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141.
Carbamazepine (CAS 298-46-4), an iminostilbene derivative and a structural congener of the tricyclic antidepressant drugs, has been used in the treatment of epileptic seizures since 1963. The bioavailability/bioequivalence of a carbamazepine sustained release formulation (Timonil retard) was compared with a reference formulation in an open 2-period crossover study in 21 healthy male volunteers (including 1 drop-out) after multiple dose administration. During a run-in phase of 6 days the daily dose was gradually increased from 100 to 400 mg. On days 9 to 15, either the test or the reference formulation was administered twice daily, followed by a switch of preparation for a further 7 days of treatment (days 16 to 22). On the pharmacokinetic profiling days 15 and 22 blood samples were drawn over a 24-h period. In addition, blood samples were withdrawn before morning administrations for determination of carbamazepine and carbamazepine-10,11-epoxide trough values. Plasma concentrations of carbamazepine and its metabolite carbamazepine-10,11-epoxide were determined using a specific and sensitive HPLC method with UV detection. The results showed that autoinduction of carbamazepine metabolism under the chosen dosage regimen was complete within 14 days after start of treatment and that the criteria for bioequivalence were met. The 90% confidence intervals of all ratios were included by a range of 80-125% (AUC0-12: 103-120; AUC12-24: 105-119; Cmax0-12: 104-118; Cmax12-24: 104-118). During the study, 12 subjects experienced a total of 24 adverse events with mild to moderate intensity. Due to a significant increase of liver enzyme activity in serum during the course of the study, one subject was excluded from further study participation. There were no serious adverse events. It was concluded that the test formulation is bioequivalent to the reference formulation with respect to rate and extent of absorption. 相似文献
142.
AL Vincent CA Ure?a Rojas EM Ayoub EA Ottesen EG Harden 《Canadian Metallurgical Quarterly》1998,84(3):557-561
Protein complexes present different degrees of stability. We have previously described a glycoprotein from Bacillus thuringiensis that appeared as a multimer unable to be dissociated by the usual SDS-containing sample buffers of pH 6.8. In order to dissociate the complex, a SDS-containing sample buffer of pH 9 was described. In the present report three additional protein complexes with different degrees of stability and the effect of that dissociating sample buffer are described. The study of SDS critical micellar concentration values as a function of pH explains the improvement of dissociating properties at pH 9. 相似文献
143.
M Tristani-Firouzi EG DeMaster BJ Quast DP Nelson SL Archer 《Canadian Metallurgical Quarterly》1998,131(3):281-285
Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic disorder causing central nervous system haemangioblastomas. The VHL gene (3p25-3p26) is known to be a tumour suppressor gene, with its inactivation being responsible for a predisposition to tumour development. As far as we know, the present report of VHL disease manifestation in identical twins is unique. Genetic inquiry into the family background did not reveal this disease among their progenitors. For presymptomatic diagnosis of 17 presently unaffected family members, constitutional DNA of the twins was screened for VHL germline mutations, using loss of heterozygosity studies and exon-specific DNA sequencing. To determine the influence of somatic mutations of the VHL gene in tumourigenesis, DNA of five surgically removed intracerebral haemangioblastomas of the identical twins was analyzed in comparison with their constitutional DNA by DNA sequencing of the complete VHL coding region. However, no allelic losses were found for the VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC, and MCC). Furthermore, no mutations were found in the constitutional DNA of either twin sister or in the DNA of all five tumour lesions. Based on our observations, we conclude that in certain VHL families, presymptomatic molecular diagnosis of the disease is not feasible and requires close clinical surveillance of all individuals at risk. 相似文献
144.
M Grinberg A Halpern EG Rossi CC Leite JC Sbano 《Canadian Metallurgical Quarterly》1998,70(3):181-183
We report MRI and angiographic findings of an unusual giant arachnoid granulation in the left sigmoid sinus in a boy with headache. Its signal intensity was lower than that of cerebral cortex on T1-weighted images and higher on T2 weighting, mimicking dural sinus thrombosis. 相似文献
145.
R Schwaab J Oldenburg EG Tuddenham HH Brackmann K Olek 《Canadian Metallurgical Quarterly》1993,83(3):450-458
In the present study DNA from 281 unrelated haemophilia A patients including 15 inhibitor patients has been analysed by Southern blotting technique. Using various restriction enzymes, cloned factor VIII cDNA probes and genomic fragments we have identified 14 mutations. Six of the mutations are novel partial factor VIII gene deletions. One deletion affects exon 1, two deletions concern exon 6, another deletion, of which breakpoints are sequenced, takes part of exon 16 and two deletions affect exon 26. Besides the deletions, eight point mutations have been found at the TaqI restriction sites of exons 18, 24 and 26. Five C-->T mutations resulted in nonsense mutations, one in exon 18, one in exon 26 and three in exon 24. Two G-->A mutations caused a missense mutation in exon 24 leading to an arginine/glutamine exchange. Although two patients showed this mutation, their clinical phenotypes were different, possibly due to an additional unidentified sequence polymorphism. A G-->T mutation in exon 26 substituted the arginine with leucine. All deletions and seven of the point mutations are associated with severe disease with a detectable inhibitor in the patient with the TaqI-point mutation in exon 18. One of the G-->A mutations is associated with mild haemophilia but the patient also has developed an inhibitor. Amongst these mutations the origin of the mutation could be determined in four kindred, one of which showed maternal mosaicism. 相似文献
146.
In order to carry out investigations in the course of sport activities of children an efficient telemetering device is essential, which can also be used on children. The Kinderspital Salzburg has developed a telemetry system in cooperation with the Technische Versuchs- und Forschungsanstalt der Technischen Hochschule Wien and the Messerschmitt-B?lkow-Blohm-Werke München. For the first time in this field a Pulse Code Modulation (P.C.M.) System was utilized, implying high accuracy on data transmission and recovery as required for scientific examinations. The children's physical capacity is determined on a bicycle ergometer, and the performance measured in this fashion is then compared with the performance achieved in sport. 相似文献
147.
Prolonged and monosymptomatic dysphasic status epilepticus 总被引:1,自引:0,他引:1
EG De Pasquet ES Gaudin A Bianchi SA De Mendilaharsu 《Canadian Metallurgical Quarterly》1976,26(3):244-247
Dysphasic seizures are an infrequent form of epilepsy, and their serial appearance as a partial status epilepticus is quite exceptional. The young patient reported here had a partial dysphasic status epilepticus of 3 weeks' duration without other temporal lobe seizures. Simultaneous serial electroencephalograms, tape recordings of the seizures, and repeated neuropsychologic ictal examinations permitted studies of increased impairment of neuropsychologic function on testing and the appearance of new irritative discharges on encephalography. 相似文献
148.
Disulfiram treatment caused marked elevations of circulating blood acetone levels in rat and man. In the rat, disulfiram (0.59 g/kg, p.o.) given singly or for three consecutive days increased the fasting blood acetone levels 5- and 25-fold, fespectively. Circulating acetone levels were also estimated noninvasively in man by measuring acetone in the expired air. A 15-fold increase in the expired air acetone levels was observed in a group of five male non-fasting subjects taking disulfiram (250 mg daily) for a minimum of one month, when compared to control subjects. 相似文献
149.
Independent intracellular activation of any one of the five identified neurones elicits a behavioral act of pneumostome closing. Similar closing is evoked by adequate stimulation of different modalities. Comparison of unconditioned reflex properties and characteristics of responses of the studied cells leads to the conclusion that neurones under discussion are command elements for the unconditioned reflex. Command neurones respond to all sensory stimuli which can evoke reflex closing. There is a lot of synchronous EPSPs in their spontaneous activity, but no action potentials. A spike discharge of command neurones evoked by an adequate stimulus always precedes the effector movements but there is no action potentials during the pneumostome closing. Conclusion is made that the functional role of command neurones in the unconditioned reflex arc consists in evaluating the sensory input and in triggering motor programmes. 相似文献
150.