Run-up to participation in ATACH II in Japan.

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial.

IFNß-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum.

BACKGROUND: Interferon-ß-1b (IFNß-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNß-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNß-1b to identify similar cases. METHODS: At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNß-1b therapy. RESULTS: Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale ≧7.0) within 90 days of the initiation of IFNß-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNß-1b therapy were more severe than those experienced by the individual patients before the use of IFNß-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFß-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. CONCLUSIONS: Our study suggests that IFNß-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFß-1b therapy, cases in NMO spectrum should be carefully excluded.

Nissui glucose fermentative gram-negative rod identification system EB-20 gives a unique profile for typical non-sorbitol-fermenting Escherichia coli O157:H7.

The 98 non-sorbitol-fermenting (NSF) Escherichia coli O157:H7 strains identified on a Nissui glucose fermentative gram-negative rod identification system (EB-20) gave a unique biochemical profile number that was not detected in 85 pathogenic and 13 nonpathogenic E. coli strains. Thus, EB-20 is useful for the identification of NSF E. coli O157:H7 and provides a simple, cost-effective, and reliable tool for clinical laboratories.

Development of oligonucleotide lateral-flow immunoassay for multi-parameter detection.

We have developed a highly sensitive and rapid oligonucleotide lateral-flow immunoassay (OLFIA), using a colloidal gold as an indicator, for the simultaneous detection of antigens and/or antibodies in specimen. This system can detect more than two types of antigens and/or antibodies in a single assay device at the same time. The device is basically composed of colloidal gold-labeled antibodies and oligonucleotide-labeled antibodies fixed in a conjugate pad, and the complementary oligonucleotide-labeled proteins are immobilized on a nitrocellulose membrane. If the target antigen is present in a specimen, the colloidal gold-labeled antibody and oligonucleotide-labeled antibody will make a complex with the antigen. Subsequently, the formed complex migrates to the place where complementary oligonucleotide is immobilized and is bound to the solid phase via the DNA-DNA interaction. As a result, more than two types of reactions can be detected on a single assay device by the combination of colloidal gold-labeled antibodies, different oligonucleotide-labeled antibodies and complementary oligonucleotide-labeled proteins immobilized at different places on a nitrocellulose membrane.

A case report: verrucous carcinoma of the endometrium--the difficulty of diagnosis, and a review of the literature.

A verrucous carcinoma is a subtype of well-differentiated squamous-cell carcinomas, arising in the vagina, vulva, and uterine cervix. But a verrucous carcinoma very rarely arises in the uterine endometrium. The present paper presents a case of a verrucous carcinoma of the endometrium that is described in association with the tumor marker SCC; this paper also includes a review of the relevant literature.

Air-puff-induced facilitation of motor cortical excitability studied in patients with discrete brain lesions.

Air-puff stimulation applied to a fingertip is known to exert a location-specific facilitatory effect on the size of the motor evoked potentials elicited in hand muscles by transcranial magnetic stimulation. In order to clarify its nature and the pathway responsible for its generation, we studied 27 patients with discrete lesions in the brain (16, 9 and 2 patients with lesions in the cerebral cortex, thalamus and brainstem, respectively). Facilitation was absent in patients with lesions affecting the primary sensorimotor area, whereas it was preserved in patients with cortical lesions that spared this area. Facilitation was abolished with thalamic lesions that totally destroyed the nucleus ventralis posterolateralis (VPL), but was preserved with lesions that at least partly spared it. Lesions of the spinothalamic tract did not impair facilitation. The size of the N20-P25 component of the somatosensory evoked potential showed a mild correlation with the amount of facilitation. The facilitation is mainly mediated by sensory inputs that ascend the dorsal column and reach the cortex through VPL. These are fed into the primary motor area via the primary sensory area, especially its anterior portion, corresponding to Brodmann areas 3 and 1 (possibly also area 2), without involving other cortical regions. The spinothalamic tract and direct thalamic inputs into the motor cortex do not contribute much to this effect. Some patients could generate voluntary movements despite the absence of the facilitatory effect. The present method will enable us to investigate in humans the function of one of the somatotopically organized sensory feedback input pathways into the motor cortex, and will be useful in monitoring ongoing finger movements during object manipulation.

Upper cervical myelopathy associated with low CSF pressure: a complication of ventriculoperitoneal shunt.

A patient who had undergone ventriculoperitoneal shunting developed upper cervical myelopathy. His CSF pressure was markedly low, and deformation of the spinal cord and shrinkage of the subarachnoid space at the upper cervical level were found in radiologic examinations. Ligation of the shunt tube resulted in almost complete recovery. The effect of excessive drainage may have caused the abnormalities.

[Acute compression neuropathy of the proximal sciatic nerve in a patient with facioscapulohumeral muscular dystrophy].

We reported a 58-year-old man with facioscapulohumeral muscular dystrophy who had acute compression neuropathy of the sciatic nerve after prolonged sitting position. MRI and percutaneous electric stimulation studies were usefull for the diagnosis. Gd-DTPA T1-weighted MRI images showed the enhanced right sciatic nerve at the level of gluteus maximus muscle. An evoked potential study by a percutaneous electric stimulation revealed evidence of a conduction block at the same level. After methylprednisolone pulse therapy, muscle weakness and sensory disturbance improved. Acute compression neuropathy of the sciatic nerve may be seen as a complication in the advanced stage of (FSH) muscular dystrophy.

Primary malignant lymphoma of the duodenum: report of a case.

We present a case of long-term survival in primary malignant lymphoma of the duodenum treated with a curative surgical resection and post-operative chemotherapy. A 72 year-old man was admitted to our hospital complaining of epigastric discomfort. Endoscopy revealed an ulcerative tumor in the duodenal bulb. The tumor was diagnosed histologically as malignant lymphoma by endoscopic biopsy. A distal gastrectomy and duodenal bulb resection were performed with lymph nodes dissection. The tumor was histologically classified as B-cell phenotype, large cell, immunoblastic lymphoma of high grade, according to the Working Formulation. The patient received CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy after the operation, and he has no sign of recurrence during a follow-up period of 6 years.

Magnetic stimulation of the descending and ascending tracts at the foramen magnum level.

To test the possibility that stimulation over the foramen magnum activates ascending tracts as well as descending tracts, we studied 4 patients with myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs) and 10 normal subjects, using our previously reported method (Ugawa et al., Ann. Neurol., 1994, 36: 618-624). For latency comparisons, peripheral nerve stimulation at the elbow and spinal motor root were also performed. In all patients, magnetic stimulation at the foramen magnum consistently elicited long loop reflexes as well as direct responses caused by stimulation of the descending tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies of both types of response were the same whether stimulation used upward or downward current in the brain, although the former was always more effective. This indicates that stimulation at the level of the foramen magnum activates ascending tracts as well as descending tracts at a fixed position. The threshold for LLRs was lower than that for activation of the descending tracts. This threshold difference is compatible with the hypothesis that large diameter fibers from muscle afferent conduct the central afferent volley for LLRs (Marsden et al., Brain, 1977, 100: 185-200).

[Autosomal dominant distal myopathy with rimmed vacuoles and cytoplasmic inclusions: report of a family].

We reported four patients with distal myopathy in the same family. Muscle weakness and atrophy started in the lower extremities, especially in the calf muscle, and it extended to the upper extremities and pelvic muscles to a variable extent. Facial and bulbar muscles were slightly involved in one case. The anterior tibial muscle tended to be better preserved than the calf muscle. Cardiac abnormalities were absent in any case. Serum creatine kinase activity was normal or mildly elevated. Skeletal muscle biopsies revealed myopathic process presenting rimmed vacuoles, eosinophilic cytoplasmic inclusions and/or subsarcolemmal mass. Ultrastructurally, cytoplasmic inclusions were composed of electron dense granular material and intermediate-sized filaments. There were membranous whorls and myelin-like figures which were the characteristic findings of rimmed vacuoles. Immunohistochemistry revealed accumulation of desmin, dystrophin and vimentin in the cytoplasm of degenerating muscle fibers and in the inclusion. In present patients, cardiac function was normal and the tibialis anterior muscle was relatively spared. These features were different from the autosomal dominant rimmed-vacuolar myopathy with desmin storage described in previous reports.

Magnetoencephalographic analysis of cortical myoclonic jerks.

We studied the pre-myoclonus spike using magnetoencephalography in patients with cortical myoclonus (6 with cortical reflex myoclonus and one with epilepsia partialis continua). The spike was estimated as a single current dipole on the pre-central gyrus in one patient with epilepsia partialis continua. In contrast, it was estimated as a single dipole on the post-central gyrus in 5 of 6 patients with cortical reflex myoclonus, and as two dipoles on the pre- and post-central gyrus in the remaining patient. We conclude that there are 3 physiological types of cortical myoclonus: (1) abnormal discharges in the motor cortex produce the myoclonus; (2) the source of the myoclonus is mainly the sensory cortex; (3) both the motor and sensory cortices play important roles in the production of myoclonus.

Clinical utility of magnetic corticospinal tract stimulation at the foramen magnum level.

We applied magnetic stimulation of the corticospinal tract at the foramen magnum level to 19 patients with various neurological disorders. Results were consistent with our previous speculation that activation occurs at the foramen magnum level. This method was clinically useful for the following conditions. (1) Detection of subclinical lesion: one patient who had transient ischemic attack that caused no clinical symptoms at examination was shown to have dysfunction of the corticospinal tract. (2) Multiple lesions: our method disclosed at least one lesion above and below the foramen magnum in two patients with multiple sclerosis. (3) Unmasking of dysfunction of the corticospinal tract masked by peripheral neuropathy: magnetic stimulation showed conduction delay in the corticospinal tract in two patients in whom no pyramidal signs were evident because of muscular atrophy due to neuropathy. One patient had multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy, the other had degenerative ataxia and neuropathy. (4) Association of disorders: conduction delay rostral to the foramen magnum, which should not occur in patients with only cervical myelopathy, was shown in a patient with cervical myeloradiculopathy and amyotrophic lateral sclerosis. We conclude that this magnetic stimulation method which is less painful than electrical stimulation has extensive clinical usefulness.

[p53 gene mutations in the human lung carcinoma].

The p53 mutations in the reported 243 lung cancers and our 59 cases were analyzed. The common base substitutions found in the lung cancer were G to T transversion (35%), C:G to T:A (26%) and A:T to G:C transitions (11%). Four types of the hot spot, 1) G to T transversion, 2) A to G transition in ApT site, 3) C to T transition in CpG site and 4) mix of the transversion and transition were identified. It is suggested that A to G transition at ApT site in the non-transcribed strand may be a new hot spot in the p53 gene in lung carcinoma. We also show that microscopic selection of cancer cells will facilitate the detection of p53 mutations in adenocarcinomas.

Input-output organization in the hand area of the human motor cortex.

The primate motor cortex consists of efferent zones which receive sensory information from a portion of limb in close anatomical relation to the muscle to which they project. To investigate a similar input-output relation in humans, we studied the effect of tactile stimuli on the size of motor evoked potentials (MEPs) elicited by transcranial magnetic and electrical stimulation. For tactile stimuli we applied air to the skin. The sizes of MEP of 3 finger muscles (flexor pollicis brevis, first dorsal interosseous, and abductor digiti minimi) with and without air stimuli were compared. Air stimuli applied to the tip of one finger facilitated mainly the magnetically evoked MEP of a muscle attached to that finger. A less obvious facilitatory effect was observed when giving stimuli on the dorsal aspect of the hand. Air stimuli had no facilitatory effect on electrically evoked MEPs. In one subject, there was no facilitatory effect even to magnetically evoked MEPs. In this subject, D-waves had the lowest threshold for magnetic and electrical stimulation. These results suggested that the effect was produced at the cortical level. This effect may correspond to the input-output relation found in the primate motor cortex.

Blood flow and metabolism of central neurocytoma: a positron emission tomography study.

BACKGROUND: New World Health Organization classifications have categorized central neurocytomas as neuronal tumors. The differential diagnosis between central neurocytomas and other tumors is important for selection of the optimal therapy modality for the management of intraventricular tumors. To characterize the pathophysiology and proliferating activity of central neurocytoma accurately, cerebral blood flow and metabolism in five patients with central neurocytoma were studied using positron emission tomography (PET). METHODS: Tracers used for the present study included C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose (rCMRGl) were quantitatively analyzed in tumor lesions and the contralateral gray matter. Four patients with central neurocytoma underwent a complete PET study, including all circulatory and metabolic parameters; one patient was studied with 11C-methyl-L-methionine and FDG tracers. RESULTS: Tumor rCBF and rCBV were higher than comparable values in the contralateral gray matter in three of four patients. This high level of perfusion corresponds to angiographic findings that show intense tumor staining in tumors fed by perforated arteries. Tumor rOEF and rCMRO2 were significantly lower than corresponding values in the gray matter (rOEF, P < 0.01; rCMRO2, P < 0.05 by Student's t test). Tumor rCMRGl ranged from 2.68 to 6.26 mg/100 ml/minutes and did not exceed contralateral gray matter values in any of the five patients. Tumor rCMRGl was significantly lower (P < 0.02) than the gray matter rCMRGl. One tumor exhibited a relatively high value of rCMRGl (comparable to gray matter rCMRGl), and increased in size 4 months after partial resection. No other tumors appeared during postoperative follow-up periods that ranged from 4 to 135 months. CONCLUSIONS: Circulation and metabolism parameters measured by PET offer insight into the biologic characteristics of central neurocytoma. Tumor rCMRGl may be an indicator of the proliferating activity in central neurocytoma.

Magnetic stimulation over the cerebellum in humans.

Magnetic stimulation performed with a double-cone coil placed over appropriate positions on the back of the head reduced the size of electromyographic responses evoked by magnetic cortical stimulation in the first dorsal interosseous muscle when it preceded the cortical stimulus by 5, 6, and 7 msec. No suppression of responses to electrical cortical stimulation occurred. Greater suppression was evoked by stronger cerebellar stimuli; lesser suppression was elicited by stronger cortical stimuli. These physiological findings correspond to those obtained with electrical cerebellar stimulation. The most effective position for magnetic stimulation over the back of the head was slightly rostral to the foramen magnum level on the ipsilateral side of the muscle studied. This indicates that the conditioning stimulus activates certain structures at the back of the head on the ipsilateral side of the muscle, consistent with the cerebellum, because the part of the cerebellum regulating limb muscles is positioned about there on the ipsilateral side. In 2 patients with only cerebellar dysfunction, this suppression effect was not elicited, which also supports that the suppression is caused by activity in cerebellar structures. We conclude that magnetic stimulation over the cerebellum with a double-cone coil elicits the same suppressive effect on the motor cortex as electrical stimulation, but with less discomfort; moreover, we believe that this effect is produced by activation of certain cerebellar structures.