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Tapani Keränen

Publications and source records attributed to Tapani Keränen.

At least 19 recordsLinked to original sources
PubMed2006

Cost-utility model of rasagiline in the treatment of advanced Parkinson's disease in Finland.

BACKGROUND: The economic burden of Parkinson's disease (PD) is high, especially in patients experiencing motor fluctuations. Rasagiline has demonstrated efficacy against symptoms of PD in early and advanced stages of the disease. OBJECTIVE: To assess the cost-utility of rasagiline and entacapone as adjunctive therapies to levodopa versus standard levodopa care in PD patients with motor fluctuations in Finland. METHODS: A 2 year probabilistic Markov model with 3 health states: "25% or less off-time/day," "greater than 25% off-time/day," and "dead" was used. Off-time represents time awake with poor or absent motor function. Model inputs included transition probabilities from randomized clinical trials, utilities from a preference measurement study, and costs and resources from a Finnish cost-of-illness study. Effectiveness measures were quality-adjusted life years (QALYs) and number of months spent with 25% or less off-time/day. Uncertainty around parameters was taken into account by Monte Carlo simulations. RESULTS: Over 2 years from a societal perspective, rasagiline or entacapone as adjunctive therapies to levodopa showed greater effectiveness than levodopa alone at no additional costs. Benefits after 2 years were 0.13 (95% CI 0.08 to 0.17) additional QALYs and 5.2 (3.6 to 6.7) additional months for rasagiline and 0.12 (0.08 to 0.17) QALYs and 5.1 (3.5 to 6.6) months for entacapone, both in adjunct to levodopa compared with levodopa alone. CONCLUSIONS: The results of this study support the use of rasagiline and entacapone as adjunctive cost-effective alternatives to levodopa alone in PD patients with motor fluctuations in Finland. With a different mode of action, rasagiline is a valuable therapeutic alternative to entacapone at no additional charge to society.

Antiparkinson Agents↗
PubMed2006

NARP syndrome and adult-onset generalised seizures.

The neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome is a maternally inherited disorder attributable to a heteroplasmic mtDNA point mutation. Catastrophic epilepsy may accompany severe, early onset forms of NARP, but seizures seem to be rare in cases with adolescent and adult onset. We describe a patient who developed clumsiness and visual problems in her teens. She had no clinical seizures but an EEG showed generalized spike and wave discharges. At this time the patient remained without a specific diagnosis. At the age of 21, the patient developed progressive ataxia and she also experienced a tonic-clonic status epilepticus. Further examinations revealed NARP syndrome. EEG abnormalities may precede adult onset seizures in the NARP syndrome.

Adult↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

Changes in plasma amino acids after electroconvulsive therapy of depressed patients.

There are indications that mood disorders may be related to perturbations in the amino acid transmitters. The amino acids may thus be targets of treatment of depression. The purpose of this pilot study was to measure the acute effects of a single administration of electroconvulsive therapy (ECT) on the plasma levels of amino acids in depressed patients. ECT was administered to 10 patients with major depressive disorder. Altogether 23 plasma amino acids were analyzed before and at 2, 6, 24 and 48 h after ECT. The levels of glutamate and aspartate increased at 6 h after ECT compared with the baseline. Also the levels of total tryptophan increased 2-24 h after ECT. There were also elevations in other amino acids at 6 and 24 h. The levels of gamma-aminobutyric acid (GABA) decreased at 2 h. In this study the acute effects of single ECT were associated with changes in the levels of glutamate, aspartate, GABA, tryptophan and some other amino acids. The preliminary data suggest that the therapeutic effects of ECT in depression may be due to mechanisms involving these amino acid transmitters.

Adult↗
PubMed2005

GABA and glutamate transporters are expressed in human platelets.

GABA and glutamate are the major neurotransmitters in the human central nervous system. Disturbances in these transmitter systems have been suggested to influence a variety of neurological and psychiatric diseases. Human platelets have been used as a model for neural amino acid transport, although it has not been known exactly which transporters participate in the transport process. In this study, we identify with reverse transcription-polymerase chain reaction (RT-PCR) BGT-1 and EAAT3 as transporters for GABA and glutamate, respectively. We also show that platelets contain transporters for dopamine, taurine and creatine. The cloning of these transporters confirms that blood platelets can be used as a model for neurotransmitter transport in the CNS.

Adult↗
PubMed2005

Retention rate of oxcarbazepine monotherapy in an unselected population of adult epileptics.

In a retrospective study we assessed the outcome of oxcarbazepine (OXC) monotherapy in a naturalistic setting. We identified all adult patients who had been treated with OXC at a single neurological outpatient center. A total of 175 patients were identified, 97 of them used OXC as their first AED (Group I), and 78 as second monotherapy (Group II), after failure of a previous AED. The 1-year retention rates of OXC treatment were 91% for Group I and 77% for Group II. Discontinuations were due to adverse effects in 3 patients (3%) in Group I and in 11 patients (14%) in Group II, and due to lack of efficacy in 2 patients (2%) in Group I and in 6 patients (8%) in Group II. We conclude that OXC monotherapy is effective and well tolerated.

Adult↗
PubMed2004

Plasma and cerebrospinal fluid amino acids in epileptic patients.

Altered plasma and cerebrospinal fluid amino acid levels may be associated with human epilepsy. We studied three groups of patients, those with a generalized epileptic syndrome, juvenile myoclonic epilepsy, patients with refractory localization-related epilepsies, and patients with acute seizures (within 24 h). Plasma levels of amino acids were studied in all patient groups, as were those in the cerebrospinal fluid (CSF) of patients with acute seizures. After acute seizures, the amino acid changes in the CSF were limited to a reduction in the level of taurine, whereas the levels of most amino acids in plasma were decreased. On the other hand, levels of the excitatory amino acids glutamate and aspartate were increased. The most notable finding in the juvenile myoclonic epilepsy patients was an increase in glutamate level in the plasma. Our study supports the conception of an altered metabolism of glutamate in generalized epilepsies.

Adult↗
PubMed2004

Uptake of GABA and activity of GABA transaminase in blood platelets from children with absence epilepsy.

Childhood absence epilepsy (CAE) is a well-defined generalized epilepsy syndrome clinically characterized by frequent absence seizures. The aim of this study was to assess the activity of GABA transaminase (GABA-T) and the kinetic parameters of GABA uptake in platelets from patients with CAE. We studied 13 patients with CAE and eight sex- and age-matched controls. The mean activity of GABA-T was lower in patients with CAE than in controls (1.22+/-0.05 vs. 1.75+/-0.10 micromol/min/kg protein). The capacity of GABA uptake into the platelets was higher in patients using valproate (0.66+/-0.09 micromol/min/kg protein), but not in those using ethosuximide (0.34+/-0.05 micromol/min/kg protein), when compared to controls (0.26+/-0.06 micromol/min/kg protein). The affinity of the transporters was not altered. The observed peripheral alterations may indicate impaired function of brain GABAergic systems in children with absence epilepsy.

4-Aminobutyrate Transaminase↗
PubMed2003

Uptake of GABA and activity of GABA-transaminase in platelets from epileptic patients.

The aim of the present study was to assess the activity of GABA-transaminase (GABA-T) and the kinetic parameters of GABA uptake in platelets from patients with distinct epileptic syndromes. We studied 14 patients with juvenile myoclonic epilepsy (JME), 19 patients with refractory localization-related epilepsy (RLE) and 20 healthy volunteers who were matched for age and sex. Acute effects of valproate (VPA) and lamotrigine (LTG) on the uptake of GABA and the activity of GABA-T in platelets in vitro were also analyzed. The mean activity of GABA-T in JME patients was significantly higher than in control subjects, whereas RLE patients did not significantly differ from controls. The capacity of GABA uptake was least in JME patients, intermediate in RLE patients and highest in controls. In vitro VPA (concentrations 150-1200 microM) or LTG (concentrations 1-100 microM) had no significant effects on GABA uptake. Our results indicate marked differences in the platelet uptake of GABA and the activity of catabolic enzyme GABA-T between patients with generalized and localization-related epileptic syndromes. The observed peripheral alterations may indicate an impairment in the function of brain GABAergic systems.

4-Aminobutyrate Transaminase↗
PubMed2003

Pharmaceutical industry's barriers and preferences to conduct clinical drug trials in Finland: a qualitative study.

The objectives of our study were to explore the barriers, preferences and attitudes of the pharmaceutical industry towards conducting clinical trials in Finland. In-depth semi-structured interviews were conducted with 18 representatives of the pharmaceutical industry with different amounts of experience of clinical trials. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Overall, the respondents had a positive attitude towards conducting clinical trials in Finland. The major barriers seemed to occur at the beginning of the trial and mostly consisted of bureaucratic obstacles. The informants hoped for a more positive attitude of the public sector, more flexibility in hospitals and professionalism in practical implementation, e.g. having special research centres or site management services. The most dismotivating factors were the high costs and the constraints imposed by bureaucracy. The variety in practices of local ethics committees was considered problematic, and the need for common standard operating procedures was pointed out. The smallest barriers were encountered in subject recruitment by the investigators and their clinical work, documentation, investigational product logistics and communication with the regulatory authorities. The quality, know-how and reliability of the study personnel, the tightening of time lines in general, an investigator register/pool and collaboration with media in disseminating information about clinical trials to the general public were reported as the most appealing factors. Training in GCP, mainly incorporated in the medical education programme, and a certificate or equivalent were generally considered necessary, though a voluntary system was preferred. The barriers and preferences pointed out suggest various improvements and ways to produce high-quality, GCP-compliant clinical drug research and to ensure the availability of sufficient conditions to carry out clinical trials also in the future.

Attitude of Health Personnel↗
PubMed2003

Investigator barriers and preferences to conduct clinical drug trials in Finland: a qualitative study.

OBJECTIVE: To explore investigator barriers, preferences, and attitudes towards conducting clinical trials in Finland. METHOD: In-depth, semi-structured interviews with 20 clinicians working in the field of cardiovascular medicine were performed. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Twenty clinicians from all (five) university hospitals in Finland and from three subgroups: 1) with long experience, 2) with limited experience and 3) reluctant to carry out clinical trials, were sampled purposefully. MAIN OUTCOME MEASURES: Barriers and (de)motivating factors in carrying out clinical trials and need for training in Good Clinical Practice (GCP). RESULTS: Overall, the investigators had a positive attitude towards conducting clinical trials. The major barriers seemed to occur at the beginning of the trial: bureaucracy, lack of time and laboriousness. The informants hoped for more specific inhouse rules and flexibility in hospitals. The greatest investigator barriers were insufficient financial incentives, trial-related reasons and administrative affairs/bureaucracy. The smallest barriers were reported in subject recruitment, clinical work, documentation, investigational product logistics and communication with ethics committees. Financial incentives, a possibility to incorporate a personal sub-study or other benefits for personal research and scientific and clinical interest in the trial were reported as the most motivating factors. Carrying out studies in practice and an opportunity to participate in a trial during one's postgraduate specialist education were considered beneficial. Training in GCP, mainly in the course of postgraduate education, and a certificate or equivalent were generally considered necessary, although a voluntary system was preferred. CONCLUSION: The interviews of clinicians provide valuable information about the barriers and preferences related to the practical implementation of clinical trials. If the trial is scientifically/clinically interesting and involves a small administrative burden and sufficient financial compensation, investigators are motivated to participate. The barriers and preferences should be considered in decision-making, to meet the various needs of all parties involved and to produce high-quality GCP-compliant clinical drug research. This would ensure the availability of sufficient conditions to carry out clinical trials also in the future.

Attitude of Health Personnel↗
PubMed2003

Transient loss of consciousness as reason for admission to primary health care emergency room.

OBJECTIVE: To study the occurrence and main causes of transient loss of consciousness in primary health care. DESIGN: A 4-month prospective survey. SETTING: Primary health care emergency room of the City of Tampere, Finland. SUBJECTS: Consecutive patients, aged over 15 years, admitted to the emergency room. MAIN OUTCOME MEASURES: The overall prevalence of loss of consciousness divided into three subgroups: seizure, syncope and uncertain, and their distribution by gender and age. The prevalence of epilepsy, coronary heart disease and alcohol abuse among these diagnostic subgroups. RESULTS: Of all emergency room visits, 1.2% were for loss of consciousness. Of these, 53% were diagnosed as seizures, 33% as syncope attacks and 14% as uncertain. In the seizure group, 75% of patients were men and 67% had a history of alcohol abuse. In the syncope group, 44% of patients had coronary heart disease and 68% were women. CONCLUSION: Loss of consciousness is a fairly frequent problem for the primary health care emergency room. A history of alcohol abuse is commonly associated with seizures.

Adolescent↗
PubMed2003

Transient loss of consciousness with and without injuries: where to treat these patients?

OBJECTIVES: Transient loss of consciousness (LOC) is a fairly common phenomenon and frequently carries a risk of injury. The aim was to study the occurrence of injuries and causes of emergency referrals versus later specialist consultation in association with LOC in the primary healthcare setting. METHODS: A four-month survey was carried out in the Primary Healthcare Emergency Department of the City of Tampere, Finland (198,000 inhabitants). The subjects comprised consecutive patients aged at least 15 years, attending a primary healthcare emergency department because of LOC. The type of LOC was determined (seizure, syncope and uncertain) and the type and site of all injuries associated with LOC were registered. All referrals to hospital or specialist consultation because of LOC were also registered and the predictors of admission were analysed by logistic regression modelling. RESULTS: Injury was associated with 43 (20%) out of 220 visits because of LOC; in 12/72 (17%) cases with syncope, in 24/118 (20%) with seizures and in 7/30 (23%) with an uncertain cause of LOC. Most of the injuries were minor. Emergency referral was required in 45/220 (20%) cases of LOC. Coronary heart disease and injury were the main predictors of emergency referral to hospital. CONCLUSIONS: Injuries are as frequent in patients with syncope as in those suffering seizures. Most patients with LOC in primary healthcare emergency departments do not seem to require emergency admission to hospital.

Adult↗
PubMed2002

The usefulness of video-EEG monitoring in elderly patients with seizure disorders.

The purpose of this paper was to evaluate the use of inpatient video-EEG (VEEG) monitoring in the evaluation of seizure disorders in elderly subjects. We retrospectively identified 36 patients aged 60 years old or over from a total of 849 patients studied at the VEEG unit of the Tampere University Hospital. Sixteen of the patients (44%) experienced at least one habitual seizure during the recording. Seven patients had epileptic seizures including two cases with status epilepticus. Nine patients had various non-epileptic disorders. VEEG had a clinically significant impact on the diagnosis and treatment in 14 of the 16 patients in whom paroxysmal events were recorded and proved to be useful in the evaluation of seizure disorders in elderly subjects.

Aged↗
PubMedDate not supplied

The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients.

PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.

Adolescent↗