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Biomedical subjects

J Kirschner

Publications and source records attributed to J Kirschner.

At least 37 records · Page 2Linked to original sources

Spin-density wave in ultrathin Fe films on Cu(100).

For Fe films epitaxially grown on Cu(100) at 300 K, the total magnetic moment as a function of film thickness and its temperature dependence have been investigated in situ with a multitechnique approach. The results exclude the collinear type-1 antiferromagnetic configuration as the magnetic structure for face-centered-cubic Fe films on Cu(100). It is proposed that a spin-density-wave state is responsible for the magnetic structure.

Journal Article↗

Geometrical and compositional structure at metal-oxide interfaces: MgO on Fe(001).

The geometric structure of MgO deposited on Fe(001) in ultrahigh vacuum by electron evaporation was determined in detail by using surface x-ray diffraction. In contrast to the common belief that MgO grows in direct contact on the Fe(001) substrate, we find an FeO interface layer between the substrate and the growing MgO structure which has not been considered thus far. This result opens new perspectives for the understanding of the Fe/MgO/Fe(001) interface and the tunneling magnetoresistance effect in general.

Journal Article↗

Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option.

Intramuscular injections of botulinum toxin type A (BTX-A) have increasingly been used to reduce spasticity in specific muscle groups in children with cerebral palsy. Targets of therapeutic efforts are improvement of gross motor function, alleviation of pain or facilitation of hygienic care. Placebo-controlled studies have shown the local and functional effectiveness of BTX-A for the treatment of dynamic pes equinus. Whether long-term treatment with BTX-A improves motor development and delays contractures is still under investigation.

Animals↗

Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol) and 3D-conformal radiotherapy of stage III inoperable non-small cell lung cancer. Results of a dose escalation study.

The purpose of this study was the determination of the maximum tolerable dose (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC-stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with PX/carboplatin followed by combined radiochemotherapy (60 Gy/6 weeks) with weekly PX which was escalated in cohorts of four patients until dose limiting toxicity (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was applied in all patients. Toxicity was determined by WHO criteria. Patients were followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients are evaluable. DLT was esophagitis III degrees, requiring interruption of radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) and one leucopenia III degrees (60 mg/m(2)) were observed. Only one patient (60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate was between 21 and 36% but showed no clear correlation with PX dose. Tumor response (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88% (30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that the MTD of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is esophagitis. Response and survival data of this sequential/combined approach are promising. A minor increase of pulmonary toxicity of irradiation is suspected.

Antineoplastic Combined Chemotherapy Protocols↗

Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure.

One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.

Adolescent↗

Visualizing spin-dependent electronic collisions In ferromagnets

This work demonstrates experimentally and theoretically that the coincident two-electron emission from a ferromagnetic surface, upon the impact of a polarized electron, carries detailed information on the spin-dependent electronic collisions in ferromagnets. The analysis of the calculated and the measured two-electron spectra reveals the potential of the electron-pair emission technique for the study of (a) surface magnetism and (b) spin-dependent electron scattering dynamics in ferromagnets.

Journal Article↗

Magnetic microstructure of the spin reorientation transition: a computer experiment.

The scenario of the spin reorientation in two-dimensional films within first-order anisotropy approximation is theoretically studied by means of Monte Carlo simulations. The magnetic microstructure is investigated as a function of the ratio of the perpendicular anisotropy energy to the dipolar one. If the anisotropy dominates, out-of-plane domains will be found while in-plane vortices appear for a vanishing anisotropy. In the range of comparable anisotropy and dipolar energies a complex domain pattern evolves yielding a continuous transition between the two structures. The structure with equally distributed magnetic moment orientations is stable at the point where anisotropy and dipolar energies cancel each other.

Journal Article↗

[Adverse (cardio-)vascular effects of vinorelbine in non-small-cell bronchial carcinoma].

Vinorelbin is an important tumouricidal substance. The (cardio-)vascular side effects are not well known. We report on four patients in highly palliative situations who were treated with vinorelbine for non-small cell lung cancer. Case one presented with myocardial infarction eleven days after onset of therapy. The second and third cases had to be admitted immediately after the beginning of vinorelbine treatment because of hypertension and angina pectoris. The fourth case suffered from angina abdominalis. A critical review of the literature showed 17 cardiac ischaemias with seven myocardial infarctions, three of them with lethal outcome.

Aged↗

Hairpins involving both inverted and direct repeats are associated with homoplasious indels in non-coding chloroplast DNA of Taraxacum (Lactuceae: Asteraceae).

Sequence variation in 2.2 kb of non-coding regions of the chloroplast genome of eight dandelions (Taraxacum: Lactuceae) from Asia and Europe is interpreted in the light of the phylogenetic signal of base substitutions vs. indels (insertions-deletions). The four non-coding regions displayed a total of approximately 30 structural mutations of which 9 are potentially phylogenetically informative. Insertions, deletions, and an inversion were found that involved consecutive stretches of up to 172 bases. When compared to phylogenetic relationships of the chloroplast genomes based on nucleotide substitutions only, many homoplasious indels (33%) were detected that differed considerably in length and did not comprise simple sequence repeats typically associated with replication slippage. Though many indels in the intergenic spacers were associated with direct repeats, frequently, the variable stretches participated in inverted repeat stabilized hairpins. In each intergenic spacer or intron examined, nucleotide stretches ranging from 30 to 60 bp were able to fold into stabilized secondary structures. When these indels were homoplasious, they always ranked among the most stabilized hairpins in the non-coding regions. The association of higher order structures that involve both classes of repeats and parallel structural mutations in hot spot regions of the chloroplast genome can be used to differentiate among mutations that differ in phylogenetic reliability.

Asteraceae↗

Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure.

Intramuscular injection of botulinum neurotoxin A is a relatively new method for treating spastic movement disorders in children. One major goal of any therapy for patients with movement disorders is to improve gross motor function. In this study, 18 patients with adductor spasm were treated with botulinum neurotoxin A. Treatment effect was determined with the Gross Motor Function Measure, a standardized, validated instrument designed to assist in assessment of gross motor function. Spastic muscle hyperactivity and joint mobility were evaluated by the modified Ashworth Scale and by range of motion, respectively. Compared to pretreatment values, significant improvement in gross motor function (P < .010), decrease in the modified Ashworth Scale, and increase in the range of motion (P < .010) were achieved. Patients with moderate impairment of gross motor function (classed at level III and level IV in the Gross Motor Function Classification System) benefited most from treatment. In patients with severe handicap (level V), only one of five treated patients showed improvement in gross motor function. Nevertheless, all patients in this subgroup benefited from improved ease in hygienic care. In conclusion, we have demonstrated that for most children with moderate functional impairment, the Gross Motor Function Measure is a useful instrument for objective documentation of improvements of gross motor function following treatment with botulinum neurotoxin A.

Adolescent↗

Absence of transcallosal inhibition in adolescents with diplegic cerebral palsy.

The role of intracortical organization in the pathophysiology of cerebral palsy (CP) is not clear. We used transcranial magnetic stimulation to investigate the paradigm of transcallosal inhibition (TI) in a group of adolescent patients with diplegic CP (n = 4), hereditary spastic paraplegia (n = 2), and healthy control adolescents (n = 4). None of the patients with CP showed TI, whereas all other subjects had normal TI. These findings indicate a lack of inhibitory control of the motor cortex in CP.

Adolescent↗

[Autocrine activation of fibroblasts following irradiation].

BACKGROUND: The most important limitation of thoracic radiotherapy is radio-toxicity of the normal lung. We distinguish the pneumonitis with acute clinical onset, histologically characterised by infiltration of inflammatory cells to alveoli and interstitium, from fibrosis, which is slowly progressive and characterised by fibroblast proliferation and collagen deposition in the interstitium. Radiogenetic fibrosis can occur without evidence of alveolitis, an active role of mesenchymal lung cells in the pathogenesis of this special disorder is assumed. METHODS: Human lung fibrobasts were irradiated in vitro with single doses of 4, 7 and 10 Gy and afterwards observed or incubated together with non-irradiated cells in a co-culture system. After 3, 6, 9, and 12 days cells were counted, and TGF beta 1 and fibronectin was measured in supernatants. RESULTS: Cell growth of irradiated fibroblasts was inhibited as expected. In contrast, we observed a significant stimulation of cell growth of the non-irradiated fibroblasts, which were incubated together with the irradiated cells. This effect was obvious from day 1 until day 9 following irradiation and was dose dependent. In irradiated cells TBF beta 1 was increased in culture supernatants up to five-fold compared to sham-irradiated cells from day 6 until day 12. Fibronectin was elevated in dose dependent manner. CONCLUSION: Irradiation of fibroblasts in vitro induces synthesis of substances which stimulate cell growth. TGF beta 1 and fibronectin may be involved in this act of "self-activation".

Cell Division↗

Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. Response to treatment is infrequent and the use of immunosuppressive agents other than corticosteroids is the subject of ongoing discussion because of uncertain efficacy and side-effects. To determine the efficacy and safety of cyclophosphamide pulse therapy in IPF, this study retrospectively analysed 18 patients with progressive IPF who were treated with intermittent i.v. cyclophosphamide (1-13 g x month(-1)) and additional oral prednisolone for 1 yr. Static lung volumes, arterial oxygen tension (Pa,O2) at rest, clinical symptoms and potential treatment-related side-effects were recorded. Cyclophosphamide had to be stopped in one patient, owing to repeated pulmonary infection; 11 patients were responders (five improving, six stabilizing) and six patients deteriorated. The change in vital capacity (VC) of responders was +6.7+/-18.0% (mean +/-SD), compared with -20.6+/-18.2% in nonresponders (p=0.008). Pa,O2 remained constant in responders (+0.13+/-0.88 kPa (+1.0+/-6.6 mmHg)), while it decreased in nonresponders (-2.08+/-1.92 kPa (-15.6+/-14.4 mmHg, p=0.008)). Additional prednisolone was reduced by 19.1+/-13.4 mg in responders, compared with 6.7+/-16.3 mg in nonresponders (p=0.02). VC at initiation of therapy was higher in responders (60.2+/-10.2 versus 40.3+/-12.9% predicted; p=0.004). No side-effects occurred, other than respiratory tract infection. These data demonstrate that intravenous cyclophosphamide pulse therapy may be a favourable regimen for certain patients with progressive idiopathic pulmonary fibrosis. Patients with a vital capacity of more than 50% predicted and a shorter duration of disease may benefit most.

Administration, Oral↗

[The diagnosis and therapy of acquired factor-VIII inhibitors in combination with lupus anticoagulants].

HISTORY AND CLINICAL FINDINGS: A 63-year-old woman, known to have a primary factor VIII inhibitor (FFI) in combination with lupus anticoagulants (LA) was hospitalised because of life-threatening bleeding from mouth and neck. INVESTIGATIONS: The activity of coagulation factor VIII was 9% under substitution, while the factor VIII inhibitor titre was 123 U/ml. A lupus anticoagulant test was positive. Antibodies against varicella-zoster virus and Epstein-Barr virus were demonstrated. The right adrenal was found to be enlarged on computed tomography. TREATMENT AND COURSE: Coagulation became normal on administration of porcine factor VIII concentrate. Three cycles of a combination of three protein A immunoadsorptions, cyclophosphamide (twice 1.0 g intravenously), IgG (30 g daily for 5 days) as well as long-term oral cyclophosphamide administration (150 mg daily) during the interval were undertaken to reduce the inhibitor and produce immuno-tolerance. The factor VIII inhibitor titre was stabilised at a low level, but factor VIII activity could not be normalised without substitution. CONCLUSIONS: The simultaneous presence of specific and non-specific inhibitors makes laboratory diagnosis and treatment more difficult. Porcine factor VIII and a combination of immunoadsorption and suppression are important components in the treatment of bleeding episodes and the production of immunotolerance.

Autoimmune Diseases↗