The employment status of 1995 graduates from radiation oncology training programs in the United States.

PURPOSE: To quantify the employment status of 1995 graduates of radiation oncology training programs in the United States. METHODS AND MATERIALS: All senior residents (149) and fellows (36) who completed training in 1995 were mailed an employment survey questionnaire by the Association of Residents in Radiation Oncology (ARRO). Telephone follow-up of nonrespondents achieved a 100% response rate. Twenty graduates who chose to continue training and five who returned to their home countries were removed from the study. Of the 160 who attempted to enter the U.S. workforce, 106 were men and 54 were women. Initial job status and job status at 6-8 months following graduation were determined. RESULTS: Unemployment was 6.9% at graduation and 4.4% at 6-8 months. Underemployment (part-time employment) was 10.6% at graduation and 11.9% at 6-8 months postgraduation. Of those working part-time 6-8 months after graduation, 63% (12 of 19) did so involuntarily after unsuccessfully seeking full-time employment. For the 20 graduates who chose to continue training with fellowships, seven (35%) did so solely to avoid unemployment, four (20%) were partially influenced by the job market, and nine (45%) were not influenced by the job market. Adverse employment search outcome was defined as being either unemployed as a radiation oncologist or involuntarily working part-time. Excluding those who chose to work part-time, a total of 19 (11.9%) graduates at 6-8 months following graduation, compared to 22 (13.8%) at graduation, were either unemployed or involuntarily working part-time. In terms of gender, this represented 18.5% (10 of 54) of females and 8.6% (9 of 105) of males. In terms of geographic restrictions in the job search, 56% of males and 70% of females with an adverse employment outcome limited their job search to certain parts of the country. This compares to 62% of all graduates in this study with geographic restrictions in their job search. In terms of perceptions of the workforce and employment opportunities, 95% of all graduates believed there was an oversupply of radiation oncologists and 95.5% believed the job market was worse than what they had anticipated on entering training. Only 42.8% of all graduates were satisfied with the job opportunities available to them. A significant number of private practice positions (41%) did not offer a partnership track, and those that did so had an increased median employment period before partnership (3.25 years) compared to previous years. CONCLUSION: This is the only employment survey for any specialty in which a 100% response rate was achieved. Upon graduation, a significant number of residents and fellows were either unemployed or involuntarily underemployed. The job market absorbed only a fraction of them at 6-8 months. Most graduates, including those employed full-time, were not satisfied with the practice opportunities available to them during their job search. Many private-sector jobs did not offer a partnership track, and those that did required an increased employment period. A higher rate of involuntary part-time employment was seen for female graduates. Geographic restrictions in job search alone could not account for graduates being unemployed or underemployed, and could not account for gender differences. An overwhelming majority of 1995 radiation oncology graduates believed that the job market had deteriorated and that there was an oversupply of radiation oncologists. As one of two major studies tracking the employment status of radiation oncology graduates, we believe this study to be superior in methodology. We also believe this study presents data in a manner useful to medical students, training program directors, and healthcare policymakers.

Inhibition of mouse mammary adenocarcinoma (EMT6) growth and metastases in mice by a modified form of C-reactive protein.

Mice were injected in the hind limb with a mouse mammary adenocarcinoma cell line, EMT6, and tumor growth at the primary site as well as the incidence of lung metastases were measured. Groups of animals were treated with the acute-phase reactant C-reactive protein, (native-CRP), or a conformationally modified form of CRP (mCRP) made by dissociating CRP subunits under chelating, denaturing conditions. Each form of CRP was injected (intravenously) through the tail vein, encapsulated in large unilamellar lipid vesicles made by an extrusion technique (LUVETs). mCRP was also injected without the LUVET carrier. Mice not treated, or treated with LUVETs alone, exhibited both progressive tumor growth at the primary site and a high incidence of metastatic lung tumors quantified at necropsy. Treatment with native-CRP encapsulated in LUVETs had little or no effect on either tumor growth or metastases. Treatment with mCRP, however, alone or encapsulated in LUVETs, effectively slowed or stopped the progression of tumor growth, and in some mice, showed a decrease in tumor size. After cessation of mCRP injections, tumor growth resumed at a rate comparable to that measured in untreated animals. Fifty to 85% of mice treated with mCRP or mCRP in LUVETs developed necrotic lesions at the primary tumor site within 24-48 h following the initial injection of protein. Furthermore, at necropsy, only 6% of mice treated with mCRP in LUVETs and 40% of mice treated with mCRP alone showed evidence of lung metastases compared to 67-80% of animals in no-treatment, native-CRP in LUVETs and in LUVET control group animals. These results show that the prototypic acute-phase reactant, CRP, has therapeutic anticancer and antimetastatic activity only when the native pentameric subunit structure is dissociated to form the mCRP conformer.

Conversion of native oligomeric to a modified monomeric form of human C-reactive protein.

C-reactive protein (CRP) is a pentameric oligoprotein composed of identical 23 kD subunits which can be modified by urea-chelation treatment to a form resembling the free subunit termed modified CRP (mCRP). mCRP has distinct physicochemical, antigenic, and biologic activities compared to CRP. The conditions under which CRP is converted to mCRP, and the molecular forms in the transition, are important to better understand the distinct properties of mCRP and to determine if the subunit form can convert back to the pentameric native CRP form. This study characterized the antigenic and conformational changes associated with the interconversion of CRP and mCRP. The rate of dissociation of CRP protomers into individual subunits by treatment in 8 M urea-10 mM EDTA solution was rapid and complete in 2 min as assayed by an enzyme-linked immunofiltration assay using monoclonal antibodies specific to the mCRP. Attempts to reconstitute pentameric CRP from mCRP under renaturation conditions were unsuccessful, resulting in a protein retaining exclusively mCRP characteristics. Using two-dimensional urea gradient gel electrophoresis, partial rapid unfolding of the pentamer occurred above 3 M urea, a subunit dissociation at 6 M urea, and further subunit unfolding at 6-8 M urea concentrations. The urea gradient electrophoresis results suggest that there are only two predominant conformational states occurring at each urea transition concentration. Using the same urea gradient electrophoresis conditions mCRP migrated as a single molecular form at all urea concentrations showing no evidence for reassociation to pentameric CRP or other aggregate form. The results of this study show a molecular conversion for an oligomeric protein (CRP) to monomeric subunits (mCRP) having rapid forward transition kinetics in 8 M urea plus chelator with negligible reversibility.

Postoperative localization of porta hepatis and abdominal vasculature in pancreatic malignancies: implications for postoperative radiotherapy planning.

PURPOSE: To evaluate changes in preoperative and postoperative positions of structures used to define target volumes (i.e., pancreatic bed, porta hepatis, local-regional lymph nodes) for postoperative irradiation of pancreatic malignancies as defined by abdominal computed tomographs. METHODS AND MATERIALS: Eleven consecutive patients who had Whipple resection and postoperative irradiation for pancreatic cancer were evaluated. Preoperative and postoperative computed tomographs of each patient were evaluated for the position of the portal vein bifurcation and the origin of the celiac axis and superior mesenteric artery. The length along the x (medial-lateral position) and y (anterior-posterior position) axes was determined with calipers to the closest millimeter. Length along the z axis (cephalad-caudad position) was determined with the computed tomographic sectional interval between images. Statistical significance of the change in the structure's position along the x, y, or z axis between preoperative and postoperative computed tomographs was assessed with the paired t-test. RESULTS: Evaluation of the preoperative and postoperative positions of the portal vein, celiac axis, and superior mesenteric artery along the x, y, and z axes revealed a statistically significant change in the location of the portal vein and celiac axis postoperatively. The median change of the celiac axis in the anterior-posterior position was significant (p = 0.0047), but the mean change was only 2 mm and not considered clinically significant. The median change for the portal vein was 0.97 cm and 1.07 cm along the y and x axes, respectively, and was significant (p = 0.008 and p = 0.0001). The range in position change for the portal vein was 0.0 to 2.0 cm along the y axis and 0.4 to 1.9 along the x axis. The remaining mean changes in position along all axes for all the structures were less than 3 mm (not statistically significant). CONCLUSIONS: The mean position of the portal vein-porta hepatis after Whipple resection is approximately 1.0 cm medial and 1.0 cm posterior compared with its preoperative position. These data suggest that postoperative abdominal computed tomographs are useful in determining treatment volumes of nodal drainage basins after Whipple resection of pancreatic malignancies.

An immunofiltration apparatus for accelerating the visualization of antigen on membrane supports.

Although proteins can be transferred and bound to a membrane with several different methods such as capillary transfer, electroblotting, etc., only the "shaker/incubation" method is commonly used for visualization of the proteins. We have tested an apparatus for the immunofiltration of solutions through nitrocellulose membrane which greatly accelerates the kinetics for the visualization of proteins. As a model system, avidin, bound on nitrocellulose membrane, was detected with 5-min filtering steps of a 1:2000 dilution of ascites of murine monoclonal antibody against avidin followed by a 1:5000 dilution of goat anti-mouse IgG-horseradish peroxidase and 0.5 mg/ml chloronapthol in the presence of 0.01% peroxide. The same solutions used with 5-min incubation steps with the shaker/incubation method could not detect avidin at almost 10 times that amount. Further studies with monoclonal antibodies specific for native C-reactive protein and modified-CRP, 15.1D6 and 13.3H12 respectively, showed that immunofiltration did not result in altered specificity compared to the shaker/incubation method. Also, data are presented showing the advantages of a 10-slot top for the immunofiltration of solutions through distinct areas of a membrane.

Comparison of D&C and office endometrial biopsy in predicting final histopathologic grade in endometrial cancer.

OBJECTIVE: To compare the accuracy of D&C and office Z-sampler endometrial biopsy in predicting hysterectomy tumor grade in women with endometrial cancer. METHODS: Between September 1987 and July 1994, 183 women with endometrial cancer had D&C or office Z-sampler endometrial biopsy before hysterectomy. RESULTS: One hundred thirty-one patients (72%) had Z-sampler biopsies and 52 (28%) had D&C. The Z-sampler correctly identified the hysterectomy tumor grade in 76 of 131 patients (58%), compared with 40 of 52 (77%) with D&C, a significant difference (P = .024). The major difference observed was an increased fraction of lesions undergraded (ie, a lower grade tumor found in the biopsy than in the hysterectomy specimen) by the Z-sampler (34 of 131, 26%) versus D&C (five of 52, 10%). CONCLUSION: Dilation and curettage was more accurate in identifying hysterectomy tumor grade and less likely to miss a higher-grade tumor than was Z-sampler biopsy. However, the inaccuracy of D&C alone necessitates further preoperative and intraoperative assessment for other risk factors to determine the aggressiveness with which an individual patient should be staged surgically.