text: content Prostate Diagnosis and Treatment Abstracts Comparison of percent free prostate specific antigen and prostate specific antigen density as methods to enhance prostate specific antigen specificity in early prostate cancer detection in men with normal rectal examination and prostate specific antigen between 4.1 and 10 ng/ml Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate Accelerated tumor proliferation rates in locally recurrent prostate cancer after radical prostatectomy Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin Prostate cancer: Relative effects of demographic, clinical, histologic, and MR imaging variables on the accuracy of staging Results of 3D conformal radiotherapy in the treatment of localized prostate cancer Induction of apoptosis and altered nuclear/cytoplasmic distribution of the androgen receptor and prostate-specific antigen by 1 alpha,25-dihydroxyvitamin D-3 in androgen-responsive LNCaP cells Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging Ischemic damage to the prostate during cardiac surgery: A clinical model Prostate-specific antigen-detected prostate cancer (stage T1c): an analysis of whole-mount prostatectomy specimens. Early stage prostate cancer treated with radiation therapy: Stratifying an intermediate risk group Enhancement of prostate tumor volume definition with intravesical contrast: A three-dimensional dosimetric evaluation Arachidonic acid stimulates prostate cancer cell growth: Critical role of 5-lipoxygenase Induction of cyclo-oxygenase-2 mRNA by prostaglandin E-2 in human prostatic carcinoma cells. Mitoxantrone: A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer. Molecular and cellular biology of prostate cancer. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. Flutamide withdrawal plus hydrocortisone resulted in clinical complete response in a patient with prostate carcinoma. Quality of life and treatment outcomes: Prostate carcinoma patients' perspectives after prostatectomy or radiation therapy. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination: Enhancement of specificity with free PSA measurements. Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: The basis for an adjuvant therapy trial. Family history of prostate cancer in patients with localized prostate cancer: An independent predictor of treatment outcome. Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer. The antiandrogen withdrawal syndrome. Comparison of percent free prostate specific antigen and prostate specific antigen density as methods to enhance prostate specific antigen specificity in early prostate cancer detection in men with normal rectal examination and prostate specific antigen between 4.1 and 10 ng/ml Morote J, Raventos CX, Lorente JA, LopezPacios MA, Encabo G, deTorres I, Andreu J Journal of Urology, 1997, Vol 158, Iss2, pp 502-504 Univ Autonoma Barcelona, Vall Dhebron Hosp, Dept Urol, E-08193 Barcelona, SPAIN Purpose: We analyzed the behavior of prostate specific antigen (PSA) density and percent free PSA to enhance the specificity of PSA in the early diagnosis of prostate cancer in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. Materials and Methods: PSA serum level, PSA density and percent free PSA were analyzed in 74 men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. All men underwent systematic prostate biopsy, and the diagnosis was benign prostate hyperplasia in 52 and prostate cancer in 22. Furthermore, we determined the decrease in unnecessary biopsies and the cancer detection rate using 0.10 versus 0.15 as cut points for PSA density, and 20 versus 25 as cut points for percent free PSA. Results: In patients with benign prostatic hyperplasia and prostate cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml. (p > 0.05), median prostate volume was 50 and 37 cc (p < 0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and median percent free PSA was 18.9 and 10.1 (p < 0.005). Using PSA density cut points of 0.15 and 0.10, the decrease in negative biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%, respectively. However, using percent free PSA cut points of 20 and 25, the decrease in negative biopsies was 36.5 and 26.9% with a sensitivity of 77.3 and 95.5%, respectively. Conclusions: Although both methods could minimize unnecessary biopsies in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective since transrectal ultrasound was not required. In this small series of symptomatic patients a percent free PSA cut point of 25 could detect at least 95% of prostate cancers and decrease 26.9% of negative biopsies. Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate NE Fleshner, M O'Sullivan, WR Fair Journal of Urology, 1997, Vol 158, Iss 2, pp 505-508 Fleshner NE, Mem Sloan Kettering Canc Ctr, Urol Serv, New York,NY 10021 USA Purpose: We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy. Materials and Methods: Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer. Results: A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. And abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. Was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.(3), PSA velocity less than 0.75, ng./ml. Per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy. Conclusions: A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative. Accelerated tumor proliferation rates in locally recurrent prostate cancer after radical prostatectomy JA Connolly, JC Presti, ML Cher, K Chew, K Shinohara, PR Carroll Journal of Urology, 1997, Vol 158, Iss 2, pp 515-518 Carroll PR, Univ Calif San Francisco, Dept Urol, Sch Med, Program Urol Oncol, Mt Zion Canc Ctr, U-575, San Francisco,CA 94143 USA Purpose: We compared the growth rates of primary cancer and prostatic fossa recurrence after radical prostatectomy. Materials and Methods: Tumor proliferative rates were studied in 26 patients with biopsy proved prostatic fossa recurrences after radical prostatectomy. Proliferation was calculated in the prostatectomy specimens and in recurrent cancer using Ki-67 antibody to detect dividing cells. Results: Mean and median labeling indexes for radical prostatectomy specimens were 2.96 and 2.51, respectively. Labeling indexes in locally recurrent tumors were significantly higher (mean 6.47, median 5.59, p < 0.001). The increase in labeling index between parent and recurrent tumors was unrelated to pathological staging at prostatectomy or interval from radical prostatectomy. Conclusions: Tumors that recur locally after radical prostatectomy appear to have a higher proliferative rate compared to parent tumors. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin M Bolla, D Gonzalez, P Warde, JB Dubois, RO Mirimanoff, G Storme, J Bernier, A Kuten, C Sternberg, T Gil, L Collette, M Pierart New England Journal of Medicine, 1997, Vol 337, Iss 5, pp 295-300 Bolla M, Univ Hosp, Dept Radiotherapy, BP 217, F-38043 Grenoble 9, FRANCE Background We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer. Methods From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin. Results Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001). Conclusions Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer. (C) 1997, Massachusetts Medical Society. Prostate cancer: Relative effects of demographic, clinical, histologic, and MR imaging variables on the accuracy of staging DJ Getty, SE Seltzer, CMC Tempany, RM Pickett, JA Swets, BJ McNeil Radiology, 1997, Vol 204, Iss 2, pp 471-479 Getty DJ, Bbn Syst & Technol Corp, 10 Moulton St, Cambridge,MA 02138 USA PURPOSE: To determine the effects on the accuracy of staging prostate gland cancer of diagnostic prediction rules based on demographic, clinical, histologic, and magnetic resonance (MR) image variables. MATERIALS AND METHODS: A total of 200 cases from four medical centers were evaluated by nine radiologists experienced in MR imaging. The accuracies of the four diagnostic variables (age, prostate specific antigen level, Gleason tumor grade, and MR imaging findings) were measured, both singly and combined in a particular sequence, by calculating the area index of the receiver operating characteristic curve. RESULTS: The accuracy of staging with single variables (age, 0.58; prostate specific antigen level, 0.74; Gleason grade 0.73, MR image findings, 0.74) increased as the variables were optimally merged. The first two variables combined to yield an accuracy of 0.74; the first three combined to yield an accuracy of 0.81; and all four variables resulted in an accuracy of 0.86. In a clinically important subset of 69 cases for which antigen level and Gleason grade together were inconclusive for the purposes of staging, the addition of MR imaging findings resulted in an increase in accuracy from 0.55 to 0.73. CONCLUSION: Optimal merging of diagnostic test results yields an improvement in the accuracy of prostate cancer staging. Results of 3D conformal radiotherapy in the treatment of localized prostate cancer N FukunagaJohnson, HM Sandler, PW McLaughlin, MS Strawderman, KH Grijalva, KE Kish, AS Lichter International Journal of Radiation Oncology Biology Physics, 1997, Vol 38, Iss 2, pp 311-317 FukunagaJohnson N, Univ Michigan Hosp, Dept Radiat Oncol, Ann Arbor,MI 48109 USA Purpose: 3D conformal radiotherapy (3D CRT) has been shown to decrease acute morbidity in the treatment of prostate cancer. Therapeutic outcome and late morbidity data have been accumulating. To evaluate the results of 3D CRT for the treatment of prostate cancer, we analyzed the outcome of a large series of patients treated with conformal techniques. Material and Methods: From January 1987 through June 1994, 707 patients with localized prostate cancer were treated with 3D CRT. Patients with pathologically-confirmed pelvic lymph node metastasis, treated with preirradiation (preRT) androgen ablation, or treated post-prostatectomy were excluded. All had CT obtained specifically for treatment planning, multiple structures contoured on the axial images, and beam's-eye view conformal beams edited to provide 3D dose coverage. Median follow-up is 36 mos; 70 patients have been followed longer than 5.5 Sears. Six hundred three had T1-T2 tumors. PreRT prostate specific antigen (PSA) was available for 649 patients: median preRT PSA was 12.9 ng/ml, 209 patients had preRT PSA > 20 ng/ml. The median dose of radiation was 69 Gy; 102 patients received greater than or equal to 69 Gy. Biochemical failure was defined as: 1) two consecutive PSA rises over 2.0 ng/ml if nadir PSA less than or equal to 2.0 ng/ml, 2) two consecutive PSA rises over nadir if nadir PSA > 2.0 ng/ml, or 3) initiation of hormonal therapy after RT. Complications were graded using the RTOG system. Results: PreRT PSA and Gleason score emerged as independent indicators of biochemical control (bNED). Patients with preRT PSA > 10 had a significantly worse bNED at 5 years than patients with preRT PSA less than or equal to 10. Five-year bNED was determined according to preRT PSA: PSA less than or equal to 4, 88%; PSA > 4 less than or equal to 10, 72%; PSA > 10 less than or equal to 20, 43%; and PSA > 20, 30%. Patients with Gleason score greater than or equal to 7 also had a significantly worse bNED than patients with Gleason score < 7. Patients were divided into two prognostic groups: a favorable group with PSA less than or equal to 10, Gleason score < 7, and T1-T2 tumors, and an unfavorable group with PSA > 10, Gleason score greater than or equal to 7 or T3-T4 tumors and studied for the effect of dose on bNED status. The bNED at 5 years was 75% for the favorable group and 37% for the unfavorable group. In addition, a group that might be considered a surgical subset was reviewed: patients with PSA less than or equal to 10, Gleason score less than or equal to 7, and T1-T2 tumors who were <70 years old. This subset had an 84% 5-year bNED rate and 98% 5-year overall survival. Complications with the techniques used here are very low: 3% risk at 7 years of Grade 3-4 complications and 1% risk at 7 years of Grade 3 bladder complications (no Grade 4). Conclusion: 3D CRT allows for treatment of prostate cancers with a very low risk of complications. Patients with relatively early disease as defined by preRT PSA, Gleason score < 7, and T1-2 tumors and patients who are candidates for radical prostatectomy have excellent 5-year bNED rates. Patients with adverse prognostic factors have a high risk of biochemical recurrence and are candidates for innovative therapy. (C) 1997 Elsevier Science Inc. Induction of apoptosis and altered nuclear/cytoplasmic distribution of the androgen receptor and prostate-specific antigen by 1 alpha,25-dihydroxyvitamin D-3 in androgen-responsive LNCaP cells TC Hsieh, JM Wu Biochemical and Biophysical Research Communications, 1997, Vol 235, Iss 3, pp 539-544 Wu JM, New York Med Coll, Dept Biochem Mol Biol, Valhalla,NY 10595 USA In addition to suppressing prostate cell growth, vitamin D also up-regulates the expression of androgen receptor (AR) and prostate-specific antigen (PSA). To study the mechanism involved in the control of these proteins, LNCaP cells were treated with 10 nM 1 alpha,25-dihydroxyvitamin D-3 and separated into cytosol and nuclear fractions. AR and PSA were analyzed by western blot analysis. A second approach involved incubating control and treated cells with [H-3]R1881, fractionating the cells into the cytosolic and nuclear components, and quantifying the amount of radioactivity associated with the respective fractions. Alternatively, immunohistochemical assays were performed by staining cells with cognate antibodies for AR and PSA, Both biochemical and immunohistochemical analyses show proportionately greater increased presence of AR in the nucleus, accompanied by relatively reduced AR in the cytosol, following treatment of LNCaP cells with vitamin D-3. Surprisingly, PSA was found to be present in the nuclear fraction in both control and treated cells. These results suggest that vitamin D-3 promotes the translocation of AR from the cytosol to the nucleus. The presence of PSA in the nucleus of LNCaP cells raises the possibility of an autogenous mode of control of PSA gene expression. (C) 1997 Academic Press. Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging Nakashima J.; Imai Y.; Tachibana M.; Baba S.; Hiramatsu K.; Murai M. Cancer (USA) , 1997, 80/2 (237-241) Dr. J. Nakashima, Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 Japan BACKGROUND. Little effort has been made at the quantitative and qualitative evaluation of patients with prostate carcinoma, including downsizing and downstaging of the primary lesion, after conservative therapy. The current study was undertaken to investigate the qualitative and quantitative effects of endocrine therapy on the primary prostate carcinoma using magnetic resonance imaging (MRI). METHODS. The primary prostate carcinoma was evaluated by endorectal MRI approximately 4 months after the initiation of endocrine therapy in 48 patients with histologically confirmed prostate carcinoma detected by endorectal MRI before therapy. RESULTS. The volumes of the prostate gland, the carcinoma, and the noncarcinomatous components were reduced to 60.2 plus or minus 2.7%, 25.5 plus or minus 2.9%, and 83.2 plus or minus 6.3% of their pretreatment volumes respectively after endocrine therapy, indicating that the tumors are more susceptible to endocrine therapy than the nontumorous components. The number of prostate carcinomas that demonstrated low signal intensity compared with the normal peripheral zone on T2-weighted images decreased after endocrine therapy and the number of carcinomas with enhancement of T1-weighted contrast-enhanced images increased after therapy. Seven of the 48 patients underwent downstaging after endocrine therapy, based on the endorectal MRI evaluation. CONCLUSIONS. The results of the current study suggest that downsizing and occasionally downstaging of the carcinoma may occur after endocrine therapy in patients with prostate carcinoma. In addition, the androgen sensitivity of the prostate carcinoma tissue is relatively high compared with the residual noncancerous prostate gland. Ischemic damage to the prostate during cardiac surgery: A clinical model C Coker, RA Sherwood, T Crayford, F Saadeh, D Mulvin, E Brakenbury, MJ Coptcoat Prostate, 1997, Vol 32, Iss 2, pp 85-88 BACKGROUND. To determine if altered tissue perfusion during cardiac surgery results in ischemic tissue damage to the prostate, as suggested by a rise in prostatic-specific antigen (PSA). METHODS. Twenty-nine male patients undergoing elective coronary artery bypass grafting were studied. Ten male patients undergoing elective gastrointestinal surgery served as controls. PSA levels were determined preoperatively and six hourly intervals postoperatively for 48 hr. All patients underwent urethral catheterization at induction of anesthesia. RESULTS. All patients (100%) who had undergone cardiac bypass surgery showed rises in serum PSA during 48 hr of postoperative follow-up. At the 6-hr postoperative interval, the mean PSA was significantly different from the mean baseline value (paired two tailed Student's t test, P < 0.001) in 27 of the 29 (93%) patients. In contrast, the PSA values in the 10 gastroenterological controls did not change at 6 hr (P > 0.2) or during the next 48 hr. One patient in the cardiac group showed a very marked elevation in serum PSA of greater than 50 times normal preoperative levels. CONCLUSIONS. Statistically significant rises in PSA levels are seen following coronary bypass surgery. This rise may be caused by ischemic nontrauma related damage to the prostate and suggests a possible pathophysiological mechanism for the clinically episodic symptoms of prostatism seen in elderly men. (C) 1997 Wiley-Liss, Inc. Prostate-specific antigen-detected prostate cancer (stage T1c): an analysis of whole-mount prostatectomy specimens. Douglas TH; McLeod DG; Mostofi FK; Mooneyhan R; Connelly R; Moul JW; Sesterhenn IA Prostate (UNITED STATES) Jun 15 1997, 32 (1) p59-64, Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA. BACKGROUND: Clinical and pathological staging of prostate cancer has been, and remains, problematic. Since prostate-specific antigen (PSA)-detected tumors are often discerned during "screening," what are their significance? METHODS: We analyzed 67 consecutive patients with stage T1c prostate cancer undergoing radical prostatectomy at our institution from August 1, 1991-September 12, 1995, and who had whole-mount specimen processing. Diagnosis was determined in all cases by transrectal ultrasound-guided biopsy. RESULTS: The mean age of our patients was 63 years, and the mean PSA at time of diagnosis was 8.6 ng/ml (median, 7.2 ng/ml). There was organ-confined cancer in 31/67 (46%) patients; 17/67 (25%) had periprostatic fat infiltration, and of these 5(7%) had seminal vesicle involvement. Thirty-one of 67 (46%) had positive surgical margins. Twenty-two (33%) had a Gleason sum of > or = 7 in the final pathological specimen. Insignificant tumors (dominant tumor volume < 0.20 cc) were found in only 4 cases. Smaller tumors were more likely to be found when the PSA was < 10 ng/ml. Multifocal disease was found in 64/67 (96%) prostate specimens. CONCLUSIONS: This study adds impetus to the growing realization that nonpalpable prostate cancer, detected because of elevated PSA, is rarely insignificant. Our findings add further emphasis to the fact that patients diagnosed by PSA elevation have, for the most part, significant cancer that should be treated aggressively. Early stage prostate cancer treated with radiation therapy: Stratifying an intermediate risk group JP Lattanzi, AL Hanlon, GE Hanks International Journal of Radiation Oncology Biology Physics, 1997, Vol 38, Iss 3, pp 569-573 Lattanzi JP, Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia,PA 19111 USA Purpose: This study identifies two early prostate cancer populations within the T1/T2AB, Gleason 2-7, pretreatment prostate specific antigen (PSA) 4-15 ng/ml grouping. By demonstrating different outcomes we may be able to more appropriately select a subgroup for whom adjuvant therapy trials or altered treatment techniques are indicated. Materials and Methods: One hundred forty-six patients with T1/T2AB, Gleason score 2-7, PSA 4-15 ng/ml prostate cancer were treated with external beam radiotherapy alone from November 1987 to October 1993. The median pretreatment PSA was 8.6 and the mean 8.7. Minimum follow-up was 2 years with a median of 38 months (mean 42 months, range 24-87). The median age was 70 years (range 58-83) and the median central axis dose delivered was 7240 cGy (mean 7273, range 6541-7895 cGy). Eleven patients received conventional radiotherapy while 135 were treated using conformal techniques. As there is evidence that a low PSA nadir is an early marker for long term biochemical control, time to post treatment PSA < 1 ng/ml was actuarially analyzed by Gleason score, pretreatment PSA, radiation dose, stage, and the presence of perineural invasion. Pretreatment PSA was the only patient characteristic predictive of achieving a PSA level < 1.0 ng/ml. Biochemical relapse free (bNED) control (non rising PSA) was then compared for patients above and below the approximate median pretreatment PSA level of 8 ng/ml. BNED control rates and the time to PSA <1.0 ng/ml were estimated using Kaplan-Meier methodology, and differences in bNED control and PSA <1.0 ng/ml according to PSA level were evaluated using the log-rank test. Results: Results from actuarial analysis revealed that pretreatment PSA was the only significant variable predictive of a PSA <1.0 ng/ml. Ninety-eight percent of patients with pretreatment PSA <8 achieved a PSA level <1.0 ng/ml within 3 years compared to 78% for patients with a PSA >8 ng/ml (p = 0.0003). BNED control for the two groups separated at a pretreatment PSA of 8 ng/ml confirms a favorable outcome, 88% bNED control at 5 years for <8 ng/ml and 74% for a pretreatment PSA greater than or equal to 8 ng/ml (p = 0.007 for overall curve comparison). Conclusion: For early prostate cancer patients (T1/T2AB, Gleason 2-7, pretreatment PSA 4-15) there is a significant break in bNED control following external beam radiation at a pretreatment PSA level of 8 ng/ml. Patients with pretreatment PSA <8 have a very favorable bNED response with radiation alone while those with a pretreatment PSA 8-15 have a significant decrease in bNED response. The 27% failure rate at 5 years in the PSA 8-15 ng/ml patients may justify altered treatment techniques or clinical trials of adjuvant androgen deprivation in this group. (C) 1997 Elsevier Science Inc. Enhancement of prostate tumor volume definition with intravesical contrast: A three-dimensional dosimetric evaluation R Sharma, M Duclos, PJ Chuba, F Shamsa, JD Forman International Journal of Radiation Oncology Biology Physics, 1997, Vol 38, Iss 3, pp 575-582 prostate cancer; intravesical contrast; three-dimensional treatment planning Pergamon-Elsevier Science Ltd, The Boulevard, Langford Lane, Kidlington, Oxford, England OX5 1GB Purpose: To assess the impact of intravesical contrast during computed tomography (CT) simulation on prostate tumor volume definition and dose distribution. Methods and Materials: Sixteen patients with localized adenocarcinoma of the prostate underwent CT-based virtual simulation in preparation for definitive radiotherapy, Patients were immobilized with a foam cradle and an initial CT was performed after oral but without intravesical contrast (noncontrast scan), A second scan was performed following administration of intravesical contrast (contrast scan), Beam apertures were designed on the noncontrast scans and digitized into the contrast scan file, Beam apertures were also designed on the contrast scans, Isodose plans were generated for several beam apertures and arrangements. Results: There was enhanced visualization of the prostate at the cephalad portion of the field for 15 of the 16 cases, The mean differences between the noncontrast and contrast volumes was significant (p = 0.0001), The mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending upon the target volume and beam arrangement. Conclusion: This study demonstrates the necessity of using intravesical contrast for defining the location of the prostate during CT simulation, The underestimation of the extent of the prostate when omitting intravesical contrast leads to significant underdosage, The value of intravesical contrast is most evident when small (prostate only) conformal fields are used. (C) 1997 Elsevier Science Inc. Arachidonic acid stimulates prostate cancer cell growth: Critical role of 5-lipoxygenase J Ghosh, CE Myers Biochemical and Biophysical Research Communications, 1997 Vol 235, Iss 2, pp 418-423 Ghosh J, Univ Virginia, Ctr Canc, POB 334, Charlottesville,VA 22908 USA Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-g poly-unsaturated fatty acids, was found to be an effective stimulator of human prostate cancer cell growth in vitro at micromolar concentrations, Selective blockade of the different metabolic pathways of arachidonic acid (e.g. Ibuprofen for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase specific inhibitors, AA861 and MK886, but not by others. Addition of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of prostate cancer cell growth similar to that of arachidonic acid, whereas the leukotrienes were ineffective, Moreover, the 5-series of eicosatetraenoids could reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed with arachidonic acid showed a dramatic increase in the production of 5-HETEs which is effectively blocked by MK886. These experimental observations suggest that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects on human prostate cancer cells. (C) 1997 Academic Press. Induction of cyclo-oxygenase-2 mRNA by prostaglandin E-2 in human prostatic carcinoma cells. Tjandrawinata RR, Dahiya R, HughesFulford M Br J Cancer 1997 APR;75(8):1111-1118 HughesFulford M, Vet Affairs Med Ctr, Lab Cell Growth 151F, 4150 Clement St, San Francisco,CA 94121 USA Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclo-oxygenases: COX-I (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E-2 (dmPGE(2)) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE(2) to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE(2) concentration. DmPGE(2) also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE(2) regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE(2) concentration, with maximum stimulation seen at 5 mu g ml(-1). The non- steroidal anti-inflammatory drug flurbiprofen (5 mu M), in the presence of exogenous dmPGE(2), inhibited the up- regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE(2) has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE(2), perhaps resulting from changes in local cellular PGE(2) concentrations. Mitoxantrone: A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer. Wiseman LR, Spencer CM Drug Aging 1997 JUN;10(6):473-485LA - English Wiseman LR, Adis Int Ltd, 41 Centorian Dr, Private Bag 65901, Auckland 10, NEW ZEALAND The antineoplastic agent mitoxantrone in combination with a corticosteroid (either prednisone or hydrocortisone) hasshown clinical efficacy as palliative treatment for a proportion of patients (about 35 to 40%) with hormone-resistant advanced prostate cancer; a disease which predominantly affects elderly men and for which few systemic treatment options are available. Palliative end-points including pain relief decreased analgesic use and reduced prostate specific antigen levels (a marker of tumour response) are reached in a greater percentage of patients receiving combination therapy than corticosteroid alone. In addition, there are generally greater improvements in quality-of-life parameters in mitoxantrone recipients. However, combined treatment offers no survival advantage over corticosteroid monotherapy.Neutropenia is the most common toxicity associated with mitoxantrone therapy and may necessitate dosage reduction in some patients. Otherwise, mitoxantrone generally has a more favourable tolerability profile than has been established for other cytotoxic agents such as doxorubicin with regard to acute adverse events (e.g. Nausea/vomiting, anorexia, constipation, alopecia, malaise/fatigue, oedema) and cardiac toxicity.In conclusion, administration of mitoxantrone plus a corticosteroid can provide palliation for some elderly patients with hormone-resistant advanced prostate cancer, and is thus a valuable first-line treatment for this indication. Molecular and cellular biology of prostate cancer. Lalani EN, Laniado ME, Abel PD Cancer Metastasis Rev 1997 JUN;16(1-2):29-66 Lalani EN, Hammersmith Hosp, Royal Postgrad Med Sch, Dept Histopathol, du Crane Rd, London W12 0NN, ENGLAND Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have al tered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatments for those in wham the disease is extra- prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. Yablonsky F, AU - Nicolas V, Riffaud JP, Bellamy F J Urol 1997 JUN;157(6):2381-2387 Yablonsky F, Labs Debat, Grp Fournier, 153 Rue Buzenval, F 92380 Garches, FRANCE The effect of a Pygeum africanum extract (Tadenan(R)) (Pa), used in the treatment of micturition disorders associated with BPH, has been examined on the proliferation of rat prostatic stromal cells stimulated by different growth factors. EGF, bFGF, and IGF-I but not KGF are mitogenic for prostatic fibroblasts in culture. Pygeum africanum inhibits both basal and stimulated growth with IC50 values of 4.5, 7.7 and 12.6 mu g./ml. For EGF, IGF-I and bFGF, respectively, compared to 14.4 mu g./ml. For untreated cells, the inhibition being stronger towards EGF. Pygeum africanum inhibited the proliferation induced by TPA or PDBu in a concentration-dependent manner with IC50 values of 12.4 and 8.1 mu g./ml. Respectively. The antiproliferative effects of Pa were not ascribed to cytotoxicity. These results show that Pygeum africanum is a potent inhibitor of rat prostatic fibroblast proliferation in response to direct activators of protein kinase C, the defined growth factors bFGF, EGF and IGF-I, and the complex mixture of mitogens in serum depending on the concentration used. PKC activation appears to be an important growth factor-mediated signal transduction for this agent. These data suggest that therapeutic effect of Pygeum africanum may be due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man. Flutamide withdrawal plus hydrocortisone resulted in clinical complete response in a patient with prostate carcinoma. Figg WD, Kroog G, Duray P, Walther MM, Patronas N, Sartor O, Reed E Cancer 1997 MAY 15;79(10):1964-1968 Figg WD, NCI, Med Branch, Bldg 10, Room 5A01, 9000 Rockville Pike, Bethesda,MD 20892 USA BACKGROUND. Combined androgen blockade plus (CAB) (medical or surgical castration plus antiandrogen therapy) is considered by many to be the optimal endocrine maneuver for patients with metastatic prostate carcinoma. When progression occurs after CAB, the discontinuation of the antiandrogen is recommended. The authors present a patient that had a clinical complete response to flutamide withdrawal plus hydrocortisone that, at last follow-up, had been maintained for more than 46 months. METHODS. A 71-year-old man with a positive family history of prostate carcinoma presented in 1989 with urinary frequency and a suspicious digital rectal examination. He was found to have a poorly differentiated adenocarcinoma (Gleason 4+4). He was started on CAB and his prostate specific antigen (PSA) concentration declined from 96 ng/mL to the normal range and was maintained for the next 24 months. In 1991 his PSA began to rise, and reached 64 ng/mL by 1993. The patient was enrolled on a clinical trial that discontinued the flutamide administration and hydrocortisone was initiated. RESULTS. Physical examination at the time of enrollment was unremarkable. His PSA declined to below the limits of detection after this maneuver and at last follow-up had been maintained there for more than 46 months. In 1995, the patient underwent a repeat biopsy of the prostate and all six tissue cores were negative for carcinoma. At last follow-up in December 1996, the patient had no evidence of disease and was being followed routinely; however, the authors were continuing treatment with testicular suppression (leuprolide) plus hydrocortisone. CONCLUSIONS. The authors believe the residual androgens and steroids produced by the adrenal cortex play a meaningful role in prostate carcinoma cell proliferation. Based on this case and data from trials supporting the activity of flutamide withdrawal plus adrenal suppression, it appears reasonable to evaluate prospectively the discontinuation of antiandrogen versus antiandrogen withdrawal plus adrenal suppression in individuals failing CAB. (C) 1997 American Cancer Society. Quality of life and treatment outcomes: Prostate carcinoma patients' perspectives after prostatectomy or radiation therapy. ShraderBogen CL, Kjellberg JL, McPherson CP, Murray CL Cancer 1997 MAY 15;79(10):1977-1986 ShraderBogen CL, Healthsyst Minnesota, Inst Res Educ, 3800 Pk Nicollet Blvd, 2 S, Minneapolis,MN 55416 USA BACKGROUND. Of the estimated 317,000 men in the United States diagnosed with prostate carcinoma in 1996, 57% will have localized disease, and their 5-year relative survival rate will be 98%. Limited information exists on patient- reported quality of life (QOL) and the incidence and severity of treatment-related side effects. The purpose of this study was to identify and compare patients' self- reported QOL and treatment side effects 1-5 years after radical prostatectomy or radiotherapy. METHODS. Data collection for this cross-sectional study included a mailed, self-administered survey with three parts: a demographic survey, the Functional Assessment of Cancer Therapy-General (FACT-G), and a newly developed Prostate Cancer Treatment Outcome Questionnaire (PCTO-Q). The FACT-G measured the effect of prostate carcinoma on overall QOL in the two treatment groups. The PCTO-Q assessed the patients' perceptions of the incidence and severity of specific changes in bowel, urinary, and sexual functions. The test-retest reliability of the PCTO-Q in a pilot study was 91.2%. RESULTS. Two hundred seventy-four eligible men completed the questionnaires; 132 (48%) reported having undergone prostatectomy and 142 (52%) reported having undergone radiotherapy. After age adjustment, the radiotherapy group reported more bowel dysfunction (P = 0.001), whereas the prostatectomy group reported more urinary problems (P = 0.03) and more sexual dysfunction (P = 0.001). Scores for the FACT-G were similar in the two treatment groups. CONCLUSIONS. Men undergoing treatment for clinically localized prostate carcinoma continue to experience difficulty long after treatment. In this study, the prostatectomy group fared worse in regard to sexual and urinary functions, whereas the radiotherapy group experienced more bowel dysfunction. Survivor-reported QOL and treatment outcomes can assist physicians in counseling patients in the selection of the preferred course of treatment. (C) 1997 American Cancer Society. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination: Enhancement of specificity with free PSA measurements. Catalona WJ Smith DS Ornstein DK JAMA 1997 MAY 14;277(18):1452-1455 Catalona WJ, Washington Univ, Sch Med, Dept Surg, Div Urol Surg, 4960 Childrens Pl, St Louis,MO 63110 USA Objective.-To determine the detection rate of prostate cancer in a screening population of men with prostate- specific antigen (PSA) concentrations of 2.6 to 4.0 ng/mL and a benign prostate examination, to assess the clinicopathological features of the cancers detected, and to assess the usefulness of measuring the ratio of free to total PSA to reduce the number of prostatic biopsies. Design.-A community-based study of serial screening for prostate cancer with serum PSA measurements and prostate examinations. Setting.-University medical center. Subjects.-A total of 914 consecutive screening volunteers aged 50 years or older with serum PSA levels of 2.6 to 4.0 ng/mL who had a benign prostate examination and no prior screening tests suspicious for prostate cancer, 332 (36%) of whom underwent biopsy of the prostate. Main Outcome Measures.-Cancer detection rate, clinical and pathological features of cancers detected, and specificity for cancer detection using measurements of percentage of free PSA. Results.-Cancer was detected in 22% (73/332) of men who underwent biopsy. All cancers detected were clinically localized, and 81% (42/52) that were surgically staged were pathologically organ confined. Ten percent of the cancers were clinically low-volume and low-grade tumors, and 17% of those surgically staged were low-volume and low- grade or moderately low-grade tumors (possibly harm less). Using a percentage of free PSA cutoff of 27% or less as a criterion for performing prostatic biopsy would have detected 90% of cancers, avoided 18% of benign biopsies, and yielded a positive predictive value of 24% in men who underwent biopsy. Conclusions.-There is an appreciable rate of detectable prostate cancer in men with serum PSA levels of 2.6 to 4.0 ng/mL. The great majority of cancers detected have the features of medically important tumors. Free serum PSA measurements may reduce the number of additional biopsies required by the lower PSA cutoff. Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: The basis for an adjuvant therapy trial. DAmico AV, Whittington R, Malkowicz SB, Schultz D, Tomaszewski JE, Wein A, J Clin Oncol 1997 APR;15(4):1465-1469 DAmico AV, Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston,MA 02215 USA Purpose: A multivariable analysis to evaluate the potential clinical and pathologic factors that predict for early biochemical failure in patients with pathologically organ-confined and margin-negative disease was performed to define patients who may benefit from adjuvant therapy. Patients and Methods: Three hundred forty-one prostate cancer patients treated with a radical retropubic prostatectomy between January 1989 and June 1995 and found to have pathologically organ-confined and margin-negative disease comprised the study population. A logistic regression multivariable analysis to evaluate the predictive value of the preoperative prostate-specific antigen (PSA) level, pathologic (prostatectomy) Gleason score, and pathologic stage on PSA failure occurring during the first postoperative year was performed. Results: Predictors of PSA failure during the first postoperative year in patients with pathologically organ- confined disease included pathologic Gleason score greater than or equal to 7 (P = .0007) and preoperative PSA level greater than 10 (P .0001). Corresponding 3-year freedom- from-PSA-failure rates for these pathologic organ-confined patients with both, one, or neither of these factors were 60%, 75% to 84%, and 95%, respectively (P .0001). Conclusion: Prostate cancer patients with pathologically organ-confined and margin-negative disease and a preoperative PSA level greater than 10 ng/mL or a pathologic Gleason score greater than or equal to 7 have significant decrements in short-term PSA-failure-free survival. Therefore, these patients should be considered for adjuvant therapy in the setting of a phase III clinical trial. (C) 1997 by American Society of Clinical Oncology. Family history of prostate cancer in patients with localized prostate cancer: An independent predictor of treatment outcome. Kupelian PA, Kupelian VA, Witte JS, Macklis R, Klein EA, J Clin Oncol 1997 APR;15(4):1478-1480 Kupelian PA, Cleveland Clin Fdn, Dept Radiat Oncol, Desk T28, Cleveland,OH 44195 USA Purpose: To determine if familial prostate cancer patients have a less favorable prognosis than patients with sporadic prostate cancer after treatment for localized disease with either radiotherapy (RT) or radical prostatectomy (RP). Patients and Methods: One thousand thirty-eight patients treated with either RT (n = 583) or RP (n = 455) were included in this analysis, These patients were noted as having a positive family history if they confirmed the diagnosis of prostate cancer in a first-degree relative, The outcome oi: interest was biochemical relapse-free survival (bRFS). We used proportional hazards to analyze the effect of the presence of family history and other potential confounding variables (ie, age, treatment modality, stage, biopsy Gleason sum [GS], and initial prostate-specific antigen [iPSA] levels) on treatment outcome. Results: Eleven percent of all patients had a positive family history, The 5-year bRFS rates for patients with negative and positive family histories were 52% and 29%, respectively (P .001). The potential confounders with bRFS rates were iPSA levels, biopsy GS, and clinical tumor stage; treatment modality and age did not appear to be associated with outcome. After adjusting for potential confounders, family history of prostate cancer remained strongly associated with biochemical failure. Conclusion: This is the first study to demonstrate that the presence of a family history of prostate cancer correlates with treatment outcome in a large unselected series of patients. Our findings suggest that familial prostate cancer may have a more aggressive course than nonfamilial prostate cancer, and that clinical and/or pathologic parameters may not adequately predict this course. (C) 1997 by American Society of Clinical Oncology. Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer. Dawson NA, Figg WD, Cooper MR, Sartor O, Bergan RC, Senderowicz AM, Steinberg SM, Tompkins A, Weinberger B, Sausville EA, Reed E, Myers CE, J Clin Oncol 1997 APR;15(4):1470-1477 Dawson NA, Walter Reed Army Med Ctr, Washington,DC 20307 USA Purpose: To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer. Patients and Methods: patients with stage D2 and poor- prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 mu g/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone. Results: Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease, The median age was 59 years (range, 42 to 79) and 31 patienf 5 had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease, Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%, Eighteen patients have died, The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible. Conclusion: The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone, Toxicity was moderate and reversible. The antiandrogen withdrawal syndrome. Wirth MP, Froschermaier SE Urol Res 1997 APR;25:S67-S71 Wirth MP, Tech Univ Dresden, Dept Urol, Fetscherstr 74, D 01307 Dresden, GERMANY In 1989 the unanticipated agonist effect of antiandrogens on LNCaP prostate cancer cells was detected. A ''flutamidewithdrawal syndrome'' was first described by Kelly andScher [15], who reported a decrease in serum prostate-specific antigen (PSA) levels after the removal offlutamide from the treatment regimen. In the last fewyears the paradoxical response to antiandrogens has alsobeen reported for bicalutamide, chlormadinone acetate andothers. Therefore the name of the syndrome has changed to''antiandrogen withdrawal syndrome.'' Several reasons suchas mutations in the androgen receptor or a directstimulatory effect of the antiandrogen for this effecthave been discussed, but the exact molecular mechanismremains unclear. However, in patients with hormonallyrelapsed prostate cancer, a trial of ''withdrawaltherapy'' is required prior to the initiation of toxictherapies.


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Kurtis Martin, MD
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subset: commoncrawl


text:
A few months back, GrabCAD, a company specializing in the development of computer-aided design (CAD) software, launched a pretty interesting contest on the internet: "Design a supercar body." The contest soon turned out to be a huge success with 194 entries in just forty days. The winner was selected by Facebook users who had to "like" the car they loved the most. The winner is: Darren McKeage's Tosa Street Car! Apart from winning the contest, Darren McKeage's supercar design concept will be put into production in 2013.
All of the cars had to be designed on a pre-determined chassis design, powered by a GM -sourced LS V8 engine. This translates to a McKeage design that is amazing and sleek, as well as fit to pack impressive performance.
According to the official details, Darren's supercar won the contest because it "has the complete package, a dynamic mature shape that's not too extreme, great physical balance, deep signature side vents and a great adherence to working with the supplied chassis, including the front and rear boxes."
Congratulations, Darren McKeage and we wish you the best of luck!


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Nearing the groove on pitch 3 (note west central gully behind)
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Townie : a memoir (edition 2011)
by Andre Dubus
Work details
Townie by Andre Dubus III
Compact | Rate recommendations
No current Talk conversations about this book.
The audio book read by the author himself is a great way to experience this gritty memoir.
Gritty. At times I found it hard to get through the violence that Dubus and his family were inflicted upon and inflicted upon others. Also, found his parents to be totally into their own worlds. Amazing that Alex turned out to be as nice and good looking as he appeared on his book jacket considering his tough upbringing.
Dubus spoke directly to the writer in me. He understands the reason I write, the drive and necessity. I feel like portions of this were a little drawn out, but it was good. It made me want to read his books and his father's. So out of one book I found two new authors to read...
From the beginning I thought I would hate this book. I picked it up because it was on sale and because I recalled liking the House of Sand and Fog by the same author. I didn't realize in my haste that this was the authors memoir. How boring! Add in the fact that as an audio book the narrator was pretty monotone. Doubly boring. But something happened as I continued listening because it was a long drive and I had nothing else. I became engrossed in the story of his unusual upbringing in a variety of South Boston neighborhoods which almost seem more non-fiction and fiction and that Southy accent of the reader became less monotone and more meditative I didn't not realize until the very end of the book that the reader was Andre Dubus himself. I normally have a rule about no books read by the author, it never turns out well, but I think an exception needs to be made when it's the author's memoir. This is simply an amazing story of what can rise from the ashes of poverty and neglect and the love of a family as nontraditional a form that it came. It worked for them. I don't know if I would recommend this book to anyone. I loved it and it came at the right time for me in my life, listening to this boy becoming a man and the struggle he had with his father and figuring out their relationship together. It can be pretty violent at times which also may not appeal to some. But for a book I swore I was going to hate in the first hour, I couldn't stop listening too by the end and now I have to read everything Andre Dubus III has ever written.
This is the memoir of Andre Dubus III, author of House of Sand and Fog. I have read none of his work, and I didn't know a single thing about him aside from the fact that he wrote that book. I approached the memoir with no expectations. Andre's father (obviously also named Andre Dubus) was a writer as well, and a college professor. His parents divorced when he was a kid, and his mother was left with four kids in a tough neighborhood in Haverhill, Massachusetts. His father was a loving but remote and somewhat oblivious figure in Andre's life. After years of feeling like he was weak and a coward as his family and he himself were victimized in various ways, Andre found his way to lifting weights and fighting. The solution created a problem of its own, however, which was that Andre began seeking out ways to exercise his new-found power, even when there was really no need for it.
The story is raw, and made more so in audio form, since it's read by the author. His voice is flat and matter-of-fact, but also expressive. I'm sure that the print version is powerful as well; Dubus' description of his father offering to play catch with him, only to realize that at age 14, young Andre doesn't know the first thing about baseball, or playing games at all, is poignant on both sides. All the same, I'd highly recommend the audio version if you're interested in the story.
References to this work on external resources.
Wikipedia in English
Amazon.com Amazon.com Review (ISBN 0393064662, Hardcover)Amazon Best Books of the Month, February 2011: Rarely has the process of becoming a writer seemed as organic and--dare I say it--moral as it does in Andre Dubus III's clear-eyed and compassionate memoir, Townie. You might think that following his father's trade would have been natural and even obvious for the son and namesake of Andre Dubus, one of the most admired short story writers of his time, but it was anything but. His father left when he was 10, and as his mother worked long hours to keep them fed, her four children mostly raised themselves, stumbling through house parties and street fights in their Massachusetts mill town, so cut off from the larger world that when someone mentioned "Manhattan" when Andre was in college he didn't know what they were talking about. What he did know, and what he recalls with detailed intensity, were the battles in bars and front yards, brutal to men and women alike, that first gave him discipline, as he built himself from a fearful kid into a first-punch, hair-trigger bruiser, and then empathy, as, miraculously, he pulled himself back from the violence that threatened to define him. And it was out of that empathy that, wanting to understand the stories of the victims of brutality as well as those whose pain drove them to dish it out, he began to write, reconciling with his father and eventually giving us novels like House of Sand and Fog and now this powerful and big-hearted memoir. --Tom Nissley
(retrieved from Amazon Mon, 30 Sep 2013 13:21:53 -0400)
After their parents divorce in the 1970's, Andre Dubus III and his three siblings grew up with their exhausted working mother in a depressed Massachusetts mill town saturated with drugs and crime. To protect himself and those he loved from street violence, Andre learned to use his fists so well that he was even scared of himself. He was on a fast track to getting killed, or killing someone else, or to beatings-for-pay as a boxer. Nearby, his father, an eminent author, taught on a college campus and took the kids out on Sundays. The clash of worlds couldn't have been more stark or more difficult for a son to communicate to a father. Only by becoming a writer himself could Andre begin to bridge the abyss and save himself.… (more)
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EEC 485 High Performance Architecture, Fall 2008
Catalog Data: EEC 485 High Performance Architecture (4-0-4). Prerequisite: EEC 483. Architecture of high-speed computer systems with emphasis on design, analysis, and cost-performance ratios, including cache and virtual memory design, pipeline design and control techniques, vector computers, multi-processor computers and parallel algorithms.
Textbook: Computer Organization & Design, by John L. Hennessy and David A. Patterson, 4th Edition, Morgan Kaufmann Publishers, Inc., 2009.
Coordinator: Dr. Chansu Yu, Associate Professor of Electrical and Computer Engineering
Room: SH 437, Tel: 2584, Email: email@example.com
Class: TR 04:00-06:00 PM, SH325
Office Hour: TR 2:00-4:00 PM or by appointment
Course objectives: To provide a comprehensive overview of the modern microprocessor organization with an emphasis on features for high performance. Topics include including pipeline design and control techniques, cache and virtual memory design, interfacing techniques, multi-processor computers and parallel algorithms.
Expected outcomes: Upon completion of this course, students should be able to (i) understand key ideas and issues regarding pipelining and cache in the design of modern microprocessors, (ii) design a simple microprocessor including datapath, control circuit for controlling datapath, ALU capable of a couple of primitive operations such as addition, subtract, logic and, etc., floating point arithmetic, exception handling, 5-stage pipeline, and cache and (iii) implement the deign using PLA, ROM and microprogramming techniques in combination with the knowledge obtained from other courses such as EEC 380 Digital Systems.
Fulfillment of EE and CE Program Objectives and Outcomes
(1) practice computer engineering
(2) define and diagnose problems, and provide and implement computer engineering solutions in an industrial environment
(5) collaborate with others as a member or as a leader in an engineering team
(a) knowledge of mathematics, science, and engineering
(c) ability to design a system, component, or process
(e) ability to identify, formulate, and solve computer engineering problems
(i) recognition of the need for, and an ability to engage in life-long learning
(k) ability to use the techniques, skills, and modern engineering tools
Contribution of Course to Meeting the Professional Component:
Math & Basic Science: 1 credits; Engineering Topics: 3 credits; General Education: 0 credits
Prerequisites by Topic:
1. Digital circuits
2. System programming
3. Assembly program
Course Topics Lecture Hours
1. Introduction to computer organization 4
2. Pipelined architecture 8
3. Hazards and exceptions 8
4. Cache design 8
5. Virtual memory 8
6. Memory hierarchy 4
7. Interfacing processors and peripherals 8
8. Multiprocessors 8
9. Review and Exam 4
Computer Usage: Design and implement cache simulator
Estimated ABET Category Content: Engineering Topics 4 credits or 100%
Grading Policy: Midterm Exam 20%
Final Exam 30% (Comprehensive)
Quiz 10% (Many pop quizzes, review & preview)
Project 30% (2-person project, four sub-parts)
Homework 10% (5 homework assignments)


text:
Model Number: 618221-010
If you've ever wished that your running capris felt a bit more like your own skin, and then looked a bit more like your most flattering little black dress...then the Nike Women's Dri-Fit Epic Run Lux Capri is for you. With its supple, yet supportive, second-skin feel and wide waistband, this piece provides superior comfort using Nike's high-quality "lux" material. Moisture wicking fabric transfers sweat away from the skin, three pockets provide ample storage space, and reflective detailing enhances visibility in low-light settings.
Important Shipping Note: U.S. sales only.
Please include any relevant information such as weekly mileage, training or race pace, or foot type.
Copyright © 2014 Running Warehouse. All Rights Reserved. Contact Us
Site Map | US: 1.800.606.9598 | firstname.lastname@example.com | Careers


text:
Herb-Roasted Spring Vegetables
Yield: 8 Servings
Cost per Serving: $2.35
More From Allyou
Nutritional Information
Amount per serving
- Calories: 167
- Fat: 11g
- Saturated fat: 2g
- Protein: 4g
- Carbohydrate: 17g
- Fiber: 4g
- Cholesterol: 0mg
- Sodium: 183mg
- 8 ounces baby-cut carrots
- 7 shallots, peeled, cut in half
- 1 fennel bulb, halved, outer leaves and core removed, cut into wedges
- 1 head of garlic, cloves separated and peeled
- 6 tablespoons olive oil
- 3 tablespoons chopped garlic
- 3 tablespoons chopped fresh tarragon
- Salt and pepper
- 8 ounces baby zucchini, ends trimmed, cut in half
- 8 ounces baby yellow squash, ends trimmed, cut in half
- 1 red bell pepper, seeded, cut into 1/2-inch strips
- 8 ounces asparagus, trimmed
- 8 ounces green beans or snap peas, trimmed (2 cups)
- Place carrots and shallots in a pan; cover with water. Bring to boil; cook until tender, 7 minutes. Drain.
- Preheat oven to 425°F. In a large bowl toss carrots, shallots, fennel and garlic cloves with 2 Tbsp. olive oil, 1 Tbsp. chopped garlic, 1 Tbsp. tarragon, salt and pepper. Spread in a single layer on a baking sheet. Roast for 15 minutes, stirring once.
- Toss remaining vegetables with remaining olive oil and garlic, 1 Tbsp. tarragon, salt and pepper. Place on a baking sheet in a single layer and roast on separate oven rack for 25 minutes, stirring occasionally. Toss all vegetables together, sprinkle with 1 Tbsp. tarragon and serve.
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Herb-Roasted Spring Vegetables Recipe at a Glance
- COURSE: Side Dishes/Vegetables
- CONVENIENCE: Entertaining, Quick/Easy, Family
- MAIN INGREDIENT: Vegetables
- DIETARY CONSIDERATION: Gluten-Free
- COOKING METHOD: Roast
- OCCASION: Spring
- PUBLICATION: All You
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Assessmet of Patients With PAH Right Ventricular Volume
This study is ongoing, but not recruiting participants.
VentriPoint Diagnostics Ltd.
Information provided by (Responsible Party):
VentriPoint Diagnostics Ltd.
ClinicalTrials.gov Identifier:
First received: August 30, 2011
Last updated: June 3, 2013
Last verified: October 2012
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No Study Results Posted on ClinicalTrials.gov for this Study
|Study Status:
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|Estimated Study Completion Date:
|December 2013
|Estimated Primary Completion Date:
|November 2013 (Final data collection date for primary outcome measure)


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Possibly the worst thing to happen just before a social gathering is the discovery of a fat, red, ugly pimple in a hard to conceal spot on the body! I have had my fair share of zits at the most inappropriate moments. My graduation, a presentation at work and this one time, at a friend's hen party, and all we ever saw of me in snaps were red, shining boils in a swanky dress!
Those embarrassing pictures set me on a path to conquer the pimple and emerge with smooth, appealing skin for a pretty snap! These techniques or remedies have helped me squash zits before a full-fledged eruption, and leave me looking presentable in an important social gathering. I have tried everything on myself so feel free to pick a fix that suits you! Know how to get rid of pimples in one day.
What Is A Pimple?
A pimple is an inflammation of the skin, caused when your sebaceous glands become infected with grime and bacteria, filled up with pus and swell up, leaving you with awful zits across your face and neck.
While some argue that a zit is caused by the lack of a proper skin care routine, I personally believe otherwise. Caking your face with exfoliants, scrubs, creams and lotions is not going to do too much good and there are only so many times you can wash your face a day.
These quick fixes should help you get rid of pimples in a day, leaving you looking fresh as a daisy for your big event!
How to Reduce Pimples in One Day?
1. Ice:
I have personally found this to be an effective cure for pimples, fast acting and safe.
Repeat this process at least four times a day. Ice improves blood circulation in the area and freezes the skin pores.
It helps to soothe the skin around the area and reduce the swelling. A one day fix, ice can reduce your fat boils to pin prick spots that you can conceal easily with a bit of powder, cream or concealer.
[ Read: Acne ]
2. Aspirin:
Unusual but effective! I have found this pretty useful pimple fix. It works fast and does a clean job of containing eruptions.
- Crush an aspirin tablet and add a few drops of water to make a paste of it, mix well to form a paste and apply to the zit.
- Let the paste dry. Aspirin is an anti-inflammatory agent, and helps reduce the swelling due to accumulated pus.
- Leave the paste overnight and wash off in the morning. The pimple is less discernible after its aspirin treatment.
3. Toothpaste:
A widely known quick-fix home treatment and one that I have found extremely effective is the toothpaste treatment.
- Apply a blob of toothpaste on the zit and leave overnight.
- Wash off in the morning. You will find that the zit is less discernible and the swelling reduced.
In my experience, this works best when it follows the ice treatment. Use white toothpaste, not a gel based one.
[ Read: Reduce Pimples Naturally ]
4. Baking Soda:
Baking Soda, king of home remedies works (Surprise!) for pimples as well. This is a zit fix I recommend to everyone since it works well on sensitive skin as well, unlike other remedies that cause patchiness or dryness.
- Add a few drops of lemon juice or water to baking soda, make a paste and apply to the pimple.
- Wash off with warm water in about five minutes and follow up with a moisturizer.
- Do not leave the paste on for more than a few minutes as it could cause skin dryness.
5. Lemon:
A few drops of lemon juice works applied on a pimple. Though it causes a little itching, it helps to reduce inflammation and swelling.
- Ensure you apply only fresh lemon juice and not bottled products.
- Dip a clean swab of cotton in the juice and apply on the zit before you go to bed.
- Another remedy is to mix a teaspoon of cinnamon powder with a tablespoon of lemon juice, make a paste and apply on the pimple.
- Leave the paste overnight and wash off in the morning with warm water. I would not recommend this remedy for people with sensitive skin though. It can cause dryness, irritation and redness.
That's it folks, this is how to get rid of pimples in a day. They should help you get through your important days zit free! Do not forget to drop in your comments.
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Any favorite moments from this season?
Of course, there is! Submit them here :)
Last night was the season premiere of Rizzoli & Isles!! Woo!! Had a favorite moment? Submit it!!
I'm sorry for the lack of posts everyone. I thought the blog was dead but turns out tumblr doesn't like giving me notifications. I'll give this blog another try since it's coming back very soon but if I don't get any submissions I'm just going to leave it.
I'll have some down time today so I'll be making as many as I can. Yesterday there was a new episode of Rizzoli & Isles so if you had a favorite moment submit it! Even if it's not go ahead and submit anyways! Submit here.
51. LLBFF's
Season 2 Episode 3
50. Giovanni licking Maura's face
Season 2 Episode 3
49. Angela's text
- *Jane's phone vibrartes*
Jane: *reads text* Homie I need a boner. What?!
*Jane hands phone to Maura*
Maura: Haha. Spelling erota. Your mother really should proof read. It's "honey I need a loner"
Season 2 Episode 3
47. Maura throwing clay at Jane
Season 2 Episode 2
48. You don't want to sleep with me…..do you?
- Jane: Tell me what you have in common with him. Alright, he's a blue collar, Boston, Italian, auto mechanic.
Maura: Well so are you. Well, except for being an auto mechanic and we're best friends.
Jane: Yes, but I'm interesting. And you don't want to sleep with me. *Maura give Jane a look*
Jane: Do you?!
Maura: No, no! But that's my point, that's all I want to do with Giovanni.
Season 2 Episode 3
46. The action figure
Season 2 Episode 2


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'I jumpedwith Trey and Jaden today. I kept thinking to myself, "This potentially may be the individual worst display of parenting in African-American history".' - Will Smith
(Source: loovecoco)
Jada Pinkett Smith:"The handsome two and I about to roll through the beautiful swamps of Louisiana with Willow and Jaden as well :)It was an amazing day, and I feel so lucky to have a beautiful family to share it with. Happy Saturday."
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Trey Smith with Kelly Rowlandat an event for luxury car company Jaguar. Kelly is nowthe new face of the auto company…
(Source: ngosikadzistyle)
(Source: melovejaden)
(via kiss-my-kali-klass-deactivated2)
Will Smith with his son Trey at Liv nightclub in Miami Friday night were Trey was DJing….
Jada Pinkett-Smith posted this pic of newborn Willow Smith + husband Will Smith to her Instagram acccount…
New Video: "Pumped Up Kicks" x Jaden Smith
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KQED Photos
Antiques Roadshow Portrait Gallery
KQED took portraits of participants at the Antiques Roadshow in San Jose on Saturday August 15, 2009.
KQED Community Gallery on Flickr
Hosted by KQED's Interactive department, KQED's Flickr photo group allows members of the community who love KQED to share their photos.
KQED historical photo gallery
Take a nostalgic trip through KQED's history, starting in the 1950s, with this interactive timeline photo gallery.
KQED Public Radio Photo Slideshows
Slideshows and audio slideshows from KQED Radio News and The California Report.
KQED's Bay Area Bites Flickr Group
This group is designed to showcase great food photography from all over the San Francisco Bay Area and beyond. Submitted photos will appear on KQED's Bay Area Bites blog as well on KQED.org and KTEH.org.
KQED's QUEST Flickr Group
Do you love photographing science, environment and nature in Northern California? Visit QUEST's Flickr pool to see photo sets by QUEST staff members and fans, then share your own!
KQED's Spark Flickr Group
Do you like art? Visit the Spark group to find self-guided art tours around the Bay Area as well as photos from the Spark educator workshops and sets on other local art happenings.
Also on KQED.org this week ...
Latino Heritage Month
KQED proudly celebrates the diversity of our community by commemorating Latino Heritage Month. During September, KQED Public TV 9 and KQED 88.5 FM schedule programs that focus on Latino themes and issues.
San Francisco Opera on KQED
Get your front row seat at one of the leading opera companies in the world! Shot in brilliant HD, the fifth season of San Francisco Opera's acclaimed series brings you four spectacular productions performed by world-class singers.


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A robotic giraffe at the White House, a photo essay of other signs on Chicago buildings, and more stories to wrap up the week.
Hostile architecture, invisible architecture, and more building stories for Thursday.
The White House hosts its first Maker Faire, Perkins+Will promotes more than a dozen employees, and more news for Wednesday.
Michael Graves designs a wheelchair, Jeff Koons' balloon dog hits fast-fashion, and more stories for Tuesday.
How Renzo Piano's latest Bay Area project could be redefining the modern suburb, and how the awards to Ban, Lambert, and Morgan may be changing architecture.
The Brussels building gets festive, Picasso's stage curtain is moving, and more stories to round out the week.
The World Cup games begin, Richard Meier gives a tour of his Model Museum, and more stories for Thursday.
Stadium news for the Orlando City Soccer Club and the Jacksonville Jaguars, as well as David Beckham's proposed Miami soccer stadium.
New York's Frick Collection announces an expansion project, a developer wants to convert the Sony Building into condos, and CannonDesign picked for York University project.
More Trump tower feedback, the problem of empty offices in Rotterdam, and more stories to start off the week.
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2014 Hanley Wood Media, Inc. All rights reserved.


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Written by:
I've searched for you here;
I've searched for you there?
Life just never seems to be fair!
I've lost you!
Can it really be true?
The raindrops are falling from my eyes;
has no one heard my cries?
My heart is calling to you...
What am I suppose to do?
This ache... what a terrible feeling!
Pray for your return, I'm kneeling;
No words come to my mind;
Even my eyes see nothing, I'm blind!
How long is this heartache gonna last?
Is this love over? Is it in the past?
We totally shared everything;
What have I got left? Nothing!
Your memory will stay in my heart;
I've been so stupid! Why couldn't I have been smart?


text:
Crime of Father Amaro I finished tonight and I do not know what to say. Some novels are so perfect, so delicately constructed that they defy the language of praise. But here are some ideas:
1) Father Amaro in the history of Portuguese literature, the eldest son of a bitch. He is so vile, so disgusting, so it's a cowardly novelist that makes it equally attractive as it is a testament to the talent ECA. How far that his vendetta against those who attack her reputation would be known, his desire for an innocent woman, his crimes avoid scams? He just does not know any moral boundaries.
2) wonderful sense of humor! ECA was a great satirist and a dirty joke without breaking a sweat can change a man's tragedy. I on the cover to prevent hipocrisy, sordidness and Eça'z cover letter without ridicule laughed.
3) What a tedious novel! I felt relief when I book off for good. The novel really fevered brain is pulsating with activity. It is complete, full of ideas, it is a huge demand on the reader.
ECA return a real pleasure. This year for me one of the best novels I've read, there's Madame Bovary and the master and with Margarita.