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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 127 records · Page 7Linked to original sources

Factors affecting size and configuration of neodymium:YAG (Nd:YAG) laser lesions in the prostate.

Laser surgery for benign prostatic hypertrophy is a clinical reality and a promising alternative to traditional transurethral electroresection of the prostatic adenoma (TURP). Current methods of laser prostatectomy involve coagulation of prostate tissue using a quartz side-firing fiber that redirects a Nd:YAG laser beam at 70-90 degrees most commonly by means of a metal reflector. In this communication we describe a method of tissue evaporation using a side-firing fiber that avoids use of a metal reflector by means of internal reflection. It is relatively resistant to damage when coming in contact with tissue. By placing the fiber tip in direct contact with tissue, much larger lesions are created because of more efficient energy transfer resulting in rapid evaporation of tissue under water. In prostate surgery, this phenomenon of accelerated evaporation can be used to bloodlessly evaporate adenomatous tissue creating a defect that resembles that of a traditional TURP.

Adenoma↗

Transurethral evaporation of prostate (TUEP) with Nd:YAG laser using a contact free beam technique: results in 61 patients with benign prostatic hyperplasia.

OBJECTIVE: This prospective study was undertaken to evaluate the safety and efficacy of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser for treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 61 patients at a mean age of 71.6 years with symptomatic bladder outlet obstruction due to BPH underwent transurethral evaporation of prostate (TUEP) using Nd:YAG laser. Twelve of the patients were experiencing acute retention. Pre- and postoperative evaluation consisted of American Urological Association (AUA) symptom questionnaire and a sexual function questionnaire, uroflowmetry, postvoid residual urine, electrolytes, blood urea nitrogen, creatinine, hematocrit, and prostate volume estimation by transrectal ultrasound. TUEP was achieved by employing a side-firing Nd:YAG laser fiber with a durable quartz reflector and high-power density (Ultraline, Heraeus LaserSonics, Milpitas, CA) that was used in a contact mode. RESULTS: All patients have been evaluated for three months, 26 for six months, and 7 for twelve months. Mean prostatic size was 41.1 g. The mean improvement in symptom scores at one, three, six, and twelve months was 69.8 percent, 70.9 percent, 76.0 percent, and 70.9 percent, respectively (P = < 0.0001). The mean increase in maximum uroflow at one, three, six, and twelve months was 63.4 percent, 66.7 percent, 41.94 percent, and 164.52 percent, respectively (P = < 0.0001). There was no instance of significant fluid absorption or bleeding. The duration of postoperative catheterization was two days in 43 patients, three to seven days in 16 patients, and two to three weeks in 2 patients. There were no deaths. All patients evaluated by TRUS at six months had open channeling defects. Videocystoscopy performed in 16 patients at two to three months postoperatively revealed tissue slough. At repeat cystoscopy in these patients at six months, the prostatic fossa was completely healed with no evidence of tissue slough. CONCLUSIONS: It is concluded that the technique of TUEP using Nd:YAG laser is safe and, in preliminary results, appears apparently effective in the management of BPH.

Aged↗

N6-adenosine methylation in mRNA: substrate specificity and enzyme complexity.

The N6-methylation of internal adenosine residues is a common post-transcriptional modification of eukaryotic pre-mRNA sequences. An in vitro methylation system which retains the precise selectivity of in vivo methylation sites has been used to further define the nature of RNA site recognition. In addition to short consensus sequences, other structural features or context effects contribute to the selection of methylation sites in pre-mRNAs. Partial purification of the mRNA N6-adenosine methyltransferase revealed unexpected levels of complexity. The methyltransferase is composed of three separate components with molecular masses of 30, 200 and 875 kDa, respectively. These components are readily separated under non-denaturing conditions and each is required for mRNA methylation activity.

Adenosine↗

Comparison of prostate specific antigen with prostate specific antigen density for 3 clinical applications.

We compared prostate specific antigen (PSA) to PSA density for 3 clinical uses: detection of nonpalpable prostate cancer, staging of clinically localized prostate cancer and prediction of PSA detectability following radical prostatectomy. Of 153 men with normal digital rectal examinations undergoing prostate biopsy 25% had prostate cancer. Analysis of receiver operator characteristic curves demonstrated that PSA density predicted the outcome of biopsy significantly better than did PSA (p = 0.0013). Pathological examination of 155 radical prostatectomy specimens revealed that 56% had pathologically uncontained disease. There was no difference between the ability of PSA and PSA density to predict the pathological findings (p = 0.2379). PSA data more than 1 year postoperatively were available in 96 of the 155 prostatectomy patients. Of these men 41% had postoperative PSA levels of 0.1 ng/ml. or more. Preoperative PSA and PSA density values were almost identical in the ability to identify these patients (p = 0.6776). While PSA density is superior to PSA for the detection of prostate cancer in patients with a palpably normal prostate, it does not offer any improvement over PSA for staging of prostate cancer or for the prediction of PSA detectability after radical prostatectomy.

Aged↗

Utility of preoperative serum prostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer.

OBJECTIVES: To determine the accuracy of the preoperative serum concentration of prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy specimens in predicting the presence of disease in the pelvic lymph nodes in patients with prostate cancer. METHODS: The medical records of all patients treated for prostate cancer at eight medical centers from January 1988 to June 1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer for whom all relevant data were available who had undergone pelvic lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The rate of false-negative predictions of metastases based on combined preoperative biopsy Gleason score and serum PSA concentration was analyzed. A multivariate logistic regression analysis was performed to assess the value of preoperative serum PSA and biopsy Gleason scores individually and in combination in predicting pelvic lymph node metastases. RESULTS: The false-negative rate of metastases was 0% for preoperative PSA concentrations < or = 6 ng/mL and biopsy Gleason scores < or = 5 (n = 142) and 1.0% for PSA concentrations < or = 10 ng/mL and Gleason scores < or = 6 (n = 388). The 95% upper confidence limit for the rate of false negativity at this PSA cut-off level was 2.0%. A combination of preoperative serum PSA levels and biopsy Gleason scores provided the best prediction for the false-negative rates. CONCLUSIONS: For patients with newly diagnosed prostate cancer who have biopsy Gleason scores < or = 6 and preoperative PSA concentrations < or = 10 ng/mL (42% of our series), a staging pelvic lymphadenectomy appears to be unnecessary. The substantial cost associated with both cross-sectional imaging and staging lymphadenectomy may therefore be avoidable in this group of patients.

Biopsy↗

Urethral anastomotic healing after radical retropubic prostatectomy: impact of positive urethral margin.

OBJECTIVES: To determine the time course of urethral anastomotic healing after radical retropubic prostatectomy and its relationship to a positive margin at the anastomosis, the type of suture used, and the incidence of bladder neck contracture. METHODS: In 119 consecutive patients a pericatheterogram was performed at 15.5 +/- 0.5 days postoperatively. A second pericatheterogram was obtained at 22.3 +/- 0.7 days for those anastomoses that were not healed, and a third pericatheterogram at 32.1 +/- 2.5 days for the remainder. Maxon sutures were used for 63 anastomoses, Dexon for 14, and chromic catgut for 42. RESULTS: Sixty-five anastomoses (55%) were healed at the first pericatheterogram and 104 (87%) by 22 days. Microscopic tumor at the apical cut end of the prostate was found in 20% of specimens; the healing period for these patients was 21.0 +/- 2.0 days compared with 21.1 +/- 0.8 days for those with a negative margin. The healing time for Maxon, Dexon, and chromic catgut was 21.6, 24.6, and 19.5 days, respectively. Of the 108 evaluable patients, in 10 (9.3%) significant bladder neck contracture developed at a mean of 15 weeks; 6 (10.7%) were associated with Maxon anastomoses, 1 with Dexon (8.3%), and 3 (7.5%) with chromic sutures. Five of 10 bladder neck contractures were in 11 patients with previous prostate surgery (45%). CONCLUSIONS: The presence of microscopic tumor at the urethral margin did not increase the risk of extravasation. There was no correlation between extravasation and bladder neck contracture, but less extravasation was associated with chromic sutures. Previous transurethral resection appeared to be a risk factor for the development of bladder neck contracture.

Aged↗

Monitoring of body weight during transurethral resection of the prostate: preliminary report.

The fear of vascular overload by irrigant during transurethral resection of the prostate is a reason for an incomplete resection. With continuous measurement of the patient's body weight and, thus, body water, irrigant entrance is immediately identified. We present a scale of proved accuracy and reliability, allowing more effective resection while eliminating the possibility of TUR syndrome.

Body Weight↗

Role of penile vascular injury in erectile dysfunction after radical prostatectomy.

OBJECTIVE: To investigate the cause of erectile dysfunction after nerve-sparing radical prostatectomy for clinically localized adenocarcinoma of the prostate (stage A or B). PATIENTS AND METHODS: Erectile function was evaluated in 20 patients, mean age 65 years (range 44-74), both pre-operatively and 1 year after surgery by intracavernosal injection of a vasoactive agent (papaverine hydrochloride or prostaglandin E1) and pulsed Doppler ultrasonography. The degree of erection, the size of the cavernosal artery and penile arterial blood flow velocity were assessed. RESULTS: Results revealed that the decreased response to intracavernosal injection of a vasoactive agent was associated with a significant reduction in both the diameter and velocity of blood flow within cavernosal arteries in 40% of patients after surgery. The pathological stage of the tumour did not correlate with the degree of vascular injury. CONCLUSION: We conclude that post-prostatectomy impotence is multifactorial but vascular injury plays a substantial role.

Adenocarcinoma↗

Neoadjuvant hormonal therapy and radical prostatectomy for clinical stage C carcinoma of the prostate.

OBJECTIVE: To determine whether hormonal therapy prior to radical prostatectomy (neoadjuvant hormonal therapy) leads to improved results in patients with stage C prostate cancer. PATIENTS AND METHODS: Thirty patients received neoadjuvant hormonal therapy for stage C carcinoma of the prostate. Eighteen patients who responded to treatment subsequently underwent extirpative surgery. RESULTS: Fourteen of the 30 patients (47%) were diagnosed as being downstaged to clinical stage B disease following therapy. No major complications occurred. Pathology staging revealed only three patients (10%) to have organ-confined disease after radical prostatectomy. CONCLUSIONS: Neoadjuvant hormonal therapy prior to radical prostatectomy offers little probability of rendering patients with clinical stage C carcinoma of the prostate free of disease. Further investigation of the efficacy of this treatment should be accomplished in randomized trials.

Adenocarcinoma↗

Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal--pelvic phased-array coils.

PURPOSE: To compare the performance of pelvic phased-array (PPA) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer. MATERIALS AND METHODS: Seventy-one men underwent magnetic resonance (MR) imaging within 3 weeks of radical prostatectomy. MR findings of tumor, extracapsular extension, seminal vesicle invasion, nodal involvement, and stage were compared with step-sectioned (3-4-mm intervals) whole-mounted pathologic specimens. Prospective consensus versus single-reader interpretation (kappa statistics) and PPA versus integrated endorectal PPA coils (McNemar test) were compared, and a rating scale of 1-6 was developed for analysis of receiver operating characteristics. Statistical significance was calculated at delta = .05. RESULTS: Comparison between consensus and single-reader image interpretation showed positive but poor agreement (kappa = .38) and no statistical significance. Staging accuracy was better (difference approached significance) for integrated endorectal PPA coils (77%) than for PPA coils (68%). CONCLUSION: The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil.

Humans↗

Evidence against norepinephrine-stimulated efflux of mitochondrial Mg2+ from intact cardiac myocytes.

We investigated the hypotheses that norepinephrine stimulates Mg2+ efflux from intact isolated adult rat ventricular cardiomyocytes and that adenosine 3',5'-cyclic monophosphate stimulates Mg2+ efflux from permeabilized myocytes and isolated mitochondria. Norepinephrine stimulation of Mg2+ release from cardiac myocytes was observed only when cells at approximately 20 mg protein/ml in Mg(2+)-containing buffer were diluted 50- to 60-fold into an Mg(2+)-free medium. Under these conditions, > 30% of total cellular lactic acid dehydrogenase activity was also released, indicating that a significant portion of the cells had died. In other protocols, where Mg2+ efflux from myocytes was not observed, extracellular Mg2+ removal and administration of 10 microM norepinephrine increased 45Ca2+ accumulation by cells in suspension. In single myocytes, Mg2+ removal and norepinephrine administration increased intracellular free [Ca2+] as measured by fura-2 fluorescence microscopy, and this was accompanied by vigorous spontaneous contractile activity followed by Ca2+ overload hypercontracture. With permeabilized myocytes and isolated mitochondria from a variety of sources, adenosine 3',5'-cyclic monophosphate did not stimulate Mg2+ efflux. These results suggest that recent evidence for direct hormonal regulation of myocardial Mg2+ homeostasis may need to be reevaluated.

Animals↗

Management of benign prostatic hyperplasia.

The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in urology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in urology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Urology of the California Medical Association, and the summaries were prepared under its direction.

Humans↗

Pharmacotherapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive.

Adrenergic alpha-Antagonists↗

13-cis-retinoic acid-mediated growth inhibition of DU-145 human prostate cancer cells.

The purpose of this study was to examine the effects of 13-cis-retinoic acid (13-cis-RA) on the growth regulation of DU-145 human prostatic cancer cells. The results of these experiments demonstrate that cell growth and metastatic potential of DU-145 cells were significantly inhibited by 13-cis-RA (10 microM). In order to elucidate the possible molecular mechanisms of 13-cis-RA action on prostate cancer cells, we examined the expression of nuclear receptor genes (hRXR alpha) and found that 13-cis-RA treated cells showed higher mRNA expression for hRXR alpha nuclear receptors compared to untreated cells. To elucidate further the possible biochemical mechanisms associated with these alterations, we analyzed the phosphorous metabolites by MR spectroscopy and found that the major metabolites were PME, (PC, PE) and DPDE (UDP-GalNAc, UDP-GLcNAc). The DU-145 cells and xenografts, which were both treated with 13-cis-RA, showed a two-fold decrease in DPDE's, compared to their controls. The higher resolution spectra of perfused cells revealed that phosphocholine levels were twice as high in 13-cis-RA-treated DU-145 cells as compared to untreated cells. These investigations demonstrate for the first time that 13-cis-RA inhibits the growth of human prostatic cancer cells, and this inhibition is associated with an increase in hRXR alpha nuclear receptor gene expression and alterations in phosphorous metabolites detected by 31P MR spectroscopy.

Animals↗

Ploidy status correlates with outcome in stage B prostate adenocarcinoma.

1. While there are extensive data showing that aneuploidy is associated with adverse outcome in stage D prostate cancer, the utility of ploidy analysis in stage B disease is unclear. We determined ploidy in radical prostatectomy specimens from 28 patients with clinical stage B prostate cancer, and with a mean follow-up of 4.1 years (2-10 years). Patients who had no recurrences had a minimum 5 years of follow-up. Patients who had only 2 years of follow-up were included if they had developed bone metastases during this period. 2. Ploidy determinations were done on Feulgen-stained 5-microns paraffin-embedded sections using a CAS 200 image analyzer. At least 400 tumor cells were counted in every case. Tumors with at least 70% diploid cells were classified as diploid, while those with less than 70% diploid cells were classified as aneuploid. The mean percentage of diploid cells in tumors classified as diploid was 90.6 +/- 7.4, while the mean percentage of diploid cells in tumors classified as aneuploid was 36 +/- 21.9. 3. Ploidy status correlated with disease progression: seven of the 10 patients (70%) with disease recurrence had aneuploid tumors, while 13 of 18 patients (72%) who remained disease-free had diploid tumors (P = 0.03, Chi-square test). 4. These data show that patients with stage B disease with aneuploid tumors at the time of prostatectomy are more likely to have recurrent disease within a mean of 3 years (2-6 years) compared to patients with diploid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Citrate alterations in primary and metastatic human prostatic adenocarcinomas: 1H magnetic resonance spectroscopy and biochemical study.

The objectives of this study were to quantitatively verify the low levels of citrate previously observed in primary human prostatic adenocarcinomas and to determine whether citrate was further reduced in metastatic prostatic cancer. This was accomplished by comparison of citrate concentrations of DU 145 xenografts (a poorly differentiated human prostatic adenocarcinoma cell line grown in nude mice) with concentrations in primary human adenocarcinomas. Following in vivo 1H NMR studies of DU 145 xenografts, citrate concentrations of DU 145 xenografts and surgically removed primary prostatic adenocarcinoma tissue were determined by quantitative high resolution 1H NMR and enzymatic assay. The most significant findings of this study were that citrate concentrations in primary human adenocarcinomas (3.74 +/- 0.19 mumol/g wet weight) were significantly lower than those observed for normal and benign hyperplastic (BPH) prostatic tissues. Furthermore there was a further ten-fold reduction of citrate associated with DU 145 xenografts (0.31 +/- 0.028 mumole/g wet weight) compared with primary prostatic cancer. DU 145 xenografts also exhibited higher levels of uridine diphosphosugars and choline containing metabolites relative to primary prostatic adenocarcinomas. These findings support the hypothesis that citrate is low in primary prostatic cancer and further reduced in metastatic disease.

Adenocarcinoma↗

Effect of glucose and confluency on phosphorus metabolites of perfused human prostatic adenocarcinoma cells as determined by 31P MRS.

A series of perfused cell 31P MRS studies were conducted using a well established human prostate adenocarcinoma cell line (DU 145) at different phases of growth, and exposed to varying glucose concentrations during growth. The spectral characteristics of perfused DU 145 cells were compared with the same cells grown in nude mice (xenografts). Perfused DU 145 cells had lower levels of inorganic phosphate and phosphocreative relative to in vivo nude mice xenografts. 31P MR spectra obtained from perfused cells at different phases of growth and exposed to varying glucose concentrations during grown suggest that increases in diphosphodiester levels are associated with high glucose concentrations and confluency. Perfused DU 145 cells grown in 5.5 mM glucose and harvested at log phase of growth best reflected the phosphorus MR spectra of the same cell line grown in nude mice.

Adenocarcinoma↗

Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy: a decision analysis.

Indications for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy have not been established. Criteria to predict lymph node metastases were derived from the preoperative evaluations of 164 prostate cancer patients undergoing pelvic lymphadenectomy. Decision analysis was used to determine which criteria would be optimal indicators for laparoscopic pelvic lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal examination suggesting uncontained tumor, which was the best indication for laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If either parameter was met, the sensitivity for identifying patients with pelvic lymph node metastases was 88 percent and the positive predictive value was 42 percent. When both were met, the sensitivity fell to 47 percent but the positive predictive value increased to 67 percent. A combination of Gleason biopsy score and PSA was the best criterion that was independent of transrectal ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6 had a sensitivity of 71 percent and positive predictive value of 48 percent for identifying patients with pelvic lymph node metastases. In selecting patients for laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy, criteria with a positive predictive value greater than 39 percent maximize the utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph node metastases that would otherwise be undetected by prostatectomy alone. The sensitivity of selection criteria, therefore, should be increased, as long as the positive predictive value remains above 20 percent.

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