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Biomedical subjects

K Andersen

Publications and source records attributed to K Andersen.

At least 19 recordsLinked to original sources

Cross-reinnervation changes the expression patterns of the monocarboxylate transporters 1 and 4: An experimental study in slow and fast rat skeletal muscle.

The monocarboxylate transporters 1 and 4 are expressed in brain as well as in skeletal muscle and play important roles in the energy metabolism of both tissues. In brain, monocarboxylate transporter 1 occurs in astrocytes, ependymocytes, and endothelial cells while monocarboxylate transporter 4 appears to be restricted to astrocytes. In muscle, monocarboxylate transporter 1 is enriched in oxidative muscle fibers whereas monocarboxylate transporter 4 is expressed in all fibers, with the lowest levels in oxidative fiber types. The mechanisms regulating monocarboxylate transporter 1 and monocarboxylate transporter 4 expression are not known. We hypothesized that the expression of these transporters would be sensitive to long term changes in metabolic activity level. This hypothesis can be tested in rat skeletal muscle, where permanent changes in activity level can be induced by cross-reinnervation. We transplanted motor axons originally innervating the fast-twitch extensor digitorum longus muscle to the slow-twitch soleus muscle and vice versa. Four months later, microscopic analysis revealed transformation of muscle fiber types in the cross-reinnervated muscles. Western blot analysis showed that monocarboxylate transporter 1 was increased by 140% in extensor digitorum longus muscle and decreased by 30% in soleus muscle after cross-reinnervation. In contrast, cross-reinnervation induced a 62% decrease of monocarboxylate transporter 4 in extensor digitorum longus muscle and a 1300% increase in soleus muscle. Our findings show that cross-reinnervation causes pronounced changes in the expression levels of monocarboxylate transporter 1 and monocarboxylate transporter 4, probably as a direct consequence of the new pattern of nerve impulses. The data indicate that the mode of innervation dictates the expression of monocarboxylate transporter proteins in the target cells and that the change in monocarboxylate transporter isoform profile is an integral part of the muscle fiber transformation that occurs after cross-reinnervation. Our findings support the hypothesis that the expression of monocarboxylate transporter 1 and monocarboxylate transporter 4 in excitable tissues is regulated by activity.

Animals↗

[Assessment of two different software solutions for the evaluation of CT colonography].

PURPOSE: To compare a commercial CT colonography software ("Colonography", Siemens, Forchheim) with a non-commercial post-processing system ("Colotux", Department of Informatics). MATERIAL AND METHODS: Identical data sets of 10 patients, who underwent an ultra-low-dose multi-detector CT colonography (ULD-MDCTC) (4x1 mm collimation, 8 mm pitch, 120 kVp, 10 mAs) were analyzed retrospectively. Assessment was performed using both software solutions by two resident radiologists, who did not have any experience with any colonography software tool before and who did not know the clinical symptoms of the patients or the results of the conventional colonoscopy. Both systems were analyzed using several subjective quality criteria including workflow, handling, image quality, endoluminal navigation and analysis of lesions with grading on a 5-point-scale. Results concerning polyps were compared between the two systems as well as with conventional colonoscopy. RESULTS: Both colonography systems detected the same number of polyps. Although both showed some advantages for single criteria, no relevant difference was noted in general for subjective assessment. The time for calculation of three dimensional interactive volumes was three times longer for "Colotux" compared to "Colonography." Linux-based "Colotux" showed a trend towards better subjective image quality and easier measurement of polyp size. An intuitive desktop and "Syngo"-workflow integration were advantages of "Colonography." CONCLUSION: The analysis of CT colonographies (4-detector-row-CT-scanner, ultra low dose technique, supine position) can adequately be achieved by both software solutions. There was no significant subjective or objective difference of quality between a "stand-alone" individual system and a commercial workflow-integrated solution. A relevant factor for decision between the two systems may be the difference in time needed for the 3D volume calculation, especially in institutes with a high frequency of examinations.

Aged↗

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

Age Distribution↗

Photopatch testing: a consensus methodology for Europe.

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

Dermatitis, Photoallergic↗

Long term risk stratification of patients with acute coronary syndromes: characteristics of troponin T testing and continuous ST segment monitoring.

OBJECTIVE: To examine the long term prognostic characteristics of troponin T testing and continuous multi-lead ST segment monitoring in combination with clinical and 12 lead ECG risk indicators in patients with acute coronary syndromes (ACS). PATIENTS AND DESIGN: Patients with suspected ACS (n = 213) were studied. Troponin T was analysed in blood samples collected during the first 12 hours after admission. Continuous vectorcardiography ST segment monitoring was performed for 24 hours and the number of ST vector magnitude episodes was registered. Patients were followed up for a median of 28 months. The end point was a composite of cardiac death and acute myocardial infarction. RESULTS: Thirty eight (18%) patients reached the composite end point. The median (interquartile range) time from study inclusion to the time of the composite end point was longer for patients predicted to be at risk by troponin T testing (n = 27) than for those predicted to be at risk by ST segment monitoring (n = 20) (8.4 (0.2-15) months v 0.3 (0.1-4.3) months, p = 0.04). Significant univariate predictors of the composite end point were age > or = 65 years, diabetes, previous myocardial infarction, congestive heart failure, use of beta blockers or diuretics at admission, 12 lead ECG ST segment depression at admission, troponin T concentration > or = 0.10 microg/l, and > or = 1 ST vector magnitude episodes. Age > or = 65 years, previous myocardial infarction, and troponin T concentration > or = 0.10 microg/l provided independent prognostic information after multivariate analysis of potential risk variables. The prognostic value of transient ischaemic episodes in ACS seems to be confined to the short term. CONCLUSIONS: Both biochemical and continuous ECG markers reflect an increased risk for patients with ACS; however, the methods exhibit different temporal risk characteristics.

Aged↗

Interferon-gamma suppresses S100A4 transcription independently of apoptosis or cell cycle arrest.

The S100A4 protein has been associated with increased metastatic capacity of cancer cells, and recent studies have suggested a correlation between the expression level of S100A4 and the prognostic outcome for patients with various types of cancer. The knowledge about the mechanisms underlying the metastasis-promoting effects is still limited, and the aim of the present study was to elucidate signal transduction pathways involved in the regulation of S100A4. After treatment of human carcinoma cells with interferon-gamma (IFN-gamma), we observed downregulation of S100A4 both at mRNA and protein levels. The effect was not dependent on IFN-gamma-induced apoptosis or IFN-gamma-mediated cell cycle arrest. Moreover, IFN-gamma-mediated decrease in mRNA stability could not account for the observed decrease in S100A4 transcript level. Finally, microarray analysis suggests ISGF3G, ETV5, ZNF133 and CEBPG as possible candidate genes involved in IFN-gamma-mediated repression of S100A4.

Apoptosis↗

Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors.

Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR)) expressed in Xenopus oocytes from rat brain RNA was investigated. At nAChR, analogues with single amine-to-methylene or amine-to-ether substitutions had similar potencies to PhTX-343 (IC(50)=16.6 microM at -100 mV) whereas PhTX-(12), in which both secondary amino groups of PhTX-343 were replaced by methylenes, was more potent than PhTX-343 (IC(50)=0.93 microM at -100 mV). Truncated analogues of PhTX-343 were less potent. Inhibition by all analogues was voltage-dependent. PhTX-343 (IC(50)=2.01 microM at -80 mV) was the most potent inhibitor of NMDAR. At AMPAR, most analogues were equipotent with PhTX-343 (IC(50)=0.46 microM at -80 mV), apart from PhTX-83, which was more potent (IC(50)=0.032 microM at -80 mV), and PhTX-(12) and 4,9-dioxa-PhTX-(12), which were less potent (IC(50)s>300 microM at -80 mV). These studies show that PhTX-(12) is a selective nAChR inhibitor and PhTX-83 is a selective AMPAR antagonist.

Animals↗

Suicide after deployment in UN peacekeeping missions--a Danish pilot study.

This pilot study looks at the frequency of suicide among Danish soldiers who took part in the UN mandated forces (UNMF) during the 1990's. In a contingent of nearly 4000 Danish UN soldiers four suicides were documented, two of whom committed suicide less than one month before deployment and two who committed suicide within a year after discharge from mission. Contributing factors, prevention strategies, and implications for future research are discussed.

Adolescent↗

Risk of dementia in Parkinson's disease: a community-based, prospective study.

OBJECTIVE: To calculate the incidence of and determine possible risk factors for dementia in PD. BACKGROUND: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. METHODS: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. RESULTS: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2). CONCLUSIONS: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.

Aged↗

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.

Blood Pressure↗

Early assessment of long-term risk with continuous ST-segment monitoring among patients with unstable coronary syndromes. Results from 1-year follow-up in the TRIM study.

A total of 323 patients who took part in the TRIM trial underwent an initial 24 h continuous electrocardiogram ST-segment monitoring. A ST vector magnitude (ST-VM) maximum > or = 144 microV predicted death or myocardial infarction within 1 year with a 78% specificity and a 52% sensitivity, an area under the ST-VM trend curve > or = 162 mu with a 86% specificity and a 42% sensitivity and presence of ST-VM episodes with a 70% specificity and a 68% sensitivity. Patients who had neither ST-VM episodes nor a ST-maximum > or = 144 microV had only a 4.5% incidence of death or myocardial infarction within one year as compared to 18% among those patients who met any of these criteria. ST-segment monitoring with continuous vectorcardiography is feasible for risk stratification at least up to 1 year after an episode of unstable coronary artery disease and several vectorcardiographic parameters may be used.

Adult↗

The potential of telemedicine for home nursing in Queensland.

The potential for telemedicine in home nursing was examined by retrospectively reviewing the case-notes relating to home visits made by nurses in Queensland. The case-notes of 166 clients were randomly selected from 10 domiciliary nursing centres run by the Blue Care nursing organization in south-east Queensland. Two experienced community registered nurses independently undertook a retrospective review of the case-notes. Each reviewer made an independent judgement as to whether any of the home nursing visits in the episode of care could have been conducted by telemedicine. Visits requiring hands-on care were deemed to be unsuitable for telemedicine. A total of 12,630 home visits were reviewed. The median number of visits per client was 27 (range 1-722). The mean age of the clients was 72 years (range 2-93 years). A total of 1521 home visits (12%) were judged suitable for telemedicine. There was no significant difference in suitability between males (13%) and females (12%). Care interventions suitable for telemedicine were more likely to be those of a supportive, educational or review nature. Forty per cent of clients lived up to 5 km from the home nursing centre, 33% lived 5-10 km from the centre and 27% lived over 10 km from the centre. The results of the present study confirm the potential for telemedicine in home nursing in Australia.

Adolescent↗

Evaluation of a program to promote positive parenting in the neonatal intensive care unit.

PURPOSE: To describe and evaluate a parent education program to promote positive parenting in the NICU. DESIGN: Program evaluations completed by parent participants and staff members. SAMPLE: 104 parents (59 mothers and 45 fathers) who attended the Parent's Circle; also 44 NICU or SCN staff members. MAIN OUTEOME VARIABLE: Family and staff evaluations of the Parent's Circle program. RESULTS: Families reported that attending Parent's Circle helped them gain perspective on their situation, feel supported, learn key developmental concepts, locate hospital and community resources, and optimize interactions with their fragile infant. Staff reported that the knowledge parents gained from Parent's Circle influenced their interactions and behaviors in the NICU.

Adaptation, Psychological↗

Recent advances in the medicinal chemistry of polyamine toxins.

This review describes the recent developments in the field of polyamine toxins, with focus on structure activity relationship investigations, including studies of importance of the polyamine moiety for biological activity, photolabeling studies using polyamine toxins as templates, as well as use of solid phase methods for the synthesis of polyamine toxins. The review is mainly concerned with effects of polyamine toxins on nicotinic acetylcholine receptors and ionotropic glutamate receptors.

Animals↗

[Comparison of treatment and prognosis after acute myocardial infarction in two university hospitals in Reykjavik, Iceland 1996.].

INTRODUCTION: The treatment of patients after acute myocardial infarction (AMI) is in part related to the available technology at the hospital of admission. In Iceland percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) was only performed at Landspítalinn at the time of the research. We compared the treatment and prognosis of patients after AMI in 1996 at the two university hospitals in Reykjavík, Iceland, Landspítalinn (LSP) and Sjúkrahús Reykjavíkur (SHR). MATERIAL AND METHODS: We retrospectivly collected informations on all patients admitted with AMI at LSP and SHR in 1996 and compared mortality, morbidity and interventional procedures at one year after admission. RESULTS: The one-year mortality was 17.7% among patients admitted to LSP compared with 20.8% among patients admitted to SHR (p=0.55). Upon discharge from LSP 82% of patients received aspirin and 68% received a ss-blocker versus 71% and 57% of patients discharged from SHR (p=0.021 and p=0.028 respectively). Conversely 29% of patients were disharged with a calsium-antagonist and 76% with a nitrate from SHR compared with 16% and 51% at LSP (p=0.004 and p<0.001 respectively). There was no diffirence in the use of thrombolytics, angiotensin converting enzyme inhibitors, digoxin, diuretics or antiarrhythmics. Within one year 32% of patients admitted to LSP had undergone PTCA but only 13% of patients admitted to SHR (p<0.001). Further, 10% of patients had undergone CABG within one year at LSP compared with 11% at SHR (p=0.75). On average patients at LSP had a 10 days shorter waiting period from admission to PTCA (p=0.001). DISCUSSION: Despite greater use of PTCA, aspirin and ss-antagonist at LSP compared with SHR there was no significant diffirence in one-year mortality between the hospitals. The greater use of calcium-antagonists and nitrates at discharge among patients discharged from SHR might indicate that they were more symptomatic than patients discharged from LSP. We find the great difference in treatment of patients after AMI according to hospital of admission unacceptable. This problem could possibly be solved by implying clinical guidelines.

English Abstract↗

Solid-phase synthesis and biological evaluation of a combinatorial library of philanthotoxin analogues.

The modular structure of philanthotoxins was exploited for construction of the first combinatorial library of these compounds using solid-phase parallel synthesis. (S)-Tyrosine and (S)-3-hydroxyphenylalanine were used as amino acid components, spermine, 1,12-dodecanediamine, and 4,9-dioxa-1,12-dodecanediamine as amine components, and butanoyl, phenylacetyl, and cyclohexylacetyl as N-acyl groups. Following automated preparative HPLC, the resulting 18 compounds were isolated as the S-forms in 40-70% yields. The purity of the products was determined by HPLC with evaporative light scattering detection and by (1)H and (13)C NMR. The thus obtained philanthotoxins were tested electrophysiologically for their antagonist properties on human muscle-type nicotinic acetylcholine receptors (nAChR) expressed in TE671 cells and on rat brain non-NMDA glutamate receptors (non-NMDAR) expressed in Xenopus oocytes. 4-Hydroxy analogues lacking the secondary amino groups (PhTX-12 and 4,9-dioxa-PhTX-12 and their analogues) were inactive on non-NMDAR, whereas the potency of the spermine derivatives (PhTX-343 and its analogues) increased with steric bulk of the N-acyl group. The analogue of PhTX-343 in which the N-butanoyl group was replaced by phenylacetyl group had IC(50) of 15 +/- 4 nM on non-NMDAR. Increasing the steric bulk of the N-acyl group was not advantageous for activity at nAChR, and a sharp decrease in potency with increased steric bulk was observed with the derivatives of PhTX-12. 3-Hydroxy analogues generally exhibited lower activity and different response to alterations of the N-acyl groups as compared to the 4-hydroxy analogues. Since the acyl group alterations in PhTX-343 and 4,9-dioxa-PhTX-12 have a similar effect on potency, which is distinctly different from that observed for PhTX-12, the two former compounds may bind to nAChR in a similar fashion but differently from that of PhTX-12. The combinatorial library approach described in this work represents a prototype methodology for future exploration of structure-activity relationships of philanthotoxins.

Animals↗