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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 109 records · Page 6Linked to original sources
PubMed1995

The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer.

OBJECTIVES: To evaluate the role of ultra sound-guided systematic and lesion-directed biopsies, biopsy gleason score, preoperative serum prostate-specific antigen (PSA) as three objective and reproducible variables to provide a reliable combination in preoperative identification of risk of extraprostatic extension in patients with clinically localized prostate cancer. METHODS: The case records of 813 patients who underwent radical prostatectomy for clinically localized prostate cancer were analyzed. All had multiple systematic biopsies, two to three from each lobe, in addition to lesion-directed biopsies. Additionally, biopsies were done on seminal vesicles (SVs), if abnormal. Based on biopsy results, patients were classified as having stage B1 (T2a-T2b) or B2 (T2c) disease, depending on whether biopsies from one or both lobes were positive and stage C (T3) if there was evidence of SV involvement by biopsy of biopsies from areas of extracapsular extension as seen on transrectal ultrasound (TRUS) were positive. Logistic regression analyses with log likelihood chi-square test was used to define the correlation between individual as well as combination of preoperative variables and pathologic stage. RESULTS: On final pathologic examination, 473 (58%) patients had organ-confined disease, 188 (23%) had extracapsular extension (ECE), with or without positive surgical margins, and 72 (9%) had SV involvement. Eighty (10%) patients had pelvic lymph node metastases. Biopsy-based staging was superior to clinical staging in predicting final pathologic diagnosis. Logistic regression analyses revealed that the combination of biopsy-based stage, preoperative serum PSA, and biopsy Gleason score provided the best prediction of final pathologic stage. Probability plots constructed with these data can provide significant information on risk of extraprostatic extension in individual patients. CONCLUSIONS: This study demonstrates that TRUS-guided systematic biopsy in combination with preoperative serum PSA and biopsy Gleason score may provide a cost-effective approach for management decisions and prognostication in patients with prostate cancer.

Biopsy↗
PubMed1995

Epididymo-orchitis after cryoablation of prostate for prostate cancer.

We report two cases of acute epididymo-orchitis developing 4 to 6 weeks after cryoablation for prostate cancer. One patient required a simple orchiectomy for epididymal abscess; the other responded to treatment with antibiotics. Since the occurrence of these two cases, we routinely perform bilateral vasectomy prior to prostate cryoablation. We suggest that an extended course of prophylactic antibiotics may also be needed in order to avoid this complication.

Abscess↗
PubMed1995

Laser effects on prostatic tissue: review of experimental data.

Laser-tissue interaction is a highly dynamic event affected by many features of the laser, the tissue, and the operative procedure. The continuous-wave lasers used in urology produce lesions in three basic phases: initial heating, protein denaturation, and evaporation with charring. There are three components of these lesions: a central cavity, a zone of char, and a coagulation zone. The configuration of the lesion differs depending on the method of laser ablation (noncontact coagulation, contact tip incision, contact free-beam evaporation). Understanding of these differences will enable the endourologist to choose rationally among the various techniques of laser prostate ablation.

Humans↗
PubMed1995

Neuroanatomy of the external urethral sphincter: implications for urinary continence preservation during radical prostate surgery.

Post-prostatectomy urinary incontinence probably is multifactorial and sphincteric nerve injury could be a contributing cause. Controversy still exists regarding the innervation of the external sphincter, and currently pudendal nerve injury is not believed to be an etiological factor in post-prostatectomy urinary incontinence. To understand better the sphincter and its innervation, we undertook an anatomical and histological study of 18 adult male cadavers, which revealed that the external urethral sphincter receives part of its innervation through special branches originating from the dorsal nerve of the penis after it splits from the pudendal nerve. These nerve branches were located 0.3 to 1.3 cm. from the prostatic apex, and in 50% of the cadavers they were identified only unilaterally or had only 1 branch on each side. The proximity of these nerves to the prostatic apex may make them liable to injury during radical prostatectomy. These nerves are most likely sensory in nature although the presence of motor components cannot be completely ruled out. Injury to these nerves may explain several features of post-prostatectomy urinary incontinence.

Aged↗
PubMed1995

Differential suppression of serum prostatic acid phosphatase and prostate-specific antigen by 5-alpha-reductase inhibitor.

OBJECTIVE: To evaluate the effect of finasteride (Proscar) on the serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirty patients on finasteride therapy for BPH formed the study group. Serum PSA and PAP levels were monitored for 2 years while the patients were receiving finasteride. RESULTS: During 12 months of finasteride therapy the serum PSA was suppressed but serum PAP was unaffected. The baseline mean PAP value was 1.303 ng/mL prior to finasteride therapy; this changed to 1.510 ng/mL (P = 0.195) at 6 months and 1.166 ng/mL (P = 0.383) at 12 months. The serum PSA was 2.630 ng/mL at baseline, 1.757 ng/mL (P < 0.001) at 6 months and 1.545 ng/mL (P = 0.001) at 12 months. CONCLUSIONS: Further studies are warranted to determine if PAP has a role as a tumour marker in patients whose PSA is suppressed as a result of finasteride therapy.

Acid Phosphatase↗
PubMed1995

The significance of prostatic intra-epithelial neoplasia.

OBJECTIVE: To investigate the relationship between the detection of prostatic intra-epithelial neoplasia (PIN) on initial prostate biopsy and subsequent invasive prostatic adenocarcinoma. PATIENTS AND METHODS: Thirty-six men (mean age 67 years, range 52-82) with PIN underwent digital rectal examination (DRE), serum prostate-specific antigen (PSA) measurement and transrectal ultrasonography (TRUS) before the initial biopsy and documentation of PIN. They were followed up with serial PSA, TRUS and a repeat biopsy every 6 months until either invasive carcinoma was identified or 2 years had elapsed. RESULTS: The initial biopsy revealed Grade I PIN in 33%, Grade II in 22%, and Grade III in 45% of the men. The repeat biopsy showed evidence of invasive carcinoma in 21 patients (58%; Group I), while 15 (42%) showed persistence of PIN (Group II). In Group I, 19 had had high-grade PIN (Grade II/III) on initial biopsy compared with one in Group II. The findings on DRE, and age, were no significantly different between groups. TRUS revealed a hypoechoic lesion in 15/21 patients in Group I compared with 7/15 patients in Group II. There was an increase in PSA level in 18 patients in Group I (from 8.4 to 11.6 ng/mL). CONCLUSIONS: PIN and invasive adenocarcinoma of the prostate were closely associated, and the likelihood for coexistence was higher in patients with high-grade PIN, increasing PSA level or positive findings on TRUS. We recommend that all patients who show high-grade PIN on prostate biopsy be followed very closely with serial PSA measurements and repeat biopsies from both the area of PIN and other areas of the prostate.

Adenocarcinoma↗
PubMed1995

Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images.

PURPOSE: To assess the frequency of changes in signal intensity after prostatic biopsy and the effect of these changes on the magnetic resonance (MR) imaging staging of prostate cancer. MATERIALS AND METHODS: Seventy-three patients with biopsy-proved prostate cancer were divided into two groups according to time between biopsy and imaging (less than and more than 21 days). The findings at MR imaging were compared with those at pathologic examination. RESULTS: Postbiopsy hemorrhage was detected in 21 of 26 (81%) patients who underwent imaging less than 21 days after biopsy and in 23 of 47 (49%) patients who underwent imaging more than 21 days after biopsy (P < .01). Postbiopsy changes persisted for as long as 4 1/2 months. Less than 21 days after biopsy, there was a tendency to overestimate tumor presence and extracapsular extension. After 21 days, tumor presence was underestimated but the positive predictive value for extracapsular extension was improved. Staging accuracy less than 21 days after biopsy was 46%; this improved to 83% after 21 days (P < .01). CONCLUSION: Staging accuracy is significantly improved when imaging is deferred for 21 days after biopsy.

Biopsy, Needle↗
PubMed1995

Functional expression of yoked human chorionic gonadotropin in baculovirus-infected insect cells.

hCG is a glycoprotein hormone composed of an alpha-subunit, common to all gonadotropins and to TSH, and a hormone-specific beta-subunit. The non-covalent association of the two subunits is an obligatory step for the formation of biologically active hormones. The correct assembly of the heterodimer is also important for efficient secretion of the hormone, receptor binding, and signal transduction. Herein, we have demonstrated that expression of the two subunits from independent promoters present in a single recombinant baculovirus resulted in subunit association and secretion of biologically active holoprotein by the insect cells. To determine whether the active conformation of heterodimer could be achieved when the two subunits were synthesized in tandem on a single polypeptide chain, two single chain or yoked hCG1, the C-terminus of the complete beta-subunit (145 amino acid residues) was conjoined to the N-terminus of the alpha-subunit. Yoked hCG2 was similar, except that it contained the N-terminal 123 amino acid residues of the beta-subunit. Both yoked hCG molecules bound LH/CG receptor with high affinity and stimulated adenylate cyclase and progesterone levels in transformed mouse Leydig (MA-10) cells. Therefore, the alpha- and beta-subunits are able to fold into a biologically active conformation when covalently linked. Interestingly, when compared with urinary hCG, the hormone expressed in baculovirus-infected insect cells binds to the LH/CG receptor with higher affinity, but exhibits diminished signaling, thus providing another example of a partial dissociation between receptor binding and activation.

Animals↗
PubMed1995

A randomized study comparing visual laser ablation and transurethral evaporation of prostate in the management of benign prostatic hyperplasia.

PURPOSE: We evaluated the safety, efficacy, failure and complications of 2 techniques of laser prostatectomy for benign prostatic hyperplasia (BPH): transurethral evaporation of the prostate (evaporation) versus visual laser ablation of the prostate (coagulation) in a randomized trial. MATERIALS AND METHODS: A total of 64 consecutive patients with symptomatic BPH was randomized to undergo evaporation (32) or coagulation (32). American Urological Association symptom score, peak urinary flow rate and post-void residual urine volume were measured at baseline, and at 1, 3, 6 and 12 months. Other parameters evaluated included prostate volume by transrectal ultrasound, total laser energy per patient and per cc volume of the prostate, number of laser fibers per prostate, duration of catheterization and hospitalization, need for re-catheterization, and failure and complication rates. RESULTS: Our main findings were that patients undergoing laser prostatectomy using the coagulation technique (visual laser ablation of the prostate) had higher reoperation rates (16% versus 0%, p = 0.0199) and were 4 times more likely to have prolonged postoperative urinary retention (25% versus 6.3%, p = 0.0389), evaporation and coagulation were effective at relieving symptoms of prostatism with significant improvement in American Urological Association symptom scores and post-void residual urine volumes compared to baseline, improvement in peak flow rates was significantly greater in patients undergoing evaporation at 1, 3, 6 and 12 months (p < 0.001) compared to coagulation, and a significantly greater amount of laser energy was required to evaporate a unit volume of prostate tissue compared to coagulation (2,251 J./cc versus 1,036 J./cc, p < 0.03). CONCLUSIONS: Between the 2 major techniques of laser prostatectomy, transurethral evaporation is associated with better results at up to 12 months of followup.

Aged↗
PubMed1995

c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization.

Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.

Chromosomes, Human, Pair 8↗
PubMed1995

Regression of LNCaP human prostate tumor xenografts in athymic nude mice by 13-cis-retinoic acid and androgen ablation.

The present study was designed to investigate the effects of 13-cis-retinoic acid (13-cis-RA) (100 micrograms/mouse/day) and androgen ablation (castration) alone and in combination on growth of a human prostatic carcinoma line (LNCaP) transplanted to athymic nude mice as an experimental model. The results of these studies suggest that; (1) androgen ablation (castration) significantly decreased the size of LNCaP xenograft as compared to untreated animals; (2) when 13-cis-RA was administered to nude mice carrying established tumors (0.51 +/- 0.04 cm3), the tumor size was significantly reduced as compared to untreated controls (0.65 +/- 0.06 cm3 versus 1.63 +/- 0.12 cm3). About 50% of the animals in this group showed xenografts necrosis followed by complete regression of tumors by five months; (3) the combination of androgen ablation and 13-cis-RA treatment to nude mice carrying tumors showed synergistic effect in decreasing the tumor size. These results indicate that combination therapies based on androgen ablation and retinoid administration may be a useful approach for the treatment of prostate cancer.

Animals↗
PubMed1994

Inhibition of tumorigenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid.

Prostate-specific antigen (PSA) is a member of the kallikrein family and has been an important biological marker for prostate cancer. The mechanisms regulating PSA expression in prostatic cancer cells are unclear. The present study was designed to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the tumorigenic potential of the human prostate cancer cell line LNCaP. The growth regulation of LNCaP cells was examined by DNA synthesis and doubling time. The tumorigenic potential of prostate cancer cells was analyzed by soft agar colony-forming assay, in vitro invasion assay, type IV collagenase assay and binding to extracellular matrix assay. The nuclear receptors for retinoic acid (RAR alpha, -beta, -gamma and RXR alpha, -beta, -gamma) as well as PSA mRNA were determined by Northern blot using specific oligonucleotide probes. Our results suggest that 13-cis-RA significantly inhibits PSA secretion and expression both at the mRNA and protein levels compared with untreated cells. Electron microscopic studies suggest that after 13-cis-RA treatment, cells become more differentiated as they contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell growth and tumorigenic potential after 13-cis-RA treatment was significantly decreased compared with controls. Nude mice tumorigenicity studies showed that 13-cis-RA-treated cells produced significantly smaller tumors compared with untreated cell tumors. There was also a significant increase in the expression of RXRa mRNA after 13-cis-RA treatment compared with untreated cells.

Animals↗
PubMed1994

Indications for and the significance of seminal vesicle irradiation during 3D conformal radiotherapy for localized prostate cancer.

PURPOSE: To evaluate the use of pretreatment prostate specific antigen, Gleason score, and clinical stage as predictors of the risk of seminal vesicle involvement in patients with clinically localized prostatic cancer, and to determine the impact of excluding the seminal vesicles on the dose received by surrounding normal tissues. METHODS AND MATERIALS: An empirically derived equation combining the preoperative prostate specific antigen and Gleason score was applied to 188 patients treated with radical prostatectomy, for whom pathologic evaluation of the seminal vesicles was available. High and low risk groups for seminal vesicle involvement were defined using this equation. The observed risks of seminal vesicle involvement was compared to the predicted risk using the preoperative prostate specific antigen, Gleason score or clinical stage alone or using the empirical equation. Dose-volume histograms for five patients treated using six-field conformal radiotherapy were compared including and excluding the seminal vesicles. RESULTS: Using the empirically derived equation, a low risk group of 109 patients was identified with a calculated risk of seminal vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the high risk group of 79 patients, which included all patients with a calculated risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk). Twenty percent of the rectal volume received on average above 86% of the total dose for the five plans which included the seminal vesicles compared to 68% for the five plans excluding the seminal vesicles. The doses to 40% of the rectal volume were 64% and 37% if the seminal vesicles were included and excluded, respectively. The dose to the bladder and femoral heads was also decreased but to a lesser extent. CONCLUSION: The empirical formula predicts risk of seminal vesicle involvement with a higher degree of significance for a larger number of patients than either Gleason score, clinical stage, or prostate specific antigen alone. Based on an analysis of our first 100 patients treated with definitive conformal therapy alone, approximately 47% of those patients could have been treated excluding the seminal vesicles. Excluding the seminal vesicles may allow us to go to a higher total dose with less rectal toxicity.

Humans↗
PubMed1994

Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex.

N6-Methyladenosine is found at internal positions of mRNA in higher eukaryotes. This post-transcriptional modification occurs at a frequency of one to three methylation/average mRNA molecule in mammalian cell lines and is sequence-specific. A highly conserved consensus recognition site for the methyltransferase has been determined from both viral and cellular messages, consisting of the sequence Pu(G/A)AC(U/A) (with A being methylated). Despite the ubiquity and the specificity of this modification, little is known about the mechanism of formation of N6-methyladenosine. Utilizing an in vitro methylation system from HeLa cell nuclear extracts, and a substrate RNA derived from the mRNA coding for bovine prolactin, the mRNA N6-adenosine methyltransferase has been characterized and partially purified. Unique among other characterized nucleic acid methyltransferases, the enzyme is composed of three components which are separable under non-denaturing conditions. The molecular masses of the components are 30, 200, and 875 kDa as determined by gel filtration and glycerol gradient sedimentation. The 200-kDa component appears to contain the S-adenosylmethionine-binding site on a 70-kDa subunit. The 875-kDa component has affinity for single-stranded DNA-agarose, suggesting that it may contain the mRNA-binding site. N6-Adenosine methyltransferase is not sensitive to treatment with micrococcal nuclease, nor to immunodepletion using an anti-trimethylguanosine antibody, suggesting that it does not contain an essential RNA component.

Animals↗
PubMed1994

Context effects on N6-adenosine methylation sites in prolactin mRNA.

The methylation of internal adenosine residues in mRNA only occurs within GAC or AAC sequences. Although both of these sequence motifs are utilized, a general preference has been noted for the extended sequence RGACU. Not all RGACU sequences in an mRNA are methylated and the mechanisms that govern the selection of methylation sites in mRNA remain unclear. To address this problem we have examined the methylation of transcripts containing sequences of a natural mRNA, namely, bovine prolactin mRNA. In this mRNA, a specific AGACU sequence in the 3' untranslated region is the predominant site of methylation both in vivo and in vitro. The degree to which N6-adenosine methyltransferase recognizes the sequence context of the consensus methylation site was explored by mutational analysis of the nucleotides adjacent to the core sequence as well as the extended regions in which the core element was found. Our results indicate that efficient methylation depends on the extended five nucleotide consensus sequence but is strongly influenced by the context in which the consensus sequence occurs within the overall mRNA molecule. Furthermore, consensus methylation sites present in an RNA duplex are not recognized by the methyltransferase.

Adenine↗
PubMed1994

Effects of diltiazem, metoprolol, enalapril and hydrochlorothiazide on frequency of ventricular premature complexes.

Ventricular arrhythmias occur frequently in patients with hypertensive left ventricular (LV) hypertrophy and have been associated with increased incidence of sudden death. In this study, the effect of various antihypertensive medications on ventricular arrhythmias was evaluated in 31 hypertensive patients with moderate to severe LV hypertrophy. Patients were assessed at baseline (after 3 weeks of placebo treatment) and after treatment with each of 4 monotherapies: diltiazem 120 or 240 mg/day, metoprolol 100 or 200 mg/day, enalapril 10 or 20 mg/day and hydrochlorothiazide 50 or 100 mg/day. Each drug therapy was administered for 4 weeks. The sequence of each treatment was determined at random. Echocardiographic measurements and electrocardiograms were obtained only at baseline. Biochemical measurements and 48-hour Holter monitoring were obtained at baseline and at the end of each treatment. All treatments resulted in a significant but similar decrease in blood pressure. In the group as a whole diltiazem decreased ventricular premature complexes (VPCs) by 65% (p < 0.05) and metoprolol by 52% (p = 0.07). Enalapril and hydrochlorothiazide had no effect. In 12 patients with > or = 5 VPCs/hour at baseline, diltiazem and metoprolol decreased VPCs by 66% (p < 0.05). It is concluded that in hypertensive patients with moderate to severe LV hypertrophy, both diltiazem and metoprolol significantly reduce VPCs.

Analysis of Variance↗
PubMed1994

Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer.

PURPOSE: To evaluate the predictive value of an empirically derived equation for identifying patients with clinically localized prostate cancer at low and high risk for harboring occult lymph node metastasis. METHODS AND MATERIALS: A simple equation for estimating the risk of positive lymph nodes was empirically derived from a nomogram published by Partin et al. demonstrating the value of combining the pre-treatment prostate specific antigen and Gleason Score in predicting the risk of lymph node metastasis for patients with clinically localized prostate cancer. The risk of positive nodes (N+) was calculated using the equation; N+ = 2/3(PSA) + (GS-6) x 10, where PSA and GS are the pre-treatment prostate specific antigen and Gleason Score respectively, and the calculated risk is constrained between 0-65% for a PSA < or = 40 ng/ml (as in the nomogram). To test the general applicability of this equation, we reviewed the pathologic features of 282 of our patients who had undergone a radical prostatectomy. RESULTS: Based on 212 patients for whom the pre-operative prostate specific antigen's and Gleason Scores were available, we identified 145 patients with a calculated risk of positive nodes of < 15%, (low risk group) and 67 patients with a calculated risk as > or = 15% (high risk group). The observed incidence of positive nodes was 6% and 40% among the low and high risk groups respectively (p < 0.001). When used alone neither clinical stage, pre-treatment prostate specific antigen nor the pre-treatment Gleason Score was as useful in identifying the largest low and high risk groups. CONCLUSION: Using the equation described we confirmed the general applicability of the nomogram reported by Partin et al. and identified patients at low and high risk for lymph node involvement. Based on these data we have adopted a policy of omitting whole pelvic irradiation in patients identified as low risk.

Biomarkers, Tumor↗