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A W Partin

Publications and source records attributed to A W Partin.

At least 217 records · Page 12Linked to original sources
PubMed1992

A quantitative histological analysis of the dilated ureter of childhood.

A quantitative histological study of the dilated ureter of childhood was performed on 26 ureters. The specimens were from 15 male and 11 female patients 10 days to 12 years old (mean age 2.0 years). A color image analysis system was used to examine and compare collagen and smooth muscle components of the muscularis layers to normal control ureters of similar age. In comparing primary obstructed (12) to primary refluxing (14) megaureters and control ureters (6), there was a statistically different collagen-to-smooth muscle ratio (p < 0.001) between the primary obstructed and primary refluxing megaureter groups. For patients with primary refluxing megaureter there was a 2-fold increase in the tissue matrix ratio of collagen-to-smooth muscle when compared to patients with primary obstructed megaureter. In the primary obstructed megaureters the amount of collagen and smooth muscle was not statistically different from controls (p > 0.01). The increased tissue matrix ratio of 2.0 +/- 0.35 (collagen-to-smooth muscle) in the refluxing megaureter group compared to 0.78 +/- 0.22 in the obstructed megaureter group and 0.52 +/- 0.12 in controls was found to be due not only to a marked increase in collagen but also a significant decrease in the smooth muscle component of the tissue. Primary obstructed and normal control ureters had similar quantitative amounts of smooth muscle with 60 +/- 5% and 61 +/- 6%, respectively, while refluxing megaureters had only 40 +/- 5% smooth muscle. The percentage collagen was 36 +/- 5 in the obstructed megaureter group and 30 +/- 5 in controls, with refluxing megaureters having 58 +/- 5% collagen on analysis. Our findings emphasize the significant differences in the structural components (collagen and smooth muscle) of the dilated ureter of childhood, and provide us with further insight into the pathological nature of these dilated ureters and their surgical repair.

Child↗
PubMed1992

Comparison of nuclear shape in aspirated and histologic specimens of prostatic carcinoma.

Nuclear shape analysis of histologic sections of operative specimens has separated patients with clinically localized prostatic carcinoma with good and poor prognoses. In order to become more useful clinically, nuclear shape should be evaluable preoperatively but is distorted by core biopsy. We used nuclear morphometry to compare histologic and cytologic specimens obtained from 20 patients who underwent radical prostatectomy for clinically localized prostatic carcinoma. Neoplastic nuclei from cytologic aspirates prepared by the Papanicolaou and Diff-Quik techniques and standard histologic sections stained with hematoxylin and eosin were digitized. Air-dried nuclei of the Diff-Quik preparation had a nuclear area of 104.2 microns 2 +/- 28.2 SD. These nuclei were nearly twice as large (paired t test, P < .001) as in the Papanicolaou (55.6 +/- 13.0 microns 2) and histologic (55.8 +/- 12.7 microns 2) preparations. However, nuclear shape was not affected. Nuclear roundness factor (deviation from circularity) and boundary curvature were similar (paired t tests, P > .05). All nuclear shape descriptors of cytologic smears fell within intraobserver variations of measurements in histologic sections. Nuclear shape is not altered in Papanicolaou- and Diff-Quik-stained cytologic specimens and should be tested for preoperative assessment of outcome in clinically localized prostatic carcinoma.

Aged↗
PubMed1992

The biology of prostate cancer: new and future directions in predicting tumor behavior.

Because the present ability to treat and cure patients with prostate cancer is limited to those patients with pathologically organ-confined disease, it has become increasingly important to diagnose this disease at an early stage when cure is most likely. Recent advances in imaging may allow the urologist and pathologist to make the diagnosis of prostate cancer much earlier in the natural course of the disease. It therefore becomes imperative to have methods available to predict which patients have a high probability of progressing so that treatment can be assigned logically and appropriately. Our current methods of prognosis determination (stage and grade) do not allow accurate assessment of tumor behavior in the majority of individual patients with prostate cancer. Therefore, more accurate quantification of nuclear and cellular changes that take place as a tumor progresses to take on the aggressive (metastatic) phenotype are urgently needed. Experimental techniques have proven useful in answering these questions in animal models and now seem ready for large-scale testing in clinical studies.

Biomarkers, Tumor↗
PubMed1991

Influence of age and endocrine factors on the volume of benign prostatic hyperplasia.

To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.

Adenocarcinoma↗
PubMed1991

Nuclear morphology of prostatic carcinoma: comparison of computerized image analysis (CAS 200) versus video planimetry (DynaCELL).

We compared mean nuclear size and mean nuclear shape (nuclear roundness) on Feulgen-stained smears from 113 cases of prostatic carcinoma analyzed by DynaCELL system at x 100 magnification versus CAS system at x 40 where DNA can be assessed simultaneously. Correlation coefficients were 0.67 for size and -0.07 for shape. A subgroup of cases were compared at x 40 versus x 100 on the CAS system by two observers: The correlation for size ranged 0.47 to 0.49, with correlations for shape ranging from -0.19 to 0.54. In this subgroup at x 100 magnification, the correlation between CAS and DynaCELL was 0.32 for size and 0.07 for shape. At x 100 magnification on the CAS system, intraobserver correlation was 0.58 for size and 0.37 for shape with interobserver correlations of 0.36 for size and -0.05 for shape. At x 40 on the CAS system, intraobserver correlation was 0.42 for size and 0.72 for shape, with interobserver correlations of 0.06 for size and 0.45 for shape. This study shows that in comparison to video planimetry of prostatic cancer nuclei, which has been shown to have a high inter- and intraobserver correlation, the CAS 200 system provided accurate measurements of size yet not shape. Intra- and interobserver correlations were suboptimal with CAS, showing better results at x 100 for size and x 40 for shape. These results in part reflect the relative narrow range of size and shape in prostate cancer in comparison to other tumors, and the use of Feulgen smears where nuclear RNA is not stained or measured by the CAS system, potentially leading to artifactually irregular shapes.

Adenocarcinoma↗
PubMed1990

Pathologic findings in clinical stage A2 prostate cancer. Relation of tumor volume, grade, and location to pathologic stage.

Transurethral resections (TUR) and totally embedded radical prostatectomies from 39 clinical Stage A2 prostate cancers were morphometrically analyzed and compared with 56 prior similarly studied clinical Stage B cancers. All the clinical A2 radical prostatectomies contained residual tumor with 26% having capsular penetration. Clinical Stage A2 tumors were much more heterogeneous than clinical Stage B tumors with respect to tumor location, grade, and amount. In particular, many clinical A2 cases were predominantly central or central and anterior in location (59%) and low-grade compared with clinical Stage B cases where most lesions were posterior, peripheral, and intermediate grade. Percent of tumor in TUR best predicted final pathologic stage versus TUR grade or volume. Despite statistically significant correlations between tumor percent and/or grade on TUR and final stage, predictability of final stage for individual patients from TUR data was poor. The complex interrelation of tumor location, grade, and amount resulted in wide and overlapping ranges for these parameters for organ-confined and nonconfined cases.

Carcinoma↗
PubMed1990

Nuclear morphometry as a predictor of response to therapy in Wilms tumor: a preliminary report.

Present therapy in Wilms tumor is based upon prognosis. Current trends suggest less intensive chemotherapy and/or radiation therapy for children with favorable histological disease who are considered at low risk for recurrence and increasing the amount of therapy for those with unfavorable histological tumors who are at high risk for recurrence. Currently, pathological stage and histological appearance are used to predict prognosis. We tested a new approach. Histological sections of surgical specimens were obtained from 9 children treated for unilateral Wilms tumor. All patients had favorable histological disease, and received postoperative chemotherapy and/or radiotherapy. These specimens were evaluated by nuclear morphometry with the Hopkins Morphometry System to determine if nuclear shape descriptors could distinguish children who responded to therapy from those whose tumor recurred. Nuclear roundness, ellipticity, convexity and bending energy accurately separated the groups. Nuclear morphometry may provide useful information that will aid in predicting which children with Wilms tumor will respond to therapy and warrants further investigations.

Cell Nucleus↗
PubMed1990

The relationship of prostate specific antigen levels and residual tumor volume in stage A prostate cancer.

Preoperative serum prostate specific antigen correlates well with morphometrically determined prostate tumor volume in prostatectomy specimens. However, since prostate specific antigen is produced by hyperplastic as well as malignant prostatic epithelium, the contribution of hyperplastic epithelium (benign prostatic hyperplasia) to serum prostate specific antigen interferes with the ability of serum prostate specific antigen to predict tumor volume in individual patients. We wondered if the removal of benign prostatic hyperplasia tissue would increase the correlation between prostate specific antigen and tumor volume, and, thus, make prostate specific antigen a more accurate predictor of residual cancer volume after transurethral resection of the prostate. A total of 67 patients with clinical stage A cancer underwent radical retropubic prostatectomy (22, or 33%, with stage A1 and 45, or 67%, with stage A2 disease), and had pre-radical prostatectomy measurement of serum prostate specific antigen and morphometric determination of residual cancer volume in the radical prostatectomy specimen. The correlation between serum prostate specific antigen and residual cancer volume for all 67 patients was 0.66, and for stages A1 and A2 disease it was 0.64 and 0.70, respectively. All stage A1 cancer patients with a serum prostate specific antigen value of 1 ng./ml. or less had residual tumor volumes of less than 0.5 cc and all stage A cancer patients with a serum prostate specific antigen value of more than 10 ng./ml. had residual tumor volumes of greater than 0.5 cc. Of the patients 51% had levels of 1 to 10 ng./ml. and serum prostate specific antigen was not useful to predict residual tumor volume in this group. Serum prostate specific antigen measurements may be helpful in stage A1 cancer patients with levels of 1 ng./ml. or less, or greater than 10 ng./ml. in choosing the most appropriate therapy.

Antigens, Neoplasm↗
PubMed1990

Nuclear morphometry as a prognostic indicator for genitourinary rhabdomyosarcoma: a preliminary investigation.

Rhabdomyosarcoma of the urogenital tract is a malignant mesenchymal tumor seen primarily in childhood. Multimodal therapy, encompassing surgery, radiotherapy and chemotherapy, has dramatically improved the survival of patients with this disease. However, the quest for markers of tumor aggression is important to decrease the morbidity of treatment given to patients with good prognosis tumors, while at the same time intensifying treatment of tumors with poor prognosis. Using archival tumor specimens from 13 patients with genitourinary rhabdomyosarcoma, a multivariate analysis of multiple nuclear shape descriptors was done with the Hopkins Morphometry System. Three nuclear shape descriptors clearly separated patients with no evidence of disease recurrence or progression from those with recurrent disease, progressive disease or death of disease. These nuclear shape descriptors were standard error of the chain code standard deviation analysis (p = 0.010), range of the feret ellipticity distribution (p = 0.016) and standard error of the chain code range analysis (p = 0.037). With multivariate analysis these shape descriptors taken together separated patients with good and poor prognoses to a level of significance of p = 0.007. Thus, nuclear morphometric analysis may prove to be useful as an individual prognostic indicator in childhood genitourinary rhabdomyosarcoma and warrants further analysis in a much larger, blinded, controlled study.

Cell Nucleus↗
PubMed1990

Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.

To evaluate the usefulness of serum prostate specific antigen in the preoperative staging of prostate cancer we examined tumor volume and differentiation, as well as benign prostatic hyperplasia volume to determine their influence on serum antigen levels. Serum prostate specific antigen was measured in 350 men with clinically localized prostate cancer and preoperatively in 72 men with documented benign prostatic hyperplasia. Although the mean antigen levels increased with advancing pathological stage, the usefulness of prostate specific antigen to predict pathological stage for an individual patient was limited: 1 of 102 men (0.9%) with prostate specific antigen levels of less than 2.8 ng./ml. had positive lymph nodes and 5 of 5 men with levels of greater than 100 ng./ml. had either seminal vesicle or lymph node involvement. However, for the majority of men (greater than 70%) with prostate specific antigen values between these 2 extremes the antigen levels did not accurately predict pathological stage. Because serum prostate specific antigen levels correlated with morphometrically determined tumor volume (r equals 0.535, p less than 0.01) they should, in fact, be predictive of pathological stage. However, most men with prostate cancer also have varying degrees of benign prostatic hyperplasia tissue in the gland producing prostate specific antigen. We have found that serum prostate specific antigen does not correlate with the volume of benign hyperplasia within the gland (r equals 0.21, p greater than 0.05). In addition, immunohistochemical studies have suggested that the lack of correlation between pathological stage and serum prostate specific antigen might be explained by a decrease in the production of antigen with increasing histological grade. Our findings of a negative correlation (r equals -0.37, p less than 0.01) between serum prostate specific antigen levels and Gleason score adjusted for tumor volume confirmed this suggestion. Consequently, serum prostate specific antigen levels do not reflect tumor burden and pathological stage accurately in individual patients for 2 reasons: 1) the unpredictable contribution from the benign prostatic hyperplasia component of the gland and 2) the decreasing production of prostate specific antigen by higher grade lesions as tumor volume increases.

Adenocarcinoma↗
PubMed1990

Nuclear shape analysis for assessment of prognosis in renal cell carcinoma.

Clinically localized renal cell carcinoma is cured by radical nephrectomy in 47% [stage T3a (II)] to 65% [stage T1, T2 (I)] of the patients. Local recurrence and metastatic disease probably result from undetectable microscopic metastases present at operation. Chemotherapy and immunotherapy may improve cure rates if administered adjuvantly. The outcome of individual patients who share surgical stage cannot be predicted reliably by tumor histology, pathological and/or nuclear deoxyribonucleic acid analysis. Two groups of 10 patients with clinically localized renal cell carcinoma were similar by sex distribution (5 men and 5 women), surgical stage (stages T1 in 1, T2 in 6 and T3a in 3 patients) and age (54.3 +/- 15.2 standard deviation versus 55.8 +/- 8.7 years). Group 1 had no recurrences with a minimum followup of 5 years and a mean followup of 10 years. Group 2 died of metastatic renal cell carcinoma after a mean of 5 years. All neoplastic areas of each paraffin-embedded operative specimen were randomly sampled and the nuclear perimeter of 150 cancerous cells was digitized. There were 25 shape descriptors calculated for each nucleus. All shape descriptors for each patient were described by 19 statistical tests. Nuclear perimeter and area as well as mean nuclear roundness factor failed to separate the 2 groups. Range median quartiles of ellipticities by Fourier analysis, coefficients of variation of chain code minimums and relative means of largest 10 convexity values produced greatest separation (Mann-Whitney-Wilcoxon test p less than 0.001, and variance normalized difference 3.21, 3.29 and 2.83, respectively). These descriptors normalized and summed provided near perfect separation (Mann-Whitney-Wilcoxon test p less than 0.001 and variance normalized difference 3.59). We developed a quantitative nuclear morphometric analysis system that permitted the correct assignment of outcome in 19 of 20 patients. Accurate prediction of prognosis in patients with clinically localized renal cell carcinoma by nuclear shape analysis may allow for selection of patients for adjuvant therapy who have clinically undetectable metastatic disease.

Carcinoma, Renal Cell↗
PubMed1989

DNA loop domains in mammalian spermatozoa.

The highly condensed and tightly packaged DNA of hamster spermatozoa was found to be organized into topologically constrained DNA loop domains attached at their bases to a nuclear matrix. The loop domains of the sperm nuclei differed from somatic cell loop domains from the same animal in two aspects. Sperm loop domains were 60% smaller than somatic cell loop domains, with an average DNA length of 46 +/- 7 kb in sperm as compared with 76 +/- 11 kb in brain. Secondly, unlike virtually all somatic cell DNA known which is negatively supercoiled, sperm DNA was devoid of detectable supercoiling. The presence of the loop domain structure in the highly condensed DNA of mammalian spermatozoa suggests that this motif is a fundamental aspect of eukaryotic DNA organization.

Animals↗
PubMed1989

A comparison of nuclear morphometry and Gleason grade as a predictor of prognosis in stage A2 prostate cancer: a critical analysis.

The natural history of stage A2 prostate cancer is unknown. Previous studies from this institution have shown that, without treatment, a third of the men with clinically localized stage A2 prostatic adenocarcinoma will have disease progression within 4 years. Presently, most patients who present with stage A2 prostate cancer receive surgical or radiation therapy. The degree of differentiation of the tumor (Gleason score) presently is used to predict the prognosis among patients with clinically localized prostate cancer. The Gleason score does well to predict the prognosis for patients with scores of 2 to 4 and 8 to 10. Unfortunately, the majority of patients fall within the range of Gleason scores of 5 to 7. Better methods are needed to predict which patients diagnosed with stage A2 prostate cancer have a high probability of disease progression. Several studies have reported that morphometrically determined nuclear shape descriptors provided accurate separation of these patients that was superior to Gleason grading methods. To evaluate critically the usefulness of nuclear morphometry for prediction of prognosis we developed a system. The Hopkins Morphometry System, that calculated and compared 15 different shape descriptors that were analyzed by 17 different statistical tests. We tested this system on 18 untreated patients with stage A2 prostate cancer with an average followup of 10.5 years (range 5 to 18 years). For each patient 17 statistical analyses of the 15 shape descriptors (255 total) were evaluated and 50 analyses (50 of 255, 19.6%), including average nuclear roundness factor, provided significant separation (p less than 0.01) of the patients on the basis of outcome, whereas the Gleason score (p equals 0.076) did not. The best separation (p less than 0.01) was provided by the lower quartile analysis of the ellipticity shape descriptor.

Adenocarcinoma↗
PubMed1989

Prediction of metastatic potential in an animal model of prostate cancer: flow cytometric quantification of cell surface charge.

The natural history of clinically localized prostate cancer in individual patients is difficult to predict using currently available techniques. The majority of these patients will undergo treatment without knowledge of whether the tumor would have progressed during their lifetime. Because more patients are being diagnosed yearly with early stage prostate cancers it is becoming increasingly important to delineate factors that will clarify which patients have tumors with invasive potential. Using the Dunning R-3327 rat prostate animal tumor model we have previously shown that an increase in cell surface charge, as measured by individual cell electrophoresis, is associated with an increase in metastatic ability. This electrophoretic technique is limited by the small number of cells that can be analyzed during each assay. Therefore, we adapted a flow cytometric method for measurement of cell surface change, utilizing a large molecule (cationized ferritin) that binds quantitatively to the negative charges at the cell surface. With a fluorescent tag attached to the ferritin molecule, flow cytometric quantification of surface charge was possible, and this method was successful in identifying tumors with high metastatic ability in the Dunning prostate tumor model.

Animals↗
PubMed1989

Morphometric measurement of tumor volume and per cent of gland involvement as predictors of pathological stage in clinical stage B prostate cancer.

Although tumor volume is an important factor in predicting prognosis in carcinoma of the prostate, direct and accurate estimation of tumor volume is not practical clinically at present because the tumor may not always be palpable (stage A) and when palpable it is difficult to estimate volume in 3 dimensions. For this reason the clinical staging of prostate cancer currently is based on estimations of the per cent of gland involved with tumor: in stage A by per cent of tissue involved with cancer and in stage B by digital palpation (less than 1 lobe, 1 lobe and 2 lobes). In stage A prostate cancer the per cent of the specimen involved with tumor and the volume of tumor have been shown to correlate with tumor progression. Our study was designed to determine if either or both of these morphometric factors would be good predictors of pathological stage in stage B prostate cancer. We analyzed 56 step-sectioned radical prostatectomy specimens: 28 without capsular penetration, 15 with capsular penetration only and 13 with seminal vesicle involvement. The per cent of gland involved with tumor (correlation coefficient 0.67, p less than 0.001) and tumor volume (correlation coefficient 0.55, p less than 0.001) correlated well with pathological stage. Stepwise linear regression showed that the combination of the per cent of gland involved with tumor and the total Gleason grade was statistically the best predictor of pathological stage.

Adult↗
PubMed1989

The rat as a model for the study of penile erection.

A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection.

Animals↗