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Biomedical subjects

P E Hansen

Publications and source records attributed to P E Hansen.

At least 19 recordsLinked to original sources

Personality traits and cancer survival: a Danish cohort study.

We conducted a population-based prospective cohort study in Denmark to investigate associations between the personality traits and cancer survival. Between 1976 and 1977, 1020 residents of the Copenhagen County completed a questionnaire eliciting information on personality traits and various health habits. The personality traits extraversion and neuroticism were measured using the short form of the Eysenck Personality Inventory. Follow-up in the Danish Cancer Registry for 1976-2002 revealed 189 incidents of primary cancer and follow-up for death from the date of the cancer diagnosis until 2005 revealed 82 deaths from all-cause in this group. A Cox proportional-hazards model was used to estimate the hazard ratios (HRs) of death from all-cause according to extraversion and neuroticism adjusting for potential confounding factors. A significant association was found between neuroticism and risk of death (HR, 2.3 (95% CI=1.1-4.7); Linear trend P=0.04) but not between extraversion and risk of death (HR, 0.9 (0.4-1.7); Linear trend P=0.34). Similar results were found when using cancer-related death. Stratification by gender revealed a strong positive association between neuroticism and the risk of death among women (Linear trend P=0.03). This study showed that neuroticism is negatively [corrected] associated with cancer survival. Further research on neuroticism and cancer survival is needed.

Age Distribution↗

Tautomerism of sterically hindered schiff bases. Deuterium isotope effects on 13C chemical shifts.

A series of sterically hindered o-hydroxy Schiff bases derived from o-hydroxyaceto- and benzophenones with very short intramolecular hydrogen bonds were described qualitative and quantitatively by deuterium isotope effects on (13)C chemical shift, (n)DeltaC(XD), (n)DeltaF(XD), (1)J(N,H) coupling constants, deltaNCH(3) chemical shifts and UV spectra. All the investigated compounds are found to be tautomeric. The tautomeric character is described by the signs of the deuterium isotope effects on the (13)C chemical shifts. For the 3-nitro-5-chloro derivatives at low temperature, the equilibrium is shifted almost fully toward the proton transferred form in CD(2)Cl(2). Intrinsic deuterium isotope effects on chemical shifts of these compounds as well as (1)J(N,H) coupling constants suggest that a zwitterionic resonance form is dominant for the proton transferred form. Structures, (1)H, (19)F, and (13)C chemical shifts, and deuterium isotope effects on (13)C chemical shifts are calculated by ab initio methods. The potential energy functions and the total deuterium isotope effects are calculated, and they are shown to correspond well with the experimental findings.

Journal Article↗

Inositol phosphates from barley low-phytate grain mutants analysed by metal-dye detection HPLC and NMR.

Inositol phosphates from barley low-phytate grain mutants and their parent variety were analysed by metal-dye detection HPLC and NMR. Compound assignment was carried out by comparison of retention times using a chemical hydrolysate of phytate [Ins(1,2,3,4,5,6)P(6)] as a reference. Co-inciding retention times indicated the presence of phytate, D/L-Ins(1,2,3,4,5)P(5), Ins(1,2,3,4,6)P(5), D/L-(1,2,4,5,6)P(5), D/L-(1,2,3,4)P(4), D/L-Ins(1,2,5,6)P(4) and D/L-Ins(1,4,5,6)P(4) in PLP1B mutants as well as the parent variety. In grain extracts from mutant lines PLP1A, PLP2A and PLP3A unusual accumulations of D/L-Ins(1,3,4,5)P(4) were observed whereas phytate and the above-mentioned inositol phosphates were present in relatively small amounts. Assignment of D/L-Ins(1,3,4,5)P(4) was corroborated by precise co-chromatography with a commercial Ins(1,3,4,5)P(4) standard and by NMR spectroscopy. Analysis of inositol phosphates during grain development revealed accumulation of phytate and D/L-Ins(1,3,4,5)P(4), which suggested the tetrakisphosphate compound to be an intermediate of phytate synthesis. This assumption was strengthened further by phytate degradation assays showing that D/L-Ins(1,3,4,5)P(4) did not belong to the spectrum of degradation products generated by endogenous phytase activity. Metabolic scenarios leading to accumulation of D/L-Ins(1,3,4,5)P(4) in barley low-phytate mutants are discussed.

6-Phytase↗

A nicked duplex decamer DNA with a PEG(6) tether.

A dumbbell double-stranded DNA decamer tethered with a hexaethylene glycol linker moiety (DDSDPEG), with a nick in the centre of one strand, has been synthesised. The standard NMR methods, E.COSY, TOCSY, NOESY and HMQC, were used to measure (1)H, (31)P and T:(1) spectral parameters. Molecular modelling using rMD-simulated annealing was used to compute the structure. Scalar couplings and dipolar contacts show that the molecule adopts a right-handed B-DNA helix in 38 mM phosphate buffer at pH 7. Its high melting temperature confirms the good base stacking and stability of the duplex. This is partly attributed to the presence of the PEG(6) linker at both ends of the duplex that restricts the dynamics of the stem pentamers and thus stabilises the oligonucleotide. The inspection of the global parameters shows that the linker does not distort the B-DNA geometry. The computed structure suggests that the presence of the nick is not disturbing the overall tertiary structure, base pair geometry or duplex base pairing to a substantial extent. The nick has, however, a noticeable impact on the local geometry at the nick site, indicated clearly by NMR analysis and reflected in the conformational parameters of the computed structure. The (1)H spectra also show much sharper resonances in the presence of K(+) indicating that conformational heterogeneity of DDSDPEG is reduced in the presence of potassium as compared to sodium or caesium ions. At the same time the (1)H resonances have longer T:(1) times. This parameter is suggested as a sensitive gauge of stabilisation.

Cations↗

1H NMR of compounds with low water solubility in the presence of erythrocytes: effects of emulsion phase separation.

When lipophilic compounds like diethyl phthalate (DEP) were added to water, two sets of resonances appeared in the 1H NMR spectrum, whereas when added in concentrations above approximately 3.5 mM to erythrocytes in a high haematocrit suspension, only one set of resonances was observed at the low-frequency position. The appearance of one set of resonances at lower frequency was found to be common to a series of lipophilic compounds in erythrocytes. The appearance of the NMR spectra is ascribed to the existence of an emulsion, meaning two different phases of a compound: a "droplet" (resonances to lower frequency) and aqueous dissolved phase (resonances to higher frequency). The absence of the resonances from the dissolved phase in erythrocyte solution is ascribed to exchange broadening. The absolute chemical shift of the compound in its "droplet" phase was also measured using a cylindrical/spherical microcell. This arrangement mimicked the geometry of the dissolved versus the phase-separated species and thus obviated the effect of a difference in magnetic susceptibility between the "droplet" solute and its aqueous solution. Factors influencing the formation of emulsion phases such as erythrocytes, haemoglobin and smaller proteins were investigated; they are found to be effective in the order given.

Blood Proteins↗

A lithium clinic for bipolar patients: 2-year outcome of the first 148 patients.

OBJECTIVE: This paper describes the outcome for the first 148 patients referred to a lithium clinic. METHOD: Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. RESULTS: Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. CONCLUSION: The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.

Adult↗

Stable ion study of regioisomeric carboxonium-substituted pyrenium ions: directive effects, charge delocalization mode, and conformational aspects.

Regioisomeric monoacyl- and monobenzoyl-substituted pyrenes are diprotonated in FSO(3)H.SbF(5) (4:1)/SO(2)ClF to give persistent carboxonium-pyrenium dications, whereas diacetyl- and dibenzoylpyrenes are diprotonated to give dicarboxonium dications. The resulting dications were studied by low-temperature NMR at 500 MHz. Conformational aspects of the carboxonium group in various regioisomers are addressed by a combination of NOED spectra and 2D-NMR and AM1 calculations. Charge delocalization pathways are gauged and compared on the basis of the magnitude of Deltadelta (13)C values.

Acetylation↗

[Repetitive transcranial magnetic stimulation. A method in the treatment of depressions].

Transcranial magnetic stimulation (TMS) has been used as a diagnostic tool in neurology for more than a decade. Recent research indicates that it when applied repeatedly as repetitive transcranial magnetic stimulation (rTMS) has an antidepressant effect. RTMS is based on the principle of electro-magnetism. An electromagnetic coil placed on the scalp produces a time-varying magnetic field, which gives rise to a current in the proximity of the cerebral cortex. Unlike electroconvulsive therapy (ECT) rTMS does normally not give rise to epileptic seizures and does not require anaesthesia. This review covers a critical summary of the literature on the subject. The results of recent placebo-controlled, randomized trials are promising. However, further investigations are required, before rTMS can be fully integrated in the antidepressant therapeutic armamentarium.

Animals↗

[A survey of forensic psychiatric resources. Trends in the flow of patients to a new unit of forensic psychiatry, Sygehus Fyn, December 31, 1985 to December 31, 1995].

The study covered 163 patients sentenced to special measures. All of them were from the county of Funen, which is a representative part of Denmark regarding forensic psychiatry. On the cross-sectional date 31st December each year the total number of patients treated in the unit was the recorded. The number of patients sectioned to psychiatric treatment in hospital increased by 150% during the observation period. The recorded rise covered both offenders sentenced according to the section 16 and section 69 of the Danish penal code and reflected an increasing number of schizophrenic patients and to lesser-extent patients with personality disorder. The increasing number of beds occupied by forensic patients was in accordance with the development in the total number of patients treated in the unit.

Bed Occupancy↗

[Psychiatric observations 1986-1993. Sygehus Fyn, Middelfart, the unit of forensic psychiatry].

Two hundred and sixty psychiatric reports for law courts conducted between 1986-1993 at the Unit of Forensic Psychiatry, Middelfart were reviewed. The aim was to record a number of essential characteristics with special focus on the number of reports, demographic data, diagnosis and type of criminal act. All the offenders were inhabitants of the county of Funen, where about 50-60 reports for law courts were carried out each year during the period of investigation. Serious crimes (homicide, attempted suicide, violence, arson and rape), were mainly (74%) committed by offenders with personality disorder, of whom few were sentenced to special measures. However, a higher percentage than expected of individuals charged with arson were psychotic (30%) and mentally retarded (10%). Schizophrenics and individuals with other types of non-affective psychosis covered a higher percentage of persons charged with violence compared to manic-depressive individuals. Fifty percent of the offenders were chronic drug abusers.

Adolescent↗

13C NMR, X-ray, and differential scanning calorimetry investigations of truncated BPTI (aprotinin) analogues.

Truncated BPTI missing residues 1 and 2 is investigated together with variants thereof (Lys-15, Arg-17, and Arg-42 are replaced by other residues in various combinations). A comparison of the X-ray structure of BPTI with that of 3-58BPTI(K15R,R17A,R42S) shows only minor variations for the backbone, but the lack of salt bridge between the terminals and the lack of two N-terminal residues provide a structure open at one end. Comparisons of amide exchange rates show a dramatic increase for the most slowly exchanging NH protons of 3-58BPTI and the analogues thereof, as compared to those of the wild-type despite only small differences in the structures. The amide exchange rates for truncated analogues increase with decreasing TTEP (temperature top endothermic peak) values. On the basis of the known structural changes comparisons to 13C chemical shifts are made. 13C chemical shifts are assigned using the D-isotope and HMBC techniques. Excellent resolution is obtained in these 1D natural abundance spectra. 13C NMR chemical shifts are shown to be able to gauge structural changes. A comparison of 13C chemical shifts of WT BPTI (aprotinin) and 3-58BPTI reveals effects caused by (i) the removal of the salt bridge of the terminii, (ii) the charge of the N-terminus, and (iii) the increased mobility of the side chain of Tyr-23. Small effects are also seen due to a conformational change of the aromatic ring of Phe-4. Ring current shifts at 13C chemical shifts are calculated. The difference in the calculated ring current effects are small comparing the wild-type with 3-58BPTI(K15R,R17A,R42S) provided the structures are relaxed. Protein unfolding as a function of pH and temperature is studied by DSC. Unfolding occurs at lower temperature with N-terminally truncated analogues, and the maximum is shifted toward higher pH.

Amino Acid Substitution↗

[Mortality--suicide and natural death--among depressed patients. Relation to type of depression].

A total of 219 inpatients with a DSM-III diagnosis of major depression, (150 women and 69 men), were followed prospectively for three to ten years and mortality was recorded. The patients were previous participants in psychopharmacological multicentre trials, which were carried out for the purpose of comparing the antidepressant effect of newer selective serotonin reuptake inhibitors (SSRI), citalopram and paroxetine, with that of the tricyclic antidepressant drug, clomipramine. Diagnostic classification according to the Newcastle-I Scale into endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as being nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk during the first three years of observation.

Adult↗

Gene technology-based antimetabolite design: the use of an in vitro protein expression system to facilitate antimetabolite design for virally-induced human diseases and malignant conditions.

A precondition for the chemotherapeutic treatment of a variety of virally-induced human diseases and malignant conditions is a highly selective interaction of the drug molecule to be used with it's biological target. To ensure the development of novel, effective drugs, it is essential that the biological target is well characterised with regard to it's structure and activity. Such characterisation relies upon adequate amounts of pure target being available. One of the most important enzymatic importers for antimetabolites is the enzyme thymidine kinase. In this article an in vitro protein expression system is described which facilitates the production of milligram amounts of pure and biologically active thymidine kinase, from a number of important biological sources. Results have shown that the in vitro produced enzyme has the exact biochemical propeties of the in vivo enzyme. Thus the in vitro protein expression system is an ideal vechicle to facilitate an in depth investigation of the enzyme's biological properties.

Journal Article↗

Tolfenamic acid versus propranolol in the prophylactic treatment of migraine.

The prophylactic effect of tolfenamic acid and propranolol was studied in a randomized double-blind cross-over trial of 76 patients with migraine with or without aura. After a 4-week run-in period patients were randomly allocated to treatment with either tolfenamic acid 100 mg three times daily or propranolol 40 mg three times daily for 12 weeks. After a placebo wash-out period of 4 weeks the patients got the alternative drug for 12 weeks; 56 patients completed the study. Both drugs significantly reduced migraine attacks as judged from the reduction in the efficacy parameters (migraine hours, migraine days, and migraine intensity) in the treatment periods compared with the run-in period. No statistical significant difference in any efficacy parameter was found between the two drugs (level 2 alpha = 0.05, alpha = 0.10). The adverse effects showed no statistical difference in frequency between the 2 treatments. Twenty patients discontinued the study: 12 patients on propranolol and 8 patients on tolfenamic acid. Side effects were the cause of premature discontinuation of study medicine in 9 patients during propranolol treatment (dizziness, fatigue, and fall in blood pressure) and in 5 patients during tolfenamic acid treatment (gastrointestinal symptoms).

Adult↗

Tolfenamic acid in acute and prophylactic treatment of migraine: a review.

The possible role of prostaglandins (PGs) in migraine has been the subject of increasing attention after the rather dramatic experiments done in man by Bergström and coworkers more than 25 years ago (1965). The role of PGs in migraine, however, is still hypothetical and not yet explained. PGs are known to sensitize nociceptors and produce hyperalgesia. PGs are involved in platelet aggregation thereby releasing serotonin. Vasodilatation, oedema and hyperalgesia in migraine have much in common with an inflammatory reaction. Tolfenamic acid (TA) inhibits PG biosynthesis and action and has an anti-aggregatory effect. TA is better than aspirin and as effective as ergotamine in treatment of acute migraine attacks. TA has fewer side effects than ergotamine. TA is as effective as propranolol in prophylactic treatment of migraine. The dose regimen of TA in acute treatment of migraine is 200 mg when the first symptoms of migraine appear. The treatment can be repeated after 2-3 hours if satisfactory effect is not obtained. The dose regimen of TA in prophylactic treatment of migraine is one sustained release tablet of 300 mg or 100 mg 3 times daily. After a treatment period of three months the regimen should be re-evaluated.

Acute Disease↗

[Educational requirements of younger psychiatrists].

In order to define the requirements junior medical staff in postgraduate psychiatric training would wish to make for future postgraduate training in adult psychiatry, a questionnaire with 66 questions was sent in June 1990 to postgraduate trainees at all departments of child psychiatry and adult psychiatry in the country. Response was anonymous. The article deals with the responses from 264 persons either intending to undergo specialist training in adult psychiatry or having already completed it. Sixty-four percent stated a need for better individual clinical guidance. The majority stated that eight hours every week should be earmarked for formal tuition and research (two hrs clinical tuition, two hrs theory, two hrs supervision in psychotherapy, and two hrs for research). On average, the trainees had used 4200 DKK of their own income and four free days on courses over the previous year. Twenty-four months was proposed as adequate for an introductory appointment. The majority held that appointments should be made on the basis of the traditional curriculum vitae (82%) and a personal interview (86%), while about 20% believed that written or oral references should also be a requirement. Sixty-nine percent believed that selection of applicants for teaching appointments should be made locally with central supervision. Twenty-six percent felt they had been passed over in appointment situations, and 68% claimed it was due to nepotism. Recommendations for modifications of the future postgraduate training according to the responses are proposed, and it is concluded that earmarked resources are necessary, if the intention in the educational reform now in progress is to be realized.

Adult↗

Ischaemia-induced (symptomatic) migraine attacks may be more frequent than migraine-induced ischaemic insults.

Fifteen consecutive patients with a diagnostic problem of ischaemia-induced migraine with aura (symptomatic migraine) or migraine-associated ischaemia (migrainous infarction) were studied in order to elucidate the mechanisms. Three had a 1 month flurry of daily attacks of migraine auras with or without headache. A severe internal carotid stenosis/occlusion and reduced regional cerebral blood flow (rCBF) was demonstrated. Borderline ischaemia may thus prime the brain for developing migrainous aura with or without migraine (symptomatic migraine). Four patients had a combination of permanent deficits after the very first migraine attack, severe atherosclerosis, risk factors for stroke, high age and no family history of migraine. In these cases the evidence indicates that thromboembolic ischaemia had triggered an attack of migraine with aura (likely symptomatic migraine). Three young females presented long-lasting typical and severe idiopathic migraine with aura. Attack-associated rCBF reduction was likely to have caused permanent, mild, visual or somatosensory deficits (migrainous infarction). In five patients the relationship between migraine and stroke remained unresolved. It seems that ischaemia-induced migraine attacks may be more frequent than migraine-induced ischaemic insults. Therefore, migraine is not as strong a risk factor for stroke as indicated by the mere coincidence of the two disorders.

Adult↗

MR imaging of the developing human brain. Part 1. Prenatal development.

To establish a baseline of the magnetic resonance (MR) imaging appearance of the fetal brain in early stages of development, the authors undertook a study of fixed and fresh specimens of embryos and fetuses of 6-28 weeks gestational age. Images of formalin-preserved and fresh specimens were comparable in their depiction of anatomic structures. On MR images of embryos of 6 weeks gestational age, the rhombic and cervical flexures, aqueduct of Sylvius, diencephalon, cerebellum, cerebral hemisphere, and fourth ventricle could be differentiated. The optic recess and chiasm, pituitary gland, pineal recess, third ventricle, pons, olfactory lobe, corpus striatum, insula, and parietal and temporal lobes could be distinguished as early as 11 weeks gestation. Although MR imaging is impractical as a screening tool for intrauterine abnormalities, it can demonstrate the fetus in great detail and allows a more specific evaluation of fetal anatomy. With the information provided by MR imaging, it may be possible to establish guidelines for assessment of the stage of development during intrauterine life.

Brain↗