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Biomedical subjects

J Ahlner

Publications and source records attributed to J Ahlner.

At least 19 recordsLinked to original sources
PubMed2006

Risk communication in consultations about hormone therapy in the menopause: concordance in risk assessment and framing due to the context.

BACKGROUND: It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making. OBJECTIVE: The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition. METHODS: Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden. RESULTS: Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview. CONCLUSION: Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking.

Communication↗
PubMed2005

Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides.

OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. METHOD: Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26,422 cases of deaths by accident or natural causes in Sweden 1992-2000. RESULTS: There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION: The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.

Adolescent↗
PubMed2004

Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions.

OBJECTIVE: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7-10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases. METHODS: Individuals (n=242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis. RESULTS: The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency P<0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors. CONCLUSIONS: The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Characterization of [3H]flunitrazepam binding to melanin.

In both clinical and forensic toxicology, the analysis of hair for drugs is an important tool to determine drug use in the past or to verify abstinence from illegal drugs during extended periods. Melanin is proposed as one of the factors that influences drug incorporation to hair and we have characterized the binding of the drug flunitrazepam to melanin in vitro. The drug was 3H labeled and melanin granules from cuttlefish, Sepia officinalis, were used according to the suggested standard for melanin studies. We observed a rapid Langmuir-like binding followed by a slower diffusion-limited binding that may be interpreted as an initial surface binding followed by deeper bulk binding. From three concentrations of melanin, with a 60-min incubation time, a mean saturation value of 180 +/- 20 pmol/mg was calculated. The binding of a group of benzodiazepines and tranquilizers was compared to the binding of [3H]flunitrazepam by means of displacement experiments. These drugs showed binding characteristics similar to [3H]flunitrazepam except phenobarbital, which had a lower affinity to melanin. The method presented in this study allowed measurements with low melanin and drug concentrations and it has the strength of directly measuring the amount of drug bound to melanin, in contrast to previous indirect methods.

Animals↗
PubMed2001

Flunitrazepam: an evaluation of use, abuse and toxicity.

The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.

Anti-Anxiety Agents↗
PubMed2001

In vivo steady-state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats.

The thymoleptic drug citalopram (CIT) belongs to the selective serotonin reuptake inhibitors (SSRIs) and is today extensively used in psychiatry. Further clarification of the enantiomer-selective distribution of racemic CIT in both clinical and toxic doses is highly warranted. By a steady-state in vivo paradigm, rats underwent chronic systemic exposure for 10 days by using osmotic pumps and the total as well as the individual distributions of the S- and R-enantiomers of CIT, and its metabolites in serum and two different brain regions, were analysed. In serum, the S/R ratios in the groups treated with 10, 20, or 100 mg kg(-1) day(-1) were 0.94, 0.83, and 0.34, respectively. The ratios were almost the same in the brain regions. In the group treated with 100 mg kg(-1) day(-1), the serum and brain total CIT levels were found to be 20 times and 6 - 8 times higher than in the rats treated with 10 or 20 mg kg(-1) day(-1), respectively. In all groups, the CIT levels were higher in brain tissue as compared to serum. In a spontaneous open-field behavioural test, a correlation between clinical and toxic drug concentrations was observed. In conclusion, the R-enantiomer was present in an increased proportion compared with the S-enantiomer when higher steady-state CIT concentration was prevailing. This is of particular interest, since the S-enantiomer is responsible for the inhibition of serotonin reuptake in vitro. The present data may be of importance, as full understanding on where different racemic or enantiomeric drug effects of CIT and its main metabolites are unravelled.

Animals↗
PubMed2001

Eosinophil cationic protein (ECP) in saliva: a new marker of disease activity in bronchial asthma.

Eosinophil cells play a crucial role in the pathogenesis of asthma, and concentration of eosinophil cationic protein (ECP) in serum has been used to monitor activity of the disease. Our aim was to determine the feasibility and usefulness of measuring ECP in saliva and to use it as a marker of the disease. Thirty-eight patients with asthma and 16 healthy volunteers were included in this study. Repeatability of measurements of ECP in saliva was acceptable [intra-class correlation coefficients (Ri) = 0.74 and coefficients of repeatability (CR) = 0.37 in five healthy subjects]. Levels of ECP in saliva were higher in asthmatics than in volunteers (P < 0.01). There was a significant inverse association between a surrogate variable reflecting disease activity (i.e. change over a few weeks in dose of inhaled corticosteroid required by a change in clinical status of asthma) and a change over the same time period in salivary ECP in 19 patients with stable asthma (r = -0.64, P = 0.02). Our findings indicate that levels of salivary ECP are elevated in patients with asthma and associated with presumed activity of disease as recorded by alteration of taken dose of inhaled corticosteroid.

Acute Disease↗
PubMed2001

Asthma care and factors affecting medication compliance: the patient's point of view.

OBJECTIVE: To identify important factors that can influence patient compliance with prescribed medication and to elucidate aspects of asthma care from the patient's point of view. DESIGN: Field investigation; the interviewer used a semi-structured questionnaire. SETTING: Patients with asthma in primary health care settings in Sweden. STUDY PARTICIPANTS: A sample of 77 patients was randomly selected from 11 primary health care centres in southern Sweden; 63 of these patients participated in the study. CONCLUSION: The factors of importance for self-reported compliance with prescribed medication were age, gender, duration of the disease, the attitude of the staff and information/education about asthma. The patients expressed important aspects of care, and these are in accordance with how an asthma nurse practice functions in Sweden.

Adult↗
PubMed2001

Incorporation of selegiline metabolites into hair after oral selegiline intake.

We have previously shown that melanin in human hair has a great impact on the incorporation of codeine into hair. The present study on 10 subjects was performed to investigate whether or not these findings could also be extrapolated to other therapeutic drugs. We chose selegiline because it metabolizes to two commonly abused central stimulants, methamphetamine and amphetamine. The results would therefore also be of interest when studying the intake of such drugs and their incorporation into human hair. Selegiline and metabolites were determined by gas chromatography-mass spectrometry, total melanin by spectrophotometry, and pyrrole-tricarboxylic acid by high-performance liquid chromatography with ultraviolet detection. Our results show strong positive exponential relationships (y = e(x)) between melanin and the metabolites, which for methamphetamine improved by normalizing for plasma area under the curve. We conclude that the major metabolites of selegiline can be detected in hair up to four weeks after a single oral dose and that the incorporation closely relates to the melanin contents.

Administration, Oral↗
PubMed2001

Enantioselective analysis of citalopram and metabolites in adolescents.

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

Adolescent↗
PubMed2000

Antihypertensive treatment and patient autonomy--the follow-up appointment as a resource for care.

Since hypertension is a chronic condition which generally requires long-term commitment to pharmacological therapy as well as alterations of patient lifestyle, the patient-physician communication in the clinical setting is an important determinant of the quality of care and health outcome. The aim of the present study was to explore the structure and content of the communication between the patient and the physician, and the process of decision-making at a routine follow-up appointment for hypertension. The study was based on 51 audio-recordings of authentic consultations. Most patients had a passive role in the consultations, and initiated few topics of conversation. The few topics that the patients initiated were usually not about hypertension. Patients' questions about medication mainly referred to unwanted effects of the drugs. Little time was invested in discussing risks related to hypertension. A collaborative shared decision-making was seldom observed in the consultations.

Adult↗
PubMed2000

Patient questionnaires in primary health care. Validation of items used in asthma care.

OBJECTIVE: To evaluate each item in a patient questionnaire for the purpose of investigating whether the validity of each item is acceptable. DESIGN: The questionnaire was completed by the patients at an ordinary follow-up visit for their asthma, and within 1 week a nurse interviewed them by telephone with the aim of analysing the validity of each item through the use of predetermined criteria. SETTINGS: Patients with asthma in primary health care settings in Sweden. STUDY PARTICIPANTS: Fifty-one patients were consecutively included from three different primary health care units. RESULTS: Nine of 13 items had an acceptable validity. The four items that were not found to have acceptable validity were developed further. CONCLUSION: Evaluating each item in a questionnaire by means of interviews with the specific patient population is a useful method of assuring that the intention of the patient questionnaire has been met.

Asthma↗
PubMed1999

Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results.

Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many toxicologically important drugs. The gene encoding for this enzyme displays a polymorphic distribution in all populations examined. We report a study on 46 cases, where analyses of the CYP2D6 gene were conducted on postmortem femoral blood in order to investigate the occurrence of poor metabolizers (PM). A polymerase chain reaction (PCR) method, designed and routinely used for therapeutic drug monitoring, was employed, only slightly modified. Samples from 22 cases, where the parent drug to metabolite ratio was unexpectedly high were analyzed as well as samples from 24 control cases. Genotyping could be carried out in all but one case. Previous freezing or addition of potassium fluoride as preservative did not prevent analysis. Only one PM (from the control group) was discovered, implying an occurrence of only 2.2% as compared to the reported frequency of approx. 7% in Sweden. Among the extensive metabolizers (EM), however, a number of individuals with mutated genes were identified. Although it seems reasonable to suspect a PM genotype in cases with a high concentration of a drug metabolized by CYP2D6, but without suspicion of acute overdose, our study does not support the opinion that this interpretation pitfall is particularly common. This study rather indicates that drug interactions in EMs constitute a more frequent and important problem.

Adult↗
PubMed1999

Asthma nurse practice--a resource-effective approach in asthma management.

The objective of this study was to evaluate the efficacy of an Asthma Nurse Practice (ANP) in primary health care. A 12-month (September 1994-August 1995) open, prospective intervention study with pre- and post-test comparisons was performed on patients with asthma treated at a primary care centre in Sweden. Sixty-three patients with mild or moderate asthma participated and medication, structured follow-up and education in self-management at an ANP were assessed over a 12-month period. The main outcome measures assessed were pulmonary function, eosinophil cationic protein (ECP) in serum, respiratory symptoms, patient knowledge of asthma and emergency visits. ANP in primary health care increased patient knowledge of asthma and medication. The number of patients with nocturnal symptoms decreased significantly. Pulmonary function was improved: vital capacity (VC) 98-106, forced expiratory volume in 1 sec (FEV1) 93-100 and peak expiratory flow (PEF) 98-115% of predicted (P < 0.001). Variation in PEF fell from 21 to 12% (P < 0.001). ECP was significantly reduced. Visits to the emergency room were 60% fewer during the year of intervention (P < 0.01). In conclusion, patients attending an Asthma Nurse Practice, comprising a structured programme for asthma management, improve their knowledge and asthma control.

Adult↗
PubMed1999

Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers.

Racemic R,S-salbutamol is taken to relieve bronchial constriction. Only the R-enantiomer has bronchodilating properties. The S-enantiomer has been proposed to cause in vitro bronchial hyperreactivity in guinea-pigs. Stereoselective elimination of salbutamol has been shown, with S-salbutamol being eliminated at a slower rate than R-salbutamol. This study questioned whether rates of stereoselective elimination were similar after oral or lung delivery, and whether the S:R ratio would increase after repeated inhalations in a situation resembling a common clinical use. Eighteen healthy volunteers received single-dose racemic salbutamol as a solution instilled in the trachea during anaesthesia, as inhaled micronized powder and/or as ingested tablets. Five volunteers inhaled repeated doses of racemic salbutamol. Concentrations in plasma and urine were measured using a technique which allowed chiral separation of samples with concentrations as low as 0.1 ng x mL(-1). The bioavailability of S-salbutamol was significantly higher than that of R-salbutamol after the different modes of administration. Stereoselective elimination was more pronounced after oral administration than after inhalation. Repeated inhalations resulted in successive increases in the S:R ratio as steady state was approached. In conclusion, the clinical consequences of increasing plasma concentrations of S-salbutamol need to be further assessed.

Administration, Inhalation↗
PubMed1999

Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease.

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66%, significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.

Coronary Disease↗
PubMed1999

Codeine concentration in hair after oral administration is dependent on melanin content.

BACKGROUND: Analysis of drugs in hair has been used on a qualitative basis to estimate earlier exposure to drugs. Clinical applications are rare because of the lack of dose-response relationships in the studies performed to date, and questions remain regarding the mechanisms of drug incorporation into hair. Several human studies have shown differences in drug accumulation between pigmented and nonpigmented hair. However, the melanin concentration in hair was not determined and correlated to the amount of drug incorporated. METHODS: Nine human subjects were given codeine as a single oral dose, and plasma codeine concentrations were determined for 24 h, using gas chromatography-mass spectrometry. Hair samples were obtained weekly for a month. Total melanin, eumelanin, and codeine were measured quantitatively in hair samples by spectrophotometry, HPLC, and gas chromatography-mass spectrometry, respectively. RESULTS: There was an exponential relationship between codeine and melanin concentrations in hair, (r(2) = 0.95 with total melanin and r(2) = 0.83 with eumelanin). After normalizing the results by the area under the curve for codeine in plasma, we obtained r(2) = 0.86 for codeine vs total melanin and r(2) = 0.90 vs eumelanin. CONCLUSIONS: Our results stress the importance of melanin determination when measuring drugs in hair. We postulate that analysis of drug concentration in hair may be worthwhile in the monitoring of drug compliance if the results are normalized for melanin content.

Chromatography, High Pressure Liquid↗