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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 91 records · Page 5Linked to original sources
PubMed1996

Transurethral vaportrode electrovaporization of the prostate: physical principles, technique, and results.

OBJECTIVES: This is a study to evaluate technique, efficacy, and safety of a new electrosurgical instrument (Vaportrode) in management of benign prostatic hyperplasia (BPH). METHODS: Forty-two symptomatic BPH patients form the subject of this study. Preoperative and postoperative International Prostate Symptom Score (IPSS), peak flow rates (PFR), postvoid residual urine (PVR), operative details, and complications were recorded in each patient. Baseline, 1, 3, and 6 months follow-up data were used for analyses. RESULTS: Results reveal that transurethral electrovaporization of the prostate (TUEVP) is a reasonable procedure to treat symptomatic BPH, and at 6 months, this procedure results in 68% reduction in IPSS, 128% improvement in PFR, and 58% reduction in PVR. Even in patients who are in retention prior to TUEVP, at 6 months the IPSS is 7.7, PFR is 20.4 cc/s, and PVR reduces to 130 cc. The procedure is well tolerated without any significant short-term complications. CONCLUSIONS: The results of this modality in improving the symptoms and PFR in symptomatic BPH patients in the short term appear promising. Advantages over transurethral resection (TUR) of the prostate and laser prostatectomy include familiarity of the transurethral route, lack of need for high-cost laser equipment and fibers, excellent intraoperative hemostasis, lack of bleeding or fluid absorption, and ability to cause a predictable TUR-like prostate defect at the end of the procedure. Further studies involving larger numbers of patients and longer follow-up are warranted to assess further the utility of this procedure.

Aged↗
PubMed1996

P53 tumour-suppressor gene mutations are mainly localised on exon 7 in human primary and metastatic prostate cancer.

Mutations in the p53 tumour-suppressor gene are among the most common genetic alterations in human cancers. In the present study we analysed the mutations in the p53 tumor-suppressor gene in 25 primary and 20 metastatic human prostate cancer specimens. DNA extracted from the paraffin-embedded sections was amplified by hot-start polymerase chain reaction, and p53 gene mutations in the conserved mid-region (exons 4-9) were examined using single-strand conformation polymorphism (SSCP) analysis and immunohistochemistry. In the present study, we used a novel hot-start PCR-SSCP technique using DNA Taq polymerase antibody, which eliminates primer-dimers and non-specific products. Because of this new technique, the results of PCR-SSCP showed very high resolution. Polymerase chain reaction products were sequenced directly for point mutations for the p53 gene. Mutations were found in 2 out of 25 primary prostate cancers (8%) and 4 out of 20 metastatic cancers (20%). Mutations were observed exclusively in exon 7 and not in exons 4, 5, 6, 8 or 9. Nuclear accumulation of p53 protein, determined by immunohistochemistry, correlated with the degree of metastasis in prostatic cancer.

Adenocarcinoma↗
PubMed1996

The proportional decrease in prostate specific antigen level best predicts the duration of survival after hormonal therapy in patients with metastatic carcinoma of the prostate.

OBJECTIVE: To examine the usefulness of a test for prostate specific antigen (PSA) to predict survival in hormonally treated patients with metastatic prostate cancer. PATIENTS AND METHODS: The study comprised 49 patients (mean age 72 years, SD 6) who underwent orchidectomy for metastatic prostate cancer. PSA was measured before orchidectomy and after 6 months, and the absolute, differential and proportional decreases calculated. A Cox proportional hazards regression model, which controlled for patient age, tumour (Gleason) grade and the number of skeletal metastases, was then used to evaluate these estimates of PSA as predictors of survival. RESULTS: The 6-month proportional decrease in PSA from the pre-operative level was the most accurate predictor of patient survival (P = 0.006) after hormonal therapy for metastatic prostate cancer. CONCLUSION: This information may help to direct appropriate patients to new and experimental therapies for metastatic disease.

Aged↗
PubMed1996

Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.7-cm3) spatial resolution.

PURPOSE: To evaluate if three-dimensional hydrogen-1 magnetic resonance spectroscopic imaging (3D MRSI) when combined with a clinical MR imaging examination could discriminate prostatic adenocarcinoma from normal prostatic zonal anatomy and benign prostatic hyperplasia (BPH) on the basis of observable metabolite levels. MATERIALS AND METHODS: Combined phased-array, endorectal MR imaging and 3D MRSI was performed in nine young healthy volunteers, five patients with BPH, and 85 patients with prostate cancer and BPH. Volume MR imaging and 3D MRSI data were analytically corrected for the reception profile of the endorectal and pelvic phased-array coils, aligned with the MR imaging data, and compared with postoperative pathologic histology findings. RESULTS: Statistically significant variations in metabolite levels with prostatic zonal anatomy, age, and pathologic condition were detected with a 3D MRSI examination added to a clinical MR imaging examination. Significantly higher choline levels and significantly lower citrate levels were observed in regions of cancer compared with BPH and normal peripheral zone tissues. The ratio (choline + creatine/citrate) in regions of cancer (2.1 +/- 1.3 [standard deviation]) had no overlap with normal peripheral zone values and minimal overlap with BPH values (0.61 +/- 0.21). An estimate of the spatial extent of prostate cancer was determined by generating metabolite images in which this metabolite ratio significantly exceeded normal peripheral zone values in multiple contiguous sections. CONCLUSION: These results suggest that a 3D MRSI examination added to a clinical MR imaging examination may help define the presence and spatial extent of prostate cancer.

Adenocarcinoma↗
PubMed1996

Mutations of Arg68 of the human chorionic gonadotrophin beta subunit lead to reduced secretion.

The Arg68-Leu69 sequence is invariant in the beta subunits of chorionic gonadotrophin and luteinizing hormone from a variety of species. Using site-directed mutagenesis of the human chorionic gonadotrophin (hCG)-beta cDNA, several replacements of Arg68, an Ala replacement of Leu69, and a multiple replacement with Ala-Ala-Ala-Ala of the tetrapeptide sequence, Arg68-Leu69-Pro70-Gly71, were prepared and characterized. The wild-type and mutant cDNAs were subcloned into a pRSV expression vector and transiently transfected into CHO cells containing a stably integrated gene for bovine a. Concentrations of secreted wild-type and mutant hCG-beta subunit and holoprotein were determined using radioimmunoassays; potencies, i.e. the ratio of biologic to immunologic activity, of several of the mutant heterodimers were measured in vitro via gonadotrophin-mediated steroidogenesis in transformed murine Leydig cells (MA-10). The Leu69-->Ala mutant formed a mutant holoprotein that was essentially equipotent with wild-type hormone in the steroidogenesis assay. The Arg68 replacements with Lys, Ala, and Leu were poorly secreted by the cells, e.g. < 10% that of wild-type hCG; however, sufficient quantities of mutant holoproteins containing Lys68 and Ala68 were obtained for biological assays, and both exhibited greater apparent potencies than wild-type hormone. Likewise, a mutant holoprotein containing the Arg68-Leu69-Pro70-Gly71-->Ala-Ala-Ala-Ala multiple replacement was apparently more potent than wild-type hormone, but it too was secreted at lower levels than wild-type. These results establish that replacements of Arg68 in hCG-beta diminish secretion, but the small amount of holoprotein that is formed and secreted appears to be of somewhat greater potency than wild-type hormone.

Animals↗
PubMed1996

Endothelin binding to NG108-15 cells: evidence for conventional ETA and ETB receptor subtypes and super-high affinity binding components.

The endothelin (ET) peptides have been identified in the CNS, but there is a paucity of information on their physiological roles. NG108-15 cells, a clonal strain of a neuroblastoma x glioma hybrid cell line, have been widely used in neurobiological research since they retain certain differentiated properties of the non-transformed parental cells. It is known that NG108-15 cells respond to the ET peptides, but only limited information is available on the characterization of the ET receptors that mediate these effects. The present study was designed to identify the type(s) of ET receptors on NG108-15 cells in a proliferative state by competitive binding assays using [125I]ET-1 as the radiolabelled ligand and the receptor-selective ligands. ET-1, ET-3, BQ-123, sarafatoxin-6-c and [Ala1,3,11,15]ET-1. The results suggested the presence of conventional ETA and ETB receptor subtypes, with ETA in excess over ETB. These findings were consistent with the results of Northern analysis in that mRNAs encoding the ETA and ETB receptor subtypes were identified in NG108-15 cells, with a preponderance of ETA to ETB. Of considerable interest was the observation of other ET-binding components with much higher affinities than the conventional receptors. It remains to be demonstrated if these particular binding components are functional and represent differ gene products or arise from association of the conventional ETA and ETB receptor subtypes with themselves or other structures, e.g. proteins or lipids, of CNS origin.

Animals↗
PubMed1995

Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.

BACKGROUND: The prevalence of hypertension and its cardiovascular complications is higher in African Americans than in whites. Interventions to control blood pressure in this population are particularly important. Regular exercise lowers blood pressure in patients with mild-to-moderate hypertension, but its effects in patients with severe hypertension have not been studied. We examined the effects of moderately intense exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension. METHODS: We randomly assigned 46 men 35 to 76 years of age to exercise plus antihypertensive medication (23 men) or antihypertensive medication alone (23 men). A total of 18 men in the exercise group completed 16 weeks of exercise, and 14 completed 32 weeks of exercise, which was performed three times per week at 60 to 80 percent of the maximal heart rate. RESULTS: After 16 weeks, mean (+/- SD) diastolic blood pressure had decreased from 88 +/- 7 to 83 +/- 8 mm Hg in the patients who exercised, whereas it had increased slightly, from 88 +/- 6 to 90 +/- 7 mm Hg, in those who did not exercise (P = 0.002). Diastolic blood pressure remained significantly lower after 32 weeks of exercise, even with substantial reductions in the dose of antihypertensive medication. In addition, the thickness of the interventricular septum (P = 0.03), the left ventricular mass (P = 0.02), and the mass index (P = 0.04) had decreased significantly after 16 weeks in the patients who exercised, whereas there was no significant change in the nonexercisers. CONCLUSIONS: Regular exercise reduced blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.

Adult↗
PubMed1995

Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men. A dose-response relationship.

OBJECTIVE: To examine the association between miles run per week and high-density lipoprotein cholesterol levels in healthy middle-aged men. BACKGROUND: Regular exercise increases levels of high-density lipoprotein cholesterol. However, the exercise requirements for such increases are not well defined. METHODS: Healthy, nonsmoking men (n = 2906; age, 43 +/- 4 years) completed a questionnaire on health habits and physical activities and a symptom-limited exercise test. They were then stratified on the basis of the number of miles run per week. Six groups, with mileages of 0, 5, 9, 12, 17, and 31 per week, were established. RESULTS: A gradual increase in high-density lipoprotein cholesterol level was observed with increased miles (0.008-mmol/L [0.308-mg/dL] increase in high-density lipoprotein cholesterol level per mile). Most of the changes were associated with distances of 7 to 14 miles per week. Levels of low-density lipoprotein cholesterol, triglycerides, and the ratio of total cholesterol to high-density lipoprotein cholesterol also improved with weekly mileage. The high-density lipoprotein cholesterol level correlated significantly with all exercise components, anthropometric measures, and alcohol consumption. Group comparisons disclosed significant differences (P < .05) in exercise time to exhaustion, miles run per week, body fat, body weight, and body mass index. Age and alcohol consumption were similar across groups. CONCLUSIONS: These results indicate a dose-response relationship between miles run per week, high-density lipoprotein cholesterol level, and other lipoprotein-lipid levels. Most changes were noted in those who ran 7 to 14 miles per week at mild to moderate intensities. A mile-age threshold for changes in high-density lipoprotein cholesterol level was not observed. However, when compared with those of the nonexercising group, high-density lipoprotein cholesterol levels attained statistical significance at 7 or more miles per week.

Cholesterol, HDL↗
PubMed1995

Transurethral Nd:YAG laser prostatectomy with a laterally firing fiber: local effects on tissue associated with erectile dysfunction.

BACKGROUND AND OBJECTIVES: Transurethral laser prostatectomy is anticipated to become a recognized alternative to conventional transurethral resection of the prostate. However, the effects of this procedure on the nerves of the pelvic plexus and erectile dysfunction remain unaddressed. The objective of this study was to evaluate the effects of laser energy on extent of prostatic damage as well as injury to periprostatic cavernosal nerves and erectile dysfunction in a canine model. STUDY DESIGN/MATERIALS AND METHODS: Six adult male mongrel dogs underwent transurethral laser prostatectomy at 30 (n = 3) and 40 (n = 3) watt power settings. Total laser energy delivered varied between 6,000 and 13,800 joules. Erectile function was evaluated by pelvic nerve stimulation at 2, 4, and 8 weeks. Animals were then sacrificed to assess histopathology of the prostate at each time point. RESULTS: Histopathologic changes were noted in the prostate in a dose-dependent manner and did not vary with different laser power settings. In dogs that received approximately 10,000 J, substantial prostate ablation confined within the capsule was achieved in every prostate gland. Adequate erectile responses were noted in five of six animals; all received < 10,000 J. In one animal that received a total dose of 13,800 J, an erectile response was not obtained, and histology revealed both prostatic capsule perforation in close proximity to the cavernous nerves and thermal neural damage. CONCLUSIONS: We conclude that cavernous nerve damage may result from excessive doses of laser energy during transurethral laser treatment of the prostate gland. In canines, the upper limit for periprostatic injury is between 10 and 14,000 joules.

Aluminum Silicates↗
PubMed1995

Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1.

This report describes the development and characterization of an epithelial cell line (BPH-1) from human prostate tissue obtained by transurethral resection. Primary epithelial cell cultures were immortalized with SV40 large T antigen. One of the isolated clones was designated BPH-1. These cells have a cobblestone appearance in monolayer culture and are non-tumorigenic in nude mice following subcutaneous injection or subrenal capsule grafting. They express the SV40 large T antigen and exhibit increased levels of p53, as determined by immunocytochemistry. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 76 (range 71 to 79, n = 28) and 6 to 8 marker chromosomes. Some structurally rearranged chromosomes were observed, but the Y chromosome was normal. The expressed cytokeratin profile was consistent with a prostatic luminal epithelial cell. This profile was the same as that of primary prostatic epithelial cultures from which the BPH-1 cells were derived. In serum-free culture in plastic dishes epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, fibroblast growth factor (FGF) 1 (aFGF), and FGF 7 (KGF) induced increased proliferation in these cells whereas FGF 2 (bFGF), TGF-beta 1, and TGF-beta 2 inhibited proliferative activity. Testosterone had no direct effect on the proliferative rate of BPH-1 cells. 5 alpha-Reductase, 3 alpha-hydroxysteroid oxidoreductase, and 17 beta-hydroxy-steroid oxidoreductase activities were detected in BPH-1 cells. Expression of androgen receptors and the secretory markers, prostate specific antigen and prostatic acid phosphatase, were not detectable by immunocytochemistry, biochemical assay, or RT-PCR analysis.

Aged↗
PubMed1995

Transition zone volume and transition zone ratio: predictor of uroflow response to finasteride therapy in benign prostatic hyperplasia patients.

OBJECTIVES: The aim of this study was to: (1) determine effects of finasteride on transition zone (TZ) volume, TZ ratio (TZ volume/total prostate volume), and total prostate volume; (2) analyze differences in TZ and total volume reduction among patients who improve peak urinary flow rates following finasteride therapy with those who do not; (3) investigate which parameters correlate with improvement in peak urinary flow rate and urinary symptom score; and (4) establish if there is any predictive value of these parameters for response to therapy. METHODS: Twenty-three patients with symptomatic benign prostatic hyperplasia (BPH) were treated with finasteride (5 mg/d) for 12 months and underwent transrectal ultrasound (TRUS) evaluation of total and TZ volume of prostate and measurement of peak flow rate and modified Boyarsky symptom score at baseline and at 12 months. Statistical analysis was done by unpaired t, Mann-Whitney, and Spearman rank correlation tests among responders (more than 3 cc/s improvement in peak flow rate) and nonresponders (less than 3 cc/s improvement in peak flow rate) to therapy. RESULTS: (1) Responders had substantial reduction in TZ volume (44.8% versus 16.05%; P < 0.03) and TZ ratio (25% versus 5% increase, P < 0.02) compared with nonresponders. (2) There was a significant correlation between reduction in TZ volume (r = 0.50; P < 0.03) and TZ ratio (r = 0.60; P < 0.006) with improvement in peak flow rates. No similar correlation was seen with total prostate volume changes. (3) Pretreatment TZ ratio helped in predicting peak flow improvement following finasteride therapy (r = 0.52; P < 0.01) and there was a 2.5-fold increased chance of improvement if baseline TZ ratio was more than 0.51. The modified Boyarsky symptom score decreased by 3.1 (mean), but there was no correlation with changes in peak urinary flow rate, total prostate volume, TZ volume, and TZ ratio. TZ ratio did not have significant predictive value for improvement in symptom score. CONCLUSIONS: This study provides data that simple measurable parameters are available which may be used prior to therapy to predict uroflow response to finasteride and similar agents.

Double-Blind Method↗
PubMed1995

Cardiorespiratory fitness and coronary heart disease risk factor association in women.

OBJECTIVES: The purpose of this study was to examine the association between cardiorespiratory fitness and coronary risk factors in healthy, nonsmoking adult women. BACKGROUND: A sedentary life-style is recognized as an independent risk factor for coronary heart disease, and increasing physical activity is strongly recommended to reduce this risk. However, studies examining the effects of increased physical activity on coronary heart disease risk factors in women are relatively few, and the findings have been equivocal. METHODS: Subjects provided written informed consent, completed a questionnaire on medical history and performed an exercise tolerance test. Blood chemistry and lipid levels were determined from fasting blood samples. Three fitness categories were established on the basis of treadmill time to exhaustion and were adjusted for age. RESULTS: The women in the lowest fitness category had less favorable lipid profiles, blood glucose levels, blood pressures and anthropometric indexes than those in the moderate and high fitness categories. CONCLUSIONS: Moderate fitness (equivalent to 10 metabolic equivalents [METs]) is required to improve the coronary risk profile in women.

Adult↗
PubMed1995

Mechanical alternans and the force-frequency relationship in failing rat hearts.

We examined contractile performance in perfused ventricles from normal rats and from SHHF/Mccfacp rats with end-stage heart failure. Changes in pacing frequency from 3 to 5 Hz evoked a complex response in normal rat myocardium. The first beat after a switch to 5 Hz was extremely weak, but each successive beat was stronger until force exceeded the 3 Hz steady state value by approximately 30%. Force then gradually declined to a new steady state where developed pressure was depressed but rate-pressure product was slightly greater than that at 3 Hz. By contrast, in failing SHHF/Mcc-facp hearts, an increase in pacing frequency from 3 to 5 Hz did not increase force development. Instead, the isovolumic left ventricles exhibited mechanical alternans. This alternation between weak and strong beats was abolished by 1 mM caffeine but restored by its washout. Inhibition of SR Ca2+ accumulation by 50-500 nM thapsigargin in normal ventricles did not evoke alternans when pacing frequencies were increased. The results indicate that mechanical alternans in failing rat hearts is due to altered reactions of the sarcoplasmic reticulum, but a decreased rate of Ca2+ accumulation is not the primary cause.

Animals↗
PubMed1995

Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy.

OBJECTIVES: This study was designed to determine whether citrate levels detected by localized 1H spectroscopy could reliably discriminate regions of prostate adenocarcinoma from surrounding regions of normal peripheral zone and benign prostatic hyperplasia (BPH). METHODS: In 28 patients and 5 volunteers stimulated echo proton spectroscopy was used in conjunction with endorectal surface coils to obtain water-suppressed 1H spectra from regions of normal prostate peripheral zone, BPH, and prostate cancer. 1H spectra from prostate cancer patients were correlated with pathologic areas identified on T2-weighted endorectal coil magnetic resonance (MR) images and histologic study of the step-sectioned gland after surgery. RESULTS: The major finding of in vivo studies was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate peripheral zone. This was reflected by significantly (P < 0.05) lower mean citrate/(creatine plus choline) peak area ratio observed for regions of cancer (0.67 +/- 0.17) compared with BPH (1.21 +/- 0.29) and normal peripheral zone (1.46 +/- 0.28). Moreover, there was no overlap of individual cancer and normal peripheral zone citrate ratios and no significant difference between citrate ratios in regions of normal peripheral zone in young volunteers (1.28 +/- 0.14) and age-matched patients (1.46 +/- 0.28). The observed alterations in vivo citrate levels were supported by citrate concentration data obtained from extracts of histologically proven samples of normal, benign, and malignant prostatic tissues removed at surgery. In vitro citrate levels in the normal peripheral zone (30.9 +/- 8.5 mumol/g wet weight) and BPH (46.3 +/- 5.4 mumol/g wet weight) were significantly higher than those for prostate cancer (3.74 +/- 0.54 mumol/g wet weight). CONCLUSIONS: These studies further demonstrate the potential of citrate as an in vivo marker for discriminating prostate cancer from surrounding regions of normal peripheral zone and BPH.

Adenocarcinoma↗
PubMed1995

Impact of prostate size on the outcome of transurethral laser evaporation of the prostate for benign prostatic hyperplasia.

OBJECTIVES: The aim of this study was to evaluate efficacy and safety of transurethral evaporation of the prostate (TUEP) using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in prostate glands of various sizes. METHODS: One hundred consecutive patients with benign prostatic hyperplasia (BPH) and prostate volumes less than 40 cc (group I, n = 41), 41 to 80 cc (group II, n = 39), and more than 80 cc (group III, n = 20), who had preoperative prostate volume estimation by transrectal ultrasound and had completed a minimum of 3 months' follow-up, underwent TUEP. At baseline, and at 3 and 6 months, American Urological Association (AUA) score, peak flow rate (PFR), postvoid residual urine (PVR), and complications, if any, were documented. RESULTS: There were no significant differences in failure rates, complications, or ability to improve symptom score, PFR, and PVR between patients with prostate glands of various sizes. The mean improvement in PFR at 6 months was: group I, 9.9 cc/s (116%); group II, 7.4 cc/s (81%); and group III, 9.2 cc/s (107%). Reduction in AUA score was: group I, 14.6 (63%); group II, 17.7 (71%); and group III, 16.2 (70%). PVR was: group I, 62.5 cc (51%); group II, 31.4 cc (16%), and group III, 71 cc (83%) (differences not significant). The patients in urinary retention were separately analyzed (group I, 9, group II, 12, and group III, 5) and mean PFR at 6 months was: group I, 18.5 cc/s, group II, 15 cc/s, and group III, 17.1 cc/s. Mean AUA score at 6 months was: group I, 25.8; group II, 21; and group III, 23.6. Mean PVR score was: group I, 370 cc, group II, 439 cc; and group III, 400 cc (differences not significant). Mean postoperative catheterization time was higher in patients with glands larger than 80 cc (2.2 versus 2.9 versus 4.7 days in groups I, II, and III, respectively, P < 0.009 between groups II and III). Incidence of urinary tract infection (10 versus 0%) was greater in patients receiving only 48-hour as opposed to 10-day postoperative antibiotics. CONCLUSIONS: TUEP appears to be a safe and effective treatment for relief of symptoms of BPH and improvement of PFR in patients with all sizes of prostate glands.

Aged↗