The purpose of this study was to determine if 4 major organophosphate impurities of malathion were active as alkylators of nitrobenzylpyridine (NBP) or as mutagens in the Salmonella typhimurium bioassay. Malathion, isomalathion, O,O,O-trimethyl phosphorothioate, O,O,S-trimethyl phosphorothioate, and O,S,S-trimethyl phosphorodithioate produced alkylated NBP at varying rates. In order of increasing NBP reactivity, the compounds ranked: O,O,O-trimethyl phosphorothioate = O,O,S-trimethyl phosphorothioate less than O,S,S-trimethyl phosphorodithioate less than isomalathion = malathion. At 37 degrees C, the most reactive compounds produced an NBP alkylation rate equal to approximately 25% of the rate produced by methyl methanesulfonate, a potent Salmonella mutagen. However, none of the organophosphates were mutagenic in S. typhimurium TA97, TA98 and TA100 when tested by the standard plate-incorporation method or by the preincubation modification of the plate-incorporation method. The possible relationships between NBP reactivity and the biological activities of these organophosphates are discussed.

Alkylating Agents↗

PubMedDate not supplied

Sensitive determination of delta 9-tetrahydrocannabinol in human tissues by GC-MS.

A reliable, simple, and sensitive method was devised to determine the levels of delta 9-tetrahydrocannabinol (THC) in human solid tissues. THC was effectively extracted with acetonitrile, and interfering compounds were removed by washing with a solution of sodium hydroxide and hydrochloric acid. THC was then derivatized by methylation and subjected to gas chromatography-mass spectrometry. Deuterated methyl THC (THC-CD3) was used as an internal standard. The calibration curves were linear in the concentration range from 1 to 100 ng/g, and the lower limit of detection was 1 ng/g in all samples examined. The accuracy and precision of the method were evaluated in every tissue sample at two different concentrations, 5 and 50 ng per sample. The coefficient of variation ranged from 3.4 to 11.6%. We used this method to identify THC in tissues from an autopsied individual, and the distribution of this drug in the tissues was evaluated based on medico-legal criteria.

Adult↗

PubMedDate not supplied

Selective determination of amitriptyline and nortriptyline in human plasma by HPLC with ultraviolet and particle beam mass spectrometry.

A selective, sensitive, and reliable method was devised to determine concentrations of amitriptyline and its major metabolite, nortriptyline, in human plasma using high-performance liquid chromatography (HPLC) combined with UV and particle beam mass spectrometry (PBMS). Amitriptyline and nortriptyline were effectively extracted in a three-step solvent extraction procedure. Imipramine was used as the internal standard (IS). Amitriptyline, nortriptyline, and the IS were clearly separated by HPLC on a silica column with the mobile phase of acetonitrile-0.1 M ammonium acetate (94:6, v/v). The calibration curves were linear in the concentration range of 10-1000 ng/g for both compounds with UV and PBMS detections. The lower limits of detection were 5 ng/g for amitriptyline and 10 ng/g for nortriptyline with UV detection and 2 ng/g for amitriptyline and 5 ng/g for nortriptyline with PBMS detection. The absolute recoveries were 58% for amitriptyline and 47% for nortriptyline at a concentration of 50 ng/g. This method proved most useful in accurately identifying amitriptyline and nortriptyline in tissues from an autopsied individual.

Acetates↗

PubMedDate not supplied

Laxative poisoning: toxicological analysis of bisacodyl and its metabolite in urine, serum, and stool.

An 11-year-old boy was hospitalized because of severe diarrhea (over 5 L/day). The child survived; however, the diarrhea continued while he was given intravenous fluids and his electrolyte balance was closely supervised. Based on observation of the patient and his family in the hospital, surreptitious administration of a poison by his mother was suspected, and toxicological analysis was carried out on stools from the boy and on medicine administered to him by his mother. Bisacodyl, a cathartic with a direct effect on the colon, was detected in the medicine, and a metabolite of bisacodyl was present in the stool. We devised a sensitive and reliable method to quantitate the bisacodyl metabolite in urine and serum. The sample was incubated with beta-glucuronidase at 37 degrees C for 2 h; bisacodyl metabolite was extracted with tert-butyl methyl ether, then derivatized by methylation, and subjected to gas chromatography-mass spectrometry. Bisphenol A was used as an internal standard. The calibration curve was linear in the concentration range from 2 to 1000 ng/0.2 mL, and the lower limits of detection were 1 ng/0.2 mL for the urine and 2 ng/0.2 mL for the serum. As concentrations of bisacodyl metabolite in the urine and serum of the patient were clearly defined, perhaps such investigations are warranted before extensive clinical therapy is prescribed.

Bisacodyl↗

PubMedDate not supplied

Amelioration of frozen gait by tandospirone, a serotonin 1A agonist, in a patient with pure akinesia developing resistance to L-threo-3,4-dihydroxyphenylserine.

A 71-year-old woman presented with severe akinesia, frozen gait, and compromised postural reflexes, without rigidity, tremor, or vertical gaze disturbance. With a working diagnosis of pure akinesia, we administered amantadine (150 mg/d) and L-threo-3,4-dihydroxyphenylserine (DOPS) (600 mg/d), which alleviated her symptoms. When frozen gait recurred 2 months later, we increased the dose of L-threo-DOPS to 900 mg/d and added levodopa (300 mg/d) combined with carbidopa, but this failed to improve the patient's symptoms. We then combined administration of tandospirone, a serotonin (5-HT) 1A agonist with L-threo-DOPS (600 mg/d), resulting in marked clinical improvement. Tandospirone is reported to activate noradrenergic neurons via the 5-HT 1A receptor, which could account for such striking improvement in a patient previously responsive to the noradrenergic precursor L-threo-DOPS given alone.

Aged↗

PubMedDate not supplied

Intramuscular solitary fibrous tumor: a clinicopathological case study.

We present a case of extrapleural solitary fibrous tumor arising within the muscle, an unusual and hitherto-undescribed tumor lesion. A 42-year-old woman presented a painless mass in her left thigh. The lesion was depicted as an intramuscular mass that enhanced on both CT and MRI, showing quite rich tumor vascularity. The histological features of the tumor were spindle cell proliferation with various histological patterns, typical fibrocollagenous background, and positive immunoreactivity for CD-34.

Adult↗

PubMedDate not supplied

Age at onset and regional cerebral glucose metabolism in Alzheimer's disease.

This study assessed 46 patients with Alzheimer's disease and 21 aged controls using positron emission tomography. Repeated analyses using a general linear model examined the effect of age at onset on the pattern of the regional cerebral metabolic rate of glucose (rCMRglc). The results showed significant age effects on the rCMRglc in the fronto-temporo-parietal association cortices and retrosplenial areas. Disease duration, overall cognitive severity or normal aging could not account for the effects. The age effects were delineated as a double dissociation, that is, early-onset patients have a more severe reduction of regional glucose metabolism in the association cortices, while late-onset patients show a more prominent metabolic deficit in the paralimbic area.

Age of Onset↗

PubMedDate not supplied

Regional hypometabolism related to language disturbance in Alzheimer's disease.

To elucidate the nature of language disturbance in Alzheimer's disease (AD) and the cerebral area involved in it, we studied 65 AD patients with the Western Aphasia Battery (WAB) and with 18F-fluorodeoxyglucose and positron emission tomography. Partial correlations were evaluated between the Aphasia Quotient of WAB and regional cerebral glucose metabolism normalized by the mean metabolic rate in the bilateral primary sensorimotor areas after controlling age, sex, education and severity of illness. Language disturbance in AD is accounted for by deficits in the semantic processing of language and is related to glucose hypometabolism in the inferior temporal gyrus and inferior parietal lobule, especially in the dominant side. These results offer further evidence suggesting that the lexico-semantic processing system is mediated in these regions.

Aged↗

PubMedDate not supplied

Clinical diagnosis of dementia with Lewy bodies in a Japanese dementia registry.

We found 15 patients with dementia with Lewy bodies (DLB) and 232 patients with Alzheimer's disease (AD) among 327 consecutive patients with mild to moderate dementia in a Japanese dementia registry, using the clinical criteria of the Consortium on DLB International Workshop. The percentage of females was significantly lower in DLB than in AD (p < 0.01), while age at examination, Mini-Mental State Examination score and duration of cognitive symptoms were comparable between the two diseases. Eight of the 15 DLB patients (53%) had spontaneous parkinsonism, which was observed in 6 of the 232 AD patients (2.6%). Visual hallucinations were reported by 11 of the 15 DLB patients (73%) and 8 of the 232 AD patients (3.4%). Cognitive fluctuation was positive in 13 of the 15 DLB patients (87%). We found two types of episodic cognitive deterioration: one was characterized by pronounced disturbances of attention and alertness (inattention type), and the other was characterized by marked and bizarre disturbances of orientation in time and places, and misidentification of persons (disorientation type). Systematized delusion was observed in 8 DLB patients, and 5 patients showed neuroleptic sensitivity. Patients with DLB have a unique dementia syndrome even in the stage of mild to moderate cognitive impairments. Further studies are recommended to establish diagnosis, treatment and management.

Aged↗

PubMedDate not supplied

A study of remote memory impairment in Alzheimer's disease by using the family line test.

We evaluated remote autobiographical memory impairment in 25 patients with probable Alzheimer's disease (AD) and 25 sex-, age- and education-matched healthy subjects by using a newly developed, highly effective assessment tool for remote memory, the Family Line Test (FLT). The FLT yields a total score, scores for 3 lifetime periods and the duration of remote memory impairment. In the patients with AD, the total score was significantly lower and the duration of remote memory impairment was significantly longer than in the healthy controls. A prominent temporal gradient in remote memory impairment was documented in the patients with AD. The total FLT score and duration of remote memory impairment correlated with recent memory and general cognitive dysfunctions.

Aged↗

PubMedDate not supplied

Features of regional cerebral glucose metabolism abnormality in corticobasal degeneration.

We studied regional cerebral glucose metabolism in 15 patients with a clinical diagnosis of corticobasal degeneration (CBD), 15 patients with probable Alzheimer's disease (AD), and 15 healthy controls for 19 brain regions. Asymmetry in regional glucose metabolism was found in the central and frontal cortices in patients with CBD as compared with either the normal controls or the patients with AD. Regional glucose metabolism in CBD patients was significantly lower in the paracentral and superior parietal areas and thalamus than in patients with AD. Relative glucose metabolism in patients with CBD was significantly higher in the posterior cingulate, medial temporal and basal frontal areas, and significantly lower in the paracentral and superior parietal areas than in those with AD. These features of regional glucose metabolic abnormality in CBD may correspond to neurological and cognitive disturbances peculiar to CBD.

Aged↗

PubMedDate not supplied

Neuronal substrates for semantic memory: a positron emission tomography study in Alzheimer's disease.

We examined 57 patients with mild Alzheimer's disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.

Aged↗