The dawn of chemical neuroanatomy in the CNS came with the discovery and mapping of the central dopamine, noradrenaline and 5-hydroxytryptamine neurons by means of transmitter histochemistry using ...the Falck-Hillarp formaldehyde fluorescence technique in the early 1960s. Our mapping of the central monoamine neurons was continued and further established with tyrosine hydroxylase, dopa decarboxylase and dopamine-beta-hydroxylase immunohistochemistry in collaboration with Menek Goldstein and Tomas Hökfelt. During recent years an evolutionary constraint in the nuclear parcellation of the DA, NA and 5-HT neurons was demonstrated in the order Rodentia and other mammals. The abundant existence of global monoamine varicose nerve terminal networks synthesizing, storing and releasing monoamines in various parts of the CNS, including the release of DA by tubero-infundibular DA neurons as a prolactin inhibitory factor from the external layer of the median eminence into the portal vessels and the appearance of extraneuronal DA fluorescence after, e.g., treatment with amphetamine in nialamide pretreated rats (Falck-Hillarp technique) were also remarkable observations. These observations and others like the discovery of transmitter-receptor mismatches opened up the possibility that monoamines were modulating the wired brain, built up mainly by glutamate and GABA neurons, through diffusion and flow in the extracellular fluid of the extracellular space and in the CSF. This transmission also involved long-distance channels along myelinated fibers and blood vessels and was called volume transmission (VT). The extracellular space (ECS), filled with a 3D matrix, plays a fundamental role in this communication. Energy gradients for signal migration in the ECS are produced via concentration, temperature and pressure gradients, the latter two allowing a flow of the ECF and CSF carrying the VT signals. The differential properties of the wiring transmission (WT) and VT circuits and communication channels will be discussed as well as the role of neurosteroids and oxytocin receptors in volume transmission leading to a new understanding of the integrative actions of neuronal-glial networks. The role of tunneling nanotubes with mitochondrial transfer in CNS inter alia as part of neuron-glia interactions will also be introduced representing a novel type of wiring transmission. The impact of the technicolour approach to the connectome for the future characterization of the wired networks of the brain is emphasized.
Steering from the centre Dahlström, Carl; Peters, B. Guy; Pierre, Jon
Steering from the centre,
c2011, 20111122, 2017, 2011, 2014, 2011-08-27, 2011-11-22
eBook
Steering from the Centredetails how chief executives in ten Western democracies have responded to governance challenges in the wake of reform ideas such as the New Public Management which stress ...deregulation and decentralization.
Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography ...(EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed.
This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality.
A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index CCI score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025).
In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk.
The review describes the initial experiments suggesting a fast intra-axonal transport of transmitter related substances, in addition to the "classic" slow flow. Early experiments were mainly ...conducted in the peripheral adrenergic system, focusing on transport of amine storage granules, the extent of the vast sympathetic adrenergic system and the importance of axonal transport of amine granules for the adrenergic system. Further, it describes important advances obtained from studies of other neuron systems regarding local axonal protein synthesis, motor proteins and new insights regarding relation between faults in the transport machinery and some neuropathological conditions.
Pharmacokinetics of oral noscapine Karlsson, M O; Dahlström, B; Eckernäs, S A ...
European journal of clinical pharmacology,
01/1990, Letnik:
39, Številka:
3
Journal Article
Recenzirano
The relative bioavailability in 20 healthy volunteers of 100 mg, 200 mg and 300 mg tablets of noscapine and 200 mg as a solution has been assessed in a four-way cross-over study, with repeated ...administration of the 200 mg dose to assess intraindividual variability. There was a disproportionate increase in the AUC of noscapine tablets, as a 3-fold increase in dose produced a 9-fold rise in AUC. This dose-dependency could mainly be attributed to saturable first-pass metabolism of the drug. Administration of noscapine as a solution resulted in a significantly higher maximal concentration at an earlier time-point and a higher AUC than the corresponding dose as tablets. Repeated administration of noscapine tablets and solution yielded higher AUC on the second dosing occasion. No cause for this carry-over effect was found, and the contribution of remaining noscapine was negligible. The terminal half-life of noscapine, which was independent of formulation or dose size was 4.5 h. Both inter- and intraindividual variability in noscapine kinetics were very high, e.g. 73% and 51% CV of the AUC for the 200 mg tablet.
Morphine kinetics in cancer patients Säwe, J; Dahlström, B; Paalzow, L ...
Clinical pharmacology and therapeutics,
November 1981, Letnik:
30, Številka:
5
Journal Article
Recenzirano
Oral and intravenous morphine kinetics were studied in seven patients with cancer who needed continuous treatment with morphine because of severe chronic pain. Single oral (20 to 30 mg) and ...intravenous (4 mg) doses were given on separate days, followed by repetitive blood sampling for morphine analysis by gas chromatography. Volume of distribution ranged from 0.95 to 3.75 l/kg and serum clearance from 5.0 to 16.1 ml/min/kg. Oral morphine in doses that were more than five times the intravenous dose gave concentrations (at 10 and 120 min after dose) between 38 and 112 ng/ml. During the 0.25‐ to 8‐hr period after the oral dose serum concentrations were higher than after the intravenous dose. There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half‐life from 58 to 467 min. These data warrant careful adjustment of the oral dose under close supervision of the patient at the onset of therapy.
Clinical Pharmacology and Therapeutics (1981) 30, 629–635; doi:10.1038/clpt.1981.214
Surgical treatment of ectopic pregnancy Dahlstrøm, B; Urnes, A
Tidsskrift for den Norske Lægeforening,
1997-Apr-20, Letnik:
117, Številka:
10
Journal Article
The influence of two different concentrations of iv naloxone infusion on the analgesia and adverse effects of epidural morphine were compared in a double-blind, placebo-controlled study. Forty-five ...patients undergoing gallbladder surgery were provided postoperative analgesia by 4 mg epidural morphine; they then received an iv infusion over a 12-h period consisting of either 5 micrograms X kg-1 X h-1 naloxone, 10 micrograms X kg-1 X h-1 naloxone, or saline. Pain relief was assessed by hourly visual analog scoring (VAS) and by direct questioning of the patient. Requirement of additional analgesia was noted. Respiratory frequency was monitored every 15 min and arterial blood gases were analyzed every 2 h for 24 h. Peak expiratory flow (PEF) was recorded 6 and 24 h postoperatively. Steady-state kinetics of naloxone were determined by a modified radioimmunoassay (RIA) method. All patients had good to excellent postoperative pain relief. Naloxone, 5 micrograms X kg-1 X h-1, did not appear to have any effect on epidural morphine analgesia. However, naloxone infusion at the rate of 10 micrograms X kg-1 X h-1 reduced the duration of analgesia by about 25%, and more frequent injections of epidural morphine were required to give effective analgesia. Complete reversal of analgesia was not seen in any patient. A dose-related stimulatory effect on respiratory frequency was noted in the groups receiving naloxone. PaCO2 values also were better in these groups as compared to values in the placebo group.
In a randomized double-blind study of thirty grossly obese patients undergoing gastroplasty for weight reduction, the effects of intramuscular and epidural morphine were compared as regards ...analgesia, ambulation, gastrointestinal motility, early and late pulmonary function, duration of hospitalization, and occurrence of deep vein thrombosis in the postoperative period. The patients were operated on under thoracic epidural block combined with light endotracheal anesthesia. A six-grade scale was devised to quantify postoperative mobilization. A radioactive isotope method using 99mTc -plasmin was employed to detect postoperative deep vein thrombosis. For 14 hr after the first analgesic injection, respiratory frequency was noted every 15 min and arterial blood gases were measured hourly. Peak expiratory flow was recorded daily until the patient was discharged from hospital. Spirometry was performed the day before and the day after surgery. Plasma concentrations of morphine were measured after both intramuscular and epidural administration. Both intramuscular and epidural morphine gave effective analgesia, but the average dose of intramuscular morphine was up to seven times greater than that required by the epidural route. A larger number of patients receiving epidural morphine postoperatively were able to sit, stand, or walk unassisted within 6, 12, and 24 hr, respectively. Being alert and more mobile as a result of superior postoperative analgesia from epidural morphine, patients in this group benefited more from vigorous physiotherapy routine, which resulted in fewer pulmonary complications. Furthermore, earlier postoperative recovery of peak expiratory flow and bowel function presumably contributed to a significantly shorter hospitalization in patients receiving epidural morphine. There was no evidence of prolonged respiratory depression in this high-risk category of patients. The 99mTc -plasmin tests revealed no significant difference between the two groups.
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