Torkel Falkenberg

Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment

Enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. We report that rats housed in an enriched environment showed improved performance in the Morris water maze and decreased spontaneous motor activity. Exposure to behavioural tests increased expression of the mRNA that encodes brain-derived neurotrophic factor in the hippocampus. This was not seen when rats subjected to impoverished housing were tested suggesting that environmental history of the animal is of importance to induce expression of brain-derived neurotrophic factor in the hippocampus that may promote neuronal changes related to learning and memory.

Circular instead of hierarchical: methodological principles for the evaluation of complex interventions

BackgroundThe reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions. At the foundation of this hierarchy are case studies, retrospective and prospective case series, followed by cohort studies with historical and concomitant non-randomized controls. Open-label randomized controlled studies (RCTs), and finally blinded, placebo-controlled RCTs, which offer most internal validity are considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy, founded on a pharmacological model of therapy, is generalized to other interventions which may be complex and non-pharmacological (healing, acupuncture and surgery).DiscussionThe hierarchical model is valid for limited questions of efficacy, for instance for regulatory purposes and newly devised products and pharmacological preparations. It is inadequate for the evaluation of complex interventions such as physiotherapy, surgery and complementary and alternative medicine (CAM). This has to do with the essential tension between internal validity (rigor and the removal of bias) and external validity (generalizability).SummaryInstead of an Evidence Hierarchy, we propose a Circular Model. This would imply a multiplicity of methods, using different designs, counterbalancing their individual strengths and weaknesses to arrive at pragmatic but equally rigorous evidence which would provide significant assistance in clinical and health systems innovation. Such evidence would better inform national health care technology assessment agencies and promote evidence based health reform.

Use of complementary and alternative medicine in the scandinavian countries

Objective To describe the prevalence of use of complementary and alternative medicine (CAM) in Norway, Denmark and Stockholm County. Design, setting, and subjects In Norway, a national representative sample of 1000 participants completed telephone interviews regarding their CAM use in 1997 (response rate 51). In Denmark, a national representative sample of 16 690 participants completed questionnaires and interviews regarding their health and morbidity in 2000 (response rate 74). In Stockholm County, a randomly selected sample of 1001 participants completed telephone interviews about their CAM use in 2000 (response rate 63). Results Prevalence of ever-use of CAM was 34% in Norway, 45% in Denmark, and 49% in Stockholm. Use of CAM is associated with poor self-reported health in all three studies, and with visits to a medical doctor in Denmark and Norway. More women than men, and more with higher education, reported use of CAM. Most frequently used CAM therapy was homeopathy in Norway, reflexology in Denmark, and massage in Stockholm County. Conclusions Use of CAM is common in the Scandinavian countries, and there are national differences regarding therapy preferences. Many individuals use both CAM and conventional health services.

Septal cholinergic afferents regulate expression of brain-derived neurotrophic factor andβ-nerve growth factor mRNA in rat hippocampus

SummaryIn situ hybridization was used to study the expression of members of the nerve growth factor family of trophic factors in rat hippocampus following stimulation of afferent cholinergic and glutamatergic pathways with quisqualate. A transient increase in brain-derived neurotrophic factor (BDNF) andβ-nerve growth factor (NGF) mRNA expression in the hippocampus was seen 4 h after a quisqualate injection into the medial septal nucleus. Both BDNF and NGF mRNA levels increased more than 4-fold in the granule layer of the dentate gyrus and for BDNF mRNA also in the pyramidal cells of CA1, while the levels of BDNF mRNA in CA3 increased 2-fold. The increase in BDNF and NGF mRNA levels were completely prevented by pretreatment with systemic injections of either scopolamine or diazepam. A quisqualate injection into the entorhinal cortex, containing glutamatergic afferents to the hippocampus, resulted in a 15-, 5- and 17-fold increase in the expression of BDNF mRNA in the ipsilateral granule cells, CA3 and CA1 pyramidal cells, respectively. Similar increases were also seen in the hippocampus contralateral to the injections. In contrast, the level of NGF mRNA did not increase significantly in any of the subfields in the hippocampus. The increase in BDNF mRNA after cortex injections was attenuated by diazepam but not by scopolamine. These findings imply that increased activity in afferent cholinergic and glutamatergic pathways to the hippocampus differentially regulate expression of the NGF family of neurotrophic factors in the hippocampus.

Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community.

Summary objective  To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1–5 years in Bavi, Vietnam.

STD management by private pharmacies in hanoi: practice and knowledge of drug sellers.

Background: Prompt treatment of sexually transmitted infections may reduce the incidence of HIV/AIDS infections. With health sector reforms private pharmacies are increasingly the first and only contact with health delivery services. Objectives: To find out how patients with STDs are treated at private pharmacies in Hanoi, and what drug sellers know about STD management. Methods: Five simulated clients were taught to adopt a scenario stating that their friend had a urethral discharge. They visited 60 randomly selected private pharmacies in urban Hanoi and noted all questions asked, advice offered, and treatment given. Afterwards interviewers administered a semistructured questionnaire to all people working in the 60 pharmacies. Results: Drug treatment was given in 84% of the 297 encounters averaging 1.5 drugs and 1.2 antibiotics per encounter. Quinolones were given 188 times. No dispensing was adequate for chlamydia or was in accordance with the national guidelines. No questions were asked in 55% of encounters and no advice was given in 61%. Questions on sexual activity were asked in 23% (69) of cases and about the health of the partner twice (1%). Advice to practise safe sex was given in 1% of encounters and for the partner to seek treatment only once. Of 69 questionnaires administered 51% said they would refer to a doctor, 16% said they would ask about the sexual activity 1% said they would ask about the health of the partner, 7% said they would advise using a condom, and 1% advised telling the partner to seek treatment. Even after prompting, 61% would ask no questions and 80% would give no advice. Conclusions: Even though 74% of pharmacists and drug sellers know that they should not treat STD patients, 84% actually did. None gave syndromically correct treatment. In both the questionnaire and during the simulated client methods, numbers advising on partner notification and condom use were very poor. Educational or peer awareness interventions are urgently needed among private pharmacists in Vietnam.

Multidrug-resistant commensal Escherichia coli in children, Peru and Bolivia.

Healthy children in urban areas have a high prevalence of fecal carriage of drug-resistant E. coli.

Improving private pharmacy practice: a multi-intervention experiment in Hanoi, Vietnam.

The objective of this study was to assess the effects of a multicomponent intervention on private pharmacy practice. From 641 private pharmacies in Hanoi, 68 pharmacies were randomly selected and matched into 34 pairs. Each pair consisted of a control and an intervention pharmacy. Three interventions were applied sequentially: Regulatory enforcement, Education, and Peer influence. Four tracer conditions were selected: uncomplicated acute respiratory infection (ARI), sexually transmitted disease (STD), requesting the prescription-only drugs prednisolone, and a short course of cefalexin. Practice was assessed through the Simulated Client Method (SCM). The intervention pharmacies improved significantly compared to the control pharmacies (P <.05) in all tracer conditions. For ARI, antibiotic dispensing decreased (P <.02) and questions regarding breathing increased (P <.01). For STD, advice to go to the doctor and dispensing the correct syndromic treatment increased (P <.01). Dispensing of prednisolone and cefalexin decreased (P <.01) and prescription requests increased (P <.01). Our conclusion is that it is possible to improve private pharmacy practice with a multicomponent intervention.

Management of Childhood Acute Respiratory Infections at Private Pharmacies in Vietnam

OBJECTIVE: To investigate the knowledge and practice among private pharmacy staff in Hanoi regarding case management of mild acute respiratory infection (ARI) in children. METHODS: Sixty private pharmacies in Hanoi were randomly selected. Knowledge was assessed through interviews with pharmacy staff using a questionnaire; practice was assessed through the Simulated Client Method. RESULTS: In the questionnaire, 20% of the pharmacy staff stated that they would dispense antibiotics. In practice, 83% of the pharmacies dispensed antibiotics. Only 36% of the cases were handled according to guidelines. In the questionnaire, 81% of interviewees stated that antibiotics are not effective in short therapeutic courses. In practice, 48% of the antibiotics were dispensed in courses less than five days. Traditional herbal medicines were dispensed in 41% of the encounters. In the questionnaire, 53% of the pharmacy staff stated that they would ask the patient about difficulty of breathing. In practice, questions related to difficulty of breathing were asked in less than 10% of the encounters. CONCLUSIONS: Dispensing of antibiotics for mild ARI was common practice among private pharmacies, and there was a significant difference between knowledge and practice. Interventions are needed to improve pharmacy practice in Hanoi.

Repeated spinal cord stimulation decreases the extracellular level of γ-aminobutyric acid in the periaqueductal gray matter of freely moving rats

Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of descending pain inhibition is the periaqueductal grey matter (PAG). The aim of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separated by a 90 min resting period) alters the extracellular neurotransmitter concentrations in the ventrolateral PAG. In a first series of experiments significantly decreased (-30%; P < 0.05; n = 7) gamma-aminobutyric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of GABA after two SCS sessions was confirmed in a second series of experiments (-30%; P < 0.05; n = 7). No spontaneous decline of GABA was observed in sham-stimulated animals (n = 6). The glutamate concentration was also determined in this latter series of experiments and a significant decrease (-23%; P < 0.05; n = 5) was observed after the second SCS session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased extracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.