PubMed Health⌕ Search

Biomedical subjects

C A Olsson

Publications and source records attributed to C A Olsson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Development of a hammerhead ribozyme against bcl-2. I. Preliminary evaluation of a potential gene therapeutic agent for hormone-refractory human prostate cancer.

BACKGROUND: The bcl-2 oncoprotein suppresses apoptosis and, when overexpressed in prostate cancer cells, makes these cells resistant to a variety of therapeutic agents, including hormonal ablation. Therefore, bcl-2 provides a strategic target for the development of gene knockout therapies to treat human prostate cancers. Towards this end, we have synthesized an anti-bcl-2 gene therapeutic reagent based on ribozyme technology and have tested its effectiveness against bcl-2 mRNA in vitro and in vivo. METHODS: A divalent hammerhead ribozyme was constructed by recombining two catalytic RNA domains into an antisense segment of the coding region for human bcl-2 mRNA. A disabled ribozyme lacking catalytic activity was also constructed as a control reagent for our experiments. The ribozymes were tested for endonucleolytic activity against synthetic and natural bcl-2 mRNAs. Simple transfection procedures were then utilized to introduce the ribozymes into cultured prostate cancer cells (LNCaP derivatives). We measured the effects of the ribozymes on endogenous expression of bcl-2 mRNA and protein in these cells as well as their ability to induce apoptosis. RESULTS: The functional but not the disabled ribozyme was able to rapidly degrade bcl-2 mRNA in vitro, without the requirement for any other cellular protein or factor. When directly transfected into LNCaP cell variants, it significantly reduced bcl-2 mRNA and protein levels within 18 hr of treatment. This activity was sufficient to induce apoptosis in a low-bcl-2-expressing variant of LNCaP, but not in a high-bcl-2-expressing LNCaP line. For the high-bcl-2-expressing variant, however, it did restore the ability to genetically respond to a secondary apoptotic agent, phorbol ester, as evidenced by the renewed ability of phorbol ester to induce NGF1A mRNA in these cells. CONCLUSIONS: This study supports the potential utility of an anti-bcl-2 ribozyme reagent for reducing or eliminating bcl-2 expression from hormone-refractory prostate cancer cells and for killing prostate cancer cells. As such, it is the first step toward an effective gene therapy against hormone-refractory human prostate cancers.

Base Sequence↗
PubMed1997

Abnormal prostate development in C3(1)-bcl-2 transgenic mice.

BACKGROUND: Recent hypotheses to explain the etiology of abnormal growth associated with prostate disease have invoked perturbations in the rate of apoptosis as an important contributor to the onset and progression of these diseases. For this reason, the apoptosis suppressing oncoprotein bcl-2 has come under scrutiny with regards to its role in prostate diseases. In order to evaluate the role of bcl-2 in human prostate disease and to develop an animal model to test anti-bcl-2 therapies, we generated transgenic mice in which bcl-2 expression is targeted to the mouse prostate gland. METHODS: Mouse embryos were microinjected with recombinant DNA constructed by fusing a modified rat C3(1) promotor element to cDNA encoding human bcl-2. Presence of the C3(1)-bcl-2 transgene in progeny was identified by Southern blot and polymerase chain reaction (PCR) analysis. RNase protection assays were used to analyze RNA from 15 organs of these mice. Western blot assays and immunohistochemical staining were used to confirm the tissue-specific protein expression of human bcl-2 and its cellular localization. RESULTS: Three lines of C3(1)-bcl-2 transgenic mice were established. Founder mice carried 2-20 copies of the transgene. Expression of human bcl-2 from the transgene was limited to the prostate gland and testis of males as well as the uterus of females. In the prostate gland, human bcl-2 protein was found only in prostatic epithelial cells. Microscopic analysis of prostate glands from individual males (three lines) showed that these glands were often abnormal, with increased accumulation of cells in the prostatic stroma as well as the epithelium. CONCLUSIONS: These transgenic mice appear to provide a novel animal model for studying neoplastic development of the prostate, with particular emphasis on the bcl-2 protein and the role of apoptosis regulation in such development.

Animals↗
PubMed1997

Expression of the tumor-associated gene MN: a potential biomarker for human renal cell carcinoma.

MN is a novel cell surface antigen originally detected in human HeLa cells. Although it is also expressed in normal gastric mucosa, this antigen was previously found to be expressed in cells with a malignant phenotype in certain tissues of the female genital tract (cervix and ovary). Using an oligonucleotide primer set specific for MN-complimentary DNA, we performed reverse transcription-PCR assays on RNAs extracted from human cell lines and tissues to evaluate whether this marker might be expressed at other sites. RNA libraries extracted from normal human heart, lung, kidney, prostate, peripheral blood, brain, placenta, and muscle were negative for MN expression. RNAs extracted from liver and pancreatic tissue were positive for MN expression. Three of six renal cancer cell lines tested revealed MN expression. In addition, 12 of 17 samples of human renal cell carcinoma tissue tested positive for MN, all 12 of which were clear cell adenocarcinomas. This survey identified a unique association of MN expression with renal cell cancers, especially those of the clear cell variety, suggesting that MN is a potential marker for the diagnosis, staging, and therapeutic monitoring of renal cell carcinoma in humans.

Antigens, Neoplasm↗
PubMed1997

Pretreatment prostate specific antigen doubling times: use in patients before radical prostatectomy.

PURPOSE: We determined whether pre-radical prostatectomy prostate specific antigen (PSA) doubling time could predict pathological stage at radical prostatectomy or PSA failure postoperatively. We also sought to compare PSA doubling times from men with prostate cancer treated with radical prostatectomy to a group treated with radiation therapy. MATERIALS AND METHODS: Detailed followup was available for 150 patients with clinically localized prostate cancer who underwent radical prostatectomy from January 1993 to August 1995. PSA doubling time was calculated for all patients with 3 or more pre-radical prostatectomy PSA levels using linear regression. We assessed the association between PSA doubling time and PSA failure, pathologic stage at radical prostatectomy, final PSA before treatment and Gleason score. We compared our PSA doubling time values and distribution to a published series of patients with prostate cancer who had undergone radiation therapy. RESULTS: A total of 56 patients had 3 or more PSA values before treatment. Median followup was 17.3 months. PSA doubling time did not correlate with PSA failure, final PSA or Gleason score, but it did with pathological stage at radical prostatectomy (p = 0.0035 for positive margins, p = 0.025 for positive seminal vesicles). Our PSA doubling time and PSA failure rates did not differ from the radiation therapy population with similar followup times. CONCLUSIONS: Although studies from the radiation literature have shown PSA doubling time to be useful in predicting PSA failure after treatment for prostate cancer, our results do not confirm this finding. We did find a correlation with pathologic stage at radical prostatectomy, and so longer followup with more patients may confirm this in the future. We also found no significant differences in PSA doubling time between our patients and a group treated with radiation. At least for this parameter, patients with prostate cancer referred for radical prostatectomy and radiation therapy may be similar.

Aged↗
PubMed1997

Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction.

OBJECTIVES: Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied. METHODS: Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 micrograms of subcutaneous recombinant EGF on a daily basis after UUO. RESULTS: Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clustering gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma. CONCLUSIONS: These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.

Animals↗
PubMed1997

Reverse transcriptase-polymerase chain reaction assays for prostate cancer.

RT-PCR, if targeted against a prostate-specific marker, can be a highly specific and sensitive assay to detect the presence of occult prostate cancer cells at sites far distant from the primary tumor. The low false-positive rate (0.8%) observed when combining most published studies and the high rate of detection of prostate cells in metastatic patients (88%) found in well-defined clinical studies address the basic requirements of a clinically effective diagnostic modality. Additionally, all reports indicate that RT-PCR positivity for PSA or PSMA increases with increased stage of prostate cancer, suggesting that RT-PCR assays may have value in staging the patient presumed to have clinically localized disease. Indeed, data from two institutions have shown the unique contribution that RT-PCR technology might lend to this most vexing problem. With the suggestive data already published, we remain optimistic that molecular staging will become a reality in the future. After all, the variability in techniques of RT-PCR (as well as differences in targets and samples assayed) used by the various laboratories now investigating this method could themselves be responsible for many of the differences reported. There is no question that standardization among laboratories is essential before clinical utility of molecular staging can be proved. Indeed, this endeavor represents the major aim of the RT-PCR consortium in the United States. Nevertheless, at our own medical center, we are struck by our finding that if a preoperative RT-PCR for PSA is negative, the patient can be assured of a successful operative outcome in 88% of cases. We also are impressed by the data showing that if the serum PSA level is greater than 10 ng/mL and the RT-PCR assay is positive, 90% of patients undergoing radical surgery have adverse pathology reports (and, in fact, have already experience operative failure in nearly half the cases). There is increasing consensus that RT-PCR assays afford prognostic information that is also unique. Three institutions have similar data comparing operative or preoperative RT-PCR strategies (employing all three potential sample sources) with treatment outcome. This may suggest the validity of RT-PCR as a staging modality or, alternatively, suggest that a truly metastatic phenotype is identified in patients with circulating PSA-synthesizing cells, or in patients harboring PSA-synthesizing cells in node or marrow tissues. In either case, RT-PCR appears already to provide information not available before the use of this technology. In fact, in the only series comparing RT-PCR with other, more established predictors (PSA, Gleason score) in a multivariate analysis, RT-PCR status provided the best prognostic information. Prostate manipulation does, in fact, appear to affect the RT-PCR assay. Although digital rectal examination and cystoscopy do not seem sufficiently invasive to release prostate cells into the circulation, a small number of individuals undergoing transrectal ultrasound biopsy will experience this phenomenon. This observation provides a cautionary note relative to timing of sample collection for RT-PCR assays. Furthermore, a significant fraction of patients undergoing prostate manipulation during radical surgery may experience shedding of prostate cells into the operative field and release of some into the peripheral circulation. This has not been universally observed and, even if true, may not share the significance of spontaneous RT-PCR positivity (before prostatic manipulation). In the one instance, a potentially metastatic phenotype is responsible for RT-PCR positivity, whereas in the other instance, PSA or PSMA synthesizing cells may have no metastatic potential at all. Further studies on the biologic half-life of such cells are required before any clinical judgement can be made regarding this phenomenon. In summary, there appears to be consensus that RT-PCR technology can differentiate controls from patients with metas

Humans↗
PubMed1997

The relationship of sperm counts to birth rates: a population based study.

PURPOSE: We determined if a statistical relationship exists between changes in sperm counts and birth rates by comparing data from a single geographic location for a 24-year period. MATERIALS AND METHODS: We retrospectively analyzed data from 660 men who banked 1,972 semen samples before vasectomy in Minnesota from 1971 to 1994. Using general linear models, annual variations in sperm count were determined after adjusting for age, duration of abstinence and seasonal (monthly) effects. Adjusted annual mean sperm count was then correlated with regional birth rate data obtained from The National Center for Health Statistics. RESULTS: Multiple regression analysis revealed a significant linear increase in mean annual sperm count at an estimated rate of 1.03 x 10(6) sperm per ml. per year (b = 0.14, t = 5.641, p < 0.0001). There was no effect of age (t = -0.814, p = 0.4156) but there were significant effects of abstinence (b = 0.14, t = 8.808, p < 0.0001) and month of sperm banking (b = 0.025, t = 5.00, p < 0.0001) on sperm counts. Using analysis of covariance there was a significant, nonlinear (year-to-year) fluctuation in mean sperm counts (F = 8.63, p < 0.001). For the study period mean birth rates in Minnesota (live births per 1,000 population) fluctuated yearly from 13.8 in 1973 to 16.7 in 1981. There was a strong correlation between adjusted mean yearly sperm count and annual birth rates (r = 0.63, p = 0.001). CONCLUSIONS: We found a statistically significant correlation between yearly variations in mean sperm counts and birth rates. Our data suggest that variations in male reproductive function may affect population based birth rates and, therefore, may be more important than previously understood.

Adult↗
PubMed1997

Molecular staging of prostate cancer. III. Effects of cystoscopy and needle biopsy on the enhanced reverse transcriptase polymerase chain reaction assay.

PURPOSE: We examined the effects of prostatic manipulations, including flexible cystoscopy and transrectal needle biopsy, on the enhanced reverse transcriptase polymerase chain reaction assay in 57 men. MATERIALS AND METHODS: The reverse transcriptase polymerase chain reaction assay was performed on 25 patients with clinically localized stages T1 to T2cN0M0 prostate cancer before and 30 minutes after cystoscopy. In addition, blood specimens from 32 patients with elevated serum prostate specific antigen and/or abnormal digital rectal examinations were tested immediately before and at 30 minutes after transrectal ultrasound guided prostate needle biopsy. RESULTS: We detected no difference between polymerase chain reaction results obtained immediately before and 30 minutes after cystoscopy in 25 men. Transrectal needle biopsy had no effect on the polymerase chain reaction results in 30 of 32 men. However, 2 men had positive reactions on post-biopsy specimens only. Pathological results of the biopsy revealed benign prostatic hyperplasia and prostatic intraepithelial neoplasia, respectively, in these 2 men. CONCLUSIONS: We conclude that cystoscopy has no clinically significant effect on the reverse transcriptase polymerase chain reaction assay. However, prostatic needle biopsy may cause a positive polymerase chain reaction for PSA in the immediate post-biopsy period.

Biopsy, Needle↗
PubMed1996

Absorbable stapling techniques in continent urinary diversion.

The principle of bowel detubularization to decrease peristaltic pressure and increase reservoir capacity is applied in contemporary continent urinary diversions. The process of detubularization and refashioning of the spatulated bowel segment approximates 1 of operating time and is the most time-consuming aspect of pouch construction. The employment of devices applying absorbable staples ("absorbable staplers") has substantially reduced the time required to fashion bowel reservoirs. This article reviews the adaptation of the absorbable stapler to continent urinary diversion using small- and large-bowel segments.

Colon↗
PubMed1996

Differential diagnosis of prostatism: A 12-year retrospective analysis of symptoms, urodynamics and satisfaction with therapy.

PURPOSE: We determined the incidence of voiding symptoms, urodynamic etiology and satisfaction with therapy in a large cohort of men with prostatism during a 12-year period. MATERIALS AND METHODS: We retrospectively analyzed the records of 2,845 consecutive men who underwent urodynamic evaluation between January 1982 and December 1994. Patients were divided into groups 1 and 2 according to the years of study (between 1982 and 1988, and between 1989 and 1994, respectively). Parameters of evaluation included prevalence and distribution of voiding symptoms, urodynamic etiology of symptoms and satisfaction with therapy (medical or surgical). RESULTS: There was 843 evaluable patients 50 to 94 years old (mean age 63.2) Group 2 patients were younger, and had a 22% higher prevalence of nocturia and a 12% higher prevalence of daytime frequency. The prevalence of all other symptoms was the same in both groups. On urodynamics 523 patients (62%) had demonstrable evidence of bladder outlet obstruction of whom 345 (66%) had concomitant detrusor instability. Of the 843 patients 647 (77%) had detrusor instability, which was the sole diagnosis in 199 (24%). We noted low pressure/low flow in 137 patients (16%) and impaired detrusor contractility in 152 (17%), including 57 (7%) in whom the latter condition was the only diagnosis. Urodynamic findings remained the same during the entire 12-year period. Global satisfaction and symptomatic improvement were better with surgical than medical therapy, although the degree of satisfaction was independent of the urodynamic etiology of symptoms. CONCLUSIONS: Symptomatic men with prostatism are presenting with a greater prevalence of significant nocturia and daytime frequency than in the past with no change in urodynamic findings. In addition, patient level of satisfaction remains greater with surgical than medical therapy regardless of the urodynamic presence of bladder outlet obstruction.

Aged↗
PubMed1996

Hypospadias repair by laser tissue soldering: intraoperative results and follow-up in 30 children.

OBJECTIVES: We examined the use of laser tissue soldering (LTS) as an adjunct to suturing of, as well as a primary means of, tissue closure in urethral reconstruction. METHODS: Since June 1994, 26 boys ranging in age from 3 months to 14 years (mean 3.0 years) underwent hypospadias repair using LTS techniques. The classification of hypospadias was subcoronal in 13, midpenile in 5, penoscrotal in 7, and scrotal in 1. Laser tissue soldering was used in an additional 4 patients: tunica vaginalis patch graft corporoplasty in 2 (scrotal hypospadias), epispadias fistulae in 1, and urethral diverticulum in 1. Of these cases, 3 hypospadias repairs were completely sutureless. An intraoperative comparision was made between suturing and LTS with respect to operative time and degree of difficulty in performing LTS. Postoperatively, patients were examined to determine complications, including stricture, fistula, or impaired wound healing. An unselected group of 25 consecutive boys undergoing hypospadias repair between 1991 and 1992 served as a historical control group. RESULTS: No intraoperative complications resulted from laser activation. In 5 of the 30 procedures (16.6%), suture disruption was noted to occur, with a higher incidence seen with finer, dyed suture material. For hypospadias repair, the average time to suture was 6.7 min/cm (n = 23), whereas it was 3.1 min/cm for adjunctive LTS (n = 23) and 1.4 min/cm for sutureless urethroplasty (n = 3). Follow-up ranged from 3 to 22 months (average 9.6). Four fistulae were noted (1 onlay, 2 skin tube grafts, 1 Thiersch tube) each following penoscrotal or scrotal hypospadias repair; a fifth fistula developed following a traumatic catheterization in a sutureless repair. The overall complication rate in the LTS group was 19% (5 of 26) versus 24% (6 of 25) for controls, whereas that for the distal forms of hypospadias was 11% (2 of 18) and 13.6% (3 of 22), respectively. CONCLUSIONS: Tissue soldering with laser and chromophore-doped solder is feasible, safe, and easy to perform. Laser tissue soldering may be an alternative to standard microsuture technique for hypospadias repair.

Adolescent↗
PubMed1996

Transperineal prostate needle biopsy guided by transurethral ultrasound in patients without a rectum.

OBJECTIVES: Patients with elevated prostate-specific antigen (PSA) and no access to the rectum present a diagnostic challenge to the urologist. This study was undertaken to determine the efficacy of transperineal prostate biopsy using transurethral ultrasound guidance for the detection of prostate cancer. METHODS: Five men status post either total colectomy or abdominoperineal resection (age range: 58 to 73 years, mean age 65.8 years) were referred to us for the evaluation of an elevated PSA (range: 5.6 to 21.4 ng/dL, mean 16.1 ng/dL). Seven procedures were performed utilizing transurethral ultrasound to guide transperineal prostate biopsies in these men. RESULTS: Biopsy results revealed benign prostatic hyperplasia in 4 procedures and prostate cancer in 3 procedures. CONCLUSIONS: Transurethral ultrasound enables the practitioner to perform accurate sonographic assessment and precise biopsy of the prostate in such patients.

Aged↗
PubMed1996

The role of the reverse-transcriptase polymerase chain reaction assay for prostate-specific antigen in the selection of patients for radical prostatectomy.

Prostate cells present in the peripheral circulation can be detected using an enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) assay. In one study, preoperative enhanced RT-PCR for PSA status was a significant predictor of surgical pathology and postoperative biomechanical recurrence. The use of RT-PCR may enhance the urologist's ability to stage potential candidates for radical prostatectomy, as the assay is a more sensitive and specific predictor of microscopic extracapsular extension than conventional staging modalities. This highly adaptable assay also may have roles in screening for recurrence and in staging other solid tumors.

Adenocarcinoma↗
PubMed1996

The use of RT-PCR for prostate-specific antigen assay to predict potential surgical failures before radical prostatectomy: molecular staging of prostate cancer.

OBJECTIVE: To assess the potential role of a recently developed reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen (PSA), that detects circulating prostate cells in patients with prostate cancer, in the management of clinically localized cancer. PATIENTS AND METHODS: A total of 138 men (mean age 62.5 years, range 49-70) scheduled for radical retropubic prostatectomy had an RT-PCR assay before surgery. The results were compared with the final pathological stage of disease, the results from local imaging techniques, serum PSA levels, digital rectal examination (DRE) and Gleason score. RESULTS: Enhanced RT-PCR for PSA was the best predictor of potential surgical failures; 70% of patients with positive surgical margins or invasion into the seminal vesicle were identified pre-operatively by a positive RT-PCR assay (odds ratio = 12.0, positive predictive value = 64%, negative predictive value = 87%). RT-PCR was able to identify pre-operatively patients with adverse pathology, despite low serum PSA values (< 4.0 ng/mL). In patients with high PSA level (> 10 ng/mL), RT-PCR discriminated between potentially curable candidates and those with established extraprostatic disease. CONCLUSIONS: RT-PCR for PSA adds unique prognostic information when considering patients for radical surgery. The final role for the RT-PCR assay is as yet undefined; however, the ability to detect potential surgical failures pre-operatively using a molecular approach should have a significant impact on the management of patients with prostate cancer.

Aged↗
PubMed1996

Pediatric continent reservoirs and colocystoplasty created with absorbable staples.

PURPOSE: For patients undergoing continent urinary diversion or bladder augmentation the process of detubularization and refashioning bowel into a spherical configuration is often tedious and time-consuming, and may cause undesirable blood loss. We sought to determine whether using absorbable staples in a pediatric population was safe, effective and economical. MATERIALS AND METHODS: We performed our technique of rapid right colon pouch construction in 18 children (average age 12.3 years) undergoing continent urinary diversion (8) or colocystoplasty (10). We evaluated the cost of performing the procedure relative to conventional suturing as well as the results of up to 3 years of followup. RESULTS: In all cases pouch construction using absorbable staples was performed easily and rapidly, and resulted in minimal blood loss. Using the staples decreased operative time by approximately 1 hour and saved nearly $350 per case. Only 1 significant complication requiring surgical intervention developed during extended followup (delayed pouch rupture) and in that case the use of absorbable staples did not contribute to morbidity. None of the patients had reservoir stones. CONCLUSIONS: The use of devices applying absorbable staples in conjunction with a 1-step method of colonic reservoir construction proves to be effective and economically sound for continent urinary diversion and bladder augmentation.

Absorption↗
PubMed1996

The American Urological Association symptom score in the evaluation of men with lower urinary tract symptoms: at 2 years of followup, does it work?

PURPOSE: The American Urological Association (AUA) benign prostatic hyperplasia (BPH) guidelines committee established criteria for the diagnosis and treatment of patients with BPH. In a prospective study we determined the usefulness of these guidelines in 145 previously untreated patients with BPH symptoms. MATERIALS AND METHODS: Patients were evaluated initially by AUA symptom score, digital rectal examination, urinalysis, serum creatinine and prostate specific antigen. Based on symptom score, patients with mild symptoms were treated with watchful waiting, while those with moderate and severe symptoms were offered watchful waiting, finasteride alpha-blockers, or laser or transurethral prostatectomy. Minimum followup was 2 years. Patients were offered a change in therapy if they had an intolerable adverse event or no improvement. Analysis included maintenance of therapy at 1 and 2 years, number of office visits and diagnostic tests performed. In addition, all patients were queried regarding which factors influenced their therapeutic choice. RESULTS: Of 37 patients with mild symptoms 31 (81%) remained on watchful waiting at 2 years and 6 advanced to medical therapy. Among 71 patients with moderate symptoms 9 of 15 (60%) remained on watchful waiting, 27 of 36 (75%) remained on alpha-blockers and 12 of 20 (60%) remained on finasteride at 2 years. Of the 37 patients with severe symptoms 1 of 5 (20%) remained on watchful waiting, 1 of 6 (17%) remained on finasteride and 9 of 15 (60%) remained on alpha-blockers, while 3 of 5 (60%) who underwent laser prostatectomy and all 6 (100%) who underwent transurethral prostatectomy received no further treatment. At 2 years 83% of the men who selected either finasteride or alpha-blockers as either the primary or secondary therapeutic choice were still on medications. Most patients with mild (61%) or moderate (51%) symptoms cited adverse events as the predominant concern when selecting therapeutic options. In contrast, efficacy was the overriding concern (70%) in patients with more severe symptoms. CONCLUSIONS: Overall, with these guidelines and the AUA symptom score 110 men (76%) were still on original therapy at 1 year and 99 (68%) at 2 years. Additionally, 31 patients (21%) changed to an alternative, nonoperative therapy. These results suggest that the AUA BPH guidelines provide a rational and balanced approach for evaluation and management of patients with symptomatic BPH. Patients can reasonably expect to remain on the initial therapeutic option for at least 2 years.

Adrenergic alpha-Antagonists↗