Biomedical subjects

T Seppälä

Publications and source records attributed to T Seppälä.

At least 19 recordsLinked to original sources

PubMed2007

Premedication with controlled-release oxycodone does not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Controlled-release (CR) oxycodone provides an option for the prevention of postoperative pain. We designed this randomized double-blinded placebo controlled study to evaluate the control of pain after premedication with CR oxycodone 15 mg in addition to ibuprofen 800 mg orally in day-case gynaecological laparoscopic surgery. METHODS: Sixty consenting patients were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day in combination with fentanyl i.v. in the recovery room and normal-release (NR) oxycodone orally after the recovery room. The visual analogue scale (VAS) scores for pain and side-effects, and the amounts of postoperative analgesics were recorded for 24 h after discharge from the hospital. After a statistical analysis of the original study, we extended the study to investigate another 10 patients, who received CR oxycodone 15 mg orally in an open-labelled fashion 60 min before surgery. The plasma concentrations of oxycodone were measured from samples drawn before and 2, 4, 6 and 8 h after premedication. RESULTS: The amounts of fentanyl [100 microg (0-330) in the CR oxycodone group; 125 microg (0-330) in the placebo group], NR oxycodone, or the VAS scores for pain during the first 24 h after the discharge from the hospital did not differ after the premedication with CR oxycodone or placebo. In the extension study group, the peak plasma concentration (C(max)) of oxycodone was 10.0 (4.6-14.7) ng ml(-1), indicating possibly a sub-therapeutic level. CONCLUSION: Oral premedication with CR oxycodone did not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

Adult↗

PubMed2006

Schistocephalus cotti n. sp. (Cestoda: Pseudophyllidea) plerocercoids from bullheads Cottus gobio L. in an Arctic river in Finland, with a key to the plerocercoids of the Palaearctic species of the genus.

We compared plerocercoids of Schistocephalus Creplin, 1829 from Cottus gobio (n = 57) and Gasterosteus aculeatus f. semiarmatus (n = 45) from the River Utsjoki, Finland, taken only from single worm infections. Segment numbers in the two populations were distinct (G. aculeatus range 55-107, average 74 (SE 1.66), median 73; C. gobio range 122-189, average 146 (SE 1.78); median 144). The mean difference between populations, 71.47, t = 28.76 with 100 degrees of freedom, two-tailed p value <0.001, was considered extremely significant. Amplification of microsatellite loci that were originally designed for Schistocephalus from G. aculeatus was positive for all larvae from G. aculeatus (n = 20), whereas in no plerocercoids from C. gobio (n = 20) were any of the six microsatellites amplified, indicating that plerocercoids from G. aculeatus and C. gobio were two distinct genetic populations of Schistocephalus. The material from C. gobio is described as S. cotti n. sp. Plerocercoids of the Palaearctic species of Schistocephalus are identified as follows: S. nemachili Dubinina, 1959 with 228-235 or more segments, specific to Barbatula spp. (Balitoridae); S. pungitii Dubinina, 1959 with 62-92 (usually 70-80) segments, specific to Pungitius pungitius; S. solidus (Müller, 1776) in two forms, one in G. aculeatus f. leiurus and f. semiarmatus, with 48-100 (usually 65-75) segments, and the other in G. aculeatus f. trachurus, with 99-138 (usually 112-122) segments; and S. cotti n. sp. with 103-189 (usually 130-159) segments, probably specific to cottids. Nearctic Schistocephalus were not considered owing to the uncertain status of some North American records. Some other species of Schistocephalus of highly doubtful status were briefly noted. Cross-infection experiments and molecular studies are recommended to further elucidate the interrelationships between the various species of Schistocephalus.

Animals↗

PubMed2004

The TL analysis methods used to determine absorbed gamma doses in vivo for the BNCT patients treated at FiR 1.

The gamma dose determination using thermoluminescent (TL) dosimeters in mixed neutron-gamma fields, such as in boron neutron capture therapy (BNCT), is difficult due to the thermal neutron sensitivity of the detectors; especially when equipment capable of glow curve analysis is not available. The two TL analysis methods used previously in Finnish BNCT to correct the measured TL signal to obtain absorbed gamma dose in vivo were studied and compared, and an enhanced method was introduced. The three TL methods were found surprisingly consistent despite, e.g. the rough estimate made in the first method.

Boron Neutron Capture Therapy↗

PubMed2004

Design and construction of shoulder recesses into the beam aperture shields for improved patient positioning at the FiR 1 BNCT facility.

Improvements have been made at the FiR 1 BNCT facility to ease the positioning of the patient with a tumor in the head and neck region into a lateral neutron beam. Shoulder recesses were constructed horizontally on both sides of the beam aperture. When shoulder recesses are not needed, they are filled with neutron attenuating filling blocks. MCNP simulations using an anthropomorphic human model BOMAB phantom showed that the main contribution to the increase in the effective dose to the patient's body due to the shoulder recesses was from the neutron dose of the arm. In a position when one arm is inside the shoulder recess, the maximal effective dose of the patient was estimated to be 0.7Sv/h. Dose measurements using the twin ionization chamber technique showed that the neutron dose increased on the sides as predicted by the MCNP model but there was no noticeable change in the gamma doses. When making the recesses into the lithium containing neutron shield material tritium contamination was confined using an underpressurized glove box and machine tools with local exhaust. The shoulder recesses give space for more flexible patient positioning and can be considered as a significant improvement of the Finnish BNCT facility.

Boron Neutron Capture Therapy↗

PubMed2004

Enhanced blood boron concentration estimation for BPA-F mediated BNCT.

The blood boron concentration regulates directly the BNCT irradiation time in which the prescribed dose to the patient is delivered. Therefore a proper estimation of the blood boron concentration for the treatment field based on the measured blood samples before irradiation is required. The bi-exponential model fit using Levenberg-Marquardt method was implemented for this purpose to provide the blood boron concentration estimates directly to the treatment data flow during the BNCT procedure. The harmonic mean bi-exponential decay half-lives of the studied patient data (n=28) were 15+/-8 and 320+/-70 min for the faster and slower half-life. The model uncertainty (n=28) was reasonably low, 0.7+/-0.1 microg/g (about 5%). The implemented algorithm provides a robust method for temporal blood boron concentration estimation for BPA-F mediated BNCT. Utilization of the infusion data improves the reliability of the estimate. The overall data flow during the treatment fulfills the practical requirements concerning the BNCT procedure.

Algorithms↗

PubMed2004

Dosimetric comparison at FiR 1 using microdosimetry, ionisation chambers and computer simulation.

Tissue equivalent proportional counter microdosimetry has been applied in the dosimetry of epithermal neutron beams as they can provide an independent and accurate method to determine gamma ray and neutron absorbed doses. Dosimetric comparison has been performed using a tissue equivalent proportional counter, dual ionisation chambers and DORT computer code at FiR 1 boron neutron capture therapy facility in Espoo, Finland. The three methods were applied to determine neutron and gamma ray absorbed doses at 25, 40, 60 and 120 mm depths along the beam centerline in a water-filled PMMA phantom. The determined absorbed doses were found to agree within the limits of the estimated uncertainties.

Boron Neutron Capture Therapy↗

PubMed2004

Concomitant abuse of anabolic androgenic steroids and human chorionic gonadotrophin impairs spermatogenesis in power athletes.

Abuse of anabolic androgenic steroids (AASs) may be an aetiological factor in male infertility among recreational power athletes. They try to avoid AAS-induced deterioration in spermatogenesis by combining doses of human chorionic gonadotrophin (HCG) and/or antiestrogens with their AAS abuse. Eighteen healthy male power athletes using massive doses of AASs were recruited for the study. Semen samples were collected during AAS abuse and 1.5 and 6 months after cessation of the abuse. They were also asked about their reproductive activity six years after the study. At the end of the AAS cycle, the sperm count was 33 +/- 49 x 10 (6) /ml (mean +/- SD), and only one subject had azoospermia. At 1.5 months after cessation of the AAS cycles, the mean sperm concentration was 30 +/- 42 x 10 (6) /ml, and after six months 77 +/- 70 x 10 (6) /ml. There were significant differences between the sample drawn six months after cessation of AAS abuse and both samples drawn during and 1.5 months after the abuse (p </= 0.05, repeated measures of ANOVA). There was a significant positive correlation between HCG dose during the cycle and the relative amount of morphologically abnormal spermatozoa (r = 0.60, p < 0.01). The concomitant abuse of HCG and supraphysiological AAS dose cause transient impairment on semen quality in males, although spermatogenesis is maintained with this regimen despite prolonged abuse of massive doses of AAS.

Adult↗

PubMed2004

Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient mice.

The importance of AMPA-type glutamate receptors has been demonstrated in neuronal plasticity and in adaptation to drugs of abuse. We studied the involvement of AMPA receptors in social interaction and anxiety and found that in several paradigms of agonistic behavior naïve male mice deficient for the GluR-A subunit- containing AMPA receptors are less aggressive than wild-type littermates. GluR-A deficient mice and wild-type littermates exhibited similar basic behavior and reflexes as monitored by observational Irwin's test, but they tended to be less anxious in elevated plus-maze and light-dark tests. Maternal aggression or male-female encounters were not affected which suggests that male hormones are involved in the expression of suppressed aggressiveness. However, testosterone levels and brain monoamines can be excluded and found to be similar between GluR-A deficient and wild-type littermates. The reduced AMPA receptor levels caused by the lack of the GluR-A subunit, and measured by a 30% reduction in hippocampal [3H]-S-AMPA binding, seem to be the reason for suppressed male aggressiveness. When we analyzed mice with reduced number of functional AMPA receptors mediated by the genomic introduced GluR-A(Q582R) channel mutation, we observed again male-specific suppressed aggression, providing additional evidence for GluR-A subunit-containing AMPA receptor involvement in aggression.

Agonistic Behavior↗

PubMed2003

Computational study of the required dimensions for standard sized phantoms in boron neutron capture therapy dosimetry.

The minimum size of a water phantom used for calibration of an epithermal neutron beam of the boron neutron capture therapy (BNCT) facility at the VTT FiR 1 research reactor is studied by Monte Carlo simulations. The criteria for the size of the phantom were established relative to the neutron and photon radiation fields present at the thermal neutron fluence maximum in the central beam axis (considered as the reference point). At the reference point, for the most commonly used beam aperture size at FiR 1 (14 cm diameter), less than 1% disturbance of the neutron and gamma radiation fields in a phantom were achieved with a minimum a 30 cm x 30 cm cross section of the phantom. For the largest 20 cm diameter beam aperture size, a minimum 40 cm x 40 cm cross-section of the phantom and depth of 20 cm was required to achieve undisturbed radiation field. This size can be considered as the minimum requirement for a reference phantom for dosimetry at FiR 1. The secondary objective was to determine the phantom dimensions for full characterization of the FiR 1 beam in a rectangular water phantom. In the water scanning phantom, isodoses down to the 5% level are measured for the verifications of the beam model in the dosimetric and treatment planning calculations. The dose distribution results without effects caused by the limited phantom size were achieved for the maximum aperture diameter (20 cm) with a 56 cm x 56 cm x 28 cm rectangular phantom. A similar approach to study the required minimum dimensions of the reference and water scanning phantoms can be used for epithermal neutron beams at the other BNCT facilities.

Boron Neutron Capture Therapy↗

PubMed2003

Study of the relative dose-response of BANG-3 polymer gel dosimeters in epithermal neutron irradiation.

Polymer gels have been reported as a new, potential tool for dosimetry in mixed neutron-gamma radiation fields. In this work, BANG-3 (MGS Research Inc.) gel vials from three production batches were irradiated with 6 MV photons of a Varian Clinac 2100 C linear accelerator and with the epithermal neutron beam of the Finnish boron neutron capture therapy (BNCT) facility at the FiR 1 nuclear reactor. The gel is tissue equivalent in main elemental composition and density and its T2 relaxation time is dependent on the absorbed dose. The T2 relaxation time map of the irradiated gel vials was measured with a 1.5 T magnetic resonance (MR) scanner using spin echo sequence. The absorbed doses of neutron irradiation were calculated using DORT computer code, and the accuracy of the calculational model was verified by measuring gamma ray dose rate with thermoluminescent dosimeters and 55Mn(n,gamma) activation reaction rate with activation detectors. The response of the BANG-3 gel dosimeter for total absorbed dose in the neutron irradiation was linear, and the magnitude of the response relative to the response in the photon irradiation was observed to vary between different gel batches. The results support the potential of polymer gels in BNCT dosimetry, especially for the verification of two- or three-dimensional dose distributions.

Boron Neutron Capture Therapy↗

PubMed2003

Evaluation of the relative biological effectiveness of a clinical epithermal neutron beam using dog brain.

This investigation was designed to determine the relative biological effectiveness (RBE) of an epithermal neutron beam (FiR 1 beam) using the brains of dogs. The FiR 1 beam was developed for the treatment of patients with glioma using boron neutron capture therapy. Comparisons were made between the effects of whole-brain irradiation with epithermal neutrons and 6 MV photons. For irradiations with epithermal neutrons, three dose groups were used, 9.4 +/- 0.1, 10.2 +/- 0.1 and 11.5 +/- 0.2 Gy. These physical doses were given as a single exposure and are quoted at the 90% isodose. Four groups of five dogs were irradiated with single doses of 10, 12, 14 or 16 Gy of 6 MV photons to the 100% isodose. Different reference isodoses were used to obtain the most comparable dose distribution in the brain for the two different irradiation modalities. Sequential magnetic resonance images (MRI) were taken for 77-115 weeks after irradiation to detect changes in the brain. Dose-effect relationships were established for changes in the brain as detected either by MRI or by subsequent gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED(50)) were calculated from these dose-effect curves for each end point, and these values were used to calculate the RBE values for the different end points. The RBE values for the FiR 1 beam, based on changes observed on MRI, were in the range 1.2-1.3. For microscopic and gross pathological lesions, the values were in the range 1.2-1.4. The corresponding RBE values for the MRI and pathological end points for the high-LET components (protons from nitrogen capture and recoil protons from fast neutrons) were in the ranges 3.5-4.0 and 3.4-4.4, respectively. This assumed a dose-rate reduction factor of 0.6 for the low-dose-rate gamma-ray component of this beam. Finally, a comparison was made between experimentally derived photon doses, for a specified end point, with calculated photon equivalent doses, which were obtained using the weighting factors for clinical studies on the epithermal neutron beam on the Brookhaven Medical Research Reactor (BNL) in New York. This indicated that the radiation-induced lesions seen in the present study were, on average, detected at a 12% lower photon dose than predicted by the use of the BNL clinical weighting factors. This indicates the need for caution in the extrapolation of results from one reactor-based epithermal neutron beam to another.

Animals↗

PubMed2002

Validation of self reported smoking by serum cotinine measurement in a community-based study.

STUDY OBJECTIVE: The validity of self reported smoking in population surveys remains an important question. An associated question is what would be the value of measuring serum cotinine concentrations in such surveys to obtain validated smoking data. DESIGN: Cross sectional analysis of data on self reported smoking and serum cotinine among a random population sample of 5846 persons aged 25 to 64 years, who participated in the FINRISK-92 survey. MAIN RESULTS: Among self reported regular smokers, 97.2% of men and 94.9% of women had a cotinine concentration of 10 ng/ml or higher in serum. Of those participants who reported to have smoked at any time during their life but not during the previous month, 6.3% of men and 5.2% of women had a serum cotinine concentration of at least 10 ng/ml. Among never smokers 2.5% of men and 2.7% of women had detectable level of cotinine in their serum. The validity of self reporting was similar among subjects from different areas, ages, and socioeconomic groups. CONCLUSIONS: In a sample of the general population in Finland the validity of self reported smoking is high, and most of the few self reported non-smokers who had cotinine in their serum had only low or moderate levels.

Adult↗

PubMed2001

Detection and assay of cis- and trans-isomers of 4-methylaminorex in urine, plasma and tissue samples.

The 4-methylaminorex (4-MAX) is an amphetamine-related psychostimulant drug that has appeared on the clandestine market with a street name of "U4Euh". This compound exists as four stereoisomers, trans-4R,5R, trans-4S,5S, cis-4R,5S and cis-4S,5R, of which the cis forms have been classified as Schedule I substances in the US. The increasing variety of designer drugs has highlighted the importance of detection, identification, and quantitative measurement of these drugs, including 4-MAX, in biological samples. In the present study, the isomers of 4-MAX were detected in urine of rats treated with the drugs by some but not all of the on-site immunoassays tested, mainly as amphetamine or methamphetamine. To facilitate identification of 4-MAX by laboratories specialized in drug analysis, the electron-ionization mass spectrum and TLC data for underivatized 4-MAX using a routine laboratory drug-screening procedure is provided. In addition, a GC/MS method is described for the quantitative determination of cis- and trans-4-MAX as tert-butyldimethylsilyl-derivatives in plasma, urine and tissue.

Animals↗

PubMed2001

Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits.

AMPA-type glutamate receptors have been suggested to be involved in the neurobiological mechanisms of drug addiction. We have made use of two mouse lines, which both have modulated AMPA receptor responses. The first line is entirely deficient in glutamate receptor-A (GluR-A) subunits (A-/- knock-out line) and, in the second one, the Q582 residue of GluR-A subunits is replaced by an arginine residue (R/R mutants), which reduces the calcium permeability and channel conductance of the receptors containing this mutated subunit. Mice of both lines are healthy, but they show slightly increased locomotor activity. Acute morphine administration enhanced locomotor activity of the GluR-A-/- and GluR-A(R/R) mice, at least as much as that of their wild-type littermates. Only in the GluR-A-/- mice did we observe reduced tolerance development in tail-flick antinociception and less severe naloxone-precipitated withdrawal symptoms after treatment with increasing morphine doses, without differences in plasma and brain morphine levels when compared with wild type. Repeated daily morphine administration sensitized the locomotor activity responses in the GluR-A-/- and GluR-A(R/R) mice only when given in the measuring cages, whereas the wild-type mice showed slightly increased responses also when the repeated treatment was given in their home cages. Normal or even enhanced context-dependent sensitization was observed also with repeated amphetamine administration in the GluR-A subunit-deficient mice. The results indicate that AMPA receptors are involved in the acute and chronic effects of morphine, including context-independent sensitization, and that the GluR-A subunit itself is important for morphine tolerance and dependence.

Acute Disease↗

PubMed2001

Oxalic acid stabilizes dopamine, serotonin, and their metabolites in automated liquid chromatography with electrochemical detection.

Use of antioxidative agents is required in automated LC assay of microdialysis samples, due to rapid degradation of the monoamine neurotransmitters and their metabolites. Addition of oxalic acid prevented degradation of dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid efficiently: after a 24-h incubation at room temperature the decreases in peak heights were less than 10%. The long-term stability of the analytes, however, was still enhanced when acetic acid and L-cysteine were included in the solution. Using this antioxidative solution, the monoamine neurotransmitters and their metabolites could be determined with an automated LC assay even at room temperature.

Automation↗

PubMed2001

Rewarding properties of methylphenidate: sensitization by prior exposure to the drug and effects of dopamine D1- and D2-receptor antagonists.

In drug addiction, a sensitization phenomenon has been postulated to play a critical role. The aim of our study was to evaluate whether sensitization occurs to the rewarding properties of methylphenidate, a psychostimulant drug known to possess abuse potential, as assessed with the biased conditioned place preference method in rats. In addition, since the brain dopaminergic system is considered to be important in drug-reward, the involvement of dopamine D1- and D2-receptors both in the rewarding properties of methylphenidate and in sensitization to these properties was assessed. Conditioning with methylphenidate at doses of 1.25 to 20 mg/kg increased preference for the paired environment, whereas a dose of 0.31 mg/kg was ineffective. However, following the 7-day sensitization treatment with methylphenidate (0.62-20 mg/kg), conditioning with a dose of 0.31 mg/kg resulted in an increased preference for the paired environment, i.e., the rewarding properties of methylphenidate appeared to be sensitized. Control experiments indicated that the enhancement of preference was not due to attenuation of sensitization treatment-induced withdrawal nor to tolerance to aversive properties of methylphenidate. When conditioned with methylphenidate, D1-antagonist SCH 23390 but not D2-antagonist raclopride prevented place preference. However, when coadministered with methylphenidate during the sensitization treatment, both SCH 23390 and raclopride prevented the development of sensitization. These data indicate that the rewarding properties of methylphenidate are sensitized by prior exposure to the drug and that both D1- and D2-receptors, the latter of which possibly more specifically, appear to be involved in the development of this sensitization.

Animals↗

PubMed2000

Driving under light and dark conditions: effects of alcohol and diazepam in young and older subjects.

OBJECTIVES: Driving at night time increases accident risk due to visual conditions, fatigue and impaired performance. In addition, the use of alcohol and benzodiazepines may enhance the risks related to night-time driving. We studied these aspects of traffic safety in a simulated driving test with young and older drivers. METHODS: In a double-blind, crossover, placebo-controlled study, nine young subjects, aged 22-24 years, performed simulated driving in both 'light' and 'dark' conditions, before and 1.5 h and 4 h after 0.8 g x kg(-1) ethanol (EOH) or 15 mg diazepam (DZ). Further, nine older subjects, aged 55-77 years, were similarly tested, but their EOH dose was 0.7 g x kg(-1) and the DZ dose was 10 mg. The tests were vigilance assessment on visual analogue scales (VAS), simulated driving under light and dark conditions for 6 min each and digit symbol substitution (DSS). RESULTS: In the young subjects, both EOH and DZ similarly impaired DSS, with DZ causing more subjective drowsiness, clumsiness, mental slowness and poor overall performance than EOH. During simulated driving, both EOH and DZ impaired simple and complex tracking (EOH > DZ) and prolonged reaction times (EOH = DZ). Impairment of performance was practically identical under light and dark conditions. In the older subjects, objective performance on DSS was poorer (-30%) than that of the young ones, and subjective impairment was marginal. During simulated driving, the baseline levels of variables in older subjects showed definite impairment (errors +100% to +500%) when compared with young subjects. Active drugs impaired several variables (EOH > DZ), but the statistical significances were fewer than in young subjects. Increase in reaction errors reached statistical significance, especially while driving in the dark. Otherwise the driving results in light and dark were not notably different. CONCLUSION: Young subjects drew good baselines but were sensitive to EOH and DZ, whilst the older subjects showed poor baselines but were less sensitive to EOH and DZ. Although the baseline driving and responses to treatments were different in young and older subjects, their driving and psychomotor impairment were unaffected by light conditions.

Adult↗

PubMed2000

Increased premature mortality of competitive powerlifters suspected to have used anabolic agents.

Misuse of supraphysiological doses of anabolic steroids is claimed to have serious side effects. The aim of the study was to determine the mortality, and the cause of premature deaths among a group of subjects who are strongly suspected to have used anabolic steroids for a non-medical purpose over several years. The mortality of 62 male powerlifters placed 1st-5th in weight series 82.5-125 kg in Finnish championships during 1977-1982 was compared with the mortality of population controls. The mortality during the 12-year follow-up was 12.9% for the powerlifters compared to 3.1% in the control population. By 1993 eight of 62 powerlifters and 34 of 1094 population controls had died, thus the risk of death among the powerlifters was 4.6 times higher (95% CI 2.04-10.45; p = 0.0002). The causes of premature death among the powerlifters were suicide (3), acute myocardial infarction (3), hepatic coma (1) and non-Hodgkin's lymphoma (1). These findings add to the growing amount of evidence of an association between anabolic steroid abuse and premature death, and support the view that measures to decrease AAS misuse among both competitive and amateur athletes are justified.

Adult↗