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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 19 recordsLinked to original sources
PubMed2006

Blockade of chemokine signaling in patients with multiple sclerosis.

We assessed the safety and efficacy of orally administered CC chemokine receptor 1 (CCR1) antagonist in 105 patients with relapsing/remitting MS (RRMS) in a 16-week, randomized, double-blind, placebo-controlled trial. The primary endpoint was the cumulative number of newly active lesions on serial MRI scans. Other MRI, immunologic, and clinical outcomes were also explored. No significant treatment difference was observed for any tested MRI variable. CCR1 does not contribute to initial leukocyte infiltration in RRMS.

Central Nervous System↗
PubMed2006

Molecular basis for the antiproliferative effect of agmatine in tumor cells of colonic, hepatic, and neuronal origin.

The aim of the present study was to challenge potential mechanisms of action underlying the inhibition of tumor cell proliferation by agmatine. Agmatine inhibited proliferation of the human hepatoma cells HepG2, the human adenocarcinoma cells HT29, the rat hepatoma cells McRH7777, and the rat pheochromocytoma cells PC-12. Inhibition of proliferation of HepG2 cells was associated with an abolition of expression of ornithine decarboxylase (ODC) protein and a doubling of mRNA content encoding ODC. In HepG2 cells, silencing of ODC-antizyme-1, but not of antizyme inhibitor, by RNA interference resulted in an increase of agmatine's antiproliferative effect. Thus, the distinct decrease in intracellular polyamine content by agmatine was due to a reduced translation of the synthesizing protein ODC but was not essentially mediated by induction of ODC-antizyme or blockade of antizyme inhibitor. In interaction experiments 1 mM L-arginine, 1 mM D-arginine, 1 mM citrulline, 100 microM N(omega)-nitro-L-arginine methyl ester, 1 and 10 microM sodium nitroprusside, and 1 microM N1-guanyl-1,7-diaminoheptane failed to alter agmatine's antiproliferative effect. Hence, the antiproliferative effect of agmatine in HT29 and HepG2 cells is due to an interaction with neither the NO synthases, the hypusination of eIF5A, nor an agmatine-induced reduction in availability of intracellular L-arginine. L-Arginine and citrulline, but not d-arginine, inhibited tumor cell proliferation by themselves. Their inhibitory effect was abolished after silencing of arginine decarboxylase (ADC) expression by RNA interference indicating the conversion to agmatine by ADC. Finally, in the four cell lines under study, agmatine-induced inhibition of cell proliferation was paralleled by an increase in intracellular caspase-3 activity, indicating a promotion of apoptosis.

Actins↗
PubMed2006

Evaluation of transient apical ballooning with cardiac magnetic resonance imaging and 31-phosphorous magnetic resonance spectroscopy.

Apical ballooning is an increasingly reported transient cardiomyopathy with yet unknown origin. In this study 2 cases of apical ballooning are described in whom we used a combined approach of cardiac magnetic resonance imaging (CMR) and 31-Phosphorous magnetic resonance spectroscopy (31P MRS). Electrocardiogram showed ST abnormalities and cardiac serum markers were mildly elevated, but CAG demonstrated smooth coronary arteries. Cine-CMR revealed severe apical akinesia and significantly decreased ejection fraction. Furthermore we detected reduced myocardial phosphocreatine to beta-ATP (PCr/b-ATP) ratios during the first week of acute disease. After 1 week we observed an improvement of PCr/b-ATP ratios by 68% and 34%, which was associated with an increase in left ventricular function. Our data suggest that 31P MRS might be a valuable tool in the evaluation of apical ballooning, but larger cohorts are needed to improve the understanding of metabolic changes during transient apical ballooning.

Aged↗
PubMed2006

Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection.

The aim of this study was to compare different oral delivery systems based on the thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for the validity of the hypothesis that unhydrated polymers provide better mucoadhesion in vivo. To achieve dry polymer application, a new, experimental dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been developed. Magnetic resonance imaging was used to localize the point of release of the thiolated polymer from the application forms via the positive magnetic resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was determined by ascertaining the residence time of the fluorescence-tagged thiomer on intestinal mucosa after 3 h. Results showed that in comparison to conventional application forms the Eutex capsules led to 1.9-fold higher mucoadhesive properties of PCP-Cys when compared to application with a conventional enteric-coated capsule, and to 1.4-fold higher mucoadhesion when compared to administration with an enteric-coated tablet of the thiomer. The findings of this study should contribute to the understanding of mucoadhesion and mucoadhesion influencing parameters in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

Animals↗
PubMed2006

Stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE)-acetabular components with alpha-tocopherol.

A stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE) with alpha-tocopherol (vitamin E) used for endoprostheses can increase its resistance against oxidative degradation remarkably. However, the method used for conventional UHMW-PE of adding alpha-tocopherol to the UHMW-PE powder before processing can not be applied for crosslinked UHMW-PE, since the alpha-tocopherol hinders the crosslinking process, which would be accompanied by a heavy degradation of this vitamin. The alpha-tocopherol has therefore to be added after the crosslinking process. This paper presents two methods for a stabilisation of finished products with alpha-tocopherol. In method 1, UHMW-PE-cubes (20 x 20 x 20 mm3) were stored in pure alpha-tocopherol under inert atmosphere at temperatures from 100 degrees C to 150 degrees C resulting in a high mass fraction of alpha-tocopherol in the edge zones. For further homogenisation, the cubes were stored in inert atmosphere at temperatures from 160 degrees C to 200 degrees C. In method 2, supercritical CO2 was used to incorporate the vitamin into the UHMW-PE. In an autoclave vessel, the cubes were treated with alpha-tocopherol dissolved in supercritical CO2 for several hours at temperatures from 100 degrees C to 170 degrees C. In both cases, the mass fraction of alpha-tocopherol was detected with the help of a FTIR-microscope. Both methods are well suited to stabilise crosslinked UHMW-PE with alpha-tocopherol. A stabilisation of the sensitive edge layer as well as a nearly homogenous distribution with varying alpha-tocopherol content may be realised by varying the process parameters. Using method 2, standard hip cups were stabilized nearly homogeneously with varying mass fraction of alpha-tocopherol. No oxidation of the UHMW-PE could be detected by infrared spectroscopy (FTIR) and HPLC studies showed a very low degradation of the alpha-tocopherol for both processes.

Acetabulum↗
PubMed2006

Accelerated ageing experiments with crosslinked and conventional ultra-high molecular weight polyethylene (UHMW-PE) stabilised with alpha-tocopherol for total joint arthroplasty.

Samples of untreated ultra-high molecular weight polyethylene (UHMW-PE), UHMW-PE sterilized with gamma-rays in nitrogen atmosphere (conventional UHMW-PE, widely used for articulating surfaces in endoprostheses) and UHMW-PE, which has been crosslinked by electron beam irradiation and annealed subsequently, were stabilized with alpha-tocopherol and aged in air at 120 degrees C as well as in 10% aqueous hydrogenperoxide with 0.04 mg/ml FeCl3 as catalyst at 50 degrees C. The oxidative degradation was monitored with the help of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), solubility measurements and size exclusion chromatography (SEC) and were compared to unstabilized samples. When aged in air at 120 degrees C, the crosslinked UHMW-PE showed a slightly slower increase of the carbonyl (CO)-number (according to DIN 53383) in FTIR than conventional UHMW-PE. A stabilisation with 0.4% w/w alpha-tocopherol resulted in an increase of lifetime by a factor of approx. 40 for all samples. Ageing in 10% aqueous H2O2 at 50 degrees C yielded similar results for all three unstabilised samples. The addition of the natural antioxidant alpha-tocopherol led to a prolongation of lifetime by a factor of approx. 2.5. A linear loss of alpha-tocopherol was detected during ageing. An increase of crystallinity as well as lamella thickness during ageing was observed with the help of DSC. The two-phase structure of crosslinked UHMW-PE with two melting endotherms at 114 degrees C and 137 degrees C was replaced very quickly by a single melting point at 130 degrees C. This effect was delayed with the stabilized samples. In the solubility and SEC measurements, a severe molecular degradation and drop of molar mass of all materials could be observed after ageing in H2O2, leading to a complete destruction and, in case of crosslinked UHMW-PE, to a serious damage of the molecular network, respectively.

Biocompatible Materials↗
PubMed2006

Animal experiments with ultra-high molecular weight polyethylene (UHMW-PE) stabilised with alpha-tocopherol used for articulating surfaces in joint endoprostheses.

Numerous investigations proved the impressive suitability of alpha-tocopherol as a stabilizer for ultra-high molecular weight polyethylene (UHMW-PE) used for endoprostheses. Regarding the biocompatibility of this new biomaterial, in-vitro celltoxicity tests gave no hint for a cyto- or genotoxic activity. In this study, animal experiments are carried out to further ensure the biocompatibility of this biomaterial. Thin UHMW-PE-films (20 x 6 x 0.23 mm3) were implanted subcutaneously into rats. Morphology and reactivity of surrounding connective tissue against either pure UHMW-PE material or UHMW-PE containing alpha-tocopherol were studied at timed intervals (2 weeks, 3 month, and 6 month after operation) in 3 groups of animals, each group comprising 10 animals. Parallel to these tests, material changes were investigated in these 3 groups of 10 animals at the same intervals after operation with the help of infrared spectroscopy (FTIR). Within the implantation time, no noteworthy oxidative degradation could be observed. The amount of lost alpha-tocopherol due to diffusion is low enough to ensure a lifetime stabilisation of the UHMW-PE. The implants were all well tolerated and definitely encapsulated already 2 weeks after operation. Presence or absence of alpha-tocopherol in the implants did not evince morphological differences. Therefore, negative consequences were not manifest in the presence of alpha-tocopherol.

Animals↗
PubMed2005

Building up of the liquid-ordered phase formed by sphingomyelin and cholesterol.

The long-range and molecular orders and dynamics in codispersions of egg sphingomyelin-cholesterol have been investigated by synchrotron x-ray diffraction and electron spin resonance using phosphatidylcholine spin-labeled at several positions on the sn-2 chain. Mixtures containing 0, 17, 33, 41, 50 mol% cholesterol exhibited a single phase by x-ray diffraction methods. The temperature dependence of the d-spacing between 20 and 50 degrees C is attenuated with increasing proportions of cholesterol, becoming invariant for cholesterol contents of 41 and 50 mol% on completion of the liquid-ordered phase. Electron spin resonance revealed two sites for 17 and 33 mol% cholesterol. One site is highly ordered and the other is less ordered than the fluid phase of pure sphingomyelin as shown by the molecular and the intramolecular order parameters reflecting the segmental motions of the probe. The two-sites exchange rate indicates a mean lifetime of the sites of approximately 0.1 micros during which the lipid displacement is approximately 1 nm. The short lifetime of the sites probed by ESR and the single phase detected by x-ray diffraction support in this binary mixture, the building up of the Lo phase by a progressive accumulation of randomly distributed sphingomyelin-cholesterol condensed complexes rather than by diffusional exchange between extended domains.

Biophysical Phenomena↗
PubMed2005

Dynamics of the self-assembly of unilamellar vesicles.

We have studied the transient stages in the formation of unilamellar vesicles with millisecond time resolution. The self-assembly was initiated by rapid mixing of equimolar amounts of anionic and zwitterionic micelles and the transient micellar entities were probed by time-resolved small-angle x-ray scattering. Within the mixing time, original micelles transformed to disklike micelles which evolved further to a critical size and then closed to form monodisperse unilamellar vesicles within a second. Subsequent growth led to an unexpected broadening of the vesicle size distribution.

Crystallization↗
PubMed2005

Sterol profiling of amniotic fluid: a routine method for the detection of distal cholesterol synthesis deficit.

OBJECTIVES: Smith Lemli Opitz syndrome (SLOS) caused by a deficit of 3beta-hydroxysterol-Delta7 reductase was the first sterol deficit described with multiple malformations. The lack of specificity of many morphological abnormalities detected by ultrasound and their frequency have justified routine screening of amniotic fluid (AF) for sterols by GC-MS. The examination contributes to an improved knowledge of the sterol status in the fluid. METHODS: A series of sterol profiles is collated here. Accumulation of 7- and 8-dehydrocholesterol are diagnostic for SLOS. However, a number of other sterols have also been detected by GC-MS in control AF and their presence may be confusing. RESULTS AND CONCLUSIONS: In addition to cholesterol, the level of which varies as function of the gestational age, lathosterol is present together with trace amounts of 7- and 8-dehydrocholesterol and other precursors such as desmosterol, lanosterol, and dimethylsterol. Phytosterols are also present in 70% of AF samples that have been tested. Besides SLOS, GC-MS examination of amniotic fluid can detect various sterol deficits associated with malformations (lathosterolosis, desmosterolosis, X-linked chondrodysplasia, and particular Antley-Bixler syndrome). Practical conclusions support GC-MS as a routine method to investigate skeletal and central nervous system malformations.

Amniotic Fluid↗
PubMed2005

[Malignant melanoma of the uvula and soft palate].

Malignant melanoma of the uvula and soft palate is very rare. We describe a case demonstrating the typical aggressive behavior of mucosal melanoma in contrast to cutaneous melanoma. Regional lymph node and distant metastases often develop rapidly in this type of melanoma. Despite aggressive surgical approaches, other treatment options are often limited and usually palliative. Therefore, early diagnosis is critical in patients with mucosal melanoma.

Adult↗
PubMed2005

[Pictorial essay: Ultrasound of tumours and tumour-like lesions of peripheral nerves].

High-resolution ultrasound is an excellent diagnostic modality for visualising peripheral nerves and differentiate tumours of the peripheral nerve. With high-frequency transducers (5-15 MHz), peripheral nerves can be visualised, the hypoechoic nerve fascicles, the surrounding tissue and tumourous lesions including the relation to their nerve of origin can be evaluated. By using colour Doppler sonography (CDS), it is possible to detect and assess vascularisation of tumours of the nerve. We present sonographic features of common and uncommon benign and malignant tumours of the peripheral nerve.

Adult↗
PubMed2004

Introductory experience with the continuous glucose monitoring system (CGMS; Medtronic Minimed) in detecting hyperglycemia by comparing the self-monitoring of blood glucose (SMBG) in non-pregnant women and in pregnant women with impaired glucose tolerance and gestational diabetes.

OBJECTIVE: To assess the detection rate of hyperglycemia with a continuous glucose monitoring system compared to a self-monitoring blood glucose profile in non-pregnant, non-diabetic pregnant women, and patients with impaired glucose tolerance or gestational diabetes.. METHODS: Eight non-pregnant (NP) and 56 pregnant women (17 dietary-treated gestational diabetics (GDM), 15 women with impaired glucose tolerance (IGT), and 24 non-diabetic pregnant women (NDP)) underwent a 72-hour measurement with the CGMS (Medtronic Minimed, Northridge, CA, USA). Self-monitored blood glucose measurements, performed 30 minutes before and 120 minutes after each meal, were compared to the duration of hyperglycemia monitored by the continuous glucose monitoring system. RESULTS: No clinically observable infection was found at the subcutaneous tissue where the electrode was placed. A statistically significant difference was found between the groups in body mass index, HbA1c, and in gestational age, but not in age or parity. Using the self-monitored blood glucose (SMBG), 88 % (7/8) of the NP and 54 % (13/24) of the NDP had no measurement above 6.7 mmol/l. However, 17 % (4/24) of the NDP and 40 % (6/15) of the IGT showed more than two measurements above 6.7 mmol/l compared to 24 % (4/17) of the dietary-treated GDM. The differences between these groups were not significant (p = 0.21). The mean durations (+/- SD) of hyperglycemia above 6.7 mmol/l/24 h were: NP 111 +/- 120 min, NDP 138 +/- 120 min, IGT 381.8 +/- 295 min, and GDM 190 +/- 155 min, p = 0.017; above 7.8 mmol/l/24 h NP 24 +/- 49 min, NDP 38 +/- 47 min, IGT 170.7 +/- 190 min, and GDM 64 +/- 88 min, p = 0.016; and above 8.9 mmol/l/24 h NP 9.3 +/- 25 min, NDP 7.5 +/- 14 min, IGT 59 +/- 77 min, and GDM 14 +/- 21 min, p = 0.026. There was no significant difference in the fetal outcome or rate of birth percentiles using the sensor data. CONCLUSIONS: The use of the sensor in pregnant women is unproblematic. a) The CGMS detected more frequent and longer durations of hyperglycemia in GDM compared to non-diabetic pregnant women than the SMBG. b) Women with an IGT exhibited higher glucose levels than patients with gestational diabetes. c) The clinical importance of these hyperglycemic intervals, e.g. with respect to the risk for macrosomia, must be assessed in larger trials.

Blood Glucose Self-Monitoring↗
PubMed2004

Extracorporeal photochemotherapy for the treatment of exanthematic pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous skin disease of unknown aetiology that has been categorized into five clinical types based on age at onset, cutaneous features and prognosis. We present a patient with chronic exanthematic type II atypical adult PRP, whose skin status was significantly improved with monthly extracorporeal photochemotherapy (ECP). Various therapeutic regimens including narrow-band UV-B, bath PUVA therapy, systemic fumaric acid esters and systemic cyclosporin had failed. Oral retinoids could not be administered due to a type IIa hyperlipoproteinemia with profound hepatic steatosis and elevated liver transaminases. The observed clinical benefit may encourage future clinical studies analysing the effectiveness of ECP in otherwise unresponsive cases of type II PRP.

Adult↗
PubMed2003

The implementation of the 'International Classification of Functioning, Disability and Health' (ICF) in daily practice of neurorehabilitation: an interdisciplinary project at the Kantonsspital of Lucerne, Switzerland.

PURPOSE: The current paper describes the implementation of ICF as a standard language and framework for description of human functioning and disability for common use in every day work by the multiprofessional team. METHOD: An interdisciplinary project team involving all rehabilitation specialities was constituted. The extensive original document of ICF was broken down to a simplified raster for body functions and structures, activities and participation, as well as for contextual factors. These rasters had to cover the most important aspects concerning the patients treated on our unit. Checklists on the basis of these rasters were worked out for use by the different specialized teams. Using these checklists, rehabilitation conferences, form and language of interdisciplinary communication, goal setting and documentation were introduced newly in every day work for the interdisciplinary rehabilitation team, structured strictly based on the ICF-criteria. RESULTS: Since April 2002 the ICF-based processes are implemented in routine work for all members of the rehabilitation staff. First experiences show good acceptance by the team members, improvements in communication and documentation as well as substantial gains in content and handling of rehabilitation conferences. As a result of the implementation we observed, that participation, context and domiciliary interventions gained quite more influence in every day work at the unit. CONCLUSION: Implementation improved considerably the quality of interdisciplinary work processes and contributed to a more systematic approach to rehabilitation tasks by the team members.

Activities of Daily Living↗
PubMed2003

[Clinical characteristics and diagnosis of Smith-Lemli-Opitz syndrome and tentative phenotype-genotype correlation: report of 45 cases].

INTRODUCTION: SLO (Smith-Lemli-Opitz) syndrome is an autosomal recessive multiple congenital malformations syndrome, including mental retardation, failure to thrive, craniofacial abnormalities, incomplete development of male genitalia, limb anomalies and various internal organ abnormalities. This syndrome is caused by a deficiency of cholesterol biosynthesis at the distal step of 7-dehydrocholesterol reductase (7DHCR). PATIENTS AND METHODS: We have reviewed 45 cases of SLO syndrome and showed the large clinical spectrum of this syndrome. RESULTS: The prenatal diagnosis should be considered when dealing with antenatal growth retardation and visceral malformations. At birth, a normal weight does not systematically exclude the diagnosis. Diagnosis was more difficult for older children especially for girls and should be suspected on the association of mental retardation, autism, short stature and microcephaly. We found a correlation between low plasmatic cholesterol measurement and clinical severity. Phenotype-genotype correlation was difficult to establish. However, homozygosity for IVS8-1G > C splice site mutation was associated with severe phenotype. CONCLUSION: Better understanding of the 7DHCR gene regulation factors and of the compensatory mechanism of foeto-maternal cholesterol transfer are necessary to explain the wide clinical spectrum of the SLO syndrome.

Adolescent↗