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Biomedical subjects

E Iisalo

Publications and source records attributed to E Iisalo.

At least 19 recordsLinked to original sources
PubMed1992

The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non-pregnant women.

1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam (n = 12) were studied in pregnant (n = 27) and non-pregnant (n = 12) subjects. 2. In early pregnancy (9-14 weeks of gestation) the mean peak plasma drug concentration (Cmax = 19 +/- 9 micrograms ml-1) after an intravenous injection of 200 mg mecillinam was significantly lower (P less than 0.05) and the volume of distribution (V = 49 +/- 20.1) significantly larger (P less than 0.05) than in non-pregnant subjects (Cmax = 35 +/- 18 micrograms ml-1, V = 29 +/- 12.1). In late pregnancy (39-40 weeks of gestation) the plasma mean peak concentration (Cmax = (29 +/- 14 micrograms ml-1) after parenteral administration of 200 mg mecillinam was slightly lower and the volume of distribution (V = 65 +/- 29.1, V = 0.9 +/- 0.4 l kg-1) significantly larger than that in non-pregnant subjects (V = 0.4 +/- 0.3 l kg-1). Also after oral administration of 200 mg pivmecillinam, equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant subjects (Cmax = 1.8 +/- 1.2 micrograms ml-1) was slightly lower than that in non-pregnant subjects (Cmax = 1.7 +/- 1.2 micrograms ml-1). 3. The mean half-life of elimination after parenteral administration of mecillinam was significantly longer during both early (t1/2,Z = 133 +/- 38 min, P less than 0.05) and late pregnancy (t1/2,Z = 107 +/- 41 min, P less than 0.05) as compared with the non-pregnant state (t1/2,Z = 75 +/- 21 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Tracheostomy in pediatric patients.

From 1978 to 1987, tracheostomy was performed on 33 children, 13 boys and 20 girls, with a male to female ratio of 0.65:1. The mean age at the time of tracheostomy was 726 days, 76% of the children being under the age of two years. The incidence of pediatric tracheostomy per hospital admissions was 0.05%. Subglottic stenosis (13 children) and respiratory distress syndrome with prolonged endotracheal ventilation (11 children) were the most common indications for tracheostomy. The mean duration of prolonged endotracheal intubation before tracheostomy was 64 days, and that of tracheostomy treatment 117 days. During the tracheostomy period, five children died, but only one death was related to tracheostomy. The total rate of complications was 30%. We emphasize the importance of strict indications for pediatric tracheostomy.

Adolescent↗
PubMed1991

Current practice regarding invasive monitoring in intensive care units in Finland. A nationwide study of the uses of arterial, pulmonary artery and central venous catheters and their effect on outcome. The Finnish Intensive Care Study Group.

As part of a nationwide evaluation of intensive care, we examined patient- and hospital-related factors which could influence the patterns of utilization of arterial cannulae and central venous and pulmonary artery catheters. We also studied the possible impact of these interventions on the short-term outcome among 14,951 consecutive ICU admissions to 25 intensive care units (75% of all ICU beds) in Finland. There was considerable variation between individual units in the use of these devices even if the differences in severity of illness were taken into account. Arterial cannulation was used in 71.2%, PA catheterization in 10.6% and CVP monitoring in 49.3% of cases in teaching ICUs, excluding cardiac surgery, and in 38.5%, 2.6% and 33.1% of cases in non-teaching ICUs respectively. The factors predicting the use of invasive monitoring included extensive surgery causing a risk of cardiovascular instability, needs for mechanical ventilation, infusion of vasoactive drugs and complicated fluid therapy. Cardiovascular problems among non-operative patients increased the odds for PA catheterization but reduced them for arterial and CV cannulation. No clear-cut benefit could be found in the form of hospital mortality reduction from invasive haemodynamic monitoring, used as described in this study.

Catheterization, Central Venous↗
PubMed1991

Beta-blocking effects of timolol at low plasma concentrations.

The concentration-effect relationship of 0.25 mg intravenous timolol with and without pretreatment with 100 mg quinidine was studied in six healthy young volunteers with a randomized, double-blind, crossover study design. Blockade of cardiac beta-adrenoceptors was assessed by determining the dose ratios (DR) of isoproterenol infusions required to increase heart rate by 25 beats/min before and after timolol infusion. The logarithm of timolol concentration in plasma was linearly related to the logarithm (DR-1) of isoproterenol infusion, with a mean Pearson correlation coefficient of 0.89 +/- 0.11 (+/- SD; n = 24) at timolol concentrations well below 1 ng/ml. The increases in cyclic adenosine monophosphate (cAMP) and norepinephrine plasma levels caused by isoproterenol infusions were attenuated after timolol. Quinidine administration increased timolol plasma levels and cardiac beta-blocking effects by 10% to 40%. It was concluded that timolol at concentrations below 1 ng/ml in plasma competitively antagonizes cardiac and noncardiac effects of isoproterenol infusions. Timolol effects are augmented after quinidine administration. The beta-blockade occurring at low plasma levels can explain side effects and actions of ocularly applied timolol.

Adult↗
PubMed1991

Systemic absorption of ocular timolol in poor and extensive metabolizers of debrisoquine.

The oxidation of timolol exhibits genetic polymorphism of debrisoquine type. After oral administration, poor metabolizers have high timolol concentrations in plasma and show an intensified systemic beta-blockade. Since the contribution of debrisoquine metabolizer status on timolol eyedrop therapy is not known we determined the systemic absorption of ocularly applied timolol in healthy subjects classified either extensive or poor metabolizers. Unlike after oral timolol ocular drug administration caused higher peak drug concentrations in plasma in extensive metabolizers. The variation in the systemic absorption of ocular timolol contributed more than the debrisoquine oxidation phenotype to timolol plasma levels after a single ocular timolol application.

Absorption↗
PubMed1991

Acute physiology and chronic health evaluation (APACHE II) and Glasgow coma scores as predictors of outcome from intensive care after cardiac arrest.

OBJECTIVES: a) To examine the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Glasgow Coma Scores as predictors of the outcome of patients following resuscitation from cardiac arrest; b) to study the impact of the components of APACHE II on the prediction. DESIGN: A nationwide study in Finland with prospectively collected data on all patients admitted to intensive care after cardiac arrest during a 14-month period. Two thirds of the cardiac arrest patients included in the study were randomly selected to derive predictive models, and the remaining one third constituted the validation sample. SETTING: A total of 25 medical and surgical ICUs in Finland (13 in tertiary referral centers). PATIENTS: Six-hundred nineteen consecutive cardiac arrest patients. Fifteen patients less than 16 yrs were excluded. MAIN OUTCOME MEASURES: Variables included in the APACHE II or Glasgow Coma Scores were collected at the time of ICU admission and then three times after admission, at 24-hr intervals. ICU- and hospital-mortality rates and a 6-month mortality rate after ICU admission were studied. RESULTS: Of 604 study patients, 370 (61.3%) patients died in the hospital. The most accurate prediction of hospital outcome was based on data collected after the first day of ICU care, not on the admission values. Twenty-one (21.9%) of 96 patients with a low APACHE II score (less than or equal to 9) died compared with 66 (84.6%) of 78 patients with a high APACHE II score (greater than or equal to 25) (p less than .001). Of 160 patients with a normal Glasgow Coma Score (14 to 15), 45 (28.1%) died, whereas there were 114 (81.4%) nonsurvivors among 140 patients with a low Glasgow Coma Score of 3 (p less than .001). The performance of predictive models, including age, the Chronic Health Evaluation, and either the Acute Physiology Score (Acute Physiology Score model) or the Glasgow Coma Score (Glasgow Coma Score model) were compared with the prediction according to the APACHE II in the validation sample. When using 80% probability of death as a decision rule, the Acute Physiology Score model determined 35 of 153 patients to have high risk of death, 29 of whom died (the positive predictive value being 82.9%). The Glasgow Coma Score model predicted 34 patients to die, 26 of whom died (positive predictive value 76.5%), and the APACHE II score predicted seven deaths, five of whom actually died (positive predictive value 71.4%). CONCLUSIONS: The APACHE II scoring system cannot be recommended as a prognostic tool to support clinical judgement in cardiac arrest patients, but by modifying it, a more accurate prediction of poor outcome could be achieved. The Glasgow Coma Score explained to a great extent the predictive power of the APACHE II.

Adult↗
PubMed1991

Effects of glycopyrrolate and atropine on heart rate variability.

Analysis of heart rate variability, combined with physiological tests (deep breathing and tilt tests) was used to characterise the effects of atropine and glycopyrrolate on the parasympathetic nervous tone of the heart in healthy male volunteers. The low dose of atropine (120 micrograms) administered as a continuous infusion in 15 min was associated with parasympatomimetic effects estimated by the slowing of the heart rate and an increase of the mean and beat-to-beat heart rate variability. The bradycardia and increase of heart rate variability following infusion of glycopyrrolate (50 micrograms) was less marked and did not differ significantly from that of placebo. The higher doses of atropine (720 micrograms) and glycopyrrolate (300 micrograms) administered as a continuous infusion in 15 min produced an equal vagal cardiac blockade characterised by significant tachycardia and a decrease in overall and beat-to-beat heart rate variability. It is concluded that at low doses the parasympatomimetic action of glycopyrrolate is less marked than that of atropine; and at higher doses only small differences exist between these two muscarinic antagonists in their effects on cardiac vagal outflow, assessed by heart rate and heart rate variability.

Adult↗
PubMed1990

Measuring the bronchial effect of bronchodilating drugs in healthy subjects after methacholine provocation. Salbutamol as a model drug.

To study whether it would be possible to assess bronchodilating drugs in healthy subjects with methacholine - induced bronchoconstriction, salbutamol 100, 200 and 300 micrograms was inhaled in random order by 12 healthy volunteers in a double-blind, placebo-controlled study. Dose response "slope" (DRS = maximum percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumols] was used as an index of bronchial reactivity, and was calculated for forced expiratory flow volume in 1 s (DRSFEV1) and area under the flow-volume curve (DRSAEFV). Bronchial reactivity and its reproducibility were first tested by a standard methacholine provocation method. An abbreviated, single-dose method was used to measure the effect of salbutamol. The reproducibility of methacholine provocation was good, and the single-dose and standard methods gave comparable results. The DRS-values of all the doses of salbutamol differed significantly from placebo and from each other. AEFV did not show any advantage over the FEV1 in this context. A significant negative association between the dose of salbutamol (microgram/kg) and airway reactivity was observed. In conclusion, use of the DRS showed it possible to evaluate the protective efficacy of beta 2-adrenergic agonists against induced bronchoconstriction in healthy subjects.

Adult↗
PubMed1990

Systemic absorption of ocular scopolamine in patients.

The systemic absorption of scopolamine 0.25% eyedrops given unilaterally was quantitated in eight patients following therapeutic drug application. Another set of eight patients received placebo drops to study the effect of scopolamine on heart rate, blood pressure and salivation. Scopolamine was rapidly and efficiently absorbed after its ocular administration. The peak plasma scopolamine concentration of 550 +/- 60 pg/ml was reached within 15 minutes in all but two patients. Ocular scopolamine did not affect patients blood pressure or heart rate when compared to patients in the placebo group. Thirty minutes after administration of scopolamine the salivary secretion was slightly but insignificantly reduced.

Absorption↗
PubMed1990

Pharmacokinetics of i.m. glycopyrronium.

A sensitive radioreceptor assay was used to determine the pharmacokinetics of glycopyrronium following a single i.m. injection of 8 micrograms kg-1 in nine surgical patients. Rapid absorption was found, with a mean peak plasma concentration after 16.1 min and mean elimination half-life of 75.4 min. Almost half (49.3%) of the drug was excreted in pharmacologically active form in the urine within 3 h. A significant increase in heart rate (P less than 0.05) occurred in 15 min, lasting up to 60 min, and an antisialagogue effect in 10 min, lasting up to 8 h (P less than 0.05). There was no measurable glycopyrronium in lumbar cerebrospinal fluid samples (n = 9) taken 40 min after administration of drug.

Blood Pressure↗
PubMed1990

Pharmacokinetics of glycopyrronium in parturients.

A sensitive radioreceptor assay was used to determine the pharmacokinetics of glycopyrronium 6 micrograms/kg after intramuscular (deltoid muscle) administration in eight Caesarean section patients. A fast absorption rate was found with a mean maximum plasma concentration (Cmax) of 6.3 (SD 1.5) ng/ml, a mean time to Cmax (Tmax) of 10.0 (3.8) minutes and the elimination half-life (t1) of 33.4 (1.92). The respective AUC0-8 h value was 5.61 (1.27) hours ng/ml. This dose produced a significant increase in the maternal heart rate after 10 minutes (p less than 0.05) and an antisialogogue effect after 30 minutes (p less than 0.05) of the drug injection. Almost half of drug (48.3%) was excreted into the urine within 3 hours. There were no measurable levels of glycopyrronium in the lumbar cerebrospinal fluid (CSF) after 60 minutes of drug injection. The concentrations of glycopyrronium in the umbilical venous (0.28 (0.25) ng/ml) and in the umbilical arterial (0.18 (0.11) ng/ml) plasma after 86 minutes of drug injection were low and clinically insignificant, as was the case in the amniotic fluid (0.15 (0.08) ng/ml).

Adult↗
PubMed1990

The effects of beta-adrenoceptor antagonists and levomepromazine on the metabolic ratio of debrisoquine.

The in vivo inhibitory effect of five beta-adrenoceptor antagonists and levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The debrisoquine phenotyping test was performed before and after 7 days' treatment with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily), timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice daily) or levomepromazine (10 mg daily), each of which was given to six-seven subjects. No clear change in the urinary metabolic ratio of debrisoquine/4-OH-debrisoquine (MR) was seen with any of the single beta-adrenoceptor antagonist treatments, but the MR value increased significantly when all beta-adrenoceptor blocker treatments were considered together. Debrisoquine metabolism was clearly impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from 1.24 +/- 1.6 to 4.70 +/- 5.23 (P = 0.018) and the excretion of 4-hydroxydebrisoquine decreased from 0.92 +/- 0.46 mg to 0.31 +/- 0.19 mg (P = 0.043). Thus, levomepromazine changes MRs towards those characteristic of phenotypically poor metabolizers, but beta-adrenoceptor antagonists at the doses examined have only a marginal effect.

Adrenergic beta-Antagonists↗
PubMed1990

Radioreceptor assay for pharmacokinetic studies of glycopyrrolate.

A sensitive radioreceptor assay for the determination of glycopyrrolate concentrations in human plasma, urine and cerebrospinal fluid (CSF) is described. The applicability of the assay for kinetic studies in human was studied by determining the plasma concentrations and the renal excretion in three gynaecological surgical patients, who received 8 micrograms/kg of glycopyrrolate as a premedication intramuscularly. Tritiated N-methyl scopolamine was used to label the muscarinic cholinergic receptors in the membrane preparation obtained from the rat brain. The limit of detection of the assay was 70 ng/l in plasma, 2 micrograms/l in urine and 140 ng/l in CSF. There was no evidence of cross-reactivity of glycopyrrolate derivatives in clinical concentrations. A very rapid absorption was found with a mean maximum plasma concentration (Cmax) of 14.26 (range 12.02-16.97) micrograms/l and mean Tmax (time to Cmax) of 13.3 (range 10-15) min. and almost 50% of the dose administered was excreted into the urine within 3 hr. The CSF levels of glycopyrrolate were under detection limit. It is concluded that the sensitivity of the method is sufficient for pharmacokinetic studies of glycopyrrolate after therapeutic dosing.

Aged↗
PubMed1990

Subglottic stenosis in neonates and children. Clinical findings and therapy.

From 1978 through 1987, acquired subglottic stenosis was confirmed endoscopically in 31 children. The mean gestational age of the children was 32 weeks and mean birthweight 2,180 g. Of the children 84% were below 12 months of age at the time of diagnosis. Respiratory distress syndrome was confirmed in 17 children. Before diagnosis, 97% of the children had been treated by endotracheal intubation for ventilatory support, the mean duration of intubation being 37 days. In 10 children, subglottic stenosis was mild and mature and these children were followed up only. Endolaryngeal prosthesis was employed in 2 children and laryngotomy with autogenous bone graft in 5 children. Mean follow-up time was 5 years 4 months. At follow-up, 18 of the children showed good or excellent results.

Child↗
PubMed1990

Vasomotor rhinitis and the systemic absorption of ipratropium bromide.

Plasma concentrations of nasally administered ipratropium bromide were analyzed in 10 subjects suffering from severe vasomotor rhinitis and 10 age-sex matched control subjects. The rate of salivary secretion and heart rate were monitored in order to measure systemic anticholinergic effects. A total dose of 360 micrograms of ipratropium bromide (60 micrograms into each nostril, repeated twice at 15 min intervals) were administered nasally to the subjects in randomized order. Ipratropium bromide was rapidly absorbed from the nasal mucosa into the systemic circulation in both groups. The peak plasma concentrations were detected within 10 min after the last drug administration. The peak concentrations were about 50% higher (380 +/- 153 pg/ml) in patients than in control subjects (245 +/- 134 pg/ml). The AUCs/0-15 min (1970 +/- 1140 pg/ml X min) in patients were about 100% higher than in the control subjects (960 +/- 560 pg/ml X min). During the experiment there was a small decrease in the heart rate (8 bpm) and salivary secretion (10%) in both groups. In conclusion, the vasomotor rhinitis increases the systemic absorption of nasally administered ipratropium bromide, but the small increase in the absorption is not likely to have any clinical consequences.

Administration, Intranasal↗
PubMed1990

Measuring the bronchial effects of bronchodilating drugs in healthy subjects with methacholine provocations: theophylline protects against induced bronchoconstriction in a dose-dependent manner.

To assess whether it would be possible to use methacholine (MCH) provocation tests with healthy subjects in the evaluation of bronchodilatory drugs, an intravenous infusion of theophylline ethylenediamine in increasing doses of 2.5, 5.0 and 7.5 mg/kg was given in random order to nine healthy non-smoking volunteers in a single-blind, placebo-controlled study. Dose response slope (DRS = maximal decline [%] in pulmonary function/the maximum dose of MCH [mumol]) was used to estimate airway reactivity. DRS was calculated to FEV1 (DRSFEV1) and to area under the flow-volume curve (AEFV, DRSAEFV). The bronchial reactivity was first tested with a standard MCH provocation method. An abbreviated, single-dose, method was used in the measurement of the effects of theophylline. The DRS-values obtained from the short method did not differ from those obtained from the standard one (p = 0.86, for DRSFEV1 and DRSAEFV), and correlation between these two methods was good (r = 0.93 and 0.98 for DRSFEV1 and DRSAEFV, respectively [p less than 0.001]). Serum theophylline concentrations achieved were (mean +/- SEM) 32.4 +/- 0.9, 63.7 +/- 3.3 and 93.4 +/- 3.3 mumol/l, which differed significantly from each other (p much less than 0.001). An inverse linear relationship between the serum theophylline concentration and the airway reactivity was observed with both indexes (r = -0.54, p less than 0.01 for DRSFEV1 and r = -0.65, p less than 0.001 for DRSAEFV). Even the lowest dose, which produced serum concentrations well under the therapeutic range, protected significantly (p less than 0.05) against MCH induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Intramuscular atropine in healthy volunteers: a pharmacokinetic and pharmacodynamic study.

In a randomized, double-blind, placebo controlled crossover study, the pharmacokinetics and some clinically important pharmacodynamic effects of intramuscular atropine (dl-hyoscyamine) were studied in 6 healthy male volunteers. The plasma concentrations of l-hyoscyamine were analyzed by radioreceptor assay (RRA) and the plasma concentrations of dl-hyoscyamine by radioimmunoassay (RIA). The absorption rate and the elimination rate of dl-hyoscyamine and l-hyoscyamine were comparable (tmax = 8.40 vs 8.67 min, t1/2el = 2.95 vs 2.43 h, dose 0.02 mg/kg) but the mean maximum plasma concentration of dl-hyoscyamine was 2.9 times and the mean AUC value 6.0 times higher than that of l-hyoscyamine which indicates a kinetic difference between the enantiomers. The concentrations of d-hyoscyamine calculated from the dl- and l-hyoscyamine concentrations reached maximum between 1 and 2 h after drug injection. The renal excretion of l-hyoscyamine occurred mostly in 6 h (34% of the dose) and no conjugated drug forms were detected. The increase in heart rate was observed only after the higher dose (0.02 mg/kg) and it was significant between 30 min and 2 h. The plasma concentrations of l-hyoscyamine and the change in heart rate expressed as percentages showed a linear correlation: concentrations under 0.5 micrograms/l caused slowing of rate, higher concentrations caused acceleration. Also, the antisialagogue effect (30 min-3 h) correlated with plasma concentrations.

Adult↗