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Biomedical subjects

M Günther

Publications and source records attributed to M Günther.

At least 19 recordsLinked to original sources
PubMed2006

Effects of hypoxia and limited diffusion in tumor cell microenvironment on bystander effect of P450 prodrug therapy.

Cytochrome P450 (CYP) enzyme 2B1 metabolizes the anticancer prodrug cyclophosphamide (CPA) to 4-hydroxy-CPA, which decomposes to the cytotoxic metabolites acrolein and phosphoramide mustard. We have evaluated the bystander cytotoxicity of CPA in combination with CYP2B1 gene-directed enzyme prodrug therapy using a cell culture-based agarose overlay technique. This method mimics the tumor microenvironment by limiting the diffusion of metabolites and by reducing the oxygen concentration to levels similar to those found in solid tumors. Under these conditions, the CYP activity of CYP2B1-expressing tumor cells was decreased by 80% compared to standard aerobic conditions. Despite this decrease in metabolic activity, a potent bystander effect was observed, resulting in up to 90% killing by CPA of a tumor cell population comprised of only approximately 20% CYP-expressing tumor cells. Similarly, transient transfection of a small fraction ( approximately 14%) of a human hepatoma Huh7 cell population with a CYP2B1 expression plasmid followed by short-term treatment with CPA (5 h) led to an eradication of 95% of the cells. No such bystander effect was observed without the agarose overlay. These findings suggest that the agarose overlay technique is very useful as an in vitro test system for investigation of the bystander effect of CYP/CPA and other enzyme/prodrug combinations under conditions that mimic the hypoxic conditions present in solid tumors in vivo.

Animals↗
PubMed2005

[Incidental carcinoma of the prostate: can we and should we recommend radical prostatectomy?].

INTRODUCTION: There is controversy regarding tumor control of incidental prostate cancer (PC). We evaluated in a large cohort if we can recommend radical prostatectomy after TURP. MATERIAL AND METHOD: In 52 (4.3%) from a total of 1207 patients undergoing radical prostatectomy the diagnosis had been made by TURP. In a retrospective analysis we evaluated morbidity, histopathological results, and tumor control of pT1a/b tumors. RESULTS: The number of incidentally detected PC decreased with time. In 5.8% in the TURP group and in 0.5% of the needle biopsy group, there was no residual tumor found (p<0.001). Morbidity was similar +/- TURP with the exception of operation time (206 vs 188 min) and catheter duration (19.3 vs 17.3 days). Postoperative continence was identical. There was no difference in tumor control for local recurrence-free survival and PSA-free survival with and without TURP. CONCLUSIONS: The rate of incidentally detected PC by TURP decreases over time, but in almost all cases we found clinically relevant cancer. TURP is not an adverse prognostic factor and morbidity is similar compared with patients who were diagnosed by needle biopsy. Our data confirm that we should recommend radical prostatectomy to patients who are candidates for further curative therapy.

Aged↗
PubMed2005

Radiation-reducing planning of cardiac catheterisation.

Any radiation exposition for medical purposes should be kept as low as is reasonably achievable. Mean patient radiation exposure of diagnostic cardiac catheterisation is high (16-106 Gy x cm2) and for this reason the International Commission on Radiological Protection (ICRP) recommends credentialing radiation protection training programmes. Twenty cardiologists each documented various dose parameters of 10 cardiac catheterisations, before and after a 90-minute mini-course of the ELICIT study group ("Encourage to Less Irradiating Cardiologic Interventional Techniques"), and could achieve a reduction of the mean dose-area product by 15.9+/-9.0 Gy x cm2, equivalent to 47%. The presented radiation-reducing planning of invasive cardiac catheterisation for this reason is the first one validated in clinical routine and consists of 6 standard runs--one for the left ventricle, 3 and 2 for the left (LCA) and right coronary artery (RCA), respectively--depending on anatomy and findings supplemented by 1...4 special projections. The caudal posteroanterior (PA) view documents the left coronary main stem, proximal and distal left anterior descending artery (LAD), and proximal and mid circumflex segments. The cranial PA view however is suitable for the left coronary orifice, circumflex periphery, LAD, all diagonal bifurcations, and collateral pathways towards the RCA. LCA standard angiography is completed by lateral 90 degrees/0 degrees left anterior oblique (LAO) angulation. The 60 degrees/0 degrees LAO angulation visualises the right posterolateral artery (RPL) and the RCA to its bifurcation. The more proximal one finds the bifurcation, the more the second standard cranial PA view for RCA should vary towards the cranial right anterior oblique (RAO) and finally 30 degrees/0 degrees RAO view. The efficiency of these less-irradiating angulations are improved by radiation-reducing techniques as follows: restriction to essential radiographic frames and runs, consistent collimation to the region of interest--particularly during coronary intubation--, adequate instead of best possible image quality, short skin-to-image-intensifier distance, inspiration during radiography, preference for projections that rotate out the spine, optimisation of fluoroscopy time, well-experienced and well-rested interventionists.

Body Burden↗
PubMed2005

Investigations for the diagnostic recording of nasal wing collapse.

BACKGROUND: The inspiratory medial movement of the nasal wing at high flow velocities is a protective physiologic mechanism. If this collapse of the nasal wing occurs at lower flow velocities, it may result in nasal obstruction. "Nasal wing collapse" is generally a clinical diagnosis. However, in the pressure-flow relationship of rhinomanometry, the medial movement of the nasal wing can be documented in the inspiratory arm of the graph. The diagnostic impact of this hysteresis was investigated. METHODS: The pressure-flow curves of three box models and three nasal models with a moveable valve (analogous to the nasal wing) in the entrance area as well as three volunteers with unstable nasal wings were investigated. We recorded synchronously the pressure-flow relationship and by endoscopy the movement of the valve in the box models and the nasal wing in the volunteers on video. For evaluation, we used the frame by frame analysis of the tape. RESULTS AND CONCLUSIONS: The medial movement of the nasal wing causes a hysteresis in the inspiratory arm of the pressure-flow curve. At this point, the graph runs on or between two border curves, termed the "no collapse curve" (for the maximally opened valve or a stable nasal wing) and the "collapse curve" (for the subtotally closed valve or a collapsed nasal wing), respectively. Analogous to the nasal wing motion, the descending course of hysteresis runs in two phases, and the ascending course runs in three phases. The medial movement of the nasal wing is expressed by a deviation of the graph from the "no collapse curve." The flow, at which the graph leaves this curve, depends on the elasticity module of the nasal wing. The extent of nasal wing collapse is reflected by the approximation of the pressure-flow curve to the "collapse curve" of the graph. The hysteresis appears because of a late opening of the collapsed nasal wing.

Adult↗
PubMed2004

Comparison between HPLC and HPTLC-densitometry for the determination of harpagoside from Harpagophytum procumbens CO(2)-extracts.

Carbon dioxide (CO(2)) extracts of the secondary roots of Harpagophytum procumbens were quantified by high performance liquid chromatography (HPLC) and high performance thin layer chromatography (HPTLC). An isocratic HPLC method was used for the quantification of the iridoid glucoside harpagoside at 278 nm. A HPTLC assay was developed for the determination of harpagoside after coloration at 509 nm. The diode array detection of both analytical assays were used to examine the purity of harpagoside peaks and compared with the standards, respectively. The assays provide good accuracy, reproducibility and selectivity for the quantitative analysis of harpagoside. The harpagoside contents of 15 different CO(2)-extracts were compared by HPLC and HPTLC-densitometry. The quantitative results of both analytical methods did not show any statistical significance between each other, although a trend to slightly lower mean values could be found for the HPTLC method.

Analgesics↗
PubMed2004

[Noninvasive measurement of relative cerebral blood flow with the blood bolus MRI arterial spin labeling: basic physics and clinical applications].

Knowledge of tumor blood flow is important for diagnosis and follow-up of brain tumors after therapy, especially to discriminate necrosis from tumor recurrence after radiation or chemotherapy. Meanwhile, perfusion and diffusion MRI, besides MR-angiography, are state of the art in stroke imaging. Until now, perfusion imaging was mostly performed using the first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) MRI. The MRI-based arterial spin labeling technique (ASL) is a novel approach for measuring relative cerebral blood flow (rCBF) without using extrinsic contrast agents, by labeling spins of flowing arterial blood as intrinsic contrast agent. This article describes physical basics of ASL and shows clinical examples in neuroimaging such as in meningeoma, glioblastoma, oligodendroglioma, and cerebral ischemia, using the Q2TIPS ASL technique. Gray matter is clearly visible, while the observed white matter signal obtained by Q2TIPS is only slightly higher than background noise. Venous blood causes artefacts in the sagittal sinus and other large superficial veins in the subarachnoid space. Meningeoma and glioblastoma show elevated rCBF, whereas oligodendroglioma and cerebral ischemia have reduced rCBF values. Arterial-spin-labeling techniques are noninvasive tools for measuring rCBF within 5 min, using a standard MRI scanner.

Blood Flow Velocity↗
PubMed2004

[Physical characterization of the therapeutic device Posturomed as a measuring device--presentation of a procedure to characterize balancing ability].

Training measures to improve neuromuscular coordination are becoming ever more popular for both prevention and rehabilitation, not only in athletes but also patients receiving joint replacements. Numerous proprioceptive training measures and devices are used to train the sense of balance. Parameters suitable for quantifying the results of therapy are largely lacking. Herein, a simple method for quantifying the balancing on one leg using the therapeutic device (Posturomed) commonly employed to train balance in the upright stance. The horizontal movements of the oscillating suspended platform were recorded in two orthogonal directions using a non-contact measurement system. To simulate disturbance of the upright stance, a mechanical deflection device was applied to the platform. The physical characterization of the measuring system was done using rigid masses. 13 volunteers adopting a one-legged stance were investigated. The measured displacement in the medio-lateral (ML) and AP directions were used to establish a balance index. Examination of the oscillatory behaviour of the platform revealed the path signal to be a suitable parameter for analyzing the platform movements. Differences in balance characteristics between AP and ML movements could be quantified. Frontal disturbance of the upright stance is equilibrated more effectively than lateral disturbances. Combined with a non-contact path measuring system the therapeutic device is suitable for characterizing balancing ability in an upright one-legged stance. To obtain more detailed information on the neuromuscular mechanisms involved, further studies are needed.

Fourier Analysis↗
PubMed2003

Airbag contact in traffic accidents: DNA detection to determine the driver identity.

A total of 34 deployed driver and passenger airbags from altogether 20 vehicles after frontal collisions were investigated. In 80% of the airbags possible biological traces could be located with an alternative light source (ALS, Polilight) at a wavelength of 450-470 nm. These traces were swabbed, a part of them additionally cut and subjected to DNA analysis, which led to comparable SGMplus profiles in about 60%. In the 20% of the airbags on which no possible biological traces could be located, the whole surfaces were swabbed. In these cases subsequent DNA profiling mostly led to non-interpretable results. For the evaluation and interpretation of the data, buccal swab samples provided by drivers and co-drivers were analysed. The results and conclusions from DNA analyses and the declarations from the involved passengers were always concordant. Thus, molecular biological analysis of deployed airbags can help to determine the occupants positions within a vehicle (driver or passenger status) at the time of impact.

Accidents, Traffic↗
PubMed2003

Intraoperative urodynamics in spinal cord surgery: a study of feasibility.

Intraoperative monitoring (IOM) of bladder function in spinal cord surgery is a challenging task due to vegetative influences, multilevel innervation and numerous supraspinal modulating factors. Despite routine use of urodynamics in neurosurgery for implantation of bladder stimulators or denervation of nerve fibres in spastic reflex bladders, application of IOM in patients with spinal cord tumours or tethered-cord syndrome is not widespread. Combining urodynamics with sphincter electromyography (EMG) in IOM enables identification of bladder efferents responsible for contraction and continence. We monitored four patients with ependymoma of the Cauda equina, one patient with tethered-cord syndrome and two patients with cervical intramedullary tumours. In all patients undergoing operations of the Cauda equina, identification of bladder efferents responsible for detrusor contraction was possible. There was good correlation between preoperative bladder dysfunction, preoperative urodynamics and intraoperative pressure increase by bladder contraction or latency between stimulation and contraction. This method proved unsuitable for intramedullary tumours where no contraction of the bladder could be observed while stimulating the spinal cord. Intraoperative monitoring of urodynamics is an effective tool for identifying bladder efferents in the Cauda equina. Intraoperative conclusions on bladder dysfunction through registration of pressure increase and latency are possible.

Adult↗
PubMed2003

[Monitoring of irradiated brain metastases using MR perfusion imaging and 1H MR spectroscopy].

PURPOSE: In follow-up examinations of irradiated brain metastases conventional contrast-enhanced morphological MR imaging is often unable to distinguish between transient radiation effects, radionecrosis,and tumor recurrence. To evaluate changes of relative cerebral blood flow (rCBF) in irradiated brain metastases arterial spin-labeling techniques (ASL) were applied and compared to the outcome of (1)H MR spectroscopy and spectroscopic imaging ((1)H MRS, SI). PATIENTS AND METHODS: In 2 patients follow-up examinations of irradiated brain metastases were performed on a 1.5-T tomograph (average single dose: 20 Gy/80% isodose). Relative CBF values of gray matter (GM), white matter (WM),and metastases (Met) were measured by means of the ASL techniques ITS-FAIR and Q2TIPS. (1)H MRS was performed with PRESS 1500/135. RESULTS: In both patients with initially hyperperfused metastases (Met/GM >1) the reduction of rCBF after stereotactic radiosurgery indicated response to treatment--even if the contrast-enhancing region increased--while increasing rCBF values indicated tumor progression. The findings were confirmed by (1)H MRS, SI and subsequent follow-up. CONCLUSION: The ASL techniques ITS-FAIR and Q2TIPS are able to monitor changes of rCBF in irradiated brain metastases. The two cases imply a possible role for ASL-MR perfusion imaging and (1)H MR spectroscopy in differentiating radiation effects from tumor progression.

Aged↗
PubMed2003

Standardization of occupational dose to patient DAP enables reliable assessment of radiation-protection devices in invasive cardiology.

PURPOSE: With the aim of assessing the effectiveness of radiation-protection devices in invasive cardiology, the goal of this study was to validate relative parameters for operator occupational exposure, standardized to the patient's primary dose. MATERIAL AND METHODS: One of these parameters was the local dose, measured in air at the operator's position per dose area product (DAP), applied to a male anthropomorphic Alderson-Rando phantom for simulation of coronary angiography. The second parameter was personal occupational dose to the operator per DAP, measured by thermoluminescence dosimeter stripes during 121 procedures in routine clinical work. RESULTS: The local and personal doses per unit DAP - using typical 0.5-mm lead overcouch and undercouch protection - were comparable (left eye 180 vs. 360, thyroid 260 vs. 260, left shoulder 280 vs. 150, chest 400 vs. 500, hands 400 vs. 550, waist 900 vs. 400 nSv/Gy x cm (2)). The results, however, were far lower than typically reported values. Our findings therefore disclose a typically inadequate use or acceptance by individual operators of available table-attached lead protection devices, and of ceiling-attached lead-glass screens. The additional use of individual 1.0-mm lead-equivalent garments reduced local doses to levels between 1. 10 %. CONCLUSIONS: DAP-standardized dose parameters - determined experimentally (phantom measurements), or in routine clinical work - are not appreciably influenced by the equipment age and type, or by the image-intensifier entrance dose rate of the respective catheterization system. They are consequently best suited for obtaining eloquent comparisons of various radiation-protection devices, and for reliable estimation of local scatter radiation exposure by simple documentation of intervention DAP.

Computer Simulation↗
PubMed2002

Reconstructing the mechanics of quadrupedalism in an extinct hominoid.

Traditionally, analogising comparative anatomical approaches, working on features of individual bony elements, have led to the Miocene hominoids Proconsul heseloni and P. nyanzae being described as arboreal, with a variety of possible locomotion modes. Whilst most researchers seemingly agree that quadrupedal was one of the most frequently adopted modes, any deeper knowledge about the kinematical characteristics of such quadrupedalism is very limited. Based on the previous studies and a computer simulation technique developed in our laboratory, a set of alternative models for Proconsul quadrupedalism was created. The body measurements and initial properties for the different models were held constant, using data from published literature if available, or otherwise estimated from data for Pan. Judged by the power output of joints, the results of computer simulation indicate that the style of quadrupedal locomotion typical of living macaques fits the body proportions of Proconsul better than that of Canis domesticus, Varecia variegata, Cebus albifrons or Pan troglodytes. It may reasonably be assumed that Proconsul's quadrupedal mode was similar to that of living macaques.

Animals↗
PubMed2001

Generation of an immortalized human CD4+ T cell clone inhibiting tumor growth in mice.

Tumor antigen-specific T cell clones represent a useful tool in tumor immunology; however, their long-term culture is limited. To generate an immortalized cytotoxic T cell clone against the human tumor antigen mucin, we exposed a previously generated T cell culture to Herpesvirus saimiri. We obtained an immortalized human CD4+ T cell clone, termed SITAM. Clonality of these cells was shown by analysis of the alpha/beta-T cell receptor (TCR) repertoire. Cytolytic activity was demonstrated against several mucin-expressing tumor cell lines and could not be detected against non-mucin-expressing cells. SITAM cells maintained their features stably for 2 years. Furthermore, growth of the tumor cell line Capan-2 in NOD/SCID mice was inhibited when SITAM cells were coinjected subcutaneously with tumor cells. SITAM cells provide an unlimited source of clonal T cells for analysis of tumor recognition and may be of help in TCR-targeted immunotherapy.

Animals↗
PubMed2001

Rapid decline of antibodies after hepatitis A immunization in liver and renal transplant recipients.

BACKGROUND: Hepatitis A vaccine is safe and achieves good seroconversion rates in liver (LTX) and renal (RTX) transplant recipients. METHODS: A study was performed to determine the anti-hepatitis A virus (HAV) antibody decline in LTX and RTX patients, and in healthy controls who have been immunized with two doses of hepatitis A vaccine. RESULTS: LTX and RTX patients had a satisfactory seroconversion rate after complete immunisation. However, 2 years later they had experienced a much more rapid antibody decline than controls, and only 59% of LTX and 26% of RTX seroconverters showed titres above the cut-off level defined as protective. CONCLUSIONS: Patients on immunosuppressive therapy may not be adequately protected against hepatitis A a few years after vaccination and alternative vaccination schemes may have to be considered.

Cyclosporine↗
PubMed2001

Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR).

Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4 degrees. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 +/- 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of -138 - 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels.

Adult↗
PubMed2001

Stable operation of an elastic three-segment leg.

Quasi-elastic operation of joints in multi-segmented systems as they occur in the legs of humans, animals, and robots requires a careful tuning of leg properties and geometry if catastrophic counteracting operation of the joints is to be avoided. A simple three-segment model has been used to investigate the segmental organization of the leg during repulsive tasks like human running and jumping. The effective operation of the muscles crossing the knee and ankle joints is described in terms of rotational springs. The following issues were addressed in this study: (1) how can the joint torques be controlled to result in a spring-like leg operation? (2) how can rotational stiffnesses be adjusted to leg-segment geometry? and (3) to what extend can unequal segment lengths and orientations be advantageous? It was found that: (1) the three-segment leg tends to become unstable at a certain amount of bending expressed by a counterrotation of the joints; (2) homogeneous bending requires adaptation of the rotational stiffnesses to the outer segment lengths; (3) nonlinear joint torque-displacement behaviour extends the range of stable leg bending and may result in an almost constant leg stiffness; (4) biarticular structures (like human gastrocnemius muscle) and geometrical constraints (like heel strike) support homogeneous bending in both joints; (5) unequal segment lengths enable homogeneous bending if asymmetric nominal angles meet the asymmetry in leg geometry; and (6) a short foot supports the elastic control of almost stretched knee positions. Furthermore, general leg design strategies for animals and robots are discussed with respect to the range of safe leg operation.

Animals↗
PubMed2000

Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.

BACKGROUND: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.

Adolescent↗