PubMed Health⌕ Search

Biomedical subjects

R Pokorny

Publications and source records attributed to R Pokorny.

14 recordsLinked to original sources

Absorption and fluorescence spectroscopic characterization of cryptochrome 3 from Arabidopsis thaliana.

The blue light photoreceptor cryptochrome 3 (cry3) from Arabidopsis thaliana was characterized at room temperature in vitro in aqueous solution by optical absorption and emission spectroscopic studies. The protein non-covalently binds the chromophores flavin adenine dinucleotide (FAD) and N5,N10-methenyl-5,6,7,8-tetrahydrofolate (MTHF). In the dark-adapted state of cry3, the bound FAD is present in the oxidized form (FAD(ox), ca. 38.5%), in the semiquinone form (FADH., ca. 5%), and in the fully reduced neutral form (FAD(red)H2) or fully reduced anionic form (FAD(red)H-, ca. 55%). Some amount of FAD (ca. 1.5%) in the oxidized state remains unbound probably caused by chromophore release and/or denaturation. Förster-type energy transfer from MTHF to FAD(ox) is observed. Photo-excitation reversibly modifies the protein conformation causing a slight rise of the MTHF absorption strength and an increase of the MTHF fluorescence efficiency (efficient protein conformation photo-cycle). Additionally there occurs reversible reduction of bound FAD(ox) to FAD(red)H2 (or FAD(red)H-, FAD(ox) photo-cycle of moderate efficiency), reversible reduction of FADH. to FAD(red)H2 (or FAD(red)H-, FADH. photo-cycle of high efficiency), and modification of re-oxidable FAD(red)H2 (or FAD(red)H-) to permanent FAD(red)H2 (or FAD(red)H-) with low quantum efficiency. Photo-excitation of MTHF causes the reversible formation of a MTHF species (MTHF', MTHF photo-cycle, moderate quantum efficiency) with slow recovery to the initial dark state, and also the formation of an irreversible photoproduct (MTHF'').

Absorption↗

Laparoscopic repair of lumbar hernias.

BACKGROUND: Lumbar hernias are rare defects in the posterolateral abdominal wall that may be congenital or acquired. Repairing these defects is difficult by virtue of their location and the inherent weakness of the surrounding tissues. We report a series of seven patients who had their lumbar hernias repaired laparoscopically at two institutions. STUDY DESIGN: We retrospectively reviewed all lumbar hernias repaired laparoscopically in our institutions within the last 16 months (August 1996 to November 1997). Postoperative followup was 1-15 months. RESULTS: Seven patients underwent laparoscopic repair. Five hernias were acquired defects and two were congenital. One to three defects were found per patient. The average size of the hernia defect was 77.8 cm2. We used a polypropylene or a polytetrafluoroethylene mesh in all patients; the average size of the mesh used was 336.4 cm2. The average length of hospital stay was 1.7 days. One patient returned with an abscess over the mesh, which necessitated removal of the graft. Otherwise, there were no complications, and the remaining six patients had no recurrences after followup of 1-14 months. CONCLUSIONS: The laparoscopic approach is safe and effective for repairing lumbar hernias. Advantages of this approach include excellent operative visualization, decreased hospital stay postoperatively, and a solid repair without recurrence during shortterm followup.

Hernia, Ventral↗

Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention in humans.

Effects of the novel competitive N-methyl-D-aspartate (NMDA)-receptor antagonist SDZ EAA 494 were investigated on memory and attention in humans. SDZ EAA 494 was administered either as single doses at a dose range of 1-50 mg, or as multiple doses over the course of 1 week at doses of 25 mg once or twice daily. Selected cognitive functions were assessed at baseline, 2 and 4 h after single dose administration, and at baseline, 2, 4 and 8 h on days 1 and 7 of multiple dose administration. The assessments included simple and complex reaction time tests to assess attention, and verbal, non-verbal and spatial memory tests with immediate and late recall. Verbal and non-verbal memory test performance was significantly impaired at a dose level of 50 mg after single administration, and of 25 mg twice daily after multiple administration, without concomitant significant impairment of reaction time. Spatial memory test performance was not significantly affected. The maximum effect occurred 2 h postmedication and was more pronounced after repeated administration. These results suggest that the inhibition of NMDA-receptors in humans may impair memory processes.

Adult↗

Exercise-induced compartment syndrome: case report.

Exercise-induced rhabdomyolysis is a frequent event occurring after severe forms of exercise. This is usually a short-lived, uncomplicated phenomenon that is seldom of any clinical significance. The rare progression of this muscle injury to compartment syndrome is, however, a limb- and life-threatening condition that typically presents in the anterior compartment of the lower leg. A case is reported of a young man who participated in physical activity well beyond his normal level of exertion and subsequently developed bilateral lower extremity compartment syndrome requiring surgical decompression. To our knowledge, this is the only description of this complication occurring in a multicompartment, bilateral distribution. The combination of the rarity and morbidity of this condition, as well as the multitude of very common benign injuries that present in the same manner as the problem discussed, make this insult especially dangerous.

Adult↗

Memory and attention test performance of young and elderly subjects after retest practice.

The effects of training on two memory and two attention tasks were investigated in 24 healthy elderly and 23 young subjects. Two training periods, each consisting of four sessions, were performed, and the effects of training were assessed during two test sessions 1 week thereafter. Significant age-related effects at the pretraining test session were found for reaction times to a simple visual stimulus, retrieval time of information from long-term storage, and the speed of focusing attention. In both age groups, performance of the first two tasks was significantly improved by training; however, the age-related effect remained significant after training. In the focused attention task, the age difference at baseline disappeared after training due to an opposite learning trend in young and elderly subjects. Thus, the cognitive performance of elderly subjects could be trained to a large extent. Significant age differences, however, could be decreased only if the test performance of young subjects did not improve.

Adult↗

Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Sirdalud).

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg's pendulum test. Blood samples, a clinical assessment of muscle tone by the Ashworth scale, and muscle strength by the British Medical Research Council scale were obtained concomitantly. Confirmatory analysis using the change in the relaxation index (R2 value) 1.5 hours after each treatment, showed a statistically significant (p = 0.0123) linear dose-response relation between single doses and antispastic action of tizanidine. Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0.014 and 0.004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually.

Adult↗

Pharmacokinetics and pharmacodynamics of tizanidine.

The relationship among tizanidine dose, plasma concentration, and antispastic action is linear in nature. Response to a given dose of this agent varies among patients, and determining the appropriate clinical dose requires individual titration.

Clonidine↗

Pharmacokinetics of recombinant human interleukin 3 administered subcutaneously and by continuous intravenous infusion in patients after chemotherapy for ovarian cancer.

Twenty chemotherapy-naive patients with ovarian carcinoma received 1, 5, 10, or 15 micrograms/kg/day (five patients per dose step) of recombinant human interleukin 3 (rhIL-3) over 7 days after carboplatin/cyclophosphamide in Cycles 1 and 3. Patients received rhIL-3 by continuous i.v. infusion or once daily s.c. injection in Cycle 1 and the alternate route in Cycle 3. Plasma rhIL-3 samples were obtained once daily on Days 1 to 6 and serially over a 24-h period on Day 7 for pharmacokinetic assessment of s.c. and i.v. administered rhIL-3 in 16 and 17 patients, respectively. Concentrations were assayed by a time-resolved fluorescence sandwich immunoassay. Pharmacokinetic parameters were derived by noncompartmental methods. Mean steady-state concentrations during continuous i.v. infusion ranged from 117 pg/ml (1 microgram/kg/day) to 2217 pg/ml (15 micrograms/kg/day) and were linearly related to dose (r = 0.87, P < 0.001). When dose normalized, the mean steady-state concentrations were comparable at all doses. The total-body clearance was approximately 4 to 5 ml/min/kg. Elimination half-life (t1/2 i.v.) could be assessed for the 5- to 15-micrograms/kg/day dose levels and was 53, 41, and 26 min for the 5-, 10-, and 15-micrograms dose levels, respectively (not significant between dose levels). Following s.c. injection, the maximum rhIL-3 plasma concentration ranged from 206 pg/ml (1 microgram/kg/day) to 6930 pg/ml (15 micrograms/kg/day). Both the maximum measured plasma concentration (r = 0.89, P < 0.0001) and the area under the plasma concentration/time curve (r = 0.93, P < 0.0001) were related to dose. Dose-normalized values were comparable over the entire dose range. Elimination t1/2s.c. was 4.8 h at the 1-microgram dose level and roughly half this time for the 5- to 15-micrograms/kg/day dose levels. The systemic clearance of approximately 5 to 6 ml/min/kg was comparable at all dose levels. Based on trough levels of the 7-day s.c. course, no rhIL-3 accumulation occurred. Bioavailability of s.c. administered rhIL-3 was nearly 100%. No correlation between creatinine clearance and pharmacokinetic parameters of rhIL-3 could be demonstrated. Since there was also no difference in hematological efficacy between the two routes of rhIL-3 administration, we conclude that the s.c. route of administration appears to have no disadvantages over the i.v. route and may facilitate its clinical application.

Adolescent↗

Differential activation of the endogenous leukotriene biosynthesis by two different preparations of granulocyte-macrophage colony-stimulating factor in healthy volunteers.

Results from in vitro investigations and recent data obtained in patients with drug-induced cytopenia or myelodysplasia suggest that leukotrienes may be involved in mediating some of the actions of granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, the possible role of leukotrienes was further characterized in 21 healthy individuals to avoid modification of response to GM-CSF by disease-specific variables. The effects of two different preparations of human recombinant GM-CSF, ie, glycosylated GM-CSF as expressed in a Chinese hamster ovary carcinoma (CHO) cell line and nonglycosylated GM-CSF obtained from Escherichia coli, were compared. GM-CSF was administered subcutaneously at a single dose of 0.7 nmol/kg body weight. Pharmacokinetic parameters and hematopoietic and adverse effects were monitored by blood analyses or physical examination, respectively. Leukotriene generation in vivo was evaluated by determination of leukotriene E4 and N-acetyl-leukotriene E4 in urine. After the injection of GM-CSF from E coli, serum concentrations increased and decreased more rapidly and reached a 2.3-fold higher maximum compared with GM-CSF from CHO. GM-CSF induced a biphasic change in leukocyte counts that proceeded considerably faster after the E coli preparation than after GM-CSF from CHO. The urinary leukotriene concentration increased 1.3- to 14-fold or 2.1- to 44-fold after the administration of GM-CSF from CHO or E coli, respectively. Urinary leukotriene concentrations correlated significantly with the maximum of basophil counts and correlated with the occurrence of some adverse reactions, ie, flu-like symptoms, bone pain, or dyspnoea. Our data confirm the conception that leukotrienes may play a significant role in GM-CSF action in vivo. They especially direct attention to the possible relevance of leukotrienes to untoward effects of GM-CSF treatment.

Adult↗

Bias effects on magnitude and ratio estimation power function exponents.

A bias model of relative judgment was used to derive a ratio estimation (RE) power function, and its effectiveness in providing estimates of exponents free of the effects of standards was evaluated. The RE bias model was compared with the simple RE power function that ignores bias. Results showed that when bias was not taken into account, estimates of exponents exhibited the usual effects of standards observed in previous research. However, the introduction of bias parameters into the RE power function virtually eliminated these effects. Exponents calculated from "equal-range segments" (e.g., low stimulus range vs. high stimulus range) judged by magnitude estimation (ME) were examined: the effects of equal-range segments on exponents were much stronger for ME than standards were for RE, using the bias model.

Attention↗

Effect of morphine on the electroencephalogram and other physiological and other physiological and behavioral parameters.

A double-blind, crossover, placebo-controlled study was carried out in 10 healthy male volunteers to investigate the effects of subcutaneously administered single doses of 4 and 8 mg morphine and 2.5 and 5 mg of a new centrally acting analgesic with a benzomorphane structure. After an adaptation session, each subject received all five treatments in a random sequence at intervals of 1 week. Quantified EEG, cardiovascular and behavioral parameters, quantitative respiratory measurements, body temperature, symptom reports, pain threshold estimates, and blood drug assays were used to assess the effects of the drugs. The measurement battery was completed before injection and after 30, 60, 120, 240 and 360 min. In addition, EEG, blood samples and respiratory signals were also taken during/after the first 5, 10, 15, 20 and 25 min. As the new compound did not show any obvious advantages over morphine, only the results with the latter substance are reported here. As the main effects of morphine on the EEG a dose-dependent slowing and monorhythmization of alpha and an increase of the average frequency of fast beta activity were observed. Slow EEG waves tended to decrease. Heart rate and body temperature decreased, whereas there was no discernible effect on blood pressure. Subjects reported feelings of drowsiness, muzziness, lethargy and mental slowness. The pain threshold increased. All these effects had a maximum between min 120 and 240, although the highest blood levels of the parent drug were measured 10-25 min after drug administration. An explanation for this delay might be that the pharmacological effects are due not to free morphine but to one of its metabolites.

Adult↗

Quantitative pharmaco-electroencephalographic differentiation between the CNS effects of bromocriptine and imipramine, drugs with qualitatively different antidepressant properties.

Two double-blind, placebo-controlled studies were carried out at two different centers using the same protocol. Eight young healthy male volunteers were recruited for each of the studies, which were both undertaken to investigate the effect of single doses of 0.6, 1.25 and 2.5 mg bromocriptine (Parlodel) in comparison with 25 and 50 mg imipramine (Tofranil) on the electroencephalogram (EEG), subjective mental and emotional states, blood pressure, heart rate, and plasma prolactin levels. Side effects were also noted. The changes in the resting EEG power spectrum after imipramine were an increase in slow wave and fast beta activity and a decrease in alpha activity. At the same time imipramine depressed subjective mental and emotional states. Bromocriptine slowed the alpha activity of the resting EEG power spectrum, depressed subjective mental and emotional states, lowered blood pressure, and reduced prolactin secretion.

Adolescent↗

Electroencephalographic and psychometric assessment of the CNS effects of single doses of guanfacine hydrochloride (Estulic) and clonidine (Catapres).

A double-blind, placebo-controlled study was carried out in 10 young healthy volunteers to investigate the effects of single doses of 1 and 2 mg guanfacine hydrochloride (Estulic) and 0.15 and 0.3 mg clonidine (Catapres) on the electroencephalogram (EEG), subjective mental and emotional state, blood pressure and heart rate. These doses are considered to be equipotent with regard to their antihypertensive effects, as shown in long-term therapeutic trials. Each subject received all five treatments in random sequence at intervals of 1 week. The EEG tracings were evaluated quantitatively by spectral analysis. Procedures were carried out before and at 1, 2, 4, 6 and 8 h after drug administration. After clonidine the EEG showed increased slow-wave activity and decreased alpha activity, these effects being dose-dependent. They were of the sedative type and did not clearly indicate specific psychotropic properties. The subjective mental and emotional state questionnaire indicated a decrease of alertness, extroversion, concentration and mood (in that order), changes which paralleled the EEG changes. The changes observed after guanfacine were qualitatively similar to those after clonidine, but were of considerably lower intensity. Our data suggest that guanfacine has less central nervous system-depressant activity than clonidine.

Adult↗