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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 145 records · Page 8Linked to original sources
PubMed1993

Combined role of transrectal ultrasonography, Gleason score, and prostate-specific antigen in predicting organ-confined prostate cancer.

Prostate cancer staging is frequently inaccurate. By combining transrectal ultrasonography (TRUS) with a retrospectively derived grade-stratified prostate-specific antigen (PSA-GS) scale, we demonstrated 77 percent staging accuracy in 155 men with clinically localized prostate cancer undergoing radical prostatectomy. When used as the first step in a staging algorithm, PSA-GS (Score > or = 7: PSA > or = 4.0 ng/mL, uncontained; Score = 5 or 6: PSA > or = 8.0 ng/mL, uncontained; Score < or = 4: PSA > or = 16.0 ng/mL, uncontained) had a sensitivity of 75 percent and a specificity of 72 percent. The addition of TRUS to the staging algorithm, necessary only in patients with negative predictions by PSA-GS (46%), increased the sensitivity to 86 percent and the negative predictive value to 79 percent, while positive predictive value was unchanged at 77 percent. The combination of TRUS with PSA < 4 ng/mL or > or = 16 ng/mL identified subsets of patients with 85 percent and 88 percent likelihood of contained and uncontained disease, respectively. Our algorithm minimizes operator dependency by requiring TRUS in less than half of the patients. It produced improved staging, but the overall results were inaccurate in 23 percent of patients. Further refinements in prostate cancer staging are still necessary.

Aged↗
PubMed1993

The syndrome of inappropriate antidiuretic hormone secretion in a patient with adenocarcinoma of the prostate.

We report the syndrome of inappropriate antidiuretic hormone secretion in a 59-year-old man with stage C adenocarcinoma of the prostate. Serum antidiuretic hormone levels returned to normal following treatment with a gonadotropin-releasing hormone analogue. To our knowledge this case represents the first in which resolution of this syndrome occurred with treatment of the carcinoma.

Adenocarcinoma↗
PubMed1993

HLA expression by benign and malignant prostatic epithelium: augmentation by interferon-gamma.

Chronic prostatitis is a poorly understood entity that is characterized by lymphocytic infiltration of benign prostatic epithelium. Previously, we and others have shown that prostatic epithelium involved by prostatitis is phenotypically different from uninvolved epithelium. In addition, we have shown that malignant prostatic epithelium is rarely, if ever, infiltrated by lymphocytes. We now report that benign prostatic epithelium expresses HLA-DR only in the presence of lymphocytic inflammation, and that benign epithelium without chronic prostatitis and malignant prostatic epithelium do not express HLA-DR. In order to determine whether HLA-DR expression is inducible on malignant prostatic epithelium and therefore, at least theoretically, susceptible to immune regulation, we studied the DU-145 cell line in culture under various conditions. DU-145 cells did not express HLA-DR under routine culture conditions. However, the addition of interferon-gamma (100 to 6000 U/ml.) resulted in HLA-DR expression by DU-145 cells at 24 hours with maximal expression by 72 hours. In contrast, other cytokines (tumor necrosis factor, interleukin-1, interleukin-2) had no effect on HLA-DR expression. These investigations show that interferon-gamma induces HLA-DR expression on the DU-145 prostatic adenocarcinoma cell line, raising the theoretical possibility that malignant prostatic cells may be induced in vivo to express HLA-DR and thus become susceptible to immune regulation.

Adenocarcinoma↗
PubMed1993

Cell proliferation in prostatic adenocarcinoma: in vitro measurement by 5-bromodeoxyuridine incorporation and proliferating cell nuclear antigen expression.

We assessed cancer cell proliferation, a marker of the biologic activity of tumor cells, by evaluating bromodeoxyuridine (BrdUrd) incorporation and proliferating cell nuclear antigen (PCNA) expression. Prostatic carcinoma specimens (N = 48) were incubated in the presence of BrdUrd to label cells undergoing DNA synthesis, and immunocytochemical staining was performed with monoclonal antibodies to BrdUrd and PCNA and a standard indirect immunoperoxidase technique. The proportion of cells staining positively (labeling index or LI) for BrdUrd and PCNA was determined in 2 ways: by counting only high-power fields with the greatest concentration of stained cells (selected LI); or by counting cells in random fields (random LI). For BrdUrd the mean selected and random LIs were 3.08% and 1.62%, respectively; for PCNA they were 6.02% and 3.47%. Random and selected BrdUrd correlated well (r2 = 0.83), as did random and selected PCNA LIs (r2 = 0.86). However, a weaker correlation was noted when LIs of both techniques were compared, with the PCNA LI usually higher. The LIs of either technique correlated rather poorly with tumor grade and concentration of prostate-specific antigen, but correlated well with clinical stage as assessed by examination and imaging. In addition, either technique discriminated among tumors known to be pathologically confined (stages A and B) and those with extension to seminal vesicles (stage C) or metastatic to regional lymph nodes or bone (p < 0.019).

Adenocarcinoma↗
PubMed1993

The value of prostate specific antigen and transrectal ultrasound guided biopsy in detecting prostatic fossa recurrences following radical prostatectomy.

The combination of prostate specific antigen (PSA) and transrectal ultrasonography was used to detect recurrent cancer in the prostatic fossa after radical prostatectomy. A total of 43 patients with persistently elevated PSA levels and negative bone scintigraphy following radical prostatectomy underwent digital rectal examination and transrectal ultrasonography. Ultrasound findings were considered suspicious if the scan showed any unusual hypoechoic tissue adjacent to the bladder neck, retro-trigone or peri-anastomotic site. Of 22 patients (51%) with biopsy proved cancer 21 (95%) had positive transrectal ultrasonography, while digital rectal examination was able to detect cancer in only 10 (45%). Among transrectal ultrasonography detected recurrences 15 (68%) were detected at the initial biopsy and 7 (32%) at repeat biopsies. Our study shows that the combination of PSA and transrectal ultrasonography provides a more effective method than digital rectal examination and PSA to detect biopsy proved cancer following radical prostatectomy.

Adenocarcinoma↗
PubMed1993

Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate cancer.

In a series of 166 patients undergoing radical prostatectomy and bilateral pelvic lymph node dissection for clinical stage A and B prostate cancer we found that 83% of patients with lymph node metastases had a final tumour Gleason score > or = 7. Gleason scoring of the pre-operative biopsy demonstrated 3 groups of patients with biopsy scores < or = 5, 6, and > or = 7, and a prevalence of lymph node metastases of 2, 13 and 23% respectively. The pre-operative serum prostate specific antigen (PSA) was of marginal value in predicting either the presence of lymph node metastases or the presence of cancer, since 15% of patients with nodal metastases had normal pre-operative PSA levels, as did 54% of patients with tumour Gleason scores < or = 5. It was concluded that the need for pelvic lymph node dissection in patients with low grade tumours is questionable because of the low prevalence of lymph node metastases, and that the pre-operative biopsy can identify those patients who are at low risk for lymph node metastases.

Biomarkers, Tumor↗
PubMed1993

Sodium nitroprusside and neurostimulation cause increased levels of cyclic guanosine monophosphate and not cyclic adenosine monophosphate during canine penile erection.

We investigated the changes of cGMP and cAMP during penile erection induced by direct electrical stimulation of the pelvic nerve or sodium nitroprusside administration. Immediately after penile erection, the samples were put into liquid nitrogen and cyclic nucleotide content was measured. The results of these investigation suggest that both pelvic nerve stimulation and sodium nitroprusside induced penile tumescence. The total content of cGMP and not cAMP were significantly higher in treated samples as compared to control. SDS-polyacrylamide gel electrophoresis revealed several differences after treatment compared to untreated samples. This study demonstrated that the total content of cGMP and not cAMP increased after pelvic nerve stimulation and sodium nitroprusside treatment in penile tissue.

Animals↗
PubMed1993

Phenotypic and cytogenetic characterization of a human corpus cavernosum cell line (DS-1).

We report here the establishment and characterization of a corpus cavernosum cell line (DS-1) from human penile tissue. This is the first cell line of its type derived from cavernosum tissue. DS-1 cells have become immortalized in culture, and show growth in monolayers. These cells have a doubling time of about 45 h in in vitro culture. Cytogenetic analysis by G-banding demonstrated a diploid karyotype with a model chromosome number of 46. The chromosome constitution of DS-1 cells was found to be male (XY), in 28/30 cells scored. Two of the 30 cells showed an extra structurally rearranged "marker" chromosome, that appeared to be a derivative of chromosome 18 with excessive chromosome on the short arm. Ploidy analysis revealed that the majority of DS-1 cells had a DNA index of one. About 35% cells were found to be in G-1 phase and 52% cells in S phase. Light and electron microscopy of DS-1 cells and original penile tissue showed typical characteristics of this tissue. Immunocytochemistry studies using antibodies to smooth muscle actin, desmin, vimentin and cytokeratin (LP34, CAM5.2) showed that the DS-1 cell line had predominantly smooth muscle cells, as these cells were positive for smooth muscle actin, desmin and vimentin.

Cell Division↗
PubMed1992

Magnetic resonance spectroscopy in prostate disease: diagnostic possibilities and future developments.

Magnetic resonance spectroscopy (MRS) is a relatively new technique for studying membrane and intracellular metabolic events occurring in cancer. A series of transrectal probes were used for performing MRS and subsequently for integrated MRS/magnetic resonance imaging (MRI) of the prostate. Studies using transrectal 31P/1H MRS showed that it can characterize metabolic differences between normal and malignant prostates. Specifically, malignant prostates are characterized by low levels of phosphocreatine and citrate and high levels of phosphomonoesters relative to normal glands. These findings were verified in biochemical studies of prostate biopsies. The images obtained by transrectal coil techniques were superior to images obtained by the conventional body coil technique. In the future, the integration of 1H imaging and multi-volume localization techniques (spectroscopic imaging) will allow the acquisition of metabolic maps of the prostate which may eventually be useful in diagnosis and in management of patients with prostate cancer.

Adenocarcinoma↗
PubMed1992

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.

Adrenergic alpha-Antagonists↗
PubMed1992

Establishment and characterization of a human primary prostatic adenocarcinoma cell line (ND-1).

A human primary prostatic adenocarcinoma cell line named ND-1 has been established in long term tissue culture. The cultured cells show growth in both monolayers and in soft agar suspension and produce subcutaneous tumors in nude mice. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 62, and multiple marker chromosomes with 25-30% structural abnormalities. Ploidy analysis revealed that the majority of ND-1 cells (67%) had a DNA mass of 10.1 picogram and DNA index of 1.41. Nineteen percent of cells had a DNA mass of 21.3 picogram and DNA index of 3.0. Electron microscopic studies revealed common features of neoplastic epithelial cells such as numerous microvilli, junctional complexes, abnormal nuclei, nucleoli, and mitochondria. Due to the absence of a structurally normal Y chromosome, confirmation of the presence of a derived Y chromosome was achieved through the use of C-banding and through fluorescent in situ hybridization with a Y chromosome repeat probe. Tandem E PSA immunoenzymatic assay revealed that these ND-1 cells secrete small amounts of prostate specific antigen.

Adenocarcinoma↗
PubMed1992

Prospective randomized trial of warfarin and intermittent pneumatic leg compression as prophylaxis for postoperative deep venous thrombosis in major urological surgery.

Postoperative deep venous thrombosis and pulmonary embolus remain a major source of morbidity and mortality for the urological surgery patient. We report the results of the first 100 patients in a prospective, randomized trial of low dose warfarin and intermittent pneumatic leg compression for deep venous thrombosis prophylaxis. All patients underwent preoperative and postoperative real-time ultrasound imaging and Doppler flow studies of the popliteal, femoral and iliac veins for the evaluation of deep venous thrombosis. Our results indicate that low dose warfarin is as effective as intermittent pneumatic leg compression for prophylaxis of deep venous thrombosis. Low dose warfarin can be used effectively without any significant bleeding complications. We recommend the use of low dose warfarin as an alternative to intermittent pneumatic leg compression for deep venous thrombosis prophylaxis of the urological patient undergoing a major urological operation.

Aged↗
PubMed1992

Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines.

Metastatic variants of human prostatic adenocarcinoma cell lines (DU-145, LNCaP, and ND-1) were studied by using soft agar colony forming efficiency, nude mice tumorigenicity, in vitro invasion assay, and type IV collagenase assay. The DU-145 and ND-1 cell line showed higher metastatic potential than LNCaP. Lipids from DU-145, ND-1, and LNCaP cells were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. The major lipids were phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, fatty acids, and cholesterol. The sphingomyelin level was significantly higher in highly metastatic cells (DU-145 and ND-1) compared with the lower metastatic variant (LNCaP). The increase in the synthetic pathway and decrease in degradation pathway of sphingomyelin in microsomal fractions was sufficient to account for the measured increase in sphingomyelin in DU-145 cells compared with LNCaP cells. The major fatty acids of these lipids were palmitic (16:0), stearic (18:0), oelic (18:1), and arachidonic acid (20:4). The arachidonic acid level was significantly decreased in DU-145 and ND-1 compared with LNCaP cells. Electron microscopic studies showed no significant changes in the morphology of DU-145, ND-1, and LNCaP cells. The results of these investigations demonstrate for the first time that sphingomyelin and arachidonic acid contents are different in high and low metastatic variants of human prostatic adenocarcinoma cell lines.

Adenocarcinoma↗
PubMed1992

Staging of prostate cancer. Accuracy of transrectal ultrasound enhanced by prostate-specific antigen.

Transrectal ultrasound (TRUS) has shown some promise in the staging of prostate cancer, while prostate-specific antigen (PSA) alone is insufficient. By combining prospective TRUS evaluation with retrospective PSA analysis, we demonstrated an increased accuracy of this combined staging method over TRUS alone. In 48 men undergoing radical prostatectomy, TRUS was performed and PSA measured pre-operatively. On the basis of TRUS, tumours were classified as contained or uncontained. An "expected" PSA value was then calculated for each patient as follows: K x volume of hypoechoic area +0.07 x prostate volume where K = 2.1 if the combined Gleason score of the initial biopsy was > or = 7, or 4.2 if the score was < or = 6. If a patient's pre-operative PSA value was less than or equal to the expected PSA, his tumour was judged to be contained. Staging by both TRUS and PSA was combined, so that if the tumour was judged uncontained by either parameter, the combined prediction was uncontained. Results of the combined staging were: sensitivity 84%, specificity 82%, positive predictive value 94%, negative predictive value 60%, accuracy 83%. This PSA formula, which takes into account the size and grade of the lesion rather than an arbitrary cut-off value, enhances the local staging of prostate cancer by TRUS.

Aged↗
PubMed1992

Downregulation of saturated fatty acid and upregulation of unsaturated fatty acid by 13-cis-retinoic acid in human prostate cancer cells.

Retinoids play a major role in regulation of epithelial cell growth and cellular differentiation, but their mechanism(s) of action are still unclear. In the present study, we examined the effects of 13-cis-retinoic acid (13-cis-RA) on cytotoxicity, growth properties, morphology, neutral lipids, phospholipids and fatty acids in cultured human prostate cancer cell lines. The results of these experiments suggest that 13-cis-RA (10 microM) inhibits the DNA synthesis and nude mice tumorigenicity by 2- to 3-fold, compared to control. Electron microscopy revealed more differentiated phenotypes after 13-cis-RA treatment. There was a significant increase in phosphatidylcholine and decrease in sphingomyelin in 13-cis-RA treated cells compared to control. The saturated fatty acids significantly decreased whereas unsaturated fatty acids were increased after 13-cis-RA treatment in prostate cancer cells. This study demonstrates for the first time that retinoic acid mediated downregulation of saturated fatty acids and upregulation of unsaturated fatty acid in human prostate cancer cells.

Animals↗
PubMed1992

Incidental lymphocytic prostatitis. Selective involvement with nonmalignant glands.

We documented the presence of lymphocytic prostatitis in all prostate specimens received over a 4-month period. Lymphocytic prostatitis was present in 44% of biopsy specimens (n = 77), 95% of transurethral prostatic resection specimens (n = 20), and 100% of total prostatectomy specimens (n = 9). The patchiness of the prostatitis within the prostate in part explains the lower prevalence in the biopsy specimens, which sample a much smaller portion of the gland compared with the other procedures. Lymphocytic prostatitis was seen in prostates both with and without adenocarcinoma. However, in specimens containing carcinoma, the lymphocytic aggregates rarely involved malignant glands. Instead, the aggregates were either stromal or involved nonmalignant glands either adjacent to or away from the tumor, including glands with hyperplasia, atrophy, and prostatic intraepithelial neoplasia. Even when malignant and nonmalignant glands were in close proximity, there was a sharp demarcation with respect to lymphocytic inflammation. Immunohistochemical staining with B-cell and T-cell markers disclosed that the vast majority are T lymphocytes. The localization of lymphoid aggregates to nonmalignant (including prostatic intraepithelial neoplasia) glands but not frankly neoplastic glands, suggests a selective escape of immune detection by neoplastic glands.

Adenocarcinoma↗