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Biomedical subjects

A Kallio

Publications and source records attributed to A Kallio.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine.

The pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine--a novel alpha 2-adrenergic receptor agonist under development for preanesthetic use--were studied in healthy male volunteers. Single intramuscular doses of dexmedetomidine (0.5, 1.0, and 1.5 microgram/kg) and placebo were administered to six subjects in a single-blind, multiple crossover study. Dexmedetomidine induced dose-related impairment of vigilance assessed both objectively and subjectively. The drug also caused moderate decreases in blood pressure and heart rate. Plasma norepinephrine was dose-dependently (maximum 89%) decreased. The intramuscular doses resulted in linearly dose-related plasma concentrations of dexmedetomidine. Pharmacokinetic calculations revealed a time to maximum concentration from 1.6 to 1.7 hours, an elimination half-life of 1.6 to 2.4 hours, an apparent total plasma clearance of 0.7 to 0.9 L/hr/kg, and apparent volume of distribution of 2.1 to 2.6 L/kg. The sedative effect of dexmedetomidine dissipated during the 6-hour observation time, but all other effects were still evident 6 hours after administration of the higher doses, paralleling the plasma concentration curves. The relationship of plasma concentrations of dexmedetomidine to pharmacodynamic variables was consistent with a linear pharmacodynamic model. The pharmacodynamic-pharmacokinetic profile of intramuscular dexmedetomidine may be suited to the proposed preanesthetic clinical use of this alpha 2-agonist.

Adrenergic alpha-Agonists↗
PubMed1992

Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery.

We studied the effects of a single i.v. dose of dexmedetomidine, a highly selective and specific alpha 2 adrenoceptor agonist, on intraocular pressure (IOP), haemodynamic and sympathoadrenal responses to laryngoscopy and tracheal intubation, and on anaesthetic requirements in ophthalmic surgery. Thirty ASA I-II patients undergoing cataract surgery were allocated randomly to receive either dexmedetomidine 0.6 microgram kg-1 or saline placebo i.v. 10 min before induction of anaesthesia in a double-blind design. After dexmedetomidine there was a 34% (95% confidence interval (CI) 27-43%) reduction in IOP (P less than 0.001) and 62% (CI 57-68%) decrease in plasma noradrenaline concentrations (P less than 0.001). After intubation, maximum heart rate was 18% (CI 3-33%, P = 0.036) and the maximum IOP 27% (CI 11-43%, P = 0.005) less in the dexmedetomidine group compared with the patients treated with placebo. Within 10 min after intubation, maximum systolic and diastolic arterial pressures were also significantly (P = 0.013 and P = 0.020) smaller in the dexmedetomidine group. The induction dose of thiopentone was smaller (23% (CI 20-26%) P = 0.012), and the use of isoflurane or fentanyl supplements during anaesthesia was less frequent in the dexmedetomidine group. The patients premedicated with dexmedetomidine recovered faster from anaesthesia (P = 0.042). These results suggest that dexmedetomidine may be a useful anaesthetic adjunct in ophthalmic surgery.

Adolescent↗
PubMed1992

Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy.

The usefulness of intravenous dexmedetomidine infusion for maintenance of anesthesia was studied in patients anesthetized with thiopental, fentanyl, nitrous oxide, and oxygen. Isoflurane was added as needed. The study was conducted in two parts, the first of which was an open dose-response study that comprised 14 women undergoing abdominal hysterectomy. After a suitable infusion regimen of dexmedetomidine was determined according to hemodynamic criteria, 20 patients were included in a double-blind, randomized placebo-controlled trial (10 receiving dexmedetomidine, 10 saline solution). Dexmedetomidine was administered as a two-step infusion to rapidly achieve a steady-state plasma concentration. The infusion was started with an initial dose given over 10 min before the induction of anesthesia; at induction the maintenance rate was begun and continued until closure of the abdominal fascia. The infusion regimens of dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min-1, followed by 6 ng.kg-1 x min-1, to 270 + 13.5 ng.kg-1 x min-1. In the second part of the study, an initial infusion of 170 ng.kg-1 x min-1 was chosen, followed by 10 ng.kg-1 x min-1 for maintenance. Anesthesia was induced with thiopental (4.0 mg/kg) and maintained with isoflurane in 70% nitrous oxide and oxygen. Isoflurane was administered according to predetermined hemodynamic criteria. Dexmedetomidine infusion did not completely abolish the need for isoflurane but diminished its requirement by > 90% (P = 0.02). The heart rate response to endotracheal intubation was significantly blunted.

Adrenergic alpha-Agonists↗
PubMed1991

Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers.

The usefulness of the plasma concentrations of two major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), as indicators of neuronal NE release was investigated. The potent alpha 2-adrenoceptor agonist, dexmedetomidine, induced only about 15% maximal reductions in the metabolite concentrations, in spite of almost total inhibition of neuronal NE release, as evidenced by 90% reductions in plasma NE concentrations. Similarly, administration of the alpha 2-adrenoceptor antagonist atipamezole was followed by only small increases in plasma DHPG and no change in MHPG levels, in spite of almost six-fold, albeit short-lasting, increases in plasma NE. In contrast, a single dose of the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide reduced plasma DHPG levels by 78% and MHPG levels by 51%. It is concluded that the plasma concentrations of DHPG and MHPG are largely determined by intraneuronal, MAO-A-dependent metabolism of NE, and do not accurately reflect acute alterations in neuronal NE release. The concentration of NE in venous plasma is clearly a more sensitive indicator of alpha 2-adrenoceptor-mediated regulation of NE release.

Adult↗
PubMed1991

A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).

Adrenergic alpha-Agonists↗
PubMed1991

The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy.

The effects of two doses of dexmedetomidine (0.3 or 0.6 micrograms.kg-1), fentanyl 2.0 micrograms.kg-1, or saline as a single intravenous bolus administered 10 min prior to the induction of anesthesia were assessed in double-blind, randomized study in 96 women undergoing abdominal hysterectomy. In each patient, anesthesia was induced with thiopental 4.0 mg.kg-1, and after the effect of succinylcholine had dissipated, isoflurane 0.3% end-tidal concentration in 70% nitrous oxide was begun to maintain anesthesia. The isoflurane concentration was adjusted to maintain blood pressure and heart rate within 20% of preoperative values, and fentanyl was given if the end-tidal isoflurane concentration exceeded 1.5%. In all groups, blood pressure and heart rate increased after tracheal intubation. However, the increase in blood pressure and heart rate was significantly less in the higher dexmedetomidine (0.6 micrograms.kg-1) group than in the saline group (P less than 0.01). Also, the postintubation increase in heart rate was significantly less (P less than 0.05) in the dexmedetomidine 0.6 micrograms.kg-1 group (increase of 18 +/- 3 beats per min) compared to the fentanyl group (increase of 26 +/- 3 beats per min). In patients receiving dexmedetomidine 0.3 micrograms.kg-1, the increase in blood pressure or heart rate did not differ from that of the saline group. The mean end-tidal isoflurane concentration was significantly less in the women receiving the higher dose of dexmedetomidine (0.35%) than in those receiving saline (0.47%) or fentanyl (0.48%), although the reduction was not clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1991

Rapid reversal of alpha 2-adrenoceptor agonist effects by atipamezole in human volunteers.

1. The ability of atipamezole, a specific and selective alpha 2-adrenoceptor antagonist, to reverse the pharmacological effects induced by the alpha 2-adrenoceptor agonist dexmedetomidine was studied in six healthy male volunteers. Each volunteer received in four sessions in a randomized and single-blind manner three different doses (6.7 micrograms kg-1, 27 micrograms kg-1 and 67 micrograms kg-1) of atipamezole or saline placebo as 5 min i.v. infusions preceded by a fixed i.v. dose of dexmedetomidine (0.67 micrograms kg-1). 2. Dexmedetomidine caused profound sedation, with the subjects actually falling asleep. This was effectively reversed by the two highest doses of antipamezole. 3. Dexmedetomidine reduced salivary flow on average by 70%. A rapid and full reversal of this effect was seen after the highest dose of antipamezole. 4. Hypotension induced by dexmedetomidine was also effectively antagonized by atipamezole. Bradycardia was very modest after dexmedetomidine in this study, and thus no reversal of alpha 2-adrenoceptor agonist-induced bradycardia could be demonstrated. 5. Plasma noradrenaline concentrations were reduced by 80% by dexmedetomidine. This was effectively antagonized by atipamezole, and the highest dose caused a 50% overshoot in plasma noradrenaline concentrations over the basal levels. 6. It is concluded that the effects of dexmedetomidine are effectively reversible by atipamezole. A dose ratio of 10:1 for atipamezole:dexmedetomidine was clearly insufficient for this purpose, but ratios in the range of 40:1 to 100:1 were found to be effective in the current experimental situation.

Adrenergic alpha-Agonists↗
PubMed1990

No involvement of alpha 2-adrenoceptors in the regulation of basal prolactin secretion in healthy men.

The role of alpha 2-adrenoceptors in the regulation of basal prolactin secretion was investigated in healthy male volunteers. Two independent, placebo-controlled, double-blind experiments were performed. In the first experiment, 50 micrograms dexmedetomidine (MPV-1440), a selective alpha 2-adrenoceptor agonist, and saline placebo were infused (IV) in five subjects. In the second experiment, 100 mg atipamezole (MPV-1248), a selective alpha 2-adrenoceptor antagonist, and saline placebo were infused in six volunteers. The concentrations of prolactin in plasma were not affected by the drugs. These results suggest that alpha 2-adrenoceptors do not a play significant role in the control of basal prolactin secretion in healthy men.

Adrenergic alpha-Agonists↗
PubMed1990

A solution hybridization method for quantification of mRNAs: determining the amount and stability of oncogene mRNA.

A solution hybridization method for the quantification of specific mRNAs is described. This assay utilizes complementary RNA probes prepared by in vitro transcription, sandwich hybridization in solution, and affinity-based hybrid collection. The possibility of using this method for crude biological samples without purifying mRNAs makes it ideal when accurate quantification of multiple samples is needed. Human N-myc oncogene transcript was used as a model and as little as 0.24 pg (2 X 10(5) molecules) of N-myc mRNA could be detected. Using this assay it was shown that human neuroblastoma IMR-32 cells contain approximately 500 N-myc mRNA molecules per cell having a half-life of approximately 35 min.

DNA Probes↗
PubMed1990

A rapid solution hybridization method for detection of human papillomaviruses.

Nucleic acid hybridization methods in routine diagnosis of micro-organisms have been limited by the tedious assay procedures. We have previously described the sandwich hybridization method which allows convenient testing of biological specimens. In this paper we describe the adaptation of the solution hydridization method into the microtitre plate format using 35S-isotope as label. Using 3-hour hybridization followed by 2-hour collection of the hybrids a sensitivity of 5 x 10(5) target DNA molecules was achieved. The method was applied for identification of human papillomaviruses in crude gynaecological specimens. A simple 1-day assay protocol was achieved with high HPV type specificity. The specificity was confirmed by testing a variety of unrelated micro-organisms, none of which gave a positive signal in the test. Results, obtained as numerical values, were easy to interpret; positive and negative samples gave clearly distinguishable signals.

Cervix Uteri↗
PubMed1990

Affinity-based collection of amplified viral DNA: application to the detection of human immunodeficiency virus type 1, human cytomegalovirus and human papillomavirus type 16.

We have devised a sensitive and convenient hybridization technique by combining the polymerase chain reaction (PCR) with affinity-based hybrid collection. In this method 5'-biotinylated primers are used to introduce biotin residues into the DNA fragments during the amplification. The amplified DNA fragments are detected by liquid hybridization using a 32P- or 35S-labelled oligonucleotide as probe. For measurement the hybrids are collected on polystyrene microparticles or onto microtitre wells taking advantage of the biotinavidin interaction. The method is highly sensitive allowing the detection of 30 molecules of DNA. It involves few and simple operations, and is thus suitable for routine diagnostics. The applicability of the method to the detection of HIV-1 DNA from blood, HCMV DNA from urine and HPV-16 DNA from cervical scrapes was evaluated.

Base Sequence↗
PubMed1990

Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery.

The effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on vigilance, thiopental anesthetic requirements, and the hemodynamic, catecholamine, and hormonal responses to surgery were investigated in healthy (ASA physical status 1) women scheduled for dilatation and curettage (D & C) of the uterus. Fifteen minutes before induction they received single iv doses of either dexmedetomidine (0.5 micrograms/kg; n = 19) or saline (n = 20) in a double-blind fashion. Anesthesia was induced with thiopental and maintained with N2O/O2 (70/30%) and thiopental. Dexmedetomidine was well tolerated and no serious drug-related subjective side-effects or adverse events were observed. The most prominent subjective effects were fatigue and decreased salivation. The total amount of thiopental needed to perform D & C of the uterus was reduced approximately 30% (from 456 +/- 141 mg [mean +/- SD] after saline to 316 +/- 79 mg after dexmedetomidine). This was mostly due to a smaller induction dose in the group receiving dexmedetomidine. Dexmedetomidine appeared to improve the recovery from anesthesia as measured by visual analogue scales (VAS) on fatigue and nausea. The plasma concentration of norepinephrine was decreased by 56% after dexmedetomidine implying decreased sympathetic nervous activity. Systolic and diastolic blood pressure were moderately reduced after dexmedetomidine administration. The authors conclude that dexmedetomidine preanesthetic medication decreases thiopental anesthetic requirements and improves the recuperation from anesthesia with no serious hemodynamic or other adverse effects. Further studies in patients undergoing more stressful surgery are indicated.

Adrenergic alpha-Agonists↗
PubMed1990

Acute hemodynamic effects of medetomidine and clonidine in healthy volunteers: a noninvasive echocardiographic study.

Single intravenous (i.v.) doses of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole, medetomidine (MED), (25, 50, and 100 micrograms) and clonidine (CLO 200 micrograms) were administered to five healthy male volunteers in a randomized, double-blind, placebo-controlled, multiple cross-over study. The hemodynamic effects of the drugs were determined by a two-dimension Doppler-echocardiographic method. Blood pressure (BP) and heart rate (HR) were monitored noninvasively. Cardiac output (CO) was maximally reduced by 23% after 100 micrograms MED and 200 micrograms CLO. Dose-related decreases were observed in systolic BP (SBP) and diastolic BP (DBP) and HR. Maximal reductions were 18 and 11 mm Hg and 11 beats/min after 100 micrograms MED, and 18 and 13 mm Hg and 12 beats/min after CLO. Calculated total peripheral resistance (TPR) and the PR interval on ECG remained unchanged. Ejection fraction (EF) and stroke volume (SV) were not significantly affected by either drug, but mean circumferential fiber shortening velocity (VCF) and the preejection period/left ventricular ejection time (PEP/LVET) ratio indicated a tendency to slightly decreased myocardial performance. We conclude that the new selective alpha 2-adrenoceptor agonist, MED, resembles CLO in its acute hemodynamic actions in healthy humans.

Adrenergic alpha-Agonists↗
PubMed1990

Pharmacological effects and pharmacokinetics of atipamezole, a novel alpha 2-adrenoceptor antagonist--a randomized, double-blind cross-over study in healthy male volunteers.

1. Single doses (10, 30 and 100 mg) of atipamezole (MPV-1248), a new potent and selective imidazole-type alpha 2-adrenoceptor antagonist, and saline placebo were administered as 20 min intravenous infusions to six healthy male volunteers in a randomized double-blind, cross-over phase I study. Later, 100 mg atipamezole was given orally to the same subjects in an open fashion. 2. The i.v. doses resulted in linearly dose-related concentrations of atipamezole in plasma. Pharmacokinetic calculations revealed an elimination half-life of 1.7-2.0 h, an apparent volume of distribution of 3.0-3.5 l kg-1 and a total plasma clearance of 1.1-1.5 l h-1 kg-1. No atipamezole could be detected in plasma after oral dosing. 3. Subjective drug effects were seen mainly after the largest i.v. dose and included increased alertness and nervousness, coldness and sweating of hands and feet, tremor and shivering, motor restlessness, and increased salivation. Salivation was also quantitated using dental cotton rolls, with dose-related increases produced by the i.v. doses. 4. The 100 mg i.v. dose increased plasma noradrenaline concentrations on average by 484 +/- 269 (s.d.)%, and also elevated both systolic and diastolic blood pressure (mean increases 17 +/- 7/14 +/- 2 mm Hg). The 30 mg dose had minor and the 10 mg dose no effects on these variables. Adrenaline and cyclic AMP levels in plasma were increased only after the largest dose. No drug effects were observed after oral dosing. 4. Plasma C-peptide and blood glucose levels were not markedly influenced by the drug, and cortisol secretion was not stimulated. 5. The observed effects are compatible with the presumed alpha 2-adrenoceptor antagonistic action of atipamezole and are in general concordance with the reported results of other alpha 2-adrenoceptor antagonists (yohimbine and idazoxan). 6. Although not orally active, atipamezole may prove to be a useful agent in studies of alpha 2-adrenoceptor function in man.

Adrenergic alpha-Antagonists↗
PubMed1990

Medetomidine premedication in dental surgery--a double-blind cross-over study with a new alpha 2-adrenoceptor agonist.

A single 50-micrograms dose of medetomidine, a highly selective alpha 2-adrenoceptor agonist, was administered intravenously as premedication 30 min before surgical third molar extraction under local anaesthesia to ten healthy male subjects in a double-blind, placebo-controlled, cross-over study. Blood pressure, heart rate, plasma catecholamines and cortisol were measured as indicators of operation-related stress. Apprehension and pain were assessed with repeated Visual Analogue Scales. The dental surgeon rated the overall effectiveness of the premedications, and the patients reported their subjective preference. Drug-induced sedation was determined with the Critical Flicker Frequency (CFF) test. The dental surgeon rated medetomidine as significantly more effective premedication than saline placebo. Apprehension was significantly reduced by medetomidine. The patients clearly preferred medetomidine premedication. Blood pressure was lower in the medetomidine session, whereas no significant differences were seen in heart rate. Plasma noradrenaline was lower after medetomidine, but adrenaline and cortisol levels were not affected. In conclusion, medetomidine may offer a useful alternative to traditional premedications in out-patient surgery, and its clinical usefulness should also be studied in other anaesthetic paradigms.

Adrenergic alpha-Agonists↗
PubMed1990

Use of AffiProbe HPV test kit for detection of human papillomavirus DNA in genital scrapes.

The presence of human papillomavirus (HPV) DNA in cervical and vaginal scrapes was analyzed by the AffiProbe HPV test kit (Orion Corp., Orion Pharmaceutica, Helsinki, Finland), which is a 1-day solution hybridization test for HPV type 6/11, 16, or 18. The AffiProbe test was compared with a commercially available dot blot test (ViraPap and ViraType tests; Life Technologies Inc., Gaithersburg, Md.). The study group consisted of 178 patients seen in a gynecological outpatient clinic. Altogether, 64 specimens (36 cervical and 28 vaginal scrapes) from 49 patients were positive by the AffiProbe test. Concurrently collected cervical scrapes from 174 patients were available for the reference test, which yielded 27 positive results for HPV type 6/11 or 16/18 and 25 positive results for HPV type 31/33/35. Agreement as to the presence of HPV type 6/11, 16, or 18 by the two tests was reached in 85% of the specimens. Eleven cervical specimens were positive by the AffiProbe test only, and nine cervical specimens were positive by the ViraType test only. Independent evidence obtained by the polymerase chain reaction, repeat examination, or the concurrent presence of HPV DNA in vaginal or vulval epithelium supported the AffiProbe and the ViraType test results for 6 of the 11 and 6 of the 9 specimens with discrepant results, respectively. Thus, the DNA tests had similar sensitivities for HPV type 6/11, 16, and 18 DNAs, but the results were obtained within 1 day by the AffiProbe test, whereas results for the ViraPap and ViraType analyses required from 4 days to 2 weeks.

Cervix Uteri↗