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H Hansen

Publications and source records attributed to H Hansen.

At least 37 records · Page 2Linked to original sources

4. Preliminary Findings of a Prospective Study of FDG-PET in Patients with Possible Lung Cancer.

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest CT of thorax/upper abdomen, and c) by whole-body PET (GE Advance, visual analysis). The CT and PET studies were performed within 2 weeks of admission and read blinded to all information except the chest X-ray report. The decision to refer to mediastinoscopy/thoracotomy was made by a tumor board using clinical information, CT and PET findings. In principle, suspected metastatic lesions were biopsied before surgery. The gold standard was histology from biopsy or thoracotomy, or resolution of the X-ray findings and symptoms.Results: One patient was excluded because of uncertain diagnosis. In 3 (15%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused by granuloma, pneumonia and BOOP. These nodules were only 1 to <3 cm, while malignant nodules were 2-8 cm. There were no false negative PET or CT studies.Conclusion: FDG-PET is valuable in patients suspected for pulmonary malignancy, since thoracotomy was avoided in 15% of patients and in 10% of patients more extensive disease was found which changed the chemotherapy regime.

Journal Article↗

Cytokines in aging and exercise.

Aging is associated with increased inflammatory activity. Increased plasma levels of tumour necrosis factor (TNF)-alpha were found in centenarians aged 100 years and in individuals aged 80-81 years when compared to a young control group. Plasma levels of TNF-alpha were linearly correlated to plasma levels of interleukin (IL)-6, TNF-receptors and C-reactive protein. High levels of TNF-alpha were directly related to dementia and to a low blood pressure ankle-arm index, indicating generalized atherosclerosis. In hospitalized patients with Streptococcus pneumonia infection, aging was associated with prolonged inflammatory activity. Similar results were found using an in vivo endotoxin challenge model in old versus young humans. Strenuous exercise induces increased levels in a number of proinflammatory and anti-inflammatory cytokines, naturally occurring cytokine inhibitors and chemokines. Thus, increased plasma levels of TNF-alpha, IL-1, IL-6, IL-1 receptor antagonist (IL-Ira), TNF-receptors (TNF-R), IL-10, IL-8 and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The cytokine response to strenuous exercise has similarities to the cytokine response to trauma and sepsis. Therefore, in future studies, exercise is suggested as an ethically applicable model to use in studies on mechanisms underlying the age-associated altered cytokine response.

Adult↗

Spatial risk assessment for Lyme borreliosis in Denmark.

A study of nymphal and adult Ixodes ricinus density was performed in well-defined spruce and beech forest habitats with different levels of roe deer abundance and soil water capacity. In 35 habitats, a total of 489 larvae, 1,611 nymphs and 193 adult I. ricinus ticks were collected. Tick density was found to be influenced by roe deer abundance and soil water capacity. Based on this evaluation, a model predicting increasing number of ticks with increasing roe deer abundance and soil water capacity was suggested. A total of 1,045 nymphs and 106 adult ticks were tested for infection with Borrelia burgdorferi sensu lato Of these, 53 nymphs and 6 adults were found to be infected, leading to an general infection rate of 5% and 6% for nymphs and adults, respectively. Prevalences of Borrelia burgdorferi sensu lato in nymphal I. ricinus were found to be independent of roe deer abundance and soil water capacity. The correlation between human neuroborreliosis incidence and the estimated number of I. ricinus based on roe deer abundance and soil water capacity was examined. Differences in human neuroborreliosis incidence were found to correspond with the expected spatial differences in tick density in 12 counties in Denmark.

Animals↗

Determination of metronidazole and hydroxymetronidazole in trout by a high-performance liquid chromatographic method.

A high-performance liquid chromatographic (HPLC) method based on solid phase extraction was developed for determination of metronidazole (MNZ) and its metabolite hydroxymetronidazole (MNZ-OH) in muscle and skin tissues of rainbow trout. Tinidazole (TNZ) was used as internal standard. The compounds were extracted with acetonitrile and the extract was evaporated and redissolved in a mixture of ethyl acetate and hexane (1:2). The extract was cleaned up by solid phase extraction on a silica cartridge. The extract was analysed by reverse phase gradient HPLC on a C18 column followed by ultraviolet detection at 325 nm. The limit of detection was 2.8 micrograms/kg for both compounds in muscle. The estimated limits of detection in skin tissue were 3 micrograms/kg for MNZ and 5 micrograms/kg for MNZ-OH. The mean recoveries of MNZ in muscle calculated without use of internal standard were 93% and 81% at levels of 10 micrograms/kg and 25-100 micrograms/kg respectively. The mean recovery of MNZ-OH in muscle was 79% at a level of 10-100 micrograms/kg. The mean relative repeatability standard deviations on spiked muscle tissue were 3.3% for MNZ and 3.2% for MNZ-OH at a level of 10-100 micrograms/kg. The method was applied to trout given feed containing MNZ in an aquaculture pilot plant. Residues of MNZ and MNZ-OH were detected in muscle and skin tissues shortly after the administration period but not 3 weeks later.

Animals↗

Auxin-induced ethylene triggers abscisic acid biosynthesis and growth inhibition.

The growth-inhibiting effects of indole-3-acetic acid (IAA) at high concentration and the synthetic auxins 7-chloro-3-methyl-8-quinolinecarboxylic acid (quinmerac), 2-methoxy-3,6-dichlorobenzoic acid (dicamba), 4-amino-3,6, 6-trichloropicolinic acid (picloram), and naphthalene acetic acid, were investigated in cleavers (Galium aparine). When plants were root treated with 0.5 mM IAA, shoot epinasty and inhibition of root and shoot growth developed during 24 h. Concomitantly, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase activity, and ACC and ethylene production were transiently stimulated in the shoot tissue within 2 h, followed by increases in immunoreactive (+)-abscisic acid (ABA) and its precursor xanthoxal (xanthoxin) after 5 h. After 24 h of treatment, levels of xanthoxal and ABA were elevated up to 2- and 24-fold, relative to control, respectively. In plants treated with IAA, 7-chloro-3-methyl-8-quinolinecarboxylic acid, naphthalene acetic acid, 2-methoxy-3,6-dichlorobenzoic acid, and 4-amino-3,6,6-trichloropicolinic acid, levels of ethylene, ACC, and ABA increased in close correlation with inhibition of shoot growth. Aminoethoxyvinyl-glycine and cobalt ions, which inhibit ethylene synthesis, decreased ABA accumulation and growth inhibition, whereas the ethylene-releasing ethephon promoted ABA levels and growth inhibition. In accordance, tomato mutants defective in ethylene perception (never ripe) did not produce the xanthoxal and ABA increases and growth inhibition induced by auxins in wild-type plants. This suggests that auxin-stimulated ethylene triggers ABA accumulation and the consequent growth inhibition. Reduced catabolism most probably did not contribute to ABA increase, as indicated by immunoanalyses of ABA degradation and conjugation products in shoot tissue and by pulse experiments with [(3)H]-ABA in cell suspensions of G. aparine. In contrast, studies using inhibitors of ABA biosynthesis (fluridone, naproxen, and tungstate), ABA-deficient tomato mutants (notabilis, flacca, and sitiens), and quantification of xanthophylls indicate that ABA biosynthesis is influenced, probably through stimulated cleavage of xanthophylls to xanthoxal in shoot tissue.

Abscisic Acid↗

Excretion of beta-lactam antibiotics in sweat--a neglected mechanism for development of antibiotic resistance?

The concentrations of beta-lactam antibiotics after standard doses were measured in blood and apocrine (axilla) and eccrine (forearm) sweat from six adult healthy persons. All persons had ceftazidime (axilla, 28.4 microg/ml; forearm, 11 microg/ml) and ceftriaxone (axilla, 8.9 microg/ml; forearm, 2.5 microg/ml) in sweat, and one person had cefuroxime in sweat (axilla, 7.8 microg/ml) (all data are mean peaks). Three persons had benzylpenicillin (axilla, 2.6 to 0.1 microg/ml) and one had phenoxymethylpenicillin (axilla, 0.4 microg/ml) in sweat. Excretion of beta-lactam antibiotics in the sweat may explain why staphylococci so rapidly become resistant to these drugs.

Administration, Oral↗

Simultaneous determination of seven penicillins in muscle, liver and kidney tissues from cattle and pigs by a multiresidue high-performance liquid chromatographic method.

A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction (SPE) was developed for determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in muscle, liver and kidney tissues of pigs and cattle. The compounds were extracted in aqueous solution by precipitation of organic materials with a mixture of sulphuric acid and sodium tungstate. The extract was cleaned up by SPE on a divinylbenzene-co-N-vinylpyrrolidone polymeric sorbent. Further clean-up was performed by liquid-liquid partition with diethyl ether. The extract was derivatised with benzoic anhydride and 1,2,4-triazole mercury (II) reagent. Chromatography was performed by reversed-phase gradient HPLC on a C18 column with ultraviolet detection at 323 nm. The limits of detection estimated by a conservative model were in the range 8.9-11.1 microg/kg for amoxicillin, penicillin G, ampicillin, oxacillin, cloxacillin and nafcillin and 18.3-20.9 microg/kg for dicloxacillin. The mean recovery range was 66-77% for amoxicillin, 73-75% for penicillin G, 81-82% for ampicillin, 73-76% for oxacillin, 74-75% for cloxacillin, 66-72% for nafcillin and 58-65% for dicloxacillin.

Amoxicillin↗

[Secondary prevention of ischemic heart disease. A questionnaire study and suggestions to improved cooperation between hospitals and general practice].

The aim of the present study was to examine the extent of secondary prophylaxis in patients following hospitalization under the diagnosis of ischaemic heart (IHD). Our data were based on hospital records and questionnaires sent to patients admitted to the Cardiological Department, Frederiksberg Hospital, under the diagnosis of IHD during the first six months of 1996. One hundred and twenty-five patients were included, of these 106 answered the questionnaire. We found that overall patients were insufficiently treated with aspirin, beta-blockers and antilipidaemic agents. Measures to reduce smoking and to increase physical exercise were sparse. We concluded that secondary intervention instituted from the Cardiological Department in question was not up to generally agreed standards. Suggestions to improve secondary prophylaxis in patients with IHD are presented. The importance of increased co-operation between hospital, general practitioner and patient is emphasized. A patient-born record designed for this purpose is presented.

Adult↗

Exercise and the immune system--influence of nutrition and ageing.

In essence, the immune system is enhanced during moderate and severe exercise, and only intense long-duration exercise is followed by impairment of the immune system. The latter includes suppressed concentration of lymphocytes, suppressed natural killer cell activity, lymphocyte proliferation and secretory IgA in saliva. During the time of immune impairment, referred to as "the open window", microbial agents, especially viruses may invade the host and infections may be established. One reason for the "overtraining effect" seen in elite athletes could be that this window of opportunism for pathogens is longer and the degree of immunosuppression more pronounced. Alterations in metabolism and metabolic factors may contribute to exercise-associated changes in immune function. Reductions in plasma-glutamine concentrations, altered plasma-glucose level, free oxygen radicals and prostaglandins (PG) released by the elevated number of neutrophils and monocytes may influence the function of lymphocytes and contribute to the impaired function of the later cells. Thus, nutritional supplementation with glutamine, carbohydrate, anti-oxidants or PG-inhibitors may, in principle, influence exercise-associated immune function. Although several intervention studies have been performed, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗

An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETA') is a potent immunotoxin against a Hodgkin-derived cell line.

The human CD30 receptor is highly overexpressed on the surface of Hodgkin Reed-Sternberg cells and has been shown to be an excellent target for selective immunotherapy using monoclonal antibody-based agents such as immunotoxins. To construct a new recombinant immunotoxin for possible clinical use in patients with Hodgkin's lymphoma, we have chosen the murine anti-CD30 hybridoma Ki-4 to generate a high-affinity Ki-4 single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv were obtained by selection of binding phage on the Hodgkin lymphoma-derived, CD30-expressing cell line L540Cy. The selected recombinant Ki-4 scFv was shown to specifically bind to an overlapping epitope on the CD30 antigen with binding kinetics similar to those of the original antibody. The Ki-4 scFv was subsequently fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). The resulting immunotoxin Ki-4(scFv)-ETA' specifically binds to CD30+ L540Cy cells and inhibits the protein synthesis by 50% at a concentration (IC50) of 43 pM. This recombinant immunotoxin is a promising candidate for further clinical evaluation in patients with Hodgkin's lymphoma or other CD30+ malignancies.

Bacterial Toxins↗

Genetic analysis of the maternally induced affinity enhancement in the non-Ox1 idiotypic antibody repertoire of the primary immune response to 2-phenyloxazolone.

The early phases of ontogeny are decisive for the development of the B-cell repertoire. Here, we demonstrate that maternal tertiary immunization of BALB/c mice with 2-phenyloxazolone (phOx) caused a drastic alteration of the primary antigen-specific repertoire of the offspring. Maternal tertiary immunization or quaternary antibodies, which exhibited an extremely weak cross-reactivity with the major Ox1 idiotype (IdOx1), induced a change in the proportion of IdOx1/non-IdOx1 antiphOx antibodies in the F1 and F2 primary repertoire. The observed variability in the level of IdOx1 expression (10-90%) exceeded even the seemingly genetically based differences between various mouse strains. In comparison with the non-IdOx1 of control mice, half of the non-IdOx1 antibodies showed a 5-100-fold enhanced affinity. Sixty per cent of these antibodies exhibited an affinity identical to that of IdOx1 antibodies, which are normally of the highest affinity, while the remaining 40% exceeded even that of IdOx1 by a factor of 10. The non-IdOx1 were encoded by VH/VL genes and/or combinations thereof which are either new, hitherto unobserved in the antiphOx response, or typical of memory responses in normal mice. The significance of these data is discussed with respect to the possibility that maternal antibodies, which are acquired through multiple immune maturation processes, may have an epigenetic (non-Mendelian) inheritable potential for the offspring.

Amino Acid Sequence↗

Crosstalk between insulin and angiotensin II signalling systems.

Insulin resistance and hypertension commonly occur together. Pharmacological inhibition of the renin-angiotensin system has been found to reduce not only hypertension, but also insulin resistance. This raises the possibility that the renin-angiotensin system may interact with insulin signalling. We have investigated the relationship between insulin and angiotensin II (AII) intracellular signalling in vivo using an intact rat heart model, and in vitro using rat aorta smooth muscle cells (RASMC). Results generated in the in vivo studies indicate that, like insulin, AII stimulates tyrosine phosphorylation of the insulin receptor substrates IRS-1 and IRS-2. This leads to binding of IRS-1 and IRS-2 to PI3-kinase. However, in contrast to the effect of insulin. IRS-1- and IRS-2-associated PI3-kinase activity is inhibited by AII in a dose-dependent manner. Moreover, AII inhibits insulin-stimulated IRS-1/IRS-2-associated PI3-kinase activity. The in vivo effects of AII are mediated via the AT1 receptor. The results of the in vitro studies indicate that AII inhibits insulin-stimulated, IRS-1-associated PI3-kinase activity by interfering with the docking of IRS-1 with the p85 regulatory subunit of PI3-kinase. It appears that AII achieves this effect by stimulating serine phosphorylation of the insulin receptor beta-subunit IRS-1, and the p85 regulatory subunit of PI3-kinase. These actions result in the inhibition of normal interactions between the insulin signalling pathway components. Thus, we believe that AII negatively modulates insulin signalling by stimulating multiple serine phosphorylation events in the early components of the insulin signalling cascade. Overactivity of the renin-angiotensin system is likely to impair insulin signalling and contribute to insulin resistance observed in essential hypertension.

Angiotensin II↗

Comparison of thymidine kinase and A-type inclusion protein gene sequences from Norwegian and Swedish cowpox virus isolates.

During the last decades, cowpox virus, a member of the genus Orthopoxvirus within the Poxviridae family, has appeared as a pathogen in domestic cats, zoo animal species, and humans. At the same time, vaccinia virus, another orthopoxvirus, has been used as a recombinant vaccine vector with foreign genes inserted in the thymidine kinase (TK) gene. By PCR and cycle sequencing, we have determined the nucleotide sequences of the TK gene and the A-type inclusion protein (ATIP) gene of virus isolates from two human cowpox cases in Sweden, as well as a human and a feline case from Norway. We also obtained the corresponding sequences from ectromelia virus (strain Moscow), cowpox virus (strain Brighton) and vaccinia virus (strain Western Reserve). The new virus isolates differed from ectromelia virus and vaccinia virus, and were confirmed to be cowpox virus strains. Isolates originating from the same country had nearly identical TK sequences and fully identical ATIP sequences. They probably represent local geographical strains of cowpox virus.

Animals↗

Reducing uncertainty in the derivation and application of health guidance values in public health practice. Dioxin as a case study.

We were requested by the U.S. Environmental Protection Agency (EPA) to clarify the relationships among the minimal risk level (MRL), action level, and environmental media evaluation guide (EMEG) for dioxin established by the Agency for Toxic Substances and Disease Registry (ATSDR). In response we developed a document entitled "Dioxin and Dioxin-Like Compounds in Soil, Part I: ATSDR Interim Policy Guideline"; and a supporting document entitled "Dioxin and Dioxin-Like Compounds in Soil, Part II: Technical Support Document". In these documents, we evaluated the key assumptions underlying the development and use of the ATSDR action level, MRL, and EMEG for dioxin. We described the chronology of events outlining these different health guidance values for dioxin and identified the areas of uncertainty surrounding these values. Four scientific assumptions were found to have had a great impact on this process; these were: (1) the specific uncertainty factors used, (2) the toxicity equivalent (TEQ) approach, (3) the fractional exposure from different pathways, and (4) the use of body burdens in the absence of exposure data. This information was subsequently used to develop a framework for reducing the uncertainties in public health risk assessment associated with exposure to other chemical contaminants in the environment. Within this framework are a number of future directions for reducing uncertainty, including physiologically based pharmacokinetic modeling (PBPK), benchmark dose modeling (BMD), functional toxicology, and the assessment of chemical mixture interactions.

Benchmarking↗

[Pathophysiology of chronic constipation and new therapy recommendation].

Three causes of constipation are known: Chagas' disease, congenital megacolon (Hirschsprung's disease) and continent obstipation. Those diseases are rare, they can be treated successfully by drugs, surgery or psychotherapy. More common is the idiopathic chronic constipation, observed manly in females. A frequent cause is the laxative abuse for many years. The possible etiologic factors are discussed. Based on the fact, that constipation never occurs in patients with a colostomy, reasons for the development of chronic idiopathic constipation are presumed in a disturbance in the distal colon and the anorectum. A possible explanation for the malfunction of defecation could be a different calibre between the usually tight pelvic colon and the wide rectum. In contrast to the apolar structure of the large bowel, the rectum shows a polar fibrous configuration. An additional disorder in the feedback mechanism between continence and defecation could impede the bowel passage. Because of these observations and thoughts, we performed a deep resection of the rectum in 18 patients instead of resecting the dilated and elongated colon. All patients operated that way experienced a major improvement of their bowel function. Postoperatively the bowel movements were regular and normal.

Adult↗

Antigen-independent suppression of the IgE immune response to bee venom phospholipase A2 by maternally derived monoclonal IgG antibodies.

The IgE immune response to ovalbumin in rats can be suppressed by prior immunization of the dams. The results reported in this paper extend this observation to include a different antigen and another species, namely the IgE immune response to bee venom phospholipase A2 (PLA2) in CBA/J mice. The degree of suppression seemed to depend on the amount of IgG antibodies transferred to the offspring. Moreover, we found that the maternally mediated suppression of the IgE response could be achieved in a completely antigen-free system in which exogenous monoclonal anti-PLA2 IgG antibodies were transferred from the dams to the offspring. The following results were obtained: (i) The IgE suppression by monoclonal IgG antibodies was induced as efficiently with one single anti-PLA2 IgG1 antibody as with a mixture of ten antibodies (nine IgG1, one IgG2b). (ii) Even after several immunizations up to an age of 6 months with a dose of PLA2 that normally induces IgE production, none of the F1 mice developed an IgE response. (iii) This long-lasting suppression was observed in mice which were first immunized at an age of 4 weeks (i.e. when low amounts of maternally derived monoclonal IgG were still present), as well as in mice which were first immunized at an age of 8 weeks, when no such maternal antibodies could be detected in their sera. The corresponding IgG responses showed, compared to normal mice, a transient enhancement in the maternally influenced mice. It is concluded that the immunological experience of the mother is of particular importance for the isotype regulation in the newborns, especially with respect to the ability to elicit an IgE response. The possible implications for the development of allergic diseases in humans are discussed.

Animals↗