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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 37 records · Page 2Linked to original sources

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.

This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P = 0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study.

Adolescent↗

A phase II study of dexamethasone, ifosfamide, cisplatin and etoposide (DICE) as salvage chemotherapy for patients with relapsed and refractory lymphoma.

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.

Adult↗

Detection of fast neuronal signals in the motor cortex from functional near infrared spectroscopy measurements using independent component analysis.

Fast changes, in the range of milliseconds, in the optical properties of cerebral tissue are associated with brain activity and can be detected using non-invasive near-infrared spectroscopy (NIRS). These changes are assumed to be caused by changes in the light scattering properties of the neuronal tissue. The aim of this study was to develop highly sensitive data analysis algorithms to detect this fast signal, which is small compared with other physiological signals. A frequency-domain tissue oximeter, whose laser diodes were intensity modulated at 110 MHz, was used. The amplitude, mean intensity and phase of the modulated optical signal were measured at a sample rate of 96 Hz. The probe, consisting of four crossed source detector pairs was placed above the motor cortex, contralateral to the hand performing a tapping exercise consisting of alternating rest and tapping periods of 20 s each. An adaptive filter was used to remove the arterial pulsatility from the optical signals. Independent component analysis allowed further separation of a signal component containing the fast signal. In nine out of 14 subjects, a significant fast neuronal signal related to the finger tapping was found in the intensity signals. In the phase signals, indications of the fast signal were found in only two subjects.

Adult↗

Endothelialization of a non-woven silk fibroin net for use in tissue engineering: growth and gene regulation of human endothelial cells.

We have previously shown that a biomaterial consisting of a non-woven fibroin net produced from silk (Bombyx mori) cocoons is an excellent scaffolding material for a wide variety of human cells of different tissue types. Endothelialization must take place for a biomaterial to be successful after implantation. Therefore, primary human endothelial cells and the human endothelial cell lines, HPMEC-ST1.6R and ISO-HAS-1, were examined for adherence and growth patterns on the fibroin nets by confocal laser scanning microscopy after vital staining of the cells and by electron microscopy. Endothelial cells adhered and spread along individual fibers of the nets and did not fill the gaps between individual fibers. Higher attachment and growth coverage was obtained if nets were first coated with gelatin, fibronectin or collagen type I. Proinflammatory markers of endothelial cells on the fibers exhibited a non-activated state and LPS-stimulated cells exhibited activation of these markers. Furthermore, a typical PECAM-1 localization at cell-cell contacts was observed. Scanning electron microscopic examination of fibroin nets after removal of cells did not demonstrate any changes to the fibroin structure. HUVEC and HDMEC on fibroin nets embedded in collagen type I gels formed microvessel-like structures. Thus, silk fibroin nets are a highly endothelial cell-compatible scaffolding material that support the growth, normal and inducible cell functions and angiogenesis potential of human endothelial cells in vitro similar to that observed in vivo.

Animals↗

[Notes on the GKV-modernization law (GMG)--a dentist's trend analysis].

Effective January 1st 2004 medical aid for patients receiving aid by means of the Federal German social welfare act has been transferred from the local social welfare offices to the statutory health insurances by decree regarding act modernisation of the statutory health insurance (GMG). The authors analyse the epidemiological and economical parameters concerning dental medical care for the city of Wuppertal on the basis of the experiences from 1994 to 2003 and attempt a well-founded forecast: the quality of medical standards will decline, whereas cost will rise.

Forecasting↗

Assessment of jaundice in preterm neonates: comparison between clinical assessment, two transcutaneous bilirubinometers and serum bilirubin values.

AIM: 1) To compare the clinical assessment of craniocaudal progression of jaundice and two transcutaneous bilirubinometers with serum bilirubin values in preterm neonates; 2) to identify factors affecting the difference between non-invasive bilirubin estimation and serum bilirubin. METHODS: Serum bilirubin was clinically estimated in healthy preterm newborn infants (34 to 36.9 gestational weeks) independently by a primary investigator and by nurses, and subsequently compared with separate measures of two transcutaneous bilirubinometers. RESULTS: A total of 107 measurements were performed on 69 infants. Minolta JM-102 showed the best performance, with ROC area under the curve of 0.96, followed by BiliCheck over the sternum (0.89) and over the forehead (0.88), clinical assessment by nurses (0.73) and by a physician (0.70). Serum bilirubin >190 micromol/l can be detected with 95% sensitivity with Minolta JM-102 > or =19 units, with BiliCheck > or =145 micromol/l over the sternum and > or =165 micromol/l over the forehead and with jaundice progression to the trunk or further (Kramer zone > or =2). Gestational age affects all non-invasive methods in the estimation of serum bilirubin, whereas skin colour affects both BiliCheck and clinical assessment. Ambient light affects only clinical assessment. CONCLUSION: Minolta JM-102 showed the best performance, closely followed by BiliCheck, with clinical assessment performing far worse than either transcutaneous method. None of the three methods are recommended as complete substitutes for serum bilirubin values in jaundiced preterm infants.

Bilirubin↗

Interferon-alpha-2b and oral cytarabine ocfosfate for newly diagnosed chronic myeloid leukaemia.

BACKGROUND: Treatment with interferon and subcutaneous cytarabine produces superior cytogenetic responses in chronic myeloid leukaemia (CML) than treatment with interferon alone, but at the expense of greater toxicity. Cytarabine ocfosfate (YNK01) is an oral precursor of cytarabine that may overcome some of the inconvenience and toxicities associated with subcutaneous cytarabine administration. PATIENTS AND METHODS: We studied the efficacy and tolerability of combination therapy with interferon-alpha-2b and YNK01 in patients with newly diagnosed, untreated CML. Forty patients were treated with interferon-alpha-2b (5 MU/m2/day) plus monthly courses of YNK01 (600 mg/day for 10 days) for 1 year. RESULTS: The 6-month complete haematological response rate was 63% and the 1-year major cytogenetic response rate was 30%, with 10% of cytogenetic responses being complete. With a median follow-up of 57 months, the estimated 5-year overall survival was 86% (95% confidence interval 70% to 94%). Treatment tolerability was poor, with toxicity leading to discontinuation of one or both drugs in 60% of cases. The median daily dose of interferon alpha-2b was 7.75 MU and the median dose of YNK01 was 600 mg/day for each 10-day treatment cycle. CONCLUSIONS: Interferon-alpha-2b and YNK01 produce cytogenetic responses comparable to those achieved with interferon-alpha-2b and parenteral cytarabine, although toxicity was excessive. Alternate dosing strategies may enhance the tolerability of YNK01.

Administration, Oral↗

[Intratympanic gentamicin treatment for intractable Menière's disease].

BACKGROUND: Intratympanic gentamicin is an accepted mode of treatment for patients with Meniere's disease who suffer from recurrent vertigo attacks in spite of conservative medical treatment. Recently, it gained popularity as the primary treatment for intractable Meniere's disease, prior to surgical procedures. However, administration methods and treatment protocols still differ from one medical center to another. OBJECTIVES: We aimed to present outcomes of gentamicin treatment for vertigo attacks and functional capacity, based on our experience with 23 patients over 3 years and review the literature on the subject. METHODS: Three specially prepared gentamicin injections, were administered once a month, according to the state of vertigo attacks, functional capacity, and hearing status. Clinical observation, frequent hearing examinations and caloric tests were used for follow-up. RESULTS: Following treatment, 20 (87%) patients no longer experienced vertigo attacks, while 16 of them (69.6%) reported full functional recovery. Two patients (8.7%) did not respond to treatment, and therefore, underwent surgical procedures. One patient (4.4%) did not complete therapy. Post treatment caloric tests showed significant deterioration (P < 0.02). Severe vestibular weakness (51-100%) was found in the treated ear in 11 of the 14 patients with unilateral disease (78.6%). The mean change in hearing examination was non-significant. However, two of the 21 patients suffered a change from moderate to severe hearing loss to complete deafness (9.5%). There was no case of post treatment infection or permanent tympanic perforation. CONCLUSIONS: Intratympanic gentamicin injection is a simple and safe procedure for intractable Meniere's patients, with a high success rate and low risk for hearing deterioration. It is recommended for patients with continuous functional disability prior to surgical treatment.

Anti-Bacterial Agents↗

Multimodal retinal image registration for optic disk segmentation.

OBJECTIVES: The analysis of the optic disk morphology with the means of the scanning laser tomography is an important step for glaucoma diagnosis. A method we developed for optic disk segmentation in images of the scanning laser tomograph is limited by noise, non-uniform illumination and presence of blood vessels. Inspired by recent medical research, we wanted to develop a tool for improving optic disk segmentation by registration of images of the scanning laser tomograph and color fundus photographs and by applying a method we developed for optic disk segmentation in color fundus photographs. METHODS: The segmentation of the optic disk for glaucoma diagnosis in images of the scanning laser tomograph is based on morphological operations, detection of anatomical structures and active contours and has been described in a previous paper. The segmentation of the optic disk in the fundus photographs is based on nonlinear filtering, Canny edge detector and a modified Hough transform. The registration is based on mutual information using simulated annealing for finding maxima. RESULTS: The registration was successful 86.8% of the time when tested on 174 images. Results of the registration have shown a very low displacement error of a maximum of about 5 pixels. The correctness of the registration was manually evaluated by measuring distances between the real vessel borders and those from the registered image. CONCLUSIONS: We have developed a method for the registration of images of the scanning laser tomograph and fundus photographs. Our first experiments showed that the optic disk segmentation could be improved by fused information from both image modalities.

Fundus Oculi↗

Electronic excitation and dynamic promotion of a surface reaction.

The mechanism of recombinative desorption of hydrogen from a Ru(0001) surface induced by femtosecond-laser excitation has been investigated and compared to thermally initiated desorption. For the laser-driven process, it is shown that hot substrate electrons mediate the reaction within a few hundred femtoseconds resulting in a huge isotope effect between H2 and D2 in the desorption yield. In mixed saturation coverages, this ratio crucially depends on the proportions of H and D. Deviations from second order desorption kinetics demonstrate that the recombination is dynamically promoted by excitation of neighboring, but nonreacting adatoms. A concentration dependent rate constant which accounts for the faster excitation of H versus D is proposed.

Journal Article↗

Coherent optical phonons and parametrically coupled magnons induced by femtosecond laser excitation of the Gd(0001) surface.

Coherent spin dynamics in the THz domain coupled to a coherent phonon is observed in the time-resolved second harmonic response of the Gd(0001) ferromagnetic metal surface. An LO phonon of 2.9 THz is excited by a transient charge displacement at the surface caused by resonant absorption of a fs laser pulse in the exchange-split surface state. This lattice vibration modulates the interlayer distance inducing a coherent variation of the exchange interaction between spins in adjacent layers. The resulting magnetization dynamics is considered as optical magnon wave packets coupled to the phonon.

Journal Article↗

Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility.

The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs.

Diagnostic Services↗

Visualization of the domain structure of an L-type Ca2+ channel using electron cryo-microscopy.

The three-dimensional structure of the skeletal muscle voltage-gated L-type calcium channel (Ca(v)1.1; dihydropyridine receptor, DHPR) was determined using electron cryo-microscopy and single-particle averaging. The structure shows a single channel complex with an approximate total molecular mass of 550 kDa, corresponding to the five known subunits of the DHPR, and bound detergent and lipid. Features visible in our structure together with antibody labeling of the beta and alpha(2) subunits allowed us to assign locations for four of the five subunits within the structure. The most striking feature of the structure is the extra-cellular alpha(2) subunit that protrudes from the membrane domain in close proximity to the alpha(1) subunit. The cytosolic beta subunit is located close to the membrane and adjacent to subunits alpha(1), gamma and delta. Our structure correlates well with the functional and biochemical data available for this channel and suggests a three-dimensional model for the excitation-contraction coupling complex consisting of DHPR tetrads and the calcium release channel.

Animals↗

Stabilisation and determination of the biological activity of L-asparaginase in poly(D,L-lactide-co-glycolide) nanospheres.

The preservation of biological activity of protein drugs in formulations is still a major challenge for successful drug delivery. The enzyme L-asparaginase, which exhibits a short in vivo half-life and is only active against leukaemia in its tetrameric form, was encapsulated in poly(D,L-lactide-co-glycolide) nanospheres by the (w/o)/w-emulsion solvent evaporation technique in presence of various potential stabilisers. Elucidation of the preparation steps revealed that the enzyme is denaturated at the aqueous/organic interface and by sonication. The preparation of L-asparaginase nanospheres with trehalose, PEG 400, and glycerol as components of the inner aqueous phase yielded colloidal formulations with increased biological activity as determined by an improved protocol for quantification of the active enzyme encapsulated. After lyophilisation the enzyme activity and particle size distribution were retained only by use of Pluronic F68 as a lyoprotectant. Despite the unaltered particle size and improved biological activity, the release profile of the enzyme was strongly altered by coencapsulation of the stabilisers resulting in increased first bursts. In consequence, the biological activity of L-asparaginase during preparation and storage can be improved by combining appropriate additives but concurrently the release profile is influenced.

Antineoplastic Agents↗

Complications of tracheal and thoracic surgery: the role of multisection helical CT and computerized reformations.

Helical computed tomography (CT) has an important role in the evaluation of a wide range of congenital and acquired thoracic abnormalities. The development of advanced computerized reformations enables the generation of bronchographic and bronchoscopic images of the tracheobronchial tree, as well as angiographic images of pulmonary arteries and veins. Additionally, it provides coronal and sagittal reconstruction imaging of parenchymal abnormalities. This information is obtained by a 20-30s procedure on a typical single channel system, which makes helical CT an optimal technique for the evaluation of patients undergoing major upper airways and thoracic interventions. The recent introduction of multisection CT scanners allows faster imaging of patients with thinner collimation, thus improving spatial resolution along the longitudinal (z) axis of the patient along with reduction of motion artefacts. This article demonstrates the use of dual and quad-section helical CT in the postoperative evaluation of patients undergoing laryngo-tracheal and thoracic interventions, including laryngoplasty, tracheal endoscopic laser ablation, lobectomy, pneumonectomy, lung transplantation, sleeve resection, pulmonary angioplasty, and pulmonary artery thromboendarterectomy. Emphasis is given to the additive value of using computerized reformations over axial images, especially for delineation of complex postoperative anatomical details in the tracheobronchial tree and pulmonary vasculature.

Adolescent↗