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Biomedical subjects

C Geppert

Publications and source records attributed to C Geppert.

9 recordsLinked to original sources

Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism.

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

Bone and Bones↗

Precision branching ratio measurement for the superallowed beta+ emitter 62Ga and isospin-symmetry-breaking corrections in A>or=62 nuclei.

A high-precision branching ratio measurement for the superallowed beta+ decay of 62Ga was performed at the Isotope Separator and Accelerator radioactive ion beam facility. Nineteen gamma rays emitted following beta+ decay of 62Ga were identified, establishing the dominant superallowed branching ratio to be (99.861+/-0.011)%. Combined with recent half-life and Q-value measurements, this branching ratio yields a superallowed ft value of 3075.6+/-1.4 s for 62Ga decay. These results demonstrate the feasibility of high-precision superallowed branching ratio measurements in the A>or=62 mass region and provide the first stringent tests of the large isospin-symmetry-breaking effects predicted for these decays.

Journal Article↗

Five-year results of laparoscopic Toupet fundoplication as the primary surgical repair in GERD patients: is it durable?

INTRODUCTION: Most surgeons operate on gastroesophageal reflux disease (GERD) patients using the concept of "tailored approach," which depends on esophageal motility. We have abandoned this concept and performed laparoscopic Toupet fundoplication in all patients suffering from GERD, independent of their esophageal motility. METHODS: In a prospective trial we have assessed and evaluated our 5-year results of the first 100 consecutive patients treated with laparoscopic Toupet fundoplication. All patients were evaluated preoperatively by endoscopy and 24-h pH manometry. The patients were followed up clinically 1, 2, 6, 12 and 60 months postoperatively. The course of clinical DeMeester score, appearance and treatment of wrap-related side-effects as well as long-term outcome and patient satisfaction were evaluated. RESULTS: The 5-year follow-up rate was 87%. Laparoscopic Toupet fundoplication achieved a 5-year healing rate of GERD in 85%. Of all operated patients, 3.5% had to be reinstalled on a regular PPI treatment because of postoperative GERD reappearance. The median clinical DeMeester score decreased from 4.27 +/- 1.5 points preoperatively to 0.47 +/- 0.9 points 5 years postoperatively (p < 0.0005). Because of persistent postoperative dysphagia, 5% of the patients required endoscopic dilatation therapy. Persistent postoperative gas-bloat syndrome occurred in 1.1%. Wrap dislocation was identified in 3.4% of patients. Reoperation rate was 5%. Total morbidity rate was 19.5% and operative related mortality rate was 0%. Overall, 96.6% of patients were pleased with their outcome at late follow-up, and 95.4% of patients stated they would consider undergoing laparoscopic fundoplication again if necessary. CONCLUSION: Our long-term results showing a low recurrence and morbidity rate of laparoscopic Toupet fundoplication encourage us to continue to perform this procedure as the primary surgical repair in all GERD patients, independent of their esophageal motility. Laparoscopic Toupet fundoplication has proven to be a safe and successful therapeutic option in GERD patients.

Adult↗

Trace determination of gadolinium in biomedical samples by diode laser-based multi-step resonance ionization mass spectrometry.

The application of high-resolution multi-step resonance ionization mass spectrometry (RIMS) to the trace determination of the rare earth element gadolinium is described. Utilizing three-step resonant excitation into an autoionizing level, both isobaric and isotopic selectivity of >10(7) were attained. An overall detection efficiency of approximately 10(-7) and an isotope specific detection limit of 1.5 x 10(9) atoms have been demonstrated. When targeting the major isotope (158)Gd, this corresponds to a total Gd detection limit of 1.6 pg. Additionally, linear response has been demonstrated over a dynamic range of six orders of magnitude. The method has been used to determine the Gd content in various normal and tumor tissue samples, taken from a laboratory mouse shortly after injection of gadolinium diethylenetriaminepentaacetic acid dimeglumine (Gd-DTPA), which is used as a contrast agent for magnetic resonance imaging (MRI). The RIMS results show Gd concentrations that vary by more than two orders of magnitude (0.07-11.5 microg mL(-1)) depending on the tissue type. This variability is similar to that observed in MRI scans that depict Gd-DTPA content in the mouse prior to dissection, and illustrates the potential for quantitative trace analysis in microsamples of biomedical materials.

Animals↗

Placebos and paradoxes in psychiatric research: an ethics perspective.

The use of placebos in clinical trials, particularly in research with mentally ill people, has emerged as a subject of considerable controversy. We first outline ethical aspects of the primary scientific arguments for and against placebo use in research. Three examples of paradoxical aspects of the ethical use of placebos are discussed: involvement of relatively more vulnerable populations, use of apparently "less than standard" therapy, and the omission of information in placebo comparisons. In the current scientific and regulatory context, placebo use in psychiatric research may be necessary for scientific reasons, and when certain conditions are present, it may be justified on ethical grounds. Four key recommendations to facilitate the ethical use of placebos in research trials are presented. We conclude that placebo trials should be undertaken only after careful evaluation of alternative scientific strategies and, as with all human research, with great respect and genuine consideration for the individuals who choose to participate in these protocols.

Clinical Trials as Topic↗

41Ca ultratrace determination with isotopic selectivity > 10(12) by diode-laser-based RIMS.

41Ca ultratrace determination by diode-laser-based resonance ionization mass spectrometry with extremely high isotopic selectivity is presented. Application to environmental dosimetry of nuclear reactor components, to cosmochemical investigations of production cross sections, and biomedical isotope-tracer studies of human calcium kinetics are discussed. Future investigations are possible use in 41Ca-radiodating. Depending on the application, 41Ca isotopic abundances in the range of 10(-9) to 10(-15) relative to the dominant stable isotope 40Ca must be determined. Either double- or triple-resonance optical excitation with narrow-band extended cavity diode lasers and subsequent non-resonant photoionization of calcium in a collimated atomic beam were used. The resulting photoions are detected with a quadrupole mass spectrometer optimized for background reduction and neighboring mass suppression. Applying the full triple-resonance scheme provides a selectivity of approximately 5 x 10(12) in the suppression of neighboring isotopes and > 10(8) for isobars, together with an overall detection efficiency of approximately 5 x 10(-5). Measurements on a variety of sample types are discussed; the accuracy and reproducibility of the resulting 41Ca/40Ca isotope ratios was better than 5%.

Calcium Radioisotopes↗

Uncertainty and opposition of medical students toward assisted death practices.

To explore medical students' views of assisted death practices in patient cases that describe different degrees and types of physical and mental suffering, an anonymous survey was administered to all students at one medical school. Respondents were asked about the acceptability of assisted death activities in five patient vignettes and withdrawal of life support in a sixth vignette. In the vignettes, actions were performed by four possible agents: the medical student personally; a referral physician; physicians in general; or non-physicians. Of 306 medical students, 166 (54%) participated. Respondents expressed opposition or uncertainty about assisted death practices in the five patient cases that illustrated severe forms of suffering which were secondary to amyotrophic lateral sclerosis, treatment-resistant depressive and somatoform disorders, antisocial and sexually violent behavior, or AIDS. Students supported the withdrawal of life support in the sixth vignette depicting exceptional futility secondary to AIDS. Students were especially opposed to their own involvement and to the participation of non-physicians in assisted death activities. Differences in views related to sex, religious beliefs, and personal philosophy were found. Medical students do not embrace assisted death practices, although they exhibit tolerance regarding the choices of medical colleagues. How these attributes of medical students will translate into future behaviors toward patients and peers remains uncertain. Medical educators must strive to understand the perspectives of physicians-in-training. Expanded, empirically informed education that is attuned to the attitudes of medical students may be helpful in fulfilling the responsibility of imparting optimal clinical care skills.

Adult↗

An invitation for medical educators to focus on ethical and policy issues in research and scholarly practice.

Medical education research and medical education practice both involve being methodical, innovative, self-observing, forward-looking, and open to peer review, and both are scholarly activities. For these reasons, distinguishing between these two activities is often difficult. There are three important reasons to clarify the distinctions: the moral difference between education research and education practice; federal regulations governing education research that require more safeguards than often exist in education practice; and the fact that student participants in research have characteristics in common with members of special populations. The authors explain why attention to issues of safeguards in education research and practice is likely to grow at academic health centers, yet maintain that these issues are neglected in the medical education literature. They demonstrate this with findings from their review of 424 education research reports published in 1988 and 1989 and in 1998 and 1999 in two major medical education journals. Each article was evaluated for documentation of six ethically important safeguards and features (e.g., informed consent). The rates of reporting the six features and safeguards were relatively low (3-27%). Nearly half (47%) of the empirical reports offered no indication of ethically important safeguards or features, and no article mentioned all six. Furthermore, those rates did not increase substantially after ten years. The authors discuss a number of implications of their findings for faculty, training institutions, students, and editors and peer reviewers, and conclude with the hope that their findings will raise awareness of these neglected issues in medical education and will stimulate all those involved to reflect upon the issues and set standards on the ethical aspects of research and scholarly practice.

Academic Medical Centers↗