Biomedical subjects

Andrew Lee

Publications and source records attributed to Andrew Lee.

26 records · Page 2Linked to original sources

PubMed2004

Racial influence on biochemical disease-free survival in men treated with external-beam radiotherapy for localized prostate cancer.

BACKGROUND: We retrospectively analyzed the clinical characteristics and outcomes of various racial and ethnic groups who underwent radiotherapy alone for localized or locally advanced prostate cancer. METHODS: From April 1987 to January 1998, 964 patients underwent full-dose, external-beam radiotherapy alone for localized or locally advanced prostate cancer and were included in the study. The patients' medical records were reviewed for pertinent information. RESULTS: Of the 964 patients, 810 were non-Hispanic white, 86 were African-American, 54 were Hispanic, and 14 were Asian. The most significant difference between groups was in the proportion of patients who presented with initial PSA levels > 20 ng/ml. More than 20% of men in all minority groups presented with a serum PSA > 20 ng/ml, compared to only 11% of whites (p = 0.0012). Similarly, 14% of minorities presented with Gleason scores > or = 8 compared to only 11% of whites (p = 0.0265). Hispanic and Asian patients exhibited a higher incidence of Gleason score > or = 8 prostate cancer. When comparing the time intervals of 1995-1998 vs. 1987-1994, the number of men presenting for EBRT with PSA levels < 10 ng/ml increased to 74% from 57% for Caucasians (p < 0,001), 71% from 40% for African Americans (p = 0.012), 67% from 49% for Hispanics (p = 0.1 18), and no change (50%) for Asians. CONCLUSIONS: The number of African-American patients presenting with favorable characteristics (PSA < 10 ng/ml) is increasing. These findings suggest that the message of screening and early detection may be reaching the African-American community. Continued diligence in screening and early detection may improve prostate cancer outcome for other minority populations.

Black or African American↗

PubMed2004

Severity of chronic kidney disease did not influence bleeding during treatment of acute coronary syndromes.

We assessed the influence of CKD on bleeding in 200 patients with ACS via retrospective chart analysis. Using K/DOQI guidelines to stratify patients based on GFR, no differences in documented bleeding or antithrombotic utilization were observed among the groups. Due to increased mortality risk of patients with CKD from cardiovascular disease, assessing benefit-to-risk ratios of various medical interventions is crucial.

Acute Disease↗

PubMed2003

Utility of the percentage of positive prostate biopsies in predicting PSA outcome after radiotherapy for patients with clinically localized prostate cancer.

PURPOSE: To determine the utility of the percentage of positive prostate biopsies (PPPB) in predicting prostate-specific antigen (PSA) outcome after external beam radiotherapy alone. METHODS AND MATERIALS: The records of 750 clinical Stage T1 and T2 patients treated by external beam radiotherapy alone with a median follow-up of 80 months were reviewed. Of the 750 patients, 345 were eligible for analysis; 255 (74%) had undergone sextant biopsies, 28 (8%) <6 biopsies, and 62 (18%) >6 biopsies. The pretreatment PSA level (<10, 10-20, >20 ng/mL), biopsy Gleason score (2-6, 7, 8-10), and clinical stage (T1-T2a, T2b, T2c), uni- or bilateral positive biopsy, radiation dose, and PPPB were analyzed as potential predictors of PSA outcome. The PPPB data were analyzed as a continuous and as a categorical variable. RESULTS: PPPB was a significant predictor of the time to PSA failure on univariate analysis as a continuous (p = 0.0053) and as a categorical (<50% vs. >or=50%, p = 0.0077) variable. In multivariate analysis, a trend was noted for worse 5-year PSA failure-free survival based on PPPB >or=50% vs. <50% (p = 0.082). Sixty-four patients experienced biochemical failure according to the American Society for Therapeutic Radiology Oncology definition. The 5-year PSA failure-free survival rate was 79% vs. 69% (p = 0.02) and the clinical disease-free survival rate was 97% vs. 86% (p = 0.0004) for patients with <50% vs. >or=50% PPPB. PPPB was not a significant predictor for the time to PSA failure within the traditional risk groups (low, intermediate, and high) on multivariate analysis. CONCLUSION: PPPB was a predictor of post-external beam radiotherapy PSA outcome in clinically localized prostate cancer; but in this cohort it did not provide additional information beyond the traditional risk stratification schema.

Aged↗

PubMed2003

Hazard rates of disease progression after external beam radiotherapy for clinically localized carcinoma of the prostate.

PURPOSE: We established hazard rates for disease progression at different intervals after external beam radiotherapy alone in patients with clinically localized prostate cancer. We determined the likelihood of biochemical failure in those free of disease 5 years after radiotherapy and identified those at risk for early versus late biochemical failure. MATERIALS AND METHODS: We reviewed the records of 964 patients treated with full dose external beam radiotherapy alone for T1 to T4, NxM0 prostate cancer. Followup prostate specific antigen (PSA) was measured 3 months after the completion of radiotherapy and every 3 to 6 months thereafter. Yearly hazard rates for biochemical failure were calculated each followup year. RESULTS: Median followup of the whole study group was 48 months. Overall 5 and 10-year biochemical disease-free survival rates were 63.7% and 53.6%, respectively. Patients had a peak overall hazard rate 2 years after treatment. The hazard rate then decreased until year 6, when it increased slightly and remained elevated even at year 10. This late increase in the overall hazard rate was associated with late increases in the hazard rate in men with favorable prognostic factors, namely pretreatment PSA less than 10 ng./ml., Gleason score less than 5, clinical T stage T1 or T2, posttreatment PSA nadir less than 0.99 ng./ml. or radiation dose less than 68 Gy. In 13 of the 307 patients (3.9%) with biochemical failure the failure occurred more than 5 years after initial treatment. CONCLUSIONS: The peak risk of biochemical failure is 2 years after radiotherapy. Patients are at slight but persistent risk for biochemical failure more than 5 years after treatment. Hazard rate calculations beyond the median followup of 4 years can underestimate the true hazard.

Carcinoma↗

PubMed2003

Loss of p16 expression has prognostic significance in human nasopharyngeal carcinoma.

PURPOSE: p16 is an important inhibitor of cell cycle progression; absence of p16 can thus result in increased cellular proliferation. In nasopharyngeal carcinoma (NPC), absence of p16 has been reported in association with presence of the EBV and pRb. We therefore examined p16, pRb, and EBV-encoded RNA (EBER) expression in biopsy specimens from 84 patients with newly diagnosed NPC, who were treated primarily with curative radiation therapy. Our objective was to determine whether there was a correlation between these parameters and clinical outcome in NPC. EXPERIMENTAL DESIGN: Sections were cut from archival formalin-fixed, paraffin-embedded tumor blocks from NPC patients. p16 and pRb expression were determined using polyclonal and monoclonal antibodies, respectively. The presence of EBV was determined by in situ hybridization for EBER. The percentage of positively staining tumor nuclei was scored for p16 or pRb immunoreactivity. Relative intensity and proportion of cells with EBER signals were also documented. RESULTS: p16 expression was reduced (</=5% positive immunoexpression) in 59 of 84 (70%) NPC samples; in contrast, pRb was observed in all (100%) tumors. EBER signals were detected in 67 of 83 (81%) NPC specimens. There was a weak correlation between EBER presence and loss of p16 (P = 0.1). Using a Cox regression model controlling for known prognostic parameters, such as age, weight loss, and tumor stage, complete absence of p16 expression (0%, i.e., no immunostaining identified throughout the specimen) was associated with an inferior overall survival rate (P = 0.022). In addition, EBER-positive NPC was strongly associated with improved overall survival (P = 0.005) as reported previously (Shi et al., Cancer, 94: 1997, 2002). CONCLUSION: These results provide the first evidence suggesting that inactivation of p16 appears to be a significant predictor for poor overall survival in NPC. Given that reduced p16 expression is observed in the majority of patients with NPC, this indicates that therapeutic strategies targeting the p16 pathway may be a biologically rational approach for NPC. The favorable prognostic value of EBER suggests that future clinical trials with NPC should consider stratifying for EBER status.

Adult↗

PubMed2002

Prognosis of ischemic internuclear ophthalmoplegia.

OBJECTIVES: To determine the prognosis of internuclear ophthalmoplegia (INO) caused by infarction. DESIGN: Multicenter, retrospective observational case series. PARTICIPANTS: Thirty three patients with ischemic-related INO. METHODS: Chart review of clinical details. MAIN OUTCOME MEASURE: Resolution of diplopia in primary position. RESULTS: Of the group, 78.8% demonstrated resolution of diplopia in primary position with an average time to resolution of 2.25 months. The presence of associated neurologic symptoms (vertigo, ataxia, dysarthria, facial palsy, pyramidal tract signs) correlated with a worse prognosis for resolution of diplopia. When performed magnetic resonance imaging (MRI) demonstrated the causative infarct in only 52% of cases; the presence of an MRI-demonstrable lesion was not significantly associated with prognosis for resolution. CONCLUSIONS: Similar to ischemic ocular motor palsies, most ischemic-based INO become asymptomatic in primary position over 2 to 3 months. The presence of associated features correlated with persistent diplopia. MRI has limited yield in demonstrating the causative infarct.

Aged↗

PubMedDate not supplied

High-throughput purification of combinatorial libraries I: a high-throughput purification system using an accelerated retention window approach.

We have developed a high-throughput purification system to purify combinatorial libraries at a 50-100-mg scale with a throughput of 250 samples/instrument/day. We applied an accelerated retention window method to shorten the purification time and targeted one fraction per injection to simplify data tracking, lower QC workload, and simplify the postpurification processing. First, we determined the accurate retention time and peak height for all compounds using an eight-channel parallel LC/UV/MS system, and calculated the specific preparative HPLC conditions for individual compounds. The preparative HPLC conditions include the compound-specific gradient segment for individual compounds with a fixed gradient slope and the compound-specific UV or ELSD threshold for triggering a fraction collection device. A unique solvent composition or solvent strength was programmed for each compound in the preparative HPLC in order to elute all compounds at the same target time. Considering the possible deviation of the predicted retention time, a 1-min window around the target time was set to collect peaks above a threshold based on UV or ELSD detection. Dual column preparative instruments were used to maximize throughput. We have purified more than 500 000 druglike compounds using this system in the past 3 years. We report various components of this high-throughput purification system and some of our purification results.

Journal Article↗

PubMedDate not supplied

Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene.

OBJECTIVE: Osteoporosis is a significant health problem in postmenopausal women. Consequently, new and effective therapies are being sought to preserve bone mass and prevent osteoporosis in this population of women. The objective of this study was to compare the effects of lasofoxifene with raloxifene and placebo on indices of bone health in postmenopausal women. DESIGN: A randomized, double-blind, placebo- and active treatment-controlled study of 2 years duration was conducted. Women included 410 postmenopausal women aged 47 to 74 years. The four treatment groups were: lasofoxifene 0.25 mg/day, or 1.0 mg/day, raloxifene 60 mg/day, or placebo daily. All women received daily calcium and vitamin D supplements. The primary endpoint was percent change from baseline to 2 years in lumbar spine bone mineral density (BMD) in all women having baseline and at least one follow-up bone density measurement. Total hip BMD, biochemical markers of bone turnover, low-density lipoprotein cholesterol, and safety were also evaluated in all women. RESULTS: Both doses of lasofoxifene significantly increased lumbar spine BMD compared with raloxifene (P < or = 0.05) and with placebo treatment (P < or = 0.05). Least squares mean increases (95% CI) from baseline in lumbar spine BMD, compared with placebo, were 3.6% (1.9, 5.2) for lasofoxifene 0.25 mg/day, 3.9% (2.4, 5.5) for lasofoxifene 1.0 mg/day, and 1.7% (0.3, 3.0) for raloxifene. The two doses of lasofoxifene and raloxifene were equally effective at increasing total hip BMD. Lasofoxifene and raloxifene significantly reduced the levels of biochemical markers of bone turnover compared with placebo. In general, the effects of lasofoxifene were greater than the responses to raloxifene. At 2 years, lasofoxifene significantly (P < or = 0.05) reduced low-density lipoprotein cholesterol levels by 20.6% and 19.7% with 0.25 mg/day and 1 mg/day, respectively, compared with raloxifene (12.1%) and placebo (3.2%). Lasofoxifene and raloxifene had a similar adverse event profile with low rate of discontinuations due to adverse events. CONCLUSIONS: Lasofoxifene may be an effective and well-tolerated treatment option for the prevention of bone loss in postmenopausal women.

Aged↗