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Biomedical subjects

H S Hansen

Publications and source records attributed to H S Hansen.

At least 55 records · Page 3Linked to original sources

Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.

BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low.

Asthma↗

Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia: a 31p NMR study.

Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium ethylenediaminetetraacetic acid (EDTA). The lower organic phases were isolated and evaporated to dryness under a stream of nitrogen and the lipids were redissolved in CDCl3-CH3OH-H2O 100.0:29.9:5.2 (v/v/v) for NMR analysis. Increasing the period of post-decapitative ischemia resulted in an accumulation of two signals in the NMR spectra at 0.18 and 0.22 ppm (relative to the chemical shift of 1,2-diacyl-sn-glycero-3-phosphocholine (PCDIACYL) at -0.84 ppm). These signals were identified as originating from 1,2-diacyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine (NAPEDIACYL) and 1-(1'-alkenyl)-2-acyl-sn -glycero-3-phospho-(N-acyl)-ethanolamine (NAPEPLAS), respectively, by spiking with authentic materials. Additionally, the identification was verified by thin-layer chromatography, which also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K-EDTA instead of the commonly used Cs-EDTA in the preparation of the NMR samples allowed the separation of the chemical shifts of N-acyl-ethanolamine phospholipids from those of the ethanolamine phospholipids. Moreover, the chemical shift of cardiolipin was moved from 0.15 ppm observed with Cs-EDTA to about 0.31 ppm with K-EDTA. The present study demonstrates that it is possible to detect and quantify post-decapitative accumulation of NAPE subclasses (NAPEDIACYL and NAPEPLAS) in rat brains by the use of 31P NMR spectroscopy.

Acylation↗

PLD2 complexes with the EGF receptor and undergoes tyrosine phosphorylation at a single site upon agonist stimulation.

Mammalian phospholipase D (PLD) activity becomes up-regulated when cells are stimulated by a variety of hormones, growth factors, and other extracellular signals. Two distinct PLDs, PLD1 and PLD2, have been identified. The mechanism through which each PLD is activated, however, is poorly understood. Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF). PLD2, but not PLD1, associates with the EGF receptor in a ligand-independent manner and becomes tyrosine-phosphorylated upon EGF receptor activation. Tyrosine 11 (Tyr-11) of PLD2 was identified as the specific phosphorylation site. Mutation of this residue to phenylalanine enhanced basal activity almost 2-fold, but did not alter the magnitude of the EGF-mediated increase in PLD2 activity. In conclusion, we show here for the first time agonist-stimulated activation of both PLD1 and PLD2 in vivo and provide evidence of a distinct type of interaction for each isoform with the EGF receptor. Moreover, our results suggest that agonist-induced tyrosine phosphorylation plays a role in PLD2 regulation.

Amino Acid Sequence↗

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group).

PURPOSE: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Carcinoma↗

Formation of N-acyl-phosphatidylethanolamines and N-acetylethanolamines: proposed role in neurotoxicity.

The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acylethanolamine (NAE), including anandamide, in mammals in relation to neurotoxicity is discussed. Data on the characterization of the NAPE-forming N-acyltransferase, the NAPE-hydrolyzing phospholipase D, and the NAE-hydrolyzing amidase are reviewed. We suggest that NAPE and NAE, including anandamide, are formed in neurons in response to the high intracellular calcium concentrations that occur in injured neurons, e.g. due to glutamate excitotoxicity. NAPE may have functions of its own besides being a precursor for NAE. The formation of both of these lipids may serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes, or mediated by activation of cannabinoid receptors. This suggestion implies that NAPE and NAE may have pathophysiological roles in the brain. Whether these lipids also have physiological roles is uncertain.

Amidohydrolases↗

Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study.

OBJECTIVE: To describe factors related to underdiagnosis of asthma in adolescence. DESIGN: Subgroup analysis in a population based cohort study. SETTING: Odense municipality, Denmark. SUBJECTS: 495 schoolchildren aged 12 to 15 years were selected from a cohort of 1369 children investigated 3 years earlier. Selection was done by randomisation (n = 292) and by a history indicating allergy or asthma-like symptoms in subject or family (n = 203). MAIN OUTCOME MEASURES: Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more obstructive airway abnormalities (low ratio of forced expiratory volume in 1 second to forced vital capacity, hyperresponsiveness to methacholine or exercise, or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk factors (odds ratios) for underdiagnosis. RESULTS: Undiagnosed asthma comprised about one third of all asthma identified. Underdiagnosis was independently associated with low physical activity, high body mass, serious family problems, passive smoking, and the absence of rhinitis. Girls were overrepresented among undiagnosed patients with asthma (69%) and underrepresented among diagnosed patients (33%). Among the risk factors identified, low physical activity and problems in the family were independently associated with female sex. The major symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or breathing trouble (50%) was reported less frequently than among those diagnosed. Less than one third of those undiagnosed had reported their symptoms to a doctor. CONCLUSIONS: Asthma, as defined by combined symptoms and test criteria, was seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent among girls and was associated with a low tendency to report symptoms and with several independent risk factors that may help identification of previously undiagnosed asthmatic patients.

Adolescent↗

[DAHANCA (Danish Head and Neck Cancer)--20 years of cooperation].

A review of the DAHANCA-group's projects concerning cancer of the head and neck over 20 years is presented. Apart from the first, all projects were randomized trials. Two projects with neoadjuvant chemotherapy have not shown any notable tumour control or better survival. More than 1800 patients suffering from cancer of the head and neck treated in the five oncological centres of the country were included in the three projects concerning radiosensitizers and radiotherapy. The radiation has been accelerated during the years making it more effective. Each of the three projects has improved the local control rate by 11-15% and the survival is enhanced by 11-13% for each project. Cooperation between our five oncological centres has given good results and increased the survival for patients with head and neck cancer. It is now routine to give the radiosensitizer tablets Nimorazol 1 1/2 hours before radiation and to give six fractions weekly to patients with squamous cell cancer in the supraglottic region, pharynx and oral cavity.

Carcinoma, Squamous Cell↗

Generic relationship between calcium intake and radiostrontium transfer to the milk of dairy ruminants.

The hypothesis is tested that there is a generic relationship between the calcium intake and the transfer of radiostrontium to milk which can be used for all dairy ruminants. In addition to the daily calcium intake, the relationship also requires values for the strontium to calcium observed ratio, which describes the discrimination in transfer of the two elements to milk (a value of 0.11 is used), and the calcium concentration in milk. The relationship had previously only been validated for dairy cattle as there were insufficient data for other ruminant species. Here, we present recently available data for dairy goats, and also a limited amount of data for sheep derived from the literature. From the comparison between these data and predicted values, we conclude that it is possible to derive a generic model of the transfer of radiostrontium to the milk of dairy ruminants.

Animals↗

A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85.

PURPOSE: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx. PATIENTS AND TREATMENT: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months. RESULTS: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications. CONCLUSION: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.

Adult↗

Salivary gland carcinomas: prognostic significance of simple mucin-type carbohydrate antigens.

The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin-type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have been shown to be of value in predicting prognosis for carcinomas in other locations. We studied the prognostic significance of the expression of these structures in a retrospective study of 133 patients with salivary gland carcinomas, using immunohistochemistry and a panel of well-defined monoclonal antibodies (MAbs) on formalin-fixed paraffin-embedded tissues. Sialosyl-Tn, T and sialosyl-T antigens were not correlated with prognosis. Univariate analyses showed no overall difference in survival or locoregional control between patients with Tn-positive and patients with Tn-negative tumours, but indicated that expression of the Tn antigen was associated with early locoregional recurrences and deaths. Tn was, however, not an independent prognostic factor by multivariate regression analysis.

Adult↗

Ambulatory blood pressure in 570 Danes aged 19-21 years: the Odense Schoolchild Study.

Ambulatory blood pressure (ABP) measurements were performed in a Danish population of 295 males and 275 females aged 19-21 years. Individualised day and night periods were defined from the subjects own recording of bedtime and rising on the day of their ABP measurements. During these individualised periods the ABP values for daytime, night-time and for the whole 24-h period were measured. The mean +/- s.d. values for systolic/diastolic ABP for the whole population were (124+/-11)/(70+/-7) mm Hg in the daytime, (106+/-12)/(60+/-9) mm Hg in the night-time, and (120+/-11)/(68+/-7) mm Hg in the whole 24-h period. Males had a mean systolic ABP of 9 mm Hg and mean diastolic ABP of 5 mm Hg higher than females. In males mean +/- s.d. systolic/diastolic ABP values in the daytime were (129+/-10)/(73+/-7) mm Hg, in the night-time (111+/-12)/(63+/-8) mm Hg, and in the whole 24-h period (125+/-10)/(71+/-7) mm Hg. The corresponding values in females were (119+/-10)/(68+/-6) mm Hg, (103+/-11)/(57+/-8) mmHg, and (115+/-10)/(66+/-6) mm Hg, respectively. In conclusion this study provides sex-specific normal values for ABP in a 19 to 21-year-old age group based on individualised daytime and night-time periods.

Adult↗

Salivary gland carcinomas--prognostic factors.

A retrospective study of factors of prognostic significance for clinical course and survival was performed using uni- and multivariate analyses in 251 patients with primary salivary gland carcinoma admitted during the period 1958-1992. Univariate analyses indicated that site of primary tumour, histology, clinical stage, presence of node metastases at primary diagnosis, and status of surgical margins were important prognostic factors for cause-specific survival, locoregional control and distant metastases. Multivariate analyses confirmed that histology was important for both locoregional control and cause-specific survival, whereas primary site was only of importance for locoregional control. Presence of node metastases at diagnosis was more important for locoregional control than clinical stage, whereas clinical stage was the most important factor for cause-specific survival. Status of surgical margins was of major importance for both cause-specific survival and locoregional control. Radiotherapy in addition to surgery improved locoregional control only, whereas survival was not affected.

Adolescent↗

A model of radiostrontium transfer in dairy goats based on calcium metabolism.

A model for the transfer of radiostrontium (90Sr) in dairy goats is presented. The novel feature of the model is that it is based on the current understanding of Ca metabolism and assumes that the transfer of radiostrontium is driven by Ca transfer. Previously published models of radiostrontium transfer in animals have ignored the influence of Ca metabolism. Unknown model parameters were obtained by fitting the model to data from a study of radiostrontium and Ca transfer in goats. The model accounted for 95 and 97% of the observed variation in the data for Ca (n = 22) and radiostrontium (n = 43), respectively. Unlike previously reported models, the model presented here could be applied to simulate the effect of additional dietary Ca as a countermeasure to the contamination of milk by radiostrontium under different circumstances.

Absorption↗

[Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function].

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.

Adolescent↗

Cell swelling activates phospholipase A2 in Ehrlich ascites tumor cells.

Ehrlich ascites tumor cells, loaded with 3H-labeled arachidonic acid and 14C-labeled stearic acid for two hours, were washed and transferred to either isotonic or hypotonic media containing BSA to scavenge the labeled fatty acids released from the cells. During the first two minutes of hypo-osmotic exposure the rate of 3H-labeled arachidonic acid release is 3.3 times higher than that observed at normal osmolality. Cell swelling also causes an increase in the production of 14C-stearic acid-labeled lysophosphatidylcholine. This indicates that a phospholipase A2 is activated by cell swelling in the Ehrlich cells. Within the same time frame there is no swelling-induced increase in 14C-labeled stearic acid release nor in the synthesis of phosphatidyl 14C-butanol in the presence of 14C-butanol. Furthermore, U7312, an inhibitor of phospholipase C, does not affect the swelling induced release of 14C-labeled arachidonic acid. Taken together these results exclude involvement of phospholipase A1, C and D in the swelling-induced liberation of arachidonic acid. The swelling-induced release of 3H-labeled arachidonic acid from Ehrlich cells as well as the volume regulatory response are inhibited after preincubation with GDP beta S or with AACOCF3, an inhibitor of the 85 kDa, cytosolic phospholipase A2. Based on these results we propose that cell swelling activates a phospholipase A2--perhaps the cytosolic 85 kDa type--by a partly G-protein coupled process, and that this activation is essential for the subsequent volume regulatory response.

Arachidonic Acid↗

[Patients' evaluation of coercion in a psychiatric department. Interview studies in psychiatric departments for adult patients at the Hillerød hospital].

During an 11 month period, use of coercion was prospectively registered in a psychiatric department. Of all patients who had been subjected to coercion 36% were (n = 86) interviewed subsequently. Eleven percent of the interviewed patients did not know, that they had been submitted to coercion, 22% did not know the reason and 30% did not agree with the motivation for the decision. Forty-seven percent were satisfied with the information they had been given concerning how to complain of their treatment, 50% were satisfied with their adviser and 70% were satisfied with their overall admission. Sixty-five percent accepted that there should be a law allowing the use of coercion in psychiatry.

Adult↗

[Centralized follow-up of patients treated for head and neck cancer].

In a prospective study, the value of the clinical follow-up after treatment for head and neck cancer has been assessed. A total of 407 visits in 377 patients were recorded during a three month period in 1993 at the two major radiotherapy departments in Denmark. The results showed that 61% of follow-up visits included one or more problems either related to treatment morbidity or tumour recurrence. About 50% of all visits included treatment related normal tissue problems, and 30% had problems that required intervention. Although the majority of problems occurred within a few years after treatment, 47% of patients at three to four years observation time still had one or more problems. A total of 34 new tumour recurrences were found in the period, and of these 11 (32%) were asymptomatic. It is concluded that head and neck cancer patients have both tumour and normal tissue problems several years after the end of treatment. Since effective salvage treatment improves local control significantly, early detection of possible recurrence is important. A follow-up period of four to five years is recommended-preferably by qualified experts in the management of both recurrent disease and treatment morbidity.

Centralized Hospital Services↗