improved significantly the decreased latency induced by the ischemia, and it was most effective at 5 mg/kg. Calcium-hopantenate (100, 250 and 500 mg/kg, i.p.) and dihydroergotoxine (5 and 10 mg/kg, i.p.) tended to increase the latency. On the other hand, physostigmine (0.025, 0.05 and 0.1 mg/kg, i.p.), a cholinesterase inhibitor, increased the latency significantly, and it was most effective at 0.05 mg/kg. 2) The pole climbing discrete avoidance response was significantly decreased by the ischemia compared with the sham operated group, and Y-8894 (5 mg/kg, i.p.) tended to improve this decreased avoidance response. 3) Y-8894 (5 mg/kg, i.p.) facilitated recovery from the changes in glycolytic metabolism, and inhibited the accumulation of choline due to the dysfunction of the neuronal membranes induced by the ischemia. These results show that Y-8894 has beneficial effects on experimental amnesia induced by transient cerebral ischemia.