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Tom F Lue

Publications and source records attributed to Tom F Lue.

At least 37 records · Page 2Linked to original sources
PubMed2006

Clinical and psychosocial characteristics of men with erectile dysfunction: baseline data from ExCEED.

INTRODUCTION: Erectile dysfunction (ED) is associated with psychological impairment, and further research is required to understand their relationship. AIM: We present descriptive baseline results from a longitudinal observational study of North American men seeking treatment for ED. METHODS: Patients completed clinical and health-related quality-of-life information at baseline and three follow-up points over 12 months; 162 patients had usable baseline data, including clinical history and current status, sociodemographic information, and standard paper-and-pencil scales of psychosocial characteristics. Scores on the International Index of Erectile Functioning erectile functioning subscale were collapsed into mild (N = 27), moderate (N = 41), or severe (N = 94) categories. Using chi-square, anova, and logistic regression, we identified baseline characteristics associated with ED severity. MAIN OUTCOME MEASURE: The main outcome measure was the degree of psychosocial impairment associated with mild, moderate, and severe ED. RESULTS: Severe ED was significantly associated with not having a regular sex partner; a history of prostate cancer; and worse scores on measures of positive affect, belonging/loneliness, sexual self-efficacy-strength, psychological adjustment, marital happiness, anxiety at last intercourse, and depression. In a multivariate logistic regression model, poorer sexual self-efficacy was most closely associated with severe ED. The model rescaled R(2) was 0.63 (area-under-the-curve, 0.91). CONCLUSIONS: Severe ED is related to impairment across a broad range of psychosocial domains, and clinicians should consider offering patients assistance in dealing with its psychosocial impact.

Adult↗
PubMed2006

Longitudinal differences in psychological outcomes for men with erectile dysfunction: results from ExCEED.

INTRODUCTION: The direction of the relationship between psychological adjustment and erectile dysfunction (ED) is unclear and may differ for different men, and few studies have examined psychological outcomes for men receiving ED treatment. AIM: This study assessed the impact of ED therapy at baseline and 12-month follow-up, using standard psychological measures. METHODS: Using an observational ED registry, we collected clinical and psychosocial data at baseline and 3, 6, and 12 months. Participants had (i) a patient-reported outcomes questionnaire at baseline and at least one follow-up; and (ii) data about ED treatments received during the study. Treated men were classified as responders based on improvements in International Index of Erectile Function scores from baseline to 12 months. MAIN OUTCOME MEASURES: The main outcome measures were changes in psychological outcomes in relation to treatment status and baseline ED severity. RESULTS: Of 153 patients, 40 responded to treatment, 49 did not respond to treatment, and 64 did not receive treatment. Treatment responders reported significant improvements in 12-month sexual self-efficacy but only small improvements or no change across five other psychological domains, whereas nonresponders reported small decrements. There was a trend for differences in sexual self-efficacy to vary by baseline ED severity, as well as by treatment response. CONCLUSIONS: Diagnosing and successfully treating ED significantly affects patient psychological adjustment, so providers should actively diagnose and treat ED.

Adult↗
PubMed2006

Expression, distribution and regulation of phosphodiesterase 5.

Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Best known as the target of the impotence drug sildenafil, PDE5 degrades cGMP in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and intestines. In addition, it regulates numerous other physiological processes such as neurogenesis and apoptosis. Like all other PDEs, PDE5 is dimeric; each subunit is approximately 100 kd in size and has two allosteric cGMP-binding sites and a catalytic domain. Protein kinase G (PKG)-mediated phosphorylation and allosteric cGMP binding upregulate PDE5 activity, while PP1 phosphatase-mediated dephosphorylation downregulates. Sildenafil and other selective inhibitors inhibit PDE5 by binding to the catalytic site. From two promoters a single PDE5A gene at human chromosome 4q26 encodes three alternatively spliced isoforms (PDE5A1-3) that differ in the N-terminus. The PDE5A promoter is located upstream of the three isoform-specific first exons (in the order of A1-A3-A2) and consists of a 139-bp core, a 308-bp upstream enhancer, and a 156-bp downstream enhancer. The weaker 182-bp PDE5A2 promoter is located between the A3- and A2-specific exons and contains an indispensable Sp1-binding sequence. Both promoters are responsive to cGMP or cAMP stimulation, and several studies have demonstrated regulation of PDE5 expression possibly through these promoters. Virtually all tissues and cell types express PDE5, with heart and cardiomyocytes being contentious. PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is specific to smooth muscle.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Non-arteritic anterior ischemic optic neuropathy (NAION) and phosphodiesterase type-5 inhibitors.

OBJECTIVE: To determine whether a causative relationship exists between non-arteritic anterior ischemic optic neuropathy (NAION) and the use of phosphodiesterase-5 (PDE-5) inhibitors for the treatment of erectile dysfunction. METHODS: A comprehensive review of the literature was performed to identify the contemporary understanding of NAION pathophysiology, epidemiology, and occurrence in men using the oral PDE-5 inhibitors sildenafil (Viagra, Pfizer), vardenafil (Levitra, Bayer AG), and tadalafil (Cialis, Lilly-ICOS LLC) for the treatment of erectile dysfunction. RESULTS: NAION is the second most common acquired optic neuropathy in men aged 50 years and older. Risk factors for NAION, cardiovascular disease, and erectile dysfunction are shared and include age, dyslipidemia, diabetes, hypertension, and cigarette smoking. To date, less than 50 cases of NAION associated with PDE-5 use have been reported to the United State's Food and Drug Administration (FDA) and five Canadian cases alerted to Health Canada. Given the large number of men safely using these agents and a limited number of events, it is not possible to determine whether NAION is directly linked to the use of PDE-5 inhibitors, underlying cardiovascular risk factors, ocular anatomical defects, a combination of these variables, or as yet unidentified factors. CONCLUSIONS: PDE-5 inhibitors have gained widespread use for the treatment of erectile dysfunction due to their safety, efficacy, and ease of use. Their role in the pathogenesis of NAION remains controversial. Reasonable and informed consent regarding the possible but low risk of NAION with the use of sildenafil, vardenafil and tadalafil is recommended. Loss or decreased vision, whether painful or painless, demands urgent patient assessment and immediate cessation of PDE-5 inhibitor use.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Physiology of penile erection and pathophysiology of erectile dysfunction.

This article reviews the physiology of penile erection, the components of erectile function, and the pathophysiology of erectile dysfunction. The molecular and clinical under-standing of erectile function continues to gain ground at a particularly fast rate. Advances in gene discovery have aided greatly in working knowledge of smooth muscle relaxation/contraction pathways. The understanding of the nitric oxide pathway has aided not only in the molecular understanding of the tumescence but also greatly in the therapy of erectile dysfunction.

Erectile Dysfunction↗
PubMed2005

Identification of potential biomarkers of Peyronie's disease.

AIM: To identify proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD). METHODS: Cells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally-appearing TA of the same patients were designated as NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase chain reaction (RT-PCR) for the expression of monocyte chemoattractant protein 1 (MCP-1). Crude protein lysates were analyzed by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) with IMAC30-Cu, CM10, and H50 chips. Each lysate was then separated into six fractions, which were further analyzed by SELDI-MS. RESULTS: RT- PCR analysis showed that PT cells expressed higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed that the crude protein lysates of all four cell strains produced similar and reproducible protein profiles on IMAC30-Cu and CM10 chips. Additional SELDI-MS analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5 kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and 46.9 kDa that were downregulated in PT cells. CONCLUSION: MCP-1, which is often involved in tissue fibrosis, was expressed at higher levels in PT than that in NT cells. Five potential biomarkers for PD were identified by SELDI-MS analysis.

Base Sequence↗
PubMed2005

Crural ligation for primary erectile dysfunction: a case series.

PURPOSE: Some men with primary erectile dysfunction (ED) have maldevelopment of the crura of the penis. We report our experience with crural ligation for primary venous leakage ED in the last 5 years. MATERIALS AND METHODS: Between December 1998 and March 2004, 11 patients with primary ED underwent crural ligation surgery for congenital venous leakage. All patients were evaluated with pertinent history and physical examinations, color duplex ultrasound, nocturnal penile tumescence study with RigiScan, cavernosometry and cavernosography. Localized crural leakage was the pathognomonic feature in these patients. Surgery involved reflection of the dorsal and cavernous arteries and nerves off of the crura, followed by ligation of the 2 crura proximal to the entrance of the cavernous artery with umbilical tapes. Followup was performed by telephone interview or personal interview at the clinic. A retrospective preoperative and postoperative questionnaire, that is the abridged 5-item version of the 15-item International Index of Erectile Function, was given at the time of the interview. Statistical analysis was performed with the paired t test. RESULTS: Median patient age at surgery was 28 years (range 22 to 39) and mean followup after surgery was 34 months (range 6 to 58). Mean International Index of Erectile Function +/- SD preoperatively and postoperatively was 8.9 +/- 4.5 and 17.5 +/- 5.0, respectively. For questions 2, 3 and 5 mean postoperative scores were significantly better than postoperative scores (p <0.05). Marked improvement in erectile function was noted in 9 of our 11 patients. CONCLUSIONS: Penile venous surgery may not have a lasting result in men in whom venous leakage is due to systemic diseases or penile smooth muscle atrophy. However, in patients with a congenital venous leak abnormality of the crura ligation of the proximal crura with umbilical tapes seems to have a satisfactory, durable result.

Adult↗
PubMed2005

Improving erectile function by silencing phosphodiesterase-5.

PURPOSE: We investigated whether phosphodiesterase-5 (PDE5) can be down-regulated by a specific small interfering RNA (siRNA) and whether this would improve erectile function. MATERIALS AND METHODS: A PDE5 siRNA encoding oligonucleotide was inserted into pSUPER-retro vector, resulting in the siRNA expressing construct, pPDE5-silencer. The construct was packaged into oncoretroviral particles and then transduced into rat cavernous smooth muscle cells (CSMCs). Cells were examined for PDE5 expression by reverse transcriptase-polymerase chain reaction, Western blotting and immunofluorescence microscopy. Cells were then treated with 10 microM sodium nitroprusside (SNP) and examined for cyclic guanosine monophosphate (cGMP) at 0, 10, 30, 60 and 240 minutes. The siRNA expressing cassette was transferred from the oncoretrovirus to lentivirus, which was then injected into rat penises. Three months later erectile function was examined by electrostimulation and PDE5 expression in cavernous smooth muscle was determined by immunohistochemistry. RESULTS: CSMCs transfected with pPDE5-silencer (CSMC plus siRNA) showed an 88.2% decrease in PDE5 compared with CSMCs transfected with control vector (CSMCs plus vector). Within 10 minutes of SNP treatment cells (CSMCs, CSMCs plus vector and CSMCs plus siRNA) showed similar sharp increases in cGMP. However, while cGMP levels in CSMCs and CSMCs plus vector returned to almost baseline in 1 hour, the cGMP level in CSMCs plus siRNA remained high even 4 hours after SNP treatment. Rats injected with the siRNA expressing lentivirus showed increased electrostimulated erectile function, as measured by peak intracorporeal pressure and the intracorporeal pressure increase, compared with rats injected with control lentivirus. PDE5 expression was decreased in the siRNA treated cavernous smooth muscle. CONCLUSIONS: PDE5 expression could be decreased by siRNA, resulting in prolonged cGMP accumulation and improved erection.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Combined external urethral bulking and artificial urinary sphincter for urethral atrophy and stress urinary incontinence.

OBJECTIVE: To describe a technique of externally bulking the urethra with a soft-tissue graft before placing another artificial urinary sphincter (AUS), as when placing another AUS for recurrent male stress urinary incontinence (SUI) other manoeuvres, e.g. placing a tandem cuff or transcorporal cuff, must be used to obtain urinary continence in an atrophic urethra, and each is associated with morbidity. PATIENTS AND METHODS: From January 2003 to July 2004, five patients (mean age 74 years, range 62-84) treated by radical prostatectomy were referred for recurrent SUI after placing an AUS (four, including one with urethral erosion) or a male sling (one, with a resulting atrophic urethra). Each patient was treated with an external urethral bulking agent (Surgisis) ES, Cook Urological, Spencer, Indiana) and had an AUS placed. RESULTS: In each patient the greatest urethral circumference was <4 cm. To place a functional 4 cm cuff, the diameter of the urethra was enhanced by wrapping it with Surgisis ES. Continence was significantly improved in all patients except one 84-year-old man who had the replanted artificial sphincter removed because of erosion 14 months after surgery. CONCLUSION: In cases of severe recurrent SUI from urethral atrophy after placing an AUS, externally bulking the urethra with Surgisis ES before placing another AUS is well tolerated, and gives satisfactory results.

Aged↗
PubMed2005

The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence.

OBJECTIVE: To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury. MATERIALS AND METHODS: Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically. RESULTS: In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group. CONCLUSION: Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.

Adenoviridae↗
PubMed2005

Phosphodiesterase type 5 inhibitors for erectile dysfunction.

The cyclic nucleotide signalling pathway mediates the smooth-muscle relaxing effects of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half-life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Cyclic nucleotide signaling in cavernous smooth muscle.

INTRODUCTION: Penile erection depends on cavernous smooth muscle relaxation that is principally regulated by cyclic nucleotide signaling. It is hoped that a comprehensive review of publications relevant to this subject will be helpful to both scientists and clinicians who are interested in the sciences of erectile function/dysfunction. AIMS. To review the roles of extracellular signaling molecules, their receptors, intracellular effectors, and phosphodiesterases in cyclic nucleotide signaling that leads to cavernous smooth muscle relaxation. The involvement of these molecules in the development of erectile dysfunction and the possibility of using them as therapeutic agents or targets are also discussed. METHODS: Entrez, the search engine for life sciences, was used to search for publications relevant to the topics of this review. Keywords used in the searches included vascular, cavernous, penis, smooth muscle, signaling molecules (adenosine, nitric oxide, etc.), and key elements in the cyclic nucleotide signaling pathways (cAMP, cGMP, cyclases, PKG, PKA, etc.). Articles that are dedicated to the study of erectile function/dysfunction were prioritized for citation. RESULTS: More than 1,000 articles were identified, many of which are studies of the vascular system and are therefore reviewed but not cited. Studies on erectile function have identified both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways in cavernous smooth muscle. Many signaling molecules of these two pathways have been shown capable of inducing erection when administered intracavernously. However, for sexually induced erection, nitric oxide (NO) is the responsible signaling molecule and it passes on the signal through soluble guanyl cyclase (sGC), cGMP, and protein kinase G (PKG). CONCLUSIONS: The NO/sGC/cGMP/PKG pathway is principally responsible for sexually stimulated erection. Detumescence is mainly carried out by the degradation of cGMP by phosphodiesterase 5. Both cAMP and cGMP signaling pathways are susceptible to genetic and biochemical alterations in association with erectile dysfunction. Several key elements along these pathways are potential therapeutic targets.

Cyclic AMP↗
PubMed2005

Neuroregenerative strategies after radical prostatectomy.

Patients with erectile dysfunction (ED) following radical prostatectomy (RP) continue to present to practicing urologists. Although nerve-sparing RP has decreased the rates of ED significantly, new therapies for cavernosal nerve protection and recovery are now being developed. This report discusses the many agents available in neuroregeneration and neuroprotection to aid in the recovery of erectile function. Multiple agents and strategies have been used for neuroprotection and neuroregeneration of the cavernosal nerve following RP and in nerve injury models. Many of these agents display promise for the treatment of impotence. Early treatment for patients recovering from RP is becoming the standard of care. Natural recovery of erections may take as long as 18 to 24 months post RP; however, treatment plans may reduce the time to erectile recovery.

Journal Article↗
PubMed2004

The effect of labor and/or ovariectomy on rodent continence mechanism--the neuronal changes.

Many women develop stress urinary incontinence (SUI) after childbirth, but the exact neuronal changes are largely unknown. This study is designed to identify the neuronal changes associated with pregnancy, delivery and ovariectomy. A total of 10 virgin and 48 pregnant rats were used. Cystometry and stress/sneeze tests were performed in the virgin once and the pregnant rats at certain time points. Postpartum the rats were equally grouped as follows: group I: delivery, group II: delivery + ballooning, group III: delivery + ovariectomy, group IV: delivery + ballooning + ovariectomy. Tissues from bladder, bladder neck, and urethra were analyzed by immunostaining for PGP 9.5, CGRP, SP, NPY, VIP, TH, n-NOS. We found complex innervation changes in the different tissue samples. Since the bladder neck and the mid-urethra play an important role in the continence mechanism the neuronal changes in these areas contribute to the observed functional changes.

Animals↗
PubMed2004

Effect of cell passage and density on protein kinase G expression and activation in vascular smooth muscle cells.

It has been shown that rat aortic smooth muscle cells (AoSMCs) lost PKG-I expression when propagated repetitively or grown at low densities. Conversely, AoSMCs isolated from PKG-I deficient mice are indistinguishable from those isolated from normal mice in morphology and growth characteristics. In this study, human AoSMCs were grown from passage 9 (p9) to passage 15 (p15) and rat AoSMCs were isolated and cultured from p1 through p15. Western blotting and immunofluorescence microscopy showed little difference in PKG-I expression among different passages. Next, rat AoSMCs of p4 were grown and harvested at different cell densities. Western blotting again showed little difference among cells seeded or harvested at different densities. To test the effect of cell passage on PKG-I activation, rat AoSMCs of p4 and p11 were treated with cGMP and analyzed by Western blotting for phosphorylated vasodilator-stimulated phosphoprotein (P-VASP). The results showed that p4 had higher level of PKG-I activation than p11.

Actins↗
PubMed2004

Prevention and treatment of erectile dysfunction using lifestyle changes and dietary supplements: what works and what is worthless, part I.

Clinicians working in urology should adhere to the same guidelines that are observed in cardiovascular medicine when dealing with a patient with ED. A golden opportunity exists to discuss lifestyle changes with any man with or concerned about ED. Providing heart-healthy recommendations to men with minimal to extensive ED may produce a twofold impact: (1) patients may be able to affect the future extent of their disease, and (2) patients may become healthier overall. Patients following a heart-healthy lifestyle after a diagnosis of ED or to prevent ED should enjoy increased quality or quantity of life. The time is more than ripe for patients to understand that heart health is tantamount to erectile health.

Adult↗