[The principles of radiotherapy].
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Female↗
Biomedical subjects
M Pitkänen
Publications and source records attributed to M Pitkänen.
The effects of NMDA receptor antagonists at anticonvulsive doses on the performance of rats in the water maze task.
In the present study we investigated the effects of two competitive NMDA receptor antagonists, CGP 37849 (DL-(E)-2-amino-4-methyl-phosphono-3-pentonoic acid) and CGP 39551 (carboxyethyl ester of CGP 37849) as well as MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenz(a,d)cycloheptene-5,10-imine hydrogen maleate), a non-competitive antagonist, administered systemically before training, on the acquisition of a water maze task used to assess spatial learning and memory in rats. The competitive NMDA receptor antagonists dose dependently impaired water maze acquisition (increased escape distance), but did not significantly affect swimming speed in rats. MK-801 induced clear behavioral effects and impaired the acquisition of the water maze task. However, as training advanced drug-treated rats did show a decrease in distance swam per trial before encountering the platform in the water pool. This suggests that drug treatments did not abolish learning. When the anticonvulsive properties of the drugs were determined, MK-801 did not show any protection in the maximal electroshock (MES) test at doses already impairing the acquisition of the water maze task while the two competitive NMDA receptor antagonists protected the rats against seizures at doses not impairing acquisition. This result suggests a wider therapeutic range for CGP 39551 and especially for CGP 37849 than for MK-801 in the treatment of epilepsy.
2-Amino-5-phosphonovalerate↗
The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats.
The present study investigated the effect of d-cycloserine, a partial agonist at the glycine binding site on NMDA receptor complex, on the performance of scopolamine-treated adult rats in a water maze task assessing spatial learning and in a delayed non-matching to position task assessing working memory in a spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.) impaired acquisition (increased escape latency and distance) and increased swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in acquisition performance but not the increases in behavioral activity. In the working memory task, scopolamine (0.2 mg/kg, i.p.) produced deficits on nonmnemonic rather than on mnemonic performance factors; scopolamine delay-independently decreased the percent correct responses and reduced behavioral activity of rats. D-cycloserine (1.0, 3.0 and 10 mg/kg, i.p.) did not reverse these performance deficits. When administered alone, the moderate to higher doses of d-cycloserine had no effects on working memory but the lower dose produced slight deficits in mnemonic performance factors; the 1.0 mg/kg dose delay-dependently decreased the percent correct responses without affecting behavioral activity of rats. In the water maze task, d-cycloserine had no effects on acquisition performance or behavioral activity of rats. These results suggest that acute, systemic administration of d-cycloserine does not improve spatial learning or working memory. However, at appropriate doses this agent may be efficacious in disease states of central cholinergic hypofunction since 1.0 mg/kg d-cycloserine was able to reverse the scopolamine-induced deficits in acquisition.
Animals↗
Effects of nitric oxide synthesis inhibition with or without nitric oxide inhalation on responses to systemic cocaine administration in rats.
The effects of N omega-nitro-L-arginine methyl ester (L-NAME) i.v. and nitric oxide (NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats. Cocaine (4 mg/kg/min i.v.) produced seizures then isoelectric electrocephalographic (isoEEG) activity as well as an initial increase in systolic blood pressure and heart rate, then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME (2 mg/kg/min i.v.) for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8). Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. No inhalation (80 ppm) did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular system (lower dose for arrhythmias and asystole), but does not affect the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.
Administration, Inhalation↗
Effects of NMDA receptor modulation on hippocampal type 2 theta activity in rats.
1. The present study was designed to investigate whether pharmacological modulation of N-methyl-D-aspartate (NMDA) receptor function could modify hippocampal type 2 theta activity in the dentate gyrus of rats. 2. The effects of pre-recording administration of d-cycloserine (DCS: 1.0, 3.0 and 9.0 mg/kg, i.p.), a partial agonist at the NMDA receptor associated glycine site, and MK-801 (0.1 mg/kg, i.p.), a noncompetitive NMDA receptor antagonist, were examined in freely moving rats. 3. Using adult Wistar rats, which had recording electrodes implanted unilaterally into the hilus of dentate gyrus, we recorded five 4 sec epochs of awake-immobility-related hippocampal EEG activity bands (1-20 Hz) 40 min after d-cycloserine and 2 hr after administration of MK-801. 4. In the off-line analysis, the spectral power and the frequency at the maximal theta power were calculated. 5. D-cycloserine (1.0-9.0 mg/kg) did not affect the frequency at the maximal theta power. However, the dose of 3.0 mg/kg, though not the 1.0 or 9.0 mg/kg doses, significantly increased the spectral power of the hippocampal immobility-related EEG activity. 6. In line with the previous findings, 0.1 mg/kg MK-801 decreased both the frequency at the maximal theta power as well as the spectral power of hippocampal type 2 EEG activity. 7. The present data show a clear relationship between NMDA receptors and hippocampal type 2 theta activity and suggest that the pharmacological modulation of the receptor function, using appropriate doses of glycine binding site agonist, d-cycloserine, may be a possible means to positively modulate the immobility-related hippocampal EEG activity.
Animals↗
Action of recombinant interferons and interleukin 2 in modulating radiation effects on viability and cytotoxicity of large granular lymphocytes.
We have evaluated in vitro the modulating effect of interferon (IFN) alpha, beta and gamma as well as interleukin 2 (IL-2) on the radiosensitivity of large granular lymphocytes (LGL) having natural killer cell activity. LGL were treated with IFNs or IL-2 in concentrations from 1 to 1000 U/ml before or after a single or a split dose of irradiation. The viability of LGL was measured by intracellular ATP, and cytotoxicity by a 51Cr release assay. Both viability and cytotoxicity were clearly higher when IFNs and IL-2 were used before irradiation. Some IFNs were slightly radiosensitizing in ATP studies. Only IFN gamma in a concentration of 1000 U/ml was significantly radioprotective in cytotoxicity tests when used before irradiation. IL-2 had a significant concentration-dependent radioprotective effect in cytotoxicity when used before or after irradiation, and in the viability of preincubated LGL. No combination of IFNs and IL-2 was more radioprotective than IL-2 used alone. IL-2 retarded the time dependent decrease of ATP and 51Cr release levels after irradiation. According to our results, IL-2 is a radioprotective substance for LGL.
Adenosine Triphosphate↗
Comparison of parenteral diclofenac and ketoprofen for postoperative pain relief after maxillofacial surgery.
Non-steroidal anti-inflammatory drugs (NSAID) effectively reduce the need for opioid analgesia after various types of surgery. The efficacy of diclofenac and ketoprofen to relieve pain after maxillofacial surgery was compared in the present study. In a randomized and double-blind fashion, 90 ASA I-II patients (16-60 yrs) were studied, divided into three groups: Thirty patients received 1.0 mg.kg-1 diclofenac i.v. after general anaesthesia induction, before surgical incision, and four hours later the same dose was given i.m. Thirty patients received ketoprofen 1.35 mg.kg-1 i.v. and i.m., as above, and a third group of 30 patients received a comparable volume of saline i.v. and i.m. The patients received supplemental analgesia using a patient controlled analgesia apparatus; the rescue medication consisted of 0.03 mg.kg-1 oxycodone i.v. (four-hour maximum dose was 0.4 mg.kg-1) during the 24-hour follow-up. The three groups were comparable regarding the type of maxillofacial surgery (osteotomies vs. soft tissue surgery). Overall, there was a lower need for i.v. oxycodone during the 24-hour period in the diclofenac group (269 doses) than in the ketoprofen group and in the saline group (388 doses, each) (P < 0.01). The significantly lower number of oxycodone administrations in the diclofenac group was a result of a distinguishable difference, particularly during the first four hours after surgery. There was no statistically significant difference in the incidence of side effects of the analgesic therapy between the three groups.
Adolescent↗
The effects of D-cycloserine and MK-801 on the performance of rats in two spatial learning and memory tasks.
The present study was undertaken to investigate the effects of modulation of the N-methyl-D-aspartate (NMDA) receptor on learning and memory. Thus, the performance of rats treated with D-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. D-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, D-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg D-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations.
Adaptation, Psychological↗
d-Cycloserine, a partial agonist at the glycine site, enhances the excitability of dentate granule cells in vivo in rats.
The present study investigated the dose-dependent effects of d-cycloserine, a partial agonist at the glycine modulatory site associated with the NMDA receptor complex, on the hippocampal field potentials of dentate granule cells in awake, freely moving rats. Five sequential field potentials were recorded from the dentate gyrus of the dorsal hippocampus, by stimulating the perforant path in the entorhinal cortex at 30-s intervals. The slope of the population excitatory postsynaptic potential (e.p.s.p.) and the amplitude of the population spike of these field potentials were analysed and averaged with a computer. The effects of d-cycloserine (1.0, 3.0, 9.0 mg/kg) were recorded 40 min and 24 h after the i.p. injection. Although the slope of the population e.p.s.p. showed no significant change after the administration of d-cycloserine, the high doses produced a substantial increase in the amplitude of the population spike. This increase was observed 40 min but not 24 h after the injection. These findings indicate that d-cycloserine does not change the synaptic input from the perforant path to the granule cells but dose dependently enhances the excitability of the hippocampal dentate granule cells. In addition, the data give further support to the suggestion that in the brain area where NMDA receptor density is relatively high, the glycine site of the NMDA receptor may not be fully saturated by endogenous glycine in normal in vivo conditions. This suggests that there is a possibility for pharmacological modulation of NMDA receptor-mediated synaptic events by exogenous glycine or glycine analogues.
Action Potentials↗
Comparison of performance standards for radiation beam uniformity characteristics of a linear accelerator.
The recent international standards published by the International Electrotechnical Commission (IEC) on the performance of medical electron accelerators describe suggested test procedures for the performance of radiotherapy accelerators. The recommendations of the Nordic Association of Clinical Physics for testing of the radiation beam characteristics include test conditions, methods and suggested tolerances that are different from those of the IEC. In this work the two publications were compared for acceptance testing of a Philips SL25 linear accelerator. It is important to gain experience on the practical use of these standards.
Europe↗
Sidebending versus flexion-extension radiographs in lumbar spinal instability.
Flexion-extension radiography is accepted as an effective method for the diagnosis of lumbar spinal instability, but the usefulness of sidebending films is less well known. Flexion-extension and sidebending radiographs of 300 patients with clinically suspected lumbar spinal instability were analyzed retrospectively. Generally used criteria for lumbar spine instability were applied in the film analysis. Although flexion-extension and sidebending films were statistically significantly interrelated in the diagnosis of instability, intertechnique agreement remained poor. Flexion-extension films more frequently revealed signs of instability than sidebending films; 84 vs 50 patients. Signs of instability on sidebending films showed the best correlation with the findings of angular motion and posterior sliding instability on flexion-extension films. Sidebending films are complementary to flexion-extension films but are unlikely to be helpful on a routine basis.
Adolescent↗
Should epinephrine be used to treat local anesthetic-induced cardiotoxicity?
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Anesthetics, Local↗
Dose-response of simvastatin in primary hypercholesterolemia.
In an 8-week, placebo-controlled multicenter study, the efficacy of dose levels of simvastatin 2.5, 5, 10, 20, and 40 mg was evaluated in 166 patients with hypercholesterolemia, of whom 163 completed the trial. The entry criteria were serum total cholesterol (TCHOL) between 6.2 and 7.8 mM and low-density lipoprotein (LDL) cholesterol between 4.3 and 50 mM on a standard diet and after the 2-week run-in period of placebo treatment. Mean percentage changes in serum lipids in each simvastatin-treated group from baseline were statistically significant. Of treated patients, 0% (placebo), 11% (2.5 mg), 7% (5 mg), 33% (10 mg), 42% (20 mg) and 55% (40 mg) had at least 40% reduction from baseline LDL cholesterol value. After 8 weeks of treatment, 0% (placebo), 11% (2.5 mg), 25% (5 mg), 26% (10 mg), 31% (20 mg), and 55% (40 mg) of patients treated reached a TCHOL level of < or = 5.2 mM. There was a significant linear dose response with regard to the decrease in LDL cholesterol, TCHOL, and triglycerides (TG) and the increase in high-density lipoprotein (HDL) cholesterol after 8 weeks of therapy. No serious clinical or laboratory adverse events related to simvastatin were observed even at higher doses. At each dose level, simvastatin reduced TCHOL and LDL cholesterol. Doses of simvastatin > or = 5 mg moderately increased HDL cholesterol and reduced serum TG. Simvastatin therapy resulted in major improvement in serum lipoprotein profile, particularly at higher doses.
Anticholesteremic Agents↗
Intraarticular morphine for pain relief after knee arthroscopy performed under regional anaesthesia.
Eighty patients scheduled to undergo knee arthroscopy were studied in random and double blind fashion. Spinal anaesthesia with hyperbaric 0.5% bupivacaine was selected for 40 overnight-in-patients. At the end of arthroscopy, 1 mg morphine or saline was injected intraarticularly. Local anaesthesia with 1% lidocaine plus adrenaline, was selected for another 40 out-patients. At the end of the arthroscopy either 1 mg morphine or saline was injected intraarticularly. As a rescue medication the spinal anaesthesia patients received oxycodone 0.14 mg kg-1 i.m. or ketoprofen 100 mg p.o. and the local anaesthesia patients received ketoprofen 100 mg p.o. The need for additional postoperative analgesic was almost similar in both spinal anaesthesia groups. The patients having local anaesthesia and given intraarticular morphine needed fewer doses of ketoprofen (22 doses) postoperatively than the control group (39 doses) (P < 0.05). Duration of analgesia was slightly longer after morphine than in the control group (ns). There was no difference between the morphine patients and the control patients in the two studies regarding the incidence of side effects. We conclude that postoperative analgesia in patients undergoing knee arthroscopy under local anaesthesia, but not under bupivacaine spinal anaesthesia, can be improved with a single intraarticular injection of 1 mg morphine.
Adolescent↗
The effect of plain 0.5% 2-chloroprocaine on venous endothelium after intravenous regional anaesthesia in the rabbit.
The possible venous endothelial toxicity of 0.5% 2-chloroprocaine without additives in intravenous regional anaesthesia (IVRA) was evaluated in rabbits. After exsanguination of a hind limb with an Esmarch's bandage a neonatal blood pressure cuff around the thigh was inflated (250 mmHg). For IVRA 4 ml of either plain 0.5% 2-chloroprocaine (pH 3.7), 0.9% NaCl (pH 6.0) or acidified NaCl (pH 3.7) was injected i.v. to the exsanguinated limb in a randomized, double-blind fashion. Each group comprised 15 rabbits. Eleven rabbits received 4 ml of 0.5 M or 1.0 M KCl, for the production of positive controls. Two hours after injection of the test solution the tourniquet was deflated and venous biopsies were taken one and 24 hours later for histological and immunocytochemical examination. Five to eight 24-hour samples from each group were also processed for electron microscopy. A macroscopic thrombus formation was observed in four rabbits after KCl and in two after acidified NaCl administration. No inflammatory changes were observed at histologic and immunocytochemical examination of any of the vein samples. Electron microscopy revealed that KCl had caused severe damage to the venous endothelium of four out of five samples and acidified NaCl had caused moderate damage to the endothelium of two out of seven samples. 2-chloroprocaine had caused moderate damage in four and severe damage in two of the vein samples; two samples were normal. No thrombus formation occurred. It is concluded that additive-free 2-chloroprocaine caused damage to the venous endothelium in rabbits when used for IVRA.
Anesthesia, Conduction↗
Technical problems and side effects associated with continuous intrathecal or epidural post-operative analgesia in patients undergoing hip arthroplasty.
Fifty-five patients undergoing hip arthroplasty under spinal anaesthesia (4 ml of 0.5% plain bupivacaine) were randomized to receive post-operative analgesia either using an intrathecal or an epidural catheter. Associated technical problems and side effects were studied. In both groups per-operative analgesia was achieved with intrathecal 0.5% plain bupivacaine, 4 ml. In the intrathecal infusion group a bolus dose of 100 micrograms morphine was injected through a spinal 28 gauge catheter followed by a 24 h infusion of 200 micrograms morphine (8.3 micrograms h-1). In the epidural infusion group a bolus dose of 2 mg of morphine was injected before the epidural 24 h infusion was started (morphine 200 micrograms h-1 + 0.25% bupivacaine 4 ml h-1). There were 10 catheter failures (two could not be inserted) in the intrathecal group and one in the epidural group. Three epidural catheter infusions failed due to other technical problems. The number of side effects was 21 in the remaining spinal group (n = 20) and 18 in the 20 epidural group patients with successful infusions. One patient in the spinal catheter group developed postdural puncture headache. For post-operative pain relief the patients in the epidural group needed less supplementary intramuscular oxycodone (five doses/four patients) than the spinal group (17 doses/nine patients) (P < 0.05).
Aged↗
Intercomparison of radiotherapy treatment planning systems for external photon and electron beam dose calculations.
Dose distributions calculated by six different treatment planning systems (TPSs), used by the hospitals in Finland or in Russia, were compared with measured dose distributions. Five typical cases of irradiation were selected: regular fields, oblique incidence, irregular field, wedge field and inhomogeneity in a water equivalent phantom. The beam data for each TPS where those pertaining to the beam where the comparative relative measurements were performed. The results indicate that the dose distributions produced by different TPSs can differ from each other as well as from the measured dose distributions up to a level which is not acceptable in terms of the ICRU recommendations. Greatest differences seem to be related to the omission or undue consideration of the scatter components of the beam.
Algorithms↗
Clinical and radiological comparison of perivascular and transarterial techniques of axillary brachial plexus block.
The perivascular technique of axillary brachial plexus block results in incomplete block of radial and musculocutaneous nerves in 10-20% of patients. With the transarterial technique and a large dose of mepivacaine, success rates of 99% have been reported. We have compared the clinical efficacy of these techniques in 50 patients using 1% mepivacaine 45 ml with adrenaline. If required, the block was supplemented with additional blocks of single nerves or i.v. alfentanil. Additionally, eight patients in each group were studied with computed tomography after contrast medium was added to 0.5% bupivacaine 40 ml. There were no statistically significant differences in sensory or motor block between the groups at 20 min or in the plasma concentrations of mepivacaine measured 0-45 min after injection. In the CT scans, both proximal and distal spread of the contrast medium were more common after perivascular than after transarterial block. The distribution of the contrast medium was not related to the efficacy of the block.
Adult↗