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O Christensen

Publications and source records attributed to O Christensen.

At least 19 recordsLinked to original sources
PubMed2001

Binding and repair of mismatched DNA mediated by Rhp14, the fission yeast homologue of human XPA.

Rhp14 of Schizosaccharomyces pombe is homologous to human XPA and Saccharomyces cerevisiae Rad14, which act in nucleotide excision repair of DNA damages induced by ultraviolet light and chemical agents. Cells with disrupted rhp14 were highly sensitive to ultraviolet light, and epistasis analysis with swi10 (nucleotide excision repair) and rad2 (Uve1-dependent ultraviolet light damage repair pathway) revealed that Rhp14 is an important component of nucleotide excision repair for ultraviolet light-induced damages. Moreover, defective rhp14 caused instability of a GT repeat, similar to swi10 and synergistically with msh2 and exo1. Recombinant Rhp14 with an N-terminal hexahistidine tag was purified from Escherichia coli. Complementation studies with a rhp14 mutant demonstrated that the tagged Rhp14 is functional in repair of ultraviolet radiation-induced damages and in mitotic mutation avoidance. In bandshift assays, Rhp14 showed a preference to substrates with mismatched and unpaired nucleotides. Similarly, XPA bound more efficiently to C/C, A/C, and T/C mismatches than to homoduplex DNA. Our data show that mismatches and loops in DNA are substrates of nucleotide excision repair. Rhp14 is likely part of the recognition complex but alone is not sufficient for the high discrimination of nucleotide excision repair for modified DNA.

Base Pair Mismatch↗
PubMed2000

Frequency analysis of autoreactive T-helper 1 and 2 cells in bullous pemphigoid and pemphigus vulgaris by enzyme-linked immunospot assay.

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are autoimmune bullous skin diseases mediated by autoantibodies against adhesion molecules of the skin. Previous studies have identified autoreactive T cells in patients with BP and PV, which may be critical in providing B-cell help for autoantibody production. OBJECTIVES: To evaluate the frequency of autoreactive T-helper (Th) 1 and Th2 cells in patients with BP (n = 7) or PV (n = 1) and in healthy controls (n = 11). METHODS: In an enzyme-linked immunospot (ELISPOT) assay, microtitre plates were coated with antihuman interleukin (IL)-5 IgG or antihuman interferon (IFN)-gamma IgG prior to culturing human peripheral blood lymphocytes (PBL) with BP180 or desmoglein (Dsg) 3 proteins for 7 days. Cytokine-producing autoreactive T cells were visualized as spot-forming units. RESULTS: One BP patient with extensive blisters had 5.1 +/- 1.5 (mean +/- SD) BP180-reactive Th1 cells and 2.9 +/- 1.5 Th2 cells per 105 PBL. In contrast, PBL from six BP patients in remission or on immunosuppressive therapy did not form IFN-gamma- or IL-5-producing spots per </= 5 x 105 PBL. The patient with oral PV had 4.7 +/- 2.4 Th1 cells and 3.0 +/- 0.4 Th2 cells per 105 PBL and a vigorous PBL response to Dsg3. In addition, three of 10 controls had BP180-reactive Th1 (2.7-13.8 per 105 PBL) and Th2 (0.3-1.8 per 105 PBL) cells and one control had 9.0 +/- 0.7 Th1 cells and 1.1 +/- 0.8 Th2 cells per 105 PBL, with reactivity to Dsg3. ELISPOT reactivity correlated with 3H-thymidine incorporation in six of seven patients and controls with autoreactive T-cell responses. CONCLUSIONS: The ELISPOT assay seems to be promising for the quantitative and qualitative analysis of autoreactive T-cell responses in BP and PV.

Autoimmunity↗
PubMed2000

Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects.

Multiple myeloma (MM) is characterized by a clonal proliferation of malignant plasma cells in the bone marrow secreting a monoclonal immunoglobulin (paraprotein) with specific antigenic determinants, the idiotype (Id), which can be regarded as a tumour-associated antigen (TAA). In order to analyse the impact of a dendritic cell (DC)-based vaccine, 11 patients with advanced MM were treated with CD34 stem cell-derived dendritic cells that were pulsed with Id peptides. Subsequently, the patients received three boost immunizations every other week with a combination of Id and granulocyte-macrophage colony-stimulating factor (GM-CSF) (nine patients) or with Id peptide-pulsed dendritic cells again (two patients). The treatment was well tolerated with no side-effects. The present clinical study was a proof of concept analysis of dendritic cell-based vaccines in MM. The capacity of the dendritic cells to activate idiotype-specific T cells was verified by in vitro stimulation experiments before the vaccination therapy. Immunological effects of the Id vaccination were analysed by monitoring changes in anti-idiotype antibody titres and idiotype-specific T-cell activity. After vaccination, three out of 10 analysed patients showed increased anti-idiotype antibody serum titres, indicating the induction of an idiotype-specific humoral immune response. The idiotype-specific T-cell response analysed by ELISpot was increased in four out of 10 analysed patients after vaccination, and one patient had a decreased plasma cell infiltration in the bone marrow. In conclusion, five out of 11 patients showed a biological response after vaccination. Thus, our data indicate that immunotherapy with Id-pulsed DCs in MM patients is feasible and safe. DC generated from CD34+ progenitor cells can serve as a natural adjuvant for the induction of clinically relevant humoral and cellular idiotype-specific immune responses in patients suffering from advanced MM.

Adult↗
PubMed2000

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.

Administration, Topical↗
PubMed1999

[Fatal poisoning with Letigen].

The anorexic agent Letigen, which contains 200 mg coffeine and 20 mg ephedrine, has been extensively used during the last decade. The case report describes a 19 year-old woman who ingested 50 Letigen tablets in a suicidal attempt. She developed severe toxic manifestations from the heart, CNS, muscles, liver and kidneys leading to several cardiac arrests, and died subsequently of cerebral oedema and incarceration on the fourth day of hospitalization. Because of the potentially life-threatening intoxication following an overdose, prescription of Letigen must be carefully administered.

Adult↗
PubMed1999

Expression and a role of functionally coupled P2Y receptors in human dendritic cells.

We investigated the physiology and function of P2Y receptors expressed in human dendritic cells (DCs) differentiated in vitro from CD14+ cells (DC-14). These were obtained after a 10 day stimulation period in GM-CSF, IL-4 and monocyte conditioned medium. DC-14 were found to express high amounts of MHC class II, B7, CD40 as well as CD83. The functional analysis, using single cell Ca2+ imaging, demonstrated the expression of at least three subtypes of P2Y receptors. We further found using patch-clamp measurements that ATP evoked a pertussis toxin insensitive non-selective cation current with a peak current amplitude of -276+/-43 pA (holding potential -80 mV, n = 23). This current was not Ca(2+)-activated, since it was still observed under conditions of high intracellular Ca2+ buffering and could be blocked by Gd3+ (0.5 mM). In addition, intracellular application of GTP-gamma-S (0.3 mM) also activated the current. Interestingly, DC-14 redirected the orientation of their dendrites as well as cell shape towards a pipette containing ATP as observed with time lapse microscopy. These data suggest that in human DCs, ATP acts via P2Y receptors and induces chemokine effects.

Adenosine Triphosphate↗
PubMed1996

[Adverse effects of selective serotonin uptake inhibitors. Hyponatremia caused by Schwartz-Bartter syndrome].

This report describes three cases of hyponatraemia/syndrome of inappropriate secretion of antidiuretic hormone. The cases are most likely caused by treatment/intoxication with three different selective serotonin reuptake inhibitors: Fluoxetine, paroxetine and citalopram. All three patients were elderly women (75-83 years). Serum sodium values returned to normal or near normal after discontinuation of the drug and concomitant fluid restriction. Hyponatraemia has previously been described as an adverse effect to fluoxetine and paroxetine, but not to citalopram.

Aged↗
PubMed1996

Effects of thoracic epidural analgesia on pulmonary function after coronary artery bypass surgery.

OBJECTIVE: A substantial reduction in lung volumes and pulmonary function follows cardiac surgery. Pain may prevent effective breathing and coughing, and as thoracic epidural analgesia may reduce postoperative pain, we investigated the effect of epidural analgesia on pulmonary function. METHODS: Fifty-four male patients, under 65 years and with an ejection fraction of more than 0.5, were randomized into two groups: a control group receiving high-dose fentanyl anaesthesia and an epidural group receiving low-dose fentanyl anaesthesia + thoracic epidural analgesia. Time to awakening and time to extubation were recorded. Further, spirometric data, arterial oxygenation, pulmonary shunt, haemodynamics, use of vasoactive drugs and fluid balance were followed for up to 6 days postoperatively. RESULTS: Patients with low-dose fentanyl and epidural analgesia awoke (1.6 vs 3.6 h) and were extubated (5.4 vs 10.8 h) significantly earlier than control group patients. A 50-70% reduction in forced vital capacity, forced expiratory volume in 1 s (FEV1.0) and peak expiratory flow rate (PEFR) was seen after surgery, but higher FEV1.0 and PEFR on days 2 and 3 were seen in the epidural group than in the control group. Pulmonary shunt and alveolo-arterial oxygen difference increased similarly in both groups, whereas oxygen delivery and mixed venous oxygen saturation were higher in the epidural group. Epidural analgesia gave better control of the postoperative hyperdynamic circulation. CONCLUSIONS: Thoracic epidural analgesia yields a slight, but significant, improvement in pulmonary function, most likely due to a more profound postoperative analgesia.

Adult↗
PubMed1996

Analgesic effect of intraarticular morphine. A controlled, randomised and double-blind study.

BACKGROUND: Opioids produce antinociceptive effect by acting on receptors on peripheral nerves. The clinical relevance of this effect is still debated. The aim of the study was to compare the analgesic effect of morphine intraarticularly with the intramuscular route of administration after knee surgery. METHODS: Sixty-one patients, ASA 1-2, having elective arthroscopic surgery of the knee were randomised to either an intraarticular or intramuscular dose of morphine 5 mg. The pain sensation was estimated by visual analogue scale and a verbal rating score 0, 1, 2 and 4 hours postoperatively and verbal rating score on the third day. The use of acetaminophen and supplementary opioids were recorded for the first 4 hours postoperatively, from 4 hours until the third day, and from day 3 to day 7 postoperatively. RESULTS: The groups were comparable. Three patients were excluded. There were no statistically significant differences in painscore and consumption of analgesics. Fifty-nine per cent in each group had macroscopic synovitis. In the intraarticular group, there was no increased effect of morphine in the patients with synovitis compared to patients without synovitis. CONCLUSIONS: The clinical analgesic effect of 5 mg morphine given intraarticularly is equal to 5 mg morphine given intramuscularly. The occurrence of villous synovitis seems to be of no clinical importance concerning the local effect of morphine.

Adult↗
PubMed1995

Effects of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass surgery.

OBJECTIVE: A possible influence of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass grafting was investigated. DESIGN: The study was prospective and randomized. SETTING: The study was performed in a university hospital. PARTICIPANTS: Thirty male patients less than 65 years of age and with ejection fraction greater than 0.5 participated. They were randomized into 3 groups: the high fentanyl (HF) group receiving high-dose fentanyl (55 micrograms/kg) anesthesia, the HF + thoracic epidural analgesia (TEA) group receiving the same general anesthesia plus thoracic epidural analgesia, and the low-fentanyl (LF) + TEA group receiving low-dose fentanyl (15 micrograms/kg) anesthesia plus thoracic epidural analgesia. INTERVENTIONS: A thoracic epidural catheter, a peripheral and central venous catheter, a radial artery catheter, a thermodilution pulmonary artery catheter, and a coronary sinus reverse thermodilution catheter were inserted. MEASUREMENTS AND MAIN RESULTS: Coronary circulatory parameters, myocardial oxygenation, and myocardial substrate utilization were investigated before bypass and for 9 hours after bypass. Before bypass, the most striking finding was a reduction in myocardial lactate extraction in all groups, but also coronary flow and myocardial oxygen consumption decreased compared with baseline. After bypass, the only significant finding was a lower coronary vascular resistance early postoperatively in the epidural groups, but coronary blood flow was adequate in all groups. Myocardial metabolism was essentially unchanged both with and without epidural analgesia after bypass. CONCLUSION: With regard to the coronary circulation and myocardial metabolism, no hard data supporting the use of thoracic epidural analgesia in coronary artery bypass grafting were found.

Aged↗
PubMed1995

Suspected scaphoid fractures. Can we avoid overkill?

Among 231 patients with clinical signs of a fractured carpal scaphoid but negative primary radiographs, only 3 fractures of the scaphoid were finally diagnosed on subsequent radiological and clinical examinations. Two of these could be seen retrospectively in the primary radiographs. After an observation period of two to three weeks in dorsal plaster casts, 88.8% of the patients were discharged from the outpatient department as having soft-tissue injuries. They required no further treatment. This "overkill" is unsatisfactory, as we agree with other studies that almost 100% of factual fractures of the scaphoid bone are visible on initial radiographs of good quality, using 4 or 5 different views and evaluated by a senior radiologist. We propose a more stringent clinical inclusion into the category of "clinical scaphoid fracture" and the use of simple supportive bandages in an observation period.

Adolescent↗
PubMed1994

Thoracic epidural analgesia in aortocoronary bypass surgery. I: Haemodynamic effects.

Tachycardia and hypertension may cause myocardial ischaemia in patients with coronary heart disease going through major surgery. Thoracic epidural analgesia (TEA) has been reported to be beneficial in this situation. The haemodynamic effects of TEA in aortocoronary bypass surgery were investigated in 30 male patients < 65 years old and with ejection fraction > 0.5. They were randomized into 3 groups: the high dose fentanyl (HF) group receiving high-dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group receiving the same fentanyl dose+TEA with 10 ml bupivacaine 5 mg.ml-1 followed by 4 ml every hour, and the low dose fentanyl (LF) + TEA group receiving low-dose fentanyl (15 micrograms.kg-1) anaesthesia+TEA. Haemodynamic parameters, the use of vasoactive and inotropic drugs and fluid balance were followed during the operation and for 20 h postoperatively. Before bypass the only significant difference between groups was a higher mean pulmonary arterial pressure in the HF+TEA group and a lower systemic vascular resistance (SVR) in the LF+TEA group, both compared to the HF group. 89% of epidural group patients needed small doses of ephedrine whereas more HF group patients were given nitroglycerine. During bypass SVR and mean arterial pressure (MAP) were significantly higher and pump flow lower in the HF group compared to the LF+TEA group. More ketanserin to HF group patients and methoxamine to epidural group patients were given. After bypass heart rate increased in all groups. Lower MAP 0.5 h after bypass and higher filling pressures in the early post bypass period in the epidural groups, most pronounced in the HF+TEA group, were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗
PubMed1994

Thoracic epidural analgesia in aortocoronary bypass surgery. II: Effects on the endocrine metabolic response.

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may-in part-be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS). Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group with the same fentanyl dose+TEA with 10 ml bupivacain 5 mg.ml-1, followed by 4 ml every hour, and the LF+TEA group receiving fentanyl 15 micrograms.kg-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively. A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and cortisol was noticed in all groups, but the increase was delayed in the epidural groups. Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.

Analgesia, Epidural↗
PubMed1993

[The circulating occupational medical record in the county of Roskilde].

The aim of the circulating occupational medical record (COMR) is to coordinate activities and documents concerning the patient who has an occupational disease. This new case record belongs to the patient, which solves the problems concerning the professional secrecy of the involved authorities. The general practitioner, the trade union and amongst others the safety organisation of the work place all have their own schematic pages in the record. The number and use of COMRs were studied. Postal questionnaires were sent to the primary users of the COMRs. Altogether 345 COMRs were started over the two year period 1989-1991. Two hundred and ninety-eight COMRs were evaluable. The page of the general practitioner was used in 90% of the records, versus 64% in the case of the unionpage and 21% in the case of the safety organisation. In 78% there were documents from medical specialists, psychologists or physiotherapists. The majority of the documents were from the department of occupational medicine. In half of the COMRs there were documents from more than four different sources. Only 76% of the patients were referred to the department of occupational medicine. It is recommended that the COMR should be extended to the whole country.

Denmark↗
PubMed1993

The influence of thoracic epidural analgesia alone and in combination with general anesthesia on cardiovascular function and myocardial metabolism in patients receiving beta-adrenergic blockers.

Thoracic epidural analgesia combined with chronic beta-adrenergic blocker medication may cause cardiac depression. We investigated the cardiovascular and myocardial metabolic effects of a T1-T12 epidural block in 18 patients (age < 65 yr, ejection fraction > 0.5), receiving chronic beta-adrenergic blocker medication and scheduled for aortocoronary bypass surgery. After randomization into a light or deeper general anesthetic group, the cardiovascular and myocardial metabolic effects of a subsequent general anesthesia induction were investigated. Thoracic epidural analgesia induced a moderate decrease in mean arterial pressure, coronary perfusion pressure, free fatty acids, and myocardial consumption of free fatty acids. General anesthesia with thiopental (2-4 mg/kg) and a low fentanyl dose (5 micrograms/kg) increased heart rate, coronary perfusion pressure, and coronary vascular resistance, whereas mean pulmonary arterial pressure and pulmonary capillary wedge pressure decreased. After thiopental (2-4 mg/kg) and a high fentanyl dose (30 micrograms/kg), mean arterial pressure and left ventricular stroke work index decreased. We conclude that a T1-T12 epidural block in well sedated, beta-adrenergic blocked patients does not induce clinically significant cardiovascular effects. Induction of general anesthesia was well tolerated, but the light general anesthetic could not prevent an increase in heart rate and coronary vascular resistance, whereas the deeper anesthetic induced slight myocardial depression. No effect on the atrioventricular conduction, as measured by the PQ-time, was noted.

Adrenergic beta-Antagonists↗
PubMed1992

Cell swelling activates K+ and Cl- channels as well as nonselective, stretch-activated cation channels in Ehrlich ascites tumor cells.

Cell-attached patch-clamp recordings from Ehrlich ascites tumor cells reveal nonselective cation channels which are activated by mechanical deformation of the membrane. These channels are seen when suction is applied to the patch pipette or after osmotic cell swelling. The channel activation does not occur instantaneously but within a time delay of 1/2 to 1 min. The channel is permeable to Ba2+ and hence presumably to Ca2+. It seems likely that the function of the nonselective, stretch-activated channels is correlated with their inferred Ca2+ permeability, as part of the volume-activated signal system. In isolated inside-out patches a Ca(2+)-dependent, inwardly rectifying K+ channel is demonstrated. The single-channel conductance recorded with symmetrical 150 mM K+ solutions is for inward current estimated at 40 pS and for outward current at 15 pS. Activation of the K+ channel takes place after an increase in Ca2+ from 10(-7) to 10(-6) M which is in the physiological range. Patch-clamp studies in cell-attached mode show K+ channels with spontaneous activity and with characteristics similar to those of the K+ channel seen in excised patches. The single-channel conductance for outward current at 5 mM external K+ is estimated at about 7 pS. A K+ channel with similar properties can be activated in the cell-attached mode by addition of Ca2+ plus ionophore A23187. The channel is also activated by cell swelling, within 1 min following hypotonic exposure. No evidence was found of channel activation by membrane stretch (suction). The time-averaged number of open K+ channels during regulatory volume decrease (RVD) can be estimated at 40 per cell. The number of open K+ channels following addition of Ca2+ plus ionophore A23187 was estimated at 250 per cell. Concurrent activation in cell-attached patches of stretch-activated, nonselective cation channels and K+ channels in the presence of 3 mM Ca2+ in the pipette suggests a close spatial relationship between the two channels. In excised inside-out patches (with NMDG chloride on both sides) a small 5-pS chloride channel with low spontaneous activity is observed. The channel activity was not dependent on Ca2+ and could not be activated by membrane stretch (suction). In cell-attached mode single-channel currents with characteristics similar to the channels seen in isolated patches are seen. In contrast to the channels seen in isolated patches, the channels in the cell-attached mode could be activated by addition of Ca2+ plus ionophore A23187.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Patency of the internal mammary artery used as sequential graft.

In 28 patients with the left internal mammary artery (IMA) used as a sequential coronary artery graft, clinical and angiographic evaluation was made 19-47 months postoperatively. Patency was 96% in the proximal anastomoses and 93% in all the anastomoses. Angiography, however, showed optimal function in only 75% of the distal graft ends. These observations indicate that routine use of left IMA as a sequential graft should be restricted to experienced surgeons. Clinical and angiographic findings did not always correlate, emphasizing that evaluation of IMA-graft patency should include angiography.

Adult↗