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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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