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T Hansen

Publications and source records attributed to T Hansen.

295 records · Page 17Linked to original sources
PubMedDate not supplied

Functionalization and cellular uptake of boron carbide nanoparticles. The first step toward T cell-guided boron neutron capture therapy.

In this paper we present surface modification strategies of boron carbide nanoparticles, which allow for bioconjugation of the transacting transcriptional activator (TAT) peptide and fluorescent dyes. Coated nanoparticles can be translocated into murine EL4 thymoma cells and B16 F10 malignant melanoma cells in amounts as high as 0.3 wt. % and 1 wt. %, respectively. Neutron irradiation of a test system consisting of untreated B16 cells mixed with B16 cells loaded with boron carbide nanoparticles were found to inhibit the proliferative capacity of untreated cells, showing that cells loaded with boron-containing nanoparticles can hinder the growth of neighboring cells upon neutron irradiation. This could provide the first step toward a T cell-guided boron neutron capture therapy.

Animals↗
PubMedDate not supplied

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia.

Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, genetic variation in the ApoD is associated with long-term clinical outcome to antipsychotic treatment. We genotyped two single-nucleotide polymorphisms in the ApoD gene in 343 chronic patients with schizophrenia spectrum disorders (ICD-10) and 346 control subjects of Danish origin. We did not find ApoD alleles, genotypes or haplotypes to be associated with disease. However, we did find that long-term clinical outcome was associated with the ApoD polymorphism rs7659 (P = 0.041) following adjustment for lifetime clinical global impression, age at first admission and gender.

Adult↗
PubMedDate not supplied

[Infections of the musculoskeletal system with chronic polyarthritis during a combination therapy with Methotrexate and Leflunomide].

AIM: The long-term results of rheumatoid arthritis are unsatisfactory despite the mono or combination therapy of conventional "disease-modifying antirheumatic drugs". Therefore in the recent past the administration of a combination of Methotrexate with Leflunomide takes place more frequently. To what extent the perioperative infection rate is influenced by the individual immune-modulating drugs, is still disputed and should quantified on the basis the rheumatism orthopaedic patient collective of an orthopaedic university clinic. METHOD: The clinical progresses of patients after operative treatment in the orthopaedic hospital, since introduction of the Leflunomide, were evaluated with regard to perioperative infection. RESULTS: Of 16 patients, who were observed during a period of 1,5 years under a combination therapy by MTX/Leflunomide, three exhibited a heavy infection of the musculoskeletal system. CONCLUSION: The combination of the two above mentioned drugs affects different pathophysiological processes. Synergistic effects in therapy but also with regard to side effects must be expected. First available reports on this combination therapy do not refer to a increased infection/risk. The observation of three serious infections under the combination MTX/Leflunomide prompted us to call attention to this risk. In particular with infection-susceptible bone-surgical operations such a combination of immune-modulating medicines should be employed with caution. The recent literature is discussed.

Antirheumatic Agents↗
PubMedDate not supplied

Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response.

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.

Adult↗
PubMedDate not supplied

Relationships among intracranial pressure, blood pressure, and superficial cerebral vasculature after experimental occlusion of one middle cerebral artery.

A cranial window conforming to the contours of the underlying cerebral cortical surface was implanted successfully in 18 cats. Subsequently the left middle cerebral artery (MCA) was occluded inside the sealed cranium and changes in the superficial cortical vasculature were related to measurements of intracranial pressure (ICP), measured extradurally, and to the resulting infarcts. Vascular changes early after MCA occlusion were not predictive of the outcome of the occlusion, except for aggregation of formed elements of the blood in arterioles, which was a bad prognostic sign. Secondary reactive hyperemia was not beneficial; increases of ICP suggested that hyperemia led to increased cerebral edema as well as to swelling.

Animals↗
PubMedDate not supplied

Clinical pharmacokinetics of methyldopa.

Absorption of methyldopa from the gastrointestinal tract is incomplete and variable; bioavailability after oral administration is about 25% (range 8 to 62%). The average time to reach maximum plasma concentration (tmax) [chemically determined] is 2 hours, when the maximum plasma concentration of active drug accounts for 50% of the radioactivity, the remainder representing various metabolites. Physicochemical determination of methyldopa shows that bi-phasic elimination occurs after both intravenous and oral administration, the half-life of the alpha-phase being 0.21 hours (range 0.16 to 0.26 hours) and of the beta-phase 1.28 hours (range 1.02 to 1.69 hours) in normal subjects. Methyldopa is less than 15% protein bound, whereas the primary metabolite, which most probably is the O-sulphate, is about 50% protein bound. The apparent volume of distribution in the central compartment is about 0.23L/kg (range 0.19 to 0.32L/kg), and the total volume of distribution (calculated as Vdarea) is about 0.60L/kg (range 0.41 to 0.72L/kg) in healthy volunteers. Acid-labile conjugates are formed after oral administration. These acid-labile conjugates, in particular the O-sulphate, are probably formed in the intestinal cells, since they are detected in very small amounts after intravenous administration. Additionally, there is a rapid formation of partly unidentified metabolites after both intravenous and oral administration. After intravenous administration the quantitatively most prominent metabolites are methyldopamine and the glucuronide of dihydroxyphenylacetone, but traces of 5 or 6 other metabolites have also been found and identified. These metabolites are probably formed in the liver, but the complete metabolic pattern is still unknown. The renal clearance of methyldopa (95 ml/min/m2) is more than 50% higher than the endogenous creatinine clearance. Renal excretion of some metabolites is slower. Extrarenal elimination accounts for about 50% of the total body clearance of the drug. Renal excretion is very low in patients with renal failure, resulting in accumulation of both active drug and, in particular, its metabolites. There is a marked accumulation of unidentified metabolites in renal failure patients, which possibly explains the strong and prolonged hypotensive action of methyldopa in these patients.

Acute Kidney Injury↗