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Biomedical subjects

E Kentala

Publications and source records attributed to E Kentala.

At least 19 recordsLinked to original sources

Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine. A comparison of two injection sites.

BACKGROUND: Intramuscular scopolamine plus morphine premedication is traditionally used when prominent sedative or antisialogogue effect is needed. Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma concentrations found after therapeutic doses. This investigation compares the pharmacokinetics and the clinical responses of this drug combination injected into two commonly used injection sites. METHODS: Twelve ASA class 1 patients scheduled for minor surgery under spinal anaesthesia received scopolamine 6 micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6 micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The absorption of morphine was similar in both groups (Tmax 16 min), but the peak plasma concentrations were higher after deltoid injection (71 vs 49 micrograms/l). The individual variation in the elimination half-lives of both scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine 1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate slowing (25%) of heart rate was found in both groups. A heavy sedation and antisialogogue effect (VAS) was found in both groups with faster occurrence of maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine premedication can be achieved after an injection into deltoid muscle.

Anesthesia, Spinal

Comparison between diagnoses of human experts and a neurotologic expert system.

The decision-making ability of a recently developed neurotologic expert system was compared with the diagnoses of six physicians. Five of the physicians were residents and one was a specialist in the field of otolaryngology. The test patients were randomly selected from vertiginous patients referred to an otolaryngology clinic. The expert system and the physicians first had identical information on patient history, symptoms, and tests. During the second phase of the study the physicians were allowed to use the full medical records. The correct diagnoses were certified by an experienced specialist in neurotology. The expert system did better in decision-making when both the expert system and the physicians had identical information on patients. However, when the physicians were allowed to use patient's complete medical records, they surpassed the expert system. The expert system diagnosed 65% of the cases, while the physicians first diagnosed 54% of the cases, and then with complete information, 69% of the cases. From the patients' medical records, the physicians obtained information on the time perspective of the symptoms and the progression of the disease. These aspects will be used to further improve the expert system.

Adult

Neural networks in neurotologic expert systems.

Artificial intelligence donates new possibilities to neurotologic research. Neural networks are a computer-based reasoning method which can be applied in expert systems created for clinical decision support. Neural networks have been used in medical imaging, in medical signal processing and to analyze both clinical and laboratory data. Principally, neural networks simulate the function of the brain. They have to be taught to make correct decisions from the input data. This learning process can be either supervised or unsupervised. The decision making is based on mathematical transformations and it occurs on a hidden level. Calculations are made on parallel manner and the decision making simulates pattern recognition method. Neural networks suit well in medical problems which cannot be defined in simple rules. A drawback of neural networks is that the decisions are irrational and cannot be motivated to the user. Another problem is neural networks' difficulty to handle incomplete input data, i.e., how to define some default or expected values for unknown input parameters. In a complex medical area, which would require multilayered neural networks, the neural networks require a large amount of solved cases for the learning process. In our experience neural networks seem not suitable for diagnosing vertigo and a better choice would be either case-based reasoning or possibly genetic algorithms or a combination of these.

Diagnosis, Computer-Assisted

Benign recurrent vertigo--true or artificial diagnosis?

The etiology of many diseases involving vertigo is still unknown although the same etiologic factors have been suggested for several diseases. In most cases the diseases are diagnosed on the basis of exclusion-other possible causes being ruled out before the diagnosis can be confirmed. Benign recurrent vertigo (BRV) has been defined as spells of vertigo characteristic of Menieres disease without auditory or clinical neurologic symptoms and signs. The etiology of this condition is also unknown. BRV has been linked to migraine and viral diseases. In a prospective study we collected the clinical history and the signs and results of neurotologic and audiologic tests from 33 patients with a BRV diagnosis. The clinical characteristics truly mimicked the vertigo seen in Menieres disease. The concept of vestibular Menieres disease is not widely accepted, and without auditory signs BRV is the only diagnosis that can be given to these patients. In other studies up to 25% of the patients initially diagnosed with BRV subsequently developed another peripheral vestibular disorder. Until the etiology of diseases involving vertigo is more clearly understood, artificial diagnoses like BRV, must be accepted.

Adult

Otoneurological expert system.

An otoneurological expert system was developed to help collect data and diagnose both central and peripheral diseases causing vertigo. Patient history and otoneurological and other examination results are used in the reasoning process. The case history data can be either mandatory or supportive. Mandatory questions are used to confirm a diagnosis, and conflicting answers are used to reject an unlikely disease. Supportive questions support or suppress a diagnosis, but their presence is not obligatory. The reasoning procedure of the otoneurological expert system scores every question independently for different diagnoses, depending on how well they agree with the symptom entity of a disease. Diagnostic criteria are set for each disease. Graphic displays illustrate the linear and nonlinear correlation between the symptoms and diseases. Emphasis is placed on diminishing the possibility of a wrong decision rather than maximizing the likelihood of reaching only one right decision, so that even rare diseases can be taken into consideration.

Diagnosis, Computer-Assisted

Characteristics of six otologic diseases involving vertigo.

To characterize otologic causes for vertigo, data on 564 patients with the six most common diseases involving vertigo were retrieved from the database of a computer-aided diagnostic system for neurotologic diseases. The diseases were Meniere's disease, vestibular schwannoma, benign paroxysmal positional vertigo, vestibular neuritis, sudden deafness, and traumatic vertigo. The prevalence of tinnitus in the study population was 76%. The most severe forms of vertigo and nausea were found in vestibular neuritis, whereas the most severe case of tinnitus appeared in Meniere's disease. Of the patients with vestibular schwannoma, 49% had had vertigo. A linear discrimination analysis using case history classified 90% of the patients into correct groups. The key questions discriminating between the diseases concerned the frequency and duration of vertigo attacks, the duration of hearing loss and vertigo, and the occurrence of head injury. Making a correct diagnosis during the first office visit can be difficult, especially for sudden deafness, vestibular schwannoma, and Meniere's disease. Neurotologic and audiometric information was of minor value in distinguishing between these six diseases. Vestibular schwannoma had significantly greater asymmetry in electronystagmography and smaller gains in smooth pursuit in comparison with the other disease. Factorial analysis did not aid the clustering of these diseases.

Adolescent

Database for vertigo.

An interactive database has been developed to assist the diagnostic procedure for vertigo and to store the data. The database offers a possibility to split and reunite the collected information when needed. It contains detailed information about a patient's history, symptoms, and findings in otoneurologic, audiologic, and imaging tests. The symptoms are classified into sets of questions on vertigo (including postural instability), hearing loss and tinnitus, and provoking factors. Confounding disorders are screened. The otoneurologic tests involve saccades, smooth pursuit, posturography, and a caloric test. In addition, findings from specific antibody tests, clinical neurotologic tests, magnetic resonance imaging, brain stem audiometry, and electrocochleography are included. The input information can be applied to workups for vertigo in an expert system called ONE. The database assists its user in that the input of information is easy. If not only can be used for diagnostic purposes but is also beneficial for research, and in combination with the expert system, it provides a tutorial guide for medical students.

Anxiety

Computer assisted data collection in vestibular disorders.

We have developed an interactive database for vertigo than can be used to assist in the diagnostic procedure and to store the data in a form of a database. The database offers the possibility to split and reunite the collected information in a desired way. The database contains detailed information about patient history, symptoms and findings in neurotological, audiological and imaging tests. The symptoms are classified into three sets of questions: vertigo (including postural instability), hearing loss and tinnitus, and provoking factors. Confounding disorders are screened. The neurotological tests involve saccades, smooth pursuit, posturography and caloric test. In addition, findings in specified antibody testing, clinical neurotological tests. MRI, brain stem audiometry and electrocochleography are included. The input information can be applied in an expert system ONE for vertigo work-up. The database is user-friendly. Besides diagnostic purposes the database is excellent for research purposes, and combined with the expert system it works as a tutorial guide for medical students.

Artificial Intelligence

Reasoning in expert system ONE for vertigo work-up.

An otoneurological expert system (ONE) was developed to help collect data and diagnose the work-up of vertigo of both central and peripheral diseases causing vertigo. Patient history and otoneurological and other examination results are used in the reasoning process. The history is interactively collected and is complemented with clinical examination results. The case history data can be either mandatory or supportive. Mandatory questions are used to confirm a diagnosis, and conflicting answers are used to reject an unlikely disease. Supportive questions support or suppress a diagnosis, but their presence is not obligatory. The reasoning procedure of ONE scores every question independently for different diagnoses, depending on how well they agree with the symptom entity of a disease. Diagnostic criteria are set for each disease, in Meniere's disease, for example, the full triad is required. Graphic displays illustrate the linear and nonlinear correlation between the symptoms and diseases. For instance, both second-long Tumarkin-type attacks and attacks lasting hours give a high score while intermediately long attacks score much lower in Meniere's disease. To be able to take even rare diseases into consideration we try to diminish the possibility of a wrong decision rather than maximize the likelihood of reaching only one right decision.

Artificial Intelligence

Pharmacokinetics and clinical response of hyoscine plus morphine premedication in connection with cardiopulmonary bypass surgery.

Plasma hyoscine and morphine levels and various pharmacodynamic responses have been examined in seven patients scheduled for a coronary-artery bypass graft. Hyoscine 0.006 mg kg-1 and morphine 0.20 mg kg-1 were administered intramuscularly as routine premedication. Surgery was performed using high-dose fentanyl anaesthesia (100 micrograms kg-1). The clinical responses followed were heart rate, blood pressure, subjective sedation and antisialogogue effect. The plasma hyoscine levels were determined by radioreceptor assay, and plasma morphine levels by liquid chromatography, both up to 24 h. The maximum levels of plasma hyoscine (6.6 micrograms l-1) and morphine (158 micrograms l-1) and the time they were reached (13.0 and 9.7 min, respectively) were comparable with the values obtained in earlier studies using young healthy subjects. After the start of cardiopulmonary bypass, significant decreases in plasma levels of both hyoscine and morphine were found. The elimination half-life of hyoscine in the plasma was 2.4 h, which is somewhat greater than obtained in earlier studies with young healthy patients under regional anaesthesia. Elimination of plasma morphine (t1/2el = 3.3 h) was not significantly altered by the procedure. The sedative and antisialogogue effects of the drugs appeared quickly and were significant, but no tachycardia or other side effects were observed. In conclusion, the kinetic properties of both hyoscine and morphine are suitable for routine use as premedicants before cardiac surgery.

Anesthesia, Intravenous

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

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

beta-Glucuronide and sulfate conjugation of scopolamine and glycopyrrolate.

The metabolism of scopolamine and glycopyrrolate was studied in 11 healthy parturients undergoing cesarean section. After a single intramuscular injection of scopolamine (5 micrograms/kg, n = 7) or glycopyrrolate (6 micrograms/kg, n = 4), the concentrations of the drugs in the urine were determined up to 8-12 h using a radioreceptor assay. This assay measures scopolamine and glycopyrrolate with their possible active metabolites. The effect of beta-glucuronidase and sulfatase incubation on the drug concentrations was also studied. The concentrations of scopolamine and/or its active metabolites were on the average 7 times higher after incubation indicating that beta-glucuronide or sulfate conjugation is an important metabolic pathway for scopolamine. On the contrary, the glycopyrrolate concentrations increased only slightly between 1 and 3 hours after the drug injection. Thus, beta-glucuronide or sulfate conjugation plays only a minor part in the metabolism of glycopyrrolate.

Female

Pharmacokinetics of scopolamine during caesarean section: relationship between serum concentration and effect.

The pharmacokinetics (radioreceptor assay, RRA) and some of the clinical effects of the anticholinergic agent, scopolamine, were studied in 16 parturients during caesarean section. Following a single 0.005 mg/kg intramuscular injection (deltoid muscle), a very fast rate of absorption was found with mean peak serum concentrations occurring after only 10 min (n = 6). Due to severe bradycardia, 0.5 mg of atropine i.v. had to be given in addition to the i.m. scopolamine treatment to one parturient. The RRA measured the total concentration produced by the two anticholinergic agents in both serum and urine. There was a fundamental difference in the diffusion of scopolamine through the placenta and the blood-lumbar (CSF-barrier (n = 15). There was significant drug penetration in the foeto-placental unit, indicating an efficient drug transfer to the child, but there were measurable levels of the drug in the lumbar CSF in only three cases. The apparent elimination phase half-life of scopolamine in serum was only around 1 h. The urinary excretion of scopolamine and/or its antimuscarinic metabolites lasted only for 6 h (2.63 +/- 1.14% of the dose). The onset of the clinical effects of scopolamine appeared to be delayed, but long-lasting in contrast to the rapid absorption and quick disappearance from the serum. Both the heart rate changes, sedative and antisialogogue effects and serum concentrations did not show any correlation. There appears to be a surprisingly great difference between the pharmacokinetic parameters and the clinical effects of scopolamine.

Absorption

Intramuscular atropine in elderly people: pharmacokinetic studies using the radioreceptor assay and some pharmacodynamic responses.

The pharmacokinetics (radioreceptor assay, RRA) and some clinical effects of atropine were studied in 7 elderly gynaecological surgery patients. The RRA measures only the pharmacologically active isomer of atropine, 1-hyoscyamine. Following a single 0.01 mg/kg intramuscular (M. deltoideus) injection, a very fast rate of absorption was found with mean peak serum concentration occurring after only 13 min. The reason for this could be either a preferential tissue uptake of the 1-form or the injection site or both. The elimination half-life was 2.27 hr. Only 23.1% of the given drug was excreted in urine in 24 hr as a pharmacologically active form. The clinical effects (heart rate rise, subjective sedation and antisialogogue effect) were seen after only 30 min. This somewhat faster appearance of clinical effects than in previous studies can be due to the injection site. The sedative effect of the drug is clear and long lasting in elderly people.

Aged

Electrocardiographic changes during microlaryngoscopy in practolol-pretreated patients under balanced anaesthesia.

Electrocardiographic (ECG) changes were studied in 82 adult patients with a mean age of 49 years undergoing microlaryngoscopy. The patients were pretreated with practolol 0.15 mg/kg i.v. 5 min before induction of anaesthesia with thiopental. Anaesthesia was maintained with nitrous oxide in oxygen, fentanyl and suxamethonium-infusion. ECG changes occurred in 49% of the patients before anaesthesia and procedure. Pre-existing ECG changes increased or new changes occurred in 39% of the patients during intubation and in 38% during the procedure. The most common preanaesthetic ECG changes were flat or negative T-wave (18%), sinus tachycardia (13%), ischaemic S-T segment depression (8.5%) and intraventricular conduction disturbance (8.5%). ECG changes during intubation were sinus tachycardia (16%), ventricular ectopic beats (12%), supraventricular ectopic beats (10%) and ischaemic S-T segment depression (10%). The most common changes during microlaryngoscopy were supraventricular ectopic beats (16%), T-wave flattening or inversion (15%), ischaemic S-T segment depression (11%) and sinus bradycardia (10%). In all patients ECG changes disappeared without any special treatment. Unlike our earlier identical study without practolol pretreatment, neither sinus tachycardia nor junctional rhythm occurred during microlaryngoscopy in the present study. The results suggest that practolol pretreatment before microlaryngoscopy is especially useful when sinus tachycardia and junctional rhythm should be avoided.

Adult

Feasibility of cutaneous blood gas monitoring during exercise stress testing.

The feasibility of cutaneous blood gas monitoring in connection with exercise testing was evaluated in 113 consecutive patients. Arterial blood samples were taken immediately after exercise. Because of loosening of electrode tapes only 99 satisfactory registrations of O2 and 98 registrations of CO2 were obtained at the end of exercise testing. In this phase the correlations between transcutaneous and arterial O2 and CO2 values were r = 0.60, p less than 0.001 and r = 0.66, p less than 0.001, respectively. Nevertheless, the correspondence for clinical work remains poor. The shape of the whole transcutaneous O2-CO2 registration curve is diagnostically more rewarding than single transcutaneous O2 and CO2 values.

Adolescent