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M C Miller

Publications and source records attributed to M C Miller.

At least 37 records · Page 2Linked to original sources
PubMed2000

Template definition by Tetrahymena telomerase reverse transcriptase.

The ribonucleoprotein enzyme telomerase extends chromosome ends by copying a specific template sequence within its integral RNA component. An active recombinant telomerase RNP is minimally composed of this RNA and the telomerase reverse transcriptase (TERT) protein, which contains sequence motifs conserved among viral reverse transcriptases (RTs), flanked by N- and C-terminal extensions specific to TERTs. We have used site-directed mutagenesis to explore the roles of Tetrahymena TERT in determining features of telomerase activity in general and in establishing the boundaries and use of an internal RNA template in specific. We identify a new ciliate-specific motif in the TERT N-terminus required for template definition. Moreover, several residues in reverse transcriptase motifs 1, 2, A and D are critical for specific aspects of internal template use. Our results indicate that the unique specificity of telomerase activity is conferred to a reverse transcriptase active site by TERT residues both within and beyond the RT motif region.

Amino Acid Motifs↗
PubMed2000

Influence of season on the incidence of DNA hypodiploidy in urinary cytology.

OBJECTIVE: This study was conducted to determine if an incidence of hypodiploidy in urinary specimens is related to seasonal temperature changes. MATERIALS AND METHODS: DNA ploidy was evaluated on 10,846 urinary specimens fixed in buffered alcohol (MOPSO/NaCl + ETOH) and received over a one year period from numerous sites throughout the United States. The percentage of hypodiploid (DNA index < 0.8) cases was evaluated in each month. As a control, DNA ploidy results from 3, 755 prostate biopsies, fixed in 10% neutral buffered formalin, received during the winter and summer months of the same year, were evaluated. RESULTS: The average percentage of hypodiploidy in cytologic specimens during the summer months was 19.6% compared to 5. 4% in the winter and early spring months (range: 20.6-4.8%). The average percentage of hypodiploid cells in histologic specimens was 0.8% for both the summer and winter months (range: 1.73-0.36%). CONCLUSIONS: The rate of hypodiploidy in urinary cytology seems to be temperature related. The hypodiploidy rate of histologic specimens fixed in formalin shows no fluctuation with the seasons.

DNA↗
PubMed2000

Children's exposure to magnetic fields produced by U.S. television sets used for viewing programs and playing video games.

Two epidemiologic studies have reported increased risk of childhood leukemia associated with the length of time children watched television (TV) programs or played video games connected to TV sets. To evaluate magnetic field exposures resulting from these activities, the static, ELF, and VLF magnetic fields produced by 72 TV sets used by children to watch TV programs and 34 TV sets used to play video games were characterized in a field study conducted in Washington DC and its Maryland suburbs. The resulting TV-specific magnetic field data were combined with information collected through questionnaires to estimate the magnetic field exposure levels associated with TV watching and video game playing. The geometric means of the ELF and VLF exposure levels so calculated were 0.0091 and 0.0016 microT, respectively, for children watching TV programs and 0.023 and 0.0038 microT, respectively, for children playing video games. Geometric means of ambient ELF and VLF levels with TV sets turned off were 0.10 and 0.0027 microT, respectively. Summed over the ELF frequency range (6-3066 Hz), the exposure levels were small compared to ambient levels. However, in restricted ELF frequency ranges (120 Hz and 606-3066 Hz) and in the VLF band, TV exposure levels were comparable to or larger than normal ambient levels. Even so, the strengths of the 120 Hz or 606-3066 Hz components of TV fields were small relative to the overall ambient levels. Consequently, our results provide little support for a linkage between childhood leukemia and exposure to the ELF magnetic fields produced by TV sets. Our results do suggest that any future research on possible health effects of magnetic fields from television sets might focus on the VLF electric and magnetic fields produced by TV sets because of their enhanced ability relative to ELF fields to induce electric currents.

Adolescent↗
PubMed2000

Quantitative nuclear grade (QNG): a new image analysis-based biomarker of clinically relevant nuclear structure alterations.

This review addresses the potential clinical value of using quantitative nuclear morphometry information derived from computer-assisted image analysis for cancer detection and predicting outcomes such as tumor stage, recurrence, and progression. Today's imaging technology uses sophisticated hardware platforms coupled with powerful and user-friendly software packages that are commercially available as complete image analysis systems. There are many different mathematically derived nuclear morphometric descriptors (NMD's) (i.e. texture features) that can be calculated by these image analysis systems, but for the most part, these NMD's quantify nuclear size, shape, DNA content (ploidy), and chromatin organization (i.e. texture, both Markovian and non-Markovian) parameters. We have utilized commercially available image analysis systems and the NMD's calculated by these systems to create a mathematical solution, termed quantitative nuclear grade (QNG), for making clinical, diagnostic, and prognostic outcome predictions in both prostate and bladder cancer. A separate computational model is calculated for each outcome of interest using well-characterized and robust training, testing, and validation patient sample sets that adequately represent the selected population and clinical dilemma. A specific QNG solution may be calculated either by non-parametric statistical methods or non-linear mathematics employed by artificial neural networks (ANNs). The QNG solution, a measure of genomic instability, provides a unique independent variable to be used alone or to be included in an algorithm to assess a specific clinical outcome. This approach of customization of the nuclear morphometric descriptor (NMD) information through the calculation of a QNG solution mathematically adjusts for redundancy of features and reduces the complexity of the inputs used to create decision support tools for patient disease management. J. Cell. Biochem. Suppl. 35:151-157, 2000.

Area Under Curve↗
PubMed2000

Analysis of repeated biopsy results within 1 year after a noncancer diagnosis.

OBJECTIVES: A prostate biopsy data base derived from patients referred to private practice urologists was analyzed for the cancer diagnosis rates of the "initial" biopsy and the repeated biopsy performed within 1 year for those patients with a noncancer diagnosis. METHODS: A retrospective analysis assessed 132,426 prostate biopsies received and processed by a single pathology laboratory between March 1994 and September 1998; none had had a previous biopsy processed at this laboratory. Prostate cancer was diagnosed in 50,521 of the patients (38.2%). The remaining 81,905 patients (61.8%) had a noncancer diagnosis of either no evidence of malignancy (NEM), high-grade prostatic intraepithelial neoplasia (HGPIN), small acinar glands suspicious for cancer (suspicious), or suspicious with HGPIN (Susp-HGPIN). We identified 6380 (7.8%) of these "noncancer" patients who underwent a repeated biopsy within 1 year. RESULTS: The incidence of NEM, HGPIN, suspicious, and Susp-HGPIN biopsy diagnoses in the "noncancer" patients (81,905) was 55.3%, 3.7%, 2.5%, and 0.3%, respectively. The rate at which these "noncancer" patients (81,905) underwent a repeated biopsy was 4.8% for patients with a diagnosis of NEM, 26.6% for HGPIN, 40.4% for suspicious, and 47.5% for Susp-HGPIN. The overall cancer diagnosis rate in the repeated biopsy patient sample (6380) was 25.7%. When stratified by the initial biopsy diagnosis, the cancer diagnosis rate for the repeated biopsies was 19.8%, 22.6%, 40.0%, and 53.1%, for the patients with NEM, HGPIN, suspicious, and Susp-HGPIN, respectively. The repeated biopsy diagnosis rates did not vary dramatically when analyzed at 3-month intervals during the 1-year period. Also, a strong correlation (79%) was observed between the number of tissue samples obtained at the initial and repeated biopsy procedures. In a subset of patients with free and total prostate-specific antigen (PSA) results obtained before the repeated biopsy (n = 813), we were able to construct a multivariate logistic regression algorithm using the patients' age, initial biopsy diagnosis, total PSA, and free/total PSA ratio that could predict the likelihood of cancer on the repeated biopsy with an accuracy of 70%. CONCLUSIONS: Men who have an initial noncancerous biopsy diagnosis remain at risk of prostate cancer, especially if the initial diagnosis was suspicious or Susp-HGPIN. These data suggest that the initial biopsy strategy needs to be improved and/or expanded to increase the overall cancer detection rate in the primary biopsy. In addition, combining factors such as the initial biopsy diagnosis, family history, digital rectal examination results, prostate gland volume, age, total PSA, and free/total PSA ratio could provide valuable information for predicting the likelihood of cancer.

Aged↗
PubMed2000

EMG responses resulting from transient and steady-state dynamic isometric loading of the human biceps can be distinguished.

In order to determine if differences in human muscle EMG response to steady-state (STD) dynamic load and transient (TRN) load could be detected, two distinct sinusoidal loads having identical amplitude and frequency were applied to the forearm, which was held in a fixed posture. The first condition used application of a constant amplitude, constant frequency, STD sinusoid, and the second condition used application of a single sinusoid of identical amplitude and frequency as the STD load. Time-domain parameters of Half-Mass, Dispersion Moments, Asymmetry Moments, Peak Ratio (ratio of cycle peak RMS EMG to cycle mean RMS EMG) and Time-to-Peak Ratio (ratio of cycle time to reach peak RMS EMG to cycle time duration) were used to quantify responses in the time domain. A single frequency-domain parameter, Dispersion Moments, was used to quantify responses in the frequency domain. Individual ANOVA's of the time domain parameter results revealed that p = 0.689 for Dispersion Moments, p = 0.111 for Half-Mass, p = 0.007 for Asymmetry Moments, p = 0.001 for Peak Ratio, and p = 0.001 for Time-to-Peak Ratio. The time-domain MANOVA and frequency-domain ANOVA revealed that EMG responses resulting from STD and TRN applied loads were statistically different in the time domain (p = 0.001), but not in the frequency domain (p = 0.810). Thus, use of Asymmetry Moments, Peak Ratio, and Time-to-Peak Ratio parameters can distinguish EMG responses to STD and TRN loads.

Analysis of Variance↗
PubMed2000

The Tetrahymena p80/p95 complex is required for proper telomere length maintenance and micronuclear genome stability.

The telomerase enzyme adds simple sequence repeats to chromosome ends. Telomerases share two essential subunits, telomerase RNA and telomerase reverse transcriptase, that associate with species-specific proteins of predominantly unknown functions. The Tetrahymena p80/p95 complex can coimmunopurify active telomerase from cell extract, and recombinant p80/p95 can interact directly with telomerase RNA and single-stranded telomeric DNA in vitro. Here, we test the functions of p80/p95 in vivo. Surprisingly, telomerase RNA accumulation and telomerase activity in cell extract are unaffected by loss of the genes encoding p80/p95. However, in the absence of p80/p95, telomeres become elongated in both macronuclei and micronuclei. Micronuclear chromosome maintenance is also compromised. These findings suggest that p80/p95 functions to maintain appropriate telomere length and micronuclear genomic stability but does so in a manner different than previously anticipated.

Animals↗
PubMed2000

Superficial urothelial (umbrella) cells. A potential cause of abnormal DNA ploidy results in urine specimens.

OBJECTIVE: To determine the DNA ploidy distribution in urothelial superficial (umbrella) cells and to assess the value of the image analysis operator's experience. STUDY DESIGN: DNA ploidy was assessed in 12 cytologically negative bladder washes stained with Feulgen stain. All 12 cases were evaluated independently by three operators with different levels of cytopathology experience and different goals. Operator 1 (experienced) selected only nuclei of urothelial cells, avoiding nuclei of superficial cells; operator 2 (experienced) selected only nuclei of superficial cells; operator 3 (inexperienced) selected the largest and most-atypical-looking nuclei. Each operator measured a total of 100 nuclei per case. RESULTS: Operator 1 found all cases to be diploid (97% of nuclei on average). Operators 2 and 3 showed a wide range of results. Almost half the nuclei (47%) analyzed by operator 2 were in the diploid region, a third (35%) were in the tetraploid region, and the remaining (18%) ones had a DNA index (DI) in the range of 1.2-1.8 or > 2.5. Operator 3 obtained the most abnormal results. Only 9% of the nuclei were diploid, while 37% were in the tetraploid region, 18% were in the hyperploid region, and 35% had a DI in the range of 1.2-1.8. Differences among results obtained by each operator were statistically significant. CONCLUSION: The nuclei of superficial (umbrella) cells often have abnormal DNA content, which may cause abnormal DNA ploidy results in cytomorphologically normal bladder washes. Consequently, the nuclei of superficial cells should be avoided in the evaluation of urine samples. DNA analysis of urine specimens requires selection of nuclei only of deep urothelial cells by an experienced operator.

Aged↗
PubMed1999

Apoptotic cell death induced by baccatin III, a precursor of paclitaxel, may occur without G(2)/M arrest.

PURPOSE: Paclitaxel has been demonstrated to possess significant cell-killing activity in a variety of tumor cells by induction of apoptosis, but the mechanism by which paclitaxel leads to cell death and its relationship with mitotic arrest is not entirely clear. In this study, baccatin III, a synthetic precursor of paclitaxel, was used to analyze whether paclitaxel-induced apoptosis can be a separate event from microtubule bundling and G(2)/M arrest. METHODS: Several different methods including DNA fragmentation, flow cytometric analyses, TdT-mediated dUTP nick end labeling (TUNEL) and time-lapse video microscopy were used to analyze apoptotic cell death induced by baccatin III and its possible correlation with cell cycle distribution. RESULTS: Our results demonstrated that baccatin III could also cause apoptotic cell death in both BCap37 (a human breast cancer cell line) and KB cells (derived from human epidermoid carcinoma), but had less effect on microtubule bundling and G(2)/M arrest. Furthermore, we demonstrated that most apoptotic events induced by baccatin III were not coupled with G(2)/M arrest. Instead, these apoptotic events occurred predominantly in the cells in other phases of the cell cycle. CONCLUSION: Baccatin III, which contains the core taxane ring, is the fundamental piece of paclitaxel structure. The finding of baccatin III-induced apoptosis independent of cell cycle arrest, on the one hand, implies that the core taxane ring may play a critical role in inducing cell death and, on the other hand, suggests that paclitaxel might induce apoptosis from other phases of the cell cycle by a similar mechanism.

Alkaloids↗
PubMed1999

Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer.

OBJECTIVES: Using arbitrarily primed polymerase chain reaction (AP-PCR) ribonucleic acid (RNA) fingerprinting, we discovered a messenger RNA (mRNA) that encoded the cytokine interleukin-8 (IL-8) that was up-regulated in the peripheral blood leukocytes (PBLs) of patients with metastatic prostate cancer (CaP) compared with similar cells from healthy individuals. We compared the total prostate-specific antigen (PSA) levels, the free/total (f/t) PSA ratios, and the immunoreactive IL-8 serum concentrations in patients with either biopsy-confirmed benign prostatic hyperplasia (BPH) or CaP. METHODS: The sera from 35 apparently healthy normal volunteers and 146 patients with biopsy-confirmed BPH and CaP obtained from two academic centers were retrospectively examined to determine the serum levels of IL-8, total PSA (tPSA), and the f/t PSA ratio. Logistic regression and trend analysis statistical methods were used to assess the results. RESULTS: Normals (n = 35), BPH patients (n = 53), patients with clinical Stages A to C CaP (n = 81), and patients with metastatic CaP (n = 1 2) had mean levels of IL-8 of 6.8, 6.5, 15.6, and 27.8 pg/mL, respectively. The IL-8 serum concentrations correlated with increasing CaP stage and also differentiated BPH from clinical Stages A, B, C, or D CaP better than tPSA and performed similarly to the f/t PSA ratio. The combination of the IL-8 levels and f/t PSA ratios using multivariate logistic regression analysis distinguished BPH from Stages A, B, C, or D CaP or only Stages A and B with a receiver operating characteristic area under the curve of 89.8% and 87.5%, respectively (P <0.0001). CONCLUSIONS: The IL-8 serum concentration in our clinically well-defined patient sample was independent of the f/t PSA ratio as a predictor of CaP. When test samples are controlled for extraneous clinical origin of inflammation or infection, the combination of the IL-8 and f/t PSA assay results may offer an improved approach for distinguishing BPH from CaP.

Adult↗
PubMed1999

Free/total PSA ratio improves differentiation of benign and malignant disease of the prostate: critical analysis of two different test populations.

OBJECTIVES: To evaluate the ability of free PSA (fPSA), total PSA (tPSA), and the free/total PSA (f/t PSA) ratio to differentiate between benign prostate disease (benign prostatic hyperplasia [BPH] and no evidence of malignancy [NEM]) and prostate cancer (CaP) using two different testing populations, and to compare predictive probabilities for the two test populations. METHODS: One test population consisted of sera from 531 men with clinically well-defined and biopsy-confirmed BPH (n = 255) or CaP (n = 276), with tPSA values ranging from 2 to 20 ng/mL. All of these serum samples were retrospective and obtained from patients evaluated in academic settings before any treatment. A second test population consisted of a prospective analysis of sera obtained from 4870 men, collected by urologists throughout the United States and processed at a single pathology laboratory. All these patients had a systematic biopsy evaluated and diagnosed at the same pathology laboratory, with the diagnosis categorized as either NEM (n = 2961) or CaP (n = 1909). No additional information on concurrent disease or pre- or current treatment status was known for this test population. For both populations, two tPSA reflex range groups, 2 to 10 and 2 to 20 ng/mL, were evaluated. RESULTS: Both test populations benefited from the application of either fPSA alone or the f/t PSA ratio to differentiate benign from malignant disease (t test P value less than 0.001). The receiver operating characteristic (ROC) curve for the f/t PSA ratio had an area under the curve (AUC) of 72% for n = 531 versus 63% for n = 4870, irrespective of the tPSA reflex range. Average fPSA values demonstrated a linear correlation to a range of tPSA concentrations for both test populations. Predictive probabilities (adjusted for established cancer prevalence rates in the academic population [n = 531]) calculated using f/t PSA ratios also demonstrated their value in contrasting the performance characteristics in the two test populations. CONCLUSIONS: The fPSA and f/t PSA ratio improved the differentiation of benign disease and CaP in two different patient samples. The f/t PSA ratio demonstrated an increased sensitivity and specificity when applied to differentiate clinically well-defined BPH and CaP (n = 531). The differences in the results between the two test samples are probably attributable to the variability of the patient's disease and treatment status in the larger, less refined, community-based population. The use of predictive probabilities provides the opportunity to provide patient-specific cancer probabilities instead of using population-based specific single cutoffs.

Aged↗
PubMed1999

Genetically engineered neural networks for predicting prostate cancer progression after radical prostatectomy.

OBJECTIVES: To use pathologic, morphometric, DNA ploidy, and clinical data to develop and test a genetically engineered neural network (GENN) for the prediction of biochemical (prostate-specific antigen [PSA]) progression after radical prostatectomy in a select group of men with clinically localized prostate cancer. METHODS: Two hundred fourteen men who underwent anatomic radical retropubic prostatectomy for clinically localized prostate cancer were selected on the basis of adequate follow-up, pathologic criteria indicating an intermediate risk of progression, and availability of archival tissue. The median age was 58.9 years (range 40 to 87). Men with Gleason score 5 to 7 and clinical Stage T1b-T2c tumors were included. Follow-up was a median of 9.5 years. Three GENNs were developed using pathologic findings (Gleason score, extraprostatic extension, surgical margin status), age, quantitative nuclear grade (QNG), and DNA ploidy. These networks were developed using three randomly selected training (n = 136) and testing (n = 35) sets. Different variable subsets were compared for the ability to maximize prediction of progression. Both standard logistic regression and Cox regression analyses were used concurrently to calculate progression risk. RESULTS: Biochemical (PSA) progression occurred in 84 men (40%), with a median time to progression of 48 months (range 1 to 168). GENN models were trained using inputs consisting of (a) pathologic features and patient age; (b) QNG and DNA ploidy; and (c) all variables combined. These GENN models achieved an average accuracy of 74.4%, 63.1 %, and 73.5%, respectively, for the prediction of progression in the training sets. In the testing sets, the three GENN models had an accuracy of 74.3%, 80.0%, and 78.1%, respectively. CONCLUSIONS: The GENN models developed show promise in predicting progression in select groups of men after radical prostatectomy. Neural networks using QNG and DNA ploidy as input variables performed as well as networks using Gleason score and staging information. All GENN models were superior to logistic regression modeling and to Cox regression analysis in prediction of PSA progression. The development of models using improved input variables and imaging systems in larger, well-characterized patient groups with long-term follow-up is ongoing.

Adult↗
PubMed1999

Test of an educational brochure on advance directives designed for well-elderly people.

The aim of this study was to test an advance directive brochure designed especially for well-elderly people. The brochure was developed using information from literature on preparing educational materials and from information gained from well-elderly focus groups. The information sought was in regard to what they knew and what they wanted to know about advance directives and what they found appealing in brochures on advance directives. Twenty well-elderly people participated in the study. Prior to data collection, the brochure was given to 10 nurses who were asked to evaluate it according to the Bernier Instructional Design Scale 2. Out of a possible 280 points, the brochure received 244. The participants in the study were asked to read the brochure and answer 15 questions about the content, user friendliness, and attractiveness of the brochure. The overall results were positive. The first five questions had to do with the appearance of the brochure. All 20 participants responded favorably to these questions. The next 10 questions had to do with understanding the content. A simple percentage was used to calculate the results. The participants understood 90.5% of the content. Based on these results, the brochure should be used in future intervention research and in discussions regarding the education of well-elderly people and the drafting of advance directives.

Advance Directives↗
PubMed1998

Station 16.3: a high-resolution single-crystal diffraction facility at the SRS, Daresbury.

SRS station 16.3 is now a fully scheduled user facility for high-resolution and high-energy single-crystal X-ray diffraction. It is based on a large three-axis diffractometer, designed and constructed at Daresbury for a wide range of physics and materials science applications. Served by wiggler 16 (a 6 T superconducting wavelength-shifter), the station has access to a broad spectrum of photon energies, extending to over 50 keV, and is designed for simple polarization-state tuning by motorized height adjustment of all optical components. This paper outlines the key design features and some of the science projects carried out during the first year of operation.

Journal Article↗
PubMed1998

The cytotoxicity of 2-formyl and 2-acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II) complexes.

2-Acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II) complexes were shown to be potent antineoplastic and cytotoxic agents against murine and human cultured cells. Numerous derivatives were as active against solid tumor growth as clinically useful agents. The agents inhibited L1210 DNA and RNA syntheses with inhibition of key regulatory enzyme activities of the purine pathway as well as nucleoside kinase activities. d[NTP] pools were reduced and DNA strand scission occurred. These agents were DNA topoisomerase II inhibitors with lower IC50 values than that of VP-16. However, they did not cause L1210 DNA protein linked breaks and actually protected against those breaks afforded by VP-16. The agents were not synergistic with VP-16 in reducing cell growth or DNA synthesis although they did reduce growth of L1210 cells in agar suspended media.

Animals↗
PubMed1998

Effects of alkyl amine carboxyboranes on L1210 DNA fragmentation and nucleic acid metabolism.

Amine-carboxyboranes with varying alkyl chain lengths were observed to be potent cytotoxic agents inhibiting the growth of a number of histological types of murine, rat, and human tumors. These agents preferentially reduced L1210 DNA synthesis with marked inhibition of the activities of regulatory enzymes of the purine pathway. Other enzyme activities which were marginally reduced were DNA polymerase alpha, ribonucleoside reductase, dihydrofolate reductase, t-RNA polymerase, and nucleoside kinases. Pyrimidine nucleotide pools were not reduced but DNA strand scission occurred after 24 h incubation with the agents. The amine-carboxyboranes were not DNA topoisomerase II inhibitors at 100 microM. The agents did not cause DNA protein linked breaks themselves; nevertheless, VP-16 [etoposide] induced DNA protein linked breaks were increased two fold in the presence of the agents suggesting synergistic effects. The amine-carboxyboranes decreased protein kinase C mediated phosphorylation of L1210 topoisomerase II protein, potentially decreasing its enzymatic catalytic activity. Thus, the amine-carboxyboranes did not function like VP-16 in affording cleavable products but were synergistic with VP-16 in causing DNA fragmentation. The agents were also additive with VP-16 in reducing tumor cell number, soft-agar colony growth and DNA synthesis and in producing DNA strand scission.

Animals↗
PubMed1998

Observations on pathology trends in 62,537 prostate biopsies obtained from urology private practices in the United States.

OBJECTIVES: To evaluate pathology trends of 62,537 first-time prostate needle-core biopsies submitted by office-based urologists, processed at a single pathology laboratory. METHODS: Prostate biopsy cases obtained over a 2-year period were assessed. Patient information included age, digital rectal examination (DRE) status, and prostate-specific antigen (PSA) serum levels. Biopsy pathology results included the number of tissue samples per case, Gleason score, presence of Gleason grades 4 or 5, percent of biopsy length with evidence of cancer, number of samples with cancer per biopsy, and determination of DNA ploidy status using microspectrophotometry. RESULTS: Adenocarcinoma, suspicious lesions, and isolated high-grade prostatic intraepithelial neoplasia (PIN) were diagnosed in 38.3%, 2.9%, and 4.1% of the biopsies, respectively. For each serum PSA and age range assessed, the positive biopsy rate and incidence of critical pathologic features increased consistently. The average percentage of biopsy length with evidence of tumor, the percentage of cases with Gleason grades 4 or 5, and the percentage of cases with an abnormal DNA ploidy all decreased significantly over the 2-year period (P <0.01). CONCLUSIONS: The number of tissue cores and anatomic sites (locations) being sampled per biopsy are increasing. The tumor size detected and percentage of cases with Gleason grades 4 and 5 are decreasing. There has been a slight increase in the number of biopsies performed on men younger than 60 years of age and a slight decrease in biopsies performed on men older than 70 years of age. The decline in meaningful pathologic features observed in biopsies over time may be clinically relevant to improved disease management.

Aged↗