Evaluation of the effect of anxiety on the masseteric silent period duration

The duration of the masseteric silent period (SPD) and environmental stress are parameters which have been associated with the symptoms of masticatory dysfunction. In this study, the relationship between differing levels of anxiety and the masseteric silent period duration, for nineteen subjects reporting a history of symptoms of mandibular dysfunction, was evaluated by a stress model based on the Sta X-1 anxiety test. The results suggest that the durations of masseteric silent periods were not significantly affected by differing levels of anxiety.     

METHIMAZOLE-INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES'' DISEASE

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.     

Neurotoxic Effects of the Anti-Varicella Zoster Virus Agent 2'-Valeryl-6-methoxypurine Arabinoside in Monkeys and Rats Dosed Orally for 90 Days

The 2'-valerate ester of 6-methoxypurine arabinoside (170U88),a nucleoside analog with anti-varicella zoster virus (VZV) activity,was given to monkeys and rats. In subchronic preclinical toxicitystudies, dosing was by gavage to monkeys (distilled water vehicle)and rats (0.5% methylcellulose vehicle) for 90 days. Groupsof 5 male and 5 female monkeys (Macaca fascicularis) were given170U88 at 0, 25, 50, or 100 mg/kg/day. The daily dose was givenin two equal portions with 6 hr between doses. Monkeys in thehigh-dose group lost weight. Food consumption was decreasedfor mid- and high-dose monkeys and for low-dose female monkeys.Slightly decreased values for erythrocyte and leukocyte countsat the mid- and high dose were fully reversed during an 8-weekrecovery period. Two high-dose male monkeys and a middose femalemonkey developed signs of central nervous system toxicity andwere necropsied before dosing was complete. These signs werefirst observed in the fifth week of dosing and included bodytremors, incoordination, reduced activity, sleepiness, stupor,and lack of eye tracking. Axonal lesions were observed in histologicsections of sciatic nerve in monkeys at all dose levels. Neitherthe signs of central nervous system toxicity nor the axonallesions reversed during the 8- week recovery period. Groupsof 14 male and 14 female CD rats (Sprague-Dawley derived) weregiven single daily doses of 170U88 at 0, 150, 300, or 600 mg/kg.Body weights were decreased at all dose levels and food consumptionwas decreased for mid- and high-dose rats. Small increases invalues for erythrocyte count, hemoglobin, and packed cell volumeand small decreases in values for glucose, serum protein, andserum albumin were limited to high-dose rats and reversed duringa 4- week recovery period. High-dose rats also had reversibleliver lesions consisting of necrosis of individual hepatocytes,megalocytosis, occasional mitotic figures, and biliary stasis.Clinical and morphologic indications of central nervous systemtoxicity in the rats consisted of altered exploratory behaviorat the high dose and groups of small vacuoles in cerebellarwhite matter at all dose levels. Cerebellar vacuolation wasobserved in rats examined at the end of the exposure periodand also in rats examined after the 4-week postdose recoveryperiod. Signs interpreted as peripheral nervous system toxicitywere limited to rats in the high-dose group and consisted ofhindquarter weakness, slow righting and placing reflexes, andataxia. Again, these findings did not reverse during the recoveryperiod. Thus, signs of both central and peripheral nervous systemtoxicity were observed in both monkeys and rats. These neurotoxiceffects resulted in the decision to stop further developmentof 170U88.     

Neurobehavioral Effects from Acute Exposures to Methyl Isobutyl Ketone and Methyl Ethyl Ketone

Subjects were tested for neurobehavioral performance in an environmentalchamber to detect the presence of subclinical central nervoussystem effects from 4-hr exposures to methyl isobutyl ketone(MIBK) at 100 ppm, methyl ethyl ketone (MEK) at 200 ppm, MIBKat 50 ppm with MEK at 100 ppm, or a placebo (i.e., a 5-min presentationof 25 ppm MEK—MIBK at each exposure period outset). Subjectswere 68 males and 75 females recruited from local universities;ages ranged from 18 to 32 years. Ethanol by ingestion (95% –0.84 ml/kg) was used as a positive control. Five psychomotortests (choice reaction time [CRT], simple reaction time [SRT],visual vigilance, dual task [auditory tone discrimination andtracking memory scanning), one sensorimotor test (postural sway),and a test of mood (profile of mood states) were used to measureneurobehavioral effects. Additionally, chemical measurements(blood and breath) and reports of sensory and irritant effectswere measured. The chemical exposures produced statisticallysignificant performance effects on only 4 of 32 measures (%correct responses-visual vigilance, movement time-CRT, SRT,% incorrect responses-dual task). These effects, however, werenot substantial and could not be attributed directly to thechemical exposures. Alcohol ingestion, however, produced significantdecrements on every performance test except memory scanningand mood. An interaction occurred between gender and alcoholingestion, such that more statistically significant performancedecrements were found for females than for males. Significantodor sensations and irritant effects were reported by the subjectsduring the chemical exposures. The MEK results agree with earlierMEK experiments at comparable exposure conditions, and the MIBKresults are consistent with a recent Swedish study that usedMIBK exposures and showed no significant behavioral performancedecrements from single MIBK exposures at 50 ppm with 50 W exercise.Additionally, the MIBK—MEK combination exposure showedno evidence of any interaction effects on either the behavioralor chemical measurements. The principal effects resulting fromexposures to MEK and MIBK at the durations and concentrationsused in the study are limited to sensory and irritant effects.     

An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene

The gene for autosomal recessive spinal muscular atrophy (SMA) has been mapped to 5q12 in a region that contains repeated markers and genes. Three cDNAs that detect deletions in SMA patients have been reported. One of these, the survival motor neuron (SMN) cDNA, is encoded by two genes (SMNT and SMNC) which are distinguished by base changes in exons 7 and 8. Exon 7 of the SMNT gene is not detectable in approximately 95% of SMA cases, due either to deletion or sequence conversion. There is limited information on the mutations in SMA patients that have detectable SMNT, these are critical for confirmation of SMNT as the SMA gene. Using SSCP analysis of the SMN exons we screened our SMA patients that possess at least one intact SMNT allele for mutations in SMNT. We identified one type I SMA patient with an 11 bp duplication in exon 6 which causes a frameshift and premature termination of the deduced SMNT protein. Dosage and SSCP analysis of SMNT in this family indicated that the father contributed a SMNT-deleted allele to the affected child whereas the mother passed on the 11 bp exon 6 duplication SMNT allele. Analysis of RNA by RT-PCR conclusively demonstrated that the 11 bp duplication is associated with the SMNT locus and not SMNC. This mutation provides strong support for SMN as the SMA-determining gene and indicates that disruption of SMNT on its own is sufficient to produce a severe type I SMA phenotype.      

T2 estimates in healthy and diseased brain tissue: a comparison using various MR pulse sequences

Fourteen patients and five healthy individuals underwent magnetic resonance (MR) imaging to determine an effective multiple spin echo pulse sequence for estimating T2. Lesions examined included infarction, glioma, multiple sclerosis, and acute hematoma. A pulse repetition time (TR) of 1,500 msec and echo delays (TEs) of 25, 50, 75, and 100 msec were used. Computed T2 images were derived from all four echoes, the first two echoes, and the first and fourth echoes. T2 values were obtained from specific brain locales using region-of-interest analysis. Use of either the first two echoes or the first and fourth in the T2 fit provided T2 estimates which closely correlated with that of the four-echo analysis. The noise level in T2 maps constructed from the 25- and 100-msec echoes was modestly (typically 10%) higher than that from four echoes; noise level from the 25- and 50-msec echoes was markedly higher, typically 60%. This behavior is remarkably consistent with that predicted from theory. All 19 subjects displayed consistent relative T2 values for specific brain structures; in 13, the absolute T2 values fell within a limited range. Despite the high sensitivity of T2 images, their specificity in the detection of most brain disease appears limited except in acute intracerebral hematoma, which exhibited a decreased T2 relaxation time using high-field-strength MR imaging.