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Biomedical subjects

R Ott

Publications and source records attributed to R Ott.

At least 73 records · Page 4Linked to original sources

Intramural esophageal hematoma after cardioversion.

Intramural esophageal hematoma is a very rare condition. We report a case of a 40-year-old male, presenting with retrosternal pain and dysphagia. On the day before admission tarry stool and minimal vomiting of old blood was noticed. Diagnostic procedures showed an intramural esophageal hematoma, which had developed 2 weeks and 3 days after cardioversion and anticoagulation therapy. Etiology, differential diagnosis, the diagnostic approach and a brief review of the literature are discussed.

Adult↗

Postembryonic development of the cerebellum in gymnotiform fish.

In contrast to adult mammals, adult teleost fish regularly generate new neurons and glial cells in many brain regions. A previous quantitative mapping of the proliferation zones in the brain of adult Apteronotus leptorhynchus (Teleostei, Gymnotiformes) has shown that 75% of all mitotically active cells are situated in the cerebellum (Zupanc and Horschke [1995] J. Comp. Neurol. 353:213-233). By employing the thymidine analogue 5-bromo-2'-deoxyuridine, we have, in the present study, investigated the postembryonic development of this brain region in detail. In the corpus cerebelli and the valvula cerebelli, the vast majority of newborn cells originate in the respective molecular layers. Within the first few days of their life, these cells migrate toward specific target areas, namely, the respective granule cell layers. In the caudal part of the cerebellum, the granule cell layer of the eminentia granularis pars medialis displays the highest mitotic activity. From there, the cells migrate through the adjacent molecular layer to the granule cell layer of the eminentia granularis pars posterior. Combination of retrograde-tracing techniques with immunohistochemistry for 5-bromo-2'-deoxyuridine showed that at least a portion of the newly generated cells develop into granule neurons. Many of the newly generated cells survive for long periods of time. A large fraction of these cells is added to the population of already existing cells, thus resulting in a permanent growth of the target areas and their associated structures.

Age Factors↗

Initial experience with a new, partially covered Wallstent for malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Metal billiary stents have been shown to be superior to plastic stents with regard to patency and the risk of dislocation. However, tumor ingrowth through the mesh continues to be a significant problem. We report here on our preliminary experience with covered metal stents. PATIENTS AND METHODS: Ten patients (mean age 68 years) with malignant biliary obstruction, who were not considered to be surgical candidates, received a partially covered Wallstent. The patients were followed up prospectively for one year, including laboratory tests, abdominal ultrasound, and plain abdominal radiographs during the first three months, and by monthly telephone interview thereafter. RESULTS: Stent insertion was technically successful in all patients, and led to a reduction in bilirubin levels from 8.4 mg/dl to 0.7 mg/dl. The mean survival of the patients was 7.5 months after the diagnosis of malignancy, and six months after stent insertion; only two patients were still alive after 12 months. During the observation period, four patients suffered from stent dysfunction for periods of one to nine months. These dysfunctions included three stent occlusions, which were successfully treated by inserting plastic stents, and one dislocation, which was treated by endoscopic replacement of the stent. There appeared to be a correlation between the narrowest stent diameter immediately after release and stent dysfunction. CONCLUSION: Covering biliary metal stents is a potential solution to prevent tissue ingrowth. However, current prototypes need to be improved in order to achieve this goal.

Aged↗

Dimensions of stigmatization in patients with psoriasis in a "Questionnaire on Experience with Skin Complaints'.

BACKGROUND: Stigmatization is a central experience of patients with psoriasis with a broad psychic and social impact. OBJECTIVE: The purpose of this study is to identify the dimensions of stigma experience by a Questionnaire on Experience with Skin Complaints (QES; 'Fragebogen zum Erleben von Hautbeschwerden'). METHODS: 187 in-patients with psoriasis were examined with the QES, an adopted and extended (German) version of the Feeling of Stigmatization Questionnaire by Ginsburg and Link. A factor analysis of the questionnaire was conducted and the construct validity was evaluated. RESULTS: Five factors were found: 'self-esteem', 'retreat', 'rejection', 'composure' and 'concealment'. Self-esteem, retreat and rejection are mainly influenced by 'problematic regions' affected by psoriasis, rejection also by 'visible parts' and retreat also by 'invisible regions'. The influences of age, age at onset and sex on the stigma experience are small but significant. CONCLUSIONS: The QES proved to be an economical and reliable psychometric instrument to differentiate the stigma experience of psoriasis patients.

Adolescent↗

Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil.

PURPOSE: To investigate and measure the metabolism of colorectal cancer liver metastases using 18F-fluorodeoxyglucose positron emission tomography (FDG PET), before and during the first month of chemotherapy. The findings were compared with tumor outcome conventionally assessed using changes in tumor size. PATIENTS AND METHODS: Patients with colorectal cancer liver metastases were treated with fluorouracil (5FU) as a protracted venous infusion (300 mg/m2/d), with or without interferon-alpha 2b for two 10-week blocks separated by a 2-week break. Before and at 1 to 2 and 4 to 5 weeks on treatment, FDG PET scans were performed. Patients fasted, were injected intravenously with FDG (50 to 100 MBq), and scanned using a large-area positron camera; the image data was processed such that regions of interest could be identified. The results were expressed as a ratio of FDG uptake in the tumor and normal liver (T:L) or as a semiquantitative standardized uptake value (SUV). These measures were compared with the tumor dimensions measured on a computed tomographic (CT) scan performed at 12 weeks from commencement of chemotherapy. RESULTS: Twenty patients were studied; however, two did not have assessable liver metastases. Objective partial responses were observed in 11 of 18 patients. A total of 27 metastatic lesions were assessable. Pretreatment T:L ratios and SUVs did not correlate with tumor response, although response was associated with lower 1- to 2-week (1.84 v 2.17; t=2.667; P < .02) and 4- to 5-week (1.36 v 2.28; t=5.02; P < .001) T:L ratios, and 4- to 5-week (3.57 v 4.95; t=2.492; P < .05) SUVs. Expressed as a percent of the baseline values of the T:L ratio, responding lesions had a greater reduction in metabolism (67% v 99%; t=7.53; P < .001). The 4- to 5-week T:L ratio was able to discriminate response from nonresponse both in a lesion-by-lesion and overall patient response assessment (sensitivity 100%; specificity 90% and 75%, respectively). CONCLUSION: Positron emission tomography used to evaluate the uptake of FDG in tumors yields data that correlate with the antitumor effect of chemotherapy in patients with liver metastases from colorectal cancer.

Antimetabolites, Antineoplastic↗

[Quality of life after survival of severe trauma].

Quality of life (QoL) was analyzed in 73 patients with severe multiple trauma (PTS > or = 40 patients) between 1 and 13 years after injury. QoL was assessed by the Aachen Longtime Outcome Score (ALOS), the Spitzer Index (SI) and individual self-assessment. The patients were asked about further social, financial, psychological and physical items. According to the ALOS, 81% of the patients showed moderate, 14% severe and 5% no disability. In 66% of the patients a favorable Spitzerindex (8-10 points) was found. Only 14% had poor SI scores (0-4 points). Also, two out of three patients regarded the current state of their health as "good" or "very good". Predominantly, handicaps resulted from permanent physical disability, in particular the lower extremities, whereas psychosocial and financial problems were reported infrequently. Besides injuries to the head or extremities, low QoL correlated with severity of injury and increasing age. Within the first 4 post-traumatic years SI and ALOS, as well as individual self-assessment, improved with time after injury. The rate of patients who returned to work (69%) was similar to other multiple trauma series, including series with less severe injuries. The reasonable long-term outcome even after severe multiple trauma seems to justify the enormous staff and economic expense required to manage these patients. Further improvement in QoL may be achieved by professional psychological support and early fracture treatment.

Adaptation, Psychological↗

[Nonelastic deformations of polyethylene inlays in hemiprostheses].

In most models of hip prosthesis, the inlay is formed by a layer of polyethylene. The attrition of polyethylene results from two components, wear and nonelastic deformation. Former studies analysed total attrition. The aim of this trial was to measure solely the non elastic deformation. Nonelastic deformation was investigated using two different types of bipolar hemiprostheses to exclude influences of different shaped metal caps. The bipolar hemiprostheses were tested with a hydraulic pulser. 1 x 10(6) cycles of a halfsinewave with a stress of 4600 N at a frequency of 8 Hz were used. The whole procedure was carried out in isotonic saline solution. Stress was applied along a single axis to prevent any wear. After the test, the inner surface of the polyethylene inlay was analysed with a touchpeg. As the inlays had different inner diameters, the analysis of the surface was defined along radials of 5 degrees, 25 degrees and 45 degrees. The nonelastic deformation in the direction of the main stress at 45 degrees was higher than at the lateral areas. The nonelastic deformation measured was between 0.2 and 0.6 mm/a, i.e. 5 to 30% of total attrition. There was a significant difference between the two types of inlays. The model with several pegs and edges for a complicated snap mechanism had a significant higher nonelastic deformation (alpha = 0.05) than the smooth shaped inlay.

Biomechanical Phenomena↗

Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement using a trapped tracer model.

Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue 64Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by 64Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of 64Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular 64Cu-PTSM infusion, cumulative arterial 64Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of 57Co microspheres. Rapid and species-dependent rates of 64Cu-PTSM decomposition to non-extractable 64Cu complexes were found in rat and human blood in vitro (70% +/- 6% and 43 +/- 5% respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by 64Cu-PTSM and 57Co microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean 64Cu, mean 57Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (-0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using 62,64Cu-PTSM, PET imaging and continuous arterial blood sampling.

Animals↗

Nickel-57-doxorubicin, a potential radiotracer for pharmacokinetic studies using PET: production and radiolabelling.

The clinical use of anthracyclines, such as doxorubicin (DXR), is hampered by tumour development of multidrug resistance (MDR). The drug efflux associated with MDR could be characterised in vivo using Positron Emission Tomography (PET) in conjunction with a suitable radiolabelled drug. We are investigating DXR labelled with the positron emitter 57Ni as a potential analogue of the parent drug. Essential to this work is the production of a high purity radionuclide in a suitable chemical form for the preparation of radiolabelled DXR. To optimise production parameters, excitation functions (reaction cross section as a function of beam energy) for proton induced reactions in cobalt were measured up to 60 MeV. The excitation function for the 59Co(p,3n)57Ni reaction shows a maximum cross section of 13.8 +/- 1.5 mb at 38 MeV. The optimum energy range for production of 57Ni was found to be 41-->26 MeV resulting in an experimental thick target yield of 17.8 MBq/muAh. The level of the 56Ni impurity is only 0.21% at the end of bombardment. A radiochemical procedure, based on cation-exchange chromatography, has been developed for the separation of radionickel from the cobalt target and other radiochemical and chemical impurities. The 57Ni activity was eluted, using 2M HCl, from a Dowex-50Wx8(H+) column, in a 95% radiochemical yield. Optimum labelling of DXR has been investigated in terms of pH, reaction time and temperature, achieving radiochemical yields > 94%. DXR labelled with 57Ni therefore shows promise as a radiotracer for pharmacokinetic studies using PET.

Doxorubicin↗

Tissue blood flow estimation with copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) and PET.

Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging the distribution of blood flow with positron emission tomography (PET). The application of a simple trapped tracer model in conjunction with tissue uptake and continuous arterial sampling to estimate blood flow has been compared with the 57Co-microsphere method in the rat. After intraventricular injection the cumulative arterial function for 64Cu increased progressively due to the presence of circulating non lipophilic complexes. The cumulative function for lipophilic 64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those reached by 57Co-microspheres. No consistent disagreement was found between cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean), brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55 mL/min/g). A simple tissue trapping model may therefore be suitable for the derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu-PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.

Animals↗

Uptake of radiolabelled tyrosine and iodo-methyl tyrosine in experimental rat tumours: influence of blood flow and tumour growth rate.

Radiolabelled amino acids combined with Positron Emission Tomography (PET) may be useful for delineation of the extent of viable tumour and may also provide a rapid and sensitive indicator of response to therapy. Promising early clinical reports led us to investigate the potential use of the amino acid analogue L-3-iodo-alpha-methyl tyrosine (IMT), which may be radioiodinated with isotopes suitable for PET or conventional single photon imaging. We have studied the biodistribution and kinetics of [125I]IMT using two transplantable tumour systems in hooded rats, and have compared the findings with those using the natural amino acid L-tyrosine (TYR) radiolabelled with tritium. Similar levels of IMT and TYR uptake were found in HSN and OES.HR1 tumours during tumour growth. Following arrest of OES.HR1 tumour growth by oestrogen ablation, reduced IMT and TYR uptake was found to be closely matched by a fall in tumour blood flow. Unlike IMT, a substantial proportion of TYR uptake in tumours was found to be protein incorporated, even following tumour growth arrest. Quantitative autoradiography revealed sharp delineation of tumour boundary using either radiotracer. We conclude that IMT and TYR kinetics are strongly influenced by blood flow and diffusion, and that tumour growth status may not be closely associated with amino acid uptake.

Animals↗

Biodistribution and kinetics of radiolabelled pyrrolidino-4-iodo-tamoxifen: prospects for pharmacokinetic studies using PET.

With a view to evaluating the role of PET imaging in early clinical studies of new anticancer drugs, we are investigating the recently developed antiestrogen compound pyrrolidino-4-iodo-tamoxifen (idoxifene). Preliminary experimental studies have been undertaken using [125,131I]idoxifene, following synthesis of a tributyl-stannyl-idoxifene precursor to facilitate radioiodination. We have investigated the tissue biodistribution and kinetics of [125I]idoxifene following i.v. infusion in hooded rats bearing the hormone-dependent transplantable mammary tumour OES.HR1. Clearance of idoxifene from the circulation is accompanied by an increase in uptake by tumour and uterus, to peak levels after 24 hours (0.33 +/- 0.037% dose/g (mean +/- 1 SD) and 0.40 +/- 0.033% dose/g, respectively). Highest uptake of idoxifene was found in the liver (11.0 +/- 0.8% dose/g), with a progressive fall after 24 hours consistent with hepatobiliary excretion of the radiotracer. No evidence of idoxifene metabolism was found in tissue extracts taken up to 48 hours. Whole body clearance of [131I]idoxifene was characterised by a single exponential decay (t1/2 = 140 hours) up to 350 hours post administration. We conclude that 124I-labelled idoxifene combined with PET imaging would facilitate human in vivo pharmacokinetic studies of this new anticancer drug and provide an opportunity to investigate relationships between drug uptake and tumour response.

Animals↗