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Sorensen B.S.,Aarhus University Hospital | Knudsen A.,Aarhus University Hospital | Wittrup C.F.,Aarhus University Hospital | Nielsen S.,Aarhus University Hospital | And 7 more authors.
Radiotherapy and Oncology

Background and purpose A 15-gene hypoxia profile has previously demonstrated to have both prognostic and predictive impact for hypoxic modification in squamous cell carcinoma of the head and neck. This gene expression profile may also have a prognostic value in other histological cancer types, and could potentially have a function as a universal hypoxia profile. The hypoxia induced upregulation of the included genes, and the validity of the previously used reference genes was established in this study, in a range of different cell lines representing carcinomas of the prostate, colon, and esophagus. Materials and methods Eleven adenocarcinoma and one squamous cell lines: Six colon carcinomas (HTC8, HT29, LS174T, SW116, SW948 and T48), 3 prostate carcinomas (LNCaP, DU-145 and PC-3) and 3 esophagus carcinoma cell lines (OE19, OE21 and OE33) were cultured under normoxic or hypoxic conditions (0% O2) for 24 hours. Total RNA was extracted and gene expression levels measured by qPCR. For each tissue type, individual reference genes were selected and applied in the normalization of the relative expression levels. Results In all three tissue types, individual, optimal, reference genes were selected. In the analysis of the hypoxia induced genes, both the original reference genes and the new selected reference genes were used. There was no significant difference in the obtained data. The gene expression analysis demonstrated cell line specific differences in the hypoxia response of the 15 genes, with BNIP3 not being upregulated at hypoxic conditions in 3 out of 6 colon cancer cell lines, and ALDOA in OE21 and FAM162A and SLC2A1 in SW116 only showing limited hypoxia induction. Furthermore, in the esophagus cell lines, the normoxic and hypoxic expression levels of LOX and BNIP3 were below the detection limit in OE19 and OE33, respectively. However, a combined analysis of the 15 genes in both adenocarcinoma cell lines and squamous carcinoma cell lines demonstrated a very consistent expression pattern in hypoxic induced gene expression across all cell lines. Conclusion This study addressed the tissue type dependency of hypoxia induced genes included in a 15-gene hypoxic profile in carcinoma cell lines from prostate, colon, and esophagus cancer, and demonstrated that in vitro, with minor fluctuations, the genes in the hypoxic profile are hypoxia inducible, and the hypoxia profile may be applicable in other sites than HNSCC. © 2015 Elsevier Ireland Ltd. Source

Norsk P.,NASA | Norsk P.,Copenhagen University | Asmar A.,Copenhagen University | Damgaard M.,Koege Hospital | Christensen N.J.,Herlev University Hospital
Journal of Physiology

Key points: Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure. It is unclear whether these changes persist throughout months of flight. Here, we show that cardiac output and stroke volume increase by 35-41% between 3 and 6 months on the International Space Station, which is more than during shorter flights. Twenty-four hour ambulatory brachial blood pressure is reduced by 8-10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space. It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station. Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1-2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± se) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further. © 2014 The Physiological Society. Source

Paarup H.M.,University of Southern Denmark | Baelum J.,University of Southern Denmark | Holm J.W.,Koege Hospital | Manniche C.,University of Southern Denmark | Wedderkopp N.,University of Southern Denmark
BMC Musculoskeletal Disorders

Background: Musculoskeletal symptoms are common in the neck, back, and upper limbs amongst musicians. Playing-related musculoskeletal disorders have been found to range from 32% to 87% with a tendency for female musicians to have more problems than males. Studies of musculoskeletal problems in instrumentalists have generally involved pre-professional musicians or populations comprising musicians of different levels. The objective of this study was therefore to investigate the prevalence, duration and consequences of musculoskeletal symptoms in professional symphony orchestra musicians. Methods. A cross-sectional questionnaire study. The study population comprised of 441 musicians from six Danish symphony orchestras; 342 (78%) completed the questionnaire. Results: During the last year 97% of the women and 83% of the men experienced symptoms in at least one of nine anatomic regions (neck, upper and lower back, shoulders, elbows, and hands and wrists). 86% of the women and 67% of the men experienced symptoms for more than seven days, while 63% of the women and 49% of the men had symptoms for more than 30 days. Woodwind players had a lower risk for musculoskeletal symptoms and a lower risk for the consequences. Among consequences were changed way of playing, reported by 73% of the musicians, difficulty in daily activities at home, reported by 55%, and difficulty in sleeping, reported by 49%. Their health behaviour included taking paracetamol as the most used analgesic, while physiotherapists and general practitioners were reported as the most consulted health care professionals concerning musculoskeletal problems. Results regarding symptoms in six anatomic regions were compared to results for a sample of the general Danish workforce. Symptoms were more frequent in musicians and lasted longer than in the general workforce. This applied to both genders. Conclusions: Within the last year most symphony orchestra musicians experienced musculoskeletal symptoms in the neck, back or upper extremities. The symptoms impacted on their level of function in and outside work and were reflected in their health behaviour. Generally women had a higher risk than men and woodwind players a lower risk than other instrumentalists. Finally, symptoms were more frequent and lasted longer in the musicians than in the general workforce. © 2011Paarup et al; licensee BioMed Central Ltd. Source

ACE-inhibitor is an antihypertensive drug which is increasingly used to treat a wide range of medical conditions. A known adverse reaction is angio-oedema of the head and neck, which can become fatal when the upper airway is involved, causing asphyxia. We present a Caucasian man, who developed severe angio-oedema of the tongue and floor of the mouth. He was successfully treated with complement C1-concentrate causing the swelling to regress within 20 min. This treatment option can be an effective alternative to bradykinin antagonists, which might not be available in the emergency room, or more invasive measures like intubation or emergency airway puncture. Source

We report a case of acute dystonia of the face, jaw and tongue caused by metoclopramide and mimicking angioedema. The patient had attacks for several years before the correct diagnosis was made and we present the first ever published video footage of an attack. This adverse drug reaction is known, but might be underdiagnosed since it can mimic a wide range of other diseases. Source

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