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Biomedical subjects

T Nielsen

Publications and source records attributed to T Nielsen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Topographical distribution of spindles and K-complexes in normal subjects.

To assess the topographical distribution of sleep spindles and K-complexes, four 15-minute samples of stage 2 sleep in a group of eight healthy young adults were analyzed. Results show that a majority of spindles generated are detected over central regions, and that K-complexes are markedly predominant over prefrontal and frontal regions. These findings are consistent with the single-spindle generator hypothesis and raise questions concerning the Rechtschaffen and Kales rules for scoring K-complexes.

Adolescent↗
PubMed1997

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. CONCLUSIONS: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Adult↗
PubMed1997

The effect of COMT inhibition by tolcapone on tolerability and pharmacokinetics of different levodopa/benserazide formulations.

This double-blind, placebo-controlled, randomized, crossover study was designed to evaluate the effects of catechol-O-methyltransferase (COMT) inhibition by tolcapone on the pharmacokinetics of levodopa given as four different formulations of levodopa/benserazide: 50/12.5 mg, 100/25 mg, 200/50 mg (all standard release), or 100/25 mg (controlled release). Sixteen healthy volunteers, in two groups of 8, were given two different levodopa/benserazide formulations with and without tolcapone in random order on 4 days, each separated by a 7-day washout period. On each treatment day, 200 mg tolcapone or placebo (blinded) was taken orally 1 h before and 3 and 7 h after a single (unblinded) dose of levodopa/benserazide. All treatment combinations were well tolerated. Continuous inhibition of erythrocyte COMT activity by approximately 75% was observed over 13 h with tolcapone; this was unaffected by levodopa/benserazide formulation. Tolcapone had similar effects on plasma levodopa concentrations with the standard-release formulations: half-life and bioavailability increased approximately 2-fold compared with placebo, and maximum plasma concentration (Cmax) and time to Cmax (tmax) were unaffected, except for a slight increase in Cmax with the levodopa/benserazide 200/ 50 mg formulation. With the controlled-release formulation, tolcapone increased the levodopa area under the plasma concentration/time curve approximately 2-fold. Although levodopa tmax appeared delayed, the absorption phase was unaffected. Onset of levodopa effect is therefore not likely to be delayed when tolcapone is coadministered with this formulation. Regardless of levodopa/benserazide formulation, 3-O-methyldopa formation was reduced by 90% with tolcapone compared with placebo. These results show that tolcapone could potentiate the antiparkinsonian effects of levodopa independently of levodopa/benserazide formulation.

Adjuvants, Pharmaceutic↗
PubMed1997

Quantitative EEG and statistical mapping of wakefulness and REM sleep in the evaluation of mild to moderate Alzheimer's disease.

Statistical probability mapping was used to quantify and localize EEG differences between 27 patients with Alzheimer's disease (AD) and 25 age- and gener-matched controls. Differences in mean activity in four EEG frequency bands (delta, theta, alpha, beta) for wakefulness and for REM sleep were examined, t-statistic maps clearly highlighted common pattern anomalies in AD patients in the two states. More specifically, Alzheimer patients were more affected than control subjects in parieto-temporal and frontal regions. These differences were more prominent in REM sleep and consisted primarily in an increase in absolute delta and theta activities, and a decrease in absolute alpha and beta activities. Discriminant analysis, using a ratio of slow over fast frequencies, yielded a classification rate of 90.4% (sensitivity 81.5%, specificity 100%) for REM sleep. For wakefulness, the same measure allowed correct classification of 80.8% of the subjects (sensitivity 66.7%, specificity 96%).

Aged↗
PubMed1996

City air pollution of polycyclic aromatic hydrocarbons and other mutagens: occurrence, sources and health effects.

The presence of polycyclic aromatic hydrocarbons (PAH), mutagens and other air pollutants was investigated in a busy street in central Copenhagen and in a park area adjacent to the street. The winter concentration of benzo(a)pyrene was 4.4 +/- 1.2 ng/m3 in the street air and 1.4 +/- 0.6 ng/m3 in the city park. The atmospheric concentrations of PAH decreased in the order of: street > city background air approximately suburbs > village > open land. The traffic contribution of PAH to street air was estimated to be 90% on working days and 60% during weekends and its contribution to city background air was estimated to be 40%. Four different approaches to evaluate the health effects are discussed. The direct effect of PAH air pollution, and other mutagens, is considered to be a maximum of five lung cancer cases each year out of one million people.

Air Pollution↗
PubMed1996

Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects.

OBJECTIVE: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. METHODS: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio 1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone; its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. RESULTS: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long halflife of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. CONCLUSION: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson's disease.

Aged↗
PubMed1995

Cofractionation of HeLa cell replication proteins with ors-binding activity.

Ors (origin enriched sequence) 8 is a mammalian autonomously replicating DNA sequence previously isolated by extrusion of nascent monkey (CV-1) DNA in early S phase. A 186 bp fragment of ors 8 has been identified as the minimal sequence required for origin function, since upon its deletion the in vivo and in vitro replication activity of this ors is abolished. We have fractionated total HeLa cell extracts on a DEAE-Sephadex and then on a Affi-Gel Heparin column and identified a protein fraction that interacts with the 186 bp fragment of ors 8 in a specific manner. The same fraction is able to support the in vitro replication of ors 8 plasmid. The ors binding activity (OBA) present in this fraction sediments at approximately 150 kDa in a glycerol gradient. Band-shift elution experiments of the specific protein-DNA complex detect by silver-staining predominantly two protein bands with molecular weights of 146 kDa and 154 kDa, respectively. The fraction containing the OBA is also enriched for polymerases alpha and delta, topoisomerase II, and replication protein A, (RP-A).

Base Sequence↗
PubMed1994

A reproducible method for identification of human genomic DNA autonomously replicating sequences.

We demonstrate a method for the isolation of autonomously replicating sequences from pools of clones obtained from genomic DNA libraries constructed using affinity purification of cruciform DNA. The selection of autonomously replicating sequences was based on their differential ability to replicate as episomes after transfection of pools of plasmid clones into human HeLa cells. Two separate libraries containing affinity-purified cruciform DNA were used, one prepared from DNA of log phase primary human genital fibroblasts and the other prepared from DNA of log phase SW48 colon adenocarcinoma cells. Representative samples of the entire phage libraries were converted to phagemid clones by filamentous helper phage-mediated mass excision to produce pBluescript libraries in Escherichia coli. Clones were grown up individually and the bacteria pooled into groups of 48 for recovery of plasmid DNA. Plasmid pools of 48 independent clones (120 micrograms total) were then transfected by calcium phosphate coprecipitation onto log phase HeLa cells, which were allowed to grow for 3 days before recovery of plasmid by Hirt lysis. The recovery of plasmid from each transfection was estimated to range from 10 to 60 ng. DpnI digestion was then used to digest plasmids which had not been replicated and therefore retained a bacterial methylation pattern which was sensitive to digestion. We estimated from agarose electrophoresis gels that 40-200 pg of recovered plasmid DNA per transfected pool of DNA was resistant to DpnI and therefore was capable of transforming competent E. coli cells. The DpnI-resistant fraction yielded from one to seven independent clones from each pool, with genomic DNA inserts ranging in size from 0.35 to 3.4 kb.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗
PubMed1994

Heart failure therapy with cilazapril: an overview.

The efficacy and safety of cilazapril in chronic heart failure have been extensively investigated in an international clinical program in patients with underlying chronic heart failure with ischemic heart disease or dilated cardiomyopathy. Cilazapril in single doses of 1.25-5 mg produced a significant dose-dependent reduction in pulmonary capillary wedge pressure and systemic vascular resistance and a significant increase in cardiac index. In placebo-controlled studies, 1-5 mg of cilazapril once daily for 12 weeks prolonged predose exercise test duration and improved New York Heart Association classification status and signs and symptoms of chronic heart failure, including paroxysmal nocturnal dyspnea. Up to 86% of patients receiving these dosages had improvement, with only 12% of patients requiring the higher dose, 5 mg. These data indicate that cilazapril is effective when administered once daily to patients with chronic heart failure receiving concomitant therapy with digitalis and/or a diuretic. The safety of cilazapril in patients with chronic heart failure has been evaluated in 1,163 patients administered from 0.5 to 15 mg once daily for treatment periods ranging from 1 day to 57 months. Cilazapril was administered to 500 patients for at least 6 months, 264 patients for at least 1 year, and 101 patients for at least 2 years. The most frequently occurring adverse events were dizziness, coughing, dyspnea, fatigue, angina pectoris, and headache. Cilazapril was equally well tolerated by young and elderly patients. Treatment was discontinued due to adverse events in 12.9% of patients, mainly as a result of coughing (1.7%) and dizziness (1%). Forty-four patients (3.8%) died during cilazapril therapy or during a period without treatment. Of these deaths, 93% were due to cardiac causes, especially rhythm disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗
PubMed1993

[Ambulatory surgery and anesthesia. An inquiry study].

Patients who had undergone surgical procedures as out-patients in either general or local anaesthesia were asked to complete a questionnaire with the aim of evaluating how they had experienced their operation, especially with respect to treatment and prevention of postoperative pain. Over a 12 month period, 851 patients (251 men and 600 women) who had undergone either abdominal, orthopaedic or gynaecological surgery as out-patients were given the questionnaire. Five hundred and fifteen patients (166 men and 349 women), i.e. 61%, answered. Nineteen percent had had their operation performed in local or regional anaesthesia, 30% in a combination of general anaesthesia with local infiltration, the remaining patients were operated under general anaesthesia. Eighty to ninety percent were satisfied with the preoperative information, and 88% were satisfied with the anaesthesia. Sixty-nine percent had had either no pain or almost no pain within the first 24 hours after the operation. Six percent found it difficult to stay home. Sixteen percent needed some kind of medical contact. Ninety-two percent said they would prefer out-patient surgery again as opposed to hospitalization, were they to need another operation. In conclusion, we found that these types of out-patient operations were acceptable to most of our patients (92%). We recommend widespread use of local anaesthetics in combination with general anaesthesia in order to minimize postoperative pain and facilitate the effect of postoperative analgetics.

Ambulatory Surgical Procedures↗
PubMed1993

Dreaming in agenesis of the corpus callosum: laboratory and home assessment of four cases.

Laboratory and home dream recall was studied in four subjects with agenesis of the corpus callosum and in four control subjects who were matched for age, gender, and handedness. In addition, the structural and emotional content of home dreams was compared for these two groups. Results indicate that acallosal subjects recalled fewer dreams in the laboratory than did control subjects, but recalled the same number of dreams at home. They also reported more contentless dreams in both situations. Furthermore, although acallosal subjects used fewer words to describe their dream content in both contexts, the number of content categories they reported differed little from the number reported by control subjects. However, some trends were found for acallosal's home dreams to differ from those of controls, i.e. more dreams with known characters and fewer dreams with unknown characters, animals, and colours. Differences in emotional contents were few; acallosals reported more distress than controls. The shorter length of acallosals' dreams might be explained, in part, by their lower verbal IQs. Other characteristics of dream content (e.g. more distress, fewer dreams with unknown and animal characters) may reflect limited social experiences in this group. However, the greater frequency of contentless dreams and the lower frequency of dreams with colour are trends consistent with the possibility that the corpus callosum may be implicated in processes of dream production and dream recall.

Journal Article↗
PubMed1993

Decreased interhemispheric EEG coherence during sleep in agenesis of the corpus callosum.

Inter- and intrahemispheric EEG coherence was studied in 4 subjects with agenesis of the corpus callosum (ACC) and in 4 matched controls through different states of the sleep/wakefulness cycle. Interhemispheric coherence was calculated between homologous prefrontal, frontal, central, parietal and occipital electrode pairs whereas intrahemispheric coherence was calculated between all adjacent, unihemispheric electrode pairs. EEG samples were recorded from stage 2, stages 3 + 4 and stage REM sleep and the eyes closed waking state. Interhemispheric coherence measures indicated lower values for ACC subjects than for control subjects for most brain regions; the occipital cortex was least affected. These results further validate the interhemispheric coherence function as a measure of activity in the corpus callosum and suggest that occipital measures may index activity localized in the posterior commissure. Intrahemispheric coherence measures indicated very few differences between the two groups, a result consistent with the suggestion that there is no specialized intrahemispheric compensation in ACC.

Adolescent↗
PubMed1992

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia.

Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response was higher (mean optical density ratio: 0.6 vs. 0.23 and 0.2, respectively; P less than .01). Changes in antibody response were investigated in 78 patients for whom serial serum samples taken around the time of bronchoscopy were available. Of the 47 patients with verified PCP, 20 (43%) mounted an antibody response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody response to P. carinii.

Antibodies, Fungal↗