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Biomedical subjects

G Hansen

Publications and source records attributed to G Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Leflunomide for active rheumatoid arthritis].

In 1999, leflunomide was introduced for the treatment of active rheumatoid arthritis. Leflunomide is a reversible inhibitor of "de novo" synthesis of pyrimidine, resulting in a restriction of lymphocyte proliferation. The pharmacodynamics are characterized by slow elimination. Leflunomide has shown an efficacy and a pattern of mild and serious side effects similar to methotrexate and sulphasalazine. Treatment is started with a loading dose of 100 mg orally for three days followed by 20 (10) mg daily. Regular haematological measurements, determination of serum chemistry and blood pressure should be performed every second week the first six months, subsequently every sixth week. If the treatment is to be terminated abruptly, a drug elimination procedure must be performed. Leflunomide will find its place in the treatment of rheumatoid arthritis. Leflunomide should follow an unsuccessful treatment attempt with methotrexate or sulphasalazine.

Administration, Oral↗
PubMed2000

End-of-life decisions in neonatal intensive care: physicians' self-reported practices in seven European countries. EURONIC Study Group.

BACKGROUND: The ethical issue of foregoing life-sustaining treatment for newborn infants at high risk of death or severe disability is extensively debated, but there is little information on how physicians in different countries actually confront this issue to reach end-of-life decisions. The EURONIC project aimed to investigate practices as reported by physicians themselves. METHODS: The study recruited a large, representative sample of 122 neonatal intensive-care units (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified random sampling (in France, Germany, the UK, Italy, and Spain) with an overall response rate of 86%. Physicians' practices of end-of-life decision-making were investigated through an anonymous, self-administered questionnaire. 1235 completed questionnaires were returned (response rate 89%). FINDINGS: In all countries, most physicians reported having been involved at least once in setting limits to intensive care because of incurable conditions (61-96%); smaller proportions reported such involvement because of a baby's poor neurological prognosis (46-90%). Practices such as continuation of current treatment without intensification and withholding of emergency manoeuvres were widespread, but withdrawal of mechanical ventilation was reported by variable proportions (28-90%). Only in France (73%) and the Netherlands (47%) was the administration of drugs with the aim of ending life reported with substantial frequency. Age, length of professional experience, and the importance of religion in the physician's life affected the likelihood of reporting of non-treatment decisions. INTERPRETATION: A vast majority of neonatologists in European NICUs have been involved in end-of-life limitation of treatments, but type of decision-making varies among countries. Culture-related and other country-specific factors are more relevant than characteristics of individual physicians or units in explaining such variability.

Adult↗
PubMed2000

Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D.

Muscarinic cholinergic signaling plays an essential role in the control of the normal airway functions and in the development of pulmonary pathologies including asthma. In this paper we demonstrate that the airways of mice deficient in a cAMP-specific phosphodiesterase (PDE4D) are no longer responsive to cholinergic stimulation. Airway hyperreactivity that follows exposure to antigen was also abolished in PDE4D(-/-) mice, despite an apparently normal lung inflammatory infiltration. The loss of cholinergic responsiveness was specific to the airway, not observed in the heart, and was associated with a loss of signaling through muscarinic receptors with an inability to decrease cAMP accumulation. These findings demonstrate that the PDE4D gene plays an essential role in cAMP homeostasis and cholinergic stimulation of the airway, and in the development of hyperreactivity. In view of the therapeutic potentials of PDE4 inhibitors, our findings provide the rationale for novel strategies that target a single PDE isoenzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

[Radical treatment of bronchial carcinoids with Nd YAG laser].

Bronchial carcinoids belong to the malignant bronchial tumours. Most of them grow only by local expansion, but some may behave in a more aggressive way. During the authors' practice with therapeutic bronchoscopies, we have done Nd YAG laser necrotizing of bronchial carcinoids in order to establish the exact localisation of the tumour basis, or to reduce the tumour for palliative reasons. Four of our six patients have shown no sign of residual tumour growth after five years of observation, and their tumour is considered eradicated. In selected patients it is possible to eradicate bronchial carcinoids with laser necrotization, and thus save them from major surgery.

Bronchial Neoplasms↗
PubMed2000

Vaccination with heat-killed Listeria as adjuvant reverses established allergen-induced airway hyperreactivity and inflammation: role of CD8+ T cells and IL-18.

Asthma is a respiratory disorder characterized by airway hyperreactivity (AHR) and inflammation and is associated with high serum IgE and overproduction of IL-4, IL-5, and IL-13 by allergen-specific Th2 cells. Our previous studies demonstrated that heat-killed Listeria monocytogenes (HKL) as an adjuvant in immunotherapy successfully reversed ongoing Ag-specific Th2-dominated responses toward Th1-dominated responses, but it was unclear if such immune modulation could reverse ongoing, established disease in target organs such as the lung. In this paper we show that a single dose of Ag plus HKL as adjuvant significantly reduced AHR in a murine model for asthma and reversed established AHR when given late after allergen sensitization. HKL as adjuvant also dramatically inhibited airway inflammation, eosinophilia, and mucus production, significantly reduced Ag-specific IgE and IL-4 production, and dramatically increased Ag-specific IFN-gamma synthesis. The inhibitory effect of HKL on AHR depended on the presence of IL-12 and CD8+ T cells and was associated with an increase of IL-18 mRNA expression. Thus, our results demonstrate that HKL as an adjuvant for immunotherapy mediates immune deviation from a pathological Th2-dominated response toward a protective immune response in peripheral lymphoid tissues and in the lungs and may be clinically effective in the treatment of patients with established asthma and allergic disease.

Adjuvants, Immunologic↗
PubMed2000

Multiple sclerosis in North Norway, and first appearance in an indigenous population.

This study was performed to determine the prevalence of multiple sclerosis (MS) in 1993 and annual incidence rates 1983-1992, and to examine whether the disease occurs among the Sami people. According to earlier reports the two northernmost counties of Norway, Troms and Finnmark with 225,000 inhabitants, have a relatively low prevalence of MS: 20.6 per 100,000 in 1973 and 31.5 in 1983. Also no person who is of pure Sami heritage (i.e., with both parents speaking Sami natively) has been found with the disease. Except for the introduction of magnetic resonance imaging as a diagnostic tool, there has been no significant change in the neurological service in the area during the past 20 years. Files of patients with the diagnosis of MS were reviewed, and questionnaires were sent to all patients alive on the prevalence day of 1 January 1993. The prevalence in 1993 was 73.0 per 100,000. The mean crude annual incidence rate was 3.5 per 100,000 during the period 1983-1992 compared with 3.0 during 1974-1982. In 1983 there were no pure Sami among the MS patients, but one had a Sami father. On 1 January 1993 there were three patients with both Sami parents and three with only one Sami parent, which is a rate that is still lower than would be expected if the prevalence of MS among the Sami were similar to that in the rest of the Norwegian population. The study shows that the incidence of MS in Troms and Finnmark has been increasing over the past 10 years, but is still lower than on the western coast and in the eastern part of Norway. The lowest incidence is found in Finnmark, where the Sami population is highest. During the past 10 years MS has also been diagnosed among the Sami population.

Adolescent↗
PubMed2000

Treatment choices for extremely preterm infants: an international perspective.

OBJECTIVE: To compare treatment choices of neonatal physicians and nurses in 11 European countries for a hypothetical case of extreme prematurity (24 weeks' gestational age, birth weight of 560 g, Apgar score of 1 at 1 minute). STUDY DESIGN: An anonymous, self-administered questionnaire was completed by 1401 physicians (response rate, 89%) and 3425 nurses (response rate, 86%) from a large, representative sample of 143 European neonatal intensive care units. Italy, Spain, France, Germany, the Netherlands, Luxembourg, Great Britain, Sweden, Hungary, Estonia, and Lithuania participated. RESULTS: Most physicians in every country but the Netherlands would resuscitate this baby and start intensive care. On subsequent deterioration of clinical conditions caused by a severe intraventricular hemorrhage, attitudes diverge: most neonatologists in Germany, Italy, Estonia, and Hungary would favor continuation of intensive care, whereas in the other countries some form of limitation of treatment would be the preferred choice. Parental wishes appear to play a role especially in Great Britain and the Netherlands. Nurses are more prone than doctors to withhold resuscitation in the delivery room and to ask parental opinion regarding subsequent treatment choices. CONCLUSION: An extremely premature infant is regarded as viable by most physicians, whereas after deterioration of the clinical conditions decision-making patterns vary according to country. These findings have implications for the ethical debate surrounding treatment of infants of borderline viability and for the interpretation and comparison of international statistics.

Adult↗
PubMed2000

Characterizing and optimizing protease/peptide inhibitor interactions, a new application for spot synthesis.

A new method is presented that uses parallel peptide array synthesis on cellulose membranes to characterize protease/peptide inhibitor interactions. A peptide comprising P5-P4' of the third domain of turkey ovomucoid inhibitor was investigated for both binding to and inhibition of porcine pancreatic elastase. Binding was studied directly on the cellulose membrane, while inhibition was measured by an assay in microtiter plates with punched out peptide spots. The importance of each residue for binding or inhibition was determined by substitutional analyses, exchanging every original amino acid with all other 19 coded amino acids. Seven hundred eighty individual peptides were investigated for binding behavior to porcine pancreatic elastase, and 320 individual peptides were measured in inhibition experiments. The results provide new insights into the interaction between the ovomucoid derived peptide and subsites in the active site of elastase. Combining these data with length analysis we designed new peptides in a step-wise fashion which in the end not only inhibited elastase 400 times more strongly than the original peptide, but are highly specific for the enzyme. In addition, the optimized inhibitor peptide was protected against exopeptidase attack by substituting D-amino acids at both termini.

Amino Acid Sequence↗
PubMed2000

Evidence for Agrobacterium-induced apoptosis in maize cells.

Agrobacterium spp. can genetically transform most dicotyledonous plant cells whereas many monocot species are recalcitrant to Agrobacterium-mediated transformation. One major obstacle is that co-cultivation of Agrobacterium spp. with plant tissues often results in cell death. Report here is that, in maize tissues, this process resembles apoptosis, with characteristic DNA cleavage into oligonucleosomal fragments and morphological changes. Two anti-apoptotic genes from baculovirus, p35 and iap, had the ability to prevent the onset of apoptosis triggered by Agrobacterium spp. in maize tissues. p35 is reported to act as a direct inhibitor of a certain class of proteases (caspase) whereas i.a.p. may act upstream to prevent their activation. This evidence raises the possibility that caspase-like proteases may also be involved in the apoptotic pathway in plant cells.

Adaptation, Physiological↗
PubMed2000

CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation.

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-beta was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secreting TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-beta-producing T cells play an important regulatory role in asthma.

Allergens↗
PubMed1999

Unusual cluster of mild invasive serogroup C meningococcal infection in a university college.

The objective of this study was to describe the epidemiology and public health response to an apparent cluster of Neisseria meningitidis serogroup C infection in university students in a residential college. A conventional epidemiological approach was taken, supported by routine and novel diagnostic techniques. Over the two days of 21-22 August 1997, three cases of suspected meningococcal infection were notified from a residential college complex at a university campus in the Sydney metropolitan area. Neisseria meningitidis was grown from throat swabs of all three cases, and was isolated from the blood of one case only. All three isolates were typed as C:2a:P1.5,2. Seroconversion was demonstrated by a novel method in the three cases. Rifampicin was given to all identified contacts. Forty-seven days after the index case, a 19 year old female living in the same complex was diagnosed with bacterial meningitis, and identified contacts given rifampicin. When this isolate was found to be group C, it was decided to vaccinate residents of the college complex. Genotyping and serotyping (C:2a:P1.5) later revealed the fourth isolate to be distinct from isolates from Cases 1-3. In conclusion the authors note that Australia's increasing capacity to type meningococcal strains is essential to understanding the epidemiology of this disease. Furthermore, typing information is of critical importance when decisions are made regarding mass vaccination. As early antibiotic treatment may inhibit isolation of the organism, development of novel approaches to diagnosis and typing should be supported.

Adolescent↗
PubMed1999

Recent advances in the transformation of plants.

Plant transformation technology has become a versatile platform for cultivar improvement as well as for studying gene function in plants. This success represents the culmination of many years of effort in tissue culture improvement, in transformation techniques and in genetic engineering. The next challenge is to develop technology that minimizes or eliminates the tissue culture steps, and provides predictable transgene expression.

Journal Article↗
PubMed1999

Molecular phylogenetic evidence for a reversible morphogenetic switch controlling the gross morphology of two common genera of green seaweeds, Ulva and Enteromorpha.

Ulva and Enteromorpha are two of the most common, ubiquitous, and environmentally important genera of green seaweeds. They are widely regarded as easily distinguishable because of their dramatically different morphologies: Ulva species are flat, lettucelike blades two cell layers thick, and Enteromorpha species form hollow liquid- or gas-filled tubes one cell thick, which may also be highly branched. We present molecular phylogenetic analyses of nuclear ribosomal RNA ITS sequences from 39 samples representing 21 purported species within these two genera. The results clearly indicate that the two genera are not respectively monophyletic and that the characteristic Ulva and Enteromorpha morphologies have arisen independently several times throughout the evolutionary diversification of the group. The analyses demonstrate that this radical change in gross morphology can also happen within clades exhibiting sequence divergence typical of conspecific assemblages of this group. We suggest that this morphological flexibility is the result of some form of developmental switch that results in either blades or tubes, but that this putative switch must be activated relatively infrequently, since there is evidence that some lineages have retained their form for significant periods. This discovery suggests a possible new model system for study of the molecular mechanisms involved in the interplay between environmental stimuli and plant development.

Chlorophyta↗
PubMed1999

Mannose induces an endonuclease responsible for DNA laddering in plant cells.

The effect of D-mannose (Man) on plant cells was studied in two different systems: Arabidopsis roots and maize (Zea mays) suspension-cultured cells. In both systems, exposure to D-Man was associated with a subset of features characteristic of apoptosis, as assessed by oligonucleosomal fragmentation and microscopy analysis. Furthermore, D-Man induced the release of cytochrome c from mitochondria. The specificity of D-Man was evaluated by comparing the effects of diastereomers such as L-Man, D-glucose, and D-galactose. Of these treatments, only D-Man caused a reduction in final fresh weight with concomitant oligonucleosomal fragmentation. Man-induced DNA laddering coincided with the activation of a DNase in maize cytosolic extracts and with the appearance of single 35-kD band detected using an in-gel DNase assay. The DNase activity was further confirmed by using covalently closed circular plasmid DNA as a substrate. It appears that D-Man, a safe and readily accessible compound, offers remarkable features for the study of apoptosis in plant cells.

Arabidopsis↗
PubMed1999

Waiting for peace: perspectives from action-oriented research on the humanitarian impasse in the Caucasus.

Cease-fires in the Caucasus during the past five years have prevented large-scale life-threatening emergencies and created space for peace negotiations. Yet genuine conflict resolution and normalisation have proven elusive, frustrating the return of uprooted populations and constraining reconstruction. This paper reviews a series of seven strategy sessions held in Moscow and the Caucasus in late 1998 to reflect upon the performance of humanitarian agencies and stimulate greater synergies with diplomatic actors. An experiment in promoting discussion of recently conducted independent policy research throughout the north and south Caucasus, the series resulted in a fresh look at the issues in the region and at agency headquarters. The generic nature of the policy challenges gives the experience potential relevance well beyond the region.

Altruism↗
PubMed1999

Parental visiting, communication, and participation in ethical decisions: a comparison of neonatal unit policies in Europe.

AIM: To compare neonatal intensive care unit policies towards parents' visiting, information, and participation in ethical decisions across eight European countries. METHODS: One hundred and twenty three units, selected by random or exhaustive sampling, were recruited, with an overall response rate of 87%. RESULTS: Proportions of units allowing unrestricted parental visiting ranged from 11% in Spain to 100% in Great Britain, Luxembourg and Sweden, and those explicitly involving parents in decisions from 19% in Italy to 89% in Great Britain. Policies concerning information also varied. CONCLUSIONS: These variations cannot be explained by differences in unit characteristics, such as level, size, and availability of resources. As the importance of parental participation in the care of their babies is increasingly being recognised, these findings have implications for neonatal intensive care organisation and policy.

Communication↗
PubMed1999

Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation.

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.

Allergens↗