Reply to the comment by C.E. Rübe on O. Mücke et al.: Irradiation causes biphasic neutrophilic granulocyte phagocytic function in: Strahlenther Onkol 2005;181:319 (No. 5).
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Humans↗
Biomedical subjects
T Auer
Publications and source records attributed to T Auer.
Head and neck tumors: fractionated frameless stereotactic interstitial brachytherapy-initial experience.
The authors used a frameless stereotactic navigation system, the Vogele-Bale-Hohner head holder, and a targeting device to reproducibly position brachytherapy needles for fractionated interstitial brachytherapy in 12 patients with inoperable cancers of the head and neck. In all cases, deviations of the needle relative to the planned position were within 1-15 mm depending on the location of the tumor.
Brachytherapy↗
Repositioning accuracy: comparison of a noninvasive head holder with thermoplastic mask for fractionated radiotherapy and a case report.
PURPOSE: To compare accuracy, clinical feasibility, and subjective patient impression between a noninvasive head holder (Vogele Bale Hohner [VBH]; Wellhoefer Dosimetry, Schwarzenbruck, Germany) developed at the University of Innsbruck and the thermoplastic mask fixation system for use in fractionated external radiotherapy. We present a case report of an actual patient fixated in the VBH head holder during radiation therapy. MATERIALS AND METHODS: The VBH head holder consists of an individualized vacuum dental cast connected to a head plate via two hydraulic arms allowing noninvasive, reproducible head fixation of even uncooperative patients. Accuracy was tested and compared with that of the thermoplastic mask using the Phillips EasyGuide navigation system on five volunteers. Specific external registration points served as landmarks and their positions were compared after each repositioning. System and operator inaccuracy were also taken into account. The times taken for production and repositioning of the respective fixation devices were compared, and subjective impressions were noted. RESULTS: Mean VBH head holder repositioning accuracy was 1.02 mm while that of the thermoplastic mask was 3.05 mm. 69% of mask repositionings showed a deviation > 2 mm and 41% > 3 mm (as opposed to 8% and 1% respectively for the VBH head holder) Those points located farthest away from the respective plane of fixation showed the largest deviations. Both production and repositioning times were similar between the systems; depending upon the patient, the VBH head holder was generally better tolerated than the mask system. CONCLUSION: Due to its significantly better repositioning accuracy compared to that of the thermoplastic mask, the VBH head holder is especially suited for external radiation requiring precise repositioning due to critical tissues in immediate surrounding of the area to be irradiated.
Adult↗
[Noninvasive head fixation for external irradiation of tumors of the head-neck area].
PURPOSE: To fully utilize the technical capabilities of radiation diagnostics and planning, a precise and reproducible method of head fixation is a prerequisite. METHOD: We have adapted the Vogele-Bale-Hohner (VBH) head holder (Wellhöfer Dosimetrie, Schwarzenbruck, Germany), originally designed for frameless stereotactic operations, to the requirements of external beam radiotherapy. A precise and reproducible head fixation is attained by an individualized vacuum upper-dental cast which is connected over 2 hydraulic arms to an adjustable head- and rigid base-plate. Radiation field and patient alignment lasers are marked on a relocatable clear PVC localization box. RESULTS: The possibility of craniocaudal adjustment of the head plate on the base plate allows the system to adapt to the actual position of the patient on the radiotherapy couch granting tensionless repositioning. The VBH head holder has proven itself to be a precise yet practicable method of head fixation. Duration of mouthpiece production and daily repositioning is comparable to that of the thermoplastic mask. CONCLUSION: The new head holder is in routine use at our hospital and quite suitable for external beam radiation of patients with tumors of the head and neck.
Equipment Design↗
[3D navigation for interstitial stereotaxic brachytherapy].
AIM: The aim of this paper is to describe the adaption of 3D-navigation for interstitial brachytherapy. The new method leads to prospective and therefore improved planning of the therapy (position of the needle and dose distribution) and to the possibility of a virtual simulation (control if vessels or nerves are on the pathway of the needle). MATERIAL AND METHODS: The EasyGuide Neuro navigation system (Philips) was adapted in the way, that needles for interstitial brachytherapy were made connectable to the pointer and correctly displayed on the screen. To determine the positioning accuracy, several attempts were performed to hit defined targets on phantoms. Two methods were used: "free navigation", where the needle was under control of the navigation system, and the "guided navigation" where an aligned template was used additionally to lead the needle to the target. In addition a mask system was tested, whether it met the requirements of stable and reproducible positioning. The potential of applying this method in clinical practice was tested with an anatomical specimen. RESULTS: About 91% of all attempts lied within 5 mm. There were even better results on the more rigid table (94% < 4 mm). No difference could be seen between both application methods ("free navigation" and "navigation with template"), they showed the same accuracy. CONCLUSIONS: The accuracy of the phantom experiments and the confirmation by the experiment with the anatomical specimen showed that excellent results can be expected in clinical practice using rigid tables and patient supporting systems.
Brachytherapy↗
[First experiences with computer-assisted frameless stereotactic interstitial brachytherapy (CASIB)].
PURPOSE: To reach an optimal treatment result and to avoid damage to critical structures a homogeneous dose distribution in the tumor volume with a rapid decreasing dose to the surrounding structures is necessary. Fractionated interstitial brachytherapy of tumors in the ENT region employing needles depends on exact localization of the target volume during all fractions. Therefore reproducibility of positioning of the needle(s) plays an important role. MATERIAL AND METHODS: We used the ISG Viewing Wand system in combination with the Vogele-Bale-Hohner (VBH) head holder and a new targeting device. Point of entrance, pathway, and target point of the needle were planned and insertion of the needle simulated in advance. To date we have treated 7 patients with inoperable tumors in the ENT region. The actual position of the needle in the control CT was compared to the planned position. RESULTS: The accuracy of positioning of the needle depended on the location of the tumor. In a patient with a recurrent retroorbital adenocarcinoma the mean accuracy was 1 mm. Due to soft tissue displacement in the neck region and the resulting necessity to readjust the targeting device the needle was placed with a mean deviation of 15 mm between the planned and the actual position. CONCLUSIONS: Computer-assisted frameless stereotactic interstitial brachytherapy allows for precise, reproducible and preplanned insertion of hollow needles into target structures closely adherent to the surrounding tissue, thus avoiding damage of neighbouring structures. This technique is of great advantage in treating deeply seated tumors which are fixed to bony structures, especially at the skull base. Inaccuracy in the neck region caused by soft tissue shift requires improvement of the immobilization in this region.
Brachytherapy↗
Disseminated pagetoid reticulosis: response to bath PUVA.
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Adult↗
[100 MHz ultrasound of psoriasis vulgaris plaque].
PURPOSE: 20 MHz sonography of inflammatory diseases has concentrated on the evaluation of the echo-poor area in the upper dermis. With regard to higher resolution, this study focuses on the alterations of the epidermis and upper dermis skin using 100 MHz sonography. METHOD: 70 fully developed psoriasis vulgaris plaques of 20 patients were examined using our 100 MHz ultrasound equipment after application of salicylic acid in petrolatum for 24 h. After informing the patient about the aims of the study, a small knife biopsy was taken from 11 plaques. RESULTS: All psoriasis plaques exhibited, in comparison with normal skin, a significant widening of the skin entry echo (p < 0.001). Focally, this echo-rich line broke up into two thinner lines. Correlating histology exhibited in these areas an orthohyperkeratosis and focal parakeratosis. The upper dermis showed an echo-poor, band-shaped area which corresponded histologically to an acanthosis, elongation of rete ridges, and widening of the stratum papillare. The mean grey level of the echo-poor area and of the dermis beneath was significantly lower (p < 0.001) than the normal adjacent dermis. The thickness of the echo-poor area correlated with the thickness of the sum of the acanthosis and the inflammatory infiltrate in the histological sections (r = 0.94). CONCLUSION: Using 100 MHz sonography changes of the skin entry echo and the upper dermis can be visualized and quantified.
Adult↗
The determination of metabolite M17 and its meaning for immunosuppressive cyclosporin therapy.
Cyclosporin A (CyA) is intensively metabolized by the hepatic cytochrome p450 III monooxygenase A system in the human liver, the most important metabolites being M1, M17, and M21. Because CyA and its metabolites have nephrotoxic, hepatotoxic, and neurotoxic side effects, CyA dosage must be calculated to avoid the risk of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In this study, we determined the whole-blood concentrations of cyclosporin and metabolite M17 by high-pressure liquid chromatography (HPLC) and by monoclonal specific and polyclonal nonspecific fluorescence polarization immunoassay (Abbott) in patients after immunosuppressive treatment. Patients with different resorption and metabolization rates showed high individual variations. CyA concentrations in patients with good liver function and low concentrations of CyA metabolites showed a good correlation between the HPLC and the FPIA (TDx-monoclonal assay) methods in ranges between 25 and 180 ng/mL. TDx-monoclonal was not always as precise as HPLC. In cases of metabolic disorders, we found false high CyA concentrations assayed with the immunologic method, caused by a crossreaction of the elevated metabolite concentration. We found that HPLC rendered more information about the extent of immunosuppressive activity and the metabolization rate and showed a good correlation with the concentration of metabolite M17 and total metabolites measured with the Abbott CyA polyclonal kit.
Antibodies↗
Comparison of skin atrophy and vasoconstriction due to mometasone furoate, methylprednisolone and hydrocortisone.
BACKGROUND/AIMS: Topical glucocorticoids with improved benefit/risk ratio are of great interest in dermatology, but there are very few trials directly comparing the efficacy and side-effects of these new preparations. In our study the vasoconstrictor effect and side-effects of two of these new glucocorticoids were evaluated and blanching effect was determined by two-dimensional laser scanning. METHODS: In a randomised, double blind intra-individual comparative trial, 10 subjects were treated with various glucocorticoids or drug-free vehicle. The test drugs were mometasone furoate (MF), methylprednisolone aceponate (MP) and hydrocortisone (OH-C). The preparations were tested for a period of 3 weeks with occlusion on the flexor side of the forearm. Skin thickness and vasoconstriction were determined using 20 MHz ultrasound scanning, laser Doppler scanning (LDS) and chromometry. RESULTS: No adverse effects were observed during the observation period. Only partial vasoconstriction occurred in most cases during the observation period. MP and MF produced maximal blanching between days 3 and 5 of treatment, while with OH-C clinically visible blanching did not occur. Ultrasound evaluation of skin thickness showed similar behaviour for all three steroids tested: there were no signs of skin atrophy in any of the cases. LDS evidenced hypoperfusion of a test area on the perfusion image in only a few patients and there were no significant differences between the steroids tested. On evaluation of vasoconstriction caused by the steroids tested using chromometry there was a significant difference between MF and OH-C on the L*a*b* scale (P < 0.005). Only at day 3 was a blanching effect caused by MP and MF demonstrable (a-value, P < 0.05). CONCLUSION: In summary, the synthetic steroids MF and MP presented side-effects similar to those of OH-C but much greater vasoconstrictor effect; after an application period of over 5 days under occlusion a blanching effect in our model was not demonstrable by means of chromometry. Two-dimensional laser scanning offers no advantage in the evaluation of the blanching effect in comparison to one-dimensional laser fluxmetry (LDF).
Administration, Topical↗
Rapid, sensitive high-performance liquid chromatographic method for the determination of cyclosporin A and its metabolites M1, M17 and M21.
Cyclosporin A (CyA) and its metabolites seem to have nephro-, hepato- and neurotoxic side effects. Immunosuppressive therapy is a narrow path between the risk of rejection by underimmunosuppression and toxic organ damage by overdosage. Thus CyA dosage must be calculated to avoid the risks of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In routine monitoring of CyA therapy, it can be important to measure not only the parent drug but also the metabolites. We describe a rapid and isocratic high-performance liquid chromatographic method for measurement of CyA and its metabolites M1, M17 and M21 in whole blood. CyA was detected by ultraviolet absorption at 212 nm with a CN analytical column maintained at 50 degrees C and recycling of hexane-isopropanol as mobile phase for improved long-term column stability and efficiency. The minimum detectable concentration of CyA and the three metabolites was 10 ng/ml blood. Our modified HPLC method for the determination of CyA and its metabolites is a simple (isocratic), rapid (the retention times were 7.1 min for CYD, internal standard, 8.9 min for CyA, 11.0 min for M21, 12.9 min for M17 and 16.3 min for M1) and economical method suitable for measuring the concentration of the major metabolite, M17, and for routine monitoring of CyA-treated patients.
Chromatography, High Pressure Liquid↗
VBH head holder to improve frameless stereotactic brachytherapy of cranial tumors.
Precise target localization is essential for brachytherapy. We have adapted the VBH (Vogele-Bale-Hohner) head holder (Wellhoefer Dosimetry, Schwarzenbruck, Germany), originally developed at the University of Innsbruck, for frameless stereotactic surgery, for use in brachytherapy of cranial tumors. The VBH head holder allows for rigid, noninvasive head fixation by means of an individualized upper dental cast. Registration rods, rigidly attached to the dental cast, provide stable external points of reference. The dental cast is sucked against the upper palate by vacuum, and then the fixated patient is scanned. During simulation, the targeting device can be positioned with respect to the virtual patient using the ISG Viewing Wand. Following simulation, the real patient is repositioned under vacuum control, the targeting device repositioned as well, and the actual brachytherapy initiated. The VBH head holder is well tolerated by patients and simple to use, and various studies have confirmed submillimeter accuracy. The modified head holder in combination with a new targeting device allows for precise and well-planned insertion of hollow needles into a tumor using frameless stereotactic systems as well as being compatible for uses in other fields.
Brachytherapy↗
Selective amplification of RNA utilizing the nucleotide analog dITP and Thermus thermophilus DNA polymerase.
The ability to selectively amplify RNA in the presence of genomic DNA of analogous sequence is cumbersome and requires implementation of critical controls for genes lacking introns. The convenient approaches of either designing oligonucleotide primers at the splice junction or differentiating the target sequence based on the size difference obtained by the presence of the intron are not possible. Our strategy for the selective amplification of RNA targets is based on the enzymology of a single thermostable DNA polymerase and the ability to modulate the strand separation temperature requirements for PCR amplification. Following reverse transcription of the RNA by recombinant Thermus thermophilus DNA polymerase (rTth pol), the resulting RNAxDNA hybrid is digested by the RNase H activity of rTth pol, allowing the PCR primer to hybridize and initiate second-strand cDNA synthesis. Substitution of one or more conventional nucleotides with nucleotide analogs that decrease base stacking interactions and/or hydrogen bonding (e.g. hydroxymethyldUTP or dITP) during the first- and second-strand cDNA synthesis step reduces the strand separation temperature of the resultant DNAxDNA duplex. Alteration of the thermal cycling parameters of the subsequent PCR amplification, such that the strand separation temperature is below that required for denaturation of genomic duplex DNA composed of standard nucleotides, prevents the genomic DNA from being denatured and therefore amplified.
DNA-Directed DNA Polymerase↗
Bacterial ghosts: non-living candidate vaccines.
Expression of cloned PhiX174 gene E in bacteria results in lysis of bacteria. It is unique among phage lysis systems as it introduces a transmembrane tunnel structure through the cell envelope complex of Gram-negative bacteria. The resulting bacterial ghosts have intact envelope structures devoid of cytoplasmic contents. E-mediated lysis has been achieved in a variety of Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Vibrio cholerae, Klebsiella pneumoniae, and Actinobacillus pleuropneumoniae. Such ghosts, derived from human or animal pathogens, have been proposed as non-living candidate vaccines and represent an alternative to heat or chemically inactivated bacteria. In 'recombinant ghosts', foreign proteins (e.g., viral proteins) are inserted into the inner membrane via specific N-, or C-, or N- and C-terminal anchor sequences prior to lysis. Relevant advantages of (recombinant) bacterial ghosts as immunogens include: (i) inactivation procedures that denature relevant immunogenic determinants are not employed in the production of ghosts used as vaccines or as carriers of relevant antigens; (ii) the recombinant proteins are inserted into a highly immune stimulatory environment; (iii) there is no size limitation of the foreign protein moieties: multiple antigenic determinants can be presented simultaneously; (iv) bacterial ghosts can be produced inexpensively in large quantities; (v) (recombinant) ghosts are stable for long periods of time and do not require the cold chain storage system. Intraperitoneal, subcutaneous or intramuscular applications of recombinant ghosts in experimental animals induced specific humoral and cellular immune responses against bacterial and viral components. Initial aerosol vaccinations of swine with ghosts from Actinobacillus pleuropneumoniae showed that protective immunity can be established by this route of application and that the well-preserved surface structures of ghosts obtained by E-mediated lysis are able to target the mucosal immune system.
Animals↗
Evoked epimyocardial electrogram for rejection diagnosis after heart transplantation.
An endomyocardial electrogram (ECG) was reported to be a sensitive and practicable method for rejection monitoring after heart transplantation. Long-term follow up was limited, however, by variations of signals. The repolarization part of ECG signals vary with changes of heart rate. Both can be avoided by using pacemaker-induced signals. For stimulation and sensing of the ventricular-evoked response, a new type of electrode with fractal surface structure was used. Twenty patients undergoing heart transplantation were evaluated. Amplitudes of the depolarization and repolarization part of the ventricular-evoked response signals were analyzed and related to the degree of acute rejection according to histological findings from endomyocardial biopsy. Signals were transferred by Internet and analyzed automatically. In the case of focal moderate rejection (grade 2, International Society for Heart Transplantation grading) and higher degrees of rejection, a significant amplitude decrease was found. This sensitive non-invasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.
Adult↗
Donor heart quality control. Analysis of echocardiographic (EC) findings and patient outcome.
In a retrospective analysis, 149 echocardiographic (EC) evaluations were compared with conventional clinical parameters for donor heart selection. Of these cases, 12% were found with severe impairment of ventricular wall motion or with morphological abnormalities. Nearly half of the echocardiographically diagnosed pathological findings in donor hearts were not detected by conventional standards for heart screening. Analysis of EC-screened donor heart outcome showed a primary graft nonfunction rate of 3.1%. We suggest EC as an additional screening instrument for further dynamic and morphological information about donor heart condition. Potential donors can be saved for transplantation and severe complications can be avoided by detecting occult cardiac dysfunction. Early detection of cardiac dysfunction may have an impact on donor therapy and can avoid unnecessary and expensive transportation of the surgical team to the harvest site.
Adolescent↗
Cytomegalovirus antigenemia as a marker for antiviral therapy after heart transplantation.
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Antigens, Viral↗
Paced epimyocardial electrograms for noninvasive rejection monitoring after heart transplantation.
BACKGROUND: Diagnosis of acute heart rejection after transplantation with the help of epimyocardial electrograms has been reported as a sensitive and practicable method. Long-term follow-up has been limited, however, by variations o signal, which can be avoided by using pacemaker-induced signals. METHODS: For stimulation and detection of the ventricular evoked response, a new type of electrode with fractal surface structure was used. Seventeen patients undergoing heart transplantation were included in the study. Amplitudes of the depolarization and repolarization parts of ventricular evoked response signals were analyzed and related to the degree of acute rejection according to histologic findings from endomyocardial biopsy. RESULTS: In cases of focal moderate rejection (grade 2, International Society for Heart and Lung Transplantation grading) and higher degrees of rejection, significant amplitude decreases were found. CONCLUSION: This sensitive noninvasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.
Biopsy↗