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Biomedical subjects

U Bergman

Publications and source records attributed to U Bergman.

At least 37 records · Page 2Linked to original sources

Methimazole toxicity in rodents: covalent binding in the olfactory mucosa and detection of glial fibrillary acidic protein in the olfactory bulb.

Methimazole is an antithyroid drug reported to affect the sense of smell and taste in humans. The aim of the present study was to examine the distribution and effects of methimazole on the olfactory system in rodents. Autoradiography showed a selective covalent binding of 3H-labeled methimazole in the Bowman's glands in the olfactory mucosa, bronchial epithelium in the lungs, and centrilobular parts of the liver following an iv injection in mice. Histopathology showed an extensive lesion in the olfactory mucosa that was efficiently repaired 3 months after two consecutive ip doses of methimazole. The effect of methimazole on various brain regions was studied by determining levels and location of glial fibrillary acidic protein (GFAP). The results showed a threefold increase of GFAP in the olfactory bulb 2 weeks after treatment with methimazole whereas no change was observed 4 days after treatment. Pretreatment of mice with thyroxine did not protect against the methimazole-induced toxicity in the olfactory mucosa and bulb. In contrast, pretreatment with the cytochrome P450 inhibitor metyrapone completely prevented the covalent binding and toxicity of methimazole in the olfactory mucosa and bulb. The present results suggest that the methimazole-induced toxicity in the olfactory mucosa is mediated by a cytochrome P450-dependent metabolic activation of the compound into reactive metabolites that are bound to various tissues including the olfactory mucosa. The increase of GFAP in the olfactory bulb of methimazole-treated mice is suggested to be a secondary phenomenon due to the primary damage in the olfactory mucosa.

Animals↗

Selective serotonin reuptake inhibitors have broadened the utilisation of antidepressant treatment in accordance with recommendations. Findings from a Swedish prescription database.

BACKGROUND: With the advent of the selective serotonin reuptake inhibitors (SSRIs), the use of antidepressants has increased drastically in Sweden. The use of tricyclic antidepressants (TCAs) has, however, decreased. METHODS: We surveyed a prescription database in the Swedish county of Jämtland and compared prescription patterns for patients prescribed SSRIs with those prescribed TCAs. RESULTS: The incidence of treatments of antidepressants increased from 0.76% to 1.33% during the period 1991-1996. There were no significant differences between SSRIs and TCAs with regard to patients having only one prescription dispensed within three months from the index prescription, or patients who switched class of antidepressant. Only a minority of the treatments were continued for at least six months, but significantly more SSRI than TCA treatments (42% and 27%). A second treatment period suggesting recurrence was three-times more common in the TCA group than in the SSRI group. CONCLUSION: Provided that the increased use of SSRIs is mainly for depression, these drugs appear, despite a lower efficacy in severe depression, to have enabled a broader utilisation of antidepressants with regard to incidence, dosage and duration, in accordance with recommendations. Further analyses of this phenomenon relative to diagnostic criteria and outcome measures are required.

Adult↗

Low use of long-term hormone replacement therapy in Denmark.

AIMS: To examine individual use of hormone replacement therapy (HRT) in a defined population of Danish women during a 5-year period. HRT may reduce osteoporosis and cardiovascular disease in postmenopausal women, but may also have side-effects. Little is known about the use of HRT in most populations. METHODS: A Pharmacoepidemiological Prescription Database was used to identify all reimbursed prescriptions for HRT in the county during the period 1991 to 1995. The Danish retail pharmacies' drug subsidy system made it possible to identify prescriptions by individual use. RESULTS: We examined 255797 HRT prescriptions issued during the period in the County of North Jutland. Total sales reached 16.5 million defined daily doses (DDDs), purchased by 31653 women, which corresponds to 26.9% of the female population above the age of 39 years. The annual prevalence proportion of current users rose from 10.4% to 14.8% during the study period, and the therapeutic intensity (DDD/1000 women/day) increased from 20.6 to 32.0. The mean DDD sum of systemic HRT per user was 73.4 in 1991; it and the proportion of users who received less than 90 DDD per year (83.4% in 1991) remained almost constant during the study period. The amount of oestrogen unopposed by progestin was high, 28.1% of all prescriptions. CONCLUSIONS: Less than one-fifth of the study population used HRT for more than 3 months per year, and only 32.8% of the women who were new users of HRT in 1992 continued this therapy throughout the study period.

Adult↗

Psychotropics and suicide prevention. Implications from toxicological screening of 5281 suicides in Sweden 1992-1994.

BACKGROUND: Systematic clinical investigations of consecutive suicides have found psychiatric disorders in 90-95% of subjects (depressive disorder 30-87%). AIMS: To investigate use of psychotropics in men and women of different ages who commit suicide. METHOD: Results of toxicological screening in 5281 suicides in Sweden 1992-94 were studied. RESULTS: Psychotropics were detected in 45.3% of the suicides. Antidepressants were detected in 12.4% of the men and 26.2% of the women (7.2% and 14.2%, respectively, of those under 30 years of age). Neuroleptics or antiepileptics (in the absence of antidepressants) were detected in 8.3%, and anxiolytics/hypnotics alone in 20.5% of the subjects. Overdose by an antidepressant was the probable cause of death in 2.1% of the men and 7.9% of the women. CONCLUSIONS: The pattern of psychotropics detected in toxicology was incongruent with the pattern of diagnoses found in the clinical investigations of suicides mentioned above. Depression appears to be under treated in individuals committing suicide, especially in men and in subjects under 30 years of age.

Adolescent↗

Transfer of some carboxylic acids in the olfactory system following intranasal administration.

The uptake of [14C]benzoic acid, 4-chloro[14C]benzoic acid, [3H]phthalic acid and [14C]salicylic acid in the nasal passages and brain was determined following a unilateral intranasal instillation in mice. An uptake of radioactivity from the nasal mucosa to the ipsilateral olfactory bulb was observed up to 4 h after administration following intranasal instillation of these carboxylic acids whereas the level was low in the contralateral olfactory bulb. Autoradiography of mice given [14C]benzoic acid and [14C]salicylic acid by intranasal instillation showed a preferential localization of radioactivity in the axonal and glomerular layer of the olfactory bulb 1 h after the administration. Four hours after administration the radioactivity was present as a gradient from the axonal layer towards the center of the olfactory bulb. Pretreatment of mice with a compound known to damage the olfactory neuroepithelium resulted in a decreased uptake of [14C]benzoic acid in the olfactory bulb. Thin layer chromatography of supernatants from the ipsilateral olfactory bulbs of mice given [14C]benzoic acid by nasal instillation indicated that the radioactivity in the bulbs represented unchanged compound. These results suggest that there is a transfer of some aromatic carboxylic acids in the olfactory pathways.

Administration, Intranasal↗

Drug utilization 90%--a simple method for assessing the quality of drug prescribing.

OBJECTIVES: To describe a simple method for assessing the quality of drug prescribing. METHODS: We tested the idea that the number of drugs accounting for 90% of drug use--drug utilization 90% (DU90%)--may serve as an indicator of the quality of drug prescribing. We ranked the drugs by volume of defined daily doses (DDD) and determined how many drugs accounted for the DU90% segment. We also compared this segment with the pharmacotherapeutic guidelines issued by the Regional (local) Drug Committee to determine the adherence to its recommendations (index of adherence). The cost per DDD within the DU90% segment and for the remaining 10% was also calculated. The utilization of drugs based on prescriptions purchased during April 1995 was determined for 24 primary health care (PHC) centres in southwestern Stockholm. RESULTS: The number of different products, defined as all products marketed under a single brand name within an ATC (anatomic therapeutic chemical) category, in the DU90% segment varied twofold (81-164) between the 24 PHC centres. Differences in the number of GPs per PHC centre accounted for a third of this variation. The compliance with the Drug Committee recommendations varied between 54% and 78%. There was no relationship between the number of products accounting for the DU90% segment and the adherence to local prescription guidelines, i.e. prescribing more products did not increase the adherence. The costs for the DU90% drugs varied from 2.26 SEK/DDD in one PHC centre to 3.75 in another one, with an average cost of 2.87 SEK/DDD, while for the remaining 10% it was the double (6:54 SEK/DDD). In all, the DU90% drugs made up 80.8% of the total cost as compared with 19.2% for the remaining 10%. In the DU90% segment, there was no clear relationship between adherence to the guidelines and the cost/DDD, i.e. following the evidence-based guidelines appeared to provide a higher quality of prescribing rather than cheaper prescribing. CONCLUSIONS: The DU90% is an inexpensive, flexible, and simple method for assessing the quality of drug prescribing in routine health care. The number of products in the DU90% segment and adherence to prescription guidelines may serve as general quality indicators. The method may be adapted to provide comparative data between PHC centres, hospitals, regions etc. that may be cross-sectional and longitudinal. Other quality criteria, specific for each class of drugs, should complement these general indicators.

Catchment Area, Health↗

Drug use in Estonia in 1994-1995: a follow-up from 1989 and comparison with two Nordic countries.

OBJECTIVE: To determine the patterns of drug use in Estonia for the years 1989 and 1994 1995, i.e. for the years before and after the pharmaceutical services in the country changed from a state monopoly to a competitive market. METHODS: The wholesale data from Estonia and the defined daily doses methodology were used. For comparison, national statistics on medicines from Finland and Sweden for the years 1994-1995 are shown. RESULTS: The general sales of drugs in Estonia decreased almost twofold in all major pharmacological groups from 1989 to 1994 and subsequently increased by 10%-30% in 1995. Substantial differences in patterns of drug use between Estonia and the two Nordic countries were observed. The amount of prescription-only medicines used in Estonia was approximately 25% of that used in Finland and Sweden. The amount of over-the-counter drugs used was 61% of that used in Finland and 58% of that used in Sweden. In the drug use patterns in Estonia, some common trends can be noted: (1) persistent traditions, such as the low use of diuretics, beta-blockers, antithrombotics and inhalant anti-asthmatic drugs; (2) changes in prescription preferences--central anti-adrenergic drugs, pyrazolones, aminoglycosides and barbiturates are being replaced by calcium channel blockers and angiotensin-converting-enzyme inhibitors, propionic acid derivatives, cephalosporins and benzodiazepines, respectively; (3) rapidly increasing use of drugs not prescribed in the 1980s, such as hormonal contraceptives, opioids and antiulcer drugs, which strongly improves the quality of pharmacotherapy in Estonia. CONCLUSION: The general trends in Estonia and the two Nordic countries are similar--the use of newer and more effective drugs is increasing and that of older ones decreasing. The changes are more rapid in Estonia than in Finland and Sweden, but, because of a short observation period, the use of newer drugs not yet prevailing. The international differences in drug utilization observed in this study may possibly be related mainly to the prescription preferences (e.g. therapeutic traditions) and less dependent on the respective health care systems (e.g. reimbursement schemes) and economic state of the country.

Drug Prescriptions↗

Effects of a movement and swimming program on vital capacity and water orientation skills of children with cerebral palsy.

Swimming and aquatic exercise are known for their effects on respiration in normal and asthmatic people. The purpose of the present study was to evaluate the effect of a 6-month movement and swimming program on the respiratory function and water orientation skills of children with cerebral palsy (CP). Forty-six kindergarten children aged 5 to 7 years were assigned either to a treatment or control group. The intervention program consisted of swimming sessions twice weekly and sessions of group physical activity in a gym once weekly, each session lasting 30 minutes, for a period of 6 months. Children in the control group were treated (30 minutes, 4 days per week) with Bobath physical therapy. The children in the treatment and control groups had comparable disability types, age, and anthropometric measurements. A 2 x 2 (group x test period) repeated measures ANOVA design confirmed a significant effect of interaction of time with group. The results also confirmed that children with CP have reduced lung function compared with normative data for children in the same age category. The treatment program improved baseline vital capacity results by 65%, while children in the control group improved by only 23%. The movement and swimming exercise program had a better effect than a physical therapy routine implemented in a previous study, consisting of respiratory exercise alone.

Analysis of Variance↗

Effects of a movement and swimming program on water orientation skills and self-concept of kindergarten children with cerebral palsy.

In this study the effect of an experimental movement and swimming program of six months on motor function in the water measured by means of the Water Orientation Score and self-perception measured by means of the Martinek-Zaichkowsky Self-concept Scale was investigated. 23 children participated in the program, completing both tests prior to and after the intervention. An age-, sex-, and disability-matched control group of 23 children completed only the Self-concept Scale at pre- and posttest. Analysis indicated a significant improvement in Water Orientation Score of children in the trained group, but no effect on scores of the Self-concept Scale.

Cerebral Palsy↗

Changes in the pattern of antidepressant use upon the introduction of the new antidepressants: a prescription database study.

OBJECTIVE: To study whether the newer antidepressants have changed the patterns of antidepressant use, and whether the claimed better adverse effect profile of the lower antidepressants is reflected in their use as monitored by a prescription database. METHOD: By means of a prescription database (OPED), the use of antidepressants from 1991 to 1993 in Odense, Denmark, was analysed. RESULTS: The 1-year prevalence of antidepressant use increased significantly from 1.60% to 2.00%, which still is below the claimed 1-year prevalence of depression of at least 5%. The increase was mainly due to a rapidly increasing use of the newer antidepressants, accompanied by a moderate decline in the use of older antidepressants (mainly tricyclic antidepressants). The patterns of antidepressant use were very polymorphic, with about 5% being on continuous use for all 3 years and groups of each 20-30% being treated with: (1) several series or (2) one series or (3) only by one prescription. The share of patients presenting only one prescription (20%) was the same for older and newer antidepressants. Likewise, the rate of shifts from older to newer antidepressants or vice versa was the same (7% vs 6%). The duration of treatment did not differ much between older and newer antidepressants. Relative to the defined daily dose (DDD), the older antidepressants were given in much lower doses (median 0.63 DDD) than the newer antidepressants (median 1.05 DDD). CONCLUSION: It is concluded that many depressed patients are still not receiving antidepressant treatment and that the claimed better adverse effect profile of the newer antidepressants was not clearly reflected in their use.

Adult↗

Use of lipid-lowering drugs from 1990 to 1994: an international comparison among Australia, Finland, Italy (Emilia Romagna Region), Norway and Sweden.

OBJECTIVE: To compare the overall utilisation pattern of lipid-lowering drugs between 1990 and 1994 in Australia, Finland, Italy, Norway and Sweden as well as the pattern of use with respect to age and gender in Italy and Sweden. METHODS: Data were retrieved from regulatory authorities in each country for the 5-year period and analysed according to the ATC/DDD methodology (Anatomical Therapeutic Chemical classification/Defined Daily Doses). Utilisation was calculated as the DDDs for 1000 inhabitants per day for all drugs of the ATC category B04 (serum lipid-reducing agents). Data from Sweden and Italy were also compared with respect to gender and age. RESULTS: In 1994, Australia demonstrated the highest degree of utilisation (11.9 DDD) and the Nordic Countries the lowest (Sweden 5.6; Norway 4.9; Finland 4.0). In all countries except Italy, a steady increase was observed; in Italy, utilisation of these drugs reached a maximum in 1992 (11.5 DDD), but then underwent a reduction which was caused by restrictions in the reimbursement status in 1993 (10.4) and 1994 (6.7). Administration of statins increased in all countries, becoming the most used group of the B04 class. In 1988, the number of different drugs listed by each national health service ranged from 4 (Norway) to 16 (Italy); in 1994 it ranged from 6 (Norway) to 9 (Sweden). Analysis with respect to gender showed the opposite pattern in Sweden (males 4.6 and females 3.3 in 1992; 6.2 and 4.5, respectively, in 1994) than in Italy (males 10.8 and females 17.8 in 1992; 6.4 and 9.2, respectively, in 1994). Exposure was highest in people aged 60-69 years in both countries, followed by age group 50-59 in Sweden and 70-79 in Italy. CONCLUSIONS: Large variations in the utilisation of lipid-lowering drugs exist between countries, with Australia and Italy much higher than others. Of the drugs in the ATC category B04, the use of statins predominates in all countries, but to varying degrees. The large difference in the degree of drug utilisation with respect to age and gender between Italy and Sweden suggests major deviations from evidence-based medicine.

Adolescent↗