Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 73 records · Page 4Linked to original sources

PubMed1998

An open study on the efficacy and safety of transurethral needle ablation of the prostate in treating symptomatic benign prostatic hyperplasia: the University of Florida experience.

PURPOSE: We determine the safety and efficacy of transurethral needle ablation of the prostate in patients with moderate to severe symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: Transurethral needle ablation of the prostate was performed on 45 consecutive patients. For an average prostate of 2.5 to 3 cm. long treatments were performed in 2 separate planes at 4 quadrants (2, 4, 8 and 10 o'clock positions) each. The 2 planes were 1 cm. below the bladder neck and 1 cm. proximal to the verumontanum. For prostatic urethral lengths longer than 3 cm. a treatment plane was added for each additional centimeter of prostatic urethra. The procedure was performed in 26 patients under local anesthesia using 20 cc 2% intraurethral lidocaine gel (11) or supplemented with intravenous 1.25 to 5 mg. midozolam (15). Of these patients 2 had a supplemental perineal block using a mixture of equal amounts of 15 cc 2% lidocaine without epinephrine and 0.25% bripivacaine, 10 underwent the procedure under general anesthesia, 2 had epidural and 4 had spinal anesthesia, and 3 had managed anesthesia care. Mean length of each procedure was 79 minutes (range 50 to 240). All procedures were done on an outpatient basis and patients were released on the same operative day. RESULTS: Mean prostatic volume on transrectal ultrasound was estimated at 48.1 cc (range 20 to 185). Following treatment the International Prostate Symptom Score decreased from a mean of 20.9 at baseline to 15.4 at 1 month, 16.1 at 3 months, 10.7 at 6 months and 9.9 at 1 year. The peak flow rate improved from a baseline mean of 8.3 to 13.4 at 3 months, 13.1 at 6 months and 14.9 at 1 year. The quality of life score improved from a baseline of 4.8 to 3.5, 2.2, 2.5 and 1.03 at 1, 3, 6 and 12 months, respectively. Of the 2 patients in whom the procedure failed; 1 required a bladder neck incision at 3 months and the other transurethral resection of the prostate. Foley catheters were left in place in all patients for an average of 4.85 days. CONCLUSIONS: After a followup of up to 12 months we conclude that transurethral needle ablation of the prostate is an effective treatment for symptomatic benign prostatic hyperplasia. This procedure has minimal morbidity, is less costly than conventional transurethral resection of the prostate and can be performed as an outpatient office procedure under local anesthesia in a significant number of patients.

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PubMed1998

A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group.

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.

Adrenergic alpha-Antagonists↗

PubMed1998

Tamsulosin: the United States trials.

Overall, tamsulosin has several advantages. Its long-acting action allows for once-daily dosing. The therapeutic effect, as indicated by > 30% increase in peak urinary flow rate, is realized in more than 50% of the patients receiving the therapy. The beneficial effect from treatment is seen as early as 2 to 3 weeks after the maximum dose is reached. In addition, the dose may be adjusted from 0.4 mg daily to 0.8 mg daily to obtain the desired decrease in urinary tract obstructive symptoms, although the vast majority of patients are effectively treated with 0.4 mg daily. Also, there is no known effect of alpha 1-adrenergic antagonists on the serum PSA concentration. The incidence of untoward cardiovascular system effects is less important because of tamsulosin's uroselective action. As with any other medical therapy for BPH, tamsulosin must be taken indefinitely to maintain the therapeutic effect.

Adrenergic alpha-Antagonists↗

PubMed1997

Effect of retinoic acid on prostatic development.

BACKGROUND AND METHODS: To assess the effect of retinoids on prostatic ductal branching morphogenesis, anterior prostates from newborn rats were cultured under serum-free conditions for 6 days in the presence of testosterone (10(-8) mM) plus 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (at-RA), or N-4-hydroxyphenyl-retinamide (4-HPR). Measures of morphologic complexity were computed and compared between specimens of different treatment groups. RESULTS: Prostatic ductal growth and branching were inhibited in a dose-dependent fashion by both 13-cis-RA and at-RA, but not by 4-HPR. This inhibitory effect of 13-cis-RA was reversible, as the prostatic ducts resumed branching and growth after removal of retinoic acid from the culture medium. Using reverse transcription polymerase chain reaction, we then investigated the expression of nuclear receptor genes for retinoic acid. CONCLUSIONS: This showed the presence of RAR-beta and RAR-gamma in the 0-day prostate, suggesting that the effects of these retinoids on ductal morphogenesis may be via these receptors.

Animals↗

PubMed1997

Effects of aerobic training on exaggerated blood pressure response to exercise in African-Americans with severe systemic hypertension treated with indapamide +/- verapamil +/- enalapril.

Hypertensive patients are likely to have an exaggerated blood pressure (BP) response during physical exertion. When moderate aerobic exercise was added to medical antihypertensive therapy in patients with severe hypertension, excessive elevations in BP during physical exertion were attenuated even with a modest reduction in BP at rest.

Adult↗

PubMed1997

Identification of endothelin receptor subtypes in sheep choroid plexus.

Endothelin (ET) and its G-protein-coupled receptors are distributed in a wide variety of tissues, including the brain. In this study, we have identified and characterized the endothelin receptor subtypes in sheep choroid plexus. Competitive binding experiments using [125I]ET-1 and the receptor subtype-selective ligands, ET-1, ET-3, BQ-123, Sarafotoxin 6c, and [Ala1,3,11,15] ET-1 demonstrated the presence of both ETA and ETB receptor subtypes in the ratio of 30:70. In addition, a small fraction of the total binding sites exhibited affinities for ET-1 in the subpicomolar range. Chemical crosslinking of [125I]ET-1 with bis(sulfosuccinimidyl)-suberate (BS3) to choroid plexus membranes revealed the presence of two bands, with apparent molecular masses of 89 and 45 kDa, corresponding to the ETA receptor, and three bands, with apparent molecular masses of 75, 58, and 33 kDa, corresponding to the ETB receptor. Of considerable interest was the finding that dimers of the [125I]ET-1-occupied ETA receptor could be identified by crosslinking, as could apparent dimers and tetramers of [125I]ET-1, but only when bound to receptor. In addition to mapping the distribution of ET receptors in sheep choroid plexus, our results strongly suggest that ET-1 binding to the ETA receptor leads to dimer formation.

Animals↗

PubMed1997

Transurethral evaporation of the prostate for treatment of benign prostatic hyperplasia: results in 168 patients with up to 12 months of followup.

PURPOSE: We assessed the safety and efficacy of transurethral evaporation of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 168 patients with symptomatic BPH underwent transurethral evaporation of the prostate. Peak flow rate, American Urological Association symptom index and post-void residual were assessed at baseline, and at 3, 6 and 12 months of followup. RESULTS: We found a statistically significant decrease in mean American Urological Association symptom index from 20.6 at baseline to 7.2 at 12 months (mean difference 13.4, 65% reduction, p < 0.0001). We also found a statistically significant improvement in mean peak flow rate from 8.2 to 18.2 cc per second, respectively (mean difference 10, 122% increase, p < 0.0001). The most frequent complications were irritative voiding symptoms in 22.6% of patients and urinary tract infections in 4.8%. There were no additional major complications. CONCLUSIONS: From these results transurethral evaporation of the prostate appears to be safe and effective for treatment of BPH at 12 months of followup.

Aged↗

PubMed1997

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group.

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.

Antihypertensive Agents↗

PubMed1996

hCG-receptor binding and transmembrane signaling.

The technique of site-directed mutagenesis has proven to be quite powerful in elucidating contact sites involved in the interaction of the heterodimeric glycoprotein hormones and their respective seven transmembrane (TM) G protein-coupled receptors. Our laboratory has focused on identification of the minimum core sequences of the alpha and beta subunits required for bioactivity, the minimum length of a conjoined (yoked) single-chain hCG, the amino acid residues on hCG and the LH/CG-receptor (LH/CG-R) responsible for high-affinity binding, and the regions of the receptor that are involved in TM signaling. A number of amino acid residues have been mapped on the alpha and beta subunits of hCG that appear important in receptor binding. When projected onto the crystal structure of HF-treated hCG, these residues, by and large, cluster on one side of the molecule and cover a sizeable surface area, indicating that the hormone-receptor binding interface is rather extensive. Based on mutagenesis studies of several conserved ionizable amino acid residues in the extracellular domain (ECD) of LH/CG-R and a model that we, in collaboration with Drs Lapthorn and Isaacs, have developed for this region based on the crystal structure of porcine ribonuclease inhibitor, a charged region that appears to play an important role in hormone-receptor recognition has been identified. We have also delineated several regions of LH/CG-R that do not appear to participate in hCG binding but are involved in hCG-mediated signaling. These regions are located in the ECD and extracellular loop III just prior to entry into the membrane via TM helices I and VII, respectively, and in TM helices VI and VII. Similarly, a homologous region in the ECD of the FSH receptor, located with ten residues of TM helix I, is important in signaling but not hormone binding. These results suggest that ligand binding and ligand-mediated receptor activation are quasi-distinct, albeit sequential phenomena. Collectively, our mutagenesis and modeling studies, coupled with results from other laboratories, argue for a ligand-induced conformational change of the receptor that may involve a relative reorientation of the TM helices.

Amino Acid Sequence↗

PubMed1996

Protein engineering of a novel constitutively active hormone-receptor complex.

Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone consisting of an alpha and a beta subunit that stimulates intracellular levels of cAMP via a G protein-coupled receptor. Herein we report the engineering and characterization of a novel molecule in which the receptor and its heterodimeric ligand were covalently linked in a single polypeptide chain. The hormone-receptor complex was expressed in cells transfected with this construct, but the cells were unable to bind significant amounts of exogenous hCG. However, cleavage of the hormone with a site-specific protease rendered the receptor accessible to exogenously added hormone. Cells transfected with the hCG-receptor construct contained elevated basal levels of cAMP; moreover, addition of hormone had no significant effect. These results are consistent with a strong and stable interaction between the single-chain hormone and its covalently linked receptor that results in a constitutively active complex.

Animals↗

PubMed1996

Effect of hydrochlorothiazide therapy on cardiac arrhythmias in African-American men with systemic hypertension and moderate to severe left ventricular hypertrophy.

The effect of hydrochlorothiazide therapy on ventricular arrhythmias was studied in 45 hypertensive African-American men with moderate to severe left ventricular (LV) hypertrophy. After medication washout, patients were treated with placebo followed by hydrochlorothiazide. Clinical, biochemical, and 48-hour ambulatory electrocardiographic data was collected after each treatment phase. Signal-averaged electrocardiograms were recorded in a subgroup of 24 patients. Average LV posterior wall thickness was 15 +/- 1.1 mm, septum 16 +/- 2 mm, LV mass 420 +/- 90 g, and LV mass index 212 = 51 g/m2. Systolic blood pressure (BP) was 168 +/- 18 mm Hg after the placebo phase and 146 +/- 15 mm Hg after hydrochlorothiazide; diastolic BP was 103 +/- 6 mm Hg and 89 +/- 9 mm Hg, respectively. Serum potassium decreased significantly from 4.2 +/- 0.4 mmol/L to 3.7 +/- 0.6 mmol/L after hydrochlorothiazide therapy. The average hourly incidence of ventricular premature contractions was 22 with placebo and 25 with hydrochlorothiazide. There were 3 and 1 couplets and 0.2 and 0.2 runs of ventricular tachycardia per patient per hour, respectively. Variables of signal-averaged electrocardiography did not differ between the 2 treatments. Thus, in hypertensive African-American men with moderate to severe LV hypertrophy, hydrochlorothiazide does not worsen ventricular arrhythmias or signal-averaged electrocardiographic variables.

Black or African American↗

PubMed1996

The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.

Adrenergic alpha-Antagonists↗

PubMed1996

Identification of conventional and novel endothelin receptors in sheep choroid plexus cells.

Previous studies have demonstrated the presence of super-high affinity endothelin receptors with apparent Kd's on the order of pM in different brain tissues. This study was designed to characterize, in detail, the receptors present in SCP cells, a non-transformed sheep choroid plexus cell line. Competitive binding assays with receptor-selective ligands indicated the presence of at least three classes of binding sites: a conventional receptor of the ETA subtype with a Kd = 0.4 nM that mediates an increase in intracellular levels of inositol 1,4,5-trisphosphate (IP3)in response to ET-1 and two additional sites with much higher binding affinities. The latter two sites are not coupled to the common signal transduction pathways of IP3, cAMP and cGMP. Northern blot analysis confirmed the presence of only the ETA subtype mRNA in SCP cells. It remains to determined if the multiple binding sites are distinct gene products, multiple affinity states of a single receptor molecule or a result of cooperative association of one site with either the ligand or with other proteins.

Animals↗

PubMed1996

Expression of functional lutropin/choriogonadotropin receptor in the baculovirus system.

The LH/CG receptor (LH/CG-R) is a G protein-coupled receptor with a relatively large glycosylated extracellular domain. The complete 674 amino acid residue rat receptor was expressed in Sf9 insect cells using the baculovirus expression system. Optimal expression under the control of the polyhedrin promoter was obtained at 72 h post-infection and a multiplicity of infection of 0.1. The recombinant LH/CG-R was expressed on the cell surface (ca. 4500 receptors/cell) and exhibited saturable, high affinity binding of human CG (hCG) with a Kd of 0.4 nM. There was no evidence of intracellular trapping of the receptor. The intracellular concentration of cAMP was increased in response to hCG binding. In contrast, baculovirus-expressed recombinant hCG only weakly stimulated intracellular cAMP levels at relatively high doses. Two forms of the receptor (approximately 75 and approximately 200 kDa) were detected by Western blot analysis. These results demonstrate that the full length LH/CG-R expressed in insect cells is functional in that it binds hormone with high affinity and is able to couple to adenylate cylase.

Adenylyl Cyclases↗

PubMed1996

Nd:YAG laser transurethral evaporation of the prostate (TUEP) for urinary retention.

BACKGROUND AND OBJECTIVE: Little information is available regarding the effectiveness of laser prostatectomy in patients with urinary retention from benign prostatic hyperplasia since there is no paper specifically dealing with laser prostatectomy in patients in urinary retention. STUDY DESIGN/MATERIALS AND METHODS: Twenty two unselected consecutive patients presenting with urinary retention due to benign prostatic hypertrophy underwent transurethral evaporation of the prostate (TUEP) using a neodymium:YAG laser and total internally reflecting side-firing free beam quartz fiber. All patients failed at least one voiding trial and averaged > 30 days of urinary catheter drainage preoperatively. A contact evaporation technique was used to evaporate a "TURP-like" channel in the prostatic fossa by means of a series of parallel evaporation troughs. RESULTS: Eighteen of 22 patients completed 6 months of follow up. Two patients were lost to follow up and two failed TUEP. The average AUA score dropped from 26 to 9 at 1 month and to 3.4 by 6 months postoperatively. All patients who successfully underwent TUEP were urinating spontaneously by 10 days. Average time to catheter removal was 3.5 days. Maximal uroflow was 15.7 ml/sec at 1 month and 20.3 ml/sec by 6 months. Postvoid residual preoperatively averaged 784 ml and decreased to 76 ml by 1 month. Pre- and postoperative hematocrit and serum sodium values did not vary by more than 5%. CONCLUSION: From this preliminary series we conclude that aggressive evaporation of prostatic tissue is feasible endoscopically and provides a reliable method of near bloodless removal of tissue.

Aged↗

PubMed1996

Comparison of transrectal ultrasound prostatic volume estimation with magnetic resonance imaging volume estimation and surgical specimen weight in patients with benign prostatic hyperplasia.

There are relatively few reports in the literature comparing transrectal ultrasound (TRUS) to magnetic resonance imaging (MRI) in estimating the volume of the prostate in the management of benign prostatic hyperplasia (BPH). In this study, we compared volumes determined by TRUS with MRI and TRUS-estimated weights with surgical specimen weights. The main findings of this study were (a) TRUS and MRI measurement of prostate volumes are quite similar; and (b) TRUS underestimates (by 10%) the prostatic weight as determined from the surgical specimens. A better volume estimate can thus be obtained by multiplying the TRUS measurement by a factor of 1.10. We conclude that because TRUS is cheap, user-friendly, noninvasive, and equally as accurate as MRI, it should be the preferred modality in the follow-up of BPH patients.

Humans↗

PubMed1996

Factors affecting size and configuration of electrovaporization lesions in the prostate.

OBJECTIVES: Transurethral electrovaporization of the prostate is a new, minimally invasive technique being used by urologists for surgical ablation of prostatic tissue. There are insufficient data concerning factors affecting the vaporization and coagulation lesions produced by this technique. The aim of this study was to determine the role of various parameters for adequate tissue evaporation. METHODS: This study compared bovine liver and human prostatic lesions made by the Vaportrode instrument with those produced by standard electrocautery loops, roller balls, and laser fibers. Additionally, two electrosurgical instruments with differing technical capabilities were compared for their ability to cause vaporization of tissue. RESULTS: Results revealed that the Vaportrode lesions were maximal with a new electrode when used with a Force 40S electrosurgical generator set at 300 W and a drag speed of 25 to 30 seconds per 10 mm of tissue. The lesions produced by this technique had a 74% greater coagulation volume compared to a standard cautery loop. The evaporation defect was comparable to a laser lesion produced in contact at 60 W. CONCLUSIONS: We conclude that electrovaporization under optimal conditions causes a vaporization lesion comparable to that produced by high power density laser prostatectomy. Additionally, the coagulation volume of a vaportrode lesion is considerably greater than that produced by standard electrocautery resection.

Animals↗

PubMed1996

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study.

OBJECTIVES: The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS: Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS: Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS: Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.

Aged↗