[Waiting lists in German radio-oncology. Egalitarian justice and evidence based medicine can be used as an aid for allocation of scarce resources].
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Evidence-Based Medicine↗
Biomedical subjects
M Herbst
Publications and source records attributed to M Herbst.
Membrane potential dependent modulations of calcium oscillations in insulin-secreting INS-1 cells.
This study was undertaken to examine the role of K(+) channels on cytosolic Ca(2+) ([Ca(2+)](i)) in insulin secreting cells. [Ca(2+)](i) was measured in single glucose-responsive INS-1 cells using the fluorescent Ca(2+) indicator Fura-2. Glucose, tolbutamide and forskolin elevated [Ca(2+)](i) and induced [Ca(2+)] oscillations. Whereas the glucose effect was delayed and observed in 60% and 93% of the cells, in a poorly and a highly glucose-responsive INS-1 cell clone, respectively, tolbutamide and forskolin increased [Ca(2+)](i) in all cells tested. In the latter clone, glucose induced [Ca(2+)](i) oscillations in 77% of the cells. In 16% of the cells a sustained rise of [Ca(2+)](i) was observed. The increase in [Ca(2+)](i) was reversed by verapamil, an L-type Ca(2+) channel inhibitor. Adrenaline decreased [Ca(2+)](i) in oscillating cells in the presence of low glucose and in cells stimulated by glucose alone or in combination with tolbutamide and forskolin. Adrenaline did not lower [Ca(2+)](i) in the presence of 30mM extracellular K(+), indicating that adrenaline does not exert a direct effect on Ca(2+) channels but increases K(+) channel activity. As for primary b-cells, [Ca(2+)](i) oscillations persisted in the presence of closed K(ATP) channels; these also persisted in the presence of thapsigargin, which blocks Ca(2+) uptake into Ca(2+) stores. In contrast, in voltage-clamped cells and in the presence of diazoxide (50mM), which hyperpolarizes the cells by opening K(ATP) channels, [Ca(2+)](i) oscillations were abolished. These results support the hypothesis that [Ca(2+)](i) oscillations depend on functional voltage-dependent Ca(2+) and K(+) channels and are interrupted by a hyperpolarization in insulin-secreting cells.
Adrenergic alpha-Agonists↗
[Diagnostic methods for the quantification of radiation injuries of the lungs].
PURPOSE: The aim of this paper is to find techniques for quantifying radiation lung injury after irradiation with lung involvement to improve an early diagnosis. METHODS: The case of a patient with NSCLC was used to demonstrate different methods in order to quantify a developing pneumopathy after radiation treatment. By means of HRCT studies in the follow-up, a procedure was developed by defining a test-ROI in high-dose areas of the lung and evaluating the corresponding HU-histogramm for the parameters of the lung peak. Changes during the follow-up can be derived from the differential HU-histogram by the determination of a parameter called delta HUrel, which quantifies the shift to higher HU values. Alternatively, a Fourier analysis of the lung pattern within the test-ROI results in a Fourier amplitude distribution, which reacts sensitively to changes during the follow-up. Furthermore, a Fourier-frequency histogram can be derived which is independent of the spatial orientation of the density pattern. RESULTS: From the HRCT follow-up study, values for delta HUrel can be derived to be 0.24, 0.44, and 0.50 (56, 100 and 422 days after beginning the treatment). The differential Fourier frequency-histogram presentations demonstrate pronounced pattern changes. CONCLUSION: The presented methods demonstrate possibilities to quantify radiation lung injury. The proven sensitivity can possibly be improved after the introduction of a breath triggered HRCT technique.
Carcinoma, Non-Small-Cell Lung↗
Appropriateness of the decision to transfer nursing facility residents to the hospital.
OBJECTIVES: To develop and test a standardized instrument, the purpose of which is to assess (1) whether skilled nursing facilities (SNFs) transfer residents to emergency departments (ED) inappropriately, (2) whether residents are admitted to hospitals inappropriately, (3) and factors associated with inappropriate transfers. DESIGN: A structured implicit review (SIR) of medical records. SETTING AND PARTICIPANTS: Using nested random sampling in eight community SNFs, we identified SNF and hospital records of 100 unscheduled transfers to one of 10 hospitals. MEASUREMENTS: Seven trained physician reviewers assessed appropriateness using a SIR form designed for this study (2 independent reviews per record, 200 total reviews). We measured interrater reliability with kappa statistics and used bivariate analysis to identify factors associated with assessment that transfer was inappropriate. RESULTS: In 36% of ED transfers and 40% of hospital admissions, both reviewers agreed that transfer/admit was inappropriate, meaning the resident could have been cared for safely at a lower level of care. Agreement was high for both ED (percent agreement 84%, kappa .678) and hospital (percent agreement 89%, kappa .779). When advance directives were considered, both reviewers rated 44% of ED transfers and 45% of admissions inappropriate. Factors associated with inappropriateness included the perceptions that: (1) poor quality of care contributed to transfer need, (2) needed services would typically be available in outpatient settings, and (3) the chief complaint did not warrant hospitalization. CONCLUSIONS: Inappropriate transfers are a potentially large problem. Some inappropriate transfers may be associated with poor quality of care in SNFs. This study demonstrates that structured implicit review meets criteria for reliable assessment of inappropriate transfer rates. Structured implicit review may be a valuable tool for identifying inappropriate transfers from SNFs to EDs and hospitals.
Advance Directives↗
Effects of adrenaline and tolbutamide on insulin secretion in INS-1 cells under voltage control.
The aim of the present study was to investigate whether mechanisms distal to the regulation of Ca2-influx are involved in tolbutamide-induced stimulation and adrenaline- and somatostatin- induced inhibition of insulin secretion in INS-1 cells. Using the patch clamp method, the membrane voltage was either kept constant at -70 mV, or Ca2+-influx was activated by short depolarising pulses to 0 my. These pulses induced an increase in cellular capacitance (Cm) caused by fusion of secretory granules with the plasma membrane. Tolbutamide did not alter, neither Cm under voltage clamp at -70 mV nor increases of Cm due to voltage pulses. The inhibitors of secretion, adrenaline and somatostatin, counteracted the augmentation of [Ca2+]i which was induced by glucose, tolbutamide and forskolin. In the voltage clamp mode, however, where no changes of [Ca2]i. were observed, adrenaline but not somatostatin inhibited the increase of Cm caused by depolarizing voltage pulses. The adrenaline effect on Cm was dependent on the addition of GTP to the pipette solution. When GTP was replaced by GDPbetaS or GTPgammaS, the effect of adrenaline on Cm was abolished. The blockade of calcineurin, by the addition of calcineurin inhibitory peptide (CIP) to the pipette solution, did not affect the adrenaline-induced inhibition of Cm. Moreover. After incubation of the cells with deltamethrin, a calcineurin inhibitor, the stimulation of secretion was attenuated, but the adrenaline-induced inhibition was not affected. Our results suggest that adrenaline-induced inhibition of insulin secretion involves a site of action directly related to the exocytotic membrane fusion. In contrast, the stimulator tolbutamide and the inhibitor somatostatin had no direct effect on exocytosis in INS-1 cells.
Cell Line↗
Mental rotation, memory scanning, and the central bottleneck.
Two reaction-time experiments using the psychological refractory period paradigm examined whether two prominent tasks, i.e., mental rotation and memory scanning, require access to a single-channel mechanism and must therefore be performed sequentially with other operations requiring the same mechanism. On each trial, subjects made speeded responses to a tone (Exp. 1) or a character (Exp. 2, with symbolic SR-compatibility of the character manipulated) as Task 1 and to a letter (for blocks with mental rotation) or a digit (for blocks with memory scanning) as Task 2. The set-size effect was constant across SOAs, suggesting that memory scanning cannot be performed in parallel with response selection of Task 1. The effect of orientation, however, decreased with decreasing SOA. The decrease was even intensified if Task 1 bottleneck processes were prolonged by symbolic SR-compatibility. The exact pattern of underadditivity, however, was not predicted by current theories of dual-task performance. The results contradict a central bottleneck model but are in line with extensions of the model proposed by Meyer and Kieras.
Female↗
Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86.
PURPOSE: The goal of the second German Soft Tissue Sarcoma Study CWS-86 (1985 to 1990) was to improve the prognosis in children and adolescents with soft tissue sarcoma by means of a clinical trial comprising intensive chemotherapy and risk-adapted local therapy. PATIENTS AND METHODS: There were 372 eligible patients. A staging system based on the postsurgical extent of disease was used. Chemotherapy consisted of vincristine, dactinomycin, doxorubicin, and ifosfamide. Radiotherapy was administered early at 10 to 13 weeks simultaneously with the second chemotherapy cycle (32 Gy or 54. 4 Gy). The single dose was reduced to 1.6 Gy and given twice daily (accelerated hyperfractionation). RESULTS: The event-free survival (EFS) and overall survival rates at 5 years were 59% +/- 3% and 69% +/- 3%, respectively. The 5-year EFS rate according to stage was as follows: stage I, 83% +/- 5%; stage II, 69% +/- 6%; stage III, 57% +/- 4%; and stage IV, 19% +/- 6%. The outcome for patients with stage III disease who required radiotherapy was much better in the CWS-86 study compared with the CWS-81 study (5-year EFS, 60% +/- 5% v 44% +/- 6%; P =.053). The most common treatment failure was isolated local relapse, with 14% of patients relapsing at the primary tumor site. CONCLUSION: The improved design of the study incorporating risk-adapted radiotherapy allowed treatment to be reduced for selected groups of patients without compromising survival.
Adolescent↗
[Pancreatitis and peritonitis--concepts for postoperative care].
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Humans↗
[Dosimetry of a blood irradiator].
BACKGROUND: Blood and blood products are irradiated to avoid the graft-versus-host disease (GVHD) in immunosuppressed patients and to destroy tumor cells during the intra-operative autotransfusion in tumor surgery. For that purpose more and more dedicated gamma irradiators are used. In most cases the equipment is supplied with a dose calibration factor for a totally filled irradiation canister. As users handle different blood product volumes, it is necessary to investigate the influence of the irradiated blood volume on the absolute dose in a reference point and the dose distribution in the irradiation volume. MATERIAL AND METHODS: The dose rate in the center of an empty irradiation canister of an IBL 437C blood irradiator (CIS Diagnostic) was investigated by means of Fricke solution dosimeters from the Physikalisch-Technische Bundesanstalt (PTB). Using thermoluminescence dosimetry (TLD) this value could be transferred to a situation with an empty or completely filled respectively with 2 blood samples (270 ml each) filled canister. Also essential for the irradiation of blood is the knowledge of the dose distribution in the irradiated volume. The distributions in the empty and the realistic filled canister were measured by positioning the TLD on the plexiglas holder in a regular pattern. The case of a completely filled container was investigated by means of the MR Fricke gel dosimetry. All distributions are presented as dose-volume-histograms (DVH). RESULTS: The TLD-measurement in the center of the completely filled canister yielded a 4.8% higher dose rate value as compared to the suppliers certificate. From the investigations using the Fricke solution dosimeters in air combined with TLD-measurements values for the complete bandwidth of different container fillings could be derived. So the dose rate in the centre of the canister in the boundary conditions empty and full canister as compared to the values for the realistic filling condition (2 bags) are 117.5% and 94% respectively. Axial dose distributions and DVH have been determined for the 3 filling conditions. CONCLUSIONS: We recommend a dose calibration measurement of a blood irradiator to determine the irradiation times for the chosen filling condition, which is typical for the hospital. The DVH presented in this work can be used to derive a value for the dose variance within the irradiated blood.
Blood↗
[Optimization of photon dose distributions with compensation].
PURPOSE: A homogeneous dose distribution according to the demands of the ICRU-publication 50 often can only be achieved by the use of compensators. Because of the expense those are seldom applied. The purpose of this work is to find practical methods for the production and verification. MATERIAL AND METHODS: Two procedures for the production of compensators using 3 different materials and suitable dose verification methods were investigated. The first procedure uses a laser system to get the patient contour, from which the compensator can be calculated. In a second method a 3D planning system calculates the dose modulators on the basis of CT-slices. The production is done by the use of a computer driven milling machine either via a founding form or direct milling. Mixtures of a polymer and lead powder, a mixture of tin granules and wax and the commercially available alloy MCP-96 were used. Dose verification was done using film-, TL- and the three-dimensional MR Fricke gel dosimetry as well as a diode array scanner. RESULTS: Though both methods can be used, the CT-based procedure proved to be more appropriate. Among the materials the direct milled MCP-96 compensator is favorable with respect to the handling, mechanical properties and inhomogeneous radiation attenuation. The dose verification has been done in an Alderson phantom for mantlefield and head-and-neck irradiation techniques. Here the dose modulation yielded an improvement of the homogeneity. The dose maxima normalized to the dose reference point could be reduced from 127% to 103% respectively 122% to 104%. Verifications of compensators for patient treatments confirmed the good results from the phantom measurements. CONCLUSION: The demonstrated investigations show a practicable way for the clinical application of compensators. The necessity for the use of them can be derived from the verified decrease of the dose maxima.
Humans↗
A polio immunization pamphlet with increased appeal and simplified language does not improve comprehension to an acceptable level.
We used a randomized trial to compare two polio vaccine pamphlets written on a sixth grade level--the vaccine information statement prepared by the Centers for Disease Control (CDC) and an easy-to-read pamphlet we developed (LSU)--for reading ability, comprehension and preference among 610 parents with a broad range of demographic characteristics. Parents at all reading levels and incomes preferred LSU (76% vs. 21%, P < 0.001). Although readers of LSU achieved significantly higher comprehension (65% vs. 60%, P < 0.05) this difference may not be clinically significant. The information items presented with instructional graphics were the only items on which differences in comprehension levels achieved both clinical and statistical significance. Comprehension was lowest for the CDC mandated information on risks and the National Injury Compensation. Our findings demonstrate that simplifying written immunization material and making it more suitable will increase appeal, but such modification may not raise comprehension to an acceptable level without use of instructional graphics. Health education materials intended for general parent populations, which are written on a sixth grade reading level, may not adequately educate parents or prepare them for a discussion with their physicians.
Academic Medical Centers↗
The real gordian knot: racemic mixtures versus pure enantiomers.
Many drugs exist as asymmetric three-dimensional (chiral) molecules and will therefore have several stereoisomers. There are often pharmacodynamic, pharmacokinetic and/or toxicological differences between enantiomers. The choice between developing a racemate or single enantiomers depends on therapeutic advances and developmental costs involved. Regarding the target environment for drug intervention, even if natural physiological mediators are achiral, their receptors may demonstrate a preference for the (-)- or (+)-enantiomer of agonists or antagonists. It is also obvious that the majority of enzymes and channels are stereospecific, at least to a variable extent. From a pharmacokinetics point of view, chirality can have an influence on drug absorption, distribution, metabolism and elimination. With a few exceptions, toxicological differences between isomers of known drugs are less dramatic than thought to be and only seldom substantiate the necessity of a racemic switch. The pharmaceutical industry is currently very interested in the so-called "racemic switch." Before proceeding to a racemic switch it is necessary to determine if 1) it is chemically feasible to produce a single enantiomer; 2) a clinical advantage is obtainable through a racemic switch; and 3) a marketing advantage is obtainable. The real goal of a racemic switch should be the rational development of compounds that are profitable for the company and--first of all--beneficial for the patient.
Journal Article↗
Adrenaline inhibits depolarization-induced increases in capacitance the presence of elevated [Ca2+]i in insulin secreting cells.
Cell capacitance (Cm), cell conductance (Gm), access conductance (Ga) and membrane voltage (Vm) were measured simultaneously in insulin secreting cells using the dual frequency method. Depolarization and stimulation of the cells with secretagogues increased Cm. EGTA abolished the increase in [Ca2+]i and prevented the rise of Cm. Adrenaline inhibited the augmentation of Cm without lowering [Ca2+]i. In pertussis toxin pretreated cells adrenaline had no effect. Thus, stimulation of insulin secretion is accompanied by an increase in Cm. Inhibition of exocytosis by adrenaline occurs even in the presence of elevated [Ca2+]i, i.e. at a more distal step of exocytosis.
1-Methyl-3-isobutylxanthine↗
[The verification of optimized 3D-dosage distributions with an MR Fricke gel].
PURPOSE: Complex 3D treatment planning techniques require a dose verification throughout the irradiated volume. Conventional dosimetry techniques only unsatisfyingly serve these needs. MATERIAL AND METHOD: The chemical dosimeter FeSO4 solution can be used for measuring spatial dose distributions with the help of magnetic resonance imaging by fixing the iron ions in a gelatin matrix. A 3D dosimetry method was developed for 3D verification in an homogeneous, anthropomorphic phantom. The verification is achieved by juxtaposition or superposition of measured and calculated isodoses. RESULTS: Different gel compositions were studied in view of their applicability as clinical 3D dosimeter concerning dose response, linearity and diffusion behaviour. A gel with 5% gelatin and 1 mM of ferrous ions proved to be the most suitable. The inverse spin-spin relaxation time T2(-1) is an indicator of the ferric ion concentration that showed to be linear with the dose in the range between 0 and 40 Gy (R2 = 0.996). The dose response was 0.057 per second and Gy. The observed diffusion of the iron ions was only influenced little by different gel compositions. To isolate the restrictions in the clinical application, measurements on the disturbing effects like, e.g. the inhomogeneous spatial response and the gel surface effects, were made and eliminated with the subtraction method. The clinical use of the method is demonstrated for the examples of the verification of calculated 3D dose distributions of a shielded 192Ir afterloading vaginal applicator and a head and neck 3-field plan with the use of asymmetric jaws and compensators. CONCLUSION: The study demonstrates the clinical applicability of the method and shows its limitations.
Brachytherapy↗
Experimental studies on acute and chronic action of azelastine on nasal mucosa in guinea pigs, rats and dogs.
Azelastine (CAS 37932-96-0) nasal spray (Allergodil, Rhinolast, Astelin) was investigated in acute experiments in guinea pigs and after a 26-week local application period with daily repeated administration for effects on ciliary beat activity (acute experiments) and morphology of nasal mucosa. The commercially available spray did not inhibit ciliary beat activity in guinea pigs nor did it cause any inflammatory or atrophic changes after 26-week daily local application on nasal mucosa in rats and dogs.
Administration, Intranasal↗
Treatment of soft tissue sarcoma in childhood and adolescence. A report of the German Cooperative Soft Tissue Sarcoma Study.
BACKGROUND: In the first German soft tissue sarcoma (STS) study, CWS-81, 344 patients younger than 19 years of age who had previously untreated soft tissue sarcoma were studied. For this analysis, there were 218 patients with chemosensitive STS (Group A: rhabdomyosarcoma [RMS], synovial sarcoma, extraosseous Ewing sarcoma, leiomyosarcoma, undifferentiated sarcoma, and malignant peripheral neuroectodermal tumor) who could be studied for a minimum potential follow-up time of 6 years. METHODS: A staging system based on the postoperative extent of the disease was used. The chemotherapy for Stage I-III disease consisted of vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA). Patients with metastatic disease and patients with Stage III disease who failed to respond to VACA were given ifosfamide instead of cyclophosphamide. The definitive procedure for local tumor control (either no radiation exposure, 40 Gy, or 50 Gy) for patients with Stage II-III disease depended on the tumor status at second-look surgery after 16 weeks of chemotherapy. RESULTS: The rates of disease-free survival (DFS) and survival after 5 years was 61% +/- 4% and 57% +/- 4%, respectively, in group A; for patients with nonmetastatic tumors (Stages I-III), the rates were 69% +/- 4% and 72% +/- 4, respectively. Patients with nonmetastatic rhabdomyosarcoma had a similar prognosis: the survival rate was 73% +/- 4%, and the DFS rate was 68% +/- 4%. There was no difference in prognosis between patients with Stage I and and those with Stage II disease (DFS rate, 88% +/- 5% and 88% +/- 6%, respectively). The DFS rate for patients with Stage III disease was 54% +/- 5% and for those with Stage IV, 11% +/- 5%. Lack of local tumor control was the primary cause of therapy failure: 10% of patients with localized disease did not achieve complete remission, whereas 18% who were in complete remission experienced local relapse. The most important prognostic factors were tumor size (P = 0.005) and the degree of tumor regression after primary chemotherapy (P = 0.007). The prognosis also differed according to primary site: paratesticular tumors had the best prognosis, whereas tumors located in the parameningeal regions of the head and neck had the worst prognosis (DFS rate, 96% +/- 4% versus 49% +/- 7%, respectively). CONCLUSIONS: The following conclusions were drawn from the CWS-81 study: (1) intensive chemotherapy (VACA for 35 weeks) provides long-term control for most patients with Stage I-II disease; (2) patients with primary unresectable tumors (i.e., Stage III) who achieve complete remission with chemotherapy alone have the same prognosis as patients with postoperative disease of Stages I and II; (3) tumor size and the degree of tumor regression after primary chemotherapy influence outcome and thus can be used as a basis for risk-adapted therapy.
Adolescent↗
[Ovariopexy and the treatment of Hodgkin's disease].
Between 1979 and 1989 a total of 113 women underwent treatment for Hodgkin's disease at the Department of Radiation Oncology of the University of Erlangen-Nürnberg. Only 17 female patients of child bearing age received total lymphoid irradiation including pelvic and inguinal nodes. 15/17 patients underwent prophylactic bilateral oophoropexy during staging laparotomy: ten had lateral, five had midline ovarian transposition. Reproductive and ovarian function was investigated in 13 patients--all in complete remission after a minimum follow-up of three years--by menstrual history and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone, dehydroepiandrosteronsulfate (DHEAS), androstendion, estradiol, progesterone, 17-OH progesterone, sexual hormone binding globulin (SHBG), free androgen index (FAI). Thyroid function was assessed by measuring thyroxine (T4), triiodothyronine (T3), thyroxine stimulating hormone (TSH) and thyroxine binding globulin (TBG). Normal cyclic ovarian activity was found in seven out of nine patients following lateral oophoropexy (including one pregnancy), but only in one out of four cases after midline fixation. Median calculated dose was 325 cGy (range 260 to 500 cGy) to the laterally fixed ovaries and 490 cGy (range 390 to 500 cGy) for midline transposition. We conclude, if ovarian protection is required prior to pelvic radiation, lateral oophoropexy should be preferred.
Adolescent↗
Mutagenicity experiments on L-cysteine and D-penicillamine using V79 cells as indicators and for metabolic activation.
Previous studies have shown that cysteine and penicillamine induce gene mutations in Salmonella typhimurium, the effect being strongly potentiated in the presence of mammalian tissue preparations. It has now been demonstrated that homogenate of V79 Chinese hamster cells is an efficient activator of thiol amino acids as well. Nevertheless, L-cysteine and D-penicillamine did not induce gene mutations (acquisition of resistance towards 6-thioguanine) in V79 cells. This was true even in the presence of the most efficient activating system, kidney postmitochondrial fraction. The result suggests the existence of an effective protective system in mammalian cells against the natural amino acid L-cysteine and its therapeutically used derivative, D-penicillamine.
Amino Acids, Sulfur↗