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Biomedical subjects

M Salonen

Publications and source records attributed to M Salonen.

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

Synergistic interaction between alpha 2-adrenergic agonists and benzodiazepines in rats.

Both alpha 2-adrenergic agonists and benzodiazepines exert anxiolytic and sedative effects when administered as preoperative medications. Clinical effects achieved with a combination of drugs, representative of these classes of compounds, is greater than that which could be expected from a simple additive response. Therefore, we investigated the nature of the interaction between dexmedetomidine, the highly-selective alpha 2-adrenergic agonist, and midazolam in a series of in vivo and in vitro studies in rats. Rats were administered midazolam, dexmedetomidine, or a combination of midazolam and dexmedetomidine intravenously to derive three dose-response curves for loss of righting reflex (LRR). LRR was determined in rats in a rotating cage (4 rotations/min) by observing whether the rat failed to maintain its upright posture for greater than or equal to 15 s exactly 2.5 min after drug administration. The effect of either flumazenil (benzodiazepine receptor antagonist) or atipamezole (the alpha 2-adrenergic antagonist) on the LRR was also determined. A probit analysis was performed and an isobologram for the ED50 was derived to assess the nature of the interaction. Rat brain membranes were prepared for receptor binding assays using [3H]-flumazenil and [3H]-rauwolscine to characterize the benzodiazepine and alpha 2-adrenergic receptors, respectively. The ability of either midazolam or dexmedetomidine to displace the radiolabeled ligand from the alternative receptor was assessed. To detect a possible kinetic interaction between the two drugs, separate cohorts of rats were administered the two drugs individually or in combination at the combination ED50 doses.(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

Difference in action between oral triazolam and zopiclone.

The effects of oral triazolam 0.25 mg and zopiclone 7.5 mg in 7 supine volunteers were compared by means of quantitative measurements of the EEG, saccadic eye movements, visual analogue scale (VAS) for alertness, critical flicker fusion frequency (CFF) and the Maddox wing. Zopiclone reached its maximum effect earlier (62 min) than triazolam (91 min; CFF). On linear regression analysis the average rate constant (regression coefficient) of onset of action of zopiclone was significantly greater than that of triazolam (0.29 vs. 0.17). Triazolam and zopiclone had similar effects, but zopiclone seemed to have a faster onset of action, probably indicating swifter absorption in supine subjects. Quantitative EEG evaluation gave parallel results to the other parameters used, but triazolam and zopiclone showed a dissimilar mechanism of action, as characterized by changes in the alpha frequency.

Administration, Oral↗
PubMed1990

Anticholinergic premedication in Finland 1988.

In order to investigate the present use of anticholinergic drugs in premedication, a questionnaire was sent to Finnish anaesthesiologists. The results indicate that there is significant variation between different parts of the country regarding the usage of these drugs. A decrease in routine use has taken place over the past 5 years. Half of the anaesthesiologists now routinely use anticholinergic drugs in premedication, while 69% were using them 5 years ago. Glycopyrrolate has gained popularity and was the most used drug. Most anaesthesiologists gave the anticholinergic premedication intravenously, briefly before induction.

Administration, Oral↗
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↗
PubMed1989

A comparison of two sedative premedications for minor oral surgery under local anaesthesia.

Two commonly used drug combinations were studied as premedications before surgical 3rd molar removal under local anaesthesia. The study was randomized, crossover and double-blind in 12 patients. Our routine premedication for lengthy operations, consisting of diazepam 10 mg p.o. plus i.m. scopolamine 0.006 mg/kg and morphine 0.2 mg/kg, was compared with a combination of diazepam 10 mg p.o. plus metoprolol 50 mg p.o. The latter combination was expected to cause fewer central nervous system side effects and be more suitable for out-patient surgery. Drug levels in blood, physiological and biochemical indicators of operation-related stress, CNS side effects, and the patients' subjective preferences were monitored. Both combinations were equally accepted by the patients, but the diazepam/scopolamine/morphine combination caused clearly more side effects after discharge than diazepam/metoprolol. The operation-related haemodynamic changes and plasma catecholamine responses were similar after both premedications.

Adult↗
PubMed1989

Propofol infusion for sedation in outpatient oral surgery. A comparison with diazepam.

An infusion of propofol was compared with intravenous boluses of diazepam as sedation for minor oral surgery under local anaesthesia in 12 healthy patients who had elective bilateral surgical extraction of lower third molars; the patients served as their own controls. Plasma catecholamine, vasopressin and cortisol concentrations were determined from repeated blood samples. The total administered dose of propofol was 3.93 (SD 1.34) mg/kg and of diazepam 0.28 (SD 0.07) mg/kg. No cardiovascular depression or airway problems occurred. Other side effects were also rare but some discomfort on injection was frequent with propofol. Recovery times were faster after propofol than after diazepam as assessed by the Maddox wing and visual analogue scales. Propofol also provided better amnesia compared to diazepam at the time of the extraction of the teeth. Eight of the 12 patients subjectively preferred propofol sedation. There was no hormonal stress response in either group.

Adult↗
PubMed1989

Temazepam or midazolam for night sedation. A double-blind study.

The effects of oral temazepam (20 mg), oral midazolam (15 mg) and a placebo were compared for night sedation on the evening prior to surgery in a double-blind study. Patients in the placebo group had significantly worse sleep than those in the temazepam (p = 0.004) or midazolam groups (p = 0.04). There was no significant difference between the two drug groups, nor between the residual effects of the three treatments. Temazepam appears to be somewhat more effective than the ultrashort-acting midazolam in pre-operative transient insomnia.

Administration, Oral↗
PubMed1989

Effect of elimination of occlusal interferences on signs and symptoms of craniomandibular disorder in young adults.

Sixty-two dental students judged not to be in need of treatment for craniomandibular disorder (CMD) were randomly divided into two groups, one receiving occlusal adjustment and the other mock adjustment. A double-blind study design was applied. After 2 years of education in dentistry, including courses in stomatognathic physiology, the increase in the subjective symptoms of CMD was significantly greater in the placebo control group than in the treatment group. The difference between the groups in the increase of sites tender to palpation was less clear, showing only a trend. However, the increase was statistically significant within the placebo group but not within the treatment group. Prophylactic occlusal adjustment thus appears to be effective in reducing the occurrence of symptoms of CMD, and possibly also the occurrence of clinical signs.

Adult↗
PubMed1988

Local dental anaesthesia with lidocaine and adrenaline. Effects on plasma catecholamines, heart rate and blood pressure.

5 volunteers took part in this double-blind, cross-over study to evaluate the role of adrenaline 1:80,000 in lidocaine used in dental local anaesthesia on haemodynamics and the concentrations of catecholamines and their metabolites in plasma. The exogenous adrenaline statistically significantly elevated the heart rate (from 66 +/- 7 to 79 +/- 9 bpm), but did not affect systolic or diastolic blood pressure. Plasma adrenaline concentrations were increased more than 10-fold (from 0.02 +/- 0.02 to 1.0 +/- 0.3 nmol/l). We conclude that the adrenaline present in the local anaesthetic is a major source of adrenergic activation during minor oral surgery.

Adult↗
PubMed1988

The effect of flunitrazepam on acoustic reflex--a methodological pilot study.

Four healthy volunteers took part in this study in four sessions at one week intervals minimum. Three intravenous dose levels of flunitrazepam as well as placebo (saline) were investigated. The sessions were randomized and the study was double blind. The results show that a significant correlation exists between the serum concentrations of flunitrazepam and acoustic reflex amplitude, latency, Maddox wing readings and subjective sedation. Critical flicker fusion frequency test was insensitive in this respect. We conclude that acoustic reflex may be a new method for determination of benzodiazepine effects in man.

Double-Blind Method↗
PubMed1987

Simple devices in differentiating the effects of buprenorphine and fentanyl in healthy volunteers.

We have tested the usefulness of the critical flicker fusion threshold-test (CFF), Maddox wing readings (MW), and visual analogue scale scores (VAS) in a double-blind, random-order study designed to evaluate the clinical effects of two different kinds of opiates, buprenorphine and fentanyl in comparison with those of placebo. The results were compared with the so-called postanaesthetic recovery score (PARS). In 7 healthy volunteers MW and VAS differentiated the effects of buprenorphine 7.5 micrograms/kg i.v. from those of fentanyl 2.5 micrograms/kg i.v. and placebo. CFF was very insensitive in this respect and PARS completely useless. Our results show that, in addition to the known usefulness of VAS, MW is also able to differentiate the effects of these opiates.

Adult↗
PubMed1987

In vivo registration of Achilles tendon forces in man. I. Methodological development.

Mechanical behavior of muscle and its control is largely unknown under normal movement conditions. The present report deals with the methodological development to record directly in vivo forces from the human achilles tendon (AT) when the subjects perform normal movements ranging from slow walking to maximal sprinting and jumping. The development began with animal experiments, which dealt with the transducer design, surgical operation procedures, and duration of implantation. The first human experiment utilized an E form transducer implanted around the AT under local anesthesia. The transducer was kept in situ for 7 days, and on the 8th day recordings were made on simple plantar flexion movements and during slow walking. Further development led to final selection of a "buckle"-type transducer, and the measurements can be made immediately after operation and they usually last 2-3 h. The AT transducer can be calibrated by placing the subject in a prone position on to a calibration table. His operated foot was placed in a special shoe, the axis of which coincided with that of the ankle joint. A pulley system with known weights was used to dorsiflex the foot. Taking into consideration the geometrical arrangement of the AT transducer, axis of rotation, and the pulley system, the exact values of AT forces could be calculated. The actual measurements incorporate the use of EMG recordings of the leg extensor muscles and various external force measurements, such as long force platform or oscillating ergometers. The transducer is removed immediately after the measurements and the subjects recover.

Achilles Tendon↗
PubMed1987

Use of simple tests to determine the residual effects of the analgesic component of balanced anaesthesia.

In order to evaluate simple means of determining the rate of recovery after general anaesthesia, the usefulness of the critical flicker fusion threshold test, the Maddox wing apparatus and the visual analogue scale were compared. The postanaesthetic recovery score was used as a reference. Two patient groups (n = 15 in each) received, in a randomized double-blind study, a similar balanced anaesthesia for Caesarean section, except that the analgesic component was either fentanyl 2.5 micrograms kg-1 i.v. or buprenorphine 7.5 micrograms kg-1 i.v. Maddox wing apparatus and visual analogue scale were sensitive enough to differentiate between the postanaesthetic residual effects of the two opioids, but critical flicker fusion threshold and, especially, postanaesthetic recovery score were insensitive in this respect. There was no difference between the two patient groups in mean arterial pressure and heart rate. Our results show that the residual effects of different kinds of opioids as an analgesic component of balanced anaesthesia can be differentiated using simple means like Maddox wing apparatus and visual analogue scales.

Adult↗
PubMed1987

Temazepam versus flunitrazepam as an oral premedication in adult surgical patients.

In a randomized study, 20 patients received temazepam 20 mg orally the night before and 20 mg in the morning of an operation performed under spinal analgesia (Group I); 20 patients received flunitrazepam I mg similarly (Group 2). Different aspects of the premedication were evaluated verbally, with the aid of a visual analogue scale, Maddox wing apparatus, the critical flicker fusion threshold test, blood pressure and heart rate measurements, serum and CSF cortisol and plasma ADH measurements, as well as CSF drug level determinations. Clinically, temazepam 20 mg proved to be comparable with flunitrazepam I mg, although the latter more effectively prevented cardiovascular changes and pre-operative hormonal stress reaction. No correlation was found between the CSF drug level (bioassayed by radioreceptor assay) and the clinical response of the two benzodiazepines, nor was there any correlation between the cortisol or ADH levels versus the CSF drug levels. On the whole, flunitrazepam proved to be marginally better than temazepam as an oral premedicant.

Administration, Oral↗
PubMed1987

Induction of general anesthesia in children with midazolam--is there an induction dose?

The pharmacodynamics of midazolam was studied in 27 children undergoing elective surgery at five different dose levels (0.075-0.6 mg/kg) in attempting to find a suitable induction dose for general anesthesia. A comparison of the highest dose was made to thiopentone 5 mg/kg. Even an induction dose of 0.6 mg/kg of midazolam was found to be unreliable in children, but effective enough to cause significant fall in systolic blood pressure after induction (p less than 0.05). In the children premedicated with atropine and pethidine thiopentone resulted in a more rapid closure of the eyes (p less than 0.01) and disappearance of the eye-lid reflex (p less than 0.01) than the high dose of 0.6 mg/kg of midazolam. Moreover, midazolam failed to induce sleep in a considerable fraction of the children even at the highest dose employed. The thiopentone group was more alert in the recovery room at 30 min after wake-up. The amnestic effect of thiopentone and midazolam were equal.

Anesthesia, General↗
PubMed1987

Midazolam as an induction agent in children: a pharmacokinetic and clinical study.

The pharmacokinetics of midazolam was studied in 21 children undergoing elective surgery at five different dose levels for induction of general anesthesia and were compared with a control group (n = 6) given thiopental, 5 mg/kg. The clearance of midazolam was found to be dose-related. The elimination half-life varied from 0.79 to 2.83 hr, which is shorter than in adult patients. Even a dose of 0.6 mg/kg midazolam was found to be unreliable as an agent for induction of anesthesia. Compared with thiopental 5 mg/kg, significantly longer times of onset to closing of the eyes (P less than 0.01) and the disappearance of eyelid reflex (P less than 0.01) were seen with midazolam.

Analysis of Variance↗