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Biomedical subjects

R Gerber

Publications and source records attributed to R Gerber.

At least 19 recordsLinked to original sources

Growth factor receptors are differentially expressed in cancers of the papilla of vater and pancreas.

OBJECTIVE: To compare growth factor receptor expression in papilla of Vater cancer and pancreatic cancer. SUMMARY BACKGROUND DATA: Cancer of the papilla of Vater has a much better prognosis than pancreatic cancer. Earlier symptoms may result in earlier diagnosis, but different biologic growth behaviors and genetic alterations might also be explanations. PATIENTS AND METHODS: Surgical specimens from papilla of Vater cancers (24 patients) and pancreatic cancers (80 patients), normal papilla of Vater tissues (20 patients), and normal pancreatic tissues (24 patients) were frozen and fixed. The authors compared the expression of the epidermal growth factor receptor (EGFR) and c-erbB2 and c-erbB3 by Northern blot, in situ hybridization, and immunohistochemistry. RESULTS: In papilla of Vater cancer, Northern blots showed comparable EGFR and c-erbB2 mRNA expression but significantly lower c-erbB3 mRNA levels than in normal papilla. In pancreatic cancer, mRNA expression was enhanced compared with normal controls for EGFR (4-fold), c-erbB2 (2.5-fold), and c-erbB3 (5.2-fold). In situ hybridization confirmed this and showed mRNA expression only in cancer cells. EGFR immunohistochemical staining scores were comparable in papilla of Vater cancer (1.17 +/- 0.22) and normal papilla (1.42 +/- 0.25). Staining scores for c-erbB2 (2.72 +/- 0.40 vs. 3.89 +/- 0.37) and c-erbB3 (2.78 +/- 0.35 vs. 3.89 +/- 0.53) were slightly lower than controls in papilla of Vater cancer. In pancreatic cancer, immunostaining scores for EGFR, c-erbB2, and c-erbB3 were significantly higher than controls. CONCLUSION: Members of the EGFR family show similar or lower expression in papilla of Vater cancer than in normal controls. In pancreatic cancer, these receptors are upregulated. This supports the hypothesis that papilla of Vater cancer and pancreatic cancer have biologic differences that may contribute to the different growth of these tumors.

Adult

Phenomenography: a qualitative research approach for exploring understanding in health care.

Phenomenography is a little-known qualitative research approach that has potential for health care research, particularly when people's understanding of their experience is the goal. Phenomenography is explained as a qualitative, nondualistic research approach that identifies and retains the discourse of research participants. This article seeks to present the major assumptions associated with phenomenographic research. An example of the way in which research outcomes are presented is included to emphasize its distinctiveness. It is noted that phenomenography has potential in the area of qualitative health research and will benefit from ongoing development and application.

Data Collection

Maternal food restriction in the second half of pregnancy affects vascular function but not blood pressure of rat female offspring.

Food restriction during pregnancy in rats induces intrauterine growth retardation with consequences persisting into adulthood. In the present study we have investigated the hypothesis that malnutrition in pregnant rats may lead to altered cardiovascular function in adult female offspring. Perinatal growth retardation was induced by a 50% reduction of normal dietary intake in rats during the second half of pregnancy. Systolic and diastolic blood pressure values and heart rate were recorded in conscious female offspring (100 d old) using a femoral artery probe. No significant differences in heart rate, or in systolic and diastolic blood pressures were recorded between control offspring and offspring of nutritionally deprived rats. In order to ascertain whether cardiovascular variables in the offspring were influenced by lactation, subgroups of offspring from food-restricted dams were fostered with lactating dams fed on a normal diet. Blood pressure and heart rate were also found to be normal in these offspring. The rise in blood pressure associated with NO inhibition was similar in all groups. Isolated resistance artery function was assessed in vitro in offspring (100-120 d old) of a second group of semi-starved dams. Small mesenteric arteries from these animals showed reduced endothelium-dependent relaxation (to acetylcholine and bradykinin), but enhanced sensitivity to exogenous NO (sodium nitroprusside). We conclude that food restriction during the second half of pregnancy and/or lactation does not induce hypertension in adult offspring, but may effect subtle changes in vascular function.

Acetylcholine

Multiple machine implementation of enhanced dynamic wedge.

PURPOSE: After acquiring 4 years of experience with Dynamic Wedge, a software-driven one-dimensional (1D) compensation system, we implemented a new software version called Enhanced Dynamic Wedge (EDW). The EDW allows larger (30 cm) and asymmetric field sizes and additional angles for wedged fields. We implemented this software on four similar dual-energy accelerators that also possess upper and lower physical wedge sets. Our goal was to implement EDW with one common wedge factor (WF) table and one set of treatment-planning files. METHODS AND MATERIALS: We measured WFs with an ionization chamber and isodose profiles with both film and a diode array. We used a calculation scheme that requires only entry of the wedge angle and fixed jaw value. Filters for computerized treatment planning were configured for each wedge angle. We also examined to what degree the multileaf collimation (MLC) orientation, which is orthogonal to the EDW direction, was compromised for specific treatment sites. As a comparative test, we examined the dosimetric consistency for the 8 sets of physical wedges on the four machines. Finally, we updated our DW quality assurance program for EDW. RESULTS: The measured EDW WF was common for all four machines to within +/- 1.5% and the calculation scheme held to within 1.5%. The EDW isodoses were consistent among the machines as measured by film and diode array. The treatment-planning filters provided computed isodose profiles that were nearly identical to measured profiles. Regarding MLC orientation, we found that the collimator angle needed for EDW did not compromise isodose distributions, as apparent in measured isodoses and calculated dose-volume histograms. The consistency of the physical wedges did not fare as well. Two of the lower wedge sets had Wfs and profiles different (> 3%) from the other wedge sets. CONCLUSIONS: We have successfully implemented EDW on four machines using only one WF table and one set of treatment-planning filters. The EDW provides for improved treatment techniques for particular sites due to the large field sizes and additional angles available. Daily treatment efficiency has increased because of the remote capability provided by EDW.

Humans

Physician resource utilization in radiation oncology: a model based on management of carcinoma of the prostate.

PURPOSE: To develop a methodology to estimate the comparative cost of physician time in treating patients with localized prostate cancer, using as an example two-dimensional (2D) vs. three-dimensional (3D) conformal irradiation techniques, and to illustrate how current cost-accounting techniques can be used to quantify the cost of physician time and effort of any treatment. METHODS AND MATERIALS: Activity-based costing, a recent innovation in accounting, widely recommended for estimating and managing the costs of specific activities, was used to derive physician resource utilization costs (actual cost of the physician services and related support services consumed). RESULTS: Patients treated with 3D conformal irradiation consume about 50% more physician time than patients receiving 2D conventional radiation therapy. The average professional reimbursement for the 3D conformal irradiation is only about 26% more than for the 2D treatment. Substantial variations in cost are found depending on the total available physician working hours. In an academic institution, a physician working 40 hours a week would have to spend an average of about 60% of available time on clinical services to break even on a 2D treatment process and over 74% of available time on clinical work to break even on a 3D treatment process. The same physician working 50 hours a week would have to spend an average of about 48% of available time on 2D clinical services and about 60% of available time on 3D clinical work to break even. Current Medicare reimbursement for 3D treatment falls short of actual costs, even if physicians work 100% of a 50-hour week. Medicare reimbursement for 2D barely allows the department to break even for 2D treatments. CONCLUSIONS: Costs based on estimates of resource use can be substantially under- or overestimated. A consistent language (method) is needed to obtain and describe the costs of radiation therapy. The methodology described here can help practitioners and researchers more accurately interpret actual cost information. Future use of such cost-estimation methodologies could provide consistent and comparable costs for negotiations with health care providers and help assess different treatment strategies.

Aged

[Treatment of bacterial osteomyelitis using ultrasonic energy waves].

The method and results of uncommon ultrasound treatment in 82 cases of osteomyelitis are presented. The method was supplemented with intraoperative Th 99m isotope diagnostics as well as fluorescence based diagnosis to identify necrotic bone fragments. Ultrasound energy had advantageous effect on soft tissue healing and osteogenesis.

Adolescent

[Percutaneous resection of osteoid osteoma].

Therapeutic management of osteoid osteomas may vary from conservative medical treatment to more aggressive, though effective, surgery. Based on observations in 4 cases in children, we demonstrate the importance of localizing the lesion on the CT-scan before percutaneous resection of the osteoid osteoma involving small bones since this method is the most conservative surgical procedure.

Adolescent

Three-dimensional treatment planning and conformal radiation therapy: preliminary evaluation.

Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8-14 min and 11.5-12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.

Bile Duct Neoplasms

Design of a fully integrated three-dimensional computed tomography simulator and preliminary clinical evaluation.

PURPOSE: We describe the conceptual structure and process of a fully integrated three-dimensional (3-D) computed tomography (CT) simulator and present a preliminary clinical and financial evaluation of our current system. METHODS AND MATERIALS: This is a preliminary report on 117 patients treated with external beam radiation therapy alone on whom a 3-D simulation and treatment plan and delivery were carried out from July 1, 1992, through June 30, 1993. The elements of a fully integrated 3-D CT simulator were identified: (a) volumetric definition of tumor volume and patient anatomy obtained with a CT scanner, (b) virtual simulation for beam setup and digitally reconstructed radiographs, (c) 3-D treatment planning for volumetric dose computation and plan evaluation, (d) patient-marking device to outline portal on patient's skin, and (e) verification (physical) simulation to verify portal placement on the patient. Actual time-motion (time and effort) recording was made by each professional involved in the various steps of the 3-D simulation and treatment planning on computer-compatible forms. Data were correlated with the anatomic site of the primary tumor being planned. Cost accounting of revenues and operation of the CT simulator and the 3-D planning was carried out, and projected costs per examination, depending on case load, were generated. RESULTS: Average time for CT volumetric simulation was 74 min without or 84 min with contrast material. Average times were 36 min for contouring of tumor/target volume and 44 min for normal anatomy, 78 min for treatment planning, 53 min for plan evaluation/optimization, and 58 min for verification simulation. There were significant variations in time and effort according to the specific anatomic location of the tumor. Portal marking of patient on the CT simulator was not consistently satisfactory, and this procedure was usually carried out on the physical simulator. Based on actual budgetary information, the cost of a volumetric CT simulation (separate from the 3-D treatment planning) showed that 1500 examinations per year (six per day in 250 working days) must be performed to make the operation of the device cost effective. The same financial projections for the entire 3-D planning process and verification yielded five plans per day. Some features were identified that will improve the use of the 3-D simulator, and solutions are offered to incorporate them in existing devices. CONCLUSIONS: Commercially available CT simulators lack some elements that we believe are critical in a fully integrated 3-D CT simulator. Sophisticated 3-D simulation and treatment planning can be carried out in a significant number of patients at a reasonable cost. Time and effort and therefore cost vary according to the anatomic site of the tumor being planned and the number of procedures performed. Further efforts are necessary, with collaboration of radiation oncologists, physicists, and manufacturers, to develop more versatile and efficient 3-D CT simulators, and additional clinical experience is required to make this technology cost effective in standard radiation therapy of patients with cancer.

Adult

Is weekly port filming adequate for verifying patient position in modern radiation therapy?

PURPOSE: The objective of this study is to use daily electronic portal imaging to evaluate weekly port filming in detecting patient set-up position. METHODS AND MATERIALS: A computer-based portal alignment method was used to quantify the field displacements on 191 digitized weekly port films and 848 daily electronic portal images in 21 radiation therapy patients. An electronic portal image data set as a control for actual daily treatment position was used to evaluate weekly port films with respect to same-day field displacement, rate of field placement error detection, and prediction of subsequent daily field displacements. RESULTS: The field displacements measured on a port film frequently deviated from the corresponding field displacements on the electronic portal image obtained in the same treatment set-up. A linear regression analysis showed that the curves fitted to the same-day field displacements had slopes that differed significantly from unity (p < 0.001). Overall, the respective frequencies of field placement error, beyond clinical tolerance limits of 5, 7, and 10 mm (corresponding to head and neck, thoracic, and pelvic sites) for port filming and electronic portal imaging were 11% and 14% (p = 0.4) in the X-direction (lateral or anteroposterior) and 24% and 13% (p = .0001) in the Y-direction (caphalad-caudad). When the data were broken down by anatomical region, this discrepancy was found to be mainly due to the differences in the thorax, and head and neck image data sets. For thoracic fields, error in Y-shifts was 28% by port filming, but only 9% by portal imaging (p = 0.01). In the head and neck region, 18% of the port films exceeded tolerance, whereas only 6% of the electronic portal images did (p = 0.0001). Field displacements on the treatment set-ups between the acquisition of port films were not predicted by those films. CONCLUSION: There are discrepancies between the field displacements and field placement errors detected by weekly port films and daily electronic portal images. This study suggests that improved methods of treatment verification may be necessary in modern radiation therapy.

Diagnostic Imaging

Soluble forms of the human T cell receptor CD4 are efficiently expressed by Streptomyces lividans.

We have developed a new gene expression and secretion system for Streptomyces lividans and used it to produce soluble forms of a human T-cell receptor CD4 at levels greater than 300 mg/l. The system uses the transcription, translation and secretion signals of the serine protease inhibitor gene STI-II which is naturally produced by S. longisporus. Using these signals, soluble derivatives of CD4 were secreted directly into the culture supernatant as correctly processed soluble, biologically active proteins. High level expression of the CD4 proteins depended on the transcription initiation signal, the amino acid sequence surrounding the signal peptide cleavage site and temporally controlled protease activities. We discuss these results in the context of the potential of this system for producing other eukaryotic proteins in Streptomyces.

Amino Acid Sequence

Complete heart block complicating retrograde left-heart catheterization of patients with cardiac allografts.

The development of complete heart block during left-sided cardiac catheterization is an uncommon event. We describe three cases of complete heart block complicating left-sided cardiac catheterization of patients with cardiac allografts. Review of the cases performed at our institution suggests that complete heart block during left-sided catheterization may be more common in patients with cardiac allografts.

Aged