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E Klein

Publications and source records attributed to E Klein.

At least 109 records · Page 6Linked to original sources

Dosimetry measurement tools for commissioning enhanced dynamic wedge.

Measurement of Enhanced Dynamic Wedge parameters requires that the dose at a measurement point be integrated during the entire exposure as the moving jaw closes to form the dose distribution. This major difference from static fields, where dose rate measurements can be made using a single moving probe, requires major modification in measurement techniques to use devices which can measure multiple points within the field simultaneously. Each of these new tools introduce unique problems in dose measurement, which must be understood prior to their use. This paper discusses these tools.

Particle Accelerators↗

The quality assurance of enhanced dynamic wedges.

Dynamic wedge distributions are produced by closing one jaw continuously while simultaneously controlling dose as each position of the jaw. This method of producing wedge distributions requires more frequent Quality Assurance checks, such as verification of wedge profile, wedge factor and verification of the accuracy of the digital position readout for the jaws used for dynamic wedge. "Hard" wedges require only the verification of wedge factor and the verification of reproducibility of mechanical position in the beam. This paper will discuss methods and equipment used for the Quality Assurance of Enhanced Dynamic Wedges.

Particle Accelerators↗

Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response.

A phase II trial was conducted in patients with metastatic renal cell carcinoma, to assess the clinical efficacy and immunoregulatory effects of continuous-infusion recombinant interleukin-2 (rIL-2) (9.0 x 10(6) IU/m2/day on days 1-5, 8-12, 15-19, and 22-26) and subcutaneously administered recombinant human interferon-alpha 2b (rHuIFN alpha 2b) (10.0 x 10(6) U/m2/day TIW). Thirty-six patients with metastatic renal cell carcinoma, performance status of 0-1, and measurable disease who had not received prior rIL-2, rHuIFN alpha 2b, or chemotherapy were treated. Patients with CNS metastases, active infections, history of another malignancy within 3 years, and those requiring corticosteroids were ineligible. Cycles of rIL-2 and rHuIFN alpha 2b were administered in the outpatient department every 6-8 weeks in stable or responding patients until patient tolerance or a complete response were reached. Doses were modified for grade III or IV toxicity. Ancillary studies included three-color immunocytometric analysis of peripheral blood lymphocytes, repetitive tumor biopsies for immunohistologic analysis of infiltrating cells and proliferative responses of tumor infiltrating lymphocytes, and preliminary studies of changes in peripheral blood T-lymphocyte signal transduction molecules [T-cell receptor (TCR)-zeta, p56ick, p59fyn]. Thirty-six eligible patients were treated, with 6 of 36 patients (17%, 95% confidence interval 6-33%) responding (3 complete response, 3 partial response). In two of the partial responders, and in an additional three patients with either minimal tumor regression (one patient) or stable disease (two patients), surgical removal of residual disease was undertaken. The median survival of all patients was 14 months. The toxicity of this regimen was severe, but outpatient administration was possible in most instances. Immunoregulatory effects on T-cell subsets included increases in various CD3+ CD25+/- HLADr+/- subsets unrelated to response. Tumor biopsies before and/or during therapy were obtained in 17 patients, and no consistent alterations in the degree of T-lymphocyte or macrophage infiltrates could be detected. In a subset of patients, tumor infiltrating lymphocyte proliferative responses and levels of peripheral blood T-cell signal transduction molecules (TCR-zeta, p56lck, p59fyn) were investigated. Abnormalities were found in selected patients, which improved during rIL-2/rHuIFN alpha 2b therapy. This cytokine combination produces tumor regression in selected patients with metastatic renal cell carcinoma. Surrogate immunologic markers associated with response were not identified; however, preliminary studies demonstrate investigation of immune defects and their reversal with cytokine therapy is possible.

Adult↗

Avoiding diarrhea after subtotal colectomy with primary anastomosis in the treatment of colon cancer.

BACKGROUND: Subtotal colectomy has been criticized as causing increased frequency of stool passage, thus adding to the patients' morbidity. We review our experience with subtotal colectomy and determine the factors affecting postoperative diarrhea. STUDY DESIGN: One hundred thirty-six patients with colon cancer were treated by primary subtotal colectomy. Of these, 30 percent underwent an emergency resection; 15 percent, semi-emergency resection; and 55 percent, elective subtotal colectomy. There were 29 complications and 3 deaths. RESULTS: The incidence of complications was higher when the operation was carried out on an emergency or semi-emergency basis. In assessing the patients' increased postoperative stool frequency, there was no difference between the groups; but, the length of the remaining colon and the resected terminal ileum had a significant effect on postoperative diarrhea. If less than 10 cm of terminal ileum is resected and more than 10 cm of colon is left above the peritoneal reflection, there is a marked decrease in the incidence of diarrhea after subtotal colectomy. CONCLUSIONS: Subtotal colectomy is an acceptable treatment for left colonic carcinoma, electively as well as in emergency situations. Postoperative diarrhea can be minimized by attention to the length of small bowel and sigmoid that are resected.

Adult↗

Prostate specific antigen decreases after withdrawal of antiandrogen therapy with bicalutamide or flutamide in patients receiving combined androgen blockade.

PURPOSE: We determined whether decreases in prostate specific antigen (PSA) would occur after withdrawal of double-blinded antiandrogen therapy with flutamide or bicalutamide for clinical progression or increasing PSA concentration in patients receiving combined androgen blockade for advanced prostate cancer. MATERIALS AND METHODS: PSA concentrations were determined weekly for at least 6 weeks and then every other week for 6 weeks in 22 patients with stage D2 prostate cancer. All patients were withdrawn from antiandrogen therapy (8 flutamide and 14 bicalutamide) due to progression or an increasing PSA concentration. Objective response was evaluated before antiandrogen withdrawal and at week 12. RESULTS: In 4 of 8 patients (50%) withdrawn from flutamide and 4 of 14 (29%) withdrawn from bicalutamide serum PSA concentrations decreased by 50% or more. PSA responses after withdrawal of flutamide therapy occurred within the first few days, whereas those after withdrawal of bicalutamide therapy occurred within 4 to 8 weeks. Of 4 patients assessed for objective response 2 had stable disease and 2 had progression. A PSA response was observed in the 2 patients with stable disease but not the 2 with progression. CONCLUSIONS: For patients with stage D2 prostate cancer and disease progression or an increasing PSA concentration, withdrawal of antiandrogen therapy with bicalutamide or flutamide may result in a PSA response. The time to PSA response is longer with bicalutamide than with flutamide. The clinical significance of the antiandrogen withdrawal phenomenon is unknown.

Aged↗

Subjective experience and attitudes towards participation in clinical trials among patients with anxiety disorders.

Fifty-two subjects with panic disorder and generalized anxiety disorder were interviewed 12-18 months after they completed an acute treatment study (9-11 weeks) with alprazolam followed by blind and controlled drug discontinuation. Patients were questioned about the severity of their anxiety disorder and degree of functional impairment at the time of follow-up, as well as about their subjective experience as participants in a clinical trial. At the time of follow-up 78% of the patients reported none or minimal anxiety symptoms and 89% had none or only minimal functional deficit, as compared to 100% reporting moderate to severe anxiety symptoms and 57% reporting significant functional deficit before entering the study. Overall, patients felt that the participation in the study was a very positive and beneficial experience and 64% said they would not hesitate to participate in a clinical trial in the future.

Adult↗

B-CLL cells experimentally infected with EBV enter DNA synthesis, produce cytokines and stimulate T-lymphocytes.

Several B-chronic lymphocytic leukemia (B-CLL) clones, represented by different patients can be infected with EBV in vitro. A proportion of the cells becomes activated by the virus, but they rarely yield immortalized cell lines. We used cells from two B-CLL patients which differed in sensitivity to EBV infection. After 7 days in culture, we studied the CLL cells exposed to the B-cell activators Staphylococcus aureus, IL-2 and/or to EBV for expression of the activation markers CD23, CD39 and the adhesion and costimulatory molecules CD54 and CD80, for DNA synthesis, for production of various cytokines and for capacity to stimulate autologous and allogeneic T-lymphocytes. Generally the frequency of cells expressing cytokines in the cytoplasm correlated with the activation status of the populations and with their capacity to stimulate T-cells. It is likely that the difference between the clones with regard to sensitivity to the viral infection, is determined by the maturation state of the CLL cells. It may therefore reflect the variation in the response within a normal B-cell population. The results obtained in the present and in our earlier experiments with EBV provide information concerning the events after primary EBV infection in vivo. The T-lymphocyte stimulatory capacity of the infected CLL cells may be considered as an in vitro correlate to the syndrome of infectious mononucleosis. The detection of cytokines in the infected B-CLL cells suggests that their production by the B-blasts contributes to the level of T-lymphocytosis induced by the primary infection.

Antigens, CD↗

Salivary flow-rate and composition in schizophrenic patients on clozapine: subjective reports and laboratory data.

The extent of hypersalivation was evaluated in a group of 25 schizophrenic patients on clozapine. A high prevalence of the complaint was detected by a questionnaire; up to 80% of the patients complained of hypersalivation at night. Salivary flow-rate and composition was examined in 17 patients who agreed to participate and in a matched group of healthy controls. No significant differences were detected in composition or flow-rates of resting and stimulated saliva. The salivary flow-rates in the schizophrenic patients on clozapine did not correlate with the subjective complaint of hypersalivation. Because the severity and prevalence of the complaint was higher at night, a possibility of an altered circadian rhythm of salivation might be suggested in these patients.

Adult↗

Reaction of lipids containing hydroxy groups with trimethylsulfonium hydroxide: formation of O-methyl derivatives.

Base-catalyzed transesterification of acyl lipids with trimethylsulfonium hydroxide (TMSH) is an easy and convenient method for the preparation of fatty acid methyl esters (FAME) for gas chromatography (GC) analyses. We have found, however, that lipids containing hydroxy groups are partially converted to the corresponding O-methyl ether derivatives which may interfere with FAME in GC separations. For example, long-chain alcohols are found to be converted to alkyl methyl ethers, rac-1-O-alkylglycerols to the corresponding 2-O- and 3-O-monomethyl ethers, as well as 2,3-di-O-methyl ethers, hydroxy fatty acids to methoxy FAME, and cholesterol to cholesteryl 3 beta-methyl ether. From our results, it is obvious that TMSH derivatization method is not recommended without limitation for lipids containing hydroxy groups; it may be, however, of some diagnostic value for the analysis of such lipids by GC/mass spectrometry.

Alcohols↗

The effect of anesthesia type on needle localization breast biopsy: another point of view.

BACKGROUND: Efforts directed at early detection of breast cancer have resulted in an increased incidence of nonpalpable mammographic lesions that warrant excisional biopsy. The most common localization method is by use of the hook wire technique, or needle localization biopsy. Although much has been written about the localization technique, the impact of the method of anesthesia on the accuracy of the biopsy and especially on the completeness of the excision has not been clarified. PATIENTS AND METHODS: We studied 450 needle localization breast biopsies to determine whether the type of anesthesia (local versus general) influenced the accuracy and completeness of the biopsy. We compared 153 biopsies performed under local anesthesia to 297 done under general anesthesia. RESULTS: The use of local versus general anesthesia did not affect accuracy; however, it did determine the inability to achieve clean margins (27.6% versus 7.3%, respectively, P <0.02). It was more difficult to excise completely specimens located deeper than 3 cm in the breast, when the localizing needle travelled more than 3 cm, and when the lesions were of the microcalcification mammographic pattern. CONCLUSIONS: For lesions mammographically suspicious for malignancy, mainly those located deeper than 3 cm, general anesthesia is preferred.

Anesthesia, General↗

Regional hyperthermic perfusion with cisplatin following surgery for malignant melanoma of the extremities.

BACKGROUND: The study was undertaken to review our experience in the treatment of extremity melanoma with hyperthermic isolated limb perfusion (HILP), using cisplatin as the chemotherapeutic agent. We also evaluated the best timing for regional lymph node dissection in relation to the perfusion. PATIENTS AND METHODS: Sixty patients with advanced malignant melanoma of the limbs were treated with HILP used mainly as an adjuvant treatment. There were 56 lower- and 4 upper-limb HILPs. Cisplatin was used at a dose of 20 mg/L of limb volume. Temperature at the tumor site was 39 degrees C to 40 degrees C. Postoperative complications, disease-free period, and time to recurrence were recorded. RESULTS: There were no deaths related to the procedure. Forty-seven percent of the patients developed local complications; most complications were minor and resolved within 60 days. The local complication rate was higher when HILP was performed shortly after or simultaneously with regional lymph node dissection. None of the patients had systemic complications. Mean survival time from treatment was 87.2 months. Currently, 35 patients (58%) are alive and free of disease 52.7 +/- 22.5 months after HILP. Twelve patients (20%) are alive with recurrent disease, of which 5 recurred locally. The average time (+/- standard error of the mean) to recurrence was 24.5 +/- 13.8 months after perfusion. CONCLUSIONS: HILP with cisplatin is a relatively safe procedure, which seems to increase locoregional control of advanced malignant melanoma of the extremity. Separating the timing of lymph node dissection from HILP by 6 to 8 weeks reduces the complication rate.

Aged↗

Correlation of clinical and pathologic factors with rising prostate-specific antigen profiles after radical prostatectomy alone for clinically localized prostate cancer.

OBJECTIVES: To better identify factors affecting prostate-specific antigen (PSA) level elevation after radical prostatectomy alone in men with clinical Stage T1-2 prostate cancer, we have reviewed our experience in the PSA era with 337 cases. The identification of these factors permits better understanding of the impact of case selection on treatment outcome in prostate cancer. METHODS: The charts of all patients treated with radical prostatectomy alone between 1987 and 1993 were reviewed. Patients with clinical Stage T3 disease, without preoperative Gleason scores or PSA levels, with synchronous bladder cancer, and who received adjuvant or neoadjuvant therapy were excluded. The distribution of cases by pretreatment PSA levels was as follows: 4 ng/mL or less (16%); greater than 4 to 10 ng/mL (48%); greater than 10 to 20 ng/mL (22%); and greater than 20 ng/mL (14%). The median pretreatment PSA level for the entire group was 8 ng/mL. Only 26 patients (8%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 43%. Margin involvement rates increased with increasing preoperative PSA levels. One hundred eighty-two patients (54%) had surgical Gleason scores of 7 or higher and 208 (62%) had extracapsular extension. The median follow-up time was 36 months. RESULTS: The 3- and 5-year relapse-free survival (RFS) rates were 74% and 61%, respectively, with relapse being defined as either a clinically detectable recurrence or detectable/rising PSA levels. Among preoperative factors, PSA level was the only independent factor predicting relapse (P = 0.006); the 5-year RFS was 89% in patients with preoperative PSA levels of 4 ng/mL or less; 62% for PSA level of 4 to 10 ng/mL; 56% for PSA level to 10 to 20 ng/mL; and 26% for a PSA level greater than 20 ng/mL. Among pathologic parameters, margin involvement was the most potent independent factor predicting relapse (P < 0.001), followed by Gleason score (P = 0.002) and capsular penetration (P = 0.006). The 5-year RFS rates for margin-positive versus margin-negative patients were 37% versus 80%, respectively (P < 0.001). With pretreatment PSA levels of 10 ng/mL or less, lymph node involvement was seen in 3%, and margin involvement in 36%; the 5-year RFS rate was 71%. With pretreatment PSA levels of greater than 10 ng/mL, lymph node involvement was seen in 16%, and margin involvement in 57%; the 5-year RFS rate was 42%. However, patients with an initial PSA level greater than 10 ng/mL and positive margins had a 5-year RFS rate of 22% versus 73% in patients with a PSA level of 10 ng/mL or less or negative margins (P < 0.001). All clinical relapses were accompanied by a rise in PSA. In patients manifesting a clinical recurrence, PSA elevations preceded clinical recurrences by an average of 15 months (range 0 to 71). Only 34 cases (10%) had clinical failures within 5 years. CONCLUSIONS: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse. The great range in the relapse-free survival rates predicted by preoperative PSA levels demonstrates the importance of pretreatment PSA levels in case selection. Gleason score, extracapsular extension, and surgical margin involvement are also independent predictors of biochemical relapse. Achieving negative margins, even in relatively advanced disease, provides excellent long-term local control.

Adult↗

Interferon-gamma and tumor necrosis factor-alpha treatment of ex vivo human carcinoma cells potentiates their interaction with allogeneic lymphocytes.

Short-term exposure of ex vivo carcinoma and sarcoma cells to IFN-gamma and TNF-alpha induced or elevated to detectable levels the surface expression of MHC class I, class II, and ICAM-1 (CD54), but only rarely the B7 (CD80) molecules. The cytokine-treated tumor cells interacted more efficiently with allogeneic blood lymphocytes collected from healthy donors compared with untreated cells. This was demonstrated (1) by the induction of DNA synthesis and generation of cytotoxic activity in mixed cultures and (2) by the elevated susceptibility to the cytotoxic effectors. Although the cytokine-induced increase in MHC and ICAM-1 on the low-expressor tumors were probably important to the interaction with lymphocytes, it is likely that other properties were also induced that contributed to the phenomenon. This was indicated by the results obtained with several tumors that expressed indigenously high levels of these molecules but reacted with the allogeneic lymphocytes only or more efficiently after treatment with IFN-gamma and TNF-alpha. In these experiments B7 expression did not influence the efficiency of interactions between lymphocyte and tumor cells. The results also showed that, under the conditions used, the untreated tumor cells that did not activate allogeneic lymphocytes were sensitive to appropriately activated effectors. Thus the afferent and efferent arms of lymphocyte-tumor cell interactions appeared to have different requirements.

Antigens, Neoplasm↗

Preliminary imaging results using In-111 labeled CYT-356 (Prostascint) in the detection of recurrent prostate cancer.

To evaluate whether In-111 capromab pendetide (an antibody conjugate directed to a glycoprotein found primarily on the cell membrane of prostate tissue) radioimmunoscintigraphy can localize residual or metastatic prostatic carcinoma in 15 patients after prostatectomy and lymphadenectomy for prostatic carcinoma with rising serum prostate-specific antigen. One patient with 0.6 ng/ml serum prostate-specific antigen had normal imaging results and 14 patients had scintigraphic evidence of residual prostatic bed or metastatic prostatic carcinoma. Two patients with borderline abnormal bone scans had abnormal activity in the same regions on In-111 capromab pendetide images. All patients had negative radiographic abdominal and pelvic cross-sectional prestudy images, and there were no adverse effects related to In-111 capromab pendetide infusion and little human antimouse antibody response.

Antibodies, Monoclonal↗

Detection efficiency of colorectal carcinoma recurrence using technetium pertechnetate-anti-carcinoembryonic antigen monoclonal antibody BW 431/26.

BACKGROUND: A new anti-carcinoembryonic antigen (CEA) antibody, BW 431/26 (Scintimun, Behring-Werke, Marburg, Germany), labeled with technetium pertechnetate (Tc-99m), is an intact immunoglobulin G1 monoclonal antibody that has been used to image colorectal cancer (CRC). This report is part of a prospective multicenter clinical trial initiated by the International Atomic Energy Agency to evaluate the role of this antibody in radioimmunoimaging of patients with suspected disease recurrence. METHODS: A group of 31 consecutive patients underwent radioimmunoimaging with Tc-99m-BW 431/26 after resection of their primary CRC. Patient referral was based on either a persistent rise in serum CEA levels of unknown origin and/or questionable findings by other imaging studies. Whole-body planar scans and single photon emission computed tomography scans of selected body regions (e.g., chest, abdomen) were performed up to 24 hours after the intravenous antibody injection. Pathologic antibody concentration localizations by radioimmunoimaging were correlated with surgical, clinical, and other imaging modality findings to validate the accuracy of radioimmunoimaging in detecting CRC recurrence. RESULTS: A total of 75 detected tumoral lesions was evaluated: 26 of 75 were of known origin (36%), and 49 of 75 were of unknown origin (65%). There were four true-negative lesions, one false-negative lesion, and no false-positive lesions; all others were true-positive lesions. Sensitivity was 96.8%, specificity 100%, and accuracy 98.6%. The study was easy to perform, without untoward side effects on patients after antibody administration. CONCLUSIONS: Anti-CEA antibody radioimmunoimaging is a highly reliable diagnostic procedure in detecting CRC recurrence and is useful especially for the diagnosis of patients with rising CEA blood levels of unknown origin, thereby significantly affecting patient management. Radioimmunoimaging should become part of the diagnostic workup of patients suspected of having CRC recurrence.

Aged↗