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S Vijayakumar

Publications and source records attributed to S Vijayakumar.

At least 37 records · Page 2Linked to original sources

Self-assessed health-related quality of life in men who have completed radiotherapy for prostate cancer: instrument validation and its relation to patient-assessed bother of symptoms.

The purpose of this study was to develop a psychometrically reliable and valid questionnaire to assess the disease-specific dimensions of health-related quality of life (HRQOL) in the urinary function (UF), bowel function (BF), and sexual function (SF) domains of prostate cancer (PCa) patients treated with radiation therapy. Patients were given a six-page questionnaire using Likert-type questions assessing three HRQOL dimensions during their follow-up visits after completing radiotherapy. Scales created from an earlier study were utilized and tested for reliability and validity. In addition, we assessed the relationship between these dimensions and the degree to which a decreased HRQOL increases the degree to which patients feel bothered about their symptoms. There are two scales within each dimension: BF, Urgency and Daily Living; UF, Urgency and Weakness of Stream; SF, Interest/Satisfaction and Impotence. Internal-consistency reliability coefficients (Cronbach's alpha) for the proposed scales range from 0.48 to 0.92, and all item-scale correlations and divergence correlations validate the use of the scales, ranging from 0.49 to 0.89. The validity of these scales is also confirmed by the rising median scores with rising reported levels of patient-perceived "bother." The different dimensions have differing quantitative influences on patients. We have developed a prostate-specific HRQOL instrument that is an adequate and suitable tool for measuring HRQOL along three distinct dimensions for patients who have completed radiotherapy for PCa. Psychometric standards for reliability and validity were met for the proposed scales. Moreover, positive correlations were found between these dimensions and how bothered patients were by their symptoms, suggesting important relationships that should be followed in PCa patients after radiotherapy. Certain scales have strong influences on patient-perceived "bothersomeness" of symptoms, such as loss of control of BF, urgency of BF, urgency of urination, and level of interest/satisfaction in sex. Compared to our earlier study on patients being treated with radiotherapy for PCa, this study produced very similar results. With some modification, the same questionnaire could be used for both groups of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 163-172 (2000).

Adult↗

Evaluating clinical skills of radiation oncology residents: parts I and II.

UNLABELLED: The purposes of this article are to: (1) underscore both the importance and the difficulty of assessing clinical skills at the graduate level, (2) review both old and new assessment methods of clinical skills in an attempt to familiarize educators with current views on evaluation modalities, and (3) assess the state of clinical-skills assessment specifically in radiation oncology. A series of articles published in The Lancet in 1995, entitled "Examining the Examiner," was used as a starting point. We then conducted an extensive literature search (using MEDLINE) to find publications that examined different examination methods, old and new, that apply to the education of radiation oncology residents. Concepts critical to understanding any discussion of clinical skills evaluation methods are also reviewed. RESULTS: Part I of the article provides an introduction critical to understanding the objectives of clinical-skills evaluation. Also, three older, well-established methods of clinical skills evaluation (ward evaluation, oral examination, and multiple-choice questions) are assessed. In Part II, the objective structured clinical examination (OSCE), the standardized patient (SP), and the patient management problem (PMP), all born of recent innovations in the field, are discussed. Part II concludes with a review of how the issues presented in both parts are relevant to the assessment of the radiation oncology resident. All evaluation methods that can be applied to the education of radiation oncology residents have perceived advantages and shortcomings. With the proper administration of many of these (save, perhaps, the PMP), any perceived difficulties in evaluating the clinical skills of radiation oncology residents may be addressed and diminished. Suggestions offered that are worthy of further discussion, debate, and study include establishment of a standardized "ward" examination, a formative oral examination to accompany the ACR In-Training examination, and the possible revision of the American Board of Radiology oral examination. An in-depth appraisal on the feasibility of using newer evaluation methods (OSCE, SP, etc.) is also needed. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 1-12 (2000).

Algorithms↗

Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406.

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. METHODS AND MATERIALS: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. RESULTS: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019). CONCLUSION: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co

Adult↗

Recruitment experience in the first phase of the African American Hereditary Prostate Cancer (AAHPC) study.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

Black or African American↗

Carbonic anhydrase IV is expressed in H(+)-secreting cells of rabbit kidney.

Carbonic anhydrase (CA) IV is a membrane-bound enzyme that catalyzes the dehydration of carbonic acid to CO(2) and water. Using peptides from each end of the deduced rabbit CA IV amino acid sequence, we generated a goat anti-rabbit CA IV antibody, which was used for immunoblotting and immunohistochemical analysis. CA IV was expressed in a variety of organs including spleen, heart, lung, skeletal muscle, colon, and kidney. Rabbit kidney CA IV had two N-glycosylation sites and was sialated, the apparent molecular mass increasing by at least 11 to approximately 45 kDa in the cortex. Medullary CA IV was much more heavily glycosylated than CA IV from cortex or any other organ, such modifications increasing the molecular mass by at least 20 kDa. CA IV was expressed on the apical and basolateral membranes of proximal tubules with expression levels on the order of S2 > S1 > S3 = 0. Because CA IV is believed to be anchored to the apical membrane by glycosylphosphatidylinositol, the presence of basolateral CA IV suggests an alternative mechanism. CA IV was localized on the apical membranes of outer medullary collecting duct cells of the inner stripe and inner medullary collecting duct cells, as well as on alpha-intercalated cells. However, CA IV was not expressed by beta-intercalated cells, glomeruli, distal tubule, or Henle's loop cells. Thus CA IV was expressed by H(+)-secreting cells of the rabbit kidney, suggesting an important role for CA IV in urinary acidification.

Amino Acid Sequence↗

Prostate-specific antigen and androgens in African-American and white normal subjects and prostate cancer patients.

Prostate cancer in African Americans is more aggressive and common than in any other racial group. An endocrine mechanism has been proposed to account for this racial difference. However, androgen levels in African-American elderly normal subjects and prostate cancer patients have been insufficiently studied. Because the Albert Einstein Medical Center (AEMC) has a large African-American population, we could contribute racial data from which observations could be made within this study and in past and future studies. Blood from 38 screened men (mean age 65) with prostate-specific antigen (PSA) less than 4 ng/mL and normal rectal examination seen at the AEMC Cancer Center was studied using standard radioimmunoassays. The blood samples also served as our control. Our experimental group consisted of 51 prostate cancer patients (mean age 71 years), all of whom had nonmetastatic prostate cancer. Subjects were categorized by cancer status, race, and age group. In our screened subjects, PSA, testosterone, and dihydrotestosterone were not higher in African Americans than in whites. Furthermore, our prostate cancer patients demonstrated no significant racial variation for PSA, testosterone, and dihydrotestosterone. Our data also did not indicate any correlation between PSA and androgen levels in our cancer patients. In our population of elderly men, no racial differences in androgen levels were found. Androgen levels did not correlate with PSA levels in prostate cancer patients.

Black or African American↗

Only multimeric hensin located in the extracellular matrix can induce apical endocytosis and reverse the polarity of intercalated cells.

When an intercalated epithelial cell line was seeded at low density and allowed to reach confluence, it located the anion exchanger band 3 in the apical membrane and an H+-ATPase in the basolateral membrane. The same clonal cells seeded at high density targeted these proteins to the reverse location. Furthermore, high density cells had vigorous apical endocytosis, and low density cells had none. The extracellular matrix of high density cells was capable of inducing apical endocytosis and relocation of band 3 to the basolateral membrane in low density cells. A 230-kDa extracellular matrix (ECM) protein termed hensin, when purified to near-homogeneity, was able to reverse the phenotype of the low density cells. Antibodies to hensin prevented this effect, indicating that hensin is necessary for conversion of polarity. We show here that hensin was synthesized by both low density and high density cells. Whereas both phenotypes secreted soluble hensin into their media, only high density cells localized it in their ECM. Analysis of soluble hensin by sucrose density gradients showed that low density cells secreted monomeric hensin, and high density cells secreted higher order multimers. When 35S-labeled monomeric hensin was added to high density cells, they induced its aggregation suggesting that the multimerization was catalyzed by surface events in the high density cells. Soluble monomeric or multimeric hensin did not induce apical endocytosis in low density cells, whereas the more polymerized hensin isolated from insoluble ECM readily induced it. These multimers could be disaggregated by sulfhydryl reagents and by dimethylmaleic anhydride, and treatment of high density ECM by these reagents prevented the induction of endocytosis. These results demonstrate that hensin, like several ECM proteins, needs to be precipitated in the ECM to be functional.

Anion Exchange Protein 1, Erythrocyte↗

Hensin remodels the apical cytoskeleton and induces columnarization of intercalated epithelial cells: processes that resemble terminal differentiation.

Intercalated epithelial cells exist in a spectrum of phenotypes; at one extreme, beta cells secrete HCO3 by an apical Cl/HCO3 exchanger and a basolateral H+ ATPase. When an immortalized beta cell line is seeded at high density it deposits in its extracellular matrix (ECM) a new protein, hensin, which can reverse the polarity of several proteins including the Cl/HCO3 exchanger (an alternately spliced form of band 3) and the proton translocating ATPase. When seeded at low density and allowed to form monolayers these polarized epithelial cells maintain the original distribution of these two proteins. Although these cells synthesize and secrete hensin, it is not retained in the ECM, but rather, hensin is present in a large number of intracellular vesicles. The apical cytoplasm of low density cells is devoid of actin, villin, and cytokeratin19. Scanning electron microscopy shows that these cells have sparse microvilli, whereas high density cells have exuberant apical surface infolding and microvilli. The apical cytoplasm of high density cells contains high levels of actin, cytokeratin19, and villin. The cell shape of these two phenotypes is different with high density cells being tall with a small cross-sectional area, whereas low density cells are low and flat. This columnarization and the remodeling of the apical cytoplasm is hensin-dependent; it can be induced by seeding low density cells on filters conditioned by high density cells and prevented by an antibody to hensin. The changes in cell shape and apical cytoskeleton are reminiscent of the processes that occur in terminal differentiation of the intestine and other epithelia. Hensin is highly expressed in the intestine and prostate (two organs where there is a continuous process of differentiation). The expression of hensin in the less differentiated crypt cells of the intestine and the basal cells of the prostate is similar to that of low density cells; i.e., abundant intracellular vesicles but no localization in the ECM. On the other hand, as in high density cells hensin is located exclusively in the ECM of the terminally differentiated absorptive villus cells and the prostatic luminal cell. These studies suggest that hensin is a critical new molecule in the terminal differentiation of intercalated cell and perhaps other epithelial cells.

Animals↗

Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall-cell lung cancer.

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.

Administration, Oral↗

Influence of erythropoietin on transfusion requirements in patients receiving preoperative chemoradiotherapy for rectal cancer.

PURPOSE: Perioperative homologous blood transfusion has been suggested to have an adverse effect on survival in patients undergoing resection of colorectal cancers. Preoperative therapy is being increasingly used for rectal cancer patients and has an adverse effect on erythropoietic capacity. The objectives of this study were to evaluate the feasibility and safety of administration of recombinant human erythropoietin to patients receiving preoperative therapy for rectal cancer and to assess the impact of such treatment on blood transfusion requirements. METHODS: The study was an open-label, Phase I and II, nonrandomized, two-center trial. All patients received 50.4 Gy of irradiation with 5-fluorouracil infusions. Ten patients diagnosed with rectal cancer received 250 U/kg of recombinant human erythropoietin subcutaneously three times per week during preoperative radiation and chemotherapy. Oral iron was given to patients receiving erythropoietin. Ten contemporaneously treated patients who received both radiation and chemotherapy were used as controls. RESULTS: Of the 20 patients 13 were males; mean age was 64 years. Surgical procedures that patients underwent were abdominoperineal resection (14 patients), low anterior resection (4 patients), coloanal anastomosis (1 patient), or none (1 patient). There were no significant differences between groups in age, gender, stage or hemoglobin levels before therapy. No adverse reactions to erythropoietin were encountered. Hemoglobin levels were significantly higher in the treatment group during Weeks 1, 3, and 5 (P < 0.02 for each). Transfusion requirements were significantly decreased in patients who received erythropoietin (0.4 vs. 3.7 units; P < 0.0003). CONCLUSIONS: The data showed that use of erythropoietin during preoperative therapy can prevent the decline in hemoglobin that commonly occurs during therapy. Further, this was not associated with adverse events and significantly decreased the need for perioperative blood transfusions. This suggests that the use of erythropoietin in support of a preoperative chemoradiotherapy regimen for patients with rectal cancer is safe and should be considered. Whether such transfusion avoidance will translate into a survival benefit in this setting will require a large, prospective, clinical trial.

Adult↗

Self-assessed health-related quality of life in men being treated for prostate cancer with radiotherapy: instrument validation and its relation to patient-assessed bother of symptoms.

OBJECTIVES: To develop a psychometrically valid and clinically useful questionnaire to assess health-related quality of life (HRQOL) in patients with prostate cancer (PCa) undergoing external beam radiotherapy. The most important factors in three dimensions (bowel function [BF], urinary function [UF], and sexual function [SF]) were identified by patient survey. METHODS: Three HRQOL dimensions were assessed using Likert-type questions. Responses were analyzed by factor analysis to create HRQOL scales. Reliability and validity of the scales were assessed. Because patients can suffer symptoms yet not report their lives to be affected, the scales were compared with patient-reported bother. RESULTS: Two scales were identified within each dimension: BF, urgency and daily living; UF, urgency and weakness of stream; and SF, interest/satisfaction and impotence. Cronbach's alpha for the scales ranged from 0.63 to 0.94, and item-scale correlations and item-scale divergence correlations supported scale validity. Rising median scores correlated with rising levels of perceived bother. CONCLUSIONS: The questionnaire is a suitable tool for assessing HRQOL in three distinct dimensions for patients undergoing radiotherapy for PCa. Six dimensions of HRQOL were found to be related to bother, suggesting important relationships to be monitored for patients. Urgency of bowel movements, urgency of urination, and level of interest/satisfaction in sex correlated most strongly with bother.

Aged↗

PSA-based outcome analysis after radiation therapy for prostate cancer: a new definition of biochemical failure after intervention.

OBJECTIVES: To examine pretreatment variables that influence biochemical failure, and to describe and test a new definition of prostate-specific antigen (PSA)-based biochemical failure. METHODS: We introduce and describe a new definition of biochemical failure, which is based on quadratic fitting of the logarithm of the follow-up PSA profile curve. From a data base of 449 patients with prostate cancer treated with definitive radiation therapy, 230 patients who had at least five follow-up PSA observations were chosen for analysis. The new definition of failure was applied to this cohort, as was the conventional definition of two consecutive PSA rises. Univariate and multivariate analyses were performed using established pretreatment prognostic factors as covariates. Also, the association of both definitions of failure with clinical outcome (local recurrence and any recurrence) was examined. RESULTS: Application of the new definition of biochemical failure resulted in smoothing of the "noise" that is inherent in using definitions based on successive PSA rises. This smoothing was verified by smaller P values for the statistically significant covariates in the univariate analysis. Furthermore, the new definition correlated better with clinical outcome, as demonstrated by the statistically significant P values on regression analysis when using the quadratic fitted nadir compared with using the observed nadir. CONCLUSIONS: We devised a new criterion based on quadratic curve fitting for PSA-based biochemical failure. This definition is based on all available PSA information, correlates with both pretreatment factors and post-treatment clinical outcome, is relatively insensitive to noise, and allows for prediction of time of failure.

Humans↗

Caution in interpreting biochemical control rates after treatment of prostate cancer: length of follow-up influences results.

OBJECTIVES: Prostate-specific antigen (PSA) based end points are commonly used to report outcomes after treatment for prostate cancer. This study examines the influence of follow-up length on biochemical control (bNED) rates. METHODS: We reviewed 437 patients with clinically localized prostate cancer treated with conformal radiotherapy without neoadjuvant androgen deprivation. Biochemical failure was defined as three consecutive PSA increases or an increase large enough to prompt androgen deprivation therapy. The failure date was projected back to the midpoint between the PSA nadir and the first PSA increase (or between the nadir and the initiation of androgen deprivation therapy). The analysis was performed by censoring patients with longer follow-up in a stepwise fashion, thus creating smaller subgroups with shorter follow-up intervals. Subgroup 1 (n = 191) and subgroup 2 (n = 273) were defined to include those patients monitored for up to 2 years and up to 3 years, respectively. RESULTS: The median follow-up intervals for subgroup 1, subgroup 2, and the original study population were 1.1, 1.5, and 2.5 years. No significant differences were seen in pretreatment prognostic factors among the three groups. The 2-year bNED of subgroup 1, subgroup 2, and the original population was 86%, 77%, and 73%, respectively. Although subgroup 1 had a superior bNED compared with the original population (P = 0.04), no differences in clinical recurrence rates were seen among any of the three groups. CONCLUSIONS: Because of projecting the biochemical failure dates back according to commonly used bNED definitions, control rates are highly dependent on the length of follow-up.

Actuarial Analysis↗

Social factors affecting interest in participating in a prostate cancer chemoprevention trial.

PURPOSE: A sample survey was conducted to assess the feasibility of recruiting participants, specifically African Americans, and to determine social factors influencing participation in a prostate cancer chemoprevention trial. METHODS: A convenience sample of adults visiting a hospital was identified and asked to participate in the survey. The survey included brief background information about prostate cancer and questions concerning four independent (age, marital status, race, insurance status) and three dependent (willingness to join a trial, involvement in long-term drug intake, interest in receiving more information) variables. RESULTS: The study analyzed 165 responses. Of the 165 respondents, 67% were African American. Marital status was a significant predictor of general willingness to participate (p = 0.047) for male respondents. No significant predictor was found for female respondents. Furthermore, for men, ethnicity/race showed a significant difference (30% white men vs 70% of minority men) for willingness to take the pills. CONCLUSION: The results suggest that African Americans are receptive to participating in chemopreventive trials. Thus, future studies exploring chemoprevention trials as an effective tool for reaching African Americans are warranted.

Black or African American↗

Racial differences in prostate-specific antigen levels and prostate-specific antigen densities in patients with prostate cancer.

To compare serum prostate-specific antigen (PSA) levels and PSA density (PSAD) among African American (AA), white, and Hispanic men with prostate cancer (PC) seen in an urban, equal-access urology clinic. Between January 1988 and January 1993, 1,105 men were screened for PC at Cook County Hospital in Chicago, Illinois. A total of 529 men underwent transrectal ultrasound-guided prostate gland biopsies for abnormal digital rectal examination, suspect transrectal ultrasound, elevated PSA, or any combination of these abnormalities. PC was found in 246 patients (204 AAs, 22 whites, and 20 Hispanics). We analyzed the differences in PSA and PSAD among the three racial groups using univariate and multivariate analyses adjusting for race, age, clinical stage, and grade. AAs have a higher mean serum PSA levels (21.56 ng/ml) than whites (mean PSA of 10.96 ng/ml) and Hispanics (mean PSA of 8.25 ng/ml) (p = 0.04). The mean PSAD also was higher in AAs than in the other two groups (0.68 versus 0.34 for whites and 0.31 for Hispanics, p = 0.05). On a multivariate analysis, the PC stage and grade were overwhelmingly significant, whereas the race and age lost their statistical significance. AAs have higher serum PSA and PSAD than whites or Hispanics in an equal-access healthcare environment. Race is a significant factor in determining PSA and PSAD on univariate but not on multivariate analysis. Preliminary studies suggest that these differences are due to sociological, not biologic causes. These findings warrant a large, prospective study to investigate the extent and the causes of the racial differences in PSA and PSAD.

Black or African American↗

Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas.

The band 3 anion exchanger is located in the apical membrane of a beta-intercalated clonal cell line, whereas the vacuolar H(+)-ATPase is present in the basolateral membrane. When these cells were seeded at confluent density, they converted to an alpha-phenotype, localizing each of these proteins to the opposite cell membrane domain. The reversal of polarity is induced by hensin, a 230-kDa extracellular matrix protein. Rabbit kidney hensin is a multidomain protein composed of eight SRCR ("scavenger receptor, cysteine rich"), two CUB ("C1r/C1s Uegf Bmp1"), and one ZP ("zona pellucida") domain. Other proteins known to have these domains include CRP-ductin, a cDNA expressed at high levels in mouse intestine (8 SRCR, 5 CUB, 1 ZP), ebnerin, a protein cloned from a rat taste bud library (4 SRCR, 3 CUB, 1 ZP), and DMBT1, a sequence in human chromosome 10q25-26 frequently deleted in malignant gliomas (9 SRCR, 2 CUB, 1 ZP). Rabbit and mouse hensin genomic clones contained a new SRCR that was not found in hensin cDNA but was homologous to the first SRCR domain in DMBT1. Furthermore, the 3'-untranslated regions and the signal peptide of hensin were homologous to those of DMBT1. Mouse genomic hensin was localized to chromosome 7 band F4, which is syntenic to human 10q25-26. These data suggest that hensin and DMBT1 are alternatively spliced forms of the same gene. The analysis of mouse hensin bacterial artificial chromosome (BAC) genomic clone by sequencing and Southern hybridization revealed that the gene also likely encodes CRP-ductin. A new antibody against the mouse SRCR1 domain recognized a protein in the mouse and rabbit brain but not in the immortalized cell line or kidney, whereas an antibody to SRCR6 and SRCR7 domains which are present in all the transcripts, recognized proteins in intestine, kidney, and brain from several species. The most likely interpretation of these data is that one gene produces at least three transcripts, namely, hensin, DMBT1, and CRP-ductin. Hensin may participate in determining the polarized phenotype of other epithelia and brain cells.

Agglutinins↗

In the radiotherapy of prostate cancer, technique determines the doses to the penile structures.

For 11 consecutive prostate cancer patients undergoing three-dimensional conformal radiotherapy (3DCRT) in our institution, penile structures (PNS) were outlined in CT images obtained for treatment planning purposes. Dose-volume histograms (DVHs) were compared in order to study dose-volume relations for three techniques: 4FLD, an axial coplanar, four-field box technique; 6FLD, a six-field coplanar technique; and 4NAX, a coplanar but non-axial, four-field technique. All three techniques delivered equal doses to the planning target volumes (PTV). Our statistical analyses strongly indicate that the three techniques can be ranked as 6FLD better than 4FLD (and 4FLD better than 4NAX) as far as irradiating PNS volume during treatment of prostate cancer (PC) is concerned. For each technique, there is a "spread" owing to differences in patient anatomy and/or target size, position, and extent, but each technique has a similar "profile" or "shape" distinct from other techniques. Whether irradiating smaller volumes of PNS will influence the sexual potency outcome remains to be demonstrated. However, PNS should be considered as another critical structure in addition to rectum, bladder and femoral heads in the radiotherapy (RT) of PC, especially in 3DCRT dose escalation studies. Sexual potency outcomes can be correlated to dose-volume relations in the future and this will help refine radiotherapy techniques further.

Humans↗