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Biomedical subjects

Peter Stadler

Publications and source records attributed to Peter Stadler.

16 recordsLinked to original sources

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis.

BACKGROUND: The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. METHODS: From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1-5: 20 mg/m2/d DDP + 750-1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69-70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. RESULTS: Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2-3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. CONCLUSION: The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients were not anemic at beginning of therapy. Therefore, we could assess the influence of pre-treatment hemoglobin on survival. However, a low hemoglobin nadir was associated with poor outcome. This result suggests an influence of anemia during therapy on prognosis.

Adult↗

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy -- case report and review of literature.

BACKGROUND: Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's wort). CASE REPORT: A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. CONCLUSION: Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative drugs because patients tend to conceal such medication as harmless.

Aged↗

Clinical results of intracoronary brachytherapy (ICBT) for multiple in-stent restenosis.

BACKGROUND AND PURPOSE: Treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. PATIENTS AND METHODS: 40 patients (27 male, 13 female, age: 66 +/- 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste((R)) Beta-Cathtrade mark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. RESULTS: The 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). CONCLUSION: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT.

Aged↗

Fragrep: an efficient search tool for fragmented patterns in genomic sequences.

Many classes of non-coding RNAs (ncRNAs; including Y RNAs, vault RNAs, RNase P RNAs, and MRP RNAs, as well as a novel class recently discovered in Dictyostelium discoideum) can be characterized by a pattern of short but well-conserved sequence elements that are separated by poorly conserved regions of sometimes highly variable lengths. Local alignment algorithms such as BLAST are therefore ill-suited for the discovery of new homologs of such ncRNAs in genomic sequences. The Fragrep tool instead implements an efficient algorithm for detecting the pattern fragments that occur in a given order. For each pattern fragment, the mismatch tolerance and bounds on the length of the intervening sequences can be specified separately. Furthermore, matches can be ranked by a statistically well-motivated scoring scheme.

Algorithms↗

Pulmonary artery wedge pressure during treadmill exercise in warmblood horses with atrial fibrillation.

The heart rate and the pulmonary artery wedge pressure (PWP) was measured in 10 healthy warmblood horses and in six warmblood horses with atrial fibrillation (AF) at rest and during standardised treadmill exercise. During treadmill exercise, the increase in heart rate was significantly higher in the horses with AF than in the healthy horses. Horses with AF showed a significantly higher increase in PWP at treadmill velocities of 5m/s and faster, than did the healthy horses. The differences in PWP between both groups increased with treadmill strain. The present study demonstrates that there is an influence on the haemodynamics in horses with AF during treadmill exercise, which could explain exercise intolerance in some horses with lone AF.

Animals↗

Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study.

PURPOSE: To analyze the relationship between pre-treatment measurements of tumor oxygen tension (pO2) and survival in advanced head and neck cancer. PATIENTS AND METHODS: Eppendorf pO2 measurements in 397 patients from seven centers were analyzed using the fraction of pO2 values < or =2.5 mmHg (HP2.5), < or =5 mmHg (HP5) and median tumor pO2 (mmHg) as descriptors. All patients had intended curative radiation therapy alone or as pre- or post-operative radiotherapy or radio-chemotherapy according to the practice at each center. RESULTS: The degree of hypoxia varied between tumors with an overall median tumor pO2=9 mmHg (range 0-62 mmHg), a median HP2.5=19% (range 0-97%) and HP5=38%, (range 0-100%). By quadratic regression median tumor pO2 correlated with Hb (2P=0.026, n=357), while HP2.5 or HP5 did not. HP2.5 above the population median was the only parameter that associated with poor overall survival (Kaplan Meier analysis, P=0.006). In a multivariate Cox Proportional Hazards analysis, stratified according to institution HP2.5 was by far the most statistically significant factor in explaining the variability in survival. After adjusting for HP2.5, clinical stage, radiation dose and surgery hemoglobin concentration was not significant in the model. The prognostic model shows that the 5-year survival is almost constant for HP2.5 values in the range from 0 to 20%, whereas the 5-year survival approaches 0% in the most hypoxic tumors. CONCLUSION: This study provides evidence that tumor hypoxia is associated with a poor prognosis in patients with advanced head and neck cancer.

Adult↗

High diversity of the 'Spumella-like' flagellates: an investigation based on the SSU rRNA gene sequences of isolates from habitats located in six different geographic regions.

We isolated 28 strains of 'Spumella-like' flagellates from different freshwater and soil habitats in Austria, People's Republic of China, Nepal, New Zealand, Uganda, Kenya, Tanzania and Hawaii by use of a modified filtration-acclimatization method. 'Spumella-like' flagellates were found in all of the samples and were often among the dominant bacterivorous flagellates in the respective environments. The small subunit ribosomal RNA (SSU rRNA) gene sequence of the isolates was determined and aligned with previously published sequences of members belonging to the Chrysophyceae sensu stricto. Phylogenetic analysis of the 28 new sequences confirmed their position within the Chrysophyceae sensu stricto and positioned them within different clades. Most of the sequences grouped within clade C and formed several subclusters separated from each other by green taxa including flagellates belonging to Ochromonas, Dinobryon, Poterioochromonas and others. All soil isolates clustered together (subcluster C1) with the soil strain Spumella elongata and the undescribed soil strain 'Spumella danica'. Aquatic isolates were affiliated with at least two branches (C2 and C3). Sequence similarity to the closest related member of the Chrysophyceae ranged between 92% and 99.6%, sequence divergence among the 'Spumella-like' flagellates was as high as 10%. We conclude that (i) the 'Spumella-like' flagellates are a diverse group both in terms of sequence dissimilarity between isolates and in terms of the number of genotypes, (ii) Spumella and Ochromonas are polyphyletic, and (iii) based on the SSU rRNA gene no biogeographical restriction of certain branches could be observed even though different ecotypes may be represented by the same genotype.

Base Sequence↗

The filtration-acclimatization method for isolation of an important fraction of the not readily cultivable bacteria.

We developed a novel method, the filtration-acclimatization method (FAM), which enables the isolation and cultivation of an important fraction of the bacterial diversity, which is not cultivable by standard methods. The method consists of a filtration step, which removes most of the readily cultivable bacteria able to overgrow slowly growing bacteria, and an acclimatization procedure that provides a slow transition from the low environmental substrate concentrations to the high concentration of standard microbial media. So far, we isolated in total 65 strains from surface freshwater habitats by utilizing FAM. The isolates are affiliated with Actinobacteria, Alpha-, Betaproteobacteria, Bacteroidetes, and Spirochaeta. All isolates are pure cultures and form visible colonies on agar plates with high substrate concentrations. For further analysis, strains sharing more than a 97% 16S rRNA gene sequence similarity were grouped into one taxon. Based on sequence similarities, 88% of the obtained taxa can be considered to be undescribed species (<97% similarity to closest species). The highest similarity value of the taxa to the respective closest related species ranged from 87.7% to 99.8%, and was on average 94.5%. For comparison we isolated, by direct plating of water samples on a rich agar medium, a similar number of taxa. Amongst these taxa the percentage of taxa, which can be considered to be undescribed species, was only half of the percentage found for the taxa isolated by FAM. More importantly, it was amongst the taxa obtained by the standard method no taxon that was closer related to an uncultured bacterium than to an isolate, while 56% of the taxa isolated by FAM were closely related to uncultured bacteria.

Bacteria↗

Strain-specific differences in the grazing sensitivities of closely related ultramicrobacteria affiliated with the Polynucleobacter cluster.

Ultramicrobacteria (cell volume < 0.1 microm(3)) are the numerically dominant organisms in the plankton of marine and freshwater habitats. Flagellates and other protists are assumed to be the most important predators of these ultramicrobacteria as well as of larger planktonic bacteria. However, due to controversial observations conducted previously, it is not clear as to whether fractions of the ultramicrobacteria are resistant to flagellate predation. Furthermore, it is not known if closely related bacteria vary significantly in their sensitivity to flagellate predation. We investigated the sensitivity of ultramicrobacteria affiliated with the cosmopolitan Polynucleobacter cluster to grazing by Spumella-like nanoflagellates. Laboratory grazing experiments with four closely related (> or =99.6% 16S rRNA gene sequence similarity) bacteria and three closely related (100% 18S rRNA gene sequence similarity) flagellates were performed. In comparison to larger bacteria, predation on the ultramicrobacterial Polynucleobacter strains was weak, and the growth of the predating flagellates was slow. Specific clearance rates ranged between 0.14 x 10(5) and 2.8 x 10(5) units of predator size h(-1). Feeding rates strongly depended on the flagellate and bacterial strain (P < 0.001). Grazing mortality rates of the three flagellate strains investigated varied for the same prey strain by up to almost fourfold. We conclude that (i) ultramicrobacteria affiliated with the Polynucleobacter cluster are not protected from grazing, (ii) strain-specific variations in grazing sensitivity even between closely related bacteria are high, and (iii) strain-specific differences in predator-prey interaction could be an important factor in the evolution and maintenance of microbial microdiversity.

Animals↗

Tumor volume and tumor hypoxia in head and neck cancers. The amount of the hypoxic volume is important.

BACKGROUND: The prognostic impact of tumor volume and hypoxia is well established. We have investigated a possible prognostic impact of the hypoxic tumor volume which can be calculated as the product of tumor volume and hypoxia. PATIENTS AND METHODS: 125 patients with squamous cell cancer of the head and neck were investigated. All had locoregionally confined disease. The total tumor volume was calculated from pretreatment CT scans as the sum of all visible macroscopic tumor lesions (e.g., primary tumor plus neck nodes), and all patients underwent measurement of tumor oxygenation by pO2 histography. The hypoxic tumor volume was calculated as the product of the total tumor volume and the relative frequency of pO2 readings < 5 mmHg. The nonhypoxic volume was the difference between total tumor volume hypoxic volume. RESULTS: The total tumor volume ranged from 2 to 283 cm3 (mean 47 +/- 53 cm3), the hypoxic volume from 0 to 199 cm3 (mean 18 +/- 30 cm3), and the nonhypoxic volume from 1 to 237 cm3 (mean 29 +/- 34 cm3), and there was a strong correlation between the three parameters. 84 patients died and 41 survived in the observation period with a median survival of 12.5 months. Tumor volume and tumor oxygenation had a significant impact on survival. The tumor volume was significantly different in patients who had died as compared to surviving patients (mean 54 vs. 34 cm3; p = 0.017). The hypoxic volume was also different (11 vs. 22 cm3; p = 0.009), whereas the nonhypoxic volume was not significantly different (24 vs. 32 cm3; p = 0.2). If the impact of large versus small tumor volumes (total volume, hypoxic volume, and nonhypoxic volume, subdivision according to each median) on survival was analyzed, a significant impact of total tumor volume (median survival 298 vs. 485 days; p = 0.03) and a marginal impact of the hypoxic volume (342 vs. 404 days; p = 0.08), but no impact of the nonhypoxic volume were found (383 vs. 374 days; p = 0.6). In a multivariate Cox regression model, the hypoxic tumor volume was a strong and independent prognostic factor for survival (p = 0.001) and more important than the total tumor volume (p = 0.02) whereas the nonhypoxic volume had no impact on prognosis (p = 0.33). CONCLUSIONS: The total tumor volume is a major prognostic factor, but its impact mainly results from the hypoxic volume and can be explained by the strong correlation between total tumor volume and hypoxic volume. The nonhypoxic volume had no impact on survival. As a consequence, methods to measure and localize the hypoxic volume should be further developed.

Adult↗

Isolation of novel ultramicrobacteria classified as actinobacteria from five freshwater habitats in Europe and Asia.

We describe the first freshwater members of the class Actinobacteria that have been isolated. Nine ultramicro-size (<0.1 microm(3)) strains were isolated from five freshwater habitats in Europe and Asia. These habitats represent a broad spectrum of ecosystems, ranging from deep oligotrophic lakes to shallow hypertrophic lakes. Even when the isolated strains were grown in very rich media, the cell size was <0.1 microm(3) and was indistinguishable from the cell sizes of bacteria belonging to the smaller size classes of natural lake bacterioplankton. Hybridization of the isolates with oligonucleotide probes and phylogenetic analysis of the 16S rRNA gene sequences of the isolated strains revealed that they are affiliated with the class Actinobacteria and the family Microbacteriaceae. The previously described species with the highest levels of sequence similarity are Clavibacter michiganensis and Rathayibacter tritici, two phytopathogens of terrestrial plants. The 16S rRNA gene sequences of the nine isolates examined are more closely related to cloned sequences from uncultured freshwater bacteria than to the sequences of any previously isolated bacteria. The nine ultramicrobacteria isolated form, together with several uncultured bacteria, a diverse phylogenetic cluster (Luna cluster) consisting exclusively of freshwater bacteria. Isolates obtained from lakes that are ecologically different and geographically separated by great distances possess identical 16S rRNA gene sequences but have clearly different ecophysiological and phenotypic traits. Predator-prey experiments demonstrated that at least one of the ultramicro-size isolates is protected against predation by the bacterivorous nanoflagellate Ochromonas sp. strain DS.

Actinobacteria↗

Enumeration of small ciliates in culture by flow cytometry and nucleic acid staining.

We developed a fast and simple protocol for accurate quantification of small freshwater ciliates by flow cytometry (FCM). The ciliates were stained with several nucleic acid stains such as TO-PRO-1, YO-YO-1 and PicoGreen, and analysed by a commercially available flow cytometer. The method was tested with cultures of the prostomatid species Urotricha farcta and Balanion planctonicum, including the small cryptophyte Cryptomonas sp. as food. Of the dyes tested, TO-PRO-1 gave the best results. Flow cytometric results agreed well with microscopic counts. Due to its greater speed and accuracy, FCM was superior to light microscopy. FCM was also superior to electronical particle counting and sizing (EPCS). Of particular importance, FCM in combination with TO-PRO-1 staining allowed unequivocal discrimination in cases of overlapping size distributions between the target population (i.e., the ciliate predators) and other particles (the cryptophyte prey, detritus).

Animals↗

Stress echocardiography in warmblood horses: comparison of dobutamine/atropine with treadmill exercise as cardiac stressors.

The purpose of this study was to determine whether the combination of dobutamine and atropine causes cardiac stress equivalent to treadmill exercise. Therefore, electrocardiography and echocardiography were performed on 10 warmblood horses before, during, and after different cardiac stress tests. Stressors consisted of a standardized treadmill exercise and combined administration of dobutamine (7.5 microg/kg/min) and atropine (5 microg/kg). Maxima heart rates were achieved during the treadmill exercise (175 +/- 10 bpm). After exercise, a rapid decrease in heart rate was observed. Subsequently, a stress echocardiography for which a heart rate >100 bpm was required could only be performed within 1 minute after exercise. The mean heart rate during echocardiography was 136 +/- 8 bpm after exercise. The combination of dobutamine and atropine also resulted in a significant increase in heart rate, up to 141 +/- 20 bpm. Maxima heart rate was significantly higher during the treadmill exercise, but the decrease in heart rate was significantly slower after dobutamine and atropine administration. Over a period of 7.9 minutes, the mean heart rate was 123 +/- 8 bpm during dobutamine and atropine administration. Consequently, the combination of both drugs offered sufficient time for detailed examinations. Overall, echocardiographic examination identified a decrease in left ventricular (LV) dimensions, an increase in LV wall thickness, and a decrease in stroke volume after the treadmill exercise and during pharmacologic stress testing compared with baseline. Changes in echocardiographic variables generally were more pronounced during dobutamine and atropine administration. Similar to stress echocardiography in humans, in horses the combination of dobutamine and atropine is useful to produce an increase in heart rate comparable with what is achieved with exercise but without the need of increasing dobutamine dosage.

Animals↗

[Day-to day variability of cardiac pressure values in horses measured with right heart catheterization on 3 consecutive days].

In the present study, a right heart catheterisation was carried out on three consecutive days in 17 healthy horses to evaluate the day-to-day variability of cardiac pressure values. Cardiac pressure values were measured in the right atrium, the right ventricle, the pulmonary artery, and the pulmonary capillaries (pulmonary artery wedge pressure). Additionally it was examined wether the cardiac pressure variability was influenced by the heart rate and if there are differences between trained and untrained horses. Beside the coefficient of variances, statistical analysis with assessment of variance components were carried out. Therefore the variation between repeated measurements at one day and within one horse, and the variation between repeated measurements over three days and within the horses (day to day intraindividual variation) as well as the variation between the horses (interindividual variation) were taken into account. The absolute interindividual variance of the pressure values and the heart rate was between 0.4 and 19.6 at all day and for all horses. Between trained and untrained horses the variation of the pressure values and the heart rate was lower than in the trained horses. A significant difference between trained and untrained horses was seen in right atrial mean pressure (p < 0.001) and right atrial diastolic pressure (p < 0.005). The coefficient of variances of the mean heart rate was 11.8%. The coefficient of variances of the different pressure values ranged between 13.1 (mean pulmonary artery pressure) and 46.4% (right ventricular pressure). By splitting the variances, 54.4-78.9% of the variation was caused by the effect of days, 6.2-30.7% of the variation was caused by the effect of horses and 12.5-23% of the variation was caused by the repeated measurements at the different days. In sumary the results shows that nearly all of the pressure values had a low effect of days on the variation, thus cardiac pressure measurements at one day seem to be sufficient.

Analysis of Variance↗