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Biomedical subjects

F Hansen

Publications and source records attributed to F Hansen.

At least 19 recordsLinked to original sources

Neutrophil apoptosis, activation and anti-inflammatory cytokine response in granulocyte colony-stimulating factor-treated patients with community-acquired pneumonia.

BACKGROUND: Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. OBJECTIVES: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. METHODS: Patients received a single dose of G-CSF (1 x 300 or 480 microg s.c.) prior to standard antibiotic treatment (n=8) or standard treatment only (n=8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessed using fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1 RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. RESULTS: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6+/-9.7 vs. 71.2+/-17.7, p<0.01), neutrophil apoptosis decreased (apoptosis: 1.36+/-0.27 vs. 0.2+/-0.12%, p <.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4+/-72.2 vs. 340.1+/-194.6 ng/ml, p<0.01; sTNF-p55,382+/-4,243 vs. 632+/-4,714 ng/ml, p<0.01; control group nonsignificant). These effects were not seen in the control group. CONCLUSIONS: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

Aged↗

Pulsatile wall motion (PWM) measurements after endovascular abdominal aortic aneurysm exclusion are not useful in the classification of endoleak.

UNLABELLED: The pulsatile wall motion (PWM) of AAA is reduced after endovascular stent-graft placement. The purpose of this study was to identify whether PWM after endografting was useful in the classification of endoleak. PATIENTS AND METHODS: 162 patients treated with EVAR underwent pre- and post-operative PWM assessment with ultrasonography. Follow-up was 1-9 years. 111 patients had well-excluded aneurysms, three patients had enlarging aneurysms without any recognizable endoleak (endotension), 16 had type I, 31 had type II and 1 had type III endoleak. RESULTS: The PWM was reduced from about 1mm pre-operatively to 0.24 mm post-operatively in well-excluded aneurysms. PWM remained stable during follow-up. Type I endoleak was associated with moderately reduced PWM (proximal endoleak 0.79 mm and distal 0.32 mm). PWM in patients with type II endoleak was higher (0.32 mm) post-operatively (p=0.002) compared to well-excluded aneurysms. CONCLUSION: PWM is permanently reduced after endografting. The smallest reduction in PWM was in patients with type II endoleaks. However, the overlap between the groups does not allow reliable identification of patients having endoleak with PWM-measurements.

Aged↗

Processes leading to a spatial aggregation of Echinococcus multilocularis in its natural intermediate host Microtus arvalis.

The small fox tapeworm (Echinococcus multilocularis) shows a heterogeneous spatial distribution in the intermediate host (Microtus arvalis). To identify the ecological processes responsible for this heterogeneity, we developed a spatially explicit simulation model. The model combines individual-based (foxes, Vulpes vulpes) and grid-based (voles) techniques to simulate the infections in both intermediate and definite host. If host populations are homogeneously mixed, the model reproduces field data for parasite prevalence only for a limited number of parameter combinations. As ecological parameters inevitably vary to a certain degree, we discarded the homogeneous mixing model as insufficient to gain insight into the ecology of the fox tapeworm cycle. We analysed five different model scenarios, each focussing on an ecological process that might be responsible for the heterogeneous spatial distribution of E. mulitlocularis in the intermediate host. Field studies revealed that the prevalence ratio between intermediate and definite host remains stable over a wide range of ecological conditions. Thus, by varying the parameters in simulation experiments, we used the robustness of the agreement between field data and model output as quality criterion for the five scenarios. Only one of the five scenarios was found to reproduce the prevalence ratio over a sufficient range of parameter combinations. In the accentuated scenario most tapeworm eggs die due to bad environmental conditions before they cause infections in the intermediate host. This scenario is supported by the known sensitivity of tapeworm eggs to high temperatures and dry conditions. The identified process is likely to lead to a heterogeneous availability of infective eggs and thus to a clumped distribution of infected intermediate hosts. In conclusion, areas with humid conditions and low temperatures must be pointed out as high risk areas for human exposure to E. multilocularis eggs as well.

Animals↗

Towards an international standard for PCR-based detection of foodborne thermotolerant campylobacters: interaction of enrichment media and pre-PCR treatment on carcass rinse samples.

As part of a large EU project for standardisation of polymerase chain reaction (PCR), a systematic evaluation of the interaction of enrichment media, type of DNA polymerase and pre-PCR sample treatment for a PCR detecting thermotolerant campylobacters was carried out. The growth-supporting capacity and PCR compatibility of enrichment in Preston, Mueller-Hinton and Bolton broth (blood-containing and blood-free) were evaluated. The effect of resin-based DNA extraction and DNA extraction by boiling on the final PCR assay was investigated. The time-course studies indicated that a 20-h sample enrichment in blood-containing Bolton broth, followed by a simple resin-based extraction of DNA and a PCR amplification using Tth polymerase, resulted in strong and clear PCR amplicons for target (287 bp) and internal amplification control (IAC, 124 bp). The enrichment PCR-based method, tested on 68 presumably naturally contaminated poultry-rinse samples, showed a diagnostic sensitivity of 97.5% (39 PCR-positive/40 total positive samples) and a diagnostic specificity of 100% (28 PCR-negative/28 total negative samples; P=0.32) when compared to a standard bacteriological method (ISO 10272).

Animals↗

Validation of a PCR-based method for detection of food-borne thermotolerant campylobacters in a multicenter collaborative trial.

A PCR-based method for rapid detection of food-borne thermotolerant campylobacters was evaluated through a collaborative trial with 12 laboratories testing spiked carcass rinse samples. The method showed an interlaboratory diagnostic sensitivity of 96.7% and a diagnostic specificity of 100% for chicken samples, while these values were 94.2 and 83.3%, respectively, for pig samples.

Animals↗

G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils.

In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects.

Analysis of Variance↗

Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension.

PURPOSE: To investigate retrobulbar blood flow velocities and the effects of topical timolol treatment in eyes with newly detected, previously untreated open angle glaucoma or ocular hypertension. METHODS: Fifteen eyes with open angle glaucoma (OAG) and 12 eyes with ocular hypertension (OH), in the same number of patients, all untreated and newly detected, were examined with colour Doppler imaging of retrobulbar vessels before and after 1 month of topical timolol treatment (0.5% Timoptic BID). RESULTS: Baseline central retinal artery end diastolic velocity was lower (48%, p=0.0002) and resistive index higher (7.6%, p=0.018) in the OAG group than in the OH group. In the glaucoma group mean end diastolic velocity increased by 41%, (p=0.006) while resistive index decreased by 5.8%, (p=0.02) on treatment, while no significant changes were seen in the OH group. Blood flow velocities in the ophthalmic artery did not change with treatment. Baseline IOP and IOP reduction did not differ between OAG and OH group. CONCLUSION: Peripheral resistance to blood flow was found to be increased in untreated glaucoma eyes as compared to a similar group of eyes with ocular hypertension. Timolol treatment diminished resistance significantly in the glaucoma group, but not in the ocular hypertension group. Thus the two groups responded differently to timolol treatment. The reaction to IOP lowering treatment could indicate defective autoregulation in the glaucoma group.

Adrenergic beta-Antagonists↗

Dual modulation of UFT with leucovorin and hydroxyurea in metastatic colorectal cancer.

The aim of the study was to investigate the possibility of dual modulation of UFT with leucovorin and hydroxyurea in a phase II trial of metastatic colorectal cancer. A total of 77 patients with measurable disease were included. UFT (300 mg/m2) was given with a fixed dose of 1-leucovorin (22.5 mg daily) and hydroxyurea (0.5 g daily) for 28 days followed by a 7 days' rest period. Treatment continued until progression or unacceptable toxicity. Sixty-three patients were evaluable for response. One patient (1.6%) had a complete remission and 13 (20.6%) a partial response for an overall response rate of 22.2%. The treatment was well tolerated. No significant bone marrow depression occurred. Grade 2 gastrointestinal toxicity was recorded in 28.5% of the patients, and grade 3 in 12.9%. The median time to progression was 6.8 months and the median crude survival was 11 months. In conclusion, hydroxyurea did not appear to increase either the response rate or the toxicity. Phase III trials along the same line cannot be recommended.

Adult↗

Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia.

BACKGROUND: In the host defence of the lung neutrophils (PMN) play a central role. Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory effects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra). METHODS: Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours. Release of IL-1ra, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNFalpha), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA. RESULTS: The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl. There was a significant correlation between the release of anti-inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours. Additional in vitro experiments showed that co-incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release. CONCLUSION: These results indicate that PMN may be responsible for the increase in anti-inflammatory cytokines in CAP. Strategies to increase neutrophil counts may exert beneficial effects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response.

Adult↗

Decreased apoptosis and increased activation of alveolar neutrophils in bacterial pneumonia.

STUDY OBJECTIVES: The central role of apoptosis in the regulation of lung inflammation is increasingly recognized. The aim of this study was to determine the parameters of cell activation and apoptosis on neutrophils from the circulation and the pulmonary compartment in patients with community-acquired pneumonia (CAP), and to assess the role of the Fas system and of complement-regulating molecules in this context. DESIGN AND METHODS: The study population consisted of nine patients with CAP (group 1) and six age-matched control patients without evidence of bronchopulmonary inflammation (group 2). Apoptosis rate and expression of CD11b, CD16, CD55, CD59, CD95, and CD114 surface molecules on systemic and bronchoalveolar neutrophils were assessed ex vivo using fluorescence-activated cell sorter analysis. RESULTS: In patients with CAP, we found a significant decrease of the mean apoptosis rate in pulmonary neutrophils compared to systemic neutrophils, without concomitant changes in Fas expression. In contrast, cell activation markers were significantly increased on pulmonary cells (CD11b, 288 +/- 98.2 relative mean fluorescence intensity [rMFI] vs 53.8 +/- 10.8 rMFI on peripheral cells), and similar changes were observed with respect to the expression of complement-regulating molecules. Pulmonary polymorphonuclear neutrophils of the control group showed analogous changes, compared to systemic neutrophils, but a significantly higher rate of apoptosis and a lower increase of activation-marker expression were found, compared to pulmonary neutrophils of patients with pneumonia. CONCLUSIONS: Pulmonary neutrophils from patients with CAP show a decreased rate of apoptosis and increased activation status in the alveolar compartment, which may be important for effective control of pulmonary inflammation.

Adaptor Proteins, Signal Transducing↗

Pressure-flow studies: short-time repeatability.

The within and between examination variation in selected test parameters and test results in repeated pressure-flow studies was determined in a prospective study of consecutive pressure-flow examinations in 22 patients. The patients were pressure-flow tested twice within a month. Furthermore, it was evaluated whether there was a systematic change in the measured parameters during retesting. By using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. Within and between examination variations in classification were evaluated. We found a systematic variation in P(det.Qmax) during testing, which in the absence of statistically significant systematic variations in P(det.Close) and Qmax, indicates a physiological effect of repeated pressure-flow studies, resulting in a less-obstructed second voiding. Supporting this, we found that all patients who changed group of classification of bladder outlet obstruction in the first examination shifted to a group of less obstruction, as did 66% of the patients who changed group of classification of bladder outlet obstruction in the second examination. Still, 80, respectively 85%, of the patients remained in the same group of classification of bladder outlet obstruction during retesting in the first and second examinations, respectively. Classifying the degree of bladder outlet obstruction by Qmax, P(det.Qmax), and P(det.Close) 85% of the patients reproduced their test results accurately in both examinations and taking only the first voiding in both examinations into account 95% reproduced their test results.

Aged↗

Human ocular vasodynamic changes in light and darkness.

PURPOSE: To determine whether changes in the retinal blood flow in light and darkness occur in humans. METHODS; The systolic and diastolic flow velocities were measured by color Doppler in the ophthalmic and the central retinal arteries in 12 healthy individuals in light and darkness. RESULTS: In the ophthalmic artery there was a trend toward lower systolic velocity in darkness compared with that in the light, but there was no change in diastolic velocity. In the central retinal artery the systolic and the diastolic flow velocities were markedly increased in darkness. After re-exposure to light the systolic flow velocity decreased. CONCLUSIONS: Darkness is associated with increased blood flow velocity in the central retinal artery, probably reflecting increased retinal metabolic demands by the photoreceptors.

Adult↗

Transurethral microwave thermotherapy for treatment of benign prostatic hyperplasia: results obtained with the Prostalund device.

The 6-month results of treatment with transurethral microwave thermotherapy (Prostalund) of 28 patients with lower urinary tract symptoms (LUTS) due to benign hyperplasia of the prostate are reported. The median International Prostate Symptom Score (I-PSS) fell from 16.5 (range 9-33) to 10.5 (range 3-30; P < 0.00005). Quality-of-life assessment improved from a median value of 4 (range 2-6) to 2 (range 1-5; P = 0.0001). In the Danish Prostate Symptom Score (DAN-PSS) the median total score fell from 20 (range 5-55) to 5 (range 0-43; P = 0.001). The median peak urinary flow increased from 10.6 to 11.5 ml/s (P = 0.20). Pressure-flow studies revealed no decrease in the median detrusor pressure at peak uroflow (PdetQmax) from 56 cmH2O preoperatively to 56 cmH2O after 6 months (P = 0.36). No change was found in postvoid residual urinary volume or in the calculated prostate volume. Complications included hematuria in most patients, urinary tract infections in 6 (21.4%) patients, and transient retention in 3 (10.7%) patients. In all, 20 (71.4%) patients responded to treatment with good symptomatic relief, but only minor changes were observed in urodynamic parameters.

Aged↗

Early T-cell apoptosis and Fas expression during antiretroviral therapy in individuals infected with human immunodeficiency virus-1.

Several lines of evidence suggest that Fas-mediated apoptosis is involved in the CD4 T-cell depletion in human immunodeficiency virus-1 (HIV-1) infection. To investigate this, we studied changes in peripheral blood, early T-cell apoptosis and Fas expression after initiation of antiretroviral therapy (ART) in 18 HIV-1-infected individuals. Flow cytometric analysis was performed with Apostain and CD4, CD8 and Fas staining. Fas expression was quantified by standardized beads. The levels of CD4 and CD8 T cells with early apoptosis were increased comparably in HIV-1-infected individuals. Despite elevated CD4 T cell counts, no decline in early T-cell apoptosis could be detected during the first 8 weeks of ART. However, after 26 weeks of ART in five patients that showed a sustained reduction of viral replication there was a marked decrease in T cells with features of early apoptosis. No difference was found for Fas expression on early apoptotic T cells. Fas expression on CD4 and CD8 T cells was reduced after initiation of ART; this was independent of the CD4 T-cell trend and indicates that the immediate CD4 T-cell expansion during ART is probably not the result of a decreased rate of early apoptosis among peripheral blood CD4 T cells. However, preliminary data imply a long-term reduction of early T-cell apoptosis and Fas expression in patients who show a sustained reduction of viral replication.

Adult↗

Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers.

Granulocyte colony-stimulating factor (G-CSF) has immunomodulating properties that could be beneficial for adjunctive treatment of severe infections. Cytokine release from stimulated whole blood and expression of neutrophil surface and apoptosis markers in response to G-CSF were studied in human volunteers under physiologic conditions and after ethanol pretreatment. Levels of interleukin (IL)-1 receptor antagonist and soluble tumor necrosis factor (TNF) receptor-1 were significantly increased after G-CSF, whereas TNF-alpha and IL-10 concentrations were reduced, and IL-1beta and IL-8 remained unchanged. There was a significant inhibition of neutrophil apoptosis and increased expression of complement regulatory protein CD55 without changes in CD11b, CD14, and CD59 expression. These effects were well preserved after ethanol pretreatment, which per se led to an increase in apoptosis and decreased CD55 expression. Thus, G-CSF treatment was associated with a reduction of the proinflammatory cytokine response and enhanced neutrophil survival in vivo, suggesting a therapeutic potential of G-CSF for severe infections in the nonneutropenic host.

Adult↗

Comparison of rhG--CSF primed bone marrow and blood stem cell autografts: an analysis of engraftment in malignant lymphomas and solid tumours.

Many studies have documented faster engraftment after transplantation with peripheral blood stem cells (PBSC) compared to bone marrow (BM) stem cells. Most comparisons, however, have been between unprimed BM and primed PBSC. We have collected engraftment data on 39 patients from 4 Danish centres and compared G-CSF primed BM with G-CSF primed PBSC in malignant lymphoma and solid tumours. In the lymphoma group 6 BM transplants were compared with 8 PBSC transplants, whereas in the testicular cancer group 16 BM transplants were compared with 9 PBSC transplants. In the lymphoma group, the time to platelet engraftment (platelets >20x10(9)/l unsupported) was median 15 d in PBSC transplants and median 34 d in BM transplants (p=0.003). In the solid tumour patients the difference in time to platelet engraftment was 11 and 18 d in PBSC and BM transplants, respectively (p<0.0001). In an attempt to explain this difference we performed CD34+ subset analysis of BM and PBSC. This analysis revealed a higher content of lineage restricted cells (CD34+CD61+ and CD34+GlyA+) in PBSC compared to BM. In conclusion, G-CSF mobilized PBSC seems to result in faster engraftment than G-CSF primed BM, which could be explained by an increased number of lineage specific progenitors in PBSC compared to BM.

Adolescent↗

Accuracy of noninvasive ultrasonic volume measurements on human kidney transplants. Presentation of a new formula.

PURPOSE: To evaluate the precision in volume measurement on human kidney transplants with the aid of noninvasive ultrasonic technique. MATERIAL AND METHODS: A Philips P700 ultrasound machine was used for noninvasive volume determination of 28 porcine kidneys compared to plethysmography. Also, the volume of 46 human transplanted kidneys in situ were measured by ultrasound. Since the configuration of the two types of kidneys differed, a new formula for volume measurement, suitable for kidney transplants, was developed with the aid of clay model experiments. RESULTS: With the standard ellipsoid formula the accuracy of ultrasonic volume determination of the porcine kidneys was good compared with plethysmography, with intra- and interobserver variability of 10.9 and 9.2%, respectively. However, since the width and depth in relation to length of the transplanted kidneys were greater than in the porcine ones (55 vs. 47.5% and 54 vs. 28%, p < 0.01), a new ellipsoid formula was created (r = 1.0, p < 0.0001). CONCLUSION: Noninvasive ultrasonic kidney volume measurements show an acceptable reproducibility (CV 10%). Since the previously used formula for calculating kidney volume was inaccurate on human kidney transplants, a new and accurate ellipsoid formula fitting for human transplanted kidneys is suggested.

Adult↗