5 alpha-Reductase inhibitors.
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5-alpha Reductase Inhibitors↗
Biomedical subjects
J D McConnell
Publications and source records attributed to J D McConnell.
Alpha-blockade downregulates myosin heavy chain gene expression in human benign prostatic hyperplasia.
OBJECTIVES: Smooth muscle (SM), a major component of prostate stroma, plays an important role in the pathogenesis of benign prostatic hyperplasia. In many muscle systems, steroid hormones and alpha(1)-adrenergic neurotransmitters tightly regulate expression of contractile proteins. In this study, SM content and the expression of myosin heavy chain (MHC) in tissues from patients with benign prostatic hyperplasia treated with androgen ablation or alpha-blockade were compared with untreated controls. METHODS: Prostatic periurethral tissue specimens from patients receiving luteinizing hormone-releasing hormone analogues (n = 12), alpha-blocking agents (n = 12), and no treatment (n = 13) were examined. The samples were analyzed for SM MHC mRNA expression using competitive reverse transcription-polymerase chain reaction. SM content was measured by morphometric analysis of trichrome-stained sections. RESULTS: Stromal SM constituted 45.4% +/- 8.6%, 48.1% +/- 18.4%, and 45.9% +/- 10.8% of the total tissue in androgen ablated, alpha-blocked, and untreated tissues, respectively. No significant difference was observed among these three groups (P = 0.84, analysis of variance). However, SM MHC mRNA expression was markedly decreased in the alpha-blockade group (0.15 +/- 0.02 attomole/mg tissue) compared with the androgen-ablated (0.58 +/- 0.15 attomole/mg tissue) or control (0.44 +/- 0.10 attomole/mg tissue) groups. The relationship between SM content and expression of SM MHC significantly differed among the groups (P = 0.02, analysis of variance). CONCLUSIONS: Androgen ablation and alpha-blockade do not appear to alter the histologic characteristics of prostate stroma in men with symptomatic benign prostatic hyperplasia. However, contractile protein gene expression in stromal SM cells is significantly altered after alpha-blockade. These data suggest that, in addition to the simple relaxation of muscle tone, alpha-blocking agents may affect the phenotypic expression of contractile proteins in prostate SM cells.
Adrenergic beta-Antagonists↗
Laparoscopic gonadectomy and excision of müllerian remnant in an adult intersex patient.
Laparoscopy can assist in the diagnosis and treatment of intersex patients. We report a rare case in which laparoscopic gonadectomy and hysterosalpingectomy were performed in a phenotypically-male intersex patient first diagnosed in adulthood.
Adult↗
The development of urology in the 21st century.
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Artificial Organs↗
Contractile protein expression in bladder smooth muscle is a marker of phenotypic modulation after outlet obstruction in the rabbit model.
PURPOSE: We determined changes in contractile protein expression before and after the relief of partial bladder outlet obstruction in the rabbit model and assessed their potential role as predictors of recovery. MATERIALS AND METHODS: We examined the ratio of the smooth muscle myosin heavy chain isoforms SM2-to-SM1, caldesmon isoform expression and bladder function in obstructed and unobstructed adult rabbit bladders. Cystometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis were done to determine changes in bladder function and contractile protein expression. RESULTS: Overall we observed significant correlation of bladder weight with the SM2-to-SM1 ratio (p <0.05). Regardless of the duration of obstruction (up to 10 weeks) the ratio appeared to stabilize around a value comparable to that in fetal rabbit smooth muscle cells, suggesting a reversal of SM2 and SM1 expression to a level similar to that at the fetal stage. The pattern of h and l-caldesmon isoform expression showed an increase in l-caldesmon expression in obstructed bladders. Except for decreased leak point pressure in the obstructed group we noted no statistically significant urodynamic changes in bladder capacity or compliance. CONCLUSIONS: There is significant correlation of bladder weight, which is the best known marker of obstruction, with the SM2-to-SM1 ratio. The myosin heavy chain isoform expression ratio appears to be an indicator of phenotypic modulation in bladder smooth muscle before and after the relief of bladder outlet obstruction. Thus, it may be useful as a marker of bladder dysfunction and predictor of functional recovery. Regression to a fetal pattern of protein expression may suggest irreversible damage to smooth muscle cells, possibly limiting recovery.
Animals↗
Myosin heavy chain gene expression in normal and hyperplastic human prostate tissue.
BACKGROUND: Benign prostatic hyperplasia (BPH) is common among aging men. Over 80% of males 50-60 years and older have various degrees of bladder outlet obstruction secondary to BPH. Despite the tremendous medical impact of BPH, its molecular pathophysiology remains unclear. Current BPH research focuses on steroid hormonal effects, stromal-epithelial cell interaction, and oncogenes and growth factors. But little is known about the potential prostatic smooth muscle (SM) alterations that may occur during stromal hyperplasia. METHODS: To study SM phenotypic modulation in hyperplastic prostatic growth, we isolated and characterized the 3' end of human SM myosin heavy chain (SMMHC) cDNA as a molecular probe. Expression of SMMHC and nonmuscle myosin heavy chain (NMMHC) in human prostates was analyzed using Western blot, Northern blot, and in situ hybridization to determine if BPH tissue expresses significantly less SMMHC and more NMMHC than a normal prostate. In addition, a competitive, reverse transcription (RT) polymerase chain reaction (PCR) method was adapted to quantify SMMHC and NMMHC mRNA expression at the sensitivity level of 10(-21) mole per mg of wet tissue. RESULTS: Western blot, Northern blot, and in situ hybridization results reveal that both SMMHC and NMMHC are expressed in the human prostate, while SMMHC is the predominant form found in normal prostate stroma. Results from competitive RT-PCR analysis indicate that NMMHC mRNA expression is approximately 10(-20) mole/mg of tissue. The SMMHC mRNA expressed is approximately 10(-18) mole/mg. No significant difference was found when NMMHC mRNA expression was compared between normal and BPH periurethral tissues. However, SMMHC expression was reduced almost fivefold in BPH compared to normal prostate, despite an increase in prostatic stromal mass. CONCLUSIONS: Our results suggest the pathogenesis of BPH is associated with a unique type of SM proliferation. Such proliferation is characterized by downregulation of SMMHC mRNA expression but without upregulation of NMMHC mRNA expression, the pattern seen in proliferating SM cells in culture and in other pathologic forms of SM hyperplasia (e.g., atherosclerosis). These findings support a model of BPH typified by active smooth muscle proliferation early in the disease process, and supports clinical observations that suggest ongoing prostate growth of the prostate is minimal in older men. Therapeutic strategies to prevent disease progression should therefore focus on early phases of prostatic growth.
Adult↗
Expression of the human mismatch repair gene hMSH2: a potential marker for urothelial malignancy.
BACKGROUND: The human mismatch repair (MMR) gene hMSH2 (human mutS homolog-2) is a DNA repair gene that has been reported to be mutated in 40% of hereditary nonpolyposis colon cancer (HNPCC) kindreds and a small percentage of sporadic tumors. HNPCC is a cancer predisposition syndrome with an increased risk of carcinoma of the colon, endometrium, stomach, small intestine, ovary, ureter, and renal pelvis. Immunohistochemical analysis demonstrated increased hMSH2 expression in sporadic colon carcinoma and in the replicative compartment of normal epithelium. A recent immunohistochemical analysis of hMSH2 in bladder tumors correlated reduced hMSH2 expression with recurrence and higher tumor grade. In the current study, we examined hMSH2 expression in urothelial malignancy using immunohistochemical analysis and developed a molecular assay for the detection of hMSH2 expression in bladder washes. METHODS: Immunohistochemical analysis of 17 tumors from the genitourinary tract and reverse transcription coupled with polymerase chain reaction (RT-PCR) of 40 bladder washes were used to investigate hMSH2 expression in noninvasive and invasive urothelial malignancies. RESULTS: Increased expression of hMSH2 was detected in all tumors examined using immunohistochemical analysis independent of grade or stage. Reverse transcription-PCR of hMSH2 mRNA from bladder washes detected 17 of 21 patients with primary or recurrent urothelial neoplasms or tumors involving the urothelial system. Four patients with urothelial malignancies without detectable hMSH2 expression from their bladder washes had high grade lesions. Ten of 13 patients without pathologic or cystoscopic evidence of bladder tumors were negative for hMSH2 expression in bladder washes. Two patients with bladder tumors and bladder washes that were positive for hMSH2 subsequently were found to be negative for hMSH2 after treatment of their tumors and at last follow-up had remained recurrence free for at least 1 year. CONCLUSIONS: The results of the current study suggest that hMSH2 expression is increased in low and high grade urothelial neoplasms, similar to the expression pattern in sporadic colon carcinoma. However, a fraction of high grade lesions may not express hMSH2 as detected by RT-PCR from bladder washes. The ability to detect hMSH2 expression in bladder washes may allow the use of hMSH2 expression as a marker for urothelial malignancy. In addition, the ability to define hMSH2 deficient tumors using bladder washes may have prognostic significance in the treatment of patients with urothelial carcinoma.
Adenosine Triphosphatases↗
Prostate cancer: where are we?
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Journal Article↗
Smooth muscle myosin heavy chains are developmentally regulated in the rabbit bladder.
PURPOSE: In smooth muscle (SM), myosin heavy chain (MHC) is expressed predominantly as two isoforms, SM1 and SM2, which are encoded by a single gene and expressed by alternative splicing mechanisms. Although functional differences of these isoforms are unknown, changes in SM1/SM2 ratio have been reported in various pathophysiologic conditions. We analyzed MHC composition of bladder detrusor SM from rabbits of different ages to determine whether SM1 and SM2 isoform expressions are developmentally regulated. MATERIALS AND METHODS: Rabbit bladders on the -11, -4, 1, 7, 14, 21, and 90th days of life were analyzed for SM MHC isoform expression at protein and mRNA levels. Porous sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), S1 protection assay, and histological analysis were employed. RESULTS: The predominant MHC isoform in fetal and neonatal bladders was SM1. In the third postnatal week, the SM1/SM2 ratio decreased from 2.3 to 1.0. A stable SM1/SM2 ratio of 0.6 was observed in the adult animal. Although expression of SM1 mRNA was 2.6-fold greater than that of SM2 in the fetus, the relative amount of SM2 mRNA increased rapidly after birth and remained the predominant isoform throughout adult life. Developmental changes in relative amounts of SM1 and SM2 protein in bladder tissues were virtually identical to those of SM1 and SM2 mRNA. SM cell growth and disappearance of primitive mesenchyme from the bladder occurred concomitantly with the MHC isoform shift. CONCLUSIONS: The parallel temporal course of MHC mRNA and protein isoform levels suggests detrusor SM MHC expression may be developmentally regulated at the mRNA level.
Animals↗
The mismatch repair gene hMSH2 is mutated in the prostate cancer cell line LNCaP.
PURPOSE: Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating and inherited mutations in the prototypic mismatch repair gene hMSH2 have been described in a cancer predisposition syndrome known as hereditary nonpolyposis colon cancer. Patients with hereditary nonpolyposis colon cancer are at increased risk for colon cancer and extracolonic cancers such as upper tract transitional cell carcinoma but not prostate cancer. We investigated expression of hMSH2 in prostate cancer cell lines using genetic and molecular analysis. MATERIALS AND METHODS: We used the 3 well described prostate cancer cell lines, DU145, LNCaP and PC3. Western blot analysis with monoclonal antibody to hMSH2 was used to assess expression. Southern blot and polymerase chain reaction of genomic DNA were used to identify genetic alterations in the hMSH2 gene. Single cell cloning, dinucleotide repeats and BAT-26 were used to assess the cell lines for microsatellite instability. RESULTS: The prostate cancer cell line LNCaP did not express hMSH2 and was found to have a homozygous deletion of hMSH2 exons 9 to 16, resulting in truncation of the protein. While microsatellite analysis did not reveal alterations at the BAT-26 locus, single cell cloning produced several LNCaP subclones with alteration at 1 dinucleotide repeat. CONCLUSIONS: The well described prostate cancer cell line LNCaP has a mutation in the hMSH2 gene, resulting in loss of expression and possible evidence of microsatellite instability. To our knowledge our finding is the first demonstration of a genetic alteration in hMSH2 in a prostate cancer cell line.
Base Pair Mismatch↗
Elastin gene expression in benign prostatic hyperplasia.
BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.
Aged↗
Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group.
OBJECTIVES: Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS: Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS: The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS: Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.
Acute Disease↗
Physiologic sequelae of partial infravesical obstruction in the mouse: role of inducible nitric oxide synthase.
PURPOSE: To develop a mouse model for partial infravesical obstruction, and determine the resultant changes in bladder function, with particular emphasis on the role of inducible nitric oxide synthase (iNOS) in the bladder response. MATERIALS AND METHODS: Wild type mice were subjected to no intervention, sham operation, and varying durations of partial outlet obstruction (1, 3, and 5 weeks). They then underwent cystometric evaluation, bladder strip stimulation studies using carbachol, and relaxation studies using l-arginine, sodium nitroprusside, and 8-bromoguanosine 3'-5' cyclic guanosine monophosphate. Bladder tissue was subjected to RT-PCR and Western analysis for iNOS. Bladders were also studied histologically using morphometric analysis. RESULTS: Bladders from mice obstructed for 5 weeks were heavier (weight increased by 110%), larger (capacity increased by 73%), and had a higher frequency of abnormal appearing cystometric curves than normal bladders. Tissue bath studies demonstrated decreased contractility in response to cholinergic stimulation at 5 weeks of obstruction (decreased by 55% at maximal stimulation). RT-PCR demonstrated iNOS in approximately 70% of bladders obstructed for 1 and 3 weeks, while the iNOS protein was apparent in 50% of the bladders from the same groups. CONCLUSIONS: This new animal model of infravesical obstruction is reliable and reproducible. Moreover, the physiologic changes noted are comparable to other models, but an added advantage is the relevance of this model with regard to studying new transgenic or knockout mice. Enhanced expression of iNOS seen early after obstruction may serve to improve oxygenation during obstruction-induced ischemia.
Animals↗
The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.
BACKGROUND: Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known. METHODS: In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men. RESULTS: During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001). CONCLUSIONS: Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.
5-alpha Reductase Inhibitors↗
Decreased elastin gene expression in noncompliant human bladder tissue: a competitive reverse transcriptase-polymerase chain reaction analysis.
PURPOSE: In low capacity noncompliant fibrotic bladders, as seen in patients with myelomeningocele, elevated storage pressures ultimately can lead to renal damage. Earlier studies have described an increased deposition of extracellular matrix protein, especially type III collagen, in the detrusor muscle. We analyzed elastin gene expression and quantified elastin gene alteration in the obstructed bladder, correlating urodynamically measured compliance with elastin messenger ribonucleic acid (mRNA) concentration. MATERIALS AND METHODS: Using a reverse transcriptase-polymerase chain reaction quantitative technique elastin mRNA can be reliably measured in 5 to 8 mg. samples of bladder tissue. We compared tissue samples from patients with urodynamically demonstrated noncompliant bladders (less than 10 cc/cm. water) to a control group with normal bladder compliance (greater than 20 cc/cm. water). Tissue samples were homogenized and sonicated, and complementary deoxyribonucleic acid (cDNA) was synthetized from mRNA using reverse transcriptase. Wild type and mutant elastin cDNA were synthetized, and target elastin cDNA with unknown concentration was competitively co-amplified with known serial dilutions of the mutant template (competitive polymerase chain reaction). Computerized densitometry allowing cDNA concentration measurement was performed and competitive reverse transcriptase-polymerase chain reaction was repeated at least twice for every sample. RESULTS: Elastin mRNA concentration ranged from 27.6 to 63.2 attomole per mg. in noncompliant bladders compared to 62 to 190 attomole per mg. in controls. The variation within the same sample was less than 10%. There was a statistically significant difference between mean plus or minus standard deviation elastin cDNA concentration in noncompliant bladders (37.48 attomole per mg. +/- 12.06) and controls (119.63+/-41.01 attomole per mg.). CONCLUSIONS: A significant decrease in elastin mRNA matches the decreased deposition of elastic fibers noted in previous immunohistochemical studies. Our data suggest that this decrease is mainly due to a transcriptional down regulation of the elastin gene in noncompliant bladders.
Adolescent↗
Smooth-muscle myosin heavy-chain isoform expression in bladder-outlet obstruction.
Bladder-outlet obstruction leads to detrusor smooth-muscle hypertrophy/hyperplasia. Despite this overall increase in muscle mass, smooth-muscle contractility decreases and bladder emptying is impaired. The goal of this study was to determine whether smooth-muscle myosin heavy-chain (MHC) alterations occur in conjunction with partial obstruction of the rabbit bladder. Total MHC and MHC-isoform protein concentrations were determined by quantitative gel electrophoresis in rabbit bladders partially obstructed for 1-4 weeks. MHC gene expression was assessed by Northern and nuclease protection assays. Two MHC isoforms (SM1/SM2) were identified in the normal rabbit bladder. After 2 weeks of obstruction the ratio of SM1/SM2 changed from 0.4:0.6 to 0.5:0.5 (P < 0.01). As compared with sham-operated values, the level of MHC mRNA decreased significantly as of 1 day after obstruction. Quantitation of MHC-isoform mRNA levels revealed a nearly 3-fold increase in the SM1/SM2 ratio. In this animal model of bladder-outlet obstruction, early changes in MHC isoforms as well as an overall decrease of MHC mRNA expression were demonstrated, suggesting that obstruction induces significant alterations in myofilament gene expression.
Animals↗
Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology.
OBJECTIVES: To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. METHODS: Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a "gold standard" for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. RESULTS: Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. CONCLUSIONS: In this study in which a "gold standard" based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.
Adult↗
Smooth-muscle physiology.
In the last several years, significant advances have been made in the understanding of bladder smooth muscle physiology. This article provides a summary for the clinician of current knowledge about the detrusor smooth muscle cell structure, function, and the relationship of structure to function in terms of bladder storage and physical properties such as compliance. The integration of this basic science knowledge into clinical practice is illustrated in discussion of two common disorders: detrusor instability, and outflow obstruction.
Action Potentials↗