A new method for characterizing hand dysfunction in cervical spondylotic myelopathy: a preliminary study.

STUDY DESIGN: A case-control investigation. OBJECTIVES: The objective of this study was to quantitatively study impaired ability to appropriately adjust pinch strength while holding a small object in patients with cervical spondylotic myelopathy (CSM). SETTING: Kochi Medical School Hospital, Japan. METHODS: The subjects consisted of 19 CSM patients who had frequent episodes of failing to grasp and hold small objects in their daily life (Group A), 13 CSM patients who did not experience such episodes (Group B) and 16 healthy subjects (Control Group). We continuously measured the dynamic internal pressure of a pneumatic rubber object called a blower pinched by the subject, following two different sets of instructions: (1) pinching with eyes open and with the minimal strength required to prevent dropping; and (2) maintaining a constant pinch strength at given levels with eyes closed. RESULTS: Compared with the other two groups, Group A subjects used a significantly (P<0.01) greater pinch strength to avoid dropping the blower held with eyes open and showed a significantly (P<0.01) greater deviation in pinch strength from the baseline values with eyes closed. These tendencies in Group A showed a significant correlation with the tactile perception threshold of the digits (P<0.01) but not with impairment of rapid repetitive movements of the digits that reflects spasticity. CONCLUSION: Our technique applied to CSM patients helps assess functional integrity primarily, if not exclusively, of the fasciculus cuneatus mediating the feedback signals from proprioceptive and cutaneous receptors in the digits, which are otherwise difficult to evaluate quantitatively.

Is the evidence of the Supreme Court Ruling of gefitinib litigation in Japan scientific?

BACKGROUND: Plaintiffs of the gefitinib (Iressa) lawsuits in Japan started in 2004 were defeated in the Supreme Court in 2013. The Court judged it was not possible to foresee the outbreak of deaths caused by interstitial pneumonia due to gefitinib from death cases before approval of this drug. OBJECTIVE: We attempted to verify validity of this judgment. METHODS: We estimated the 95% confidence interval (CI) of the proportion of onset and death cases among 23 onset and 13 death cases occurring from "within 1 week" to "within 4 weeks" from clinical data before approval of this drug using data admitted to the Court. RESULTS: For death cases, all of the upper limits of the 95% CI exceeded 50% within 1-4 weeks. This fact suggested that the cases of acute interstitial pneumonia were included in the clinical trial before the approval of gefitinib. CONCLUSION: It was possible to foresee the outbreak of death cases after drug approval. This conclusion showed the Court's ruling was not reasonable and was unscientific.

Factors associated with deterioration of mini nutritional assessment-short form status of nursing home residents during a 2-year period.

OBJECTIVE: A number of other studies have been conducted to verify the Mini Nutritional Assessment (MNA) or the MNA short form (MNA-SF) as a nutritional assessment/screening tool in various clinical settings or communities. However, there are few longitudinal studies using these tools to analyze which factors affect the incidence of deteriorating nutritional status. We tried to identify the factors associated with deterioration of MNA-SF status of nursing home residents during a 2-year period. METHODS: Participants were 392 people with a mean age of 84.3 in 12 nursing homes in Japan. The factors associated with deterioration in MNA-SF categories during the study period compared to stable/improved MNA-SF categories were identified. RESULTS: At baseline, 19.9% of the participants were malnourished and 60.2% were at risk of malnutrition, according to the MNA-SF classification. After 2 years, 66.3% participants maintained and 6.1% participants improved their nutritional status according to the MNA-SF classification, while 27.6% showed deterioration in MNA-SF status. Stepwise logistic-regression procedure indicated that basic ADL impairment and hospitalization during the follow-up period were associated with declining MNA-SF status. CONCLUSIONS: Poor basic ADL status and hospitalization during the follow-up period were associated with malnutrition and risk of malnutrition as assessed by MNA-SF of nursing homes residents during a 2-year period.

Maximum voluntary ventilation as a sensitive measure to monitor the ventilatory function in cervical spondylotic myelopathy.

STUDY DESIGN: A prospective clinical cohort study. OBJECTIVES: To test if maximum voluntary ventilation (MVV), which is currently underutilized in diseases, serves for assessing subclinical ventilatory impairment in cervical spondylotic myelopathy (CSM). SETTING: Kochi Medical School, Japan. METHODS: We studied ventilatory function in 49 CSM patients and 20 age- and sex-matched control patients with either lumbar stenosis or lower limb osteoarthritis. All patients underwent ventilatory function studies consisting of flow volume curves, vital capacity (VC) and the MVV in 12 s before and after surgery. Tetraparesis was assessed by the functional scale of the Japanese Orthopaedic Association (JOA). RESULTS: The CSM group had significantly smaller %forced VC , %peak expiratory flow rate (%PEFR) and %MVV than the control group preoperatively. In contrast to the control group, the CSM group showed a significant increase in %MVV from 74.9±18.7% preoperatively to 80.3±19.0% postoperatively (P<0.005), but not in any other ventilatory measures. This postoperative increase in %MVV significantly correlated with the JOA score (r=0.493; P<0.001). As a possible effect of diaphragmatic recovery, the %PEFR significantly increased postoperatively only in patients with the primary site of involvement at or rostral to C3-4. CONCLUSION: Of the various ventilatory measurements, MVV was most sensitive to changes in tetraparesis in CSM, presumably because MVV, unlike the other ventilatory measures, reflects the coordination in addition to the strength of respiratory muscles.

SSR analysis of genetic diversity among maize inbred lines adapted to cold regions of Japan.

Information regarding diversity and relationships among breeding material is necessary for hybrid maize ( Zea mays L.) breeding. Simple-sequence repeat (SSR) analysis of the 60 loci distributed uniformly throughout the maize genome was carried out for 65 inbred lines adapted to cold regions of Japan in order to assess genetic diversity among the inbred lines and to assign them to heterotic groups. The mean value (0.69) of the polymorphic-index content (PIC) for the SSR loci provided sufficient discrimination-ability for the assessment of genetic diversity among the inbred lines. The correlation between the genetic-similarity (GS) estimates and the coancestry coefficient was significant ( r = 0.70). The average-linkage (UPGMA) cluster analysis and principal-coordinate analysis (PCOA) for a matrix of the GS estimates showed that the Northern flint inbred lines bred in Japan were similar to a Canadian Northern flint inbred line CO12 and a European flint inbred line F283, and that dent inbred lines bred in Japan were similar to BSSS inbred lines such as B73. These associations correspond to the known pedigree records of these inbred lines. The results indicate that SSR analysis is effective for the assessment of genetic diversity among maize inbred lines and for the assignment of inbred lines to heterotic groups.

First total synthesis of dragmacidin A via indolylglycines.

The first total synthesis of dragmacidin A has been accomplished using condensation of two indolylglycines followed by cyclization and reduction. The general and practical method for synthesis of indolylglycines via Wittig reaction, azide addition, and reduction from indolin-3-ones is also described.

[Clinical applications and the effect of mexiletine on refractory epilepsies].

Twenty-four patients with refractory epilepsy were treated with mexiletine as an additional antiepileptic drug. As the initial responses, seizures were decreased by 50% or more in 7 (46.7%) of 15 patients with symptomatic partial epilepsy (SPE), in none of 7 with symptomatic generalized epilepsy (SGE), and in 1 of 2 with undetermined epilepsy. Seizures increased in 3 patients (20.0%) with SPE, and in 3 (42.9%) with SGE. Concerning seizure types, mexiletine had significant effects on 1 of 2 patients with simple partial seizures, on 7 of 13 with complex partial seizures, on 1 of 5 with secondarily generalized seizures, and on 1 of 8 with tonic seizures. No patients with a myoclonic seizure or atypical absence improved. Exacerbation of the seizures was observed in 2 of 13 patients with complex partial seizures, in 1 of 5 with secondarily generalized seizures, in 3 of 8 with tonic seizures, and in 2 of 3 with myoclonic seizures. Partial seizures were controlled well, whereas generalized seizures sometimes worsened. EEG improved in 3 patients with SPE; decrease of focal spikes in 2 patients and disappearance of secondary generalization in 1. Follow-up for more than 3 months showed seizures to be lessened in 2 patients. Mexiletine is useful for the treatment of refractory epilepsies, especially SPE.

Ac as a tool for the functional genomics of rice.

To examine whether the maize autonomous transposable element Ac can be used for the functional analysis of the rice genome, we used Southern blot analysis to analyze the behaviour of Ac in 559 rice plants of four transgenic families through three successive generations. All families showed highly active transposition of Ac, and 103 plants (18.4%) contained newly transposed Ac insertions. In nine of the 12 independent transpositions analyzed, their germinal transmission was detected. Partial sequencing of 99 Ac-flanking sequences revealed that 21 clones exhibited significant similarities with protein-coding genes in databases and four of them matched rice cDNA sequences. These results indicate preferential Ac transposition into protein-coding rice genes. To examine the feasibility of PCR-based screening of gene knockouts in rice Ac plants, we prepared bulked genomic DNA from the leaves of approximately 6000 rice Ac plants and pooled the DNA according to a three-dimensional matrix. Of 14 randomly selected genes, two gene knockouts were identified, and one encoding a rice cytochrome P450 (CYP86) gene was shown to be stably inherited to the progeny. Together, these results suggest that Ac can be efficiently used for the functional analysis of the rice genome.

Photosensitive fits elicited by TV animation: an electroencephalographic study.

BACKGROUND: We carried out a clinical and electroencephalographic (EEG) study to reveal the pathophysiology of acute symptoms elicited by a TV animation program. METHODS: Clinical data and EEG were obtained from 20 patients ranging in age from 6 to 30 years. A pattern presentation and an intermittent photic stimulation were performed. RESULTS: Of 20 patients, 13 had a convulsion and seven had other symptoms, mainly nausea and/or vomiting. A photoparoxysmal response (PPR) was confirmed in 12 of 13 patients (92.3%) who had a convulsion. Only one of seven patients (14.3%) without a convulsion showed a PPR. The incidence of PPR was significantly higher in patients with convulsion than those without convulsion. There were no significant differences in the family history of convulsion, gender, parameters associated with TV watching and basic EEG between the two groups. All patients with PPR had a convulsion or consciousness disturbance. CONCLUSION: Acute symptoms, such as convulsion and impairment of consciousness, are supposed to be based on photosensitivity.

Transposon tagging in rice.

To develop an efficient gene isolation method for rice we introduced the maize Ac/Ds system into rice. Extensive analysis of their behavior in rice for several generations indicated that Ac and Ds in the presence of Ac transposase gene actively transpose in rice. A wide spectrum of mutations affecting growth, morphogenesis, flowering time and disease resistance have been obtained in the population carrying Ac/Ds and some of them were genetically analyzed. Main efforts are currently being made to isolate genes responsible these mutations. In addition, a number of Ac/Ds were mapped on chromosomes and mapped elements will be used in the future for directed tagging of genes with known chromosomal positions.

Effects of high-dose antiepileptic drugs on event-related potentials in epileptic children.

N200 and P300 of event-related potentials (ERPs) were recorded from 22 epileptic children receiving high-dose antiepileptic drugs. The patients were undergoing monotherapy with supratherapeutic serum level and were not mentally retarded. P300 latency was prolonged in 5 of 8 patients (62.5%) of the carbamazepine (CBZ) group and in 4 of 7 patients (57.1%) of the phenytoin (PHT) group. Only one child of the PHT group showed abnormality in brain-stem auditory evoked potentials (BAEPs). Abnormality of P300 was more frequent than that of BAEP. In patients of the PHT group who underwent examinations consecutively before and after changing the dose, P300 latency was prolonged rapidly when the PHT level exceeded 30 micrograms/ml. This suggested that the prolongation was dose dependent. In all patients of the valproic acid (VPA) group, P300 latency was normal. Only 2 patients of the PHT group had P300 prolongation simultaneously with clinical signs of intoxication. Others demonstrated changes in P300 without symptoms of side effects.

The effects of age on the N200 component of the auditory event-related potentials.

This study was undertaken to determine the effects of development and aging on N200 of event-related potentials from childhood to adulthood. Event-related potentials were recorded from 164 normal subjects ranging in age from 4 to 77 years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed marked developmental changes. During childhood, the N200 latency decreased rapidly with age to the minimum (217 +/- 17.3 ms) at 16 years of age, while it was prolonged gradually with age during adulthood. The latency/age slope in the subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in those from 16 to 77. The N200-P300 interpeak latency remained constant in all age groups and showed no age-related changes. The N200 amplitude decreased as age increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in evaluating the developmental and aging processes in the central nervous system. The results of this study could be used as normative data in clinical practices.

Nonconvulsive status epilepticus with continuous diffuse spike-and-wave discharges during sleep in childhood.

On three epileptic conditions with common characteristics of almost continuous diffuse spike-and-wave discharges during sleep in EEG, clinical and electroencephalographic studies were undertaken to elucidate their pathophysiologies and interrelationships; namely on five cases of epilepsy with electrical status epilepticus during slow sleep (ESES), seven cases of a peculiar type of nonconvulsive status epilepticus in childhood (PNSE) and three cases of atypical benign partial epilepsy (ABPE). The dominant seizure types were absences and/or GTC in ESES, whereas they were focal motor seizures in PNSE and ABPE with more focalized epileptic discharges on EEGs than those in ESES. All the three conditions showed both features of generalized and partial epilepsies, although the former features were more prominent in ESES and the latter in PNSE and ABPE.