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Biomedical subjects

H Blume

Publications and source records attributed to H Blume.

At least 37 records · Page 2Linked to original sources

Neurophysiologic correlates of implicit face memory in intracranial visual evoked potentials.

Visual evoked potentials were recorded in the amygdala, hippocampus, mid- and inferotemporal cortex, orbitofrontal cortex, and lateral frontal cortex of seven epileptic patients while they were engaged in a difficult task requiring the discrimination between repeated and nonrepeated faces. The explicit recognition of previously seen faces was at chance levels, as measured by the accuracy of push-button responses. Nevertheless, all subjects showed clear-cut differential evoked responses to repeated versus nonrepeated faces, indicating implicit encoding of the distinction between the two types of stimuli. Differential responses were more frequent in neocortical recording sites (especially in the mid- and inferotemporal leads) than in limbic recording sites such as the amygdala and hippocampus. The authors conclude that implicit encoding processes are modulated by neocortical visual association areas of the temporal lobes.

Adult↗

Enantioselective determination of diprafenone in human plasma.

A sensitive (10.0 ng/ml) and stereoselective HPLC method for analysis of S(-)- and R(+)-diprafenone in human plasma has been developed. The assay is based on derivatization with homochiral R(-)-1-(1-naphthyl)ethyl isocyanate to give the diastereomeric derivates and their separation and quantitation using HPLC with UV-detection (220 nm). Details of this stereoselective assay procedure which has already been applied to the multisample analyses from a human pharmacokinetic study are described. The data obtained indicated that the stereoselective disposition of diprafenone enantiomers is quite different from their structural and pharmacological analog propafenone.

Administration, Oral↗

[The relative bioavailability of paracetamol in suppositories in comparison to tablets].

Relative Bioavailability Studies on Paracetamol in Suppositories as Compared to Tablets. Relative bioavailabilities of 250 mg paracetamol (CAS 103-90-2) in ben-u-ron 125 mg and ben-u-ron 250 mg suppositories were determined in comparison with that of cut-in-half Benuron tablets 500 mg in an open intraindividual 3-period-changeover-study in 18 healthy volunteers. Plasma concentrations of paracetamol were analyzed by means of a specific and sensitive HPLC-method with UV-detection. For the assessment of the bioavailability AUC, Cmax, tmax and HVD (half value duration) were used as pharmacokinetic characteristics. Relative bioavailability of paracetamol was 102% for 125 mg and 93% for 250 mg suppositories, compared with that of cut-in-half 500 mg tablets. Mean maximum paracetamol plasma concentrations (Cmax) were determined as 2.1 micrograms/ml (CV = 31%; (CV = Coefficient of Variation), 2.0 micrograms/ml (CV = 27%) and 3.5 micrograms/ml (CV = 27%) after administration of 125 mg and 250 mg suppositories and 500 mg cut-in-half tablets, respectively. These maximum concentrations were achieved 2.2 +/- 0.7, 1.8 +/- 0.7 and 0.6 +/- 0.3 h (tmax) after administration of the respective preparations. The corresponding HVD-values were 3.8 +/- 1.0, 3.5 +/- 0.9 and 1.8 +/- 0.8 h, respectively. Extent of bioavailability of paracetamol (dose: 250 mg) following administration of 125 mg as well as 250 mg suppositories in comparison with 500 mg tablets was shown to be equivalent. The results obtained in this study confirm the adequate bioavailability of both suppositories compared with tablets. On the other hand both suppository preparations were assessed as being bioequivalent concerning AUC and Cmax.

Acetaminophen↗

Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain.

Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task-related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding. In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set.

Adult↗

Clinical pharmacological equivalence of a novel FCH-free GTN spray with low ethanol content vs a FCH-containing GTN spray.

The overall therapeutic equivalence of a fluorochlorohydrocarbon (FCH)-free glyceryl trinitrate (GTN) pump spray with a low ethanol content (TL) was investigated relative to an FCH-containing GTN spray (Nitrolingual; R), in terms of: (1) pharmacokinetic bioavailability, (2) pharmacodynamic responses as assessed by digital plethysmography (DPG), and (3) clinical perception upon application. Pharmacokinetically, the time courses of the plasma concentrations of GTN and its dinitrate metabolites, 1,2- and 1,3-GDN, subsequent to the sublingual administration of 0.8 mg GTN showed somewhat lower bioavailability of GTN and its metabolites than to the reference. Pharmacodynamically, the changes in the DPG signals after the application of 0.8 mg GTN with TL were biostatistically equivalent with R (estimated ratio TL/R for the maximum decrease of the ratio between the systolic a wave and c incisure: 0.98; 90% CI: 0.84-1.14; and for the average decrease of the c: a ratio: 0.97; 90% CI: 0.80-1.16). The time of occurrence of the maximum effect of TL was not significantly different from that of R (estimated difference TL-R: -2.25 min; 95% CI:-9.5 min to 2 min). In contrast, after the administration of an FCH-free GTN spray with a higher ethanol content (TH, active control), the effect had a slightly earlier onset (TH-R: -6 min, 95% CI:-9.5 to -2 min) and there was a higher average response (TH/R: 1.12: 90% CI: 0.95 to 1.34). However, TH was consistently judged to cause an extremely unpleasant burning sensation in the mouth and thus was perceived as distinctly different from R. In contrast, TL was well tolerated and could not be distinguished from R.

Adult↗

NBQX blocks acute and late epileptogenic effects of perinatal hypoxia.

Clinically, and in experimental models, perinatal hypoxic encephalopathy is commonly associated with seizures. We previously described a rat model in which hypoxia induces seizures and permanently increases in seizure susceptibility in immature rats [postnatal day (P) 10-12] but not in older rats. In the present study, we compared the effect of pretreatment with the excitatory amino acid antagonists MK-801 and NBQX versus lorazepam in our rat model of perinatal hypoxia. Animals exposed to hypoxia at P10 without treatment have frequent seizures during hypoxia and subsequently exhibit increased seizure susceptibility to flurothyl. Treatment with 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX 20 mg/kg) effectively suppressed hypoxia-induced seizures in immature rats and also protected against permanent changes in flurothyl threshold in adulthood, whereas treatment with MK-801 (1 mg/kg) or lorazepam (LZP 1 mg/kg) did not prevent these hypoxia-related epileptogenic effects. These results suggest that activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptors may partly mediate the age-dependent epileptogenic effect of hypoxia in the perinatal period.

Age Factors↗

DQE(f) of four generations of computed radiography acquisition devices.

Measurements were made of the MTF(f), NPS(f), and DQE(f) of four generations of computed radiography (CR) imaging plates and three generations of CR image readers. The MTF generally showed only a minor change between generations of plates and readers, but the DQE(f) has improved substantially from a very early plate/reader combination to a more recent one. The DQE in the more recent plate/reader combination is 1.3X greater at low frequencies and about 3X greater at high frequencies than the much earlier versions. Thus there has been substantial improvement in the imaging performance obtainable with CR since some of the early observer studies which indicated poorer performance with CR than with screen-film.

Humans↗

[Comparison of the bioavailabilities of erythromycin estolate and erythromycin ethylsuccinate dry suspension preparations in steady state].

Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound.

Adult↗

Reference tables for the intrasubject coefficient of variation in bioequivalence studies.

Bioequivalence studies are usually performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. However, this information is usually not accessible in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. It is the purpose of the present communication to provide reference values of the intrasubject coefficient of variation for various previously investigated drugs. The presentation includes pertinent pharmacokinetic characteristics for immediate- and extended-release formulations in single- and multiple-dose crossover studies.

Administration, Oral↗

[HPLC-determination of loratadine and its active metabolite descarboethoxyloratadine in human plasma].

The quantitative determination of loratadine (1) and its active metabolite descarboethoxyloratadine (2) is described. Because of the high difference in polarity between 1 and 2, the two analytes were determined in two HPLC-systems separately. As internal standards propyl-4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]-cyclohepta-[1,2-b]- pyridin-11-ylidin)-1-piperidincarboxylate (3) and 1-ethyl-4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]-cyclohepta- [1,2-b]-pyridine-11-ylidin)-piperidine (4) were used for 1 and 2, respectively. After extraction with organic solvents from 1 ml plasma, 1 and 2 were reextracted with diluted phosphoric acid from the organic phase. Chromatographic separation on a RP-18 column and fluorescence detection allowed a sufficiently sensitive determination of 1 and 2 in plasma with a lower limit of quantitation of 0.5 ng/ml for both analyts. The method was successfully applied to human plasma samples from 16 subjects after oral administration of 20 mg 1.

Chromatography, High Pressure Liquid↗

[Relative bioavailability of paracetamol in suppositories preparations in comparison to tablets].

Relative Bioavailability of Paracetamol as Suppositories Compared to Tablets. The relative bioavailability of paracetamol (CAS 103-90-2) in ben-u-ron 500 mg and ben-u-ron 1000 mg suppositories (test formulations) was compared with that of Benuron tablets 500 mg (reference product) in an open, intraindividual, 3-period-changeover-study in 18 healthy subjects. Plasma concentrations of paracetamol were determined using a specific and sensitive HPLC method with UV detection. For the assessment of bioavailability AUC, Cmax, tmax and HVD were used as pharmacokinetic characteristics. Bioequivalence of the rectal formulations was tested by calculating 90% confidence intervals using the Two-one-sided-t-tests-procedure and log-transformed data of AUC and Cmax. For AUC the confidence intervals were required to be in the 80 and 125% range, for Cmax between 70 and 143% (inclusion rule). Data from 17 subjects could be evaluated. Bioavailability of paracetamol was 89 and 90% for the 500 and 1000 mg suppositories, respectively compared with that of the 500 mg reference tablets. Mean maximum paracetamol plasma concentrations (Cmax) were 3.55 and 6.02 or 7.16 mg/l after administration of the 500 and 1000 mg suppositories or the 500 mg tablets, respectively. These maximum concentrations were achieved 2.0, 2.7 and 0.6 h (tmax) after administration of the respective preparations. The corresponding HVD values were 4.3, 5.2 and 2.0 h, respectively. After dose adjustment of the results for the 1000 mg suppositories relative bioavailabilities of paracetamol from both rectal formulations exceeded 80% of that from the tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Presentation of the intrasubject coefficient of variation for sample size planning in bioequivalence studies.

Bioequivalence studies are generally performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. Unfortunately, this information is usually not presented in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. Thus, the essential information for sample size planning of future studies is not made available to other researchers. In order to overcome such shortcomings, the presentation of results from bioequivalence studies should routinely include the intrasubject coefficient of variation. For the relevant coefficients of variation, theoretical background together with modes of calculation and presentation are given in this communication with particular emphasis on the multiplicative model.

Humans↗

[The bioavailability of enteric coated diclofenac formulations. 2. Bioavailability following single administration of a multiple-unit formulation in comparison to a single-unit formulation under fasting and non-fasting conditions].

Relative bioavailability of enteric-coated diclofenac (CAS 15307-86-5) was investigated after a single-dose administration of a multiple-unit formulation (Diclo-Puren 50, test) in comparison to a single-unit formulation (reference). The study was carried out in a four-way change-over design including a group of 12 healthy male volunteers. Each formulation was administered after 10 h of fasting or just after (5 min) finishing a meal (standard breakfast). Diclofenac plasma concentrations were measured using a selective and sensitive GLC-MS method after liquid-liquid extraction and derivatisation. Area under the curve (AUC), maximum plasma concentrations (Cmax), time of maximum plasma concentration (tmax), time of delay of first measurable concentrations (tlag) and plateau time of concentrations above minimum effective concentrations (MEC) of 50 ng/ml (tMEC(50)) and 100 ng/ml (tMEC(100)), respectively, were evaluated as pharmacokinetic characteristics. Additionally, for AUC and Cmax, 90%-confidence intervals (parametric: ANOVA, ANOVAlog, non-parametric: Mann-Whitney) were calculated to evaluate the influence of food on bioavailability of each formulation. Mean (median) relative bioavailabilities of diclofenac of the test formulation (comparison: postprandial vs. fasting conditions) were determined for the test formulation as 96% (103%) and for the reference product as 70% (83%). Mean +/- SD (median) maximum plasma concentrations of the test formulation were determined as 695 +/- 313 (677) ng/ml (fasting) and as 452 +/- 163 (456) ng/ml (postprandial). Maximum plasma concentration occurred 1.2 +/- 0.5 (1.0) h and 4.8 +/- 1.0 (5.0) h after administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Determination of E. coli with MUG (Fluorocult)-lauryl sulfate broth for the testing of microbial contamination in drugs].

A test method for the determination of Escherichia coli in plant materials with the MUG (Fluorocult)-lauryl sulfate broth is described. It was found that more than 75% of the commonly used vegetable drugs exhibit fluorescence quench effects to different degrees when determining E. coli with the MUG-lauryl sulfate broth. Therefore a simple combination of two procedures was evaluated in order to avoid the matrix interferences: in a first step the drug sample was diluted eight times in a proportion of 1:10 with MUG-lauryl sulfate broth in eight separate tubes from 1 g down to 10(-7) g/tube (1st test series) and the resulting samples were incubated for 40 h at 36 degrees C. Subsequently, the tubes were tested for fluorescence. If the first tube of this series was found without fluorescence, in a second step a subsequent series of MUG-lauryl sulfate broth (2nd test series) was inoculated with 0.5 ml of the incubated culture from each of the first three tubes of series 1 and incubated again for 24 h at 36 degrees C. The results were evaluated from gas production, fluorescence as well as indole formation. Thus, the method allowed a simple and reproducible enumeration of E. coli for the test on microbial contamination in medicinal plant materials. The method was successfully applied to samples of 38 vegetable drugs for quantitative determination of E. coli (8 samples were found being contaminated with E. coli).

Culture Media↗

[HPLC determination of diprafenone and its active metabolite 5-hydroxydiprafenone in human plasma].

A simple, specific and sensitive HPLC method is described, which allows the quantitation of diprafenone and its active metabolite 5-hydroxydiprafenone in human plasma. Propafenone is used as internal standard. After extraction by diethyl ether from plasma, the analytes are reextracted with 5% phosphoric acid from the organic phase. Chromatographic separation on a RP-18 column and UV detection (220 nm) allows the sensitive determination of diparafenone and 5-hydroxydiprafenone in plasma with a lower limit of quantitation of 5.0 ng/ml for both substances. The method was successfully applied to human plasma samples from 24 subjects after oral or i.v. administration of 300 mg or 50 mg diprafenon hydrochloride, respectively.

Administration, Oral↗

Differential neural activity in the human temporal lobe evoked by faces of family members and friends.

In 6 patients, depth electrodes revealed differential evoked responses to familiar versus novel faces. These differential responses were obtained in the amygdala, hippocampus, and temporal neocortex but not in the dorsolateral frontal or cingulate cortex. The limbic and temporal structures that differentiated novel from familiar faces did not respond differentially to variations in luminance. Limbic structures and temporal cortex thus appear to participate in face recognition and in encoding the familiarity of visual experiences.

Adult↗