Leadership Centre for Health. One thing leads to another. Interview by Lynn Eaton.
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Administrative Personnel↗
Biomedical subjects
D Arnold
Publications and source records attributed to D Arnold.
Virus-induced autoimmune reactions in the CNS.
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Animals↗
An automated results notification system for PACS.
The purpose of this study was to determine if the interval between an examination being ordered by an Emergency Department physician and his or her review of the report and images could be shortened by notifying the physician that the results were available. This hypothesis was based on work done previously in the Medical Intensive Care Unit that showed that physicians would wait to review results for a time considerably longer than the time required for the radiologist to review the images and provide a preliminary report. The software developments operate properly and show that even simple integration of multiple information systems (PACS, RIS, speech recognition) can provide useful features. Early results indicate that the Emergency Department (ED) physicians prefer the notification system over the previous (travel to check on images and reports) methods. The hypothesized time reductions did occur, although it is not clear that the notification system accounted for all of them. A system for automated notification of radiology results availability has been shown to be possible and practical. To do this automated interaction of 3 systems with a low-level or no electronic integration was required. Although not fully successful for this study, early physician response has been positive, and requests to expand this service hospitalwide now are common.
Emergency Service, Hospital↗
Intercomparison of efficiency transfer software for gamma-ray spectrometry.
The EUROMET project 428 examines efficiency transfer results for Ge gamma-ray spectrometers when the efficiency is known for a reference point source geometry. For this, different methods are used, such as Monte Carlo simulation or semi-empirical computation. The exercise compares the application of these methods to the same selected experimental cases to determine the usage limitations versus the requested accuracy. For carefully examining these results and trying to derive information for improving the computation codes, this study was limited to a few simple cases. The first part concerns the simplest case of geometry transfer, i.e., using point sources for 3 source-to-detector distances: 2, 5 and 20 cm; the second part deals with transfer from point source geometry to cylindrical geometry with three different matrices. The general conclusion is that the deviations between the computed results and the measured efficiencies are mostly within 10%. The quality of the results is rather inhomogeneous and shows that these codes cannot be used directly for metrological purposes. However, most of them are operational for routine measurements when efficiency uncertainties of 5-10% can be sufficient.
Journal Article↗
Regulation of cell death and survival in intestinal intraepithelial lymphocytes.
Intraepithelial lymphocytes (IEL) of the small murine bowel represent a unique population of mostly CD8(+) T lymphocytes that reside within the epithelial cell layer of the intestinal mucosa. The close interaction with epithelial cells appears to be crucial for IEL survival since isolation and ex vivo culture induces massive apoptosis in this lymphocyte population. Here, we provide evidence that this form of IEL cell death may be mediated at least in part by endogenously produced glucocorticoids since adrenalectomy or treatment of mice with a glucocorticoid receptor antagonist significantly enhanced ex vivo survival of IEL. We further demonstrate that ex vivo activation of IEL induces upregulation of anti-apoptotic gene products, compensates for the lack of survival cytokines and rescues from apoptotic cell death. Thus, similar to thymocytes and T cell hybridomas, IEL survival may be regulated by the antagonistic action of TCR activation and glucocorticoids.
Actins↗
Antisense expression of an Arabidopsis ran binding protein renders transgenic roots hypersensitive to auxin and alters auxin-induced root growth and development by arresting mitotic progress.
We cloned a cDNA encoding an Arabidopsis Ran binding protein, AtRanBP1c, and generated transgenic Arabidopsis expressing the antisense strand of the AtRanBP1c gene to understand the in vivo functions of the Ran/RanBP signal pathway. The transgenic plants showed enhanced primary root growth but suppressed growth of lateral roots. Auxin significantly increased lateral root initiation and inhibited primary root growth in the transformants at 10 pM, several orders of magnitude lower than required to induce these responses in wild-type roots. This induction was followed by a blockage of mitosis in both newly emerged lateral roots and in the primary root, ultimately resulting in the selective death of cells in the tips of both lateral and primary roots. Given the established role of Ran binding proteins in the transport of proteins into the nucleus, these findings are consistent with a model in which AtRanBP1c plays a key role in the nuclear delivery of proteins that suppress auxin action and that regulate mitotic progress in root tips.
Amino Acid Sequence↗
Autoschizis: another cell death for cancer cells induced by oxidative stress.
Scanning and transmission electron microscopy (SEM and TEM) were employed to characterize the cytotoxic effects of vitamin C (VC), Vitamin K3 (VK3) or a VC:VK3 combination on a human bladder carcinoma cell line (T24) following vitamin treatment. T24 cells exposed to VC alone showed membrane defects. VK3-treated cells show greater damage than VC treated cells because they exhibit membrane defects, cytoskeletal damage, excision of cytoplasm, and a substantial decrease in the number of viable cells. VC: VK3 treatment exacerbates the damages, especially intranuclear and nucleolar and induces an extreme reduction of cell size by cytoplasmic self-excision. Conversely, the nuclear envelope remains intact and the rough endoplasmic reticulum (RER) maintains its integrity until karyorrhexis occurs through a new phenomenon of cell death that we have named "autoschizis". From our morphological studies and previous biochemical reports on the topic, we are able to propose that this autoschizic cell death found is induced by oxidative stress.
Antineoplastic Combined Chemotherapy Protocols↗
[Adjuvant therapy of pancreatic carcinoma].
The poor prognosis in pancreatic carcinoma has been increased especially by improved diagnostic procedures and decreasing perioperative mortality. Median survival after complete resection is commonly less than 20 months and the 5 years survival is in the range of about 20%. Postoperative radiochemotherapy reduces the local recurrence rate but not the overall survival however. Pancreatic carcinoma is characterized by a low chemosensitivity of the drugs commonly used like 5-FU. More aggressive chemotherapy protocols are limited by the reduced status of the patient. Multimodal and prolonged adjuvant schedules did not show a prognostic benefit. The current ESPAC--study investigates the role of simultaneous radiotherapy and 5-FU alone or in combination with neoadjuvant 5-FU and folic acid for 6 months. New protocols will investigate the value of regional adjuvant chemotherapy ESPAC 2) [44] and of gemcitabine, 5-FU or control in a three arm study.--In a multicenter German trial the benefit of gemcitabene as weekly monotherapy for 6 months is investigated. The treatment starts soon after resection due to low toxicity and good patient compliance.
Combined Modality Therapy↗
Accurate computation of coincidence summing corrections in low level gamma-ray spectrometry
The GESPECOR (Germanium Spectrometry Correction factors) software, previously developed for computing the self-attenuation and coincidence summing corrections, was applied to the computation of the coincidence summing correction factors for a well-type and two coaxial HPGe detectors. Cylindrical samples as well as Marinelli beaker samples were considered. The computed values are in good agreement with carefully measured values. A detailed study of the uncertainties assigned to the results was carried out. The analysis shows that the procedures used in GESPECOR are reliable and provide results with a well defined accuracy.
Journal Article↗
The PTB underground laboratory for dosimetry and spectrometry
In 1991, the Physikalisch-Technische Bundesanstalt established an underground laboratory for dosimetry and spectrometry (UDO) at the Asse salt mine, near Braunschweig. Due to the depth of 925 m below ground (equivalent to about 2100 m of water), the cosmic ray muon intensity in this facility is reduced by more than 5 orders of magnitude. In addition, the low specific activity of the pure rock salt and a low concentration of radon lead to an extremely low ambient dose equivalent rate of less than 1 nSv/h. The UDO facility is therefore well suited for dosimetry at very low dose rates, as well as for Ultra-Low-Background (ULB) gamma-ray spectrometry. In 1998, a coaxial low-background HPGe-detector (88% relative efficiency, FWHM 2.0 keV at 1.33 MeV) with an extended shielding (20 cm low-activity lead, 1 cm electrolytic copper, N2-flushing) was installed at UDO; the count rate per mass of germanium, integrated over the energy range from 40 to 2750 keV, was measured to be 0.012 s(-1) kg(-1). Results from test measurements and first applications are reported. The design of a ULB gamma-detector system, presently under construction, is described.
Journal Article↗
Coincidence-summing in gamma-ray spectrometry by excitation of matrix X-rays
Sources containing 75Se in a Pb(NO3)2 solution and in water matrices were measured using a well-type and a coaxial HPGe detector. The excitation and detection of characteristic lead X-rays increase coincidence losses from the peaks of 75Se in the case of the Pb(NO3)2 source. Sum peaks between gamma-rays of selenium and lead X-rays are observed in the spectra. The experimental results are in accordance with results of computations carried out with an extension of the GESPECOR Monte Carlo program.
Journal Article↗
A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer.
BACKGROUND: Gemcitabine (Gemzar) and 5-fluorouracil (5-FU) plus folinic acid (FA) both have proven activity in the treatment of patients with advanced pancreatic cancer. The present study was initiated to investigate the efficacy of gemcitabine in combination with 5-FU-FA. PATIENTS AND METHODS: Thirty-eight patients, median age 60 years (range 34-70) with inoperable, stage IV, pancreatic cancer were enrolled into the study and treated on an outpatient basis. All except one patient received at least one cycle of treatment with gemcitabine (1000 mg/m2), followed by FA (200 mg/m2) and 5-FU (750 mg/m2) administered as a 24-hour continuous infusion on days 1, 8, 15 and 22 of a 42-day schedule. No patient had received prior chemotherapy or radiotherapy. All 38 patients were assessed for efficacy, toxicity and time to progressive disease. RESULTS: Two patients (5%), achieved a partial response and thirty-four patients (89%) achieved stable disease. There were two early deaths (< or = 4 weeks). The median time to progression was 7.1 months (range 0.4-18.1+; 95% confidence interval (95% CI): 5.3-7.9 months). Three patients had a progression-free interval of greater than 12 months and 12 of 38 patients (32%) survived longer than 12 months. The median overall survival was 9.3 months (range 0.5-26.5; 95% CI: 7.3-13.0 months). The incidence of grade 3 and 4 toxicities was low. CONCLUSIONS: The combination of gemcitabine and 5-FU-FA is active and well tolerated and seems to offer an improvement in progression-free interval over both gemcitabine monotherapy and 5-FU-FA therapy.
Adult↗
[Putting it into practice is difficult. A qualitative study on the theory-practice transfer in the case of kinesthetics].
The theory-practice-gap in nursing is a well-known phenomenon. However, to date there is only very little well-founded evidence in nursing research available on this topic, especially in the context of the FRG. Therefore, a qualitative nursing research project, oriented by the methods of Grounded Theory, on theory transfer into practice using the example of a continuing in-service education program on kinesthetics in nursing was carried out that aimed at examining factors that influence the implementation of kinesthetics into nursing practice. After the program, the researcher conducted mainly semi-structured interviews with the participants about their experiences with using what they had learned in their daily work on the ward. As part of the results, the impact of the category "attributes of kinesthetics" on the theory-practice-transfer of the participants in the continuing education program on the topic will be shown. That is to say something about whether the fact that kinesthetics is perceived as practical, strange and exotic, connected with closeness, or as difficult or risky, has an influence on the use of newly learned knowledge in practice. Finally, the relation of this category to the key-category "working in knowledge and new things" will be shown. The findings of this study suggest that putting emphasis on transfer of knowledge alone is not sufficient to account for the complex structure of the process of theory-practice-transfer.
Diffusion of Innovation↗
Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma.
Although the prognosis for patients with pancreatic adenocarcinoma is still poor, gemcitabine has shown significant impact upon survival and quality of life. Our aim was to examine the potential effectiveness of a second- or third-line therapy with paclitaxel (Taxol) after confirmed progression with a gemcitabine-containing schedule for patients remaining in good clinical condition. Eighteen patients with stage IVb disease participated in this study. Pretreatment with gemcitabine was performed either as monotherapy and/or in combination with 5-fluorouracil (5-FU) and folic acid (FA). Paclitaxel was administered at weekly intervals on an outpatient basis. We observed 238 weekly treatments with a median number per patient of 12 treatments. The median dosage was 73 mg/m2 paclitaxel (range 55-88 mg/m2). Regarding toxicity, only one patient each presented with anemia and leukocytopenia of WHO grade III. Hepatotoxicity with a temporary increase in aminotransferase of WHO grade II occurred in three patients. Higher-grade symptomatic toxicity was rare, except alopecia. At this time, the median survival time is 17.5 weeks (range 7-88 weeks) since the start of therapy. Stable disease was observed in five patients. One patient achieved complete remission within 37 weeks. At this time, he has survived for more than 56 weeks after confirmed progression under first-line therapy. In conclusion, this schedule demonstrates that weekly therapy with paclitaxel after pretreatment can be effective with a low toxicity profile. This opens up an additional therapeutic option for a selected patient group with a poor prognosis so far.
Aged↗
The role of gemcitabine alone and in combination in the treatment of pancreatic cancer.
Pancreatic cancer, one of the most frequently reported gastrointestinal tumors, has a 5-year survival of less than 5%. Despite representing only 2-3% of the total cancer incidence, it is the fifth leading cause of cancer death. This is because it is commonly only diagnosed at an advanced stage. Until recently the traditional therapy for patients with advanced disease was palliative 5-fluorouracil (5-FU)-based chemotherapy. However, the novel antinucleoside gemcitabine (Gemzar) has demonstrated a survival benefit over 5-FU, and an improvement in disease-related symptoms and quality of life in patients with advanced disease. This review presents an overview of the clinical studies of gemcitabine, either alone or in combination, with other chemotherapeutic agents and/or radiation therapy, in the treatment of these patients. A comparison of these studies is made with those using alternative treatment regimens. The data suggest that gemcitabine in combination with biomodulated 5-FU should be considered the standard palliative treatment to which other new drug combinations or combined modality chemoradiation regimens should be compared.
Antimetabolites, Antineoplastic↗
Combined carotid artery injury and laryngeal fracture secondary to dog bite: case report.
Approximately 914 new dog bite injuries requiring emergency department visits occur daily in the United States. Attacks by dogs with training and strength to attack should be triaged cautiously because of the possibility of serious internal injury. A high index of suspicion is needed when treating patients with neck injuries secondary to dog bites. We report a case of successfully treated combined carotid artery and laryngeal injury produced by a dog bite.
Adult↗
Processing, activity, and inhibition of recombinant cyprosin, an aspartic proteinase from cardoon (Cynara cardunculus).
The cDNA encoding the precursor of an aspartic proteinase from the flowers of the cardoon, Cynara cardunculus, was expressed in Pichia pastoris, and the recombinant, mature cyprosin that accumulated in the culture medium was purified and characterized. The resultant mixture of microheterogeneous forms was shown to consist of glycosylated heavy chains (34 or 32 kDa) plus associated light chains with molecular weights in the region of 14,000-18,000, resulting from excision of most, but not all, of the 104 residues contributed by the unique region known as the plant specific insert. SDS-polyacrylamide gel electrophoresis under non-reducing conditions indicated that disulfide bonding held the heavy and light chains together in the heterodimeric enzyme forms. In contrast, when a construct was expressed in which the nucleotides encoding the 104 residues of the plant specific insert were deleted, the inactive, unprocessed precursor form (procyprosin) accumulated, indicating that the plant-specific insert has a role in ensuring that the nascent polypeptide is folded properly and rendered capable of being activated to generate mature, active proteinase. Kinetic parameters were derived for the hydrolysis of a synthetic peptide substrate by wild-type, recombinant cyprosin at a variety of pH and temperature values and the subsite requirements of the enzyme were mapped using a systematic series of synthetic inhibitors. The significance is discussed of the susceptibility of cyprosin to inhibitors of human immunodeficiency virus proteinase and particularly of renin, some of which were found to have subnanomolar potencies against the plant enzyme.
Amino Acid Sequence↗
The HLA-A*6601 peptide motif: prediction by pocket structure and verification by peptide analysis.
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Binding Sites↗